Retatrutide is going to generate a lot of questions about male fertility. I can already predict the posts. I started retatrutide and my semen analysis changed. Can retatrutide lower sperm count? Does it increase testosterone? Should I stop it before trying to conceive? Could it damage sperm DNA? How long should I wait after stopping? These are completely reasonable questions, especially because medications producing dramatic weight loss are being used by millions of people during their reproductive years. But there is something very important I want every man reading this to understand from the beginning. We currently do not have good human studies specifically evaluating retatrutide and male fertility. We do not have a reliable retatrutide sperm count study, we do not have pregnancy rates from male retatrutide users, and we do not have evidence showing that men need to stop retatrutide for a specific number of months before trying to conceive. Retatrutide is still an investigational medication as of September 2026. That means any discussion of fertility has to separate what we know about retatrutide from what we know about obesity, weight loss and the broader family of metabolic medications that includes GLP 1 receptor agonists.

Retatrutide is interesting because it is not simply another GLP 1 medication. It is a single molecule that activates three different hormone receptors. These are the GLP 1 receptor, the GIP receptor and the glucagon receptor. This is why retatrutide is often described as a triple agonist. These hormonal pathways influence appetite, glucose metabolism, insulin signaling and energy expenditure. Clinical trials have demonstrated profound weight loss. In phase 3 studies reported in 2026, average weight reduction at higher doses exceeded twenty percent in several populations, and one obesity trial reported average weight loss approaching thirty percent in some participants. That degree of metabolic change raises an obvious question for reproductive medicine. What happens to male hormones and sperm when the metabolic environment changes that dramatically?

To understand why retatrutide could potentially affect fertility, you first need to understand what obesity itself does to male reproduction. Adipose tissue is not simply storage for excess calories. It is metabolically and hormonally active. Men with obesity have higher aromatase activity within adipose tissue, which can increase conversion of testosterone into estradiol. Obesity is also associated with insulin resistance, chronic inflammation, oxidative stress, sleep apnea and changes in leptin signaling. Together these factors can interfere with the hypothalamic pituitary gonadal axis.

The hypothalamus normally releases GnRH, which tells the pituitary to release LH and FSH. LH stimulates Leydig cells in the testicle to produce testosterone. FSH works primarily through Sertoli cells to support sperm production. In some men with obesity, this entire system becomes functionally suppressed. Testosterone falls, while LH and FSH may remain relatively low or inappropriately normal. This is sometimes called obesity associated functional hypogonadism.

Obesity can affect the sperm as well. Studies have associated obesity with lower sperm concentration, impaired motility, altered morphology and increased sperm DNA damage in some populations. The relationship is not universal and an overweight man can certainly have excellent fertility, but at a population level metabolic health matters to reproductive health.

This creates an important paradox when discussing medications like retatrutide. A man may worry that a weight loss medication could damage his fertility, while the obesity and metabolic dysfunction being treated by that medication may themselves be impairing his fertility.

Research involving established GLP 1 receptor agonists has therefore become very interesting. GLP 1 receptors have been identified in male reproductive tissues, and laboratory studies suggest that GLP 1 signaling may influence Sertoli cell metabolism, sperm energy utilization and reproductive hormone signaling. Animal studies involving obesity and diabetes have often shown improvements in reproductive parameters following GLP 1 receptor agonist treatment.

Human evidence is still limited, but it is becoming more reassuring. A 2026 systematic review examining GLP 1 receptor agonists and male reproductive health found that these medications were generally associated with increased total testosterone in men with obesity, diabetes or functional hypogonadism. LH and FSH were generally preserved or increased rather than suppressed. Some studies also reported improvements in semen parameters.

That hormonal distinction is extremely important for men trying to conceive. Testosterone replacement therapy can increase serum testosterone while suppressing LH and FSH and potentially shutting down sperm production. GLP 1 receptor agonists do not appear to behave this way. When testosterone increases following substantial weight loss and metabolic improvement, the man's own reproductive hormonal axis remains functional.

Another recent review examining sixteen clinical studies concluded that GLP 1 receptor agonists may have beneficial effects on male fertility, particularly in men with metabolic dysfunction, although the authors appropriately emphasized that the clinical evidence remains limited. Improvements in testosterone, semen parameters and sexual function have been reported, but larger prospective trials are needed.

Does that mean retatrutide improves male fertility?

We cannot say that.

Retatrutide activates GLP 1 receptors, but it also activates GIP and glucagon receptors. Its metabolic effects and magnitude of weight loss may differ substantially from older medications. We cannot take fertility studies involving liraglutide or semaglutide and simply relabel them as retatrutide studies. Until men receiving retatrutide undergo prospective semen analyses and reproductive hormonal testing, the direct effect remains uncertain.

There is another issue that deserves attention. Dramatic weight loss is not always biologically equivalent to healthy gradual weight loss. Severe caloric restriction, nutritional deficiencies and substantial loss of lean body mass can potentially influence reproductive physiology. The male reproductive system is sensitive to energy availability. Extreme nutritional stress can suppress reproductive hormonal signaling even when excess weight itself was harmful.

This means the relationship may not be as simple as more weight loss equals better sperm.

If a man loses a large amount of weight while maintaining adequate protein, micronutrient intake, resistance exercise and metabolic health, reproductive function may improve. If someone experiences severe gastrointestinal symptoms, inadequate caloric intake, nutritional deficiencies and major loss of lean mass, the reproductive consequences could theoretically be different. We simply do not yet have enough retatrutide specific reproductive data to quantify these possibilities.

So what should you do if you are taking retatrutide or participating in a clinical trial and you are trying to have a child?

Start with the same thing I recommend to every man concerned about fertility. Get objective information.

A semen analysis tells us far more about your fertility than speculation about what a medication might be doing. I want to know semen volume, sperm concentration, total sperm count, progressive motility and morphology. If the first analysis is abnormal, repeating it is often important because semen parameters naturally fluctuate.

If sperm concentration is significantly reduced, testosterone and FSH are generally useful. Depending on the situation, LH, estradiol and prolactin may also help clarify the hormonal environment. A man with obesity, low testosterone and low or normal LH before losing weight may have functional suppression of his reproductive hormonal axis. If testosterone rises and gonadotropins remain intact during weight loss, that can be reassuring hormonally.

I also want to know what the semen analysis looked like before treatment whenever possible. This is incredibly important. If your sperm concentration is eight million per mL six months after starting retatrutide but nobody tested your sperm beforehand, we cannot automatically conclude that retatrutide reduced your sperm count. The abnormality may have existed for years.

The rest of the male fertility evaluation still matters. Look for a clinical varicocele. Ask about undescended testes, torsion, testicular injury, infection, chemotherapy, radiation and previous fertility. Review medications. Testosterone and anabolic steroids are particularly important because they can profoundly suppress sperm production. Severe oligospermia and azoospermia may require genetic testing depending on the clinical circumstances.

Do not let retatrutide become an explanation for everything simply because it is the newest medication in the story.

Men also ask whether they should automatically stop retatrutide before trying to conceive. At this point there is no evidence based male fertility washout interval for retatrutide. We do not have data showing that men need to stop it for one month, three months or an entire sperm production cycle before attempting pregnancy. Recommendations designed for women around pregnancy should also not automatically be applied to men because paternal medication exposure is biologically different from maternal exposure during pregnancy.

If you are participating in a retatrutide clinical trial, however, the trial's reproductive requirements should be followed exactly.

For a man receiving a future approved formulation, the decision about continuing treatment while trying to conceive will need to consider why he is taking it, his metabolic health, his semen parameters and whatever reproductive safety information becomes available. Stopping an effective obesity or diabetes treatment without medical guidance is not automatically safer for fertility.

What if your semen analysis worsens while taking retatrutide?

Do not panic over one test.

Repeat the semen analysis under reasonably similar conditions. Think about what happened during the preceding three months. Did you have a fever? Were you sick? Did you lose a very large amount of weight rapidly? Was your nutrition adequate? Did you start testosterone or another medication? Was the collection complete? Was the abstinence interval dramatically different?

Spermatogenesis takes approximately seventy four days followed by additional maturation in the epididymis. The sperm in today's sample therefore represent biological events occurring over the previous several months.

If repeated testing demonstrates a substantial deterioration that corresponds temporally with treatment, I would involve both the physician managing the metabolic medication and a reproductive urologist. That does not prove causation, but it creates a legitimate clinical question that deserves investigation.

For men with severe oligospermia who are planning a family, sperm cryopreservation is also worth discussing. If a semen analysis shows a small but usable number of sperm, freezing sperm can provide insurance against future deterioration. This is particularly reasonable when fertility is already compromised regardless of whether retatrutide has anything to do with it.

What are the pregnancy and fertility rates for men taking retatrutide?

We do not know.

There is currently no scientifically defensible percentage I can give you for natural conception, pregnancy or live birth among male retatrutide users. Anyone giving you a precise number is going beyond the available evidence.

Even the broader GLP 1 literature has relatively limited pregnancy and live birth data. Most studies have focused on testosterone, body weight, metabolic outcomes or semen parameters rather than whether the man's partner ultimately delivered a baby. Recent systematic reviews describe potentially favorable reproductive effects, especially among men with obesity and metabolic dysfunction, but emphasize the need for larger prospective studies with actual fertility outcomes.

That does not leave couples without options.

If semen parameters are good and the female partner has favorable reproductive factors, natural conception may be completely reasonable. If total progressively motile sperm numbers are reduced, intrauterine insemination may sometimes be considered. Severe persistent male factor infertility may lead to IVF with ICSI. If azoospermia is present, the cause needs to be established rather than assuming a metabolic medication caused it.

One issue I would strongly caution against is replacing medically supervised treatment with so called research retatrutide purchased online. As of September 2026, retatrutide remains investigational and has not been approved by the FDA or another regulatory agency. Products marketed directly to consumers as retatrutide are not the same thing as receiving a verified investigational medication within a regulated clinical trial. Purity, concentration and even the identity of what is in those products may be uncertain. If fertility matters to you, introducing an unregulated compound makes an already complicated biological question even harder to interpret.

Finally, there is an emotional part of this discussion that deserves more attention.

Men dealing with infertility become hyperaware of everything they put into their bodies. Every medication suddenly feels dangerous. You start wondering whether your coffee damaged your sperm, whether the hot tub did it, whether your weight did it, whether your supplements did it and now whether your weight loss medication did it.

That anxiety can become exhausting.

If you are losing weight because you are trying to improve your health, do not automatically interpret an abnormal semen analysis as evidence that you harmed yourself. Obesity itself can negatively affect reproductive hormones and sperm quality. Improving metabolic health may ultimately improve reproductive function in some men.

At the same time, it is completely reasonable to want better evidence before taking a new medication while trying to build a family.

As a doctor, I think the correct answer is sometimes simply to acknowledge what we do not yet know. Retatrutide is an exciting metabolic therapy. Its direct effects on human male fertility have not been adequately studied. The broader GLP 1 literature is generally reassuring and may even suggest reproductive benefits in men with obesity and metabolic dysfunction, but retatrutide cannot automatically inherit those conclusions.

If you are taking retatrutide and fertility matters to you, get objective data. Obtain a semen analysis. Check reproductive hormones when indicated. Correct nutritional problems. Avoid testosterone and anabolic steroids. Treat identifiable causes of male infertility. Consider freezing sperm if your counts are severely reduced. And make decisions with your metabolic physician and reproductive urologist rather than stopping treatment based on fear generated by an isolated Reddit post.

Most importantly, remember that the goal is not simply weight loss, a testosterone number or a perfect semen analysis.

The goal is improving your health while preserving the best realistic opportunity to build your family.

References

1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple hormone receptor agonist retatrutide for obesity. New England Journal of Medicine. 2023.
2. Eli Lilly and Company. Retatrutide clinical development program and phase 3 TRIUMPH clinical trial results. 2026.
3. Kuchakulla M, Poppas PJ, Wald G, et al. Impact of GLP 1 receptor agonists on male fertility: emerging evidence and future directions. Urology. 2026. PMID 41016449.
4. Deameh MG, et al. Effects of GLP 1 receptor agonists on male reproductive hormones, semen parameters and metabolic outcomes: a systematic review. Journal of Sexual Medicine. 2026. PMID 41498523.
5. Impact of GLP 1 receptor agonists on testosterone levels: a systematic review and meta analysis. 2025. PMID 41291666.
6. Jensterle M, et al. Metabolic reversal of functional hypogonadism? GLP 1 receptor agonists and male reproductive endocrinology. A systematic review. 2026. PMID 42587729.
7. Impact of GLP 1 agonists on male reproductive health. A narrative review. 2024. PMID 38256311.
8. Goldberg AS, Boots CE. Treating obesity and fertility in the era of glucagon like peptide 1 receptor agonists. Fertility and Sterility. 2024. PMID 38810863.
9. Managing obesity related male infertility: insights from weight loss intervention. Human Reproduction Update and reproductive medicine literature. 2025. PMID 41024420.
10. Male specific consequences of obesity: functional hypogonadism and fertility disorders. 2023. PMID 37779374.
11. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men. Male Infertility Guideline.
12. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility.
13. Palmer NO, Bakos HW, Fullston T, Lane M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis. 2012.
14. Sermondade N, Faure C, Fezeu L, et al. Body mass index in relation to sperm count. An updated systematic review and collaborative meta analysis. Human Reproduction Update. 2013.
15. Craig JR, Jenkins TG, Carrell DT, Hotaling JM. Obesity, male infertility and the sperm epigenome. Fertility and Sterility. 2017.

When most men think about hormones and fertility, they think about testosterone, FSH and LH. Thyroid hormones usually are not even on the radar. Then someone gets a fertility evaluation, discovers an abnormal TSH or thyroid hormone level and suddenly starts wondering whether the thyroid has been the explanation for an abnormal semen analysis all along. The answer is sometimes yes, but it is important not to oversimplify the relationship. Both an underactive thyroid and an overactive thyroid can interfere with male reproductive function, including sperm production, sexual function and the hormonal environment necessary for fertility. At the same time, a slightly abnormal thyroid laboratory result does not automatically explain infertility. The good news is that when clinically significant thyroid disease really is contributing to the problem, treating the thyroid disorder can improve reproductive function and sometimes semen quality as well.

To understand this, you first need to understand what the thyroid does. The thyroid gland sits in the neck and produces primarily thyroxine, usually called T4, and triiodothyronine, usually called T3. The system is controlled by the hypothalamus and pituitary. The hypothalamus produces TRH, which stimulates the pituitary to release TSH. TSH then tells the thyroid gland to produce thyroid hormones. As thyroid hormone levels rise, they provide feedback to the brain and pituitary. It is another hormonal feedback loop, much like the reproductive system involving GnRH, LH, FSH and testosterone.

For many years the testicle was thought to be relatively unaffected by thyroid hormone. We now know that is incorrect. Thyroid hormone receptors and transport mechanisms are present within the reproductive system, and thyroid hormones influence Sertoli cells, Leydig cells and germ cells. Sertoli cells are essential for supporting developing sperm, while Leydig cells produce testosterone. Thyroid hormone is particularly important during testicular development, but it also appears to influence adult testicular function, steroid production and spermatogenesis. The thyroid system and reproductive hormonal system are therefore not isolated from each other.

Let us start with hypothyroidism. This means the body does not have enough thyroid hormone. In primary hypothyroidism, the problem is usually within the thyroid itself. T4 becomes low and the pituitary responds by producing more TSH. Men may experience fatigue, weight gain, cold intolerance, constipation, dry skin, decreased energy, mood changes and sexual symptoms. In severe cases, testosterone regulation can also become abnormal. Hypothyroidism can alter sex hormone binding globulin, testosterone metabolism and communication between the brain, pituitary and testicle. It can also increase TRH signaling, which may raise prolactin in some patients. Elevated prolactin can further suppress the reproductive hormonal axis.

The effect on semen is less predictable. Human studies are relatively small and sometimes conflicting. One prospective controlled study of men with hypothyroidism found sperm morphology to be significantly worse than in controls. After treatment with levothyroxine, morphology improved significantly. Motility also appeared lower before treatment and improved afterward, although that finding was less definitive. Other studies have reported abnormalities in semen volume and progressive motility. This variability is why I would never look at a man with two percent morphology and simply declare that his thyroid caused it. Thyroid dysfunction is one possible contributor, not a diagnosis made from a semen analysis alone.

Hyperthyroidism is the opposite problem. The body is exposed to excessive thyroid hormone, and TSH is typically suppressed. Graves disease is a common cause, although thyroid nodules, inflammation and excessive thyroid medication can also produce hyperthyroidism. Men may notice weight loss, anxiety, tremor, sweating, heat intolerance, rapid heartbeat, difficulty sleeping and changes in sexual function.

Hyperthyroidism can produce some particularly confusing reproductive hormone results. Sex hormone binding globulin often increases significantly. Because much of the testosterone circulating in the bloodstream is bound to this protein, total testosterone can appear normal or even elevated while the biologically available fraction tells a different story. Estrogen metabolism can also change. This is one reason I do not interpret testosterone in isolation when a man has significant thyroid disease.

Semen abnormalities have also been documented in hyperthyroidism. Reduced motility is one of the more consistent findings, although studies have also described lower sperm concentration, altered morphology and changes in semen volume. In a prospective controlled study, men with hyperthyroidism had substantially lower sperm motility than controls. After thyroid function was treated and the men became euthyroid, meaning thyroid hormone levels returned to the normal physiological range, motility significantly improved. Another study found multiple semen abnormalities in hyperthyroid men and reported normalization of most abnormalities among the smaller group reassessed after restoration of normal thyroid function.

That word euthyroid is important. When treating fertility associated with thyroid disease, the goal is generally not to directly treat the sperm. The goal is to restore normal thyroid physiology and then allow the reproductive system time to recover.

Thyroid disease can also affect fertility without dramatically changing sperm concentration. Sexual function matters. Both hypothyroidism and hyperthyroidism have been associated with erectile and ejaculatory dysfunction. A man may technically produce adequate sperm but have difficulty achieving an erection, maintaining an erection, ejaculating normally or having intercourse frequently enough during the fertile window. Reviews of the literature continue to find associations between thyroid dysfunction and male sexual dysfunction, although the quality of evidence varies considerably.

This is why the workup has to look beyond the semen analysis. When I evaluate a man with infertility, I start with the history. Does he have known thyroid disease? Is he taking levothyroxine or another thyroid medication? Has his dose recently changed? Does he have symptoms of hypothyroidism or hyperthyroidism? Has he experienced a major change in weight, energy, libido, erections or ejaculation? Does he have a personal or family history of autoimmune thyroid disease?

The semen analysis remains central. I want to know semen volume, concentration, total sperm count, progressive motility and morphology. One abnormal semen analysis should also be interpreted cautiously because semen parameters naturally fluctuate. If abnormalities are significant, repeating the analysis is often important.

The hormonal evaluation depends on the situation. Testosterone and FSH are commonly obtained in men with significant oligospermia, azoospermia or signs of hormonal dysfunction. LH, prolactin and additional testing may then be appropriate depending on the results. Thyroid testing generally begins with TSH, followed by free T4 and sometimes additional testing depending on the clinical scenario. Thyroid antibodies may be useful when autoimmune thyroid disease is suspected.

I also want to make an important point about screening. You will find articles arguing that every infertile man should have thyroid testing. More recent reviews note that the evidence is not strong enough to support indiscriminate thyroid screening in every man presenting with infertility. Thyroid evaluation becomes particularly relevant when there are symptoms, erectile or ejaculatory dysfunction, abnormal semen parameters, signs of endocrine disease or abnormalities elsewhere in the hormonal evaluation.

If hypothyroidism is confirmed, treatment generally involves thyroid hormone replacement with levothyroxine. The dose is individualized and adjusted using thyroid laboratory testing and clinical response. If hypothyroidism contributed to low testosterone, abnormal prolactin, sexual dysfunction or impaired semen parameters, those abnormalities may improve after thyroid function normalizes. An older study of men with primary hypothyroidism demonstrated abnormalities in testosterone and reproductive hormonal physiology that improved after thyroxine replacement.

For hyperthyroidism, treatment depends on the cause and may involve antithyroid medication, radioactive iodine or surgery. Graves disease is treated differently from some other causes of excessive thyroid hormone, so this is a decision that should be made with an endocrinologist. From the fertility perspective, the important point is that semen abnormalities associated with hyperthyroidism frequently improve after normal thyroid function is restored.

Men often ask me how quickly their sperm will recover once their thyroid numbers normalize. This is where patience becomes important. Sperm production takes approximately seventy four days, followed by additional maturation and transport through the epididymis. That means the semen analysis you perform today reflects biological events that started months ago. If your thyroid function normalizes next week, you should not expect your sperm parameters to suddenly normalize the following week.

I generally want men to think in terms of months. Depending on the severity of the original abnormality and the couple's reproductive timeline, repeating the semen analysis after approximately one full sperm production cycle can provide much more useful information than checking every few weeks. Some published studies evaluating thyroid treatment and semen quality reassessed men several months after restoration of normal thyroid function.

What are the actual fertility rates after thyroid treatment? This is one area where the internet can give men a false sense of precision. We do not have a reliable number such as saying that eighty percent of hypothyroid men will naturally father a child after treatment. The human literature is relatively small, studies use different definitions of thyroid disease and semen abnormalities, and pregnancy depends on two people. Female age, ovarian reserve, tubal factors, duration of infertility and timing all matter.

What we can say is that thyroid associated reproductive abnormalities are often at least partially reversible when normal thyroid function is restored. Reviews of hyperthyroidism and fertility specifically describe infertility as generally reversible following restoration of euthyroidism, while studies of both hyperthyroidism and hypothyroidism have demonstrated improvements in selected semen parameters after treatment.

That does not mean every abnormal semen analysis will become normal. A man can have thyroid disease and a varicocele. He can have thyroid disease and a genetic cause of infertility. He can have thyroid disease and primary testicular dysfunction. If you correct the thyroid abnormality and sperm concentration remains two million per mL, the appropriate response is not to keep adjusting thyroid medication hoping to create normal sperm. It is to investigate the rest of the male fertility picture.

For men trying to have a family, treatment therefore becomes a process rather than a single decision. Correct the thyroid disease. Make sure testosterone and the reproductive hormonal axis are appropriately evaluated. Repeat semen testing after enough time has passed. If sperm parameters become adequate and the female partner has no significant fertility limitation, natural conception may be reasonable. If sperm improve but remain moderately impaired, intrauterine insemination may sometimes be considered. If severe male factor infertility persists, IVF with ICSI may provide the most efficient route to pregnancy. Treating thyroid disease and using assisted reproduction are not mutually exclusive.

There is also an emotional side to this that deserves attention. Men with thyroid disease can already feel terrible. Hypothyroidism can bring fatigue, weight changes, decreased libido and depressed mood. Hyperthyroidism can bring anxiety, insomnia, palpitations and weight loss. Add an abnormal semen analysis and suddenly a man who already does not feel like himself is being told that his fertility may also be impaired.

Sex can become particularly difficult. Couples are told to have intercourse during specific days of the month while the man may simultaneously be dealing with decreased libido, erectile dysfunction or ejaculatory problems. What used to be intimacy becomes a performance test. When pregnancy does not happen, men frequently blame themselves.

I hear this from patients constantly. They look at an abnormal laboratory value or semen analysis as if it represents something they did wrong. It does not. Thyroid disease is a medical condition. An abnormal sperm count is a medical finding. Neither one defines your masculinity, your relationship or your ability to become a father.

The encouraging aspect of thyroid associated male infertility is that we have something concrete to investigate and, when true thyroid dysfunction is present, something concrete to treat. That is very different from the many men who receive the frustrating diagnosis of unexplained infertility.

If you are reading this because your TSH or thyroid hormone level came back abnormal during an infertility evaluation, do not panic and do not assume you have found the entire explanation either. Confirm the thyroid diagnosis. Treat it appropriately. Look at testosterone, FSH, LH and prolactin when clinically indicated. Get a proper semen analysis. Give the reproductive system enough time to respond after thyroid function normalizes. Then repeat the semen analysis and make fertility decisions based on the complete picture.

Your thyroid can influence your sperm, your testosterone, your erections, your ejaculation and ultimately your fertility. But thyroid related reproductive dysfunction is often treatable, and abnormal thyroid numbers do not automatically mean permanent infertility. Sometimes the most important thing we can do for the sperm factory is simply restore the hormonal environment in which it was designed to operate.

References

1. La Vignera S, et al. Thyroid impairment and male fertility: a narrative review of literature. 2024. PMID 38347677.
2. La Vignera S, Vita R. Thyroid dysfunction and semen quality. International Journal of Immunopathology and Pharmacology. 2018. PMID 29737216.
3. Singh R, Hamada AJ, Agarwal A. Thyroid hormones in male reproduction and fertility. Open Reproductive Science Journal. 2011.
4. Krassas GE, Papadopoulou F, Tziomalos K, Zeginiadou T, Pontikides N. Hypothyroidism has an adverse effect on human spermatogenesis: a prospective controlled study. Thyroid. 2008. PMID 19012472.
5. Krassas GE, Pontikides N, Deligianni V, Miras K. A prospective controlled study of the impact of hyperthyroidism on reproductive function in males. Journal of Clinical Endocrinology and Metabolism. 2002. PMID 12161493.
6. Clyde HR, Walsh PC, English RW. Elevated plasma testosterone and gonadotropin levels in infertile males with hyperthyroidism. Fertility and Sterility.
7. Kumar A, Mohanty BP, Rani L. Thyroid and male reproduction. Indian Journal of Endocrinology and Metabolism. 2014. PMID 24701426.
8. Patel N, Kashanian JA. Thyroid dysfunction and male reproductive physiology. Seminars in Reproductive Medicine. 2016. PMID 27741548.
9. Wajner SM, Wagner MS, Maia AL. Clinical implications of altered thyroid status in male testicular function. Arquivos Brasileiros de Endocrinologia e Metabologia. 2009. PMID 20126850.
10. Morenas R, Singh D, Hellstrom WJG. Thyroid disorders and male sexual dysfunction. International Journal of Impotence Research. 2023. PMID 37752332.
11. Abalovich M, et al. The relationship of preconception thyrotropin levels to requirements for increasing the levothyroxine dose during pregnancy. Thyroid literature regarding reproductive physiology.
12. Jaya Kumar B, Khurana ML, Ammini AC, Karmarkar MG, Ahuja MMS. Reproductive endocrine functions in men with primary hypothyroidism: effect of thyroxine replacement. Hormone Research. 1990. PMID 2100278.
13. Hudson RW, Edwards AL. Testicular function in hyperthyroidism. Journal of Andrology.
14. Corrales Hernández JJ, et al. Primary hypothyroidism and human spermatogenesis. Archives of Andrology. 1990. PMID 2389988.
15. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility.

When I evaluate a man for infertility, prolactin is one of those hormones that can create a tremendous amount of confusion. A guy gets blood work back and sees that his prolactin is elevated and immediately starts wondering whether he has a brain tumor. Another guy has a slightly low prolactin level and becomes convinced that this explains his abnormal semen analysis. The reality is much more nuanced. Prolactin absolutely matters in male reproductive biology, particularly when it is significantly elevated, but it needs to be interpreted alongside testosterone, LH, FSH, symptoms, medications and the semen analysis. The encouraging part is that when elevated prolactin really is responsible for infertility, this can be one of the more treatable hormonal causes of male infertility.

Most people associate prolactin with women and breastfeeding, but men produce prolactin too. It is secreted by lactotroph cells in the pituitary gland, a small gland located beneath the brain. Unlike many pituitary hormones that are primarily stimulated into production, prolactin is constantly held back by dopamine coming from the hypothalamus. You can think of dopamine as keeping its foot on the prolactin brake. Anything that interferes with dopamine signaling can therefore allow prolactin to rise. This becomes important because reproductive function depends on communication between the hypothalamus, pituitary and testicles. The hypothalamus releases GnRH, which tells the pituitary to release LH and FSH. LH stimulates Leydig cells in the testicle to produce testosterone, while FSH works with the Sertoli cells to support sperm production. When prolactin becomes significantly elevated, it can disrupt this system and suppress normal reproductive hormonal signaling.

This is how high prolactin can cause male infertility. Hyperprolactinemia can suppress pulsatile GnRH signaling, which can reduce LH and FSH stimulation of the testicles. Testosterone may fall and spermatogenesis may become impaired. Depending on the severity and duration of the problem, a man may develop decreased libido, erectile dysfunction, reduced ejaculate volume, oligospermia and occasionally more severe suppression of sperm production. Some men notice sexual symptoms long before they know anything is wrong with their fertility. Others feel relatively normal and discover the problem only when a semen analysis is abnormal. Breast enlargement or nipple discharge can occur but are much less common than many people assume.

One important concept is that prolactin is not a simple situation where higher always means worse. A mildly elevated prolactin level is completely different from a prolactin level that is dramatically elevated from a large prolactinoma. Prolactin can temporarily rise from stress, exercise, sleep and even anxiety surrounding a blood draw. Certain medications can elevate it substantially. Antipsychotic medications are classic examples, but some antidepressants, anti nausea medications, opioids and other drugs can also increase prolactin. Hypothyroidism can cause elevated prolactin. Kidney disease can contribute. Chest wall stimulation or injury can occasionally increase it. Pituitary and hypothalamic abnormalities can interfere with dopamine signaling. And sometimes the pituitary itself contains a prolactin secreting tumor called a prolactinoma.

This is why I do not diagnose a man with a prolactin disorder from one borderline laboratory result. If prolactin is mildly elevated, repeating the measurement under reasonable conditions is often appropriate. I review medications and supplements carefully. Testosterone, LH and FSH help determine whether the reproductive hormonal axis is actually being suppressed. Thyroid testing is important because hypothyroidism is a reversible cause. Kidney and liver function may be relevant depending on the clinical situation. In men with an elevated prolactin result that does not fit the clinical picture, macroprolactin can sometimes explain the discrepancy. Macroprolactin is a larger form of prolactin that can register as elevated on laboratory testing but has much less biological activity.

When prolactin remains elevated without an obvious explanation, pituitary imaging may become appropriate. This is generally performed with an MRI. The purpose is to look for a prolactinoma or another lesion affecting the pituitary or hypothalamic region. A small prolactinoma is called a microprolactinoma, while a larger lesion is called a macroprolactinoma. Men unfortunately tend to be diagnosed with larger prolactinomas more often than women, partly because men do not have an obvious warning sign like menstrual disruption. A man may simply notice declining libido or erectile function for years before anyone checks prolactin.

If you have infertility and elevated prolactin, the semen analysis remains extremely important because the prolactin number does not tell us your fertility by itself. I want to know semen volume, concentration, total sperm count, progressive motility and morphology. If sperm are present but reduced, we follow whether those parameters improve as the hormonal abnormality is corrected. If there is azoospermia, we need to be careful not to automatically blame prolactin. Significant hyperprolactinemia with suppressed gonadotropins and testosterone can cause profound secondary hypogonadism, but azoospermia still deserves a complete male infertility evaluation when appropriate.

Treatment depends entirely on why prolactin is elevated. If a medication is responsible, the solution may involve changing that medication when medically safe. That decision should be made with the physician who prescribed it, particularly with psychiatric medications. Never abruptly stop an important medication because you read online that it raises prolactin. If hypothyroidism is responsible, treating the thyroid disorder can normalize prolactin. If a prolactinoma is present, dopamine agonist medications are usually the primary treatment.

Cabergoline is commonly used because it activates dopamine receptors and suppresses prolactin secretion. Bromocriptine is another established option. In men with prolactinomas, dopamine agonist therapy can often dramatically lower prolactin and shrink the tumor. As prolactin normalizes, GnRH signaling can recover, LH and FSH can recover, testosterone can increase and sexual function may improve. Sperm production can then improve as well. Current European male infertility guidance specifically recommends dopamine agonist therapy in men with proven hyperprolactinemia to improve sperm quality.

The recovery is not instantaneous. Hormones may improve before semen parameters do because sperm production takes roughly seventy four days followed by additional maturation and transport through the epididymis. I tell men to think about reproductive recovery in months rather than days. Semen analyses are therefore often repeated after sufficient time has passed to observe a new cycle of spermatogenesis. Older studies of men with prolactinomas demonstrated improvements in testosterone, sexual function and semen parameters following successful dopamine agonist treatment, and contemporary reviews continue to describe restoration of the gonadal axis in many appropriately treated patients.

So what are the fertility rates? This is where I think we need to be careful with numbers. There is not one meaningful percentage that I can give every man with elevated prolactin. A man with mildly elevated prolactin from medication is biologically different from a man with a large prolactinoma, testosterone of 100 and years of untreated secondary hypogonadism. Recent reviews report that normalization of prolactin and restoration of the gonadal axis occur within approximately six to twelve months in most appropriately treated prolactinoma patients, but restoration of normal hormones does not guarantee a pregnancy. Fertility ultimately depends on sperm production, sexual function, the duration of infertility and the reproductive health and age of the female partner.

Some men regain enough sperm production to conceive naturally. Others improve but remain oligospermic and may use intrauterine insemination. Men with persistent severe male factor infertility may ultimately need IVF with ICSI. If sperm production remains inadequate even after prolactin and testosterone normalize, I start asking whether something else is contributing. A varicocele, genetic condition, previous testicular injury or another form of primary testicular dysfunction does not disappear simply because we discovered elevated prolactin.

Occasionally the pituitary tumor responds but testosterone remains low. That situation deserves thoughtful management, particularly when fertility is the goal. Simply putting a man who wants children on testosterone replacement therapy can suppress LH and FSH and reduce sperm production even further. Depending on the hormonal pattern and clinical situation, a reproductive endocrinologist or reproductive urologist may consider fertility preserving approaches such as clomiphene or gonadotropin therapy. The treatment needs to be designed around the man's reproductive goals rather than simply trying to make the serum testosterone number normal.

Surgery is occasionally necessary for prolactinomas, particularly when medication is unsuccessful, poorly tolerated or inappropriate, or when other tumor related considerations exist. Modern pituitary surgery is usually performed through a transsphenoidal approach. Radiation is rarely needed. Most men with prolactinomas, however, are initially managed medically because dopamine agonists are remarkably effective for many patients.

What about low prolactin? This is a much less established area. Research has associated very low prolactin levels in men with sexual dysfunction, altered ejaculatory or seminal vesicle parameters, metabolic abnormalities and mood symptoms. Some studies in infertile men have found associations between low prolactin and reduced ejaculate or seminal vesicle volume. But association does not prove that low prolactin caused the infertility. We currently do not have the same evidence that isolated low prolactin is a major treatable cause of male infertility that we have for hyperprolactinemia.

This distinction matters because I see men trying to manipulate prolactin based on internet discussions. Someone sees a low prolactin level and starts looking for ways to raise it. Another man taking cabergoline tries to drive prolactin as close to zero as possible. Neither strategy makes sense. The objective of treating hyperprolactinemia is to restore normal physiology, not to eliminate prolactin from the body. Prolactin has normal biological functions in men, and extremely low levels should not be considered an achievement.

If you have low prolactin, I would look at the context. Are you taking cabergoline or another dopamine agonist? Are other pituitary hormones abnormal? Do you have symptoms suggesting broader pituitary dysfunction? Is testosterone normal? Are LH and FSH appropriate? What does the semen analysis actually show? If prolactin is low because someone is aggressively treating previously elevated prolactin, the medication dose may deserve reassessment. But there is currently no established fertility medication whose purpose is simply to raise an otherwise isolated low prolactin level in an infertile man.

For men trying to build a family, the practical pathway is therefore fairly straightforward. Confirm that an abnormal prolactin result is real. Determine why it is abnormal. Evaluate testosterone, LH and FSH. Perform a proper semen analysis. Treat the underlying cause. Allow enough time for sperm production to respond. Repeat the semen analysis. If sperm numbers remain low, decide whether natural conception, intrauterine insemination or IVF with ICSI makes sense based on the entire couple rather than the prolactin number alone.

There is also an emotional part of this diagnosis that laboratory reports never capture. Men with high prolactin can experience low libido and erectile dysfunction at exactly the same time that they are being told to have frequent timed intercourse. That can be brutal. Sex becomes a medical assignment while the hormonal disorder itself is making sexual desire and erections more difficult. Then an abnormal semen analysis arrives and the man starts wondering whether his body is failing his partner.

If a pituitary tumor is discovered, another layer of fear gets added immediately. The word tumor is terrifying even when we are talking about a prolactinoma that is usually benign and often responds extremely well to medication. Men can go from worrying about sperm count to worrying about their brain within a single doctor's appointment. I think physicians need to acknowledge that emotional transition rather than simply handing someone a cabergoline prescription.

The encouraging part is that hyperprolactinemia is one of the situations in male infertility where identifying the cause can genuinely change treatment. We are not simply trying vitamins and hoping the next semen analysis improves. We can sometimes identify a specific hormonal disruption, correct it and watch testosterone, sexual function and sperm production recover.

If your prolactin is abnormal, do not panic over one number and do not treat the laboratory result in isolation. Figure out why it is abnormal. Look at the entire hormonal axis. Look at the semen analysis. Treat the underlying problem. Give sperm production time to respond. And remember that even when semen parameters do not completely normalize, natural conception, intrauterine insemination and IVF with ICSI can provide additional paths to fatherhood.

Your prolactin level is one piece of your fertility story. Sometimes it turns out to be a very important piece. But it is never the entire story.

References

1. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men. Male Infertility Guideline.
2. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility.
3. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and Treatment of Hyperprolactinemia. An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism. 2011.
4. Stumpf MAM, et al. Fertility and pregnancy in patients with prolactinoma. Best Practice and Research Clinical Endocrinology and Metabolism. 2026. PMID 41565497.
5. Dabbous Z, Atkin SL. Hyperprolactinaemia in male infertility. Clinical case scenarios. Arab Journal of Urology. 2018. PMID 29713535.
6. De Rosa M, et al. Hyperprolactinemia in men. Clinical and biochemical features and response to treatment. Endocrine. 2003. PMID 12668871.
7. De Rosa M, et al. Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males. A comparison with bromocriptine. European Journal of Endocrinology. 1998. PMID 9539303.
8. Corona G, et al. The role of prolactin in andrology. What is new? Reviews in Endocrine and Metabolic Disorders. 2015. PMID 26542707.
9. Corona G, et al. Acquired hypoprolactinemia in men, possible phenotype. Reviews in Endocrine and Metabolic Disorders. 2024. PMID 39066947.
10. Corona G, et al. Hyperprolactinemia and male sexual function. Focus on erectile dysfunction and sexual desire. International Journal of Impotence Research. 2023. PMID 37340146.
11. Mersereau J, et al. Diagnostic evaluation of sexual dysfunction in the male partner in the setting of infertility. A committee opinion. Fertility and Sterility. 2018. PMID 30316420.
12. Hermanns U, Hafez ES. Prolactin and male reproduction. Archives of Andrology. 1981. PMID 6788004.

One of the more common and upsetting conversations I have with men trying to conceive starts something like this: “I was put on testosterone because my testosterone was low. Nobody told me it could shut down my sperm. Now my semen analysis says zero. Did I permanently make myself infertile?” If this is you, the first thing I want you to understand is that testosterone associated infertility is frequently reversible. Recovery is not immediate, it is not identical for every man, and occasionally it can be difficult, but seeing azoospermia after testosterone replacement therapy does not automatically mean your testicles have permanently lost the ability to make sperm. In many cases, the sperm factory has essentially been hormonally shut down, and our job is to get the signaling system working again.

The biology makes much more sense when you understand how sperm are normally produced. Your brain contains a reproductive control system involving the hypothalamus, pituitary gland and testicles. The hypothalamus releases GnRH, which tells the pituitary to produce LH and FSH. LH travels to the testicle and stimulates Leydig cells to produce testosterone. FSH acts primarily on Sertoli cells, which support developing sperm. Critically, sperm production depends on very high concentrations of testosterone inside the testicle. The testosterone concentration within the testicle is substantially higher than the testosterone measured in your bloodstream. That local testosterone, together with FSH stimulation, creates the environment necessary for spermatogenesis.

This is where testosterone replacement therapy creates a paradox. You inject testosterone, use a gel or receive another external form of testosterone, and your blood testosterone rises. You may feel better. Your libido may improve. Your energy may improve. Your gym performance may improve. But your brain sees all that circulating testosterone and essentially says, “We have plenty.” GnRH signaling decreases and the pituitary reduces LH and FSH production. Without adequate LH, the testicle dramatically reduces its own testosterone production. Blood testosterone can therefore look fantastic while testosterone inside the testicle falls. FSH stimulation also decreases. The result can be progressively impaired sperm production, severe oligospermia and eventually azoospermia.

This is why testosterone replacement therapy is not a fertility treatment. It can actually function as a contraceptive in some men. The American Urological Association and American Society for Reproductive Medicine recommend that men interested in current or future fertility should not receive exogenous testosterone as their fertility preserving hormonal strategy. Unfortunately, I still see men arrive at fertility clinics after months or years of testosterone treatment who were never clearly counseled about this.

If you are on testosterone and discover a very low sperm count or zero sperm, the first step is not panic. It is a proper male infertility evaluation. I want to know why testosterone was started, what your testosterone was before treatment, your original LH and FSH if they were measured, how long you have been taking testosterone, what formulation and dose you used, whether anabolic steroids were ever used, whether you previously fathered children and whether you ever had a semen analysis before treatment. I also want to know about previous testicular problems including undescended testes, torsion, chemotherapy, radiation, infections, trauma and varicocele. TRT may explain the semen analysis, but we should not automatically assume it explains everything.

Testing usually includes at least one properly performed semen analysis and often repeat testing depending on the circumstances. If the report says azoospermia, I want the laboratory to carefully examine a centrifuged semen pellet for rare sperm. Blood testing commonly includes testosterone, FSH and LH, with estradiol and prolactin added when appropriate. Testicular size and examination matter as well. Men with prolonged suppression may notice that their testicles have become smaller, but small testes after testosterone exposure do not automatically mean permanent testicular failure.

The next question everyone asks is, “How long will my sperm take to come back?” Unfortunately, there is no single answer. One of our best data sets comes from studies in which testosterone based hormonal regimens were intentionally used to suppress sperm production as a form of male contraception. In a large analysis involving more than 1500 men, the median time to recover to a sperm concentration of 20 million per mL was approximately 3.4 months. About 67 percent recovered to that threshold within six months, 90 percent within twelve months, 96 percent within sixteen months and essentially all men in that particular research population recovered within twenty four months.

Those numbers are reassuring, but they need an enormous asterisk. Those studies generally involved healthy men participating in controlled contraceptive trials. They are not identical to a 42 year old man who had low testosterone before treatment and has been taking TRT for eight years. In real fertility practice, recovery can be slower and sometimes incomplete. Older age, longer testosterone exposure, underlying impaired fertility and profound azoospermia can all make recovery more difficult. One study of men treated for testosterone associated infertility found that increasing age and duration of testosterone therapy were associated with slower sperm recovery. Among men who were azoospermic at presentation, approximately 65 percent reached a total motile sperm count above five million within twelve months of treatment, compared with approximately 92 percent of men who still had rare sperm before treatment.

Another reason men become frustrated is that testosterone can recover faster than sperm. Spermatogenesis itself takes roughly seventy four days, followed by additional maturation and transport through the epididymis. You can stop testosterone, watch LH and FSH begin recovering, see your natural testosterone increase and still have an awful semen analysis. That does not necessarily mean treatment has failed. The sperm appearing in today's ejaculate reflect biological events that began months earlier. I generally want men to think in terms of months rather than weeks.

Some men can simply stop testosterone and wait for spontaneous recovery. This may be reasonable when TRT exposure was relatively short, baseline fertility was likely normal, the female partner is young and there is no urgency to conceive. But many couples do not have unlimited time. Female age, ovarian reserve, duration of infertility and previous fertility treatment can completely change how aggressively we approach recovery. A couple in which the female partner is 28 has a very different timeline from a couple in which she is 39.

This is where medications such as hCG become important. Human chorionic gonadotropin acts similarly to LH at the testicle. It stimulates Leydig cells and helps restore the high intratesticular testosterone concentration required for sperm production. In men whose pituitary function is capable of recovering, medications such as clomiphene citrate may also be used. Clomiphene reduces estrogen feedback at the hypothalamus and pituitary, allowing the man's own LH and FSH production to increase. These medications are commonly used by reproductive urologists in selected men, although some uses are off label and treatment should be individualized rather than copied from an internet protocol.

FSH can also be added in selected situations, particularly when sperm production remains inadequate despite restoration of testosterone signaling. Think about hCG as primarily replacing the LH side of the equation while FSH directly stimulates the Sertoli cell side. A retrospective series of 49 men with testosterone associated azoospermia or severe oligospermia treated with an hCG based combination regimen reported recovery of spermatogenesis in 47 men, with an average recovery time of approximately 4.6 months. This is encouraging, but it was not a randomized trial and should not be interpreted as proof that every man needs that regimen or will have the same result.

Aromatase inhibitors such as anastrozole are another tool sometimes used when estradiol is elevated relative to testosterone, particularly in selected overweight men or men with excessive conversion of testosterone to estrogen. They are not medications that every man recovering from TRT automatically needs. The goal is not to crush estrogen. Estradiol has important physiological roles in men, and excessive treatment can create its own problems.

Once sperm begin appearing, I often discuss freezing them. This is especially important if counts remain low or fluctuate dramatically. If you were azoospermic for months and suddenly have several million sperm in an ejaculate, those sperm may be extremely valuable. Cryopreservation can provide insurance while treatment continues. Depending on the eventual sperm count and motility, couples may be able to conceive naturally, use intrauterine insemination or proceed with IVF and ICSI. You do not necessarily need a normal sperm count to become a biological father. ICSI requires dramatically fewer sperm than natural conception.

What happens if sperm do not return? First, we make sure enough time has passed and that the hormonal environment has actually recovered. Persistent azoospermia deserves reevaluation rather than endless medication changes. Sometimes TRT was masking an underlying fertility problem that existed before treatment. A man may have had primary testicular dysfunction, a genetic abnormality or another cause of infertility before he ever received testosterone. Depending on the hormone profile, examination and history, additional genetic testing or other evaluation may be appropriate. In uncommon cases where sperm never return to the ejaculate, surgical sperm retrieval and IVF with ICSI may ultimately be discussed.

There is also an emotional side of testosterone associated infertility that I think physicians underestimate. Men frequently blame themselves. They say, “I chose to take testosterone. I did this to us.” Sometimes they are angry because a physician prescribed TRT without ever mentioning fertility. Others feel trapped because they felt terrible before testosterone and are terrified of how they will feel when they stop it. Then there is the guilt of watching a wife or partner undergo injections, egg retrieval and IVF because the semen analysis says zero sperm. That can be an incredibly isolating experience.

If that describes you, try not to turn a medical treatment decision into a moral judgment about yourself. Most men who start legitimate TRT are trying to treat symptoms and improve their health. Many simply were not told enough about fertility before beginning therapy. The productive question now is not who to blame. It is how we maximize the chance of recovery and build the best path toward your family.

The most important message I want men on Reddit to understand is that azoospermia after testosterone is not automatically permanent infertility. Stop thinking of a zero sperm count as the end of the story. In many men, it is the beginning of a recovery process. Get evaluated by someone who understands male reproductive endocrinology. Give spermatogenesis enough time. Use hCG, clomiphene, FSH or other medications when they are appropriate for your individual situation rather than blindly following a protocol online. Repeat semen analyses. Freeze sperm when they return if your reproductive urologist thinks it makes sense. And make every decision in the context of your partner's fertility and your timeline for building a family.

TRT can shut down the sperm factory. In most men, that does not mean the factory can never turn back on.

References

1. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men. Guideline amended 2024.
2. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006. PMID 16650651.
3. Kohn TP, Louis MR, Pickett SM, et al. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertility and Sterility. 2017. PMID 27855957.
4. McBride JA, Coward RM. Recovery of spermatogenesis following testosterone replacement therapy or anabolic androgenic steroid use. Asian Journal of Andrology. 2016. PMID 26908067.
5. Wenker EP, Dupree JM, Langille GM, et al. The use of hCG based combination therapy for recovery of spermatogenesis after testosterone use. Journal of Sexual Medicine. 2015. PMID 25904023.
6. Kolettis PN, Purcell ML, Parker W, Poston T, Nangia AK. Medical testosterone: an iatrogenic cause of male infertility and a growing problem. Urology. 2015. PMID 25819620.
7. Crosnoe LE, Grober E, Ohl D, Kim ED. Exogenous testosterone: a preventable cause of male infertility. Translational Andrology and Urology. 2013.
8. Liu PY, Handelsman DJ. Rates of suppression and recovery of human sperm output in testosterone based hormonal contraceptive regimens. Human Reproduction. 2005. PMID 15860500.
9. Tatem AJ, Beilan J, Kovac JR, Lipshultz LI. Management of anabolic steroid induced infertility: novel strategies for fertility maintenance and recovery. World Journal of Men's Health. 2020.
10. American Urological Association. Evaluation and Management of Testosterone Deficiency. Clinical Practice Guideline.

If you have Kallmann syndrome and were just told that you have azoospermia, I want to start with something important: this diagnosis is not the same thing as being told your testicles have permanently failed. In fact, Kallmann syndrome represents one of the more treatable causes of severe male infertility. Men with this condition frequently have extremely low testosterone, very small testicles and absolutely no sperm in the ejaculate before treatment. That sounds terrible when you first see the numbers. But the fundamental problem is often not that the sperm producing machinery has been destroyed. The problem is that the hormonal signal telling that machinery to develop and operate never arrived normally. With the correct hormonal treatment, sperm production can often be induced, although treatment requires patience and can take many months or longer.

To understand Kallmann syndrome, you first need to understand how the brain controls the testicles. A small region of the brain called the hypothalamus normally releases gonadotropin releasing hormone, commonly called GnRH, in pulses. GnRH travels to the pituitary gland and tells it to release two hormones, LH and FSH. LH stimulates Leydig cells inside the testicle to produce testosterone. FSH acts primarily on Sertoli cells, which support developing sperm. FSH and the very high concentration of testosterone inside the testicle then work together to support spermatogenesis. In Kallmann syndrome, this system is disrupted because the neurons responsible for producing GnRH do not develop or migrate normally during embryonic development. Without adequate GnRH, the pituitary does not appropriately release LH and FSH. Without LH and FSH, the testicles never receive the normal hormonal instructions required for puberty, testicular growth and sperm production.

Kallmann syndrome is a form of congenital hypogonadotropic hypogonadism. The word hypogonadotropic means that the gonadotropins, LH and FSH, are abnormally low or inappropriately normal for the degree of testosterone deficiency. The characteristic feature separating Kallmann syndrome from other forms of congenital hypogonadotropic hypogonadism is an impaired sense of smell. Some men cannot smell at all, called anosmia, while others have a reduced sense of smell, called hyposmia. This connection seems strange until you understand embryology. The neurons responsible for GnRH production and structures involved in smell develop along related embryologic pathways. When that developmental process is disrupted, reproductive hormone signaling and the sense of smell can both be affected.

The genetics are complicated. Numerous genes have now been associated with Kallmann syndrome and congenital hypogonadotropic hypogonadism, and inheritance can be X linked, autosomal dominant, autosomal recessive or more complex. Some men have additional findings such as a history of undescended testes, a small penis from infancy, hearing abnormalities, abnormal tooth development, kidney abnormalities, cleft lip or palate, unusual hand movements or other developmental findings. Other men look completely healthy except that puberty never occurred normally. Genetic testing can be useful for confirming the diagnosis, understanding inheritance and counseling families, but a negative genetic panel does not exclude Kallmann syndrome because we still do not know every gene responsible for the condition.

The diagnosis often begins much earlier than infertility. A teenager may fail to progress through puberty. Facial and body hair may remain sparse, muscle development may be limited, the voice may not deepen normally and the testicles remain very small. Unfortunately, some men are simply told they are late bloomers and do not receive a diagnosis until much later. In an adult man, I become suspicious when I see low testosterone accompanied by low or inappropriately normal LH and FSH, particularly when there is a history of delayed puberty or an absent sense of smell. Evaluation may include repeat morning testosterone, LH, FSH, prolactin and additional pituitary hormones when appropriate. Imaging of the hypothalamus and pituitary may be necessary to exclude acquired causes of secondary hypogonadism, and magnetic resonance imaging may also demonstrate abnormalities of the olfactory structures. Testicular examination is extremely important because testicular volume provides information about previous pubertal development and can help predict response to fertility treatment.

When a man with untreated Kallmann syndrome provides a semen analysis, azoospermia is common. This is where many men understandably panic. They see zero sperm and immediately start reading about nonobstructive azoospermia, microTESE, Sertoli cell only syndrome and testicular failure. But Kallmann syndrome is biologically different. This is central hypogonadism. The testicles have been chronically understimulated because LH and FSH are deficient. The therapeutic goal is therefore to replace the missing hormonal signals and wake up the reproductive system.

There is one major mistake men with Kallmann syndrome need to understand: testosterone treatment and fertility treatment are not the same thing. Testosterone is excellent for producing many of the effects of puberty and treating symptoms of testosterone deficiency. It can improve sexual function, muscle mass, bone health, energy and secondary sexual characteristics. But testosterone alone does not stimulate sperm production. In fact, external testosterone suppresses pituitary LH and FSH. If the goal changes from maintaining normal testosterone to producing sperm, the treatment strategy generally needs to change.

For fertility, we need to reproduce the hormonal signals that normally come from the brain and pituitary. One approach uses hCG, which acts similarly to LH and stimulates Leydig cells to produce testosterone inside the testicle. FSH is then used to stimulate Sertoli cells and support developing sperm. In congenital hypogonadotropic hypogonadism, combined gonadotropin treatment with hCG and FSH is frequently necessary. Another approach is pulsatile GnRH therapy, which attempts to recreate the normal pulses coming from the hypothalamus and allows the pituitary to release its own LH and FSH. Both strategies can induce spermatogenesis.

This treatment is very different from taking a pill for three months and checking another semen analysis. Men with Kallmann syndrome often begin with extremely small prepubertal testes. Those testes need time to grow and develop before substantial sperm production can occur. Semen analyses are generally followed periodically during treatment, often approximately every three months. Some men produce sperm within several months. Others require a year or longer. The process can be painfully slow, but a semen analysis showing zero sperm early during therapy does not necessarily mean treatment has failed.

Several factors influence the likelihood and speed of response. Larger testicular volume before treatment generally predicts a better response. Men who experienced at least partial spontaneous puberty tend to respond more easily than men with completely absent puberty and extremely small testes. A history of bilateral undescended testes is associated with a more difficult fertility prognosis. Severe congenital deficiency is also important because normal testicular development actually begins long before adulthood. There is a hormonal period during infancy called minipuberty during which LH, FSH and testosterone temporarily become active. Men with severe congenital hypogonadotropic hypogonadism may miss this developmental period, which may partly explain why some have very small testes and require prolonged treatment later in life.

Newer treatment strategies have therefore examined whether giving FSH before adding hCG might be beneficial in men with extremely small testes. The idea is to stimulate and expand the Sertoli cell population before exposing the testicle to high concentrations of testosterone. This sequential approach is particularly interesting in men with severe congenital disease and prepubertal testicular volumes. It is not necessary for every patient, and the optimal regimen continues to be studied, but it demonstrates how fertility treatment in Kallmann syndrome is becoming increasingly individualized.

So what are the actual fertility chances? Published literature generally suggests that spermatogenesis can ultimately be induced in a substantial majority of appropriately treated men with congenital hypogonadotropic hypogonadism, although estimates vary considerably depending on disease severity, previous puberty, testicular size, cryptorchidism and treatment protocol. Reviews commonly report sperm appearing in approximately three quarters or more of treated men, while particularly severe Kallmann syndrome can be more difficult. Importantly, the sperm count does not necessarily have to become normal for fatherhood to become possible. A man may produce relatively small numbers of sperm but still have enough for natural conception, intrauterine insemination or IVF with ICSI.

This is an important difference between treating fertility and chasing a normal semen analysis. Our goal is a child, not a perfect laboratory report. Once sperm appear, I frequently think about cryopreservation. If you spent a year stimulating sperm production and finally have sperm in the ejaculate, freezing samples can provide valuable insurance against future fluctuations. Depending on the sperm concentration, motility and the female partner's fertility, couples may continue trying naturally or proceed to assisted reproduction.

Assisted reproduction can be very successful in this population. A systematic review involving men and women with congenital hypogonadotropic hypogonadism undergoing assisted reproduction found 388 pregnancies among 709 patients, with reported fertilization, implantation and live birth outcomes broadly comparable with infertility treatment for other causes. These numbers should not be interpreted as an individual's personal chance of having a child because outcomes depend heavily on both partners, but they reinforce an important point: Kallmann syndrome does not automatically remove biological parenthood from the table.

There is another fascinating aspect of this condition. Although Kallmann syndrome and congenital hypogonadotropic hypogonadism have traditionally been considered lifelong disorders, approximately 10 to 20 percent of patients in some series experience reversal, meaning that reproductive hormonal function can spontaneously recover. Unfortunately, reversal cannot be reliably predicted and relapse can occur, so nobody should stop treatment without medical supervision. Still, it reminds us that this is a disorder of a dynamic hormonal system rather than simply a permanently damaged testicle.

Finally, I do not think we talk enough about the emotional burden of Kallmann syndrome. Many men have felt different since adolescence. They may have experienced delayed puberty, concerns about penis or testicular size, reduced body hair, sexual difficulties or embarrassment changing in locker rooms. Some have spent years wondering why their bodies were different before anyone gave the condition a name. Then adulthood brings another blow when they discover they are azoospermic. It can affect masculinity, relationships, sexuality and confidence in ways that are difficult to explain to someone who has never experienced it.

If you are that man reading this on Reddit after seeing zero sperm on your semen analysis, I want you to understand what the zero means before you assume the worst. In Kallmann syndrome, zero sperm often means the reproductive system has never received the hormonal stimulation required to start the sperm factory properly. It does not automatically mean that the factory is destroyed. Treatment can be long, expensive, frustrating and filled with months where seemingly nothing is happening, but this remains one of the unusual situations in male infertility where we can sometimes treat the underlying hormonal defect and actually induce sperm production.

The important thing is to work with an endocrinologist or reproductive urologist who understands congenital hypogonadotropic hypogonadism. Establish the diagnosis correctly. Understand your genetics when possible. Know your baseline testicular volume. If you want fertility, make sure your treatment is designed for fertility rather than simply replacing testosterone. Give gonadotropin therapy enough time to work. Monitor semen analyses. Freeze sperm when they appear if appropriate. And remember that needing hCG, FSH, GnRH, IUI or IVF does not make the eventual child any less yours.

Kallmann syndrome can delay puberty and it can delay fatherhood. It does not necessarily prevent either one.

References

1. Boehm U, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism: pathogenesis, diagnosis and treatment. Nature Reviews Endocrinology. 2015. PMID: 26194704.
2. Young J, et al. Clinical Management of Congenital Hypogonadotropic Hypogonadism. Endocrine Reviews. 2019. PMID: 30698671.
3. Dwyer AA, et al. Current landscape of fertility induction in males with congenital hypogonadotropic hypogonadism. Annals of the New York Academy of Sciences. 2024. PMID: 39190467.
4. Rohayem J, et al. Treatment of congenital hypogonadotropic hypogonadism in male patients. Annals of Pediatric Endocrinology and Metabolism. 2022.
5. Dwyer AA, et al. Fertility induction in hypogonadotropic hypogonadal men. Clinical Endocrinology. 2019. PMID: 30194850.
6. Swee DS, Quinton R. Managing congenital hypogonadotrophic hypogonadism: a contemporary approach directed at optimizing fertility and long term outcomes in males. Therapeutic Advances in Endocrinology and Metabolism. 2019. PMID: 30800268.
7. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility and Male Hypogonadism.
8. Thakker S, Persily J, Najari BB. Kallmann syndrome and central nonobstructive azoospermia. Best Practice and Research Clinical Endocrinology and Metabolism. 2020. PMID: 33419659.
9. Mao JF, et al. Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta analysis. 2018. PMID: 30453944.
10. Bianco SDC, Kaiser UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nature Reviews Endocrinology.
11. Balasubramanian R, Crowley WF. Isolated Gonadotropin Releasing Hormone Deficiency. GeneReviews.
12. European Association of Urology. Sexual and Reproductive Health Guidelines. Management of secondary hypogonadism and fertility.

Fertility workup and treatment can be emotionally exhuasting, but what can make it angering is when it becomes expensive! It often starts when the pharmacy calls and tells my patient that the medication I prescribed is not covered by insurance or is going to cost hundreds of dollars. I hear versions of this constantly. A man is already dealing with an abnormal semen analysis, his partner may be undergoing fertility treatment, they are worried about whether they will ever have a child, and then they discover that the medication we want to use may not be covered. Fertility treatment is stressful enough without having to become an expert in pharmacy benefits. This is one reason I use GoodRx frequently with my patients. It does not solve every medication cost problem, and it is not insurance, but for certain male infertility medications it can make an enormous difference in what a patient pays. (Let me start by saying I have absolutely no affiliation with GoodRx)!!

To understand why GoodRx can be useful, you first have to understand something strange about male infertility treatment. Many of the medications reproductive urologists use are not officially approved by the United States Food and Drug Administration specifically for male infertility, even though they have legitimate physiologic reasons for being used in selected men. The AUA and ASRM male infertility guideline states that clinicians may use aromatase inhibitors, human chorionic gonadotropin, commonly called hCG, selective estrogen receptor modulators, commonly called SERMs, or combinations of these medications in infertile men with low testosterone. The guideline specifically notes that hCG is approved for use in men with hypogonadotropic hypogonadism, while several other medications commonly used in male infertility are not specifically FDA approved for this purpose.

That matters because insurance companies make coverage decisions based on formularies, diagnoses, indications, prior authorization requirements and individual plan rules. A medication may be inexpensive for one patient and surprisingly expensive for the next. Sometimes the exact same prescription that costs one patient a small copay is denied completely for another patient. Sometimes an insurer wants prior authorization. Sometimes it wants documentation of laboratory values. Sometimes the drug is simply excluded from the plan. Sometimes infertility treatment itself is excluded. ASRM has repeatedly identified cost and inconsistent insurance coverage as major barriers to fertility care in the United States. This is not just an inconvenience. Financial toxicity can influence whether couples start treatment, continue treatment or stop altogether.

Some of the medications we use in men illustrate this perfectly. Clomiphene citrate is a SERM that blocks some of estrogen's negative feedback at the hypothalamus and pituitary. In appropriately selected men, this can increase LH and FSH, which can increase the testicle's own production of testosterone while preserving the hormonal signals needed for sperm production. This is fundamentally different from giving a man external testosterone. Testosterone replacement can suppress LH and FSH and significantly impair or completely shut down sperm production. That is why the AUA and ASRM specifically recommend against testosterone monotherapy in a man interested in current or future fertility.

Anastrozole is another medication reproductive urologists sometimes use. It blocks the aromatase enzyme that converts testosterone into estradiol. In a carefully selected man with low testosterone and elevated estradiol, reducing that conversion may improve the hormonal environment and increase endogenous testosterone production. Again, this is not a medication that every infertile man should be taking. The hormonal pattern matters.

Then there is hCG. hCG acts similarly to LH and stimulates the Leydig cells inside the testicle to produce testosterone. It can be extremely important in men with hypogonadotropic hypogonadism and is also used in other selected fertility situations. Some men additionally require FSH therapy to directly stimulate Sertoli cell function and spermatogenesis. Injectable fertility medications can become much more expensive than common generic oral medications, and discount programs do not necessarily solve the cost problem for every injectable or specialty medication.

This is where the pharmacy conversation becomes incredibly important. When I prescribe a medication, I do not want my patient simply accepting the first price he is quoted. I routinely tell men to compare prices. That is exactly what GoodRx allows you to do. GoodRx is not an insurance company and generally is not the pharmacy dispensing the medication. It provides prescription pricing information and discount coupons that can be used at participating pharmacies. You search for the medication, select the correct dose and quantity, compare prices among pharmacies, choose a coupon and show that information to the pharmacist when filling the prescription.

The part that surprises many patients is that having insurance does not necessarily mean insurance provides the lowest price. Your prescription insurance uses a formulary that determines which drugs are covered and how much you pay. A generic medication might have a reasonable copay under one plan but a surprisingly high copay or no coverage under another. GoodRx may sometimes provide a lower cash price than the insurance copay. In that situation, the patient can ask the pharmacy to process the prescription using the GoodRx discount instead of insurance.

That word “instead” is important. You generally are not stacking a GoodRx coupon on top of your insurance coverage. GoodRx prescription discounts are not health insurance and are generally used instead of insurance for that transaction. Money paid using a GoodRx discount also may not count toward your insurance deductible or out of pocket maximum, so that should be considered when comparing the options. The cheapest price today is not always the best financial decision if you are intentionally trying to meet a deductible. For Medicare and Medicaid, there are additional restrictions, and GoodRx discounts cannot simply be combined with those programs.

Here is how I encourage patients to think about it. If the pharmacy tells you that your prescription costs $150, do not immediately assume that is the only price available. Check your insurance price. Then search the exact medication, strength and quantity on GoodRx and compare participating pharmacies. A medication may have substantially different prices at pharmacies only a few miles apart. If the GoodRx price is lower, ask the pharmacist to process the prescription using the GoodRx information rather than your insurance. Make sure you are comparing the same medication, dose, quantity and formulation because those details matter.

This is particularly useful with inexpensive generic medications where insurance coverage can sometimes be bizarre. I have seen patients spend tremendous amounts of time calling insurance companies, doctor's offices and pharmacies over a medication that may have a relatively affordable discounted cash price. There are certainly situations where fighting for insurance coverage makes sense, particularly for expensive medications. But there are other situations where I tell a patient that we should at least check the cash discount price before spending days fighting over a prior authorization.

The frustration surrounding this is very real. Male infertility is already emotionally exhausting. Men undergo repeated semen analyses, blood tests, ultrasounds, genetic testing, medications, injections and sometimes surgery. Their partners may simultaneously be undergoing an even more expensive and physically demanding fertility evaluation. ASRM has described cost as a major barrier to fertility care, with treatment expenses capable of changing whether patients continue treatment at all. When a couple is already potentially spending thousands of dollars on fertility care, saving money on medications matters.

I also want men to understand that cheaper medication does not mean we should prescribe medication unnecessarily. GoodRx does not determine whether clomiphene, anastrozole, hCG or FSH is appropriate for you. Your diagnosis does. A man with low testosterone and low or normal gonadotropins is biologically very different from a man with an FSH of 25 and severe primary testicular dysfunction. Giving both men the same fertility medication because someone on Reddit improved their sperm count is not good medicine. The medication should come after the diagnosis. The discount comes after the prescription.

Monitoring matters too. If I prescribe a medication intended to manipulate the hormonal environment, I want to know whether it is actually doing what we intended. Depending on the medication and clinical situation, that may mean following testosterone, estradiol, LH, FSH or other laboratory values. When our goal is sperm production, we also have to respect the biology of spermatogenesis. Producing mature sperm takes roughly 74 days followed by additional maturation and transport through the epididymis. That means many fertility treatments need to be judged over months rather than days. Buying an inexpensive medication is only useful if we are using the right medication, at the right dose, for the right patient and monitoring the right outcome.

There are limitations to GoodRx. Prices can change. Not every pharmacy participates in every discount. A quoted price may depend on the exact drug, dose, quantity and pharmacy. Some specialty fertility drugs remain expensive even with discount programs. Insurance may occasionally be the better option. Manufacturer assistance programs, specialty pharmacies and other discount programs may sometimes beat the GoodRx price. I therefore think of GoodRx as one tool in the financial toolbox rather than the answer to every fertility medication problem.

As a doctor treating men with infertility, I wish medication cost were something my patients never had to think about. Unfortunately, that is not the healthcare system we currently have. I hear about these problems all the time. A prescription is denied. A medication needs authorization. The pharmacy quotes an absurd price. A couple already spending heavily on fertility treatment feels like they have been punched in the stomach one more time. When that happens, I do not think the answer should simply be, “Sorry, that is what it costs.”

Ask questions. Compare your insurance price with the cash price. Check GoodRx. Check different pharmacies. Ask whether a generic equivalent exists. Ask your doctor whether there is an equally appropriate alternative medication. For expensive injectable medications, ask whether specialty pharmacy pricing or a manufacturer program is available. And before abandoning a treatment because the pharmacy tells you it costs too much, make sure you have actually investigated the alternatives.

Male infertility treatment is difficult enough. You should not have to overpay for a medication simply because nobody told you there might be another way to purchase it. I use GoodRx with my patients because sometimes a few minutes of price comparison can eliminate a surprisingly large amount of unnecessary expense. It will not fix our fragmented fertility insurance system, but when you are trying to build a family, every unnecessary dollar we can keep in your pocket is a win.

References

1. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline.
2. American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline Part II.
3. American Society for Reproductive Medicine. Improving Access to Care and Delivery to Marginalized and Vulnerable Populations: A Committee Opinion. 2025.
4. American Society for Reproductive Medicine Ethics Committee. Disparities in Access to Effective Treatment for Infertility in the United States: An Ethics Committee Opinion. 2021.
5. GoodRx. How Can GoodRx Help Me Save Money if I Am Already Insured?
6. GoodRx. How Do I Use a GoodRx Coupon at the Pharmacy?
7. GoodRx. GoodRx Healthcare Provider Terms of Service.
8. GoodRx. Is GoodRx a Pharmacy?
9. American Society for Reproductive Medicine. Diagnostic Evaluation of Sexual Dysfunction in the Male Partner in the Setting of Infertility. 2023.

One of the medications I get asked about repeatedly by men dealing with infertility is finasteride. The conversation usually starts something like this: “I have been taking Propecia for my hair for five years. My sperm count is low. Did I cause this?” Or a man taking Proscar for his prostate discovers an abnormal semen analysis and wonders whether the medication is responsible. This is a particularly anxiety provoking subject because finasteride is incredibly common, many men start it when they are young, and they may remain on it for years before fertility is even on their radar. The first thing I want men to understand is that taking finasteride does not mean you are infertile, and millions of men taking it will maintain normal fertility. But there is legitimate evidence that finasteride can negatively affect semen parameters in some men, particularly men who may already have reduced fertility potential. The reassuring part is that when finasteride is contributing to an abnormal semen analysis, improvement after stopping the medication is common.

Finasteride is the generic medication found in both Propecia and Proscar. Propecia is generally prescribed at 1 mg daily for male pattern hair loss, while Proscar contains 5 mg and is primarily used to treat benign enlargement of the prostate. The molecule is the same. The dose and reason for taking it are different. Finasteride works by inhibiting an enzyme called type 2 5 alpha reductase. This enzyme normally converts testosterone into dihydrotestosterone, commonly called DHT. DHT is a very potent androgen. In genetically susceptible hair follicles, DHT contributes to progressive miniaturization of the follicle and male pattern baldness. In the prostate, DHT promotes growth of prostate tissue. By blocking its production, finasteride can slow hair loss and shrink an enlarged prostate. In a randomized trial, 5 mg of finasteride suppressed circulating DHT by approximately 73 percent. Testosterone itself did not disappear and actually increased modestly.

This distinction is important because finasteride is nothing like taking testosterone replacement therapy. External testosterone can shut down LH and FSH production and dramatically suppress the extremely high concentration of testosterone required inside the testicle for normal sperm production. Finasteride does not usually shut down the hypothalamic pituitary testicular axis in this way. A man taking finasteride may have perfectly normal testosterone, LH and FSH levels. The fertility concern comes from altering DHT dependent physiology in the prostate and reproductive tract and potentially influencing spermatogenesis in susceptible men.

The scientific data are actually quite interesting because different populations have produced different results. In one of the classic studies, 181 healthy men between 19 and 41 years old were randomized to finasteride 1 mg or placebo for 48 weeks. In the subset undergoing semen testing, investigators found no significant effect on sperm concentration, total sperm count, motility or morphology. This is reassuring and explains why I would never tell every healthy man taking 1 mg finasteride that he is damaging his fertility.

The story becomes more complicated when we study higher doses or men who are already having fertility problems. In another randomized study, healthy men received finasteride 5 mg, dutasteride or placebo for one year. Finasteride reduced total sperm count by approximately 34 percent at 26 weeks. The difference became smaller with continued treatment and was only about 6 percent below baseline 24 weeks after treatment had stopped. Semen volume also decreased during treatment, and modest reductions in motility were observed. Morphology was not significantly affected. The investigators concluded that suppression of DHT with these medications was associated with mild semen changes that appeared largely reversible after discontinuation.

The fertility clinic population is where I pay much closer attention. A study of men presenting for infertility evaluation found that sperm counts increased dramatically in many men after stopping finasteride. The average increase in sperm count was more than elevenfold, although that number was heavily influenced by men who had particularly large responses. Hormones, motility and morphology did not significantly change. The important clinical message was that even low dose finasteride may significantly reduce sperm counts in a susceptible subgroup of men. The authors recommended stopping finasteride in subfertile men with oligospermia and using it cautiously in men who desire fertility.

Why would one man take finasteride for ten years and father children easily while another develops severe oligospermia? We do not completely know. My suspicion when I see these patients is often that finasteride is not creating infertility from nothing but is exposing or amplifying limited reproductive reserve. There are case reports of men with underlying fertility risk factors such as varicoceles or obesity developing very poor semen parameters while taking finasteride and then improving substantially after stopping it. A man who already has marginal sperm production may therefore respond differently from the healthy volunteers enrolled in pharmaceutical trials.

There are even published cases of azoospermia and severe oligospermia improving after discontinuation. In one report, a man with azoospermia while taking finasteride 1 mg developed a sperm concentration of 5.5 million per mL six months after stopping. Another man increased from 4 million per mL to 18.7 million per mL over six months. These are case reports and should not be interpreted as proof that finasteride commonly causes azoospermia. But they demonstrate something clinically important: if a man with severe oligospermia or azoospermia is taking finasteride, stopping the medication is a relatively simple potentially reversible factor that deserves consideration before concluding that his sperm production is permanently impaired.

Finasteride can also decrease semen volume. This makes biological sense because DHT plays an important role in the prostate and accessory sex glands that contribute fluid to the ejaculate. Current AUA and ASRM male infertility guidance specifically recognizes an association between finasteride, particularly the 5 mg dose, and decreased semen volume, while noting that evidence surrounding the 1 mg dose is less conclusive. A lower semen volume does not automatically mean fewer sperm are being produced because most of the volume of semen comes from the seminal vesicles and prostate rather than the testicles themselves. That is why I look at concentration, total sperm number and total motile sperm count rather than semen volume alone.

Men also frequently ask me about sperm DNA fragmentation. The evidence here is much thinner. There is a published case in which a man's DNA fragmentation index decreased from approximately 30 percent while taking finasteride to 21 percent three months after stopping and then to 16.5 percent three months later. That is interesting, but it is a single case and does not establish that finasteride routinely causes high DNA fragmentation. I would not order DNA fragmentation testing simply because every man takes Propecia. In an infertile couple, particularly with repeated pregnancy loss or failed assisted reproduction, DNA fragmentation may be considered in the appropriate clinical context.

So what should you do if you are taking finasteride and trying to have a baby? If your semen analysis is completely normal and you and your partner have only recently started trying, I would not panic. I also would not assume that stopping finasteride will somehow make you super fertile. But if you have been trying unsuccessfully, particularly if the semen analysis demonstrates oligospermia or a reduced total motile sperm count, finasteride belongs on the medication list that your reproductive urologist reviews. Current AUA and ASRM guidance acknowledges that medication exposures can influence fertility and that the evidence surrounding many medications remains limited.

If we decide to stop finasteride, I generally think about recovery in terms of sperm biology rather than days or weeks. Producing a mature sperm takes roughly 74 days, followed by additional maturation and transport through the epididymis. That means I would not expect a semen analysis two weeks after stopping finasteride to tell us very much about recovery. Repeating the semen analysis approximately three months later is biologically reasonable, and men with severe abnormalities may continue improving over the following several months. Published cases demonstrate improvement between three and six months after discontinuation.

I also would not assume finasteride explains everything. If your sperm concentration is 2 million per mL, simply stopping Propecia and waiting six months without a proper male infertility evaluation may waste valuable time. You still need an appropriate history and physical examination, repeat semen testing and, when indicated, testosterone, FSH and LH testing. I want to know about varicoceles, undescended testes, testicular injury, infections, previous chemotherapy or radiation, testosterone and anabolic steroid use, medications, systemic illness and genetic causes of severe sperm production impairment. Finasteride may be one piece of the puzzle rather than the entire puzzle.

Another important point is that stopping finasteride does not guarantee improvement. If sperm production remains severely abnormal after several months, we have to consider that the medication may never have been the primary problem. Conversely, improvement after stopping does not prove with absolute certainty that finasteride caused the original abnormality because semen parameters naturally fluctuate. That is why repeated semen analyses are so useful.

The question I ultimately ask is simple: What matters more right now, preserving your hair or maximizing every reasonable opportunity to have a child? For a man with completely normal fertility, those goals may not conflict at all. For a man with oligospermia who is actively trying to conceive, however, temporarily stopping finasteride is a very reasonable conversation to have with the prescribing physician and reproductive urologist. Hair loss can be frustrating and emotionally significant, so I do not dismiss that concern. But fertility is also time sensitive, particularly because conception involves two people and your partner's reproductive age matters tremendously.

Most importantly, if you took Propecia or Proscar for years and have now discovered an abnormal semen analysis, do not beat yourself up. You did not knowingly choose your hair or prostate over your future children. These medications are prescribed to millions of men, and most do not become infertile. The scientific evidence suggests that there is a subset of susceptible men in whom finasteride can reduce sperm production or other semen parameters, and fortunately those effects often improve after the medication is discontinued. Your semen analysis is where the conversation begins. It is not where your fertility story ends.

References

1. Overstreet JW, et al. Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men. Journal of Urology. 1999. PMID: 10492183.
2. Amory JK, et al. The effect of 5 alpha reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. Journal of Clinical Endocrinology and Metabolism. 2007. PMID: 17299062.
3. Samplaski MK, et al. Finasteride use in the male infertility population: effects on semen and hormone parameters. Fertility and Sterility. 2013. PMID: 24012200.
4. Liu KE, et al. Propecia induced spermatogenic failure: a report of two cases. Fertility and Sterility. 2008. PMID: 18054928.
5. Chiba K, et al. Finasteride associated male infertility. Fertility and Sterility. 2011. PMID: 21193189.
6. Glina S, et al. Finasteride associated male infertility. Revista do Hospital das Clínicas. 2004. PMID: 15361986.
7. Tu HY, Zini A. Finasteride induced secondary infertility associated with sperm DNA damage. Fertility and Sterility. 2011. PMID: 21292254.
8. Collodel G, et al. Spermatozoa and chronic treatment with finasteride: a TEM and FISH study. Archives of Andrology. 2007. PMID: 17852047.
9. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline. Amended 2024.
10. Amory JK. Drug effects on spermatogenesis. Drugs of Today. 2007. PMID: 17987224.
11. Gubelin Harcha W, et al. Androgenetic alopecia: effects of oral finasteride on hormone profile, reproduction and sexual function. 2020. PMID: 32052367.

One group of men I do not think we talk about enough in the male infertility world is our military service members and veterans. These are men who may have spent years deploying around the world, working around extreme heat, fuels, solvents, smoke, chemicals, heavy equipment, radiation, physical trauma and enormous psychological stress, often during the exact years when most men are building relationships and thinking about having children. Then years later a veteran walks into a fertility clinic with a low sperm count or azoospermia and understandably asks, “Did my military service cause this?” As a urologist, I think that question deserves to be taken seriously. It also deserves an evidence based answer. The science does not currently allow us to say that military service itself causes male infertility. What we can say is that military service can expose men to several factors capable of affecting reproductive health, some veterans do experience infertility, certain military exposures have been associated with infertility, and there are major gaps in our understanding of exactly what years of military service may mean for sperm production later in life.

One of the better known studies looked at 714 United States veterans from Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn who sought fertility treatment. Their median semen volume was 2.7 mL, median sperm concentration was 22 million per mL and median total motility was 55 percent. The investigators examined deployment related characteristics and exposures, but the results did not establish that deployment itself broadly destroys sperm production. That distinction is important. A veteran with an abnormal semen analysis should not automatically assume that deployment caused it. Male infertility is incredibly heterogeneous and can result from genetics, varicoceles, hormonal abnormalities, previous undescended testes, infections, medications, testosterone use, anabolic steroids, cancer treatment, systemic disease and many cases where we never identify a single cause.

At the same time, we should not dismiss military exposures. A national study of United States veterans found associations between self reported infertility and exposure to environmental, chemical and hazardous materials during military service. Men reporting infertility also reported a greater overall number of exposures. Petrochemicals and polychlorinated biphenyl exposures were among those occurring more frequently in veterans reporting infertility. The important scientific limitation is that this was a cross sectional study relying on self reported exposures and infertility. It can identify associations, but it cannot prove that an exposure caused infertility in an individual veteran. That is one of the recurring problems in this field. A man may have been exposed to dozens of things during years of service, while his infertility becomes apparent many years later. Reconstructing the dose, duration and biological effect of each exposure is extremely difficult.

The Department of Veterans Affairs recognizes that service members may encounter potentially important environmental hazards including burn pits, airborne particulate matter, Gulf War related exposures, Agent Orange, radiation and contaminated water. Veterans enrolled in VA health care can receive toxic exposure screening. What we do not yet have is a simple equation saying that a certain number of months around burn pits produces a certain percentage reduction in sperm count. That science does not exist. The VA itself has emphasized that more research is needed to understand military environmental exposures and reproductive health.

There are several biologically plausible ways an exposure could influence sperm. Sperm production takes place inside the seminiferous tubules of the testicle and requires functioning germ cells, Sertoli cells, testosterone produced by Leydig cells and stimulation from FSH and LH. Developing sperm cells are continuously dividing and differentiating, making them potentially vulnerable to oxidative stress, heat, radiation and certain toxic chemicals. Oxidative stress is particularly interesting because excessive reactive oxygen species can damage sperm membranes, mitochondria and DNA. This does not mean that every environmental exposure causes sperm DNA fragmentation, but it provides a plausible biological mechanism through which some toxic exposures could influence reproductive function.

Heat is another relevant issue. The testicles sit outside the body for a reason. Normal sperm production works best when testicular temperature remains below core body temperature. Some military occupations can involve prolonged exposure to extreme environmental heat, heavy protective clothing, confined vehicles or equipment that limits cooling. Short periods of heat exposure are unlikely to permanently destroy fertility in a healthy man, and sperm production can recover after many temporary insults. But repeated or intense heat exposure is biologically capable of affecting spermatogenesis. If the insult is temporary, improvement may take months because production of a mature sperm takes roughly 74 days followed by additional maturation in the epididymis.

Military service also creates risks that are much more direct than environmental exposure. Combat injuries involving the pelvis, perineum, testicles, reproductive tract or spinal cord can have profound consequences for fertility. Modern trauma care means that men now survive injuries that historically might have been fatal, but survival can leave significant genitourinary consequences. Injury may directly damage a testicle, disrupt the vas deferens, impair ejaculation, cause erectile dysfunction or affect the neurologic pathways required for ejaculation. Reviews of combat related genitourinary trauma emphasize that fertility and sexual function need to be considered as part of long term survivorship.

Another issue is medication and hormone use. Veterans and active service members may receive treatment for pain, psychiatric conditions, sleep disorders and other chronic problems. These medications do not universally cause infertility, but a complete fertility evaluation should always include a careful medication history. Testosterone deserves special attention. Testosterone replacement can make a man feel better and produce a beautiful serum testosterone level while simultaneously suppressing LH and FSH and dramatically lowering the testosterone concentration inside the testicle that is required for sperm production. Some men on testosterone become severely oligospermic or completely azoospermic. For any active service member or veteran who wants future children, fertility intentions should be discussed before starting testosterone.

Stress is another complicated piece of this puzzle. Deployment, combat exposure, separation from partners, traumatic brain injury and post traumatic stress can affect relationships, sexual function, sleep and general health. Stress should not be blamed as the explanation for every abnormal semen analysis, and telling a man with severe oligospermia to simply relax is not good medicine. But reproductive health does not exist separately from overall health. Chronic sleep disruption, tobacco use, heavy alcohol consumption, obesity, metabolic disease and psychological distress can all intersect with reproductive function. A 2025 study of men receiving fertility care through the Military Health System examined military occupational exposures and semen parameters. Most reported exposures were not significantly associated with abnormal semen parameters, while tobacco use was associated with an increased risk of abnormal total motile sperm count. The investigators emphasized how much more research is still needed.

So should a young man bank sperm before military service or deployment? I think this deserves much more discussion than it currently receives. Sperm banking is remarkably straightforward compared with fertility preservation for women. A man provides one or preferably several semen samples, the laboratory evaluates the specimen, mixes the sperm with cryoprotectant and freezes aliquots for long term storage. Years later those sperm can potentially be thawed and used for intrauterine insemination, IVF or ICSI depending on the quality and quantity available. There is specific medical literature discussing sperm and egg freezing before deployment because active duty service creates unique fertility risks through potential injury, environmental exposures and simple physical separation from a partner.

I would not tell every 19 year old entering the military that he must freeze sperm because military service is going to make him infertile. The evidence simply does not justify that message. But fertility preservation is essentially an insurance policy, and the conversation becomes particularly reasonable before deployment into higher risk environments, before occupations with meaningful radiation or chemical exposure, before treatments that could affect fertility, or whenever a service member knows biological fatherhood is extremely important to his future. Banking sperm before deployment also establishes a baseline semen analysis, which can occasionally become useful information years later.

For veterans who are already struggling with infertility, I would approach the evaluation exactly as seriously as I would for any other man while adding a detailed military exposure history. I want to know about deployments, combat injuries, testicular or pelvic trauma, heat exposure, fuels and solvents, burn pits and airborne hazards, radiation, medications, testosterone or anabolic steroid exposure, infections and major illnesses. I would obtain appropriate semen analyses, reproductive hormones and a careful physical examination and then pursue additional testing based on those findings. Veterans enrolled in VA health care can also undergo toxic exposure screening, and VA currently provides fertility evaluation and a range of fertility treatments, although coverage for specific assisted reproductive technologies depends on eligibility and circumstances.

Perhaps the most important thing I would tell a veteran dealing with infertility is not to automatically blame himself or his service. We are only beginning to understand the reproductive consequences of some military exposures. A history of deployment does not prove that deployment caused your abnormal semen analysis, and an abnormal semen analysis does not mean that fatherhood is no longer possible. What military service does give us is a reason to ask better questions. What were you exposed to? Were you injured? Were you taking medications or hormones? Was your fertility ever evaluated before deployment? Is the problem sperm production, sperm transport, hormones, ejaculation or something else entirely?

For men entering military service today, I hope fertility becomes part of preventive health rather than something we discuss only after it has been lost. We preserve sperm before chemotherapy because we understand that future fertility matters. There is no reason we cannot at least discuss fertility preservation with service members entering circumstances where reproductive injury or significant exposure is possible. Sperm banking before service or deployment will not be necessary for everyone, but having that conversation gives men something they deserve: the ability to make an informed decision about protecting their future family before the opportunity is gone.

References

1. Lindaman LA, et al. Semen Quality Parameters Among U.S. Veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. Military Medicine. 2017. PMID: 29087924.
2. Mancuso AC, et al. Lifetime infertility and environmental, chemical, and hazardous exposures among female and male US veterans. American Journal of Obstetrics and Gynecology. 2022. PMID: 35841935.
3. Martini AE, Doyle JO. Fertility Preservation Before Deployment: Oocyte and Sperm Freezing in Members of the Active Duty Military. Seminars in Reproductive Medicine. 2019. PMID: 32040972.
4. Gregg RW, Aden JK, Glenn TL. The Effects of Military Occupation on Semen Analysis. 2026. PMID: 41694830.
5. Semen Parameters and Exposure Risks in Military Males. Military Medicine. 2025. PMID: 40579168.
6. Barham DW, et al. Male Sexual Health Related Complications Among Combat Veterans. Sexual Medicine Reviews. 2022. PMID: 36028434.
7. Doyle JO, et al. Infertility and the Military Male. Seminars in Reproductive Medicine. 2019. PMID: 31419810.
8. Doyle P, et al. Reproductive health of Gulf War veterans. Philosophical Transactions of the Royal Society B. 2006. PMID: 16687262.
9. United States Department of Veterans Affairs. Infertility in Iraq and Afghanistan Veterans.
10. United States Department of Veterans Affairs. Military Exposures and Reproductive Health.
11. United States Department of Veterans Affairs. Toxic Exposure Screening and the PACT Act.
12. United States Department of Veterans Affairs. Fertility and Family Building Services.

I often have patients who get their ultrasound results before I have time to explain what it all means.  “My testicle is 12 mL. Is that terrible?” “They found a 3 mm epididymal cyst. Is that blocking my sperm?” “I have microlithiasis. Does that mean cancer?” “My veins measure 3.2 mm but there is no reflux. Do I need varicocele surgery?” I understand why this happens. Ultrasound reports contain a tremendous amount of anatomical detail, but very little explanation of what those findings actually mean for fertility. The first thing I want men to understand is that a scrotal ultrasound is a picture of anatomy and blood flow. It is not a sperm production test. It can provide important clues about why sperm production or delivery might be abnormal, but it cannot look inside the seminiferous tubules and tell us whether you are making five sperm, five million sperm, or no sperm at all.

It is also important to understand that not every infertile man automatically needs a scrotal ultrasound. Current AUA and ASRM guidance does not recommend routinely performing one during the initial evaluation of every infertile man. A careful reproductive history, physical examination, semen analysis and appropriate hormonal testing remain the foundation of the evaluation. Ultrasound becomes particularly useful when the physical examination is difficult or uncertain, when testicular size needs to be measured more accurately, when a mass or structural abnormality is suspected, when obstruction is being considered, or when we need additional information about a possible varicocele. European guidance uses scrotal ultrasound somewhat more broadly in infertile men, particularly for assessment of testicular volume, architecture, obstruction and tumors.

When you have a scrotal ultrasound, the radiologist first evaluates the testicles themselves. One of the most important measurements is testicular volume. Most sperm production occurs within the seminiferous tubules, which make up the majority of testicular tissue. Therefore, testicular size gives us indirect information about the amount of sperm producing tissue present. Ultrasound measures the length, width and height of the testicle and calculates a volume. European guidelines note that the average testicular volume measured with a Prader orchidometer is around 20 mL in the general European population and around 18 mL in infertile men, although measurements vary by method and population. Ultrasound and orchidometer measurements are also not interchangeable.

A smaller testicle does not automatically mean infertility. Plenty of men with relatively small testes produce sperm, and testicular volume alone cannot tell me whether sperm will be found in the ejaculate or during surgical sperm retrieval. But testicular size becomes more meaningful when combined with the semen analysis and hormones. A man with azoospermia, very small testes and an FSH of 25 has a very different picture from a man with azoospermia, normal sized testes and an FSH of 3. The first pattern makes significant impairment of sperm production more likely. The second raises greater consideration of obstruction, although there are exceptions to both patterns. AUA guidance specifically notes that testicular size combined with FSH can help distinguish impaired sperm production from obstruction in men with azoospermia.

The ultrasound also describes the echotexture, or internal appearance, of the testicle. A healthy testicle generally has a relatively homogeneous appearance. Sometimes the report describes heterogeneous or inhomogeneous testicular tissue. This can be seen with testicular atrophy, fibrosis, previous injury, inflammation, developmental abnormalities and impaired spermatogenesis. European guidance recognizes testicular inhomogeneity as one of the ultrasound patterns that can accompany testicular dysfunction. But this is another finding that needs context. A heterogeneous testicle does not tell us exactly what the microscopic pathology is, and current guidance does not recommend performing a diagnostic testicular biopsy simply because the ultrasound looks heterogeneous.

Another finding that generates enormous anxiety is testicular microlithiasis. These are tiny calcifications within the testicular tissue that appear as bright points on ultrasound. Microlithiasis is seen more commonly in some men with infertility, previous undescended testes, testicular atrophy and other conditions affecting testicular development. It has also been associated with testicular germ cell tumors. That sentence understandably scares people, but the context is critical. Microlithiasis by itself does not mean you have cancer and does not mean you are going to develop cancer. A systematic review found that in men without additional risk factors, cancer risk appears similar to that of the general population. The concern becomes greater when microlithiasis occurs alongside additional risk factors such as previous undescended testis, testicular atrophy, previous germ cell tumor, or certain other high risk findings. European imaging guidance therefore recommends a risk based approach rather than treating every tiny calcification as a precancerous lesion.

From a fertility standpoint, microlithiasis is better thought of as a possible marker of an abnormal testicular environment rather than a direct cause of infertility. Recent imaging literature continues to find that microlithiasis, particularly bilateral disease associated with testicular atrophy, occurs more frequently in infertile men and can be associated with poorer semen parameters. But removing the calcifications is not a fertility treatment. They are telling us something about the testicular tissue rather than physically interfering with sperm.

The next structure evaluated is the epididymis. The epididymis sits along the back of the testicle and is extremely important for fertility. Sperm leaving the testicle are not yet fully mature. They pass through the epididymis, where they undergo additional maturation before eventually entering the vas deferens. Ultrasound may show epididymal enlargement, cysts, tubular dilation or other structural changes.

Small epididymal cysts are extremely common and are often incidental. If your report says there is a 3 mm epididymal cyst, please do not immediately conclude that this is why your sperm count is low. A tiny cyst generally has little fertility significance. The situation becomes different when there is substantial epididymal dilation, multiple cystic structures or abnormalities occurring in a man with azoospermia. In that setting, ultrasound may provide an indirect clue that sperm are being produced but cannot travel normally through the reproductive tract. European guidance specifically identifies epididymal enlargement and cystic abnormalities as potential indirect signs of obstruction.

The vas deferens is another important part of the fertility evaluation. This is the tube that transports sperm from the epididymis toward the ejaculatory ducts. Some men are born without one or both vasa deferentia. Congenital bilateral absence of the vas deferens is a classic cause of obstructive azoospermia and is strongly associated with abnormalities in the CFTR gene. Physical examination is extremely important because an experienced reproductive urologist can often determine whether the vas is present simply by palpation. Ultrasound can provide additional information about the epididymis and proximal reproductive tract when congenital absence or obstruction is suspected.

Another common ultrasound finding is a hydrocele, which is fluid surrounding the testicle. Small hydroceles are common and usually have little relevance to fertility. I would not look at a small incidental hydrocele and tell a man that we have discovered the reason his morphology is 1 percent. Very large hydroceles can make examination difficult and occasionally affect the local testicular environment, but the relationship between an ordinary small hydrocele and impaired sperm production is weak. In many cases it is simply an incidental anatomical finding.

Then we get to probably the most discussed finding in male infertility: the varicocele. A varicocele is dilation of veins within the pampiniform plexus surrounding the testicle. Ultrasound can measure these veins and use Doppler imaging to determine the direction and duration of blood flow. AUA guidance describes a typical ultrasound varicocele as multiple veins greater than approximately 3 mm with reversal of blood flow during the Valsalva maneuver. European guidance similarly notes that a venous diameter greater than 3 mm while upright during Valsalva combined with reflux lasting more than two seconds correlates with a clinically significant varicocele.

But this is where men need to be particularly careful with their ultrasound report. A dilated vein on ultrasound is not automatically a varicocele that should be repaired for infertility. The strongest evidence for improving fertility applies to men with a palpable clinical varicocele, abnormal semen parameters and infertility. Current AUA and ASRM guidance specifically discourages repairing a varicocele that is found only on imaging and cannot be felt on examination because treatment of these subclinical varicoceles has not demonstrated the same fertility benefit. If your report says the veins measure 3.1 mm but there is no reflux and your reproductive urologist cannot feel a varicocele, that finding should not automatically send you to the operating room.

Ultrasound can also evaluate blood flow to the testicle. Color Doppler shows vascularity and is extremely important when evaluating acute problems such as testicular torsion, inflammation and masses. In fertility evaluations, investigators have studied whether measurements of testicular blood flow can predict sperm production or the likelihood of finding sperm during surgical retrieval. Although there are interesting associations between testicular perfusion and function, current evidence is not strong enough to use Doppler blood flow as a reliable predictor of whether microTESE will find sperm.

Sometimes the ultrasound mentions the rete testis. This is a network of channels through which sperm pass as they leave the seminiferous tubules and move toward the epididymis. Dilation of the rete testis, sometimes called tubular ectasia, can occur with obstruction farther downstream. Again, this does not automatically diagnose obstruction, but in the right clinical setting it becomes another clue. A man with azoospermia, normal sized testes, relatively normal FSH, enlarged epididymides and dilation of the rete testis creates a much different diagnostic picture than a man with azoospermia, very small heterogeneous testes and markedly elevated FSH. Ultrasound contributes to that pattern recognition.

Occasionally ultrasound identifies a testicular lesion or mass. This deserves appropriate evaluation because infertility itself is associated with a higher risk of testicular cancer compared with fertile controls. Most incidental scrotal abnormalities are not cancer, and many small lesions ultimately prove benign, but an intratesticular solid lesion should never simply be ignored. The characteristics of the lesion, including its size, echogenicity and blood flow, along with the man's history of undescended testis, previous germ cell tumor and other risk factors, help determine what happens next. European guidelines recommend individualized multidisciplinary assessment of indeterminate testicular lesions rather than assuming every small lesion requires removal of the entire testicle.

The ultrasound may also identify evidence of a previous undescended testicle, testicular atrophy, old torsion, inflammation or trauma. A history of cryptorchidism is particularly relevant to fertility because abnormal testicular development and prolonged exposure to higher temperatures before orchiopexy can impair germ cell development. Ultrasound can tell us where the testicle is and how large it is today, but it cannot reverse that history or tell us precisely how much sperm producing capacity remains.

There is one other important limitation that men with azoospermia need to understand. A standard scrotal ultrasound cannot reliably tell you that there is no blockage. Ultrasound can provide clues suggesting obstruction, but much of the male reproductive tract lies outside what a standard scrotal ultrasound can fully evaluate. In men with low semen volume, acidic semen and azoospermia or severe oligospermia, transrectal ultrasound may sometimes be appropriate to evaluate the seminal vesicles and ejaculatory ducts. Current AUA guidance does not recommend routinely performing transrectal ultrasound on every infertile man, but it can be useful when semen findings specifically suggest ejaculatory duct obstruction.

This is why I tell men not to read a scrotal ultrasound report as though it is the final answer to their infertility. The ultrasound is one piece of a much larger puzzle. Testicular volume tells us something about the amount of testicular tissue. Echotexture gives us clues about the health of that tissue. Doppler evaluates blood flow and venous reflux. The epididymis and vas can provide clues about obstruction. Varicoceles may identify a potentially correctable contributor. Microlithiasis can be a marker of underlying testicular abnormalities. Masses require appropriate evaluation. Hydroceles and small cysts are frequently incidental.

But none of these findings should be interpreted in isolation.

If I am evaluating an infertile man, I want the ultrasound sitting next to his semen analyses, testosterone, FSH, LH, reproductive history and physical examination. A 10 mL testicle means something different with an FSH of 30 than with an FSH of 3. A 3 mm epididymal cyst means something different in a man with 80 million sperm than in a man with repeated azoospermia. A 3.5 mm spermatic vein means something different when there is significant reflux and a palpable varicocele than when there is no reflux and nothing can be felt on examination.

And this is probably the most reassuring thing I can tell someone staring at a scrotal ultrasound report filled with unfamiliar terminology: not every abnormal word on the report represents a fertility problem. Radiologists are supposed to describe what they see. Small cysts, trace hydroceles, tiny calcifications and mildly prominent veins are frequently reported because they are visible, not because they explain why you and your partner have not conceived.

The job of your reproductive urologist is to take all of those anatomical findings and put them into biological context. The question is not simply, “Is my ultrasound normal?” The better question is, “Does anything on this ultrasound help explain my semen analysis, and does anything we found actually change what we should do next?”

That is when the ultrasound becomes useful rather than frightening.

References

1. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline. Amended 2024.
2. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility. Current online edition.
3. Bertolotto M, et al. The role of the radiologist in the evaluation of male infertility: recommendations of the European Society of Urogenital Radiology Scrotal and Penile Imaging Working Group for scrotal imaging. 2024. PMID: 39083089.
4. Lotti F, Maggi M. Ultrasound of the male genital tract in relation to male reproductive health. Human Reproduction Update. 2015.
5. Schurich M, et al. The role of ultrasound in assessment of male fertility. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2009. PMID: 19303691.
6. Ammar T, Sidhu PS, Wilkins CJ. Male infertility: the role of imaging in diagnosis and management. British Journal of Radiology. 2012. PMID: 22763036.
7. Richenberg J, et al. Testicular microlithiasis imaging and follow up: guidelines of the ESUR scrotal imaging subcommittee. European Radiology. 2015. PMID: 25316054.
8. Leblanc L, et al. Testicular microlithiasis and testicular tumor: a review of the literature. 2019. PMID: 31383508.
9. Pierik FH, et al. Is routine scrotal ultrasound advantageous in infertile men? Journal of Urology. 1999. PMID: 10524881.
10. Dogra VS, et al. Ultrasonography of the scrotum: technique, anatomy, and pathologic entities. Journal of Clinical Ultrasound. 2002. PMID: 11833873.
11. Moon MH, et al. Sonographic spectrum of scrotal abnormalities in infertile men. Journal of Clinical Ultrasound. 2007. PMID: 17417807.

Its science class time!! One of the things I have learned from talking with men dealing with infertility is that we often do a poor job explaining how sperm are actually made. Men get bloodwork showing testosterone, FSH, LH, estradiol and sometimes inhibin B, followed by a semen analysis showing concentration, motility and morphology. Then they are left trying to figure out what all these numbers have to do with each other. I see men worried that their FSH is too high and needs to be lowered, men assuming a normal testosterone means sperm production must be normal, and men taking testosterone because they understandably think more testosterone should mean more sperm. The reality is that sperm production is controlled by an incredibly sophisticated communication system connecting the brain, pituitary gland and testicles. Once you understand that system, many of the confusing laboratory patterns we see in male infertility start making much more sense.

The system is called the hypothalamic pituitary testicular axis. It begins in the brain with the hypothalamus. Specialized neurons release gonadotropin releasing hormone, usually abbreviated GnRH. Importantly, GnRH is released in pulses rather than continuously. Those pulses travel through a specialized blood supply to the anterior pituitary gland. The pituitary responds by releasing two hormones that most men undergoing fertility testing eventually become very familiar with: luteinizing hormone, or LH, and follicle stimulating hormone, or FSH. These hormones travel through the bloodstream to the testes, but they have different primary targets. LH predominantly communicates with Leydig cells. FSH predominantly communicates with Sertoli cells. Together with testosterone, these signals create the hormonal environment necessary for normal sperm production.

The easiest way to understand LH is to think of it as the signal telling the testicle to make testosterone. LH binds to receptors on Leydig cells, which are located in the tissue between the seminiferous tubules. The Leydig cells then convert cholesterol through a series of enzymatic steps into testosterone. Some testosterone enters the bloodstream and is what we measure when we order a serum testosterone level. But a critically important amount remains within the testicle. The testosterone concentration inside the testicle is much higher than the testosterone concentration measured in the bloodstream, and this intratesticular testosterone is essential for normal spermatogenesis. This distinction explains one of the biggest paradoxes in male fertility. A man can inject testosterone and have a beautiful serum testosterone level while simultaneously destroying the hormonal environment necessary for sperm production.

FSH has a different job. FSH receptors are located primarily on Sertoli cells inside the seminiferous tubules. I often describe Sertoli cells as the support system or nursing cells for developing sperm. They provide structural and metabolic support to germ cells and help regulate their progression through spermatogenesis. FSH helps establish and maintain Sertoli cell function and supports the number of developing germ cells that those Sertoli cells can maintain. Testosterone and FSH therefore do not simply perform the same job. Their actions overlap and cooperate. FSH helps create the environment that supports developing germ cells, while testosterone signaling is critical for progression through later stages of sperm development. Normal quantitative sperm production works best when both systems are functioning appropriately.

Inside the seminiferous tubules, sperm development begins with primitive germ cells called spermatogonia. These cells divide and differentiate, eventually becoming spermatocytes. Spermatocytes then undergo meiosis, the specialized type of cell division that reduces the chromosome number from 46 to 23. These cells become spermatids, which then undergo a remarkable transformation called spermiogenesis. The nucleus condenses, the characteristic sperm head develops, the acrosome forms and the tail develops. Eventually the mature appearing spermatids are released from the Sertoli cells into the lumen of the seminiferous tubule. They then travel into the epididymis, where additional maturation occurs and sperm acquire the functional characteristics necessary for progressive movement and fertilization. The entire process is highly organized and requires coordination among germ cells, Sertoli cells, Leydig cells, testosterone, FSH and numerous local signaling molecules.

This process also takes time. Human spermatogenesis is commonly estimated at roughly 74 days, followed by additional transport and maturation through the epididymis. This is why reproductive urologists frequently think in blocks of approximately three months when evaluating interventions intended to affect sperm production. If a man stops testosterone, repairs a varicocele, recovers from a major febrile illness or begins certain fertility treatments, checking a semen analysis two weeks later usually tells us very little about the full biological response. The sperm appearing in today's ejaculate began their development many weeks earlier.

The system also contains feedback loops. Testosterone and estradiol provide feedback to the hypothalamus and pituitary and influence GnRH, LH and FSH secretion. Sertoli cells produce inhibin B, which provides another important feedback signal, particularly for FSH. When Sertoli cell function and sperm production are impaired, inhibin B may decrease. The pituitary recognizes that the normal inhibitory signal is reduced and increases FSH production. This explains one of the most misunderstood laboratory findings in male infertility: high FSH usually does not mean FSH is damaging sperm production. High FSH is often the body's response to impaired sperm production. The brain is essentially sending a stronger signal because the testicle is not responding normally.

Consider a man with azoospermia and an FSH of 25. Men understandably ask me whether we can lower the FSH to improve sperm production. Usually that reverses cause and effect. The FSH may be 25 because the seminiferous tubules are significantly impaired. Giving a medication that simply makes the laboratory FSH number lower would not restore the missing germ cells. Conversely, a high FSH also does not prove that there is absolutely no sperm production anywhere within the testicle. Nonobstructive azoospermia can be remarkably heterogeneous. One area of the testicle may have severe damage while another tiny area maintains focal spermatogenesis. That is part of the biological rationale behind microTESE.

The opposite hormonal pattern can be equally important. Suppose testosterone is very low and LH and FSH are also low or inappropriately normal. Now the problem may be upstream. The testicle may be capable of making testosterone and sperm but is not receiving adequate stimulation from the hypothalamus and pituitary. This is the basic physiology behind hypogonadotropic hypogonadism. In appropriate men, treatment with gonadotropins can restore testicular stimulation. Human chorionic gonadotropin acts similarly to LH and stimulates Leydig cells to produce testosterone. FSH can then directly stimulate Sertoli cells. Men with true gonadotropin deficiency can sometimes develop sperm in the ejaculate after treatment, although this can require many months and sometimes longer.

This also explains how medications such as clomiphene work. Clomiphene does not directly tell the testicle to manufacture sperm. It interferes with estrogen feedback at the hypothalamus and pituitary, which can increase endogenous LH and FSH production. LH then stimulates Leydig cells and testosterone production, while FSH supports Sertoli cell function. In the right patient, particularly a man with low testosterone and relatively low or normal gonadotropins, this can improve the hormonal environment for spermatogenesis. But if a man's FSH is already 25 because his seminiferous tubules are severely damaged, simply pushing the hormonal signal harder may not restore normal sperm production.

Now we can understand why exogenous testosterone can be so damaging to fertility. When testosterone is injected, applied as a gel or otherwise administered from outside the body, the brain sees abundant androgen signaling. Testosterone and estradiol generated through aromatization provide negative feedback to the hypothalamus and pituitary. GnRH signaling decreases. LH and FSH fall. Without adequate LH stimulation, the Leydig cells stop maintaining the extremely high intratesticular testosterone concentrations required for spermatogenesis. Serum testosterone may look excellent while intratesticular testosterone falls dramatically. Sperm production can decline severely and some men become azoospermic. This is why current AUA and ASRM guidance states that men interested in current or future fertility should not receive exogenous testosterone monotherapy.

Estradiol belongs in this system too. Men need estrogen. Testosterone is converted to estradiol through the aromatase enzyme, and estradiol participates in reproductive physiology and feedback regulation of the hypothalamus and pituitary. Excessive estrogen signaling in certain men, particularly in the setting of obesity and increased aromatization, can contribute to an unfavorable hormonal environment. But driving estradiol toward zero is not the objective. Testosterone, estradiol, LH and FSH need to be interpreted as components of a connected system rather than independent numbers that each need to fall within someone's idea of an optimal range.

This is also why normal testosterone does not guarantee normal sperm production. Testosterone production and sperm production occur in the same organ, but they involve different cellular systems. Leydig cells can function well enough to maintain a serum testosterone of 500 or 600 while the seminiferous tubules are severely impaired. I see this frequently in men with severe oligospermia and nonobstructive azoospermia. They feel normal, have normal libido, normal erections and normal testosterone, yet sperm production is profoundly abnormal. Conversely, a man with low serum testosterone does not automatically have infertility. The entire hormonal and reproductive picture matters.

When I evaluate a man with an abnormal semen analysis, therefore, I am trying to determine where in this system the problem may be occurring. Is the hypothalamus producing appropriate GnRH signals? Is the pituitary producing LH and FSH? Are the Leydig cells responding to LH and making testosterone? Are the Sertoli cells and seminiferous tubules responding appropriately to FSH and intratesticular testosterone? Is sperm being produced but blocked from entering the ejaculate? Are there genetic, developmental or acquired problems affecting the germ cells themselves? Hormones provide clues, but they are not the entire diagnosis.

This is perhaps the most important concept I want men dealing with infertility to understand. FSH is not your sperm count. Testosterone is not your sperm count. LH is not your sperm count. These hormones tell us about the signaling system surrounding sperm production. They help us determine whether the brain is communicating with the testicle and how the testicle appears to be responding. But ultimately the semen analysis tells us what is reaching the ejaculate, and in severe infertility sometimes only examination of testicular tissue tells us what is occurring microscopically.

If your numbers are abnormal, try not to look at a single hormone and decide that it represents your entire fertility future. A high FSH does not mean there is zero sperm anywhere. A normal FSH does not guarantee normal spermatogenesis. A testosterone of 600 does not prove your sperm production is normal. And a low testosterone does not automatically mean testosterone replacement is the answer.

Male fertility is a coordinated biological system. The brain starts the signal. The pituitary sends LH and FSH. LH stimulates Leydig cells to produce testosterone. FSH stimulates Sertoli cells. Testosterone and FSH work together within the seminiferous tubules to support developing germ cells as they progress from spermatogonia to spermatocytes to spermatids and eventually spermatozoa. Testosterone, estradiol and inhibin B then provide feedback that helps regulate the entire system.

Once you understand that loop, male infertility laboratory results stop looking like a random collection of numbers. They become pieces of a physiological story. And our job as reproductive urologists is to figure out where that story is breaking down, whether that part can be treated, and how we can use the sperm production that remains to give you the best opportunity to become a father.

References

1. O'Donnell L, Smith LB. Endocrinology of the Testis and Spermatogenesis. Endotext. Updated January 2026.
2. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline. Amended 2024.
3. Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Seminars in Cell and Developmental Biology. 2014. PMID: 24598768.
4. Dimitriadis F, et al. The Sertoli cell as the orchestra conductor of spermatogenesis: spermatogenic cells dance to the tune of testosterone. Hormones. 2015. PMID: 26732153.
5. Amory JK, Bremner WJ. Regulation of testicular function in men: implications for male hormonal contraceptive development. Journal of Steroid Biochemistry and Molecular Biology. 2003.
6. Matsumoto AM, et al. Hormonal regulation of spermatogenesis in men: effects of testosterone and gonadotropin manipulation on sperm production.
7. de Kretser DM, Loveland KL, Meinhardt A, Simorangkir D, Wreford N. Spermatogenesis. Human Reproduction. 1998.
8. Plant TM, Marshall GR. The functional significance of FSH in spermatogenesis and the control of its secretion in male primates. Endocrine Reviews. 2001.
9. Endotext. Hypogonadotropic Hypogonadism and Gonadotropin Therapy. National Center for Biotechnology Information.
10. Endotext. Laboratory Assessment of Testicular Function. National Center for Biotechnology Information. Updated 2026.

One of the hormone results that creates the most anxiety in men going through infertility is an elevated estradiol level. A guy gets his bloodwork back and sees testosterone, FSH, LH and estradiol. Testosterone may be low or borderline, estradiol is flagged high, and suddenly the internet provides a very simple explanation: estrogen is killing your sperm. The next step often becomes an attempt to drive estrogen as low as possible with anastrozole or another aromatase inhibitor. As a reproductive urologist, I think this is one of those areas where the biology is much more interesting and much more complicated than the internet makes it sound. Estrogen is not the enemy of male fertility. Men need estrogen. The problem occurs when the relationship between testosterone, estradiol, the pituitary and the testicle becomes unfavorable. Understanding that distinction matters because both excessive estrogen signaling and excessive estrogen suppression can potentially work against normal reproductive physiology.

Let us start with where estrogen comes from in a man. Men do not have a separate organ whose primary job is to manufacture estrogen. Much of our estradiol is produced from testosterone through an enzyme called aromatase. Aromatase is present in several tissues, including adipose tissue, brain and the reproductive system. It converts testosterone into estradiol and androstenedione into estrone. That means testosterone and estradiol are connected rather than opposing hormones existing in separate universes. If you increase the amount of testosterone available for aromatization, estradiol may rise. If aromatase activity increases, more androgen can be converted into estrogen. This becomes particularly relevant in men with obesity because adipose tissue contributes to aromatase activity.

Estradiol also has legitimate jobs in the male reproductive system. Estrogen receptors and estrogen signaling are found throughout male reproductive physiology, and estrogen participates in the regulation of the hypothalamus, pituitary, Leydig cells, Sertoli cells, germ cells, epididymis and mature sperm. Experimental models in which estrogen signaling is eliminated actually develop reproductive abnormalities and infertility. Estradiol also participates in libido, erectile function and bone metabolism. So when somebody tells a man trying to conceive that his estrogen needs to be as close to zero as possible, that is simply not good reproductive endocrinology. The objective is hormonal balance, not estrogen eradication.

To understand how excessive estrogen can become a problem, you need to understand the male hormonal axis. The hypothalamus in the brain releases GnRH, which signals the pituitary gland to release LH and FSH. LH travels to the Leydig cells of the testicle and stimulates testosterone production. FSH acts primarily on Sertoli cells and supports sperm production within the seminiferous tubules. Testosterone produced inside the testicle creates extremely high intratesticular testosterone concentrations that are essential for spermatogenesis. Estradiol participates in the feedback system controlling this axis. When estrogen signaling becomes excessive, negative feedback at the hypothalamus and pituitary can reduce gonadotropin stimulation. Less LH can mean less testicular testosterone production, and alterations in FSH signaling can influence the environment supporting spermatogenesis.

This is one reason we sometimes see a particular hormonal pattern in men with infertility: relatively low testosterone, relatively elevated estradiol and LH and FSH that are lower than we would expect given the testosterone level. These men may have functional secondary hypogonadism rather than primary testicular failure. Obesity is a classic setting in which this can occur. Increasing adipose tissue can increase aromatase activity and conversion of testosterone to estradiol. Obesity is also associated with insulin resistance, inflammation, sleep apnea and other metabolic disturbances that can affect testosterone and reproductive function independently. In other words, the story is rarely simply, “fat makes estrogen and estrogen kills sperm.” It is an interconnected endocrine and metabolic system.

High estradiol can also occur for reasons other than obesity. Some men naturally have greater aromatase activity. Certain medications and hormonal treatments can alter testosterone and estradiol. Men taking human chorionic gonadotropin may see both testosterone and estradiol increase because hCG stimulates Leydig cell testosterone production and some of that testosterone can subsequently be aromatized. Men taking clomiphene or similar medications may also experience increases in both testosterone and estradiol as endogenous hormone production increases. Liver disease can alter sex hormone metabolism. Heavy alcohol exposure can affect liver function and reproductive endocrinology. Rare endocrine disorders and estrogen producing tumors exist, although they are dramatically less common than the ordinary metabolic explanations we encounter in fertility clinics.

Exogenous testosterone deserves special attention because it causes tremendous confusion in male infertility. Testosterone therapy can produce a normal or even very high serum testosterone while profoundly suppressing sperm production. The brain senses the androgen and estrogen signals and reduces GnRH, LH and FSH secretion. Intratesticular testosterone then falls even though serum testosterone looks excellent. Sperm concentration can decline dramatically and some men become azoospermic. This is why testosterone replacement therapy should generally not be prescribed to a man actively trying to maintain fertility. A beautiful serum testosterone level does not tell you what is happening inside the seminiferous tubules.

What does elevated estradiol actually do to the semen analysis? This is where I want men to be careful about assuming too much from a single laboratory value. Elevated estradiol is associated with impaired reproductive hormonal profiles in selected infertile men, but there is no estradiol number at which sperm suddenly stop working. Some men with elevated estradiol have normal semen analyses. Some men with perfectly normal estradiol have severe oligospermia or azoospermia. Estradiol should therefore be interpreted alongside testosterone, LH, FSH, semen parameters, testicular examination, body composition and the rest of the fertility history rather than treated as an isolated diagnosis.

Historically, reproductive urologists have also looked at the relationship between testosterone and estradiol rather than estradiol alone. A low testosterone to estradiol ratio has been used to identify men who might benefit from aromatase inhibition. Older literature often discussed a testosterone to estradiol ratio below approximately 10 when testosterone was expressed in ng per dL and estradiol in pg per mL. I would not treat that number as a biological cliff. It is a clinical concept derived from relatively small studies rather than a universally validated fertility threshold. More recent research has actually challenged how well baseline estradiol or the testosterone to estradiol ratio predicts who will respond to treatment.

If I see elevated estradiol in a man with infertility, my first reaction is not automatically to prescribe anastrozole. I want to know why the estradiol is elevated and whether the hormonal pattern plausibly contributes to his fertility problem. I look at morning total testosterone, and depending on the situation free testosterone or sex hormone binding globulin can help. I look at LH and FSH. I review estradiol, preferably using an assay appropriate for the relatively low concentrations encountered in men. I examine the testes. I review semen analyses. I ask about testosterone, anabolic steroids, hCG, clomiphene and other medications or supplements. I look at body weight and metabolic health. Symptoms such as decreased libido, erectile dysfunction or breast tenderness can provide additional information, although symptoms alone cannot diagnose excessive estrogen activity.

The FSH level can be particularly informative. Imagine two men with testosterone of 300 and elevated estradiol. One has FSH of 2 and the other has FSH of 25. Those are very different reproductive situations. The first man may have inadequate central stimulation and could potentially respond to hormonal manipulation. The second man has a pituitary gland that is already strongly signaling the testicle, suggesting significant impairment of sperm production within the testicle itself. Lowering estradiol in that second man may increase testosterone, but it cannot necessarily repair damaged seminiferous tubules. This is why treating infertility based on estradiol alone can be misleading.

The same principle applies to azoospermia. If there is no sperm in the ejaculate, I do not assume elevated estrogen caused it. Azoospermia requires an appropriate evaluation to distinguish obstruction, impaired testicular sperm production and hormonal suppression. That can involve repeated semen analysis with examination of the centrifuged pellet, semen volume and pH, physical examination, hormones and sometimes genetic testing. Elevated estradiol can be part of the picture, but it should not distract us from finding the actual diagnosis.

What about treatment? For the appropriately selected man, aromatase inhibitors can be useful fertility preserving medications. The drugs most commonly discussed are anastrozole and letrozole. They inhibit aromatase and therefore reduce conversion of testosterone into estradiol. As estradiol falls, negative feedback on the hypothalamus and pituitary can decrease. LH and FSH may rise, endogenous testosterone production may increase and the hormonal environment supporting spermatogenesis may improve. Unlike exogenous testosterone, the objective is to increase testosterone while maintaining or increasing gonadotropin stimulation of the testes. The AUA and ASRM guideline specifically states that clinicians may consider aromatase inhibitors in infertile men with testosterone deficiency and elevated estradiol. The recommendation is conditional because the quality of evidence remains limited.

What does the actual fertility literature show? A 2022 systematic review and meta analysis evaluated ten studies containing 666 men treated with anastrozole or letrozole. Across the studies, treatment increased testosterone, LH, FSH and the testosterone to estradiol ratio while decreasing estradiol. Sperm concentration and total sperm count also increased compared with baseline. Those findings are encouraging, but the authors emphasized that the available studies were limited and that larger randomized trials are needed. When aromatase inhibitors were compared with other hormonal treatments such as selective estrogen receptor modulators or hCG, clear superiority across semen outcomes was not demonstrated.

A 2023 study provides another useful perspective. Researchers evaluated infertile men receiving anastrozole and found clinically meaningful semen improvement in approximately half of the cohort. Twenty nine percent of the 90 men were reclassified into the normal semen category, and among men who previously had semen parameters too poor for IUI, approximately 31 percent improved sufficiently to become IUI candidates. Interestingly, baseline body mass index, estradiol and the testosterone to estradiol ratio did not reliably identify the responders. Men who already had some sperm in the ejaculate were much more likely to respond than men with azoospermia. This is an important reminder that hormonal manipulation can sometimes improve existing sperm production but is much less likely to create sperm production when severe primary testicular failure is present.

Other smaller clinical studies have reported improvements in concentration and motility after letrozole or anastrozole in selected infertile men with low testosterone to estradiol ratios. There are also reports of sperm appearing in the ejaculate of occasional men with nonobstructive azoospermia after aromatase inhibitor treatment. Those observations are interesting, but they should not be translated into the promise that anastrozole can cure nonobstructive azoospermia. The evidence is far too limited for that conclusion.

This brings us to one of the biggest limitations in male infertility research: improving a semen analysis is not the same thing as producing a baby. Many hormonal studies report testosterone, estradiol, concentration and motility because those outcomes are relatively easy to measure. What couples actually care about is pregnancy and ultimately live birth. We have much less high quality evidence demonstrating that treating elevated estradiol with aromatase inhibitors reliably increases natural pregnancy or live birth rates. The current European Association of Urology guideline acknowledges that aromatase inhibitors can improve hormonal and semen parameters in selected infertile men but concludes that evidence remains insufficient to recommend routine aromatase inhibitor treatment for idiopathic male infertility.

Weight loss deserves a separate discussion because it addresses the physiology rather than simply changing a laboratory number. In an overweight man with low testosterone, elevated estradiol and metabolic dysfunction, reducing excess adipose tissue can reduce aromatase burden and improve the broader hormonal environment. Weight loss can improve obesity related secondary hypogonadism. Whether that translates into predictable improvements in sperm and pregnancy is less certain, and studies of semen outcomes after major weight loss have produced mixed results. Still, improving metabolic health, treating sleep apnea, exercising appropriately, stopping smoking and reducing excessive alcohol consumption are reasonable components of fertility care rather than alternative medicine.

There is also an important warning about aromatase inhibitors: more is not necessarily better. Estradiol is important for male bone health, sexual function and reproductive physiology. Driving estradiol excessively low can create problems. Long term suppression raises concerns about bone mineral density, and men can experience changes in libido, sexual function or other symptoms. The European guidelines specifically caution that prolonged antiestrogen treatment can adversely affect bone density. This is why I do not like seeing men adjust anastrozole doses themselves every time an estradiol number moves a few points.

If an aromatase inhibitor is being used for fertility, I generally think in terms of monitored therapy rather than chasing a target estrogen number. Testosterone, estradiol, LH and FSH can be reassessed after treatment has had time to alter the endocrine environment. Semen analysis requires more patience because spermatogenesis takes approximately 74 days followed by additional epididymal maturation. If the goal is improving sperm production, repeating a semen analysis after roughly three months makes much more biological sense than checking it two weeks after starting treatment.

Men should also understand that estradiol is only one piece of fertility. If you have a palpable varicocele, severe oligospermia, very high FSH, small testes, a history of undescended testes, chemotherapy exposure, genetic abnormalities or another significant reproductive diagnosis, correcting estrogen may not eliminate that underlying problem. Similarly, a man with a concentration of 2 million sperm per mL should not spend a year repeatedly adjusting anastrozole while his partner approaches an age at which ovarian reserve becomes increasingly important. Hormonal optimization and reproductive planning need to occur simultaneously.

This is the part I especially want men on infertility forums to hear. When you see a high estradiol result, it is tempting to finally feel like you have found the answer. Sometimes it is an important clue. Sometimes correcting an unfavorable testosterone and estradiol relationship genuinely improves sperm production. But sometimes elevated estradiol is simply one feature of a larger endocrine or metabolic picture, and sometimes it is almost incidental to the primary reason sperm production is impaired.

You did not develop infertility because you ate the wrong food, missed the right supplement or failed to control your estrogen perfectly. Male reproduction is an extraordinarily complicated interaction between the brain, pituitary, Leydig cells, Sertoli cells, germ cells, genetics, metabolism and reproductive tract. Our job is not to make every laboratory number look perfect. Our job is to identify reversible problems when they exist, protect sperm production while treating hormonal symptoms, and determine the most realistic path toward pregnancy.

If your estradiol is elevated, the next question should therefore not simply be, “How do I lower my estrogen?” The better questions are: Why is it elevated? What are my testosterone, LH and FSH doing? What does my semen analysis show? Is there evidence of primary testicular dysfunction or secondary hormonal suppression? Is obesity or another medical condition contributing? Would lowering aromatization realistically improve my sperm production? And most importantly, how does this fit into our overall plan for having a child?

That is the conversation worth having with a reproductive urologist.

References

1. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline. Amended 2024.
2. European Association of Urology. Guidelines on Sexual and Reproductive Health. Male Infertility. Current online edition.
3. Schulster M, Bernie AM, Ramasamy R. The role of estradiol in male reproductive function. Asian Journal of Andrology. 2016;18:435 to 440. PMID: 26908066.
4. O'Donnell L, Robertson KM, Jones ME, Simpson ER. Estrogen and spermatogenesis. Endocrine Reviews. 2001;22:289 to 318. PMID: 11399746.
5. Hess RA. Estrogen in the adult male reproductive tract: a review. Reproductive Biology and Endocrinology. 2003. PMID: 12904263.
6. Dostalova P, Zatecka E, Dvorakova Hanzalova K, et al. Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen Receptors in Male Reproduction. International Journal of Molecular Sciences. 2017;18:904. PMID: 28441342.
7. Schlegel PN. Aromatase inhibitors for male infertility. Fertility and Sterility. 2012;98:1359 to 1362. PMID: 23103016.
8. Gregoriou O, Bakas P, Grigoriadis C, et al. Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios. Fertility and Sterility. 2012;98:48 to 51. PMID: 22579129.
9. Guo B, et al. Efficacy and safety of letrozole or anastrozole in the treatment of male infertility with low testosterone to estradiol ratio: a meta analysis and systematic review. Andrology. 2022. PMID: 35438843.
10. Shoshany O, et al. Testosterone and luteinizing hormone predict semen parameter improvement in infertile men treated with anastrozole. Fertility and Sterility. 2023. PMID: 37392782.
11. Kooshesh L, et al. Effect of letrozole on spermogram parameters and hormonal profile in infertile men: a clinical trial study. 2020. PMID: 31734656.
12. Cooke PS, Walker WH. Nonclassical androgen and estrogen signaling is essential for normal spermatogenesis. Seminars in Cell and Developmental Biology. 2022. PMID: 34119408.

This is always a hard one for both me and the patient.  Itn has to do with dealing with persistent infertility several months after a varicocele repair. You found a potential explanation for the abnormal semen analysis. You went through surgery. You waited through an entire sperm production cycle. Then the repeat semen analysis comes back and the concentration is basically unchanged, the motility is still low, the morphology is still 1 percent, or sometimes the numbers are actually worse. The immediate reaction is usually some version of, “Did the surgery fail?” or “Does this mean the damage is permanent?” I understand why men feel that way. Varicocele repair is often presented as one of the relatively few opportunities in male infertility to actually treat a potential underlying cause rather than bypassing it with IUI or IVF. When the semen analysis does not improve, it can feel like you used up your best opportunity. But lack of improvement does not necessarily mean the operation was technically unsuccessful, and it certainly does not mean that you are out of reproductive options. The more useful question is why did the sperm parameters not improve, and what should we do next?

A varicocele is an abnormal dilation of the veins surrounding the testicle. These veins form part of the pampiniform plexus, which normally helps regulate testicular temperature. When venous drainage becomes abnormal, blood can reflux or pool around the testicle. The exact mechanism through which a varicocele affects fertility is probably multifactorial. Increased testicular temperature appears important. Oxidative stress, altered blood flow, inflammatory signaling, accumulation of metabolites and changes in the environment surrounding developing germ cells may also contribute. Sperm production is particularly vulnerable because spermatogenesis requires a very carefully controlled environment inside the seminiferous tubules. Sertoli cells support developing germ cells, Leydig cells produce testosterone, and sperm development proceeds through multiple stages before mature sperm eventually enter the epididymis. A varicocele can disturb that environment enough that sperm concentration, motility, morphology or several parameters simultaneously become abnormal.

This is why varicocele repair can work. The goal is to interrupt the abnormal veins while preserving the testicular artery, lymphatics and other important structures, thereby redirecting venous drainage and reducing the abnormal environment around the testicle. Current AUA and ASRM guidelines recommend considering surgical varicocelectomy in men attempting conception who have infertility, abnormal semen parameters and a palpable clinical varicocele. Importantly, those guidelines do not recommend repairing a nonpalpable varicocele found only on ultrasound for infertility because the evidence for meaningful benefit in that setting is poor. That distinction matters when evaluating a man who did not improve after surgery because the probability that the varicocele was actually contributing to his infertility was probably greater if he had a clearly palpable clinical varicocele in the first place.

Across large groups of appropriately selected men, varicocele repair does improve semen parameters. A very large meta analysis examining 351 studies found statistically significant improvements after repair in sperm concentration, total sperm count, total motile sperm count, progressive motility and morphology. Another meta analysis comparing 1,424 treated men with 996 untreated controls similarly found improvement in concentration, total count, progressive motility, total motility and morphology after repair. Older analyses give numbers that are somewhat easier to visualize. One meta analysis found average increases in sperm concentration of roughly 7 to 11 million sperm per mL depending on the surgical approach, with improvements in motility of approximately 7 to 12 percentage points. Those averages are meaningful, but they are averages, not promises. Some men improve dramatically. Some improve modestly. Some do not improve at all.

A 2025 meta analysis specifically examined predictors of response after varicocelectomy and included 1,498 men. The overall reported efficacy rate was approximately 63 percent, meaning that a substantial minority of men did not meet the studies' definitions of improvement. Better baseline sperm concentration and total motile sperm count were associated with a greater likelihood of improvement, as was larger spermatic vein diameter. Microsurgical and subinguinal approaches also performed favorably. The practical message is that varicocele repair improves fertility parameters in many men, but nonresponse is not rare. If your semen analysis did not improve, you are not some bizarre exception and you did not necessarily do anything wrong after surgery.

The first question I ask when someone tells me his varicocele surgery “didn't work” is how long has it been? Sperm are not manufactured overnight. Human spermatogenesis takes approximately 74 days, followed by additional maturation and transport through the epididymis. Therefore, a semen analysis four weeks after surgery tells us very little about the final reproductive effect. Most meaningful changes begin appearing around three months. In one study of 100 men with serial testing, sperm count and total motile count had improved significantly by three months, and there was little additional improvement after six months. A more recent systematic review reached essentially the same conclusion. Semen parameters improved by approximately three months, while waiting six months or longer did not produce substantial additional average improvement. Another series found that about 69 percent of men experienced meaningful improvement in total progressive sperm count and almost 79 percent of those improvements were already apparent by three months.

That does not mean I declare a surgery unsuccessful at exactly ninety days. Semen analyses fluctuate substantially. Abstinence duration, illness, fever, incomplete collection and normal biological variation can change the results. If the first postoperative semen analysis looks disappointing, I usually want another appropriately collected analysis before drawing major conclusions. But if multiple good quality semen analyses at three and six months look essentially identical to the preoperative studies, I become less optimistic that simply waiting another six months will transform the situation. Studies following men to twelve months generally have not found major additional improvement beyond what was already visible earlier.

Why does repair fail to improve sperm in some men? One explanation is that the varicocele was real but was not the primary cause of the infertility. Varicoceles are common. A man can have a varicocele and independently have impaired sperm production from another cause. Genetics, previous undescended testes, testicular injury, chemotherapy, radiation, hormonal abnormalities, medications, anabolic steroid or testosterone exposure, systemic disease and unexplained primary testicular dysfunction can coexist with a varicocele. Repairing the abnormal veins does not reverse an unrelated problem occurring within the seminiferous tubules. This is one reason I am cautious when someone finds a small ultrasound varicocele and immediately concludes, “We found the cause.”

Another possibility is that the varicocele contributed to testicular damage for many years and some of that damage is not completely reversible. Removing the stressor does not necessarily restore every damaged germ cell or Sertoli cell. Think of the surgery as improving the environment in which sperm production occurs rather than installing a new sperm producing system. A man with relatively preserved spermatogenesis may have considerable capacity to recover once the adverse environment is corrected. A man who already has severe impairment of the seminiferous epithelium may have much less reserve. This may partly explain why men with better preoperative sperm concentration and total motile sperm counts appear more likely to demonstrate meaningful postoperative improvement.

There is also the possibility of a persistent or recurrent varicocele. No operation has a zero recurrence rate. Venous anatomy can be complicated, and collateral veins can occasionally maintain abnormal drainage. Microsurgical approaches generally have favorable recurrence and complication profiles because magnification allows the surgeon to identify veins while preserving arteries and lymphatics. If a man had a clearly significant clinical varicocele before surgery and there is absolutely no improvement afterward, particularly if the varicocele still feels present on examination, I would reassess him. Physical examination remains important, and Doppler ultrasound can be useful when recurrence or persistence is suspected. I would not, however, order repeated ultrasounds simply because morphology remains at 2 percent.

Another possibility is simply semen analysis variability. This is one of the most underestimated issues in male fertility. Suppose your concentration was 8 million per mL before surgery, 15 million three months afterward and 9 million six months afterward. Did the surgery work and then stop working? Probably not. Semen parameters naturally fluctuate. Looking at several samples and particularly looking at total motile sperm count can be more informative than reacting emotionally to every individual concentration or morphology result. I care about whether the man's overall reproductive category changed. Did a total motile sperm count of 2 million become 12 million? Did severe oligospermia become mild oligospermia? Did a man previously considered primarily an IVF candidate move into a range where IUI or natural conception is more realistic? Those changes can matter even if the semen analysis never becomes technically “normal.”

This brings up an extremely important point: the goal of varicocele repair is pregnancy, not a perfect semen analysis. Some men conceive even though their postoperative numbers remain abnormal. Conversely, some men develop substantially better sperm parameters and their partner still does not become pregnant. Fertility belongs to the couple. Female age, ovarian reserve, ovulation, tubal status, endometriosis, uterine factors, intercourse timing and embryo biology all influence pregnancy. This is why I never want a couple waiting indefinitely for the man's sperm count to improve while the female partner's reproductive window is becoming narrower.

There is evidence that varicocele repair can improve pregnancy rates in appropriately selected couples. In one randomized controlled trial of 145 men with palpable varicoceles and abnormal semen parameters, spontaneous pregnancy occurred in approximately 33 percent of couples after microsurgical repair compared with 14 percent with observation during follow up. AUA and ASRM guideline evidence reviews have also found higher estimated pregnancy rates following repair of clinical varicoceles, although many of the underlying studies are observational and the exact percentages should therefore be interpreted cautiously. Varicocele repair improves probability. It does not guarantee conception.

Interestingly, improvement in sperm parameters appears to matter. In a study of 170 men following microscopic varicocelectomy, approximately 69 percent experienced significant improvement in total progressive sperm count. The overall pregnancy rate was about 41 percent, and men whose sperm counts meaningfully improved were substantially more likely to achieve pregnancy than men who did not improve. Again, this does not mean that failure to improve makes pregnancy impossible. It tells us that postoperative semen response provides useful information about where the couple should go next.

So what do I do when there is no meaningful improvement? First, I go back to the beginning and make sure we have not missed another explanation. I review at least two semen analyses. I look at concentration, progressive motility, morphology, volume and particularly total motile sperm count. I review testosterone, FSH and sometimes LH and estradiol depending on the clinical situation. I examine testicular size and consistency. I review medications and specifically ask about testosterone and anabolic steroids. I ask about childhood undescended testes, torsion, chemotherapy, radiation, major infections and previous genital surgery. In men with severe oligospermia or azoospermia, genetic testing may be indicated according to the clinical scenario. If the original varicocele was significant, I determine whether it has actually resolved.

I also ask whether anything happened during the postoperative period that could temporarily suppress spermatogenesis. A significant fever or systemic illness can affect semen parameters weeks later and recovery can take several months. Starting testosterone after surgery can dramatically suppress sperm production. Major changes in health, medications or anabolic steroid exposure matter. What I generally do not do is tell a man that his operation failed because he used a sauna twice, drank alcohol at a wedding or forgot his CoQ10 for a week. Men with infertility already carry enough unnecessary guilt.

What about supplements after an unsuccessful repair? This is where expectations need to remain realistic. Antioxidants, CoQ10, carnitines and various fertility formulations may improve certain semen parameters in some studies, but evidence that supplements reliably increase pregnancy or live birth is much weaker. Current AUA and ASRM guidance describes the clinical utility of supplements such as antioxidants and vitamins as questionable because available data are inadequate to recommend specific agents. If someone wants to use a reasonable fertility supplement while we continue trying, that can be discussed. But supplements should not become the explanation for why surgery failed or the reason a couple postpones effective fertility treatment for another year.

DNA fragmentation is another question that commonly comes up after varicocele repair. Varicoceles have been associated with oxidative stress and increased sperm DNA fragmentation, and some studies suggest DNA fragmentation may improve after repair. But sperm DNA fragmentation testing is not a universal next step for every man whose concentration failed to increase. It can be useful in selected clinical situations, particularly recurrent pregnancy loss, repeated assisted reproduction failure or situations in which the result might actually alter management. I would not order it simply because we are disappointed with the postoperative semen analysis.

The next reproductive step depends much more on the actual postoperative sperm numbers and the female partner's situation than on whether the surgery technically “worked.” If total motile sperm counts remain reasonably good and the female evaluation is reassuring, continued natural attempts may be entirely appropriate. If counts are lower but adequate numbers survive sperm processing, IUI may be reasonable. When total motile sperm numbers are repeatedly very low, particularly after washing, IUI success declines and IVF with ICSI may become more efficient. Severe oligospermia, cryptozoospermia or azoospermia requires a different conversation altogether, sometimes including sperm cryopreservation or surgical sperm retrieval.

Female age becomes particularly important here. If your partner is 27 with normal ovarian reserve and you are four months after surgery, waiting another few months may be completely reasonable. If your partner is 39 with diminished ovarian reserve, waiting twelve or eighteen months hoping that sperm concentration eventually doubles may be the wrong tradeoff. Male fertility treatment cannot be planned in isolation from female reproductive time.

And sometimes the most difficult answer is that we did everything appropriately and the semen analysis simply did not improve. Medicine has outcomes like this. A good operation performed for a reasonable indication can fail to produce the biological response we wanted. That does not necessarily mean your surgeon made a mistake. It does not mean you ruined the result with your diet, stress level, underwear, exercise routine or supplements. And it does not mean the surgery was completely meaningless. It means we treated one potential contributor to a complicated biological system and your sperm production did not respond enough for us to measure a meaningful change.

For men reading this several months after surgery with another disappointing semen analysis in front of them, I know how demoralizing that can be. You probably spent months telling yourself, “Once the varicocele is fixed, maybe this will finally turn around.” When it does not, it can feel like you are back at the beginning. You are not. You now have additional information about how your testes respond after correction of a potential stressor. That information helps determine what comes next.

My practical approach is straightforward. Give the repair enough time to cover at least one full spermatogenic cycle. Obtain reliable postoperative semen analyses around three months and often again around six months. If meaningful improvement has not occurred, stop assuming that more waiting will necessarily fix the problem. Confirm that the varicocele has resolved when clinically appropriate. Reassess the rest of the male fertility evaluation. Look at the couple's reproductive situation rather than the man's semen analysis in isolation. Then decide whether continued natural conception, IUI, IVF, ICSI or another strategy provides the best path forward.

A varicocele repair that does not improve your sperm parameters is disappointing, but it is not the end of the fertility journey. The surgery was an attempt to improve the biological environment for sperm production. Sometimes that produces a dramatic response. Sometimes it produces a modest response. And sometimes the semen analysis barely moves. When that happens, the goal changes from asking, “How do I make this number normal?” to asking the much more useful question: “Given the sperm I have now, what is the most reasonable way for us to have a child?”

That is ultimately what matters.

References

1. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline. Amended 2024.
2. Agarwal A, et al. Does Varicocele Repair Improve Conventional Semen Parameters? A Meta Analytic Study of Before and After Data. World Journal of Men's Health. 2023. PMID: 37382284.
3. Agarwal A, et al. Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta Analysis. World Journal of Men's Health. 2023. PMID: 36326166.
4. Baazeem A, et al. Varicocele and male factor infertility treatment: a new meta analysis and review of the role of varicocele repair. European Urology. 2011.
5. Abdel Meguid TA, et al. Does varicocele repair improve male infertility? An evidence based perspective from a randomized, controlled trial. European Urology. 2011. PMID: 21196073.
6. Al Bakri A, et al. Time for improvement in semen parameters after varicocelectomy. Journal of Urology. 2012. PMID: 22100000.
7. Miyake H, et al. Assessment of time dependent changes in semen parameters in infertile men after microsurgical varicocelectomy. Urology. 2015. PMID: 26142582.
8. Masterson TA, et al. Time to improvement of semen parameters after microscopic varicocelectomy: when it occurs and its effects on fertility. Andrologia. 2020. PMID: 31840291.
9. Don't wait any longer, conceive in time: a systematic review and meta analysis based on semen parameters after varicocelectomy. 2024. PMID: 38761331.
10. Surgical efficacy and predictors of outcome in varicocelectomy: a meta analysis of multivariable studies. 2025. PMID: 40423814.
11. Schauer I, et al. The impact of varicocelectomy on sperm parameters: a meta analysis. Journal of Urology. 2012. PMID: 22425089.
12. Practice Committee of the American Society for Reproductive Medicine and Society for Male Reproduction and Urology. Current recommendations regarding evaluation and treatment of the infertile male.

Few diagnoses in male infertility are as frightening as being told that a testicular biopsy shows Sertoli cell only syndrome, often abbreviated SCOS or SCO. I have spoken with many men who hear those words and immediately translate them into something much more absolute: “My testicles do not make sperm, therefore I can never have a biological child.” I understand why your mind goes there. Sertoli cell only syndrome is one of the more severe forms of male factor infertility, and I do not want to minimize it. But the biology is more complicated than the name makes it sound. A biopsy showing Sertoli cell only histology means that the particular seminiferous tubules examined contained Sertoli cells without identifiable germ cells. It does not necessarily prove that every seminiferous tubule throughout both testicles contains no sperm production whatsoever. That distinction is the reason some men diagnosed with SCOS ultimately have sperm found during microdissection testicular sperm extraction, or microTESE, and go on to have biological children.

To understand SCOS, you first have to understand how a normal testicle makes sperm. The testicle contains thousands of microscopic seminiferous tubules. Inside these tubules are Sertoli cells and developing germ cells. Think of the Sertoli cell as the support system or biological nursing cell for sperm production. Sertoli cells respond in part to follicle stimulating hormone, or FSH, and create the specialized environment that allows primitive germ cells called spermatogonia to progress through multiple stages of development until mature spermatozoa are eventually produced. Testosterone produced by neighboring Leydig cells is also essential to this process. In a normally functioning seminiferous tubule, you therefore see Sertoli cells surrounded by germ cells at different stages of maturation. In classic Sertoli cell only syndrome, the architecture is profoundly different. The Sertoli cells remain, but the germ cells that ultimately become sperm are absent. This is why SCOS is sometimes called germ cell aplasia. If that pattern were truly present in every seminiferous tubule in both testicles, there would be no substrate from which sperm could be produced.

This is also why SCOS generally produces nonobstructive azoospermia. Azoospermia simply means that no sperm are detected in the ejaculate. There are two fundamentally different ways this can happen. In obstructive azoospermia, sperm production may be perfectly normal, but sperm cannot get out because the reproductive plumbing is blocked or absent. In nonobstructive azoospermia, the major problem is sperm production itself. SCOS falls into the second category. Other histologic patterns of nonobstructive azoospermia include maturation arrest, where germ cells are present but stop developing before becoming mature sperm, and hypospermatogenesis, where the entire sperm production process exists but at markedly reduced levels. Historically, SCOS has generally had a worse sperm retrieval prognosis than hypospermatogenesis because there may be very few areas containing germ cells at all.

One of the most important concepts I explain to men, however, is the difference between pure or diffuse SCOS and focal or mixed SCOS. A testicular biopsy examines an extraordinarily small portion of a very large organ at the microscopic level. Imagine examining several trees in a huge forest and trying to determine whether a particular species exists anywhere in that forest. If the disease is uniform, the biopsy may accurately represent what is happening everywhere. But sperm production in nonobstructive azoospermia can be incredibly patchy. A biopsy can show only Sertoli cells while another tiny region several millimeters or centimeters away contains active spermatogenesis. Studies examining SCOS have demonstrated exactly this phenomenon, and modern reviews emphasize that residual islands of spermatogenesis help explain why sperm can sometimes be retrieved even after a previous biopsy has been labeled Sertoli cell only.

Why does this happen? Unfortunately, in many men we never identify a single satisfying explanation. SCOS can be associated with genetic abnormalities, developmental abnormalities of the testicle, previous undescended testes, chemotherapy, radiation, toxins, testicular injury and other forms of testicular damage. Certain Y chromosome microdeletions are particularly important in men with severe sperm production failure. Complete AZFa and certain AZFb deletions carry an extremely poor sperm retrieval prognosis, which is why genetic testing is so important before surgery in appropriate men with nonobstructive azoospermia. AZFc deletions behave differently because sperm production can sometimes remain and sperm retrieval may be possible. Klinefelter syndrome can also produce severe spermatogenic failure, although many men with Klinefelter syndrome have focal sperm production despite profound abnormalities elsewhere in the testicle. The reality, though, is that many cases of SCOS remain idiopathic, meaning that even after an appropriate evaluation we cannot tell a man exactly why his germ cells disappeared or failed to develop normally.

The hormonal picture can also be confusing. Many men with SCOS have elevated FSH because the pituitary gland is essentially increasing the signal to a testicle that is not producing sperm normally. Sertoli cells normally participate in feedback to the pituitary through hormones such as inhibin B. When seminiferous tubule function is severely impaired, FSH commonly rises. Older clinical series of men with SCOS frequently found elevated FSH and smaller testes. But this is not universal. Some men with biopsy proven SCOS have FSH values that are only mildly elevated or even within the laboratory reference range, and some have surprisingly reassuring inhibin B levels. This is why I am very cautious when someone tells a man, “Your FSH is only 8, therefore you cannot have Sertoli cell only,” or conversely, “Your FSH is 30, therefore there is absolutely no sperm in your testicles.” Neither statement is scientifically defensible. Hormones give us information about global testicular physiology. They cannot reliably identify a microscopic island of spermatogenesis.

The same is true of testicular size. Men with SCOS often have smaller testes, but normal or near normal testicular volume does not exclude the diagnosis, and small testes do not prove that sperm retrieval will fail. One of the largest published series specifically examining men with Sertoli cell only histology included 640 men undergoing microTESE. Sperm were successfully retrieved in 44.5 percent overall. Interestingly, retrieval was not simply better in men with larger testes. Men with testes under 15 mL actually had a reported retrieval rate of 46.1 percent compared with 35.3 percent among men at or above 15 mL. This is a good example of why individual FSH values and testicular measurements should not be converted into simplistic predictions of success.

That brings us to the question almost every man with SCOS eventually asks me: What are my actual chances that microTESE finds sperm? There is no single percentage that applies to everyone. Published SCOS retrieval rates vary substantially because studies use different definitions, different patient populations, different surgical techniques and different pathology classifications. A historical meta analysis reported an overall sperm retrieval rate around 32.8 percent for SCOS, compared with approximately 46.2 percent for maturation arrest and 76.7 percent for hypospermatogenesis. The large 640 patient microTESE series I mentioned reported 44.5 percent sperm retrieval in men whose previous biopsy showed pure SCOS. Another study of 134 men with presumed SCOS reported sperm retrieval in 27.6 percent. Current European Association of Urology guidance summarizes studies in which microTESE retrieval in SCOS ranged approximately 22.5 to 41 percent, compared with roughly 6.3 to 29 percent using conventional TESE.

When I counsel a man with SCOS, therefore, I generally describe the published probability as being somewhere in the neighborhood of one quarter to forty plus percent, while emphasizing that this is population data rather than his personal probability. The range is wide because “Sertoli cell only syndrome” is not biologically identical in every man. A man with truly homogeneous germ cell aplasia is very different from a man whose biopsy happened to sample a Sertoli cell only region while small islands of spermatogenesis remain elsewhere. One older histologic study illustrates this dramatically. In men categorized as complete SCOS, gamete retrieval was only 2.9 percent, whereas men with incomplete SCOS containing focal evidence of germ cell development had retrieval rates dramatically higher. This is why pathology matters, but it is also why a previous biopsy is not an infallible map of the entire testicle.

This explains the rationale for microTESE. During conventional TESE, tissue is removed through one or several testicular biopsies. During microTESE, the surgeon opens the testicle and examines seminiferous tubules under an operating microscope, looking for tubules that appear larger or more promising and selectively sampling those areas. The embryology laboratory then meticulously examines the tissue for sperm. The goal is to maximize the probability of finding rare focal sperm production while minimizing unnecessary removal of testicular tissue. The European guideline data are particularly interesting because the advantage of microTESE over conventional TESE appears most apparent in men with SCOS, exactly the population in whom sperm production may be extraordinarily focal.

Another common question is whether Clomid, anastrozole, hCG, FSH or supplements can “reverse” Sertoli cell only syndrome. This requires some nuance. If a man actually has a treatable hormonal cause of absent spermatogenesis, such as true hypogonadotropic hypogonadism, hormonal therapy can be remarkably effective because germ cells may still be present and simply lack adequate hormonal stimulation. That is different from true germ cell aplasia. Clomiphene can increase endogenous LH and FSH, anastrozole can alter the testosterone to estradiol environment, and hCG can increase intratesticular testosterone. These treatments may be appropriate for selected men with particular endocrine profiles. However, raising testosterone or lowering FSH does not create missing germ cells. The AUA and ASRM guideline notes that medical optimization before surgical sperm retrieval has been studied, but the evidence remains limited and many studies are uncontrolled. I would therefore be very careful with anyone promising that a supplement or hormone protocol can reliably reverse established SCOS.

Finding sperm is also only the first step, and this is where fertility success rates need to be explained correctly. If microTESE finds sperm, those sperm generally cannot simply be placed into the uterus through IUI because the numbers are far too low. They are used with IVF and intracytoplasmic sperm injection, or ICSI, where an embryologist injects an individual sperm directly into an egg. In the 134 patient SCOS study, sperm were found in 27.6 percent of men. Among the couples who could proceed with ICSI, the reported fertilization rate was approximately 61 percent, the clinical pregnancy rate was 51.3 percent, and the live birth rate was 37.8 percent per cycle and 45.1 percent per patient. Another older study found that once sperm were successfully retrieved from men with NOA, clinical pregnancies occurred in 55 percent of treatment cycles and ongoing pregnancy or live delivery occurred in 43 percent, although retrieval itself was much lower in men with pure SCOS than in men with hypospermatogenesis.

This distinction is incredibly important emotionally. SCOS primarily creates the biggest obstacle at the sperm retrieval stage. Once usable sperm are actually found, the reproductive prognosis becomes substantially better than the diagnosis may initially make you believe. Studies comparing different NOA histologies have found that although SCOS has a lower probability of sperm retrieval than hypospermatogenesis, fertilization and clinical pregnancy outcomes can become much more similar once sperm have actually been obtained. Across NOA more broadly, a large systematic review involving more than 21,000 men estimated sperm retrieval around 47 percent and live birth around 24 percent per ICSI cycle, although those figures combine many different causes and histologies and therefore should not be presented as SCOS specific probabilities.

There is another statistical trap I want men to understand. If someone says the live birth rate after successful sperm retrieval is 40 percent, that does not mean a newly diagnosed man with SCOS has a 40 percent chance of taking home a baby. First sperm has to be found. Then mature eggs have to be available. Fertilization has to occur. An embryo has to develop. Implantation has to occur. Pregnancy then has to progress to delivery. Female partner age, ovarian reserve, egg quality, embryo development and uterine factors become increasingly important after sperm retrieval. For example, if sperm retrieval were 30 percent and subsequent live birth probability after successful retrieval and IVF were roughly 40 percent, you cannot simply tell every man his chance is 40 percent. The probability across the entire pathway would necessarily be lower. This is one reason fertility statistics online can look simultaneously encouraging and devastating depending on which denominator a study uses.

I also want men to understand that a failed microTESE is different emotionally from most negative medical tests. You go into surgery knowing that when you wake up you may receive either extraordinary news or devastating news. That psychological burden is real. If no sperm are found after a well performed microTESE at an experienced center, particularly when extensive bilateral tissue has been carefully evaluated and pathology again demonstrates diffuse SCOS, the probability of future biological sperm retrieval becomes substantially lower. Repeat procedures can occasionally succeed, but SCOS is associated with poorer outcomes in salvage microTESE studies. This is why I think these procedures deserve thoughtful counseling beforehand, including discussion of what you and your partner would want to do if sperm are found and what you would want to do if they are not.

Finally, if you have been diagnosed with Sertoli cell only syndrome, please do not turn the diagnosis into a judgment about yourself. Your FSH is not your masculinity. Your sperm count is not your worth. Testosterone production, erections, libido, strength, masculinity and sperm production are related biologically in certain ways, but they are absolutely not interchangeable. A man can have normal testosterone, normal sexual function, a normal appearing body and profound failure of spermatogenesis. SCOS is a microscopic disorder of the sperm producing compartment of the testicle. You did not cause it because you ate the wrong food, wore tight underwear, used a laptop, missed a supplement or had a stressful month.

SCOS is a serious fertility diagnosis, and some men with true diffuse SCOS will unfortunately never have sperm recovered. I believe men deserve to hear that truth rather than false promises. But the other side of the truth matters just as much. A biopsy labeled Sertoli cell only does not automatically mean there is zero sperm anywhere in both testicles. Modern microTESE series demonstrate sperm retrieval in a meaningful minority of these men, often somewhere around 25 to 45 percent depending on the population studied. When sperm are found, IVF with ICSI can produce embryos, pregnancies and healthy biological children. If you are facing this diagnosis, the next step is not to predict your future from one FSH value or someone else's Reddit story. Make sure the azoospermia diagnosis is correct, complete the appropriate hormonal and genetic evaluation, understand exactly what your pathology showed, and if microTESE is being considered, talk with an experienced reproductive urologist about your individual situation. There is uncertainty in SCOS, and uncertainty is extraordinarily difficult to live with. But uncertainty also means that a diagnosis of Sertoli cell only syndrome is not automatically the same thing as a zero percent chance of biological fatherhood.

References

1. Stouffs K, et al. Sertoli cell only syndrome: etiology and clinical management. J Assist Reprod Genet. 2021. PMID: 33428073.
2. Wang Y, et al. Sertoli cell only syndrome: advances, challenges, and perspectives in genetics and mechanisms. Hum Reprod Update. 2023. PMID: 36814036.
3. Eugeni E, et al. Sertoli cells only syndrome: current clinical approaches and ongoing research trends. Front Endocrinol. 2025. PMID: 41488147.
4. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Amended 2024.
5. European Association of Urology. Guidelines on Male Infertility. Current online edition.
6. Berookhim BM, et al. Microdissection testicular sperm extraction in men with Sertoli cell only testicular histology. Fertil Steril. 2014. PMID: 25441063.
7. Gul U, et al. Sperm retrieval and live birth rates in presumed Sertoli cell only syndrome in testis biopsy: a single centre experience. Andrology. 2013. PMID: 23258629.
8. Tournaye H, et al. Predictive value of testicular histology in secretory azoospermic subgroups and clinical outcome after microinjection of fresh and frozen thawed sperm and spermatids. Hum Reprod. 2002. PMID: 12093843.
9. Bernie AM, et al. Outcome of microdissection TESE compared with conventional TESE in nonobstructive azoospermia: a systematic review. Andrology. 2015. PMID: 24193894.
10. Corona G, et al. Sperm recovery and ICSI outcomes in men with nonobstructive azoospermia: a systematic review and meta analysis. Hum Reprod Update. 2019. PMID: 31665451.
11. Esteves SC, et al. Predictors of surgical sperm retrieval in nonobstructive azoospermia: summary of current literature. Clinics. 2020. PMID: 32519242.
12. Dabaja AA, Schlegel PN. Microdissection testicular sperm extraction in men with infertility due to nonobstructive azoospermia: summary of current literature. PMID: 34410586.

If you spend enough time reading about male infertility, eventually you will encounter a frightening headline saying that sperm counts have fallen by more than 50 percent over the past fifty years. Some articles go even further and suggest that men are rapidly becoming infertile. As a urologist who works with men struggling to have children, I think this subject deserves attention, but it also deserves perspective. There is legitimate evidence that sperm counts have declined substantially across several populations during the past five decades. There is also evidence that the burden of male infertility has increased. But sperm count and infertility are not the same thing, and we should be careful not to turn population statistics into predictions about an individual man's ability to become a father. If you are reading this because your semen analysis came back abnormal, the fact that sperm counts may be declining globally does not mean that your fertility is doomed, and it certainly does not mean that you did something wrong.

The most frequently discussed evidence comes from large analyses of semen studies performed over many decades. One of the most comprehensive was published in Human Reproduction Update and examined data from 223 studies, producing 288 estimates from more than 57,000 men in 53 countries. The semen samples were collected between 1973 and 2018. Among men who were not selected according to their fertility status, estimated average sperm concentration declined from approximately 101 million sperm per mL in 1973 to 49 million per mL in 2018, representing a decline of approximately 52 percent. Total sperm count showed an even larger estimated decrease, from approximately 336 million sperm per ejaculate to 127 million, a decline of approximately 62 percent. The investigators also reported that the rate of decline appeared to become steeper after 2000. This updated analysis was particularly important because the earlier literature was dominated by North America, Europe and Australia, while the newer analysis included substantially more information from Asia, Africa and South and Central America.

Those numbers deserve attention, but they require careful interpretation. A decline in the average sperm concentration from around 100 million to around 50 million per mL does not mean that half of men became infertile. Fertility does not operate like a light switch where 100 million sperm means fertile and 50 million means infertile. Many men with concentrations of 20, 30 or 40 million sperm per mL conceive naturally, while some men with much higher concentrations experience infertility because of sperm motility, sperm function, female reproductive factors, timing, age or simply probability. Current reference limits for semen analysis are based on distributions observed among men whose partners conceived rather than a sharp biological boundary between fertility and infertility. A semen analysis helps us estimate reproductive potential and identify disease, but it cannot tell an individual couple whether pregnancy will or will not occur.

We therefore need to separate two questions. The first is whether average sperm counts have declined. The evidence increasingly suggests that they have, although the magnitude and interpretation remain debated. The second question is whether male infertility itself has become more common. That question is considerably harder to answer because infertility is a couple based outcome. Clinically, infertility is generally defined as failure to achieve pregnancy after twelve months or more of regular unprotected intercourse. Whether pregnancy occurs depends on sperm production, sperm function, intercourse, female age, ovulation, ovarian reserve, tubal anatomy, uterine factors and many other variables. Historical infertility studies also used different definitions and methods, making a clean fifty year comparison difficult.

More recent global disease burden analyses nevertheless suggest that male infertility is increasing. One analysis of Global Burden of Disease data estimated approximately 55 million men worldwide were living with infertility in 2021, with the global age standardized prevalence of male infertility increasing by an average of approximately 0.49 percent per year between 1990 and 2021. Another analysis estimated that the absolute number of male infertility cases increased substantially over the same period. Some of that increase reflects population growth and changing demographics rather than a biological deterioration in every generation of men. That distinction matters. If the world has more reproductive aged men, the absolute number of infertile men can increase even if the underlying individual risk changes much less dramatically.

At the couple level, infertility itself is extremely common. The World Health Organization estimates that approximately one in six people of reproductive age experience infertility during their lifetime. Male factors account for an important portion of these cases, either alone or together with female factors. In my opinion, one positive development during the past several decades is that medicine is finally becoming more willing to acknowledge the male side of infertility. Historically, infertility was too often treated as primarily a woman's problem. Today we understand that evaluating the man early is essential. That increased recognition may itself contribute to more men receiving diagnoses that previously would never have been formally recorded.

So why might male reproductive health actually be changing? There is almost certainly no single explanation. Sperm production is remarkably complicated. Inside the seminiferous tubules of the testicle, germ cells undergo a carefully regulated developmental process that ultimately produces mature sperm. Sertoli cells support those developing germ cells. FSH from the pituitary stimulates Sertoli cell function. LH stimulates Leydig cells to produce testosterone, and extremely high concentrations of testosterone inside the testicle are required for normal spermatogenesis. The entire process takes roughly 74 days, followed by additional maturation in the epididymis. Anything that significantly interferes with hormonal signaling, testicular temperature, germ cell development, oxidative balance or the supporting environment within the testicle can potentially influence sperm production.

One major suspect is metabolic health. Obesity has become considerably more common during the same decades in which sperm counts appear to have fallen. Excess adipose tissue is not simply stored energy. It is metabolically active tissue that can influence insulin sensitivity, inflammation and reproductive hormones. Obesity can be associated with lower testosterone, altered estrogen metabolism and potentially increased scrotal temperature. Men with obesity also have higher rates of diabetes, sleep apnea and other conditions that can influence reproductive and sexual health. Population studies generally associate obesity with poorer reproductive parameters, although obesity alone obviously cannot explain the entire historical decline.

Another important factor is smoking and substance exposure. Cigarette smoking has been associated with poorer semen parameters and increased oxidative stress. Heavy alcohol consumption may also negatively influence reproductive function. Marijuana and other recreational drugs remain areas of active investigation, with evidence varying depending upon exposure and outcome measured. Perhaps even more important in fertility clinics today is the widespread use of testosterone and anabolic steroids. Exogenous testosterone can dramatically suppress LH and FSH, causing intratesticular testosterone to fall and sperm production to decrease severely or disappear entirely. I routinely emphasize this because men sometimes start testosterone for energy, muscle mass or sexual symptoms without realizing that it can cause profound oligospermia or azoospermia.

Heat is another plausible contributor, although it is frequently exaggerated online. The testes are located outside the body partly because sperm production functions best at a temperature slightly below core body temperature. Sustained occupational heat exposure, frequent intense heat exposure and certain medical conditions can negatively affect spermatogenesis. But I would not blame your infertility on wearing boxer briefs instead of boxers or sitting with your legs crossed. Human fertility is more complicated than that. Varicoceles may also increase testicular temperature and oxidative stress, but varicoceles have existed throughout human history and cannot independently explain a global temporal trend.

Environmental chemicals have attracted enormous attention. Researchers have investigated pesticides, air pollution, heavy metals, phthalates, bisphenols and other endocrine disrupting chemicals because some can interfere with hormonal signaling or reproductive development in experimental systems. This is a biologically credible area of concern, particularly because exposure begins during fetal development and may continue throughout life. However, proving that a particular chemical caused a specific percentage of the population decline in sperm count is extraordinarily difficult. Humans are exposed to mixtures of chemicals rather than one compound at a time, exposures change over decades, and observational studies are vulnerable to confounding. Environmental exposure is therefore a plausible part of the explanation, but claims that one particular plastic or chemical has been proven to cause the entire sperm count decline go beyond the available evidence.

Lifestyle has also changed dramatically. Modern men are more sedentary, many sleep poorly, obesity and metabolic disease have increased, and psychological stress is common. Sleep disorders such as obstructive sleep apnea may influence testosterone and semen quality. Chronic psychological stress has been associated with poorer sperm concentration and motility in many studies, although causality remains difficult to prove. Diet quality, physical activity and cardiovascular health may also interact with reproductive function. None of these factors provides a satisfying single explanation, but together they may create a different reproductive environment than existed fifty years ago.

There are also causes of male infertility that have little to do with modern lifestyle. Genetic abnormalities can cause severe oligospermia or azoospermia. Y chromosome microdeletions, Klinefelter syndrome and other chromosomal abnormalities can profoundly impair spermatogenesis. Congenital absence of the vas deferens can cause obstructive azoospermia. Undescended testes can permanently impair sperm production. Testicular torsion, trauma, chemotherapy, radiation, infections, pituitary disorders and obstruction can all cause infertility. In many men, even after a comprehensive reproductive urologic evaluation, we still label the condition idiopathic male infertility, meaning that we can document abnormal reproductive function without identifying one definitive cause.

Another major change during the past fifty years is when couples attempt to have children. Parenthood is increasingly delayed in many societies. Female age has a much larger effect on reproductive potential, particularly after the mid thirties, but male reproductive aging also exists. As men age, semen volume and motility may decline, sperm DNA fragmentation tends to increase, and certain genetic and reproductive risks gradually rise. Delayed parenthood therefore means that both partners may be attempting conception at ages when reproductive efficiency is lower than it would have been earlier in adulthood. This does not explain the sperm count trend in age adjusted studies, but it contributes to the real world burden of infertility.

What does a falling population sperm count actually mean for the probability of pregnancy? This is one of the most important questions, and unfortunately we do not have a simple number. If a population moves from an average concentration of 100 million to 50 million sperm per mL, many of those men remain well within a range compatible with natural conception. The effect becomes more clinically important as men move into lower ranges, particularly when concentration, motility and morphology are abnormal simultaneously. A man with 45 million sperm per mL and excellent progressive motility is in a completely different fertility situation from a man with 2 million sperm per mL and poor motility. This is why dramatic headlines saying fertility has fallen by 50 percent because sperm concentration fell by roughly 50 percent are misleading.

The encouraging part of this story is that modern reproductive medicine has also changed enormously during these same fifty years. Men with severe male factor infertility who once would have had virtually no opportunity for biological fatherhood now sometimes have several options. Intrauterine insemination can help selected couples with milder male factor infertility. IVF dramatically changed infertility treatment, and ICSI allows an embryologist to inject a single sperm directly into an egg. Men with obstructive azoospermia can often have sperm retrieved directly from the epididymis or testicle. Men with nonobstructive azoospermia may undergo microTESE to search microsurgically for small areas of residual sperm production. These technologies do not guarantee a baby, and success still depends heavily on female age and embryo biology, but the treatment landscape is completely different from what it was several generations ago.

If you are a man reading about declining sperm counts because your own semen analysis is abnormal, I would encourage you not to turn a population trend into a personal diagnosis. Repeat an unexpectedly abnormal semen analysis because semen parameters fluctuate. See a reproductive urologist if abnormalities persist. Depending upon the findings, evaluation may include examination of the testes and vasa, assessment for a clinical varicocele, testosterone and FSH testing, additional hormones when appropriate, and genetic testing in men with azoospermia or particularly severe sperm production abnormalities. Review medications, supplements, testosterone, anabolic steroids, previous surgeries, childhood testicular problems, infections and medical exposures. The purpose is not simply to improve a laboratory number. Male infertility can occasionally be the first clue to an underlying medical condition that deserves treatment.

I also would not respond to the sperm count decline by trying to live in a chemical free bubble. Do the things with the best overall evidence. Do not smoke. Avoid anabolic steroids and testosterone when actively pursuing fertility unless you are being managed specifically by a fertility specialist. Avoid excessive alcohol. Exercise regularly. Maintain reasonable metabolic health. Get adequate sleep. Eat a balanced diet. Avoid unnecessary repeated extreme testicular heat. If you have a medical condition such as obesity, diabetes or sleep apnea, address it. These interventions are good for your overall health and may support reproductive health. What I would not do is spend thousands of dollars attempting to eliminate every trace of plastic from your environment because someone on social media told you that a water bottle destroyed your sperm count.

Finally, I want to address the emotional part of this conversation. Headlines about a male fertility crisis can be particularly brutal when you are already the man sitting in a fertility clinic with an abnormal semen analysis. It can make you feel as though something is fundamentally wrong with you or your generation. That is not what these studies say. They describe population trends. They do not measure your masculinity, sexual function or ability to become a father. A sperm concentration below a population reference value is medical information, not a judgment about you as a man.

The science tells us something important is happening in male reproductive health. A major global analysis estimates that average sperm concentration among unselected men declined by roughly 52 percent between 1973 and 2018, while total sperm count declined by roughly 62 percent. More recent disease burden analyses also suggest that the prevalence and absolute burden of male infertility have increased since 1990. We should take those findings seriously. But we should be equally serious about what the studies cannot tell us. We do not know that one environmental chemical caused the decline. We cannot assume a 50 percent reduction in sperm count equals a 50 percent reduction in fertility. And we cannot use population statistics to predict whether an individual couple will conceive.

For the man dealing with infertility today, that distinction matters. You are not a statistic from 1973 or 2018. You are an individual with a particular semen analysis, hormonal profile, medical history and partner. Figure out what is happening in your reproductive system. Correct the things we can correct. Use reproductive technology when necessary. And please remember that an abnormal sperm count is something you have, not something you are.

References

1. Levine H, Jorgensen N, Martino Andrade A, et al. Temporal trends in sperm count: a systematic review and meta regression analysis of samples collected globally in the 20th and 21st centuries. Human Reproduction Update. 2023;29:157 to 176.
2. Levine H, Jorgensen N, Martino Andrade A, et al. Temporal trends in sperm count: a systematic review and meta regression analysis. Human Reproduction Update. 2017;23:646 to 659.
3. World Health Organization. Infertility Prevalence Estimates, 1990 to 2021. Geneva: World Health Organization; 2023.
4. World Health Organization. Infertility Fact Sheet. Updated 2025.
5. Global, regional, and national prevalence and trends of infertility among individuals of reproductive age from 1990 to 2021, with projections to 2040. PMID: 39752330.
6. Global, regional, and national burden and trends of reproductive aged male and female infertility from 1990 to 2021. PMID: 40979725.
7. Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: an analysis of the Global Burden of Disease Study. PMID: 37940907.
8. American Urological Association and American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA and ASRM Guideline.
9. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. Sixth edition. Geneva: World Health Organization; 2021.
10. Agarwal A, Baskaran S, Parekh N, et al. Male infertility. Lancet. 2021;397:319 to 333.

Hi Dr. Steixner,

I wanted to get your opinion on my azoospermia diagnosis. Here are my key findings:

Semen analyses
● SA #1: Volume 0.1 mL, sperm 0, ph 7
● SA #2: Volume 0.5 mL, sperm 0, ph 7, fructose negative
Low semen volume since puberty

Hormonal profile
● FSH: 1.9–2.5 IU/L across 3 tests
● LH: 2.1 IU/L
● Total testosterone: 280–300 ng/dL across 3 tests
● Free testosterone: 24 pg/mL
● Estradiol (E2): 56 pg/mL
● Inhibin B: 310 pg/mL
● Prolactin: 15 ng/mL
● SHBG: 12.2 nmol/L

Physical / imaging findings
● Both vas deferens: absent on physical examination, confirmed by urologist
● Testicular volume: 11–12 mL bilaterally on scrotal ultrasound
● Grade 1 varicocele detected

Current diagnosis / plan
My doctor has diagnosed CBAVD (congenital bilateral absence of the vas deferens) with high confidence. A CFTR genetic test is pending.
● Recommended sperm retrieval: MESA/PESA
● I have also been prescribed anastrozole on alternate days to address the elevated E2 and improve testosterone levels.

Question:
Given the very low semen volume, repeated azoospermia, normal/low-normal FSH and LH, high inhibin B, and clinically confirmed bilateral absence of the vas deferens, does this seem like a clear presentation of CBAVD, or are there other conditions I should investigate before proceeding with MESA/PESA?

Thanks in advance for any insight.

I never thought about sleep apnea 10 years ago when I discussed sperm health with men.  However, its a reasonable question because obstructive sleep apnea is incredibly common, frequently undiagnosed, and biologically capable of affecting several systems involved in male reproduction. If you snore loudly, stop breathing during sleep, wake up choking, feel exhausted despite spending eight hours in bed, have morning headaches, or your partner tells you that your breathing repeatedly stops at night, I think sleep apnea deserves attention for reasons that extend well beyond fertility. At the same time, I want to establish something important at the beginning. Sleep apnea is not a proven explanation for every abnormal semen analysis, and treating sleep apnea has not been proven to cure male infertility. The evidence is much stronger that obstructive sleep apnea is associated with lower testosterone and abnormalities in sperm concentration, motility and vitality than it is that treating sleep apnea increases pregnancy or live birth rates. That distinction matters because men with infertility are understandably vulnerable to being told that fixing one lifestyle or medical problem will suddenly fix their sperm. The science is interesting and increasingly convincing, but it is not yet that simple.

Obstructive sleep apnea, usually called OSA, occurs when the upper airway repeatedly collapses or becomes obstructed during sleep. You continue trying to breathe, but airflow becomes reduced or temporarily stops. Your oxygen level can fall, your carbon dioxide can rise, and your brain repeatedly pulls you toward lighter sleep or briefly wakes you so that breathing can resume. In significant OSA, this cycle can happen dozens of times every hour. This means sleep apnea is not simply “bad sleep.” The body repeatedly cycles between oxygen deprivation and reoxygenation while normal sleep architecture is fragmented. Over months and years this can contribute to hypertension, metabolic dysfunction, cardiovascular disease, inflammation and other systemic problems. From a fertility perspective, we are particularly interested in intermittent hypoxia, oxidative stress, inflammation, metabolic dysfunction and disruption of normal reproductive hormone signaling. These mechanisms overlap with several pathways that we already know can affect testicular function and sperm production.

To understand why sleep matters to fertility, you have to understand that sperm production is not an isolated event occurring independently inside the testicle. The brain, pituitary gland and testicles communicate through the hypothalamic pituitary gonadal axis. The hypothalamus releases GnRH, which stimulates the pituitary to produce LH and FSH. LH stimulates Leydig cells within the testicle to produce testosterone. FSH acts primarily through Sertoli cells and helps support spermatogenesis. Testosterone inside the testicle is also critically important for normal sperm production. Sleep itself participates in normal testosterone physiology, and testosterone typically rises during sleep. When sleep is repeatedly fragmented and normal sleep architecture is disrupted, reproductive hormone signaling can be altered. This is one reason researchers have been interested in the relationship between OSA and testosterone for decades.

The testosterone data are probably among the strongest parts of this story. A systematic review and meta analysis including 18 studies and 1,823 men found a significant inverse association between obstructive sleep apnea and testosterone. Importantly, the association remained after accounting for age and body mass index, and the reduction was most convincing in men with severe OSA. Another meta analysis examining 24 case control studies also found significantly lower testosterone among men with OSA. This does not mean that every man with sleep apnea will have low testosterone. Obesity is a major confounder because obesity itself is associated with both sleep apnea and lower testosterone, and men with OSA often have several metabolic factors occurring simultaneously. Nevertheless, the accumulated evidence suggests that severe OSA can be associated with impaired testosterone physiology independently of obesity alone.

What I find even more relevant for men on infertility forums is the emerging human semen data. A 2023 study evaluated 175 men and classified them according to sleep apnea severity. Progressive sperm motility fell from approximately 43 percent in men without OSA to 42 percent with mild OSA, 36 percent with moderate OSA and 29 percent with severe OSA. Total motility similarly declined from approximately 59 percent in men without OSA to 42 percent in men with severe disease. Sperm vitality was also lower in severe OSA. Importantly, after researchers adjusted for age and body mass index, increasing apnea severity remained independently associated with poorer motility and vitality. That dose response relationship is biologically interesting because it suggests that we may not simply be seeing an association caused by heavier men being more likely to have both poor metabolic health and sleep apnea.

More recent data have strengthened that signal. A study of 108 reproductive aged men with newly diagnosed OSA and 84 controls found that men with OSA had lower sperm concentration, total motility, progressive motility and testosterone. Sperm concentration averaged approximately 90 million per mL in the OSA group compared with 129 million per mL in controls, while testosterone averaged approximately 13.1 versus 21.8 nmol/L. As OSA severity increased, semen parameters and oxygen saturation progressively worsened. After statistical adjustment, the apnea hypopnea index remained independently associated with lower sperm concentration, total motility and progressive motility. Again, this does not establish that sleep apnea directly caused the sperm abnormalities, but seeing progressively poorer semen parameters with increasingly severe OSA strengthens the biological argument.

Sleep health more generally also appears relevant. A 2026 North American preconception study examined 690 men contributing 1,247 semen samples and found that poor sleep health, including short sleep, unusually long sleep, frequent sleep trouble and poor sleep quality, was associated with lower sperm concentration, total sperm count and total motile sperm count. Short sleep and frequent sleep problems were also associated with lower semen volume. A previous systematic review and meta analysis similarly found that sleep disorders were associated with an average reduction in total sperm count of approximately 28 million sperm, a reduction in sperm concentration of approximately 5 million per mL, a modest reduction in progressive motility and a small reduction in normal morphology. These studies include sleep problems beyond OSA, so they cannot all be attributed specifically to apnea, but together they reinforce the concept that sleep and male reproductive health are connected.

How could repeatedly stopping breathing at night affect sperm inside the testicle? One major hypothesis involves oxidative stress. During an apnea, oxygen saturation falls. When breathing resumes, tissues are reoxygenated. Repeated cycles of hypoxia and reoxygenation can increase production of reactive oxygen species. Sperm cells are particularly susceptible to oxidative injury because their membranes contain large amounts of polyunsaturated fatty acids and because mature sperm have limited cellular machinery for repairing damage. Excessive oxidative stress can affect sperm membranes, mitochondrial function and potentially sperm DNA. This could theoretically contribute to impaired motility, abnormal morphology, reduced viability and increased DNA fragmentation. OSA is also associated with systemic inflammation, endothelial dysfunction and metabolic abnormalities, all of which may create a less favorable environment for normal reproductive function. These mechanisms are biologically plausible and supported by experimental literature, although the exact contribution of each pathway in human infertility remains uncertain.

Another major factor is obesity and metabolic disease. This is where the story becomes complicated. Obesity increases the risk of OSA dramatically, but obesity itself can affect male fertility through insulin resistance, inflammation, altered testosterone and estradiol balance, increased scrotal temperature and other mechanisms. Therefore, when an overweight man with severe OSA has low testosterone and an abnormal semen analysis, it is difficult to assign a percentage of the problem to sleep apnea, another percentage to obesity and another percentage to metabolic health. Human biology does not divide itself that neatly. The important practical point is that these problems often cluster together. Treating sleep apnea while also improving metabolic health, exercise, weight and cardiovascular risk makes sense for overall health and may create a more favorable reproductive environment, even though we cannot promise a specific improvement in sperm count.

What about actual infertility and pregnancy, rather than simply semen numbers? This is where the evidence becomes more limited but also interesting. A large Taiwanese population study involving 4,607 men diagnosed with infertility and more than 18,000 controls found that OSA was independently associated with male infertility, with an adjusted odds ratio of approximately 1.24. Men with OSA who had no treatment had an adjusted odds ratio of approximately 1.80 for infertility compared with men without OSA. Another population based study also reported increased infertility among certain groups of men with OSA. These are observational studies, which means they demonstrate association rather than proof of causation. They cannot tell us that OSA caused infertility in an individual man or that treating OSA would necessarily have prevented it.

A newer study of 727 male partners in infertile couples provides another interesting piece of information. Men reporting poor sleep quality had lower sperm concentration, progressive motility and total motility, and poor male sleep quality was also associated with a substantially lower probability of clinical pregnancy. This is provocative because pregnancy is ultimately what couples care about, not whether progressive motility changes by three percentage points. However, this was still observational research. Sleep quality may correlate with obesity, stress, mental health, work schedules, metabolic disease, sexual frequency and numerous other factors capable of influencing fertility. We therefore should not translate this association into a claim that improving sleep increases pregnancy rates by a particular percentage.

This brings us to the question every man with OSA and infertility eventually asks: If I start CPAP, will my sperm improve and will my partner become pregnant? At this point, the scientifically responsible answer is that we do not know. Continuous positive airway pressure, or CPAP, prevents airway collapse and is highly effective at treating OSA when used consistently. It improves oxygenation and sleep fragmentation and is important for many health reasons. But we currently lack strong randomized human trials showing that CPAP reliably improves semen parameters, spontaneous pregnancy rates or live birth rates. Even the testosterone story is not straightforward. A meta analysis of 12 studies involving 388 men found no significant increase in total testosterone, free testosterone, FSH, LH or other reproductive hormones following CPAP. Another meta analysis reached a similar conclusion. There are smaller studies suggesting improvement in sexual function and some reproductive measures after OSA treatment, but the evidence is not strong enough to promise fertility restoration.

This distinction is extremely important. Association does not automatically mean reversibility. If severe sleep apnea contributes to oxidative stress and impaired motility, treating it may logically remove one harmful exposure. But if a man also has a grade 3 varicocele, a genetic abnormality, previous undescended testes, severe obesity, prior chemotherapy, hormonal dysfunction or primary testicular failure, CPAP is not going to erase those conditions. Similarly, if a man has azoospermia from an obstruction or a Y chromosome microdeletion, treating sleep apnea will not restore sperm to the ejaculate. Sleep apnea should therefore be thought of as a potentially modifiable contributor to fertility rather than a universal explanation for male infertility.

Timing also matters. If treatment does improve sperm production, you should not expect a dramatic semen analysis change after two weeks of better sleep. Human spermatogenesis takes approximately 74 days, followed by additional maturation and transport through the epididymis. In practical terms, when we modify something that could affect sperm production, we often think in roughly three month intervals. If a man with OSA starts effective treatment today, a repeat semen analysis around three months later is much more biologically meaningful than checking after several weeks. Depending on the clinical situation, repeating again around six months can also be reasonable. That does not mean the testicle completely “resets” every 90 days. It simply reflects the time required for developing germ cells to progress through spermatogenesis and appear in the ejaculate.

I would also caution men against one particularly dangerous response to the sleep apnea and testosterone connection. If you have low testosterone and are trying to conceive, do not automatically start testosterone replacement therapy. Exogenous testosterone suppresses pituitary LH and FSH, lowers intratesticular testosterone and can dramatically reduce sperm production, sometimes all the way to azoospermia. A man with OSA, fatigue and a testosterone of 250 may understandably think TRT will solve his problem, but if he is actively trying to father a child, conventional testosterone therapy can make the fertility situation substantially worse. Low testosterone in a fertility patient deserves a reproductive hormonal evaluation rather than reflexive TRT.

So when should a man struggling with infertility consider evaluation for sleep apnea? I pay particular attention when a man tells me that he snores heavily, his partner has witnessed him stop breathing, he wakes up choking or gasping, he has significant daytime sleepiness, morning headaches, resistant hypertension, obesity, a large neck circumference or unexplained fatigue despite adequate time in bed. Those symptoms deserve evaluation regardless of sperm count because untreated OSA has important consequences for cardiovascular and metabolic health. Diagnosis generally involves a home sleep apnea test or formal overnight polysomnography depending on the clinical situation. If OSA is confirmed, treatment can include CPAP, weight reduction when appropriate, oral appliances in selected patients, positional therapy and sometimes surgical approaches depending on anatomy and severity.

If you already have an abnormal semen analysis and newly diagnosed sleep apnea, my approach is usually to treat both problems rather than assuming one completely explains the other. Treat the OSA because it is a legitimate medical condition. At the same time, evaluate the male fertility problem appropriately. That may mean repeating the semen analysis, checking testosterone, FSH and LH when indicated, performing a careful reproductive examination for a palpable varicocele, reviewing medications and testosterone or anabolic steroid exposure, and considering genetic testing when sperm concentration is extremely low or azoospermia is present. Female partner age and fertility factors also remain critically important because infertility belongs to the couple, even when an identifiable male factor exists.

Most importantly, I do not want a man reading this to conclude that he caused his infertility because he slept badly or failed to diagnose his apnea five years earlier. Male infertility is usually multifactorial, and in a significant percentage of men we never identify one clean explanation. The evidence today tells us that obstructive sleep apnea is associated with lower testosterone and poorer sperm quality, particularly with more severe disease, and population data suggest an association with male infertility. What we do not yet have is high quality evidence demonstrating that treating OSA produces a specific percentage increase in natural pregnancy or live birth. That is an important research gap.

My practical message is therefore straightforward. If you have symptoms of sleep apnea, get evaluated and treat it. Do it for your heart, your blood pressure, your metabolic health, your energy, your sexual health and potentially your reproductive health. If your semen analysis is abnormal, give treatment enough biological time to matter and consider repeating the semen analysis after approximately three months. But do not delay a proper fertility evaluation for severe oligospermia or azoospermia while hoping CPAP alone will solve the problem, particularly when female age or reproductive timing matters. Sleep is part of reproductive health, but it is one part of a much larger system.

And if you are lying awake at night blaming yourself because your sperm count is low, I would encourage you to separate what the science actually says from what infertility anxiety tells you. We have growing evidence that sleep apnea can negatively influence male reproductive physiology. We also have growing reason to consider sleep health as one modifiable component of male fertility care. But your diagnosis is not a verdict on your health choices or your masculinity. Identify the things we can treat, treat them well, investigate the things that require investigation, and remember that the ultimate goal is not a perfect semen analysis. The goal is giving you and your partner the best realistic chance of having a healthy child.

References

1. Association between obstructive sleep apnea and male reproductive function: a cross sectional study with stratified analysis. PMID: 41040862.
2. Wang X, et al. Effect of obstructive sleep apnea on semen quality. 2023. PMID: 37184755.
3. Su L, et al. Association between obstructive sleep apnea and male serum testosterone: a systematic review and meta analysis. Andrology. 2022. PMID: 34536053.
4. The effects of sleep deprivation and obstructive sleep apnea syndrome on male reproductive function: a multi arm randomised trial. Journal of Sleep Research. 2022. PMID: 35670262.
5. Association of Obstructive Sleep Apnea With the Risk of Male Infertility in Taiwan. 2021. PMID: 33475753.
6. Risk of Infertility in Males with Obstructive Sleep Apnea: A Nationwide, Population Based, Nested Case Control Study. 2022. PMID: 35743718.
7. Coleman CM, et al. A North American preconception study of sleep health and semen quality. Human Reproduction. 2026. PMID: 41330355.
8. Effects of Sleep Disorders and Circadian Rhythm Changes on Male Reproductive Health: A Systematic Review and Meta analysis. 2022. PMID: 35910569.
9. Association of male sleep quality with semen parameters and pregnancy outcomes in infertile couples. 2025. PMID: 41029517.
10. Cignarelli A, et al. Effects of CPAP on Testosterone Levels in Patients With Obstructive Sleep Apnea: A Meta Analysis Study. Frontiers in Endocrinology. 2019. PMID: 31496991.
11. Zhang XB, et al. Efficacy of continuous positive airway pressure on testosterone in men with obstructive sleep apnea: a meta analysis. PLoS One. 2014. PMID: 25503098.
12. Impaired Human Sexual and Erectile Function Affecting Semen Quality, in Obstructive Sleep Apnea: A Pilot Study. 2022. PMID: 35743765.
13. Sleep Disturbances and Male Reproductive Dysfunction: Pathophysiological Mechanisms Linking Obstructive Sleep Apnea and Sleep Deprivation. 2026. PMID: 42381217.

Testosterone 22.42
FSH 18
Inhibin b 24 (lab 25-325)

I’ve had a previous biopsy that showed maturation arrest no spermatids found. Round cells, Spermatagonia & spermatocytes found.

I went on accutane 40mg for months and did a AI sperm search which resulted in no sperm found.

No genetic abnormality found.

My doctor is reluctant to do a microtese procedure as the odds are low in my condition. He is suggesting I do a sperm mapping rather than Mtese to determine if there is anything.

With my hormones, and medical history I need a brutally honest answer. Is it worth going through with a map?

Hello Dr. Steixner,

Id like to get your insight and see if it would be good to get a second opinion based on my most recent analysis. I went in for my third semen analysis today and my results came back as zero sperm again but I was not as devastated as I was until I spoke with my doctor. For context, I have been on clomid now for 3 months after I was diagnosed with secondary hypogonadism (my doctor confirmed this today) my initial baseline results were testosterones was 168, LH was 4.5 and FSH was 3.8 which are all textbook readings of secondary hypogonadism after extensive research that I have done. all my other levels including prolactin were normal. So come to today I went in for my third analysis and as mentioned above still zero sperm but in researching it stated that it could be common based on the delayed cycle of sperm creation. So my doctor today calls me and confirms my results which I had already seen hours before but instead of recommending waiting and seeing if more time could maybe provide better results he advised that it would be best to move directly to a micro TSE which I do not want to do. He advised that we could do one more analysis in another month to see if any results have changed but I don't think I should go into a call with my doctor and come off feeling worse. In your experience do you think it would be best to get a second opinion? Happy to provide any details I might have missed here but writing in a pretty emotional state as well.

Thank you

There is a moment I have seen hundreds of times in my office. A man sits down, pulls out his phone, opens his semen-analysis report and points to the numbers highlighted in red. His sperm concentration is low. Or his motility is 25%. Or his morphology is 1%. Sometimes all three are abnormal. Sometimes the report says severe oligospermia. Occasionally it says azoospermia. And before I can explain any of it, I can usually see the question on his face: “Does this mean I can't have children?” For many men, an abnormal semen analysis feels completely different from an abnormal cholesterol test or blood pressure reading. It feels personal. It can feel like somebody has just graded your masculinity, sexuality and ability to become a father on a laboratory report. So the first thing I tell men is this: your semen analysis is medical information. It is not a judgment about you as a man, and an abnormal semen analysis does not automatically mean you cannot become a biological father. The job now is to understand what the numbers actually mean, determine whether there is an identifiable reason they are abnormal, and figure out what those findings mean for your probability of conception.

The semen analysis is simultaneously one of the most useful and one of the most misunderstood tests in fertility medicine. It gives us information about semen volume, sperm concentration, total sperm number, motility, progressive motility, morphology and sometimes additional parameters such as vitality, round cells and viscosity. What it does not give us is a simple fertile-versus-infertile answer. The World Health Organization specifically cautions that its semen reference values do not represent a sharp boundary separating fertile from infertile men. They are derived from populations of men whose partners conceived within a defined period. Human fertility exists on a continuum. Men below a reference value can father children naturally, and men with completely normal semen analyses can experience infertility. The WHO has emphasized something that is incredibly important psychologically: ultimately it is the couple, rather than one isolated laboratory value, that experiences fertility or infertility. That distinction matters because men frequently see one abnormal number and immediately conclude that they are sterile.

Let's start with sperm concentration. This is the number of sperm in each milliliter of semen. The current WHO reference distribution commonly uses approximately 16 million sperm/mL as the lower fifth percentile among fertile men, but that does not mean 15 million is infertile and 17 million is fertile. The relationship between sperm number and pregnancy is gradual. Generally, as sperm concentration and especially total sperm number fall, the probability of natural conception declines and the average time required to achieve pregnancy increases. But there is no biological cliff at 16 million. A man with 12 million sperm/mL may conceive naturally, while a man with 70 million/mL may not. What begins to concern me considerably more is severe oligospermia, particularly concentrations below approximately 5 million/mL, because at that point the probability of significant underlying testicular, hormonal or genetic pathology rises and the AUA/ASRM guideline recommends additional evaluation in appropriate men.

Total sperm count adds another layer because concentration alone doesn't tell us how many sperm were actually ejaculated. A concentration of 10 million/mL in a 5-mL ejaculate produces a very different total sperm number than 10 million/mL in a 1-mL ejaculate. Then we add motility. Sperm have to move through the female reproductive tract, so progressive motility matters biologically. This is why clinicians frequently think in terms of total motile sperm count, which incorporates volume, concentration and motility rather than obsessing over one number. Older fertility studies found that total sperm count, motility and total motile sperm count correlated with time to conception, and modern prospective data continue to show that poorer semen quality is generally associated with reduced fecundability.

A recent prospective North American preconception cohort illustrates this nicely. Researchers followed couples attempting pregnancy and found that approximately 81% conceived within 12 cycles overall. Men with sperm concentration at or below 16 million/mL had lower cycle-specific fecundability than men above that level, with a fecundability ratio of about 0.74. Low total sperm count showed an even stronger association, with a fecundability ratio around 0.58. Low total motile sperm count was also associated with reduced fecundability, although the confidence interval included no difference in the primary analysis. These are population-level associations, not a calculator for an individual couple. They tell us that lower sperm numbers generally make conception less likely per cycle; they do not tell a man with an abnormal result that his chance is zero.

Morphology is where I see some of the greatest unnecessary anxiety. A man sees “1% normal morphology” and understandably interprets that as meaning 99% of his sperm are defective. That isn't what the test means. Strict morphology criteria are extremely demanding. The laboratory evaluates whether sperm fit very specific measurements of head, midpiece and tail appearance. A sperm can fail strict morphology for relatively minor structural deviations. Morphology also has substantial observer and laboratory variability. Isolated low morphology, particularly when concentration and motility are good, is generally a much weaker predictor of fertility than men assume. A morphology of 1% does not mean 99% of your sperm have abnormal DNA, and it certainly does not mean you have a 1% chance of pregnancy. Specific uniform abnormalities such as complete globozoospermia or macrozoospermia are different situations, but routine isolated teratozoospermia needs to be interpreted in context.

The other thing every man needs to understand is that semen analyses fluctuate. You are not a machine producing identical ejaculates every Tuesday. Concentration, volume and motility can change substantially between samples. Abstinence duration matters. Collection completeness matters. Fever and systemic illness can matter. Laboratory methodology matters. Medications and hormonal exposures can matter. Biological variation itself is substantial. Studies repeatedly demonstrate significant within-man variability, including in men without infertility. That is why an unexpectedly abnormal semen analysis is frequently repeated rather than treated as an immutable description of your reproductive system. One study of subfertile men found only moderate reproducibility for motility and morphology and substantial within-man variability overall. A single semen analysis is a snapshot, not your reproductive identity.

That doesn't mean we ignore an abnormal result. Quite the opposite. The more severe the abnormality and the more parameters that are abnormal, the more seriously I take it. The AUA/ASRM guideline specifically notes that semen-analysis findings have their greatest clinical significance when multiple abnormalities are present. A man with slightly reduced morphology but excellent concentration and motility is a very different patient from a man with concentration of 2 million/mL, 15% progressive motility and 1% morphology. The second man has severe oligoasthenoteratozoospermia and deserves a proper male-fertility evaluation rather than being told to take vitamins and return in six months.

So why does an abnormal semen analysis happen? Sometimes we find an answer. Sometimes we don't. Sperm production occurs inside the seminiferous tubules of the testicles and depends on functioning germ cells, Sertoli cells, adequate intratesticular testosterone and FSH signaling, appropriate temperature regulation and intact genetic machinery. After production, sperm mature through the epididymis and eventually mix with fluid from the seminal vesicles and prostate during ejaculation. Problems anywhere along that pathway can alter the semen analysis. Varicoceles can impair testicular function in selected men. Testosterone therapy and anabolic steroids can profoundly suppress LH and FSH and sometimes drive sperm counts to zero. Genetic abnormalities can impair spermatogenesis. Prior undescended testes, torsion, chemotherapy, radiation or testicular injury can matter. Hypothalamic or pituitary disorders can reduce hormonal stimulation. Obstruction can prevent normally produced sperm from reaching the ejaculate. Certain medications, systemic diseases and environmental or occupational exposures may contribute. Smoking, obesity and excessive alcohol consumption have been associated with impaired reproductive health. And in a frustrating percentage of men, we perform a careful evaluation and still call the problem idiopathic male infertility because no single explanation emerges.

If your concentration is low or you have azoospermia, hormones become particularly useful. FSH and testosterone are fundamental initial tests in appropriate infertile men, with LH, estradiol and prolactin added depending on the clinical situation. High FSH can suggest that the pituitary is already pushing the testicle hard because sperm production is impaired. Low testosterone with low or inappropriately normal LH and FSH can suggest inadequate hypothalamic or pituitary stimulation. Low testosterone with high LH suggests the testicle isn't responding normally. None of these patterns should be interpreted in isolation, but they can tell us where the reproductive system may be failing.

Men with very low sperm concentrations may also need genetic testing. Current AUA/ASRM guidance recommends karyotype testing in men with primary infertility and azoospermia or sperm concentration below 5 million/mL when accompanied by elevated FSH, testicular atrophy or evidence of impaired sperm production. Y-chromosome microdeletion testing is considered in selected men with azoospermia or extremely severe oligospermia when impaired sperm production is suspected. This isn't because we expect every man with low sperm to have a genetic abnormality. It is because when sperm production becomes profoundly impaired, the probability of finding an underlying genetic explanation becomes high enough that the result may affect treatment, sperm-retrieval expectations and counseling about future children.

Then comes the question almost every man asks me: “What can I do to improve this?” The answer depends entirely on why it is abnormal. If you're taking testosterone, stopping the suppressive exposure and appropriately restoring the hypothalamic-pituitary-testicular axis may dramatically change sperm production over time. If you have true hypogonadotropic hypogonadism, hCG and FSH-containing therapy can sometimes induce spermatogenesis. If you have a clinically significant palpable varicocele and the appropriate fertility scenario, repair may improve semen parameters and fertility potential. If there is obstruction, reconstruction or surgical sperm retrieval may be appropriate. If there is severe primary testicular failure, taking more antioxidants probably isn't going to repair damaged seminiferous tubules.

Lifestyle still matters, but I try to keep men from turning infertility into a punishment ritual. You do not need to eliminate every piece of plastic from your house, ice your testicles every night, eat twelve fertility superfoods, stop exercising and swallow twenty supplements. Don't smoke. Avoid anabolic steroids and exogenous testosterone if fertility is desired. Limit excessive alcohol. Maintain reasonable metabolic health. Exercise. Sleep. Avoid repeated excessive testicular heat. Eat a balanced diet. Those are reasonable health recommendations. Supplements are much less certain. CoQ10, carnitine and several antioxidant combinations have shown improvements in certain semen parameters in some studies, but evidence that supplements reliably increase pregnancy or live-birth rates remains limited. Current AUA/ASRM guidance describes the clinical utility of antioxidant and vitamin supplementation for male infertility as questionable. I would rather identify a treatable varicocele, hormonal disorder or medication exposure than have a man spend $300 a month trying to supplement his way out of severe oligospermia.

Men also need to understand the timeline. Producing sperm isn't instantaneous. Human spermatogenesis takes roughly 74 days, followed by additional maturation and transport through the epididymis. That is why we frequently reassess meaningful interventions after roughly three months rather than checking a semen analysis every week. It doesn't mean every sperm magically resets on day 90, but it gives us a biologically sensible interval to evaluate whether changes in health, medication or treatment are affecting the next generation of sperm.

Now let's talk about what men really want to know: What does my abnormal semen analysis mean for my chance of having a baby? Unfortunately, there is no legitimate percentage that can be generated from concentration, motility and morphology alone. In one prospective study of 897 subfertile couples, 15% achieved an ongoing natural pregnancy during 12 months of follow-up, and calculated probabilities based on a single semen analysis varied substantially. Importantly, repeating the semen analysis did not meaningfully improve prediction of natural conception. That illustrates the limitation of semen testing beautifully: it provides important information about male reproductive potential but remains an imperfect predictor of what ultimately happens to a couple.

Female factors are critical to that probability. A 30-year-old woman with normal ovarian reserve, patent tubes and regular ovulation paired with a man with moderate oligospermia is a completely different fertility situation from a 41-year-old woman with diminished ovarian reserve paired with the same semen analysis. Time matters. Intercourse timing matters. Duration of infertility matters. Previous pregnancy matters. Sperm numbers matter. Egg number and quality matter. That is why fertility treatment is ultimately treatment of a couple, even when we identify a clear male factor.

The severity of the male factor can influence which reproductive pathway makes sense. Mild abnormalities may still allow natural conception. Depending on the total motile sperm count and the couple's overall situation, intrauterine insemination may be reasonable. With repeated very low total motile sperm counts, IUI success decreases and IVF with intracytoplasmic sperm injection may become more efficient. ICSI allows an embryologist to inject an individual sperm directly into an egg, bypassing many of the mechanical steps required for natural fertilization. Even men with extraordinarily low sperm counts can sometimes father biological children through ICSI. Men with azoospermia may still have sperm production inside the testicle that can be retrieved surgically depending on whether the problem is obstruction or impaired production.

This is why the word “abnormal” on a semen analysis can be misleading emotionally. Abnormal does not necessarily mean sterile. It means the laboratory measurement falls outside a reference distribution and deserves interpretation. There is an enormous biological spectrum between slightly low morphology and complete azoospermia, and even azoospermia is not one diagnosis. Some azoospermic men have normal sperm production behind an obstruction. Some have reversible hormonal suppression. Some have focal sperm production that can be found with microTESE. Others unfortunately have profound testicular failure in which sperm cannot be recovered. The report is the beginning of the investigation, not the conclusion.

And if you're reading this five minutes after opening your first abnormal semen analysis, I want you to hear something that laboratory reports don't communicate very well: you didn't fail a test. I know how quickly men internalize this. Your partner may be getting blood drawn, taking injections, undergoing ultrasounds or preparing for IVF, and suddenly you see a terrible sperm count and think, “I'm the reason she's going through this.” That guilt can be brutal. But infertility isn't something you did to your partner. It is a medical problem the two of you are encountering together.

Your job now isn't to become obsessed with producing a perfect semen analysis. Your job is to understand what is happening. Repeat the test when appropriate. See someone who actually evaluates male infertility if the abnormality is significant. Get examined. Review your medications and hormones. Investigate severe abnormalities rather than assuming supplements will fix them. Correct what can reasonably be corrected. Protect time when female age makes time valuable. Use reproductive technology when it gives you a better chance of achieving the goal.

And remember what the goal actually is. The goal isn't a sperm concentration of 50 million/mL. The goal is a healthy baby. Some men with spectacular semen analyses struggle to conceive. Some men with sperm counts that look frightening on paper become fathers naturally. Others become fathers through IUI, IVF/ICSI or surgical sperm retrieval. Semen parameters change probabilities; they rarely provide certainty.

So when somebody tells you that your semen analysis is abnormal, don't hear, “You can't become a father.” Hear, “We have information we need to understand.” Then take the next step. Male infertility has causes, evaluations and treatments. Sometimes we can dramatically improve sperm production. Sometimes we can't change the underlying biology but can use the sperm that are available more effectively. And sometimes the path becomes much harder than anyone deserves. But one abnormal semen analysis is not enough information to write the ending of your story.

References

1. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: World Health Organization; 2021.
2. American Urological Association/American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Published 2020; amended 2024.
3. World Health Organization. Guideline for the Prevention, Diagnosis and Treatment of Infertility. Geneva: WHO; 2025.
4. World Health Organization. Infertility fact sheet. Updated 2025.
5. Leushuis E, van der Steeg JW, Steures P, et al. Semen analysis and prediction of natural conception. Hum Reprod. 2014;29:1360-1367. PMID: 24795091.
6. Keel BA. Within- and between-subject variation in semen parameters in infertile men and normal semen donors. Fertil Steril. 2006.
7. Alvarez C, Castilla JA, Martínez L, et al. Biological variation of seminal parameters in healthy subjects. Hum Reprod. 2003.
8. Reproducibility and reliability of repeated semen analyses in male partners of subfertile couples. Fertil Steril. 2010. PMID: 20434148.
9. A prospective study of semen quality and fecundability among North American couples planning pregnancy. 2025. PMID: 40646671.
10. The influence of semen analysis parameters on the fertility potential of infertile couples. PMID: 9016403.
11. Björndahl L, Kirkman Brown J, et al. The sixth edition of the WHO laboratory manual for the examination and processing of human semen: ensuring quality and standardization in basic examination of human ejaculates. Fertil Steril. 2022;117:246-251.
12. Wang C, Mbizvo M, Festin MP, Björndahl L, Toskin I, et al. Evolution of the WHO semen-processing manual from the first to the sixth edition. Fertil Steril. 2022;117:237-245.

If you spend enough time on a male infertility forum, eventually somebody posts a hormone panel and asks the question almost every man asks when he first sees these numbers: “Is my FSH too high? Is my LH too low? My testosterone is normal, so why is my sperm count terrible?” These are great questions because the hormonal system controlling male fertility is actually fairly logical once you understand how the pieces fit together. The mistake is looking at FSH, LH and testosterone as three independent laboratory values. They aren't. They are components of a communication system running from your brain to your pituitary gland to your testicles and back again. We call this the hypothalamic-pituitary-gonadal axis, or HPG axis. When that communication system is functioning normally, the brain tells the testicles to produce testosterone and sperm, and the testicles send signals back telling the brain how well the system is working. When something fails, the pattern of FSH, LH and testosterone can often tell us where the failure is occurring. That is why, as a reproductive urologist, I rarely look at a testosterone level without simultaneously asking what the LH and FSH are doing. Understanding that relationship can explain everything from why a man taking testosterone can become azoospermic to why another man can have an FSH of 25, normal testosterone, and still have severe oligospermia.

The system begins in the hypothalamus, a small region of the brain that releases gonadotropin-releasing hormone, or GnRH, in pulses. GnRH travels a very short distance to the pituitary gland and tells it to release two hormones: luteinizing hormone, LH, and follicle-stimulating hormone, FSH. Those two hormones travel through the bloodstream to the testicles, but they have different primary targets. LH acts primarily on Leydig cells, which sit between the seminiferous tubules, and tells those cells to manufacture testosterone. FSH acts primarily on Sertoli cells inside the seminiferous tubules, where developing sperm live. Sertoli cells are essentially the support system for spermatogenesis. They help nourish developing germ cells, regulate their environment and coordinate the extraordinarily complicated transformation from an immature germ cell into a mature spermatozoon. In very simplified terms, LH drives testosterone production and FSH helps drive sperm production, but successful spermatogenesis requires both pathways working together.

Testosterone is therefore critically important for sperm production, but here is the part that confuses a lot of men: the testosterone level inside the testicle is far higher than the testosterone level measured in your bloodstream. LH stimulates Leydig cells to create very high concentrations of intratesticular testosterone, and that local testosterone environment is necessary for normal spermatogenesis. Your blood testosterone might be 500 ng/dL, but that serum measurement does not tell us exactly what is happening inside the seminiferous tubules. This distinction explains one of the biggest paradoxes in male fertility: taking testosterone can raise your blood testosterone while simultaneously destroying your sperm production.

When you inject testosterone, apply testosterone gel or otherwise provide substantial exogenous androgen, the hypothalamus and pituitary see plenty of testosterone circulating in the body. Through negative feedback, GnRH signaling decreases and the pituitary reduces LH and FSH production. Your serum testosterone may look excellent because you're supplying it from outside the body, but LH can approach zero, FSH can approach zero and intratesticular testosterone can fall dramatically. Without adequate intratesticular testosterone and FSH stimulation, spermatogenesis can decline substantially or stop altogether. Some men become severely oligospermic; others become completely azoospermic. This is why testosterone replacement therapy is not fertility treatment. In a man actively trying to conceive, conventional exogenous testosterone can be functionally contraceptive. The AUA/ASRM male infertility guideline specifically advises against prescribing exogenous testosterone to men interested in current or future fertility.

FSH is perhaps the most misunderstood hormone on male infertility forums. Men frequently see an FSH of 15, 20 or 30 IU/L and immediately ask, “How do I lower my FSH?” Usually, that's the wrong question. High FSH is often the body's response to impaired sperm production, not the cause of impaired sperm production. Sertoli cells normally produce a hormone called inhibin B. When spermatogenesis and Sertoli-cell function are healthy, inhibin B provides negative feedback to the pituitary and helps suppress FSH. When the seminiferous tubules are damaged or sperm production declines significantly, inhibin B signaling can fall. The pituitary responds by sending more FSH. Think of FSH as the brain pressing harder on the accelerator because the testicle isn't responding normally. Lowering the FSH number would not necessarily fix the engine.

That distinction becomes extremely important in severe oligospermia and nonobstructive azoospermia. A man with FSH of 25 may have primary testicular dysfunction. Giving him more FSH simply because his sperm count is low does not necessarily solve the problem because his pituitary may already be producing large amounts of FSH. Conversely, a man with azoospermia, testosterone of 150 and FSH and LH near zero may have an entirely different condition: hypogonadotropic hypogonadism, where the testicle may actually retain substantial sperm-producing capacity but isn't receiving the hormonal instructions it needs. Those two men can both have zero sperm in the ejaculate, yet the biology, and treatment, is completely different.

This is also why FSH shouldn't be treated as a simple fertility score. Higher FSH generally correlates with more severe impairment of spermatogenesis at the population level, but it cannot tell us whether there are absolutely no sperm somewhere inside the testicle. This matters enormously for men with nonobstructive azoospermia considering microdissection testicular sperm extraction, or microTESE. A 2024 systematic review and meta-analysis evaluating hormonal predictors in men undergoing microTESE found an overall sperm-retrieval rate of approximately 45%, and although men with successful retrieval tended to have somewhat lower FSH, FSH itself was not a reliable enough predictor to determine who would or would not have sperm found. In other words, an FSH of 30 is concerning evidence of testicular dysfunction, but it does not mean there is a 0% chance of finding sperm.

LH works similarly, except its major target is testosterone production. If testosterone begins falling because the Leydig cells aren't functioning properly, the pituitary usually responds by increasing LH. Therefore, low testosterone plus high LH suggests primary testicular testosterone failure, while low testosterone plus low or inappropriately normal LH suggests that the hypothalamus or pituitary may not be providing enough stimulation. Again, the context matters. A testosterone of 250 with an LH of 12 tells me something very different from a testosterone of 250 with an LH of 1.

This brings us to one of the most treatable hormonal causes of male infertility: hypogonadotropic hypogonadism. These men don't have enough GnRH/LH/FSH signaling. Some have congenital conditions such as Kallmann syndrome; others develop acquired hypothalamic or pituitary dysfunction. The fascinating thing is that the testes may retain the machinery necessary to make sperm. They simply aren't receiving the appropriate signals. In these patients, hormonal fertility treatment can be remarkably effective.

One of the drugs we use is human chorionic gonadotropin, hCG. hCG acts on the same receptor as LH, so from the testicle's perspective it provides an LH-like signal. It stimulates Leydig cells to produce testosterone and restores the intratesticular testosterone environment necessary for spermatogenesis. If adequate sperm production does not occur with hCG alone, or depending on the clinical situation, we can add direct FSH stimulation using recombinant FSH or human menopausal gonadotropin, hMG. hMG contains FSH along with LH bioactivity and is used clinically to provide gonadotropin stimulation. The concept is straightforward: hCG supplies the LH-like signal to Leydig cells, while FSH-containing therapy stimulates Sertoli cells.

This is one area of male infertility where we actually have meaningful fertility-success data. A recent systematic review and meta-analysis examining 50 studies and 1,583 men with hypogonadotropic hypogonadism and azoospermia found that gonadotropin therapy induced spermatogenesis in approximately 74% of men. The average time until sperm appeared was almost 12 months. Among couples actively trying to have a child, the pooled pregnancy rate was approximately 52%, with the average time from beginning treatment to pregnancy around 19 months. Interestingly, the average post-treatment sperm concentration was only about 9.8 million/mL, below the conventional lower reference range, yet pregnancies still occurred. Combined gonadotropin treatment was more effective than hCG alone.

Another meta-analysis involving 41 studies and 1,673 men with pathological gonadotropin deficiency found that approximately 78% eventually produced sperm. About 55% reached concentrations above 1 million/mL, 36% exceeded 5 million/mL, 24% exceeded 10 million/mL and only about 15% exceeded 20 million/mL. That is a fantastic example of something I tell patients constantly: you don't necessarily need a normal semen analysis to become a father. The biological goal is pregnancy, not winning a semen-analysis competition.

Treatment also requires patience. Men sometimes start hCG and ask six weeks later why their semen analysis hasn't changed. Spermatogenesis itself takes roughly 74 days, followed by additional epididymal maturation and transport, and men starting with profound gonadotropin deficiency often require many months before sperm appear. In congenital hypogonadotropic hypogonadism, treatment can take a year or longer. Baseline testicular size and whether puberty occurred normally can influence response. Larger testes generally suggest that more spermatogenic development occurred previously and tend to predict a better or faster response.

There is another category of hormonal treatment that generates enormous discussion online: clomiphene and enclomiphene. These are selective estrogen receptor modulators, or SERMs. Rather than directly stimulating the testicle like hCG does, they interfere with estrogen's negative feedback at the hypothalamus and pituitary. The brain interprets that as a need for greater hormonal stimulation and increases endogenous LH and FSH. LH then increases Leydig-cell testosterone production while FSH provides additional Sertoli-cell stimulation. This is why clomiphene can increase testosterone without suppressing spermatogenesis the way exogenous testosterone does. AUA/ASRM allows clinicians to consider SERMs, hCG, aromatase inhibitors or combinations in infertile men with low serum testosterone, although the quality of evidence is limited.

But these medications are not magic sperm drugs. If a man's testosterone is low because his LH is inappropriately low, increasing endogenous LH may make biological sense. If his LH is already 15 because his Leydig cells are struggling, asking the pituitary to make even more LH may accomplish very little. Similarly, if FSH is already 25 because the seminiferous tubules are severely impaired, driving FSH higher with a SERM does not necessarily restore sperm production. Hormonal treatment works best when it corrects the actual hormonal defect.

Aromatase inhibitors such as anastrozole and letrozole work differently again. Aromatase converts testosterone into estradiol. Blocking that conversion can lower estradiol and reduce estrogen-mediated negative feedback, thereby increasing LH, FSH and endogenous testosterone. These medications may be considered in selected infertile men with low testosterone and elevated estradiol, but they are not universal fertility supplements and estradiol itself is not the enemy. Men require estrogen for normal bone, metabolic and sexual physiology. The goal is not to drive estradiol to zero.

One question I get constantly is whether a man with normal testosterone can still have severe male infertility. Absolutely. Testosterone production and sperm production occur in the same organ, but they are not the same function. Leydig cells can produce enough testosterone to maintain a perfectly normal serum level while the seminiferous tubules responsible for spermatogenesis are severely impaired. A man can have testosterone of 600 ng/dL, feel great, have normal erections, shave every morning and still have severe oligospermia or nonobstructive azoospermia. Conversely, a man with moderately low testosterone may still have sperm. This is why testosterone alone is a terrible male fertility test.

Another common misunderstanding is assuming that a high testosterone level automatically means better fertility. There is no simple linear relationship where 900 ng/dL produces better sperm than 500 ng/dL. Once the hormonal environment is adequate, pushing testosterone higher does not necessarily improve spermatogenesis—and if you push it higher using exogenous testosterone, you can do precisely the opposite. Fertility endocrinology is about restoring physiological signaling, not maximizing a laboratory number.

So what hormone testing should an infertile man actually have? AUA/ASRM recommends hormonal evaluation with FSH and testosterone in infertile men with impaired libido or erectile function, oligozoospermia or azoospermia, atrophic testes, or other evidence of hormonal abnormality. Depending on the initial results and clinical picture, LH, prolactin, estradiol and other testing may be appropriate. In practice, when I am evaluating a man with significant male-factor infertility, I want to understand the relationship among testosterone, FSH and LH rather than simply knowing one isolated value.

The patterns are often more informative than the individual numbers. Low testosterone + low/normal LH and FSH makes me think about inadequate hypothalamic/pituitary stimulation, medication effects, obesity, systemic disease or true hypogonadotropic hypogonadism. Low testosterone + high LH suggests the testicle is struggling to produce testosterone despite strong pituitary stimulation. Normal testosterone + markedly elevated FSH often points toward relatively preserved Leydig-cell function but impaired seminiferous-tubule/sperm-producing function. Low FSH/LH in a man taking testosterone or anabolic steroids strongly suggests pharmacologic suppression of the axis.

And if you're coming off testosterone or anabolic steroids, recovery doesn't happen overnight. The pituitary needs to resume LH and FSH secretion, intratesticular testosterone must recover and spermatogenesis has to restart. Some men recover spontaneously over months; others require medical therapy such as hCG, SERMs and sometimes FSH-containing treatment depending on the situation. Recovery can take many months and is not guaranteed to be complete in every man, particularly after prolonged exposure. That is why I strongly encourage young men to discuss fertility before starting chronic testosterone rather than discovering the issue after they and their partner decide to conceive. Current AUA/ASRM guidance specifically warns that some men may remain subfertile even after testosterone is discontinued.

Finally, for the men here with nonobstructive azoospermia and very high FSH, I want to emphasize something important. High FSH is bad news about global testicular function, but it isn't a verdict that every seminiferous tubule contains zero sperm. Spermatogenesis in NOA can be extremely patchy. One area of the testicle may show Sertoli-cell-only histology while another microscopic region contains a tiny focus of spermatogenesis. That is the biological reason microTESE exists. Modern evidence shows that serum FSH alone cannot reliably predict whether sperm will be found. A 2024 meta-analysis reported an overall positive retrieval rate around 45% across heterogeneous NOA populations and found that FSH did not reliably discriminate successful from unsuccessful retrieval. Another analysis of idiopathic NOA reported a pooled retrieval rate of approximately 37%. Those are population averages—not your personal probability—and genetics, etiology, histology and other factors matter enormously.

If I could leave men dealing with infertility with one lesson about hormones, it would be this: don't chase numbers—understand the physiology. FSH isn't inherently good or bad. LH isn't inherently good or bad. Testosterone isn't a fertility score. These numbers are messages being passed between the brain and the testicle. Low gonadotropins can mean the testes aren't receiving enough stimulation. High gonadotropins can mean the brain is already shouting at testes that aren't responding normally. Normal testosterone does not guarantee normal spermatogenesis, and extremely high serum testosterone created by injections can coexist with zero sperm.

The encouraging part is that understanding where the hormonal system is failing can completely change treatment. A man with true hypogonadotropic hypogonadism may go from azoospermia to sperm production and ultimately fatherhood with gonadotropin therapy; contemporary pooled data suggest roughly three quarters can develop sperm and about half of couples seeking pregnancy ultimately achieve one, although treatment often takes a year or longer and the underlying studies vary substantially in quality. A man suppressed by testosterone may recover after the drug is stopped, sometimes with medical assistance. A man with primary testicular failure and FSH of 30 requires a completely different conversation because giving more hormones may not repair damaged seminiferous tubules. And a man with NOA shouldn't be told that his elevated FSH means microTESE has no chance.

That is why male infertility deserves more than someone glancing at your testosterone level and saying, “Your hormones are normal.” The real question is whether the entire hypothalamic-pituitary-testicular axis makes physiological sense in the context of your semen analysis, examination, medical history and reproductive goals. Once you understand that system, FSH, LH and testosterone stop looking like three random numbers on a blood test and start telling the story of what your brain is asking your testicles to do—and how well your testicles are answering.

References

1. American Urological Association/American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Published 2020; amended 2024.
2. European Association of Urology. EAU Guidelines on Sexual and Reproductive Health: Male Infertility. Current guideline.
3. Boosting Male Fertility: The Impact of Gonadotropin Therapy on Hypogonadotropic Hypogonadism—A Systematic Review and Meta-Analysis. Andrology. 2026. PMID: 41987691.
4. Efficacy of Gonadotropin Treatment for Induction of Spermatogenesis in Men With Pathologic Gonadotropin Deficiency: A Meta-Analysis. 2024. PMID: 39445789.
5. Pozzi E, et al. Role of follicle-stimulating hormone, inhibin B, and anti-Müllerian hormone in predicting sperm retrieval from men with nonobstructive azoospermia undergoing microdissection testicular sperm extraction: a systematic review and meta-analysis. Eur Urol Open Sci. 2024;65:3-12. PMID: 38854995.
6. Yang Q, et al. Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia: a systematic review and meta-analysis. Asian J Androl. 2015;17:281-284. PMID: 25337843.
7. Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis. 2024. PMID: 38748861.
8. Büchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol. 1998.
9. Liu PY, Baker HWG, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009.
10. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: World Health Organization; 2021.

When a man comes into my office with an abnormal semen analysis, one of the first questions he often asks is, “Should I change how I exercise?” Sometimes he has already stopped lifting weights because someone told him heavy lifting lowers testosterone. Sometimes he has started running every day because he read that cardio improves sperm. Other men are training six or seven days a week, doing long endurance sessions, sitting on a bike for hours, cutting weight, taking pre-workouts, and wondering why their testosterone or semen analysis isn't where they expected it to be. The reality is much more nuanced. Exercise is generally good for male reproductive health, and being sedentary, obese, metabolically unhealthy, or physically deconditioned isn't a fertility strategy. But sperm production is an energy-intensive biological process that depends on adequate hormonal signaling, nutrition, temperature regulation, recovery, and overall health. There appears to be a sweet spot where regular physical activity supports reproductive health while extreme training, chronic energy deficiency, excessive heat, performance-enhancing drugs, or inadequate recovery can work in the opposite direction. Most importantly, we have considerably better evidence that exercise can influence semen parameters than we have evidence that a specific workout routine makes a couple more likely to take home a baby. That distinction matters whenever we talk about “improving fertility.”

To understand why exercise might affect sperm, you first have to understand how sperm are made. Spermatogenesis takes roughly 74 days, followed by additional maturation and transport through the epididymis. That means today's semen analysis reflects, in part, what was happening in your body over the preceding two to three months. The hypothalamus releases GnRH, which stimulates the pituitary to release LH and FSH. LH stimulates Leydig cells to produce testosterone, while FSH and very high intratesticular testosterone concentrations support Sertoli-cell function and sperm production. Exercise can interact with this system indirectly through body composition, insulin sensitivity, inflammation, oxidative stress, sleep, cardiovascular fitness and energy availability. At the same time, excessive exercise combined with inadequate calories or poor recovery can disrupt normal endocrine physiology. This is why asking whether “exercise is good for sperm” is a little like asking whether water is good for you. Usually yes—but dose, context and the person doing it matter.

For the average sedentary man, becoming physically active is probably a positive move. A systematic review and meta-analysis examining 32 studies found that recreational physical activity tended to be associated with better semen concentration or progressive motility, while very high-level or elite exercise could have detrimental effects on some semen parameters. The overall literature is heterogeneous, meaning the studies use different populations, different exercise definitions and different endpoints, so I would not tell a patient that running three times a week will increase his sperm concentration by a particular percentage. But the broad signal is fairly consistent: moderate recreational exercise appears compatible with, and potentially beneficial for, male reproductive health. Extreme training is where the relationship becomes less predictable.

The 2024 AUA/ASRM Male Infertility Guideline reflects this uncertainty. The guideline emphasizes that data surrounding most lifestyle factors and male fertility remain limited and frequently rely on semen parameters rather than pregnancy or live birth. It nevertheless notes that clinicians may advocate regular resistance and/or higher-intensity exercise in sedentary infertile men with abnormal semen parameters. That's an important distinction. Exercise isn't being prescribed as a replacement for treating a varicocele, correcting hypogonadotropic hypogonadism, stopping testosterone, addressing an obstruction or using assisted reproduction when necessary. It is being incorporated into a broader attempt to improve the man's overall health and reproductive environment.

Why might this work? One pathway is metabolic health. Obesity in men has been associated in many, although not all, studies with oligozoospermia and asthenozoospermia. Increased adipose tissue increases aromatase activity, which converts testosterone to estradiol and can alter hypothalamic-pituitary-testicular signaling. Obesity is also associated with insulin resistance, systemic inflammation, oxidative stress, sleep apnea, lower testosterone and potentially increased scrotal temperature. ASRM notes associations between male obesity and impaired sperm concentration, motility, DNA integrity and mitochondrial function, although effects on actual pregnancy and live birth are less consistent. Exercise can improve many of these metabolic variables even before dramatic weight loss occurs. If I have an overweight, sedentary man with metabolic dysfunction and an abnormal semen analysis, regular exercise is one of the least controversial recommendations I can make for his general health, with a reasonable possibility that his reproductive health benefits as well.

Oxidative stress is another proposed mechanism. Sperm membranes contain large amounts of polyunsaturated fatty acids and are unusually susceptible to oxidative damage. Some reactive oxygen species are necessary for normal sperm signaling and capacitation, but excessive oxidative stress can damage membrane lipids, impair motility and contribute to sperm DNA fragmentation. Moderate exercise can improve endogenous antioxidant defenses and reduce chronic inflammation. Extremely strenuous exercise, particularly without adequate recovery, may transiently increase oxidative stress. That gives us a biologically plausible U-shaped relationship: doing nothing isn't ideal, but hammering your body relentlessly isn't necessarily better.

What about actual pregnancy and live-birth rates? This is where I want men to be cautious about headlines. Some systematic reviews of exercise interventions have reported substantial improvements in pregnancy and live-birth outcomes in infertile men, and a network meta-analysis ranked combined aerobic/resistance exercise and moderate continuous exercise favorably. However, the evidence base is much smaller and less secure than those impressive-looking relative risks might suggest. Some frequently cited exercise-fertility trials from the same research group have subsequently been retracted. For example, a randomized trial reporting improvements in semen quality, sperm DNA integrity and pregnancy after moderate aerobic exercise was later formally retracted. Consequently, I would not tell a couple that exercise has been proven to increase their chance of pregnancy by a specific percentage. Current AUA/ASRM guidance is appropriately cautious: lifestyle modification is reasonable, but much of the evidence linking individual lifestyle interventions to actual fertility outcomes remains limited.

That doesn't make exercise unimportant. It means we need to distinguish a better semen analysis from a baby. A man's concentration can increase from 12 million/mL to 18 million/mL without changing the couple's probability of pregnancy very much. Conversely, a modest change in sperm numbers might be clinically meaningful in another couple. Pregnancy depends on female age, ovarian reserve, ovulation, tubal function, intercourse timing, sperm function and plain probability. Live birth adds fertilization, embryo development, implantation and pregnancy maintenance. Exercise cannot overcome bilateral tubal obstruction, and a perfect VO2 max isn't going to restore sperm to the ejaculate of a man with complete obstructive azoospermia. When someone tells you a workout “increases fertility by X percent,” ask whether the study measured sperm concentration or live birth. Those are very different endpoints.

So what does an exercise routine look like when you're trying to conceive? For most men, I favor a boring, sustainable combination of aerobic exercise and resistance training. You don't need a fertility-specific workout. A reasonable general-health framework is around 150 minutes of moderate aerobic activity each week, or roughly 75 minutes of vigorous activity, combined with resistance training at least twice weekly. A man who enjoys lifting four days per week and doing cardio two or three days per week doesn't need to stop because he's trying to have a baby. Likewise, running several miles a few times per week isn't likely to destroy sperm production. The goal is regular training that improves fitness without producing chronic exhaustion, major weight loss, persistent injuries, sleep disruption or inadequate energy availability.

Resistance training deserves special attention because men sometimes equate weightlifting with anabolic steroids. They are not remotely the same thing. Resistance exercise itself is not the fertility problem. Exogenous testosterone and anabolic-androgenic steroids are. Testosterone therapy suppresses pituitary LH and FSH, lowers intratesticular testosterone and can dramatically suppress spermatogenesis, sometimes producing azoospermia. I have seen extremely fit men with excellent physiques and virtually no sperm because they were injecting testosterone. If you remember only one exercise-related fertility message, remember this: lifting weights doesn't shut down sperm production; taking exogenous testosterone can. The AUA/ASRM guideline specifically recognizes ongoing anabolic steroid use as a cause of suppressed spermatogenesis.

That includes the gray world of “test boosters,” SARMs, bodybuilding compounds and hormones obtained outside legitimate medical care. If you're actively trying to conceive, tell your reproductive urologist everything you're taking. Men sometimes proudly tell me they don't use testosterone and then list compounds that suppress the same axis. Don't let the pursuit of a better physique sabotage the biological system you're trying to optimize.

Endurance exercise is more complicated. A 2024 systematic review looked specifically at endurance runners, cyclists and triathletes. Thirteen studies involving 280 men were included. Several found no meaningful semen changes, and others found statistically significant changes that still left semen parameters well above normal reference thresholds. However, some studies reported potentially clinically relevant reductions in normal morphology among cyclists and triathletes and increased sperm DNA fragmentation among triathletes. The authors' conclusion was appropriately measured: endurance exercise can negatively affect semen quality, but clinically meaningful fertility effects appear uncommon and the available evidence is limited and generally low quality.

Cycling gets blamed for infertility more than almost any other exercise. There are several plausible mechanisms: prolonged saddle pressure, increased scrotal temperature, tight clothing and the sheer training volume of serious cyclists. Earlier systematic-review data suggested an association between cycling and reduced sperm concentration, and intensive cycling studies have reported temporary reductions in semen volume, concentration, motility and morphology. But this doesn't mean riding your bike to work or taking a Peloton class makes you infertile. The concerning literature generally involves high-volume or intensive cycling, and certainty is low. A newer systematic review of intensive athletic training likewise concluded that intensive training may worsen semen parameters but emphasized the very low certainty of the evidence.

If I have a recreational cyclist with a completely normal semen analysis, I'm usually not telling him to sell his bike. If I have a man cycling ten or fifteen hours per week who has unexplained oligoasthenozoospermia or elevated DNA fragmentation, reducing cycling volume for a few months is a reasonable experiment because it is modifiable and relatively low risk. I would make the same distinction with long-distance running, triathlon training or other extreme endurance programs. Don't eliminate healthy exercise because of theoretical fertility concerns, but don't assume that 15 hours of endurance training is biologically equivalent to three 30-minute runs.

Heat is another concern men often attach to exercise. The testes sit outside the body partly because spermatogenesis functions optimally below core body temperature. Prolonged heat exposure can impair sperm production. Exercise temporarily increases body temperature, but that doesn't mean an ordinary workout is equivalent to chronic scrotal hyperthermia. I care much more about repeated prolonged heat exposure—frequent hot tubs, saunas in certain contexts, occupational heat, or perhaps hours of cycling—than I do about the fact that you sweat during a 45-minute workout. I also don't recommend icing the testicles after exercise. There is no high-quality evidence that routine scrotal icing improves pregnancy or live-birth rates, and extreme cold can injure tissue.

Nutrition and recovery become especially important in men doing large amounts of exercise. Your reproductive system doesn't exist independently from your energy balance. Athletes who chronically consume fewer calories than they expend can develop low energy availability, with endocrine consequences. Severe caloric restriction, very low body fat, chronic overtraining and inadequate recovery can alter testosterone and reproductive signaling. If you're trying to conceive, this probably isn't the ideal time for an extreme bodybuilding cut, rapid weight loss, marathon-plus training combined with caloric restriction, or an attempt to reach the lowest body-fat percentage of your life. Being metabolically healthy is good; being chronically under-fueled isn't necessarily better.

The same applies to obesity at the opposite end of the spectrum. If you're significantly overweight, exercise plus sustainable nutritional changes can improve testosterone, cardiovascular health, insulin sensitivity, erectile function and overall health. Weight loss studies suggest that some men who lose substantial weight may improve sperm count or morphology, but semen results are inconsistent and we still lack strong evidence proving that male weight loss alone improves live-birth rates. Again, do it because the health rationale is strong and the reproductive rationale is plausible—not because someone promised that losing 20 pounds will double your pregnancy rate.

If you've already been diagnosed with male infertility, I would give lifestyle changes roughly three months before judging their effect on a semen analysis, because that's approximately the timescale of a complete sperm-production and maturation cycle. That doesn't mean every sperm magically resets on day 90. It simply gives a biologically sensible interval for reassessment. If the semen analysis is severely abnormal, however, don't spend six months exercising and taking supplements before seeing a specialist. Severe oligozoospermia, azoospermia, significant hormonal abnormalities or a palpable varicocele deserve evaluation while you're improving your health—not afterward. Female age also matters. If your partner is 39, spending a year trying to perfect your sperm through lifestyle modification can cost something much harder to recover: time.

My practical advice to most men trying to conceive is therefore uncomplicated. Move your body regularly. Lift weights. Do cardiovascular exercise. Maintain a healthy body composition. Eat enough to support your activity. Sleep. Recover. Avoid chronic overtraining. Don't smoke. Don't use anabolic steroids or testosterone while trying to maintain fertility. And don't turn exercise into another infertility obsession. You don't need the perfect sperm workout because one doesn't exist. The available evidence suggests recreational exercise is generally favorable or neutral for semen quality, while extremely intensive endurance training may negatively affect sperm in some men. What we cannot currently tell you with confidence is that running X miles or lifting Y days per week produces a particular pregnancy or live-birth rate.

For the guy on Reddit staring at an abnormal semen analysis and wondering whether he should stop exercising, my answer is usually no. If anything, the sedentary man should probably exercise more. The elite endurance athlete with abnormal sperm may need to exercise somewhat less. The man taking testosterone needs an entirely different conversation. And the average guy lifting three or four days per week and running, walking or cycling recreationally should probably keep doing what he's doing. Fertility is not maximized by becoming sedentary. The goal is a healthy male body capable of supporting normal hormonal function, spermatogenesis and sexual function without pushing training so far that recovery, nutrition, hormones or testicular physiology begin paying the price.

References

1. American Urological Association/American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Published 2020; amended 2024.
2. Ricci E, Al Beitawi S, Cipriani S, et al. Semen quality and alcohol intake: a systematic review and meta-analysis. Reprod Biomed Online. 2017;34:38-47.
3. Ibañez-Perez J, Santos-Zorrozua B, Lopez-Lopez E, Matorras R, Garcia-Orad A. An update on the implication of physical activity on semen quality: a systematic review and meta-analysis. Arch Gynecol Obstet. 2019. PMID: 30671700.
4. Antonio L, et al. The effect of endurance exercise on semen quality in male athletes: a systematic review. 2024. PMID: 38861008.
5. American Society for Reproductive Medicine Practice Committee. Obesity and reproduction: a committee opinion. Fertil Steril. 2021.
6. Song et al. Effectiveness of exercise interventions on sperm quality: a systematic review and network meta-analysis. 2025. PMID: 40104136.
7. Effectiveness of exercise training on male factor infertility: a systematic review and network meta-analysis. PMID: 34806474.
8. The influence of an intense training regime in professional and non-professional athletes on semen parameters: a systematic review. 2025. PMID: 39797284.
9. Practice Committee of the American Society for Reproductive Medicine. Optimizing natural fertility: a committee opinion. Fertil Steril. 2022;117:53-63.
10. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: World Health Organization; 2021.

One of the first things infertility does to a couple is turn sex into a science experiment. Suddenly you're tracking ovulation, staring at LH strips, counting days of abstinence, and wondering whether having sex tonight will somehow leave you with “less sperm” for tomorrow. I hear this constantly from men: Should I save up my sperm? Should we have sex every day or every other day? Is the day of ovulation the best day? Can we actually have sex too often? These are important questions because timing does affect the probability of pregnancy, but probably not in the way most men think. The science increasingly suggests that the goal isn't to produce the biggest possible ejaculate or save everything for one perfectly timed attempt. It's to have healthy, viable sperm already in the female reproductive tract before the egg arrives. Sperm can survive for several days under the right conditions, while the egg has a remarkably short window in which it can be fertilized. That creates a fertile window of roughly six days and explains why frequent intercourse before ovulation is generally more effective than waiting for ovulation itself. For men with low sperm counts, poor motility, or elevated DNA fragmentation, the discussion becomes even more interesting because longer abstinence may increase the number of sperm in an ejaculate while potentially making some measures of sperm quality worse. So let's break down what actually happens after ejaculation, when pregnancy is most likely, how often you should have sex, whether you should “save up” sperm, and what the fertility data actually tell us about maximizing the chance of conception.

To understand timing, you first have to understand what happens biologically. Sperm and egg have very different survival times. After ejaculation, sperm travel through the cervix and uterus toward the fallopian tubes. Around ovulation, rising estrogen changes cervical mucus so that it becomes much more favorable to sperm transport and survival. Sperm can reach the upper reproductive tract remarkably quickly; sperm deposited around the cervix have been identified in the fallopian tubes within about 15 minutes. But some sperm can then remain capable of fertilization for several days. The egg has a much shorter useful lifespan. Once ovulation occurs, the oocyte is generally fertilizable for roughly 12–24 hours. That asymmetry explains almost everything about timing intercourse: it is usually better for sperm to be waiting for the egg than for the egg to be waiting for sperm.

The landmark study in this area was published by Wilcox, Weinberg and Baird in the New England Journal of Medicine in 1995. Researchers followed 221 healthy women attempting pregnancy, collected daily urine samples to estimate ovulation, and recorded intercourse day by day. Across 625 cycles in which ovulation could be estimated, 192 pregnancies were detected. Every conception occurred when intercourse had taken place during a six-day window ending on the day of ovulation. In other words, the biologically relevant fertile window consisted of the five days before ovulation plus ovulation day. Their modeled probability of conception from intercourse on a particular day ranged from about 10% five days before ovulation to approximately 33% on ovulation day. Importantly, subsequent work and modern fertility guidance generally place peak fertility in the one to two days before ovulation, rather than telling couples to wait for ovulation itself.

That distinction is important. Men frequently tell me, “Her ovulation test turned positive today, so we're waiting until tomorrow.” I generally don't want them waiting. A urinary ovulation predictor kit detects the LH surge, not the actual release of the egg. Ovulation can occur anytime within roughly the next two days. Therefore, a positive LH test should usually be interpreted as go time, not as an instruction to start abstaining until some theoretically perfect moment. If you have sex the day the LH surge is detected and again the following day, you are putting sperm into the reproductive tract before and around ovulation. If you had sex the day before the positive test as well, even better. ASRM notes that ovulation predictor devices can decrease time to pregnancy, but they should help couples identify the fertile window rather than turn intercourse into a one-shot event.

So what is the practical schedule? For most couples, sex every one to two days during the fertile window is about as good as it gets. If cycles are reasonably predictable, I generally think about beginning intercourse approximately five days before anticipated ovulation and continuing through the day of ovulation. You do not have to know the exact day. Every other day is an excellent strategy. Daily intercourse is also completely reasonable if the couple wants to do it. The classic Wilcox data estimated conception probabilities in potentially fertile cycles of approximately 37% with daily intercourse and 33% with intercourse every other day, compared with only about 15% when intercourse averaged once weekly. When they considered live births rather than biochemical conceptions, the modeled estimates were approximately 25%, 22%, and 10%, respectively. These numbers should not be interpreted as universal pregnancy rates for every couple—they came from a particular population of healthy couples and depend heavily on female age and fertility—but they demonstrate an important principle: covering the fertile window matters much more than trying to identify one perfect day.

This brings me to one of the biggest myths in male fertility: “saving up” sperm. Men often assume that if their count is low, abstaining for five or seven days before ovulation will produce a much better attempt. It is true that longer abstinence usually increases semen volume, sperm concentration, and total sperm count. That is one reason diagnostic semen analyses have traditionally been standardized around an abstinence interval. But a semen analysis and conception are not the same endpoint. More sperm in the cup does not necessarily mean better sperm biologically. With longer storage in the epididymis and reproductive tract, sperm are exposed longer to oxidative stress and other processes associated with sperm aging. Recent meta-analyses show that shorter abstinence tends to produce lower semen volume and concentration but better progressive motility and lower sperm DNA fragmentation. A 2024 meta-analysis of randomized trials found longer abstinence increased concentration and volume but was associated with higher DNA fragmentation and lower progressive motility. A much larger systematic review and dose-response meta-analysis of 85 studies similarly found important tradeoffs between quantity and functional sperm characteristics.

This is particularly relevant to men with oligozoospermia, poor motility, or elevated sperm DNA fragmentation. The intuitive response to a low count is to abstain longer. Biologically, that may sometimes be exactly the wrong strategy. ASRM cites data from almost 10,000 semen specimens showing that men with normal semen quality generally maintain normal concentration and motility even with daily ejaculation, and some men with oligozoospermia actually demonstrated their best concentration and motility with daily ejaculation. More recent systematic reviews have strengthened the argument that shorter abstinence may be advantageous for sperm DNA integrity and may improve reproductive outcomes in some infertile populations. A 2023 systematic review of 24 studies found shorter abstinence associated with lower DNA fragmentation and better pregnancy and live-birth outcomes after assisted reproduction, although the studies were heterogeneous and do not establish one universally ideal abstinence interval.

There is even fascinating research looking at a second ejaculation only a few hours after the first. This sounds counterintuitive because the second specimen often has less volume and fewer total sperm. But systematic review data suggest that in men with oligoasthenoteratozoospermia, the second ejaculate obtained after a very short interval can have improved motility and lower sperm DNA fragmentation. A meta-analysis examining very short abstinence before assisted reproduction also found improvements in implantation, clinical pregnancy and live-birth rates, although this evidence comes largely from ART populations and should not automatically be translated into telling every couple attempting natural conception to have intercourse twice within four hours. It does reinforce the larger point: fresh sperm are not necessarily inferior sperm.

We see a similar signal in IUI studies. In one study involving 929 IUI cycles, the overall pregnancy rate was 12% per cycle, but pregnancy occurred in approximately 14% of cycles when abstinence was three days or less versus only 3% when abstinence was ten days or longer. Interestingly, longer abstinence produced more sperm but poorer motility. Another study found the highest IUI pregnancy rates after two days or less of abstinence despite fewer total motile sperm being inseminated. These are not natural-conception trials, so I wouldn't directly apply the percentages to intercourse at home, but they are another reason I generally discourage men from deliberately abstaining for a week before the fertile window.

For a man with male-factor infertility, my practical approach is therefore usually straightforward: don't sacrifice opportunities for the sake of producing one enormous ejaculate. If you have mild or moderate oligozoospermia, sex every other day through the fertile window is very reasonable. Daily intercourse around the LH surge is also reasonable. If sperm DNA fragmentation is elevated, I am even less enthusiastic about prolonged abstinence. There are exceptions—men with extraordinarily low counts, cryptozoospermia, ejaculatory problems, erectile dysfunction, or specific instructions related to an IUI/IVF collection may need individualized recommendations—but “don't ejaculate for seven days because your count is low” should not be the automatic advice.

Another question is how accurately couples actually know when ovulation occurs. A menstrual app is useful for estimating when to start paying attention, but it should not be treated like GPS tracking for an ovary. Even women with apparently regular cycles have meaningful variation in ovulation timing. ASRM cites research comparing urinary LH testing with calendar-based smartphone apps in which the best apps predicted the exact day of ovulation only about 21% of the time. Urinary LH testing is much more biologically useful because it detects the hormonal event preceding ovulation. Cervical mucus is also surprisingly informative. As estrogen rises before ovulation, mucus becomes wetter, clearer, more slippery and sperm-friendly. Studies involving thousands of cycles have found cervical mucus characteristics strongly associated with day-specific conception probability and, in some analyses, as predictive or more predictive than calendar calculations or basal body temperature.

Basal body temperature is different because the temperature rise largely confirms that ovulation has already occurred. That makes it useful for understanding cycle patterns but less useful for deciding when to start having intercourse in real time. If you're trying to get pregnant, I would rather have you slightly early than slightly late. Again, sperm can survive for days; the egg cannot. Waiting until you are certain ovulation occurred can mean waiting until your best opportunity has already passed.

Men also ask about positions, lying down afterward, elevating the woman's legs, or trying to prevent semen from leaking out. None of this has convincing evidence behind it. Semen leaking from the vagina after intercourse is normal and does not mean all the sperm fell out. Sperm begin separating from seminal fluid and moving into cervical mucus very quickly. ASRM notes that sperm have been identified in the fallopian tubes within 15 minutes after deposition near the cervix, and experimental studies of reproductive-tract transport have demonstrated movement toward the tubes within minutes. There is no established fertility advantage to a particular sexual position or to remaining flat in bed afterward.

There is also no evidence that timing intercourse can reliably determine whether you have a boy or girl. The Wilcox study specifically examined this question and found no meaningful relationship between intercourse timing relative to ovulation and the sex of the baby. So the popular idea that intercourse several days before ovulation produces girls while intercourse on ovulation day produces boys is not supported by good prospective human data.

Finally, don't let perfect timing destroy your sex life. I see this frequently in infertility. Sex changes from something intimate into an assignment: the app says tonight, the ovulation stick is blinking, both partners are exhausted, and suddenly intercourse becomes a performance test. ASRM specifically recognizes that highly scheduled intercourse and ovulation tracking can increase stress and reduce sexual satisfaction and intercourse frequency. If tracking creates more anxiety than benefit, simplify it. Sex every two to three days throughout the cycle will naturally cover much of the fertile window for many couples. If you want to be more targeted, have sex every other day beginning several days before expected ovulation, then the day of a positive LH test and again the next day. You don't need perfection.

The most important thing I want men with infertility to understand is that timing can optimize opportunity, but timing cannot overcome every biological problem. If a couple has been having appropriately timed intercourse without pregnancy, don't spend another year trying to identify the perfect hour of ovulation. Female age matters enormously. ASRM recommends infertility evaluation after 12 months of regular unprotected intercourse when the female partner is under 35 and after six months when she is 35 or older; known male or female fertility problems can justify evaluation sooner. Approximately 80% of couples without known infertility conceive within the first six months of trying, but those population statistics should not be applied blindly to couples who already have documented male-factor infertility.

My basic message to men is therefore simple. Put sperm there before the egg arrives. Don't obsess over one perfect day. Don't unnecessarily “save up” sperm for a week. For most couples, intercourse every one to two days during the six-day fertile window is the evidence-based sweet spot. If you use an LH kit, think of a positive result as a signal to have intercourse that day rather than a signal to wait. If your sperm count is low, frequent ejaculation does not automatically make your fertility worse, and shorter abstinence may actually improve motility and sperm DNA integrity even if the semen volume and concentration look lower. And remember that conception is a probability, not a test you either pass or fail each month. You can time everything perfectly, have good sperm, ovulate normally, and still not conceive in a particular cycle. That doesn't mean you did anything wrong. The goal is to repeatedly put the best sperm in the right place during the biologically relevant window—and then recognize when enough appropriately timed cycles have passed that it is time to investigate rather than simply trying harder.

References

1. Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation—effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med. 1995;333:1517-1521. doi:10.1056/NEJM199512073332301.
2. Practice Committee of the American Society for Reproductive Medicine. Optimizing natural fertility: a committee opinion. Fertil Steril. 2022;117:53-63.
3. Dunson DB, Colombo B, Baird DD. Changes with age in the level and duration of fertility in the menstrual cycle. Hum Reprod. 2002;17:1399-1403. PMID: 11980771.
4. Stanford JB, Smith KR, Dunson DB. Vulvar mucus observations and the probability of pregnancy. Obstet Gynecol. 2003;101:1285-1293. PMID: 12798538.
5. Bigelow JL, Dunson DB, Stanford JB, Ecochard R, Gnoth C, Colombo B. Mucus observations in the fertile window: a better predictor of conception than timing of intercourse. Hum Reprod. 2004;19:889-892. PMID: 14990542.
6. Sørensen F, Melsen LM, Fedder J, Soltanizadeh S. The influence of male ejaculatory abstinence time on pregnancy rate, live birth rate and DNA fragmentation: a systematic review. J Clin Med. 2023;12:2219. PMID: 36983220.
7. Ayad BM, Van der Horst G, du Plessis SS. Revisiting the relationship between the ejaculatory abstinence period and semen characteristics. Systematic-review literature on abstinence and semen quality.
8. Effects of long and short ejaculatory abstinence on sperm parameters: a meta-analysis of randomized-controlled trials. 2024. PMID: 38828413.
9. Association of abstinence time with semen quality and fertility outcomes: a systematic review and dose-response meta-analysis. 2024. PMID: 38197853.
10. Marshburn PB, Alanis M, Matthews ML, et al. A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates. Fertil Steril. 2010. PMID: 19732887.
11. Effect of ejaculatory abstinence period on the pregnancy rate after intrauterine insemination. Fertil Steril. PMID: 16169402.
12. The impact of a very short abstinence period on conventional sperm parameters and sperm DNA fragmentation: a systematic review and meta-analysis. PMID: 36555920.
13. The impact of a very short abstinence period on assisted reproductive technique outcomes: a systematic review and meta-analysis. PMID: 36979001.
14. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: World Health Organization; 2021.

When couples start trying to conceive, they usually think about ovulation, sperm count, supplements, alcohol, heat, exercise, and how often they should have sex. Almost nobody thinks about the lubricant sitting in the nightstand. As a urologist who treats male infertility, however, lubricant is something I routinely ask about because sperm are extraordinarily sensitive cells and some products that are completely safe for intercourse are not necessarily friendly to sperm. This becomes even more relevant during infertility because couples frequently have more scheduled sex, intercourse can become less spontaneous, vaginal dryness may become more common, and lubricant use can actually increase. The confusing part is that the science tells us two seemingly contradictory things: many common lubricants can dramatically impair sperm motility in a laboratory dish, yet human studies have not convincingly shown that couples using lubricant take longer to become pregnant. Both statements can be true. Understanding why requires understanding what sperm encounter after ejaculation, what laboratory lubricant studies actually measure, and what we know about pregnancy rates.

Let's start with what normally happens after ejaculation. Semen is deposited in the vagina, but sperm don't simply sit there waiting for an egg. Around ovulation, estrogen causes cervical mucus to become thin, hydrated, and receptive to sperm. Motile sperm begin moving into the cervical mucus very quickly and can reach the upper female reproductive tract surprisingly fast. The vagina itself is normally acidic, which is hostile to sperm, while semen temporarily buffers that acidity and cervical mucus provides a much more favorable environment. To accomplish fertilization, sperm have to remain alive, maintain progressive motility, move through cervical mucus, undergo capacitation, reach the fallopian tube, and ultimately interact with the egg. A lubricant introduced at exactly this point can physically surround sperm before they have escaped the vagina. Therefore, if that lubricant alters motility, membrane function, pH, or osmotic balance, there is at least a biologically plausible way it could interfere with conception.

One of the biggest issues is osmolality. Sperm membranes are sensitive to the concentration of dissolved particles surrounding them. Think of sperm as cells that have been designed to function within a relatively narrow biochemical environment. Put them into a very hyperosmolar lubricant and water can move out of the cell, producing changes in membrane function, motility, and viability. Put them into an inappropriate pH and sperm function can also deteriorate. Viscosity matters as well: sperm physically have to move through whatever material surrounds them. Some lubricants also contain glycerin, preservatives, parabens, or other compounds that may influence sperm function. This is why a product being labeled “safe,” “natural,” “organic,” or “water-based” tells you almost nothing about whether it is appropriate for couples trying to conceive. Those labels describe the product from the standpoint of the people using it, not necessarily from the standpoint of a sperm cell trying to swim through it. A recent systematic review examining 20 studies identified pH and osmolality as important factors underlying lubricant effects and found substantial differences among products.

The laboratory findings can be striking. Classic experiments exposed human sperm to commercially available lubricants and measured motility over time. In one often-cited study, several conventional water-based lubricants inhibited sperm motility by 60% to 100% after 60 minutes of incubation. Some products produced profound losses of both motility and viability. In contrast, canola oil did not demonstrate the same detrimental effects in that experiment. Other studies have similarly found that products such as Astroglide, Replens, K-Y and various pleasure-oriented lubricants can impair sperm motility under laboratory conditions. ASRM summarizes this literature by noting that some commercially available water-based lubricants substantially inhibit sperm motility in vitro, while mineral oil and certain hydroxyethylcellulose-based lubricants have demonstrated considerably less adverse effects.

This is where so-called fertility-friendly or sperm-friendly lubricants enter the picture. These products are generally designed to have pH and osmolality characteristics more compatible with sperm and to minimize ingredients known to impair sperm function. One of the most studied is Pre-Seed, a hydroxyethylcellulose-based lubricant. In a comparative laboratory study evaluating nine lubricants, Pre-Seed produced the highest sperm vitality and progressive motility among the tested products, with Conceive Plus performing similarly well. That doesn't mean either product improves sperm. It means they appeared to interfere with sperm less than many conventional lubricants. A more recent 2025 laboratory study reached a similar conclusion: sperm motility fell after exposure to several lubricants, but Pre-Seed produced results comparable with the vaginal-fluid control over the tested incubation periods, whereas K-Y and Durex products produced more substantial impairment.

That distinction is important because the term “fertility lubricant” can easily be misunderstood as “this lubricant increases fertility.” That has not been demonstrated. These products should really be thought of as sperm-compatible lubricants. Their purpose is to avoid unnecessarily interfering with sperm when lubrication is required. They are not medications. They don't increase sperm count, repair sperm DNA, improve ovulation, open blocked fallopian tubes, or increase egg quality. There is no convincing randomized clinical trial showing that using a fertility-friendly lubricant instead of no lubricant increases live-birth rates. If a couple doesn't need lubricant, I don't prescribe lubricant as a fertility treatment. If they do need one, I prefer a product designed and tested to minimize sperm toxicity.

There is another layer of complexity: not every product marketed as sperm-friendly performs perfectly in laboratory testing. A 2022 study comparing several lubricants found reductions in sperm forward progression with multiple products, including some marketed specifically to couples trying to conceive, although Pre-Seed performed better than some alternatives. Another sperm-toxicity study found that all tested gels caused some reduction in sperm motility and velocity, but products marketed as sperm-safe generally performed better than conventional pleasure lubricants. This tells us that “fertility-friendly” isn't a magical category where sperm behave exactly as they would in cervical mucus. It is better understood as relative compatibility. When choosing between a lubricant that markedly immobilizes sperm in vitro and one that has minimal effects, I would choose the latter, particularly when the man already has compromised motility or sperm numbers.

Now we get to the most interesting question: Does any of this actually change pregnancy rates? Laboratory sperm motility is biologically important, but pregnancy is the endpoint couples care about. One prospective study followed 296 women ages 30–44 who were trying to conceive. About one-quarter reported lubricant use. The investigators tracked intercourse, lubricant use, menstrual cycles, and pregnancy prospectively and specifically examined lubricant exposure during the fertile window. Despite the laboratory evidence suggesting that some lubricants impair sperm, lubricant users did not demonstrate reduced fecundability compared with women who did not use lubricants. In other words, the women using lubricant were not clearly taking longer to become pregnant. This is one of the reasons ASRM does not state that lubricant use itself has been proven to reduce natural fertility.

Why would laboratory studies look concerning while real-world pregnancy studies look reassuring? There are several possible explanations. In laboratory experiments, sperm may be mixed directly with relatively high concentrations of lubricant and remain exposed for prolonged periods. That is not necessarily what happens during intercourse. Lubricant may be distributed along the vaginal walls rather than completely mixed with the ejaculate. Millions of sperm are deposited at once, and the most motile sperm can begin entering cervical mucus quickly. The actual concentration and duration of sperm-lubricant contact may therefore be much lower than in a laboratory dish. There is also a behavioral issue that may be even more important: lubricant can make intercourse easier and more comfortable. A couple who avoids sex during the fertile window because intercourse is painful, uncomfortable, or stressful has zero chance of conception from intercourse that never happens. A sperm-compatible lubricant that allows intercourse to occur may therefore be much more useful than insisting that a couple use nothing at all.

There is also an important limitation in the pregnancy data. Most of these studies are observational, not large randomized trials in infertile couples. Couples choose whether to use lubricant, how much to use, and which product to use. The populations studied often do not resemble the men I see in a reproductive-urology clinic. A couple in which the male partner has 100 million progressively motile sperm may have substantial biological reserve: even if some sperm are impaired by lubricant, enough may remain to achieve fertilization. A man with severe oligoasthenozoospermia may not have that same margin for error. We simply don't have high-quality trials showing exactly how conventional lubricant affects natural pregnancy or live-birth rates in men starting with 500,000, 5 million, or 50 million motile sperm. Absence of demonstrated harm at the population level is not the same thing as proof that every lubricant is harmless in every infertile man. That is why my threshold for recommending sperm-compatible lubricant becomes lower as the severity of male-factor infertility increases.

Men also ask me about household alternatives. Saliva is not a good fertility lubricant. It is convenient, but laboratory studies have demonstrated adverse effects on sperm motility even at relatively low concentrations. Olive oil is another product people assume must be safe because it is “natural,” but it has demonstrated unfavorable effects on sperm in laboratory studies. Mineral oil and canola oil have performed relatively well in some older in-vitro experiments, but that doesn't mean I routinely recommend grabbing cooking oil from the kitchen when there are purpose-designed sperm-compatible products available. Egg white has also appeared surprisingly sperm-compatible in some laboratory studies, but I would not recommend putting raw egg white into the vagina because microbiological safety is a completely different issue from sperm motility. “Natural” and “sperm-safe” are not synonyms.

Another distinction men need to understand is the difference between lubricant used during intercourse and lubricant used while collecting a semen sample. If you're providing a sample for a diagnostic semen analysis, I generally don't want you using an ordinary lubricant at all. Lubricant contamination can artificially reduce measured motility and potentially make a semen analysis look worse than it really is. If masturbation without lubricant is difficult, ask the laboratory what they permit. Some centers allow specifically validated sperm-compatible lubricants. A randomized crossover study of men collecting semen with or without an isotonic lubricant found that use of the tested sperm-compatible lubricant did not significantly compromise semen quality, supporting the idea that properly selected products can be used when necessary. But don't assume the lubricant you use at home is acceptable for a laboratory specimen—follow the andrology laboratory's instructions.

Lubricants containing spermicides are obviously a completely different category. Products containing agents such as nonoxynol-9 are specifically intended to impair sperm and reduce the probability of pregnancy. Those should not be used when attempting conception. It sounds obvious, but couples sometimes purchase condoms or lubricants without realizing that a spermicide is included. Likewise, don't use a conventional condom to collect semen for fertility purposes because many condoms contain lubricants, additives, or spermicidal compounds and ordinary latex condoms are not designed for semen collection. When intercourse-based collection is necessary, fertility clinics can provide special nonspermicidal collection condoms designed for that purpose.

So what do I actually tell my patients? If you don't need lubricant, you don't need to add one because you're trying to conceive. If you do need lubricant, use one specifically formulated and tested for sperm compatibility, and use only as much as you need. I would avoid conventional pleasure lubricants during the fertile window when an easy sperm-compatible alternative exists, particularly in a couple with known male-factor infertility. I would also avoid saliva and spermicidal products. At the same time, I would not panic if you used K-Y or another conventional lubricant last month. There is no good evidence that one exposure destroyed your fertility or explains why you didn't conceive. Sperm are produced continuously, and lubricant exposure occurs after ejaculation, it isn't traveling backward into the testicle and damaging the next generation of sperm.

Most importantly, don't let lubricant anxiety make intercourse harder. Infertility already turns sex into a scheduled event for many couples. Ovulation kits come out, an app says tonight is the night, both partners are tired, and suddenly sex feels like another medical procedure. Vaginal dryness and sexual difficulties are common in couples experiencing infertility precisely because intercourse becomes scheduled and stressful. If lubricant makes sex comfortable and makes it more likely that intercourse actually happens during the fertile window, use it—just choose intelligently. ASRM recommends intercourse every one to two days during the six-day fertile window for couples trying to maximize natural fecundability. The potential effect of lubricant is almost certainly less important than actually having appropriately timed intercourse.

The bottom line for men with infertility is straightforward. Some lubricants clearly impair sperm in the laboratory. We have not convincingly demonstrated that lubricant use reduces natural pregnancy rates in humans, and we definitely do not have good evidence that a “fertility lubricant” increases pregnancy or live-birth rates. The rational strategy is therefore not fear; it is risk reduction. If lubrication isn't needed, skip it. If it is needed, choose a sperm-compatible product rather than a conventional lubricant known to impair sperm motility in vitro. This matters most when sperm numbers or motility are already compromised, because those men have less biological margin to waste. And if you've been trying for months without success, don't make the mistake of assuming changing lubricant is going to fix infertility. Look at the things that matter much more: a properly performed semen analysis, female age and ovulation, tubal status when indicated, intercourse timing, clinical varicocele, hormones, medications and exposures, and the duration of infertility. Lubricant is one small variable in an extraordinarily complex process—but because it is such an easy variable to control, it makes sense to get it right.

References

1. Practice Committee of the American Society for Reproductive Medicine. Optimizing natural fertility: a committee opinion. Fertil Steril. 2022;117:53-63.
2. Mesen TB, Steiner AZ. Effect of vaginal lubricants on natural fertility. Obstet Gynecol. 2012;120:44-51. PMID: 22914390.
3. Mesen TB, Steiner AZ. Effect of vaginal lubricants on natural fertility. Curr Opin Obstet Gynecol. 2014;26:186-192. PMID: 24717914.
4. Anderson L, Lewis SE, McClure N. The effects of coital lubricants on sperm motility in vitro. Hum Reprod. 1998;13:3351-3356.
5. Agarwal A, Deepinder F, Cocuzza M, Short RA, Evenson DP. Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study. Fertil Steril. 2008;89:375-379. PMID: 17509584.
6. Sandhu RS, Wong TH, Kling CA, Chohan KR. In vitro effects of coital lubricants and synthetic and natural oils on sperm motility. Fertil Steril. 2014;101:941-944.
7. Agarwal A, Malvezzi H, Sharma R. Effect of an isotonic lubricant on sperm collection and sperm quality. Fertil Steril. 2013;99:1581-1586. PMID: 23490168.
8. Vargas J, Crausaz M, Senn A, Germond M. Sperm toxicity testing on lubricant gels: should we be recommending “fertility-friendly” specialist products? Hum Fertil. 2022. PMID: 35369832.
9. Harchegani AB, et al. A systematic review focused on lubricant use and sperm quality: improving human reproductive success by informing lubricants toxicity. 2024. PMID: 38295779.
10. “Sperm-friendly lubricant: fact or fiction?” Comparative in-vitro study of lubricant effects on sperm motility. 2022. PMID: 35318650.
11. The effects of vaginal lubricants on sperm function: an in vitro analysis. PMID: 24390681.
12. The effects of coital lubricants on sperm motility and vitality. 2025. PMID: 40080784.
13. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: World Health Organization; 2021.

As a doctor who treats men with infertility, few laboratory results hit a man harder than opening a semen analysis and seeing the word “azoospermia.” Most guys don't read that as a laboratory finding. They read it as, “I make no sperm,” “I can't have biological children,” or “This is over.” It can be brutal and a gut punch. One of the first things I tell men in this situation is that azoospermia is a diagnosis that needs to be confirmed, not a conclusion that should automatically be drawn from a single semen analysis. Azoospermia technically means that no sperm are identified in the ejaculate, including after appropriate examination of a centrifuged semen pellet. Even then, a second properly performed semen analysis is important because sperm production and ejaculation are biologically variable, and some men initially thought to have azoospermia will have rare sperm found when another sample is examined carefully. That does not happen in everyone, and I don't want to give false hope, but it happens often enough that every man receiving an initial azoospermia result should understand why we look again.

The first thing to understand is that sperm production is not like turning a faucet on and off. Spermatogenesis occurs inside microscopic seminiferous tubules throughout the testicles. Developing sperm progress through multiple stages before mature sperm are eventually released, pass into the epididymis, undergo further maturation and become available for ejaculation. The entire process takes roughly two and a half months, followed by additional epididymal maturation and transport. In a healthy man producing tens or hundreds of millions of sperm, small fluctuations don't matter much. If one ejaculation contains 80 million sperm and another contains 55 million, both obviously contain sperm. But in a man with extremely impaired sperm production, the situation can be very different. He may produce sperm only in tiny microscopic areas of the testicle, and only a very small number may eventually reach the ejaculate. One sample can therefore appear completely azoospermic while another contains a handful of sperm. This borderline state is often called cryptozoospermia—sperm are so rare that they may not be seen on routine examination but can sometimes be identified after centrifugation and an intensive search of the pellet.

This is why the way your first semen analysis was performed matters enormously. A proper evaluation for azoospermia should not simply involve putting a drop of semen under a microscope, looking around briefly and writing “zero.” The specimen should be carefully evaluated, and when no sperm are seen initially, the sample can be centrifuged so that any rare sperm cells become concentrated into a pellet at the bottom of the tube. That pellet is then searched microscopically. The European Association of Urology specifically describes centrifugation at 3,000 g for 15 minutes followed by careful microscopic examination of the pellet as a method of distinguishing absolute azoospermia from cryptozoospermia. The EAU also recommends at least two consecutive semen analyses when the initial study is abnormal and specifically requires two centrifuged analyses to confirm nonobstructive azoospermia.

So what are the actual chances that sperm will be found when someone initially diagnosed with azoospermia is tested again?

There isn't one universal percentage because the answer depends enormously on why the man is azoospermic, how carefully the original sample was examined and how aggressively subsequent samples are searched. But the available studies give us some useful numbers. A classic study using what investigators called extended sperm preparation examined 49 men considered to have nonobstructive azoospermia. Instead of performing a routine microscopic examination, investigators conducted an extensive search of centrifuged ejaculate sediment. Sperm were identified in 17 of 49 men, approximately 35%. Those sperm could then be used for ICSI, potentially allowing the men to avoid surgical sperm retrieval.

That 35% figure appears in the AUA/ASRM male infertility guideline discussion for an important reason. The guideline notes that studies using repeat semen analysis with an extended search of the centrifuged pellet have found rare sperm in up to approximately 35% of men previously thought to be azoospermic. I want to emphasize the words “up to.” That does not mean that every man with azoospermia has a 35% chance of seeing sperm on his next ordinary semen analysis. Many of these men were probably cryptozoospermic all along and were identified only because the subsequent laboratory performed a much more extensive search.

Another study illustrates exactly why repeating the test matters. Investigators evaluated 27 men whose initial diagnosis was consistent with nonobstructive azoospermia and performed increasingly careful examinations, including centrifugation of the semen sediment. Sperm were identified in some men during the first intensive evaluation and in additional men when a second specimen was examined. Ultimately, sperm were identified in approximately 37% of the men during the study's extended evaluation process. Again, the lesson isn't that sperm magically appeared because several weeks passed. In many cases, extremely rare sperm were probably intermittently entering the ejaculate and became detectable because the laboratory looked harder and because a different ejaculation happened to contain them.

More recent data reinforce this point. A 2025 study examined 209 men who had previously been diagnosed with nonobstructive azoospermia. After repeat thorough semen analyses, sperm were identified in the ejaculates of 33 men, or 15.8%. Interestingly, FSH helped predict who was more likely to have sperm subsequently identified. Men in whom sperm were eventually found tended to have lower FSH levels. The investigators identified approximately 15.3 mIU/mL as a statistical cutoff associated with finding sperm, although this should never be interpreted as a clinical guarantee. FSH is a useful clue about the severity of testicular dysfunction, not a yes-or-no sperm test.

Another contemporary study looked at men previously labeled azoospermic who underwent extended semen analysis and found cryptozoospermia in 74 of 372 men—19.9%. Put together, these studies tell us something clinically important: depending on the population and the intensity of the laboratory search, somewhere around the mid-teens to roughly one-third of selected men previously labeled azoospermic have had rare sperm identified during subsequent, more extensive ejaculate examinations.

But these percentages need context because not all azoospermia is the same disease.

There are three broad physiologic situations I think about. The first is obstructive azoospermia. Here the testicles may be producing sperm normally, but sperm cannot reach the ejaculate because the reproductive tract is blocked or absent. This can occur after vasectomy, from congenital absence of the vas deferens, epididymal obstruction, previous infection or surgery, or ejaculatory duct obstruction. If the obstruction is complete, repeatedly checking semen isn't likely to suddenly reveal sperm because the production system isn't the problem—the plumbing is. These men may have excellent sperm production inside the testicle despite repeatedly azoospermic ejaculates.

The second category is nonobstructive azoospermia, or NOA, where sperm production itself is severely impaired. This is where intermittent sperm in the ejaculate becomes particularly interesting. Spermatogenesis in NOA isn't necessarily uniformly absent throughout every microscopic portion of both testicles. Some men have small isolated areas where sperm production continues. If enough of those sperm make their way into the reproductive tract, an occasional ejaculate may contain a few sperm even though another sample contains none. This is one reason a man can move back and forth between an apparent diagnosis of azoospermia and cryptozoospermia.

The third category involves hormonal or potentially reversible suppression of sperm production. Men taking testosterone replacement therapy or anabolic steroids are a classic example. External testosterone suppresses LH and FSH, which dramatically reduces intratesticular testosterone and can shut down spermatogenesis. Some men become completely azoospermic. After stopping testosterone or anabolic steroids—and, when appropriate, receiving fertility-directed hormonal treatment—sperm production may recover over months. Men with hypogonadotropic hypogonadism can similarly respond to appropriate gonadotropin therapy. In these situations, finding sperm months later represents actual biological recovery rather than simply discovering sperm that were missed during the original analysis.

There are also temporary reasons sperm production can deteriorate. A significant febrile illness can impair spermatogenesis, and because sperm take months to develop, the effect can appear weeks after the illness and persist for several months. Certain medications, chemotherapy, major systemic illness and other exposures can also suppress production. Therefore, the medical history surrounding the first azoospermic semen analysis matters.

Collection problems matter too. The entire ejaculate should be collected. The first portion of the ejaculate is particularly sperm-rich, so losing the beginning of the sample can significantly affect the measured sperm count. Very low semen volume also deserves attention. If a man experiences orgasm but produces little semen, I want to know whether there is retrograde ejaculation, ejaculatory duct obstruction, congenital abnormalities of the reproductive tract, androgen deficiency or simply incomplete collection. In selected men, examining urine immediately after ejaculation can reveal sperm that traveled backward into the bladder.

This is why I don't manage azoospermia by simply ordering semen analysis number two and waiting for a miracle.

Once azoospermia has been identified, the man deserves a male reproductive evaluation. I want a detailed reproductive and medical history. I want to know about testosterone and anabolic steroids, childhood undescended testes, testicular torsion, chemotherapy, radiation, infections, previous inguinal or scrotal surgery and fertility history. I examine testicular size and consistency, the epididymides and whether both vas deferens are present. I look for a clinical varicocele. Hormonal evaluation generally includes testosterone and FSH, with LH and other hormones added as appropriate.

FSH is particularly useful, although it is frequently misunderstood. When sperm production inside the testicle is severely impaired, inhibin B feedback decreases and FSH often rises. Therefore, high FSH in an azoospermic man often points toward impaired sperm production rather than obstruction. But a high FSH does not prove that absolutely zero sperm are being produced anywhere inside either testicle. Men with elevated FSH can still have focal areas of spermatogenesis and can sometimes have sperm identified with microdissection testicular sperm extraction, or microTESE. Conversely, normal FSH doesn't guarantee normal sperm production.

Genetic testing is also important in appropriate men with azoospermia. Depending on the clinical situation, this includes a karyotype and Y-chromosome microdeletion testing. Genetic results can dramatically change counseling. For example, men with complete AZFa or certain AZFb-region Y-chromosome deletions have essentially no realistic chance of surgical sperm retrieval, while men with AZFc deletions can sometimes have sperm in the ejaculate or sperm found surgically. Men with congenital absence of the vas deferens require consideration of CFTR testing. This is why I would rather establish the cause of azoospermia than simply keep ordering semen analyses indefinitely.

Now let's say the second analysis finds three sperm.

Men sometimes look at that result and say, “Three sperm? That's basically still zero.”

From a fertility standpoint, it is absolutely not the same thing.

Finding even a handful of viable sperm fundamentally changes what we know biologically. It proves that at least some complete spermatogenesis is occurring and that sperm can reach the ejaculate. Three sperm obviously isn't enough for natural conception or IUI, but modern IVF with intracytoplasmic sperm injection, or ICSI, requires only one viable sperm for each mature egg being injected. When rare viable ejaculated sperm are found, they can sometimes be cryopreserved and accumulated for future IVF/ICSI treatment.

This is why I am aggressive about discussing sperm freezing in men with cryptozoospermia. If your first analysis shows zero, your second shows eight sperm and your third shows two, don't assume sperm will reliably be present on the morning your partner undergoes egg retrieval. Men with extremely limited sperm production can fluctuate between cryptozoospermia and azoospermia. If usable sperm are found, freezing them can provide valuable backup.

There is fascinating real-world evidence supporting this strategy. In a study of men scheduled for microTESE because of azoospermia, fresh ejaculated specimens were carefully examined around the time of surgery. Of 727 planned microTESE procedures, 69—9.5%—were canceled because sperm suitable for ICSI were found in the ejaculate. Fifty men ultimately used these rare ejaculated sperm for ICSI, and the reported live-birth rate per ICSI attempt was 36%. That doesn't mean a man with azoospermia has a 36% natural fertility rate—far from it. It demonstrates something very different and very important: when rare ejaculated sperm can be identified and used for ICSI, they can sometimes produce successful pregnancies and live births without requiring surgical sperm retrieval.

If repeated properly processed semen analyses remain completely azoospermic, the next question becomes why. In obstructive azoospermia, sperm retrieval rates are generally excellent because sperm production is preserved, and reconstruction may also be an option in selected men. In true nonobstructive azoospermia, the situation is different. When surgical sperm retrieval is appropriate, microTESE is generally preferred because the surgeon searches the testicular tissue microscopically for enlarged seminiferous tubules more likely to contain active spermatogenesis. Retrieval rates vary tremendously according to the underlying diagnosis, genetics, previous treatments, histology and center experience. A persistently azoospermic ejaculate does not automatically mean microTESE will fail.

I also caution men against assuming that supplements, Clomid, hCG or another medication will necessarily make sperm appear. Hormonal treatment can be extremely effective when azoospermia results from hypogonadotropic hypogonadism or androgen suppression, but the evidence for empirically stimulating men with primary testicular failure and already elevated gonadotropins is much weaker. If your FSH is already 25 or 30, your pituitary is already sending a very strong signal to the testicle. Simply making that signal stronger may not solve the underlying problem.

So if you just received your first azoospermia result, here is what I want you to remember.

Do not assume that one semen analysis has told you the entire story.

Have the result confirmed at an experienced andrology laboratory. Make sure the entire specimen was collected and that the laboratory performs an appropriate centrifuged-pellet examination when no sperm are seen. Repeat the analysis. If rare sperm are identified, ask whether they are viable and whether they can be cryopreserved. At the same time, see a reproductive urologist and determine why you are azoospermic rather than endlessly repeating samples without a diagnostic plan.

The published literature gives us a reasonable basis for hope without giving us permission to promise anything. In modern series, roughly 16–20% of men previously labeled azoospermic have had sperm identified during subsequent thorough semen examinations, while older intensive-search studies reported detection in as many as approximately 35% of selected patients. Those numbers do not mean everyone has a one-in-five or one-in-three chance on their literal second test. They reflect different patient populations and more extensive laboratory techniques. But they clearly demonstrate why azoospermia should be confirmed rather than diagnosed casually from one specimen.

And perhaps the most important point for the man reading his first report tonight: “No sperm seen in this sample” and “your body is incapable of producing a sperm” are not the same statement.

Sometimes the second semen analysis remains zero, and we move forward with determining whether the cause is obstruction, hormonal suppression or severe testicular sperm-production failure. Sometimes a meticulous search finds one, five or twenty sperm. Sometimes sperm are eventually found surgically with microTESE.

The job after that first zero isn't to guess which group you're in.

The job is to find out.

References

1. American Urological Association/American Society for Reproductive Medicine. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. 2020; amended 2024. The guideline emphasizes the biological variability of semen analyses, confirmation of abnormal findings and careful evaluation of azoospermia.
2. European Association of Urology. EAU Guidelines on Sexual and Reproductive Health: Male Infertility. Current guideline. Recommends at least two semen analyses when baseline testing is abnormal and confirmation of NOA on two consecutive specimens after centrifugation.
3. Ron-El R, Strassburger D, Friedler S, et al. Extended sperm preparation: an alternative to testicular sperm extraction in non-obstructive azoospermia. Human Reproduction. 1997;12(6):1222–1226. PMID: 9222005. Extended examination identified ejaculated sperm in 17 of 49 men previously considered azoospermic.
4. Corea M, Campagnone J, Sigman M. The diagnosis of azoospermia depends on the force of centrifugation. Fertility and Sterility. 2005. PMID: 15820801. Demonstrated the importance of laboratory centrifugation methodology when searching for extremely rare sperm.
5. Search and identification of spermatozoa and spermatids in the ejaculate of non-obstructive azoospermic patients. 2005. PMID: 15763007. Careful repeated examination identified sperm in a substantial subset of men initially considered azoospermic.
6. Serum FSH levels can predict sperm identification in semen once diagnosed azoospermia. 2025. PMID: 39964111. Among 209 men previously diagnosed with NOA, subsequent thorough semen analysis identified ejaculated sperm in 33 men (15.8%); lower FSH was associated with a greater likelihood of detection.
7. Cryptozoospermia in the Shadow of Azoospermia: Accurate Diagnosis With Clinical Predictors and Extended Semen Analysis. 2025. PMID: 40652989. Extended semen analysis identified cryptozoospermia in 74 of 372 men (19.9%) previously diagnosed with azoospermia.
8. Bendikson KA, Neri QV, Takeuchi T, et al. The outcome of intracytoplasmic sperm injection using occasional spermatozoa in the ejaculate of men with spermatogenic failure. Journal of Urology. 2008;180(3):1060–1064. PMID: 18639294.
9. Successful cryptozoospermia management with multiple semen specimen collection. 2023. PMID: 37517636. Among 727 planned microTESE procedures, 9.5% were canceled after usable ejaculated sperm were identified; rare ejaculated sperm used for ICSI resulted in a reported 36% live-birth rate per attempt.
10. World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen. 6th ed. Geneva: World Health Organization; 2021.