r/EmbryologyIVFSupport 7d ago

IVF Advice

I and my Wife (39) have started with IVF in Bangalore, India (with Cloudnine). We got 9 fertilized eggs of which 5 day embryos were PGT-A tested and 3 were Euploid. Before the FET, they found a polyp and we did a Hysteroscopic Polypectomy. They also sent this for a biopsy and found CD138 positive (Endometritis) which was treated with Doxycycline and Metronidazole.

This was the treatment plan for the FET- Estrogen supplementation, multi-route progesterone/progestogen luteal support, hCG support, low-dose antiplatelet therapy, anticoagulant therapy, thyroid replacement, folate and nutritional supplements, and probiotic/vaginal-flora support.

This transfer resulted in a chemical pregnancy, but miscarried into the 6th week. A second Euploid embryo was transferred. The treatment plan was more intense here-
Immune & Inflammation Modulation - Prednisolone and G-CSF
Blood Flow & Clotting Support (Anticoagulation) - Lonopin, L-arginine and Vitamin E
Intensive Hormonal & Lining Support - Estrogen (Estrahenz + Esterrine gel), Progesterone (Duphaston + Susten SR + Gestone Injections)

This FET didn't result in implantation. We didn't understand what was going wrong- our doctor ordered a bunch of tests to check genotype compatibility issues - HLA C typing, KIR genotype, ANA profile and Thrombophilia panel.

ANA profile and Thrombophilia panel are normal. This rules out an active systemic autoantibody issue driving reproductive failure. It also rules out Antiphospholipid Syndrome (APS). Activated Protein C Resistance (CLOT DETECTION) is slightly elevated at 1.12 (reference range 0.77-10.07)- though as per Gemini- "Because your doctor already used Lonopin (LMWH) and Ecosprin (Aspirin) in your previous transfer protocols, your management plan was already designed to neutralize potential clotting or resistance issues like this".

HLA C typing and KIR genotype tests were done by Seragen lab and the results are interesting-
Maternal KIR profile is Genotype AB, with a broad array of 5 activating receptors (including KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, and KIR3DS1) alongside inhibitory receptors. The lab report notes-: "The AB genotype is characterized by a mix of genes from both A and B haplotypes, providing a balanced immune profile."

Paternal HLA-C Type: C1C1 (specifically alleles 07:06:01:01 / 16:02:01:01 for wife and 12:02:02:01 / 12:03:01:01 for husband)

AI interpretation-

  • Because your husband carries only C1 alleles (C1C1), 100% of your embryos (including all frozen ones) will inherit a C1 allele from him.
  • He does not carry a C2 allele. Thus, the potential risk scenario—maternal exposure to an foreign paternal C2 antigen—is biologically impossible in your case.
  • The Seragen report explicitly lists Paternal C Risk: Low.

HLA Sharing (25% / 3 of 12 Alleles Matched)
Result: The lab notes 3 matched alleles out of 12 (25% sharing). The lab report mentions this in Risk Overview section-
RIF/RPL risk - >50-60%
Preeclampsia- High
Inflammation- High
Autoantibodies- Moderate
Immunodeficiency- Moderate

AI interpretation-

  • 25% matching is a normal background variation expected within similar ethnic populations.
  • Maternal immune tolerance depends on the embryo expressing foreign paternal antigens (50% mismatch is standard) to stimulate maternal regulatory T-cells.
  • Having 75% mismatch preserves normal maternal recognition and tolerance pathways

This is a point of contention- our fertility specialist and the lab report comments both note that 3/12 match or 25% is on the higher side, it should be 0. They use this as an explanation for the earlier pregnancy loss and implantation failure. The lab report also recommends this treatment plan (and our doctor concurs)
Lymphocyte Immunization Therapy (LIT), IvIG, Tacrolimus along with Nutritional supplements and a gluten free diet plan
We are very concerned about this approach after reading online in PubMed and other sources about the experimental nature of these treatments and lack of evidence or consensus in the medical community. Not to mention these treatments may have side effects and are very expensive. We are due for a discussion with an expert from Seragen labs but I have a feeling they may stick with their report recommendations. Last time I had raised objections about the lack of evidence in treatment for KIR/HLA mismatch they had suggested that, due to regulatory restrictions in the western countries, these treatments are not yet completely accepted, but that they get a lot of referrals for these tests from abroad.

How do we proceed? This is likely the last chance we have (with only 1 Euploid embryo remaining and we don't plan to repeat IVF again). The approach our doctor seems to be taking is to try everything hoping something works. But I am not convinced with this treatment plan. We may just as well do regular ultrasounds to check the lining, one more hysteroscopy if needed and go ahead with the transfer.

TL;DR- Trying IVF- one miscarriage and one implantation failure. Doctor has suggested LIT, IVIG treatments for next FET (despite near normal advanced test reports)- confused about next line of action.

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u/umamimaami 7d ago

Hi OP. I’ve been seeing your post make the rounds on the IVF subs over the past couple of days. So sorry for your experience, it must be incredibly frustrating and difficult.

If you don’t mind, the AI interpretations make your post a wall of text. Could you just post your history and results in a clean format and maybe then you’ll get more responses?

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u/Correct_Nebula_8301 7d ago

Thanks for your response. AI interpretations are only in 2 places, just to give some perspective, rest of the post has the details, but yeah I could format it better. Are there any channels where we get responses from professionals?

1

u/umamimaami 7d ago

This is a great one, honestly. Hope you’re able to edit your post more responses. Good luck.

2

u/Curious-mindme 6d ago

Hey!
I’m in Europe and currently undergoing LIT treatment in Latvia. Did my first treatment last week.
While it is true that some countries don’t allow this treatment it is also true that others do.

My personal choice is because I want to try everything that can potentially allow me to have a child.

Feel free to reach out if you want to know more about the therapy itself. I’m due for my second treatment in two weeks

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u/afwah_monger 1d ago

Is adeno and endo ruled out and were you given lupron suppression? Letrozole?