Recurrent implantation failure- anyone who can help?

[Endoivfff]

Looking for anyone’s advice, experiences, opinions, and fresh eyes from anyone who may be willing to help (apologies in advance for a long post)-

brief back story / health.

Recurrent implantation failure :

Currently 29 years old. (Eggs collected at 27.)

In a same sex relationship- IVF.

Pcos

Endometriosis stage 3

MTHFR

Pai-1

High deft womb lining test (95th percentile) - Professor Brosens (done in 2023)

Low uterine NK cells from biopsy - Professor Brosens ( done in 2023)

Most recent tests:Dr Gorgy diagnosis -

NK cells

50:1 :30.4

Cd19 :15

Cd19+5+ : 14.3

Cytokines TNfalpha : 48.3

KIR receptors (three missing)

I’ve had 4 medicated FETS- most containing Clexane, aspirin, cyclogest, lubion and one including an era suggested time , and prednisolone.

I am absolutely drained from the last few years and have reached a point where it feels as though different drs don’t really know what to do with me or give me any direction. I feel like a total freak case with nobody to turn to.

I have just had endometriosis surgery at the end of January (1st one was in 2021) and have some decapeptyl to surpress my endo and have been recovering. My plan originally was to go into a natural modified fet with a theory from dr brosens - no extra meds, 1A grade and 1 c grade embryo in the hope that the lower grade embryo will trigger a response and bring my robust lining (95th percentile) back to a normal range enough to let the A to implant. He also suggested taking away the prednisilone that he prescribed me for one of the previous fets that was supposed to help my lining. Effectively just seeing what my body would do.

However most recently whilst recovering I have been to see Dr Gorgy and have been tested for NK, antibodies, th1/th2 cytokines, KIR genotyping -we are unable to pay out the ridiculous costs of all the tests that are offered.

Now with these results I feel completely compelled to do an immune treatment for my next fet. Dr Gorgy didn’t really understand dr brosens theory and said he wouldn’t rely on the embryos to bring down the lining. He also said to transfer one A grade.

His treatment from my results :

-l-thyroxin ( TSH was 2.56)

-hydroxychloroquine- to calm NK cells + cytokines

-Humira + Intralipids -bring down TNF alpha

Retest TNF alpha - if lowered can progress to fet

For a FET he also mentioned:

Neupogen

Neupogen wash

(Not really too sure what for, I think KIR receptors?)

I have raised concerns with the drug humira as my ivf dr said a lot of his patients in the past that have had this ended up quite poorly. I work with young children and constantly around illness so I have said I don’t want to take it. Dr Gorgy apparently messaged back saying I can just have the Intralipids if I don’t want to take humira. ( Can’t seem to get any real response from them on whether Intralipids would even be a viable treatment option in terms of bringing TNalpha down on their own).

I’m in such a debate with what protocol I should do, how many embryos , what drugs , what to do about my lining etc. my ivf dr is happy with whatever we choose but we don’t feel qualified to make decisions like this. He didn’t feel that putting two embryos back was a good idea, and taking humira but that was about it.

My head is scrambled from all of it and have found the experience with Dr Gorgy clinic poor so far. Nothing is explained well enough even when asking basic questions, and no guidance on when and how etc. Emailing, ringing and constantly chasing for basic information to be sent. At this point in time I feel as though I have just come up myself with 3/4 different protocol options;

1. natural modified Dr brosens theory for my robust lining: grade A and C embryos - no immune drugs (apart from Clexane/aspirin, Progesterone, see what my body does.

2. Natural modified -No immune apart from trying prednisilone for my robust lining again (Clexane , aspirin, progesterone) 1 A grade embryo

3. Natural modified - with immune- Intralipids, prednisolone, hydroxychloroquine, neupogens etc - (Clexane , aspirin, progesterone) - 1 A grade embryo - main concern for this is having to wait to be retested and if levels haven’t gone down enough having to do more treatment meaning more delay to an FET - am I just wasting all the suppression and surgery I’ve just had?

4. Natural modified -only using prednislone and asking to look into something to support implantation and low NK cells such as hcg wash or neupogen? and possibly carry on taking hydroxychloroquine as an extra as it can fit in with having an fet soon

As I’ve been suppressed since October and had surgery this January I really want to have an fet asap so that I’m giving myself better chances in terms of endo. I’m thinking is it best to go into a modified natural cycle once the withdrawal bleed from decapetyl comes. If I was to choose to go with the immune protocol I most likely won’t be able to even start another FET for at least another 7/8 weeks due to having Intralipids and further retesting etc. Also if i go for a retest and the number for cytokines doesn’t reduce enough, then I imagine it will be even more treatment and even longer before I can start an FET - feel like am I wasting time when I could be getting on with a transfer and not wasting my 4 injections of suppression ? So unsure of whether to scrap the immune protocol for now because of this reason?

I feel so conflicted with different drs opinions and what’s the best choices to make, especially when it costs us everything we have. I’m majorly concerned about my lining being so robust , and the low NK cells in my uterus that was tested from 2023. Part of my gut tells me this is surely more detrimental to implantation than all of the immune stuff in blood??

If anyone could even just tell me what they would if they were in my position I would be so so grateful. I can’t count how many tears I’ve shed over the last few weeks.

[Whatwillbewillbe_]

I can’t provide an opinion on all of the above but just to share my experience.

My TNFa was around 37 and it’s taken about 6 months for it come down to 20 on 300mg of Hydroxychloroquine per day

[Endoivfff in reply to Whatwillbewillbe_]

Thank you. Was you only taking hydroxychloroquine without any additional treatments such as Intralipids etc?

[Whatwillbewillbe_ in reply to Endoivfff]

I took intralipids alongside hydroxy for two of my transfers because the levels hadn’t reduced enough. Those transfers failed ( we don’t know why). Now that they have come down to 20 they don’t think I need intralipids.

[Endofitall]

hey lovely I think we have some similarities and I’ve had a very similar experience with Gorgy recently. As I work in health care I’ve decided that Humira etc are too risky and plus the possible risks and side effects are too extreme for me (my DH very against me taking risks). We definitely cannot afford LIT or IVIg.

So I’ve decided trying Hydroxychloroquine for my TNF and Tcell issues, and intralipids around transfer (already had high progesterone, pred and clexane in my protocol for a while) as these seem low risk and something that just might help. I haven’t been advised retest when just doing these - just to start hydroxy at least 6-8 weeks before transfer (ideally longer but whatever time you have) and intralipid 5-7 days before transfer.

I’ve also seen prof Brosens though my results showed high cytotoxic NK cells so pred was my only recommendation. What I would say is that Brosens recommendations come only from a place of research and trying to help. I do suspect there’s an element that some other places making a profit is a huge factor too…

I hope you can some up with a plan you feel happy with. I know how you feel when there’s so many options, so little evidence and all becomes confusing to know what to do for the best.

[Endoivfff in reply to Endofitall]

Thank you so much for your reply! Maybe it wouldn’t harm me trying the same as you and just try and take the hydroxy and Intralipids with the time I have right now. I feel like fga havent explained any of the risks of these drugs. It wasn’t until my own ivf dr queried the humira with me I realised how dangerous it could be for me. Have you had any problems with hydroxychloroquine? Does it affect your immune system a lot? I’m so worried about it all.

I totally agree with the profit element. That’s why I’m so unsure whether to trust this ‘immune’ world. I’m so conflicted all round. I feel like whatever I choose will be wrong 😞

[Endofitall in reply to Endoivfff]

No they really don’t explain anything or provide proper info. Especially when they don’t do clinic letters either.

Hydroxychloroquine is much less immunosuppressive than even prednisolone so I thought in grand scheme it was worth a go without too much risk. Looking at meds govt view as making people extremely vulnerable to COVID is a good indicator and hydroxy doesn’t. It seems much much lower risk than Humira or tacrolimus.

I’ve found somewhere more local that does intralipids and slightly cheaper so I’m going to use them for that come transfer time. My immune fertilysis report said I could do LIT or intralipids for my immune issues on their report so I’m happy to stick to the cheaper option that doesn’t have the LIT risks.

I’ve been very unsure about immune stuff as it’s so experimental and so expensive. But it gets to point that you feel you need to try everything possible. I feel I’m getting a balance between feeling tried everything within reason, keeping risk to me low (my DH doesn’t put his foot down often but he does on this) and without completely bankrupting us!

I do try and socialise outdoors as much as possible etc but work it’s hard to avoid germs isn’t it. So have to take that risk into account. Xx

[Endoivfff in reply to Endofitall]

Yes they definitely aren’t helpful. I’ve had to practically beg for some sort of plan and timeline in an email because we don’t understand any of it. It’s causing even more stress! I think I would be happy to try prednisolone again as it’s only a couple days before transfer I would start taking it however I don’t know if this is the right thing to do for my robust lining and low uterine nk cells. It’s all so confusing. I did have someone say have you asked for tacrolimus instead of humira but haven’t even had time to look into that and if it’s a risky med.

So good you’ve found somewhere cheaper for Intralipids! Where are you based?

Agree with you totally with the germ risk. It puts so much strain on me when trying to get to an fet normally because I don’t watch to become ill and have treatment cancelled- that’s without any immune suppressing!

Have they said how many times you need Intralipids ? Was your TNF alpha really high? Fga has said twice before preparing for an fet but I’m very doubtful this alone is going to lower such a high level. I wish I had an answer as to whether I’m wasting my time with the immune stuff or should I just be focusing on the immediate environment of the uterus. Why is it such a hard journey 💔

[Chel91]

I also went through recurrent implantation failure (10 embryos no success). I also have PCOS, endo, and was in my 20's at the time. Plus have some of the similar other issues like blood clotting, immune issues, etc. So you are definitely not alone in this situation!

Was your endo surgery excision with a specialist? Did they manage to get it all?

I don't get what he means by a "robust" lining? Do you mean really thick? Is that at baseline or around the time of ovulation / transfer? My lining has also always been massively thick too before transfer. What mm was yours? If it is about thickness then I would question whether natural or modified natural would make it any thinner, as personally mine is not any thinner naturally or with ovulation induction drugs. I tried to look into whether a thick lining was an issue, but it seems like it possibly isn't an issue, although it is very rare it seems. It's so frustrating to not know the precise cause, I definitely felt the same way xx

[Endoivfff in reply to Chel91]

Thanks for your reply. Sorry to hear about your transfers. It’s horrid isn’t it. I had a uterine biopsy at Coventry and the cells in my lining came back as too robust for implantation. Dr Brosens gave me prednisolone and I also did an extra day of progesterone from an era and a medicated fet. I’m really adamant I want to try a natural modified next time as every single one has been medicated. My surgeon is not an excision specialist but he is actually my ivf dr and deals a lot with endo and has told me preserving my fertility was very important to him which I appreciate.

Did you have any luck treating the immune issues? X

[Chel91 in reply to Endoivfff]

Oh that's so interesting. I've never heard of that term used that way before. Hopefully the natural modified will make a big difference to your lining. I felt like my chances really improved after endo surgery too, so hopefully it will be the same for you as well. I did do different immune things over several cycles, but I think the surgery mostly made the difference for me as I had my success the very next cycle. I also think the prednisone, blood thinners and such probably have a good effect too though, but it's really hard when you don't know for sure isn't it xx

[Endoivfff in reply to Chel91]

It’s so hard isn’t it!!! I think I’m leaning more for a modified natural at present and delaying the immune stuff just so I can see what my body does. I’m also considering letrozole as I’m worried that my ovaries won’t wake up from suppression to enable a modified natural x

[irishlass2023]

Have u tried endo scratch and uterine prp?

[Endoivfff in reply to irishlass2023]

I have tried a scratch before but this didn’t help. My clinic doesn’t offer uterine prp 😞 x

[Vix12345]

Have you tested the embryos? It seems that you have done so much for the lining and receptivity side, but if the embryos are not viable then none of that will make any difference. x

[Endoivfff in reply to Vix12345]

I would love to test them but financially we can’t. Although my dr has said most of them should be okay as I was young when I had retrieval .. I’m hoping this is true 😫x

[Vix12345 in reply to Endoivfff]

In all honesty, that's the only way to know if the embryos are viable, the grading means nothing as they can't see inside. We had 5 failed transfers of 7 embryos before we decided to do the testing, best thing we did. If it is something that becomes financially viable later on I would definitely consider it, as no matter what else you do, it's still the embryo that is the most important part of it. Good luck x

[Endoivfff in reply to Vix12345]

Yes definitely!! If I had the money I definitely would! It’s all so hard, especially financially x

[Zassa]

Have you previously been downregulated / suppressed before FET? This is the first thing worth trying because of your endo. Another thing would be microbiome/ endometritis. I'm not an expert regarding immune issues but seems you've been testing most things. Blood clotting is another thing to possibly look into. I hope you find the answer!

[Endoivfff in reply to Zassa]

Thank you! Yes, always been suppressed. I’m currently waiting on a biopsy for endometritis, also have been taking Clexane with every fet. I’m hoping is it just a numbers game 😞 x

[Ranie]

All.of this is just so much! Inknow these docs support immune more, but have you checked for an endometrial infection, taken vaginal probiotics and/or antibiotics especially since you have had endometrial surgery? I had failed inplantation and got pregnant after intensely treating an enterococcus infection, after the lactobacilli reestablished. I mean is it worth making tour mind work overtime that you may be sick in such detailed level when you may just have a hostile microbial environment? There is queues on end for Alice/emma testing but recently someone told me the immunology docs dont support the efficacy! I know many women who have gotten immediate results. I have a 15 mo old daughter now after 12 failed transfers! I would just vow on the benefit the lactobailli have, so would a lot of ivf clinics that dont really push for these extra super stuff! Kindly

[Ranie in reply to Ranie]

Oh yes and PGS testing! Not worth without it in these circumstances

[Endoivfff in reply to Ranie]

Wow congrats on your daughter!! I am currently waiting on a biopsy to come back to check for endometritus so I’m hoping that will be available soon. I did have antibiotics after my surgery so hoping that would prevent anything after hysterscopy and lap. May I ask if you have endo or any other underlying conditions? X

[Ranie in reply to Endoivfff]

I had 2x 5cm fibroids removed in 2019, nothing much else apart from ovarian failure later on, froze eggs early though.

[MontsJ]

Just to throw another option in the mix, consider a consult with Dr Rahi Victory in Canada just to get his thoughts. He’s big into endo + immune management

[Endoivfff in reply to MontsJ]

does he offer online consultations for UK? X

[MontsJ in reply to Endoivfff]

Yes he does, sorry for the late reply x