Failed embryo transfers...losing hope :-(

[BJPMT]

I’m a 34-year-old woman with PCOS and my husband has reduced fertility. We started our first ICSI-cycle at the start of 2023, which yielded 7 embryos. The initial fresh transfer resulted in an ectopic pregnancy and the 6 subsequent FETs failed.

I’m overall healthy; I have an active lifestyle, diverse diet and a normal BMI. I don’t have any severe symptoms during IVF-cycles and my endometrial lining is optimal every time. Last cycle, I did get a ‘unfavourable’ vaginal microbiome test, but the result is not considered reliable for my ethnicity (south Asian).

Our initial cautious optimism is gone, so now we are considering our options (both at home and abroad).

· ERA to see if my implantation window is different than usual. That would have to been done abroad, since this is not available here.

· Work on my vaginal microbiome with probiotics to increase its Lactobacillus population.

· Start a new cycle at home and hope for success with the next fresh transfer.

· Transfer 2 PGT-A tested embryos in an overseas clinic.

o Since our ‘home’-clinic does not offer PGT (they consider it unreliable), we have gone in the meantime to a private clinic to check it. This resulted in 9 embryos; of which at least 5 were PGT-A normal.

If someone has had similar experiences with recurrent failures or has suggestions, I would be very happy to hear them. My husband is supportive, since we are happy together and children would be a bonus, but I frequently feel heartbroken and desperate.

[DeckingLover]

I’m sorry, I don’t have any advice but I just wanted to say I’m sorry for all your lost embryos and I hope you have luck soon 🤍

[BJPMT in reply to DeckingLover]

Thank you for your wishes ❤️ We also feel sorry and try to be positive that we have embryos abroad. Though, those BFNs really mess me up for some days.

[Jmfl]

Hi,

I just did my first ICSI transfer and unfortunately it has failed. I’m also 34 and the infertility is male factor. First retrieval only yielded 2 blastocysts so we need to prep for another retrieval. We are at Chelsea Westminster Hospital where they do not offer PGTA testing so we might go to another clinic or if there’s a way to move them to a facility to be tested. We opted for a double transfer because the grading of the embryos were the same. Long story short, neither implanted. This is the hardest journey that most of us will ever be on so we need to try our best to try to learn from each transfer. These are some of my takeaways:

1. Based on what I’ve learned, if you’re at risk of OHSS, just go straight to frozen transfer

2. If a natural cycle did not work, try the fully medicated cycle next transfer or vice versa.

Hope this helps and sending you hugs

[BJPMT in reply to Jmfl]

Thank you! I wish you the best too. Unfortunately, natural cycle with PCOS seems to be not possible since I do not ovulate regularly. Regarding OHSS, last two cycles, I didn't have the problem. However, my fresh transfer did end up as an ectopic pregnancy and my left fallopian tube had to be removed. So, I am indeed a bit scared to go for a fresh transfer...

[fidgetmcgee]

I’m sorry for your losses, it is so hard all this.

Remembryoman recently posted research that found that non medicated FETs had higher success rates so that might be worth considering if your previous transfers were medicated.

Probiotics seem like a good non invasive thing to try too to me. Anecdotally and non fertility related but I used to get repeated UTIs and thrush and starting probiotics for feminine health (I’ve used pro-Ven and Boots own brands) and haven’t had any since. I don’t know if they will help with transfers as I haven’t had any yet but they do seem to do something!

Sorry if I’ve misunderstood your post but if you do have pgt-a tested embryos available I would personally get one of those transferred next rather than go through another cycle for a fresh transfer as if you have pcos they might switch you to freeze all anyway due to OHSS risk. I currently have mild/moderate OHSS and I feel awful so it’s really not worth the risk imo

I hope you and your husband take good care of yourselves and each other. It’s really hard going through this. Best of luck

[BJPMT in reply to fidgetmcgee]

Thank you very much for your reponse. By non medicated cycle, you mean 'natural' cycle, correct? Do you know if this is an option for PCOS patients? I can certainly then discuss with my clinic. I am also in doubt if I should first go for PGT-A tested embryos. We will have to go abroad and I cannot go until the end of the year because of work. Therefore, i thought perhaps in the meantime, I undergo one more round of IVF here. This way I have some more embryos before I turn 35 and also can keep going until the end of the year...

Thanks for suggesting probiotics. I also am getting more and more interested in this vaginal microbiome. I read many research papers and the data seem convincing. Though this research area is in its infancy still.

[fidgetmcgee in reply to BJPMT]

I haven’t dug too much into the research because we’ve never yet made it to a frozen transfer but I think natural is what is meant yes, if you Google remembryoman he has a recent post about it. I don’t know if PCOS would mean clinics wouldn’t advise it as an option or not im afraid

I can see your logic of wanting to bank more embryos if can’t transfer your others for a while. I think it’s probably a personal decision depending on how difficult the cycles are for you and how many children you think you want.

Best of luck with it all

[Zassa]

I'm sorry for all your implantation failures. I'm thinking if your new embryo batch had so many PGT-A embryos then I'm thinking your previous one should also have had some PGT-A normal so most likely the endometrium is not in the best state.Where have you heard that vaginal microbiome is not reliable for a South Asian? I had an unfavourable microbiome and I know for sure it causes implantation failures.

Is there another test you can do that is more incorporating in bacteria? I would think Fertiliysis would be applicable for all but very expensive. Another option is an endometrial biopsy to check both bacteria and also inflammation markers / plasma cells often caused by bad bacteria. With that I would check your husband too for bacteria as some bacteria are known to cause infertility/ reduced fertlity in men.

Best of luck!

[BJPMT in reply to Zassa]

Thank you for your kind wishes. I also thought that logically it only make sense to think that atleast some of those 7 embryos were chromosomally normal (PGT A passed). So you are correct perhaps and I also think that there might be an endometrial reason. I am considering an ERA to define implantation window. The immuneassays you mentioned also seem interesting. Can you guide me where can I read more about them? Clinics in the Netherlands (where I live), do not perform any additional assays. So I will consider all this for our cycles abroad.

Regarding the vaginal microbiome, I am participating in an ongoing research at my clinic which investigates vaginal microbiome. Initially they didn't include me because according to them, vaginal microbiome differs as per ethnicity and current understanding of certain vaginal microbiome to be beneficial for successful implantation is limited to Caucasian population. However, I insisted to participate arguing that they can use me to further investigate the differences if any. In the meantime, I read some research papers to see if there was some research done regarding the microbiome of my ethnicity. I found certain papers and it seems pretty similar to Caucasian ones. Therefore, I do feel that working on vaginal microbiome may help in my case. Being a scientist by training, i am planning to show all these papers and argue this at my clinic and insist on them suggesting me probiotics to increase Lactobacillus population in my vaginal microbiome. I know it may not be the only factor, but I feel my clinic doesn't investigate anything and that is not how it should be.

[Zassa in reply to BJPMT]

Ok I see, I live in Sweden and in general clinics don't do it there. I read the book 'It Starts with the Egg' and joined the facebook group and learnt a lot from there. When I started suspecting there was something wrong, I sent my period blood to Serum IVF in Greece. I know they're quite good at microbiome test there as Fertilysis is also based there but more expensive. The good thing is that you get a consultation with a doctor for free so you can check with them first whether this is applicable for you. After I found out my results I got prescribed antibiotics and also took vaginal probiotics (suppositories and oral). I heard from another facebook group 'Endometritis' that sometimes you can get inflammation in terms of plasma cells caused by infection and a useful biopsy is CD 138. Next I'm planning to have a recheck of bacteria and CD 138 biopsy but I will need to travel for that, checking clinics now. I have 'unexplained' secondary infertility and this is nothing I was told about from the beginning.Good luck with your decision!

[BJPMT in reply to Zassa]

Thanks for sharing this. I wish you goodluck with your further testing and I hope that these tests help you further in your journey. All the best! If I have further insights regarding this matter, I will get back to you.

[Boo718]

hello. I did the era Emma and Alice tests to check bacteria infection and optimal transfer timing. We found that I needed transfer on day 6 instead of 5 xxx

[BJPMT in reply to Boo718]

Thank you very much for the information. i hope that the results were useful for positive outcome for you :))

[Boo718 in reply to BJPMT]

They were indeed she is now 1 after 5 transfers and numerous cancelled rounds xxz

[BJPMT in reply to Boo718]

How wonderful! Thank you for sharing 😊

[HedgehogMad]

Hi lovely, I'm so sorry you are going through this, it's so tough to have persistent failures when everything always looks optimal 😞Have you had a second opinion from a different clinic as to what would be next steps? I'm guessing you had a 2nd retrieval with those PGTA results?

I understand the pain as we have transferred 6 untested and 3 tested embryos with no positives. I can recommend reading the ESHRE guidelines which detail the evidence for different tests/treatments for recurrent implantation failure: academic.oup.com/hropen/art...

Lots of tests/treatments are advised by clinics but very little actually have scientific evidence of being helpful.

From our point of view we spoke with Prof Childs from Oxford fertility and a RIF specialist in Spain who both said if we continued we would probably eventually have success, but couldn't say how many transfers it would take. After our 7th transfer our consultant suggested surrogacy as an option. I have since been diagnosed with deep pelvic endometriosis which has been causing awful pelvic pains which worsen after each egg collection so I knew I couldn't go through another one - the specialist said with this type of endo surgery is unlikely to help with implantation. So for this reason we saved our embryos for surrogacy and are on a journey with our amazing friend who offered to carry out embryos for us.

There's no right answer and a huge lack of studies into recurrent implantation failure and why it happens. I think you can only go by what feels right for you, taking into account the advice given by the specialists (and I'd definitely speak to more than one). Sending love xx

[BJPMT]

Dear HedgehogMad,Thank you so much for this detailed response. I will look at these guidelines. I am also amazed to hear about your difficult but beautiful journey...I wish you the best with surrogacy and wish that it will be all worthwhile when you have those little ones in your arms.

I completely agree to have multiple opinion and at least demand an investigation. I agree that the understanding of RIF is limited. Though I also think, at least with available diagnostics, you can try and see if that helps at this point. Our clinic unfortunately doesn't change anything... And cycle after cycle, it just feels a bit disappointing as well as frustrating. In the end, of course losing embryos is heartbreaking but I also think it takes toll on our bodies too with these high doses of hormones.

Thank you again.

[HedgehogMad in reply to BJPMT]

Hopefully you will find it useful - it definitely helped us to decide on which investigations we felt it was worth spending even more money on!In the UK clinics offer a modified natural cycle for ladies with PCOS which involve a mild level of stims to encourage ovulation - I wonder whether your clinic might offer this to try a change in protocol? It might be that medicated FETs aren't right for your body. Both our brief positives were on completely natural cycles.

Wishing you every luck on your next steps xx

[BJPMT]

Many thanks. I did not know about this option. Certainly worth trying. I will talk about this at my clinic.