Failed FET double transfer need some hope

[Hopefulforhappytimes]

Hi guys

Feeling so down today and just think need some help and advice and positive stories on what to do next. I am 37 and just found out this morning that our recent FET of two embryos has failed (clearblue test this morning 11dp5dt).

We are currently on our second cycle. First cycle we had one fresh transfer and two FETs (all with single embryos) and all failed with no implantation.

On our second cycle we had a fresh double embryo transfer in October and finally got pregnant (single pregnancy). We were so happy!! Unfortunately I miscarried at 8.5 weeks.

We have just had another FET transfer with two embryos (both good quality) and this has failed.

Just feel so sad and like I don't know what to do next. After any ideas of things we could try, whether to carry on with another cycle and any of your stories welcome.

Much love x

Hi @Hopefulforhappytimes I’m sorry to hear about your current cycle and your miscarriage, sending hugs

Just to clarify- you’ve had a fresh cycle- had a single transfer, followed by 2 x single embryo FET transfers. You then had another fresh cycle with a double transfer and then a double FET transfer.

So altogether 7 embryos transferred in 5 fresh/frozen cycles? 1 implanted but miscarries the rest didn’t implant?

As to what you do next, it depends on if you have further frozen embryos? I think your case sounds quite complicated, so you likely need to have a proper conversation with your specialist about what to do next, you may even want to ask about paying for a double appointment, because there is a lot to discuss.

I personally would want to know:

• Are the embryos euploid? If you have any remaining embryos I would suggest looking into doing PGT-A testing on them. If you don’t then I would consider a freeze all cycle and wait to find out which are euploid.
• Is there an implantation issue? I am currently having level 1 implantation tests which include a thrombophilia screen and autoantibodies, ask your specialist if this could be beneficial.
• Is your transfer window out of sync with the timing of the transfers, this is more relevant if you’ve been on medicated FET, I’m currently planning an ERA to look into this, they look at the genes in the endometrium and tell you exactly how long you should take progesterone before a transfer.

As to if you should carry on, only you know the answer to that, I think I personally would, but it’s easy for me to say that after 2 unsuccessful cycles. However, I would want to ensure the situation has been investigated properly before another transfer. There is a huge physical and emotional impact of an unsuccessful cycle, set yourself up for the best chance moving forward.

Thank you so much for your response 😊 It's so nice to hear from people in or who have been in a similar situation!

Yes that is completely correct about the transfers 7 embryos transferred in total and 1 implanted but led to a miscarriage. We have one frozen embryo left in storage (but it was noted as not great quality and they weren't sure whether to freeze this one initially..)

I think I will defintely be wanting them to do some tests regarding possible implantation issues. I also do worry about immune responses etc reacting when the embryos are transferred.

With regards to the trabfer window being out of sync do you know what is involved in this? I have read things where it can delay treatment for a few months as they have to take samples but not sure if this is correct. If it works though then would definrely be worth it!!

Thanks again. I do want to carry on and know we will but just feeling a lite raw tight now x

@Hopefulforhappytimes I completely understand and you need to let yourself grieve. Have you considered speaking with the counsellor, I just had a session and it was useful to get some coping strategies.

Your clinic seem a bit hands off when it comes to investigations, which clinic are you under? Have you considered moving elsewhere? The UK as a whole has this emphasis on trial and error, but you have had a lot of transfers now and I really think they should be doing more to investigate.

In my case we are doing the investigations after 2 unsuccessful transfers, but we are doing things quite early for a number of reasons:

1. I have had really high rates of high quality blastocytes and euploid rates, I’m 35, I had 9 blastocytes from my fresh cycle, half of them 1,1 and when we just did PGT-A testing- 5 out of the 6 remaining were euploid (very high rates of normal embryos). So my specialist is quite sure I have implantation failure as I’ve never had a BFP and I have raynauds and progesterone hypersensitivity, making it more likely that there is something weird going on.
2. I’m a doctor and I have insisted that the situation is investigated, this is potential life that is being transferred and I’m not willing to risk any more embryos before we know more about what’s going on.

In most people recurrent implantation failure is diagnosed after 2 or 3 transfers of high quality embryos. Maybe your situation is a bit different though since there has been a successful transfer, but that doesn’t mean there isn’t an underlying issue that then caused the miscarriage or an underlying issue with the embryos- aneuploid embryos can implant and them miscarry. Have a read of this paper, it goes through various reasons for a unsuccessful implantation and the treatment options: www.ncbi.nlm.nih.gov/pmc/articles/PMC6282265/

As for the ERA, you will go through a mock medicated FET cycle, instead of a transfer they will take a biopsy of the endometrium. It will go to the lab you can have just the ERA (Progesterone timing) or the same sample can also be sent for ALICE and EMMA, these tests look at good bacteria (not enough and you’ll be put on probiotics) and bad bacteria (treatment would be antibiotics). So yes there will be a delay, my clinic like a normal cycle inbetween each FET cycle, so it will delay my next transfer by about 2 months. However, this is the best option for me to have a better chance of success.

Give that you have 1 embryo left I think your options are:

1. Have another FET and hope for the best.
2. Go through the tests and then try the transfer of the FET
3. Keep the frosty frozen and go through another fresh cycle, freeze all and PGT-A test, then go through the ERA and any other tests your specialist recommends before the transfer. I would probably be looking at this option if I was in your position, perhaps at a different clinic.

Overall if I was in your situation I personally would pause and investigate, you might be lucky if you try again without tests, but you have had a lot of unsuccessful transfers.

@gardenlady543 thank you again for all your information and support it is all really helpful. It's difficult knowing what route to go through as all clinics and specialists seem to have different views on what is best.

For our first cycle we were with Create but after 3 failed transfers they were still reluctant to do further tests and were still suggesting that it was more just a case of trial and error as you say in just keeping transferring the embryos. They were not keen on genetic testing etc.

We just didn't feel that confident in the clinic so we changed to the Oxford Fertility Clinic who have been really helpful and there seems to be more offers in terms of what they will do there (even the add ons such as glue & assisted hatching that Create didn't seem to offer). Our first transfer at this clinic was successful in terms of implantation and initial pregnancy so we didn't really discuss further options at that point.

I think the testing of embryos and implantation window will be the way forward now. I do worry they do the transfers too late as I always ovulate early in my natural cycles although not sure if this would make a difference in medicated cycle as hormone controlled?

I think you are right though and have given me more confidence to ask more questions and for tests rather than just transfer without further review. Has anyone mentioned NK cells to you? Not sure if this would stop implantation though or is more to do with recurrent miscarriage?

X

@Hopefulforhappytimes if you’ve been having medicated FET then your clinic will he scanning you to check the ovaries aren’t releasing a egg. You can have FET with downregualrion, my understanding is this shuts off the ovaries completely. Or FET without downregulation, this is what I’ve had, I think the body can still release an egg with this protocol, which is why they have to scan, if you do ovulate naturally then they need to switch to natural FET. Anyway your clinic would have told you if you’ve ovulated during a cycle, so presumedly you haven’t and as the medication is controlling the cycle, it’s unlikely that your natural cycle is interfering.

Endometrial receptivity is quite complicated and not fully understood, but it is felt that progesterone has an important part to play. So once it gets over a certain threshold it’s felt to trigger a series of events that lead to the endometrium becoming receptive to implantation, and this window can be short. The standard FET protocols usually involve a transfer on the 6th day of progesterone, but there has been no consensus on how long people should be on progesterone or the best dosage to give. From the results of ERAs: 1 in 3 women are found to have a transfer window outside of the normal protocol though. So I’d say it’s definitely worth doing it in your case.

From hearing about your journey it sounds like you’ve started at one clinic and then restarted from scratch when you moved clinic. There has been some reassurance from the successful transfer. So things haven’t been investigated to date. But I’d say now is the time to start discussing investigations, in general there are 3 reasons for an unsuccessful transfer:

1. The embryo (this is the issue for most people)
2. The receptivity of the endometrium
3. Immune issues

I did discuss NK cells briefly, my specialist said that there is a huge amount of immune testing that can be undertaken, in the first instance the level 1 tests are the most appropriate (thrombophilia screen and autoantibodies), I am on board with this as the evidence is strong when it comes to these issues impacting on success. I am less convinced when it come to NK cells, I haven’t fully researched this area, but as far as I’m aware the evidence isn’t that strong and I’ve heard it gets very expensive. I think an escalating targeted investigation plan looking at all 3 of the factors I‘ve mentioned would probably be best.

I should say I’m not anything to do with fertility medicine though. This is just my opinion on what I’d do as someone who is also having IVF that’s read a lot of the research. I think your next steps would be to write a list of the topics we’ve spoken about and make sure you bring each one up in your specialist appointment and get a plan in place moving forward that you’re happy with.

This has been really helpful thanks @Gardenlady543 @Hopefulforhappytimes

I have just had my second failed transfer and want to look into some tests before we go again. However I am NHS funded so not sure they will let me even if I am willing to pay myself. I am with Care and they don't seem to offer as many extensive tests as others.

Just wondered how both your test results came back and if they showed anything?

Hi @Narwhal88 sorry to hear about your recent transfer. I'm with Care as well.

I had my embryos PGT-A tested.

I had thrombophilia screen and autoantibodies, I was found to have a MTHFR mutation (this is very common, I take methylfolate now), I had an abnormal PAI gene and the C4M2 mutation (this is specific to care). They put me on aspirin and heparin during cycles now.

I then had an ERA EMMA ALICE, the ERA showed I was prereceptive. The EMMA and ALICE look at bacteria in the uterus, I had 0% good bacteria which is shocking as evidence suggests over 90% is needed for success. I took 7 days of antibiotics and 10 days of vaginal probiotics. During the procedure it was difficult for my specialist to get the biopsy and she mentioned Ashermans syndrome as I had had a thin lining and light periods.

I got in touch with a specialist in Ashermans and he arranged a HSG. This was normal, but having a HSG or saline scan is really useful as Ultrasounds can miss abnormalities.

I then went into a cycle with a euploid embryo, the microflora hopefully fixed, the aspirin and heparin and the tailored receptive window. It was unsuccessful which was gutting. At this point I don't know if there is something else going on or if it was just bad luck. I'm reassured that there is evidence that the chance of success with euploid embryos remains pretty stable even if 3 euploid transfers have been unsuccessful.

I'm going to repeat the ERA and EMMA now to see if I need any more treatment for my flora. I'm also on the waiting list for the recurrent implantation clinic they focus on NK cells. I'm not sure if it will make a difference, but I'm looking forward to hearing the opinion of the specialist there.

@Gardenlady543 sorry to hear you have not had success yet but it seems like you have some more answers at least. It's frustrating as like you say it could just be bad luck. All these tests add up as well! Do Care do the EMMA and ALICE tests then as I couldn't see them on their website?
We have severe MF so I'm going to get dna fragmentation done and then make an appt with Dr Ramsey to see what he suggests. I also worry about my lining as I think I have endo/adeno but the NHS wouldn't look into this further during my fertility testing. However I had an MRI for hip pain which showed possible adenomyosis. I had to get referred again for this and my appt isn't until September. I also have very light periods (1 day light bleeding) but my lining was 8.7mm both for my fresh and frozen when transfer was booked, not the thickest but ok. I have already had a HSG which didn't show anything but I have read a hysteroscopy is better as it looks inside the womb.

@Narwhal88

Yes, Care can do that Emma and Alice, it is the same lab that does the ERA and they use the same biopsy sample. My particular care clinic had not done the Emma and Alice before but were fine with adding it on as part of the ERA. The cost is £1000 just for the ERA and an additional £500 for the Emma and Alice. Obviously I would recommend adding it on because in my case the result was as bad as it could’ve been and it seems to give some form of explanation for why I have very high-quality embryos but they never implant. It’s very easy to treat microflora issues as well.

The DNA fragmentation tests sound like a good idea. I think there is some debate about how good the tests often done in the Uk are compared with the USA. So make sure you look into the tests you’re getting and check they are the best ones you can get.

That’s interesting about the endo/adeno, I’m glad you’ve got an appointment to discuss that further. It sounds like you need some further investigations to look into this.

So my lining was interesting, in a natural cycle it was 5.4 mm at 9 dpo which is very thin. In my fresh cycle it got up to 9 mm, in the first FET it got up to 8 mm, when the doctor did the transfer they noted that the lining looked very thin though. Then I had the ERA cycle, I got up to 9 mm but the quality looked awful, my specialist said it was a mix of black and white and while it appeared that there was lining there on the ultrasound, when she biopsied it she just got blood. Since I had the microflora treated there has been an improvement, my understanding is that microflora doesn’t specifically affect the thickness but it does affect the quality, throughout my recent FET everyone noted how good the lining looked and on the day of transfer it also looked good. So perhaps I have resolved the issue and it was just bad luck that the recent cycle didn’t work. I’ve also found that my period looks healthier in color since having the microflora treated. Essentially I think a lot of lining issues are not down to the thickness (which is often focused on) but actually the quality of the lining that is there.