IVF 3 failed transfers - what next

[FuzzyBee1234]

Hi,

I would really appreciate some stories/advice from people who have been in a similar circumstance and what they did next as I just feel a bit lost and overwhelmed by it all at the moment.

I have just had a 3rd IVF transfer which has ended in a BFN; first transfer was fresh and was BFN, second was FET and ended biochemical/miscarriage at 6 weeks, 3rd transfer which was FET ended BFN.

We are not sure if we should be doing more tests before another transfer or if we have just been unlucky and it's just a case of keep going with the same protocal. We have 2 FETs left, both 4BB grade and my cycles are always medicated, 1 embryo transfered at a time. I have Psoriasis so immune suppressers maybe a potential option ?! People have also mentioned endometrial scratch and PGS testing.

I'm hoping there are some people out there with some 4th transfer success and can maybe tell us if there was anything they did differently for that round they would recommend. Thank you in advance:)

No advice I'm afraid but following - I've just had a third failed transfer too. I have a daughter from a 2019 FET but the embryos just don't seem to be sticking at all any more

Because I'm lucky enough to have my daughter already and 5 blasts in the freezer, I'm kind of inclined not to change anything and go again immediately with the protocol that gave us DD but I also don't want to keep doing the same thing and hoping the outcome will be different...

Hi both

So this is difficult to answer. I personally knew something was wrong in my case and went for a whole host of investigations after my 2nd unsuccessful transfer. In my case I had never had a BFP before. I had a thin lining in a natural cycle and light periods. I had excellent results from my fresh cycle, 12 eggs were retrieved, all mature, all fertilized and we got 9 blasts, half were the best possible grading. After the 2nd transfer I had my remaining blasts Pgt-A tested, 83% were euploid. So it seemed to be a clear case of an issue with implantation.

I had

• blood tests to look for abnormal thrombophilia genes and autoantibodies
• An ERA EMMA ALICE
• HSG

My EMMA came back to say I had 0.00% lactobacillus (good bacteria in my uterus). When that was treated issues I'd had with my lining seemed to resolve and my periods seemed healthier in colour and quality.

Unfortunately another FET has been unsuccessful since. But at this stage it's difficult to say if it's just bad luck.

I'm glad I pursued the extra tests as in my case something very bad was found that was easy to treat but I've recently seen a article that might have made me hold off.
The study authors had looked at people with a morphologically normal uterus (to determine this someone would need to have a HSG, saline scan or other form of detailed imaging, this is worth pursuing if you haven't had any of these already- us can miss abnormalities). The participants were having euploid embryo transfers (doi.org/10.1016/j.fertnstert.2020.07.002), the chance of implantation with the first was 69.9%, for those that were unsuccessful the chance with the second was 59.8%, and for those who needed a third it was 60.3%. The authors say they even looked at those who were unsuccessful three times in a row and on the fourth the chance of a live birth was still very high at 56%. Their conclusions are that only 3-4% of people would not have success after 4 euploid transfers, so investigations aren't needed until this kind of time. And if you've both had untested embryos it would suggest perhaps even longer. They feel that recurrent implantation failure exists but don't know at what point it should be diagnosed or further explored.

So I guess the question is do you feel you have something wrong that needs exploring. If so then the tests I've had may be warranted. Or do you think you've been unlucky in which case you might want to try further transfers before exploring.

They did a journal club where specialists discussed this paper and someone mentioned that if someone has 1 miscarriage the likelihood is they will be fine and not have another and don't need further tests. But if someone has 10, there is clearly something wrong. At one point in time both of these women would have has 1 miscarriage and deciding when to look into things further is difficult to determine. With unsuccessful cycles it's the same conundrum.

Thanks, @Gardenlady543 - I've seen some of your posts on other threads and you're clearly a real expert in this stuff!

I have wondered about the bacteria stuff as I have a history of recurrent cystitis (and all the antibiotics required then to treat that...) and thrush, which obviously is all roughly the same area. I did have a saline scan before the latest transfer which didn't show any issues but I do also get cyclical shoulder pain during my period so I've wondered about endometriosis too.

I find all the waiting for IVF excruciating so I think I'll probably go again immediately as I've got a decent number of frosties but I'm also scared of wasting another embryo if there is an underlying issue

@FabricPigeon I mean my opinion would be to do the microflora test if you're considering it, but I'm biased because my result was as bad as it can get. It would involve doing a mock cycle and then on the day they would have done the transfer they take an endometrial biopsy. I would do all of the ERA EMMA ALICE at the same time. The ERA looks at receptivity and tells you how long you need on progesterone from the genes that are switched on. The EMMA looks at percentages of bacteria: good and bad and the ALICE looks for the bacteria that causes endometritis.

I am no expert on endometriosis. I did watch a discussion on the impact of endometriosis on the endometrium today though. Many others will know a lot more about the condition than I do. My understanding is it mostly affects egg quality. In the USA they do a test called receptiva which looks for a protein that is raised in the condition. But it's hard to get the test in the UK. Other tests are more invasive Eg a laparoscopy. The condition is complicated and essentially you get cytokines released from the patches of endometrium in the peritoneal cavity causing a state of inflammation. It affects the ovaries and oocyte transport along the tubes can be affected as well. But overall implantation shouldn't really be affected, at least that's my understanding of the research from the discussion I watched.

@FuzzyBee1234, it might be worth speaking with a psoriasis specialist to see if there's anything they'd recommend? There have been some recent papers (in the past few years) discussing potential links between psoriasis and fertility issues and considering interventions.

Thanks so much, @Gardenlady543 - you've really helped clarify my thinking after what's been quite a gloomy day. Thank you so much for sharing your knowledge.

I'd been thinking about doing an endometrial scratch but I understand than that ERA/EMMA/ALICE performs that function anyway, so definitely worth thinking about that aspect of it too. I'd actually seen the recommendations for good bacteria on your other thread so have been using them, but perhaps I need antibiotics on top? My lining has previously always been very good but this time wasn't trilaminar though thickness was great - maybe too many bacteria now!

I feel so frustrated that I got pregnant from my first two transfers (one miscarriage and then DD) and now nothing on three transfers. I don't really feel able to discuss it all in detail with anyone other than DH (who is wonderful) as no one else really understands so it's so helpful to get views from others going through it too!

@FabricPigeon As far as I'm aware I don't think you can over do it on gynae good bacteria. As the best outcomes have more than 90% lactobacillus. My microflora was so bad that no amount of probiotics would have helped as the bad bacteria had taken over and I needed antibiotics, to wipe it all out so I could start over.

It's interesting that your lining wasn't trilaminar, you should have a chat with your specialist about that to see if that could be improved on.

From a statistics perspective you are still in the normal category most likely. The chance of each transfer working is somewhere between 1 in 3 to 1 in 4. You were lucky that you got there with the second transfer in the past. The more transfers somewhere has, the more likely it is that they'll get success, but people can get unlucky multiple times in a row without any reason for it.

I would probably look at the ERA EMMA ALICE if I were in your position, but if you wanted to give another transfer a go first, then I think that's reasonable too.

The trilaminar thing was really odd as my lining is normally consistently great - the nurse who was scanning me at the time was very vague and just said "it looks a bit homogeneous" and also said she thought I might have a haemorrhagic cyst but again wasn't sure, so it was all confusing and not terribly helpful. I was only scanned once before the last FET so not monitored particularly closely.

You have helped so much though and given me some mega useful food for thought, @Gardenlady543 - I really appreciate it. I get so anxious and frustrated about it that it's hard to see the wood for the trees sometimes. I'll be keeping my fingers crossed for success for you too!

Thank you for coming back on this thread:) just as an update my consultant is going to have me do blood tests for thrombophilia before we move onto another transfer, she did say that 90% of people they test tend to come back normal but worth checking in case I am in that 10%.

@FuzzyBee1234 that sounds like a good idea. Mine came back with 1 abnormal thrombophilia gene and also the c4m2 mutation which is specific to my clinic. I now take aspirin and heparin in cycles, some clinics put everyone on these medications, so it's worth checking if you're under a clinic that doesn't routinely use them.

Hi @FuzzyBee1234 - you don't say how old you are but we had similar results to yours - first fresh transfer BFN, second FET was chemical then third FET ended in miscarriage at six weeks - d&c showed us that it was an abnormal embryo.

Although I never got diagnosed with any immune related issues I was on Clexane regardless as my clinic said it couldn't hurt! I didn't want to go through another failed transfer so we found the money to PGS test our remaining embryos and 50% came back normal. I'm now 26 weeks pregnant with one of the normal embryos and our 4th transfer! Did Clexane again and we also did an endo scratch the month before.

In the end I think it was probably my age and the quality of embryos which was the cause but who knows!

Wishing you lots of luck. Don't give up x

I should have said I was a month off turning 41 at the time of our last transfer. I think Clexane and Heparin (that @Gardenlady543 mentions) are the same drug. After I stopped the Clexane around week 16 I carried on with a low dose aspirin.