Should I have all these tests? (IVF)

[Mouseorchestra7]

I am about to start my second round of IVF. Had a failed transfer from the first round (with a 4AA blast). As I always seem to end up doing, I've gone down a bit of a rabbit hole looking at the reasons for failed transfers. There seems to be a lot of mention of all these different tests, NK cells, thrombophilia, ERA. In the US, they seem to do a lot of them as standard.

I'm panicking that I should be getting these tests and that I'm just setting myself up for more disappointment with another failed transfer, etc. because there may be an issue that the tests would pick up.

If you had these tests, at what stage did you do so? Do you think it's worth doing these tests to check there is nothing wrong before my next transfer or is the fail more likely to be down to bad luck?

Hi @Mouseorchestra7

So when you go for further tests is a difficult decision. I would hold off if it has been 1 transfer, if this was an untested embryo then the chance of success would be 1 in 3. If it was euploid then the chance would be around 50-70%.

A recent study 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- an ultrasound 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.

In my case I pursued tests after 2 unsuccessful transfers. I know this seems early but I had high rates of high quality euploid embryos. So it made no sense that I had never had a BFP ever.
I had

• blood tests to look for abnormal thrombophilia genes and autoantibodies (I had an abnormal thrombophilia gene so I’ve been put on aspirin and heparin, the evidence for this being beneficial is pretty sketchy, but some clinics use these treatments in all patients so I was fine with it)
• An ERA EMMA ALICE, the authors of the study I discusssed say these aren’t validated tests though, I was prereceptive and I had 0.00% lactobacillus (good bacteria) in my uterus which is shocking, this is pretty rare and I’m hoping it explains the lack of success.
• HSG (this was normal luckily, in other countries they do this kind of imaging routinely, I don’t know why they don’t in the UK)

Unfortunately another FET has been unsuccessful since. But at this stage it's difficult to say if it's just bad luck. Given my microflora was so bad and some women need two courses of treatment I’m going to repeat the EMMA.

I think personally I would have at least another transfer before considering further tests. Statistically even in someone with no issues it will take around 3 transfers to work. Although it is worth considering how many embryos you have, my friend with DOR had ERA EMMA ALICE before any transfers because you can't take a trial and error approach when you've been through months of embryo banking.

As for NK cells I would leave that until much later, I’m on the waiting list for coventry’s recurrent implantation clinic to discuss this. Mostly because there isn’t anything else I can pursue. There isn't a good evidence base for this so I think this is best reserved for recurrent implantation failure and recurrent miscarriages.

Hi @Mouseorchestra7 I can't give you as comprehensive a response as @Gardenlady543 but I can give my perspective/experience. The first question I would have is how old are you? Age has a huge bearing on the likelihood of a euploid ('normal') blast, far more so than the grading.

I'm 41. I got two blasts from my first round of IVF, a 5AA and a 4BB. The 5AA was a fresh transfer, and BFN. There was no suggestion of any tests at that point, failure was put down to the high likelihood that my age meant the embryo was aneuploid. I left my 4BB in the freezer and did a second round before I aged too much more, and got 5 blasts that time (freeze-all due to OHSS risk).

My first FET from that second round was another 5AA, and another BFN. At the follow-up review I said I wanted to know whether there was anything I should be investigating. The consultant agreed that after two top quality transfers it was worth doing some tests, even if my age meant the euploid rate was probably the main issue.

I had thrombophilia tests and auto-immune tests, neither of which threw up anything much but the consultant suggested low-dosage Clexane injections would not hurt for my next FET. My third transfer recently was a 4AA, natural FET, with cyclogest and Clexane from 3 days before transfer. I also had an endometrial scratch in my previous cycle, which has mixed evidence for it but my view was it doesn't (as far as I understand) have any major downsides and at £200 it wasn't stupidly expensive in the grand scheme of IVF costs.

This time I did get a BFP, though sadly it was a chemical so turned to BFN shortly after. But that's the furthest I've got so far. Whether that means my body needed a bit of extra help (from the Clexane or scratch) for an embryo to implant is impossible to say. I've not had my follow up review yet but doubt the consultant could say for sure either.

I think the suggestion to do another transfer before tests is sensible. It sounds like you had one embryo for transfer from round 1 and I completely understand that it feels like so much rides on each transfer. I do wonder whether one of my 5AAs may have succeeded if I'd had the extra meds earlier, but clinics in the UK seem to prefer a more test and learn approach, plus I'd not PGS-tested any so it's quite likely they were aneuploid.

I'd say try one more transfer, and if no joy start with the most 'evidenced' investigations. As you say, you can really go down a rabbit hole and knowing where to stop is hard. Lots of luck.

@Gardenlady543 Thank you for this comprehensive and helpful response!

Very interesting results from the study - my embryo was not tested and I will not (at least not at this stage) be getting any PGT testing, so this makes me think that I should at least give it three goes until I start to look into further testing. The 3/4% figure is very interesting.

Part of the reason I started worrying about this is because I’m in a few (predominantly US) groups where HSG, ERA, etc is all standard (as well as PGT testing ). It just seems that implantation issues are so common if you go by the US clinics and all the testing they do. I start to wonder how anyone has success with IVF in the U.K.! Thank you for the takeaways. So based on what you say I could probably do one or two more transfers, then if that doesn’t work consider some blood testing (such as for thrombophilia and ERA, ALICE etc).

I really hope you get some answers from the Coventry implantation clinic and wish you success for your next transfer.

@lucymills1234 thank you for your response! I’m 35, so probably have a few aneuploids? Think you’re right about the testing, but part of me just wants to know now if there is something (so I don’t ruin a chance). Unfortunately my clinic doesn’t do much testing, so I’d probably have to move to another if I wanted to do things like the ERA, etc.

When you say the most evidenced investigations, would you say those are the thrombophilia and immune tests you had?

Best of luck with your next transfer.