Unexplained infertility and IVF - how to deal with not knowing the cause?

[desperatelytryingforno2]

I’ve been on this unexplained secondary infertility journey for two years now, and after six months of banking embryos, I’ve got 10 PGTA-tested euploids in the bank. I’ve had countless tests done, and everything came back normal. The eggs-to-euploids ratio isn’t anything alarming for my age (30), which is a relief, but still… I can’t shake this feeling of being stuck.

Here’s what keeps me up at night: I’ve made at least one euploid across 24 cycles of ovulation, yet none of them have implanted. So why should this time be any different? I’ve poured my heart, time, and money into these embryos, and now they’re going to end up in the same uterus that’s failed to conceive so far.

For anyone who’s been down this road, how do you handle the gut-wrenching uncertainty of not knowing what’s wrong? How do you quiet those overthinking spirals and actually start believing there’s a real chance this could work?

I'm not really clear on your situation. Have you had failed FETs? How many? x

@loulamayno failed FETs.
I’ve had 2 years of unexplained infertility trying naturally. Then a fresh transfer that ended in a mc at 6 weeks (untested).
then I banked embryos for a few months and PGT tested them. 10 euploid in total.
FET of the first euploid next month.

im just concerned because they didn’t find anything wrong. And presumably something IS wrong if in 24 months of trying naturally before IVF not a single embryo stuck. So I’m nervous going into the first transfer because, there was no issue making the embryos in the lab (as in, egg to embryo conversion ratios were ok for my age), so it looks like the uterus is the problem rather than production of embryos. But they haven’t found what. So what hope is there that this embryo will stick in that same uterus.

In the kindest possible way - I think you're getting ahead of yourself.

You've got 10 euploid embryos, this is creating a context of really great odds of eventual success. If often takes more than one transfer for an embryo to stick - it took 4 transfers for each of my children and it's often just a numbers game!

I would be keeping an eye on things such as lining thickness, which is a contributing factor, progesterone levels and asking for the need for a blood thinner or steroids if there IS any potential for uterine issues.

Breathe! You've done amazing work to get this far. Do all you can to prep for the transfer ask all the questions, but don't give up hope yet! x

@loulamaythank you!! May I ask if that’s 4 euploids or 4 untested?

Don’t worry too much. We had 5 years of unexplained infertility, tests always came back fine for both of us. One natural pregnancy during that whole time which we sadly had to terminate for medical reasons at 13 weeks. We then did IVF, 4 embryos (untested). Fresh transfer resulted in DD, then almost 3 years later currently pregnant with DS. He was our very last embryo. Of those, 1 very early miscarriage, 1 BFN and 1 success. There is just no knowing why those 2 didn’t work, and why we didn’t get pregnant naturally. You have every chance or one of those working. 10 euploids is amazing. Good luck!

A mixed bag!

First fresh transfer - BFN (think I might have had mild OHSS as felt awful!)
Second FET - chemical (added Clexane to protocol)
Third FET - Miscarriage and D&C which showed chromosomal issue

PGTA tested the rest of our embryos

Fourth FET with euploid - successful pregnancy

Sibling round:
Fifth FET with euploid - BFN (added extra progesterone)
Sixth FET with euploid - BFN (should say that protocol for these two apart from extra progesterone was exactly the same as the fourth which worked)

No more embryos left, was 44, tried with OE but all aneuploid after three rounds, moved to donor eggs.

Seventh FET with untested embryo - BFN (lining thickness wasn't great)
Eighth FET with untested embryo - successful pregnancy (did estrogen patches from the start which increased lining thickness and added prednisolone)

I agree with @Frenchie86 - it's a bit of a lottery. But I do sympathise as someone who also likes to understand the 'why'. Good luck.

@loulamayand @Frenchie86thank you so much for the detailed responses!!
its interesting that you said about changing protocols @loulamaybetween FETs or adding things in for subsequent cycles, did they do that for you as well @Frenchie86between cycles? My doc is very much of the “it’s always the embryo, almost never the uterus” mentality and that we should just keep putting euploids in and within 3 transfers it’ll almost certainly work…

The only thing they changed between cycles, which we actually asked for was adding embryo glue for the last round we did. I know research isn’t super conclusive but our consultant said he’d seen good results in our clinic, and we thought it was worth it for an extra £200ish. Whether that made the difference, who knows? My progesterone levels for all 3 rounds were relatively low so I had injections on top of the pessaries, which I didn’t have for the fresh transfer.

Not sure if you are private or NHS and with the caveat that I am not a Dr (!) I would disagree with that approach.

Yes, the quality and chromosomal normality of the embryo is obviously paramount, but there can be a myriad of issues to do with the uterine environment such as the presence of polyps/fibroids or scar tissue, undiagnosed endometriosis and adenomyosis, the thickness of the lining at the time of transfer, imbalanced microbiome etc etc.

Had totally forgotten that my last two transfers we also did embryo glue! But like @Frenchie86 says, the evidence is under developed.

I always say that IVF is a slog and if you have the emotional and financial capacity to see it out then your chances of success are good. I would go ahead with your FET and see what happens but have on hand a set of questions for your clinic if it doesn't work out and you're not happy with their approach of 'let's just rinse and repeat'. If you ARE private then I also wouldn't be afraid to change clinics if you're not happy with them.

I was in the same boat- tried for 24 months or so and nothing. Was successful on first round of my fresh ICSI cycle. How do you know it’s not a male factor? One thing I would recommend if you haven’t already is doing a vaginal microbiome test- there is a lot of emerging research on this and it’s impact on fertility. I used DAYE for mine.

From what I’ve read on website of fertility clinics abroad, (some) European clinics especially those in Spain, seem to have (strong) expertise in treating unexplained infertility. One of the most important things is finding a doctor or clinic that understands how to approach unexplained cases—or at least can guide you in the right direction.

Hi is there an update @desperatelytryingforno2 struggling after my first failed FET with an euploid. I have more in the freezer.