Embryologist analysis/second opinion - is it the sperm or the egg?!

[Eggbert83]

Hi all

Apologies for the following essay but hoping someone else with similar hellish ivf journey will see this and can offer advice or share their story!

Myself and DH entered into ivf as he has obstructive azoospermia. He had a retrieval with Dr Ramsey, so I assume he would have been checked out at the same time for any issues like varicocele etc (he had an mri) We did not do dna frag test as he was young (33), healthy and assumed not to have any issues except absence of vas deferens. I was 38 at the time. On our first round the protocol turned out not to be powerful enough. We had one fertilised egg (from 3 only mature) but it went onto form a euploid/normal 4AA, which unfort was BFN.

We’ve since had 5 more cycles (!!!) Each time we get a good level of fertilisation via icsi - 80/90% and embryos are doing well to day 3 but then they seem to slow down and we tend to get day 6 more than day 5. On 5th cycle we had a day 5 4AA but it didn’t not survive the thaw, so was assumed to be abnormal. We had a day 6 4BA which implanted via FET, but it stopped developing between 8/9 weeks. Have been told everything about this pregnancy was indicative of abnormality with embryo. We are assured I do not have any implantation issues as I’ve had APS screening and am on clexane as a result, and also take prednisone as a precaution. I also did the ERA/EMMA/ALICE tests with no issues flagged.

Following the miscarriage, for our 6th cycle, we did pgt testing once more (having not done it since cycle one) On that round I’d really worked hard re egg quality - I’ve always been healthy and taken some level of ISWTE supplementation, but for this one specifically followed the nutrition and supplement advice of a very well respected fertility nutritionist. I am now 40 so recognise that age will undoubtedly have impacted quality but remain hopeful as I don’t have a history of not conceiving naturally and there’s a strong history of older pregnancies in my family - both g/mothers had babies at 40, and a maternal aunt had natural healthy pregnancy at 43. Don’t know if that relevant, but gives me hope nonetheless. In the lead up to this round, as we’d run out of sperm, DH had another retrieval - this time testicular sperm rather than epididymus, and he’d also followed all advice in advance of this - nuts, proceed, impryl etc. From 5 mature eggs 4 fertilised and on day three all had the right number of cells and the lowest possible score for fragmentation. In the end 3/4 made blasts, but only by day 6. One was v poor and two 5BBs were biopsies and frozen. Both came back aneuploid which was sort of expected, but what came as a shock was the long list of abnormalities - one is described as ‘abnormal’ and the other ‘complex abnormal’. We asked if these indicated anything specific re sperm or egg quality. Some were things they’d definitely expect to see in 40 year old eggs (infamous trisomy 22 in one, which is synonymous with miscarriage apparently) but it was also mentioned there were segmental issues in both embryos, which are usually down to the sperm. I’ve obviously been googling the hell out of this ever since and it seems segmental issues only affect 5-15% of embryos, but both of ours had such issues.

It really feels like we are up against it. We insisted on a sperm frag test but due to the way it was retrieved they could not analyse it. They tried but said it is often not possible with testicular sperm. We really don’t know where to go from here. We are realistic that my egg quality and both worry that perhaps we have ran down the clock on my eggs while trying to use sperm that may have always been problematic. I know it’s not the case for all, but I seem to know of and read of so many wonderful success stories for women 40+ who are single or LGBT+ and using donor sperm.

Given we cannot have sperm frag test we are now asking the clinic whether their embryology team can offer any detailed analysis of what they’ve seen with our sperm, eggs and embryos. They have embryoscope and we wonder if there are any patterns that might be diagnostic. Has anyone ever had this before, a real deep dive? Or if not a thing has anyone gotten their reports and taken them to a private embryologist or another clinic for a second opinion. Fortunately we do have a lot of faith in our clinic and have a follow up soon so will see what they say, but just wanted to reach out to this community ahead of that to get all ideas.

We are now really open to using a donor as trying to have a baby together clearly isn’t working for us but really want some more info to push us to sperm or egg. I’m open to egg donor but we would do 1:1 matching and I cannot bear the idea of an amazing selfless person going through a retrieval for us only for their efforts to result in poor embryos again due to sperm.

Help! (And thanks for reading if you’d made it this far!)

@Eggbert83 I am so sorry for your struggle. Your situation is a difficult one. I am not aware of such deep-dives anywhere in the UK (please do let us know if you find anything). I don't have any comparable experience, so can't give you any advice on that. I just wanted to respond because no one has so far. We are currently going through DE cycle, with the first transfer failing and now waiting for FET. Of your options-

1. Use your own eggs and donor sperms. In this case, you need to hurry as there is dramatic fall in egg quality post-40. I was told that even a month counts! But as you have said, there are many success stories for this age group using donor sperms.
2. Use donor eggs and DH's sperm. Since his sperms always need to be surgically removed, I am not sure this is a good option (just by reading your struggle). If his sperms can't be tested for DNA fragmentation, then it's a bit like gambling again. But maybe consult Dr Ramsay again to see what his opinion is?
3. Use both donor eggs and donor sperms.
4. Embryo adoption- this saves you the agony of waiting to find out whether a viable embryo is going to result or not, from either of the above scenarios. This is also a good option, if you are going for double donation anyway.

Of course #3 and #4 are out of question if you want to keep genetic material from at least one parent. It all also depends your resources- how many cycles can you have? If more than one, then you could try both #1 and #2 scenarios. It is frustrating that so much is unknown in IVF. All the best in whatever you decide to do.

@Serendipity24 Thanks so much for your thoughtful response. It is really helpful seeing the options laid out as it consolidates my own thinking. I completely dread the idea of another egg collection but feel strongly the last few days that this may be the best course of action for us, combined this time with donor sperm to see if we get a better outcome. I am in a position to go again in April and in the meantime am trying a bit of dhea for the first time (have had levels checked and they are continuing to be monitored) My reserve seems to be holding up, at last retrieval we got 11, so if we can do better on maturity this time we may have a decent shot. I keep telling myself that “we didn’t come this far to come this far”, so if it takes one final push from me then so be it. If that’s not a goer then perhaps it will show DE would be best. I would be gutted if we ended up not being able to use either my eggs or his sperm. Esp as when we entered this process that seemed totally possible, but we’ll see.

Wishing you all the best for your FET. Really hope that is the one for you x

Hi @Eggbert83
So sorry for what you've both been through, it's an all-consuming, emotional wreckage of a journey. So sad that your euploid AA embryo didn't implant too, hopes must've been rightly very high.
Ive done a double digits number of egg collections and had a high number of aneuploid blastocysts with several having segmental errors. I too read that segmental issues are often from the sperm so I wanted to find out more.
If your clinic uses Cooper Genomics, they have a test called PGT-Complete, where it can tell you the source of the aneuploidy (maternal or paternal). I believe it's a few hundred £'s per embryo (on top of the normal PGT-A prices). You can do it retrospectively on the biopsied samples already sent to Cooper. I did it on four blastocysts, three with segmental issues. All four came back with maternal issues only. I was 42 at the time.
It is likely that it's a maternal issue but perhaps worth doing PGT-C to find out.

Sounds like your reserve is decent and you are still making blastocysts. If you wish to continue with own eggs and sperm, your best shot might well be additional banking retrievals with PGT-A and hopefully more euploids turn up. It's soul destroying and requires an enormous amount of grit and determination with no guarantees at the end. There is not necessarily a significant decline in egg quality every month after 40 as PP mentioned.

@CailinInUK I cannot thank you enough! This is exactly the sort of mad test or investigation I was hoping existed when I made this post, and on the back of your suggestion I asked our geneticist who has said that it is a possibility for us! I don’t think our clinic has done this before, that’s the impression I get, even though we are with a major London clinic. We need to both do cheek swabs and there is as you said an extra cost, but it looks like it may well provide us with the additional info we need. It’s interesting as it seems it’s not possible in mosaic embryos so ironically the fact our embryos are so massively aneuploid may be a good thing (in terms of applying the test) This gives me so much hope as I can cope with any outcome I just hate currently feeling like there’s a gap in the info and then as a result not knowing what to do next.

You sound like you’ve been through it massively yourself, but it also sounds like you are incredibly strong - I guess some of us have no choice though. Have you had a positive outcome or what are your next steps?