Recurrent loss despite normal RPL panel & PGTA embryos – what further testing helped you?

[MyAzureKoala]

Hi everyone,

I’m currently going through my second miscarriage, this time at 5 weeks. Both pregnancies were from ICSI Zymot Day‑5 FET transfers using PGTA‑tested embryos.

• My first transfer was a grade AA embryo, and I miscarried just shy of 11 weeks.

• This recent transfer was a grade AB embryo.

For both transfers, I was already on Clexane and progesterone. The first transfer was a fully medicated cycle, and this recent one was a modified natural cycle.

Between the two transfers, I completed a full recurrent pregnancy loss panel, and everything came back normal. Before creating the embryos, my husband had a sperm analysis which was normal except for low morphology (1% when ≥4% is considered normal), which is why we proceeded with ICSI Zymot.

Our fertility doctor is now recommending we see Lesley Regan, but we’ve also seen very positive things about Raj Rai, so we’re unsure who to go with. We still have three embryos remaining, but before moving forward we want to understand what might be causing these losses and whether any further testing could help.

For my husband, we were considering sperm DNA fragmentation testing, but since we already used ICSI Zymot and have embryos frozen, we’re unsure whether it would provide any useful information at this stage.

If anyone has had similar experiences, or has seen either Lesley Regan or Raj Rai, I would really appreciate hearing your thoughts. I’m also curious what additional investigations they might suggest, given that my recurrent pregnancy loss panel was normal.

Thank you so much in advance.

I’m so sorry for your losses.

did you manage to have any of the miscarried babies tested for any obvious issues? Chromosomal etc?

im surprised you weren’t on prednisone so I’d perhaps ask about that? If all your embryos have been PGTA tested normal (which it’s great to get 5 through testing!) then must be something else at play - how much progesterone were you on? My only successful transfer out of 5 I upped it to 3 per day
what about a hcg shot prior to transfer?
I agree dna fragmentation isn’t really that important since you do seem to make a good number of euploids

I’m so sorry OP. It must add another layer of difficulty to experience losses following IVF and PGT.

I saw Lesley Regan earlier this year. Slightly different situation in that I’d not yet had any NHS recurrent miscarriage testing. It seemed to me that she did basic NHS recurrent miscarriage testing, plus additional genetic thrombophilia tests (eg PAI-1) and also the TEG/thromboelastogram. She also interprets the APS tests with more expertise than I’d imagine my local RM clinic would (and diagnosed me with APS despite the tests only being mildly - but persistently - raised). Similarly I had confidence that the 3D womb ultrasound was performed and interpreted with more expertise than I’d had when I had that test at a fertility clinic.

She’s very thorough and hugely knowledgeable. If you’re looking to see someone who you can trust will take a fully evidenced based approach, then I think she’s brilliant (and I suspect Raj Rai takes a similar approach as I believe they work together). However, if you’re looking for more experiential tests or treatment (eg NK cells) then looking elsewhere would probably be best.

I’d recommend buying her book to get an impression of her approach and testing she does - especially re the TEG/thromboelastogram.

Thank you so much for taking the time to reply, really appreciate it.

We’ve unfortunately had two miscarriages after transferring PGT-A tested euploid embryos, so we’re trying to leave no stone unturned before using our remaining embryos. We’ve already done ICSI, PGT-A and ZyMōt, but we’re now wondering whether there could be something else that’s been missed.

It’s really helpful to hear your experience with Lesley Regan. The additional testing you mentioned, particularly the thrombophilia tests, TEG/thromboelastogram and the more specialist interpretation of APS, sounds interesting as these haven’t really been discussed with us.

If you don’t mind me asking, after seeing her did your treatment change, and did you go on to have a successful pregnancy?

Thank you again for sharing your experience - it gives me another avenue to look into.

Thank you so much for your reply, I really appreciate it.

Unfortunately, after my first miscarriage we only had histology done after the D&C, so we didn’t have chromosomal testing performed on the pregnancy itself. The embryo had already been confirmed as euploid with PGT-A before transfer, so we were left without an explanation. The second miscarriage was also from a PGT-A-tested euploid embryo, which is why I’m trying to investigate every possible cause before using my remaining embryos.

I wasn’t on prednisolone for either transfer, so that’s definitely something I’ll ask my consultant about. For my first transfer I was on Lubion injections twice a day and Cyclogest 400mg pessaries twice a day. For the second, I had a modified natural cycle with progesterone support and Clexane. I also had an hCG trigger before transfer.

My clinic feels DNA fragmentation is unlikely given we created five euploid embryos using ICSI, ZyMōt and PGT-A, although I’m still considering having the test just to rule it out.

Thank you again for taking the time to reply. It’s really helpful to hear from someone who’s been through a similar journey.

Totally understandable to do more testing at this point - I’d be doing the same!

Yes, I’ve been given a treatment plan for APS but yet to have an opportunity to try it.

Wishing you the absolute best with it all

Thank you very much and wishing you the best on your journey also 🙏