Third IVF miscarriage - help / advice?

[Wren1985]

Hi there. I’m unfortunately going through the heartbreak of my third IVF miscarriage and hoping for some advice about next steps. Here’s my background:

• My husband and I can only conceive through ICSI. We are lucky enough to have a four year old daughter from our first round of IVF ICSI back in 2019. We have not been anywhere near as lucky in trying to give her a sibling.
• Although our original issue was sperm, I am now 38 with low AMH (7) and low AFC (9). I am a healthy weight (BMI 21) and I do not drink alcohol or caffeine. I eat a healthy diet with lots of fruit, veg, beans, fish, chicken, eggs, nuts etc. I have been on ubiquinol, DHEA and extra vitamin D plus pregnacare conception max (for methylfolate) since we started trying sibling IVF in 2021.
• Our past three IVF transfers (one FET in 2021 from our daughter’s round, one fresh in 2022 then one fresh in December 2023) have ended in miscarriage. The first two were missed miscarriages at 8 and 10 weeks. The miscarriage I’m currently going through was a suspected chemical pregnancy at first but has now been diagnosed as a 7 weeks miscarriage.
• After my second miscarriage I was tested for thrombophilia, auto antibodies and blood clotting disorders. All came back normal.
• For my December 2023 cycle I was on extra progesterone (Lubion as well as Progesterone) and Inhixia (although I do not have blood clotting issues my consultant said Inhixia could help implantation and would do no harm).
• We have one frozen embryo in storage which we will be looking to transfer as soon as my body is back to normal after this miscarriage.

I am torturing myself with why I have now had three consecutive miscarriages and if there’s anything else our IVF clinic can check / do to try to prevent future miscarriages and (hopefully) help IVF work for us again. We know how lucky we are to have our daughter but we would love to give her a sibling and, now I’m 38, we worry time isn’t on our side.

To the many women out there who have also struggled through this journey, is there anything else I should be asking our clinic to test / check / do? Is there anything I can personally do to increase our chances of IVF success and decrease my chance of miscarrying again?

Huge questions, I know, but I’m feeling desperate and just devastated to be miscarrying again. IVF is such a tough journey and the pain of recurrent miscarriage on top of it is devastating. Thank you for reading and any advice would be gratefully received. X

I am so sorry for this awful journey to your second baby you have been on.

In our case we had our first child naturally but struggled for three years to have our second, got pregnant with our first round of IVF but it was a 9 week miscarriage. The embryo had stopped growing at 6 weeks. I was completely heart broken. Our clinic was pretty certain it was due to genetic abnormality so in our next round we did PGTA testing, we got one normal embryo and she’s now asleep as I write this so for us PGTA testing really helped. It also gave me confidence in the transfer. Is it something you’ve tried yet or considered? We were with Lister in London if it helps

I was almost 38 for our second round also x

So sorry to hear about your miscarriages and the one you are going through now. I’ve also had 3 miscarriages all from embryo transfers, it’s just awful isn’t it after going through all the treatment you feel like we don’t deserve to have to go through miscarriages too 😢 I found a book called beyond grief that I found really comforting to read when I was going through my last miscarriage, would recommend it xxx

we have done the miscarriage bloods the same as you and we also did a DNA fragmentation test for my partner to see if it was male factor. Beyond that they seem to be stumped, some people do immune testing but I’m not as convinced so I have t gone down that route!

i have naughtily started taking baby aspirin although medical evidence is meh, it seems people rave about it helps implantation and early pregnancy 🤷‍♀️

as @Bkue said I believe genetic testing of embryos is now listed as ‘green’ for recurrent miscarriages, it may be worthwhile looking into this? Bear in mind though if it comes back abnormal the embryo is not allowed by law to be transferred (seems so harsh!) There does seem to be some questioning as well if some embryos can correct themselves? Might be worth chatting with your embryologist at the clinic!

i hope you have support and help right now? Sorry I don’t have any answers, just couldn’t not post as I feel your pain ❤️xxx

Thank you @Bkue and @Ellenn for your thoughtful replies. It's sad to think of so many others struggling through a similar experience. Your willingness to provide support and give advice is appreciated.

Our clinic has not yet mentioned PGTA but I can see that it's worth considering. I didn't know it was now rated green by the HFEA for women who have had several miscarriages. That's interesting. The thing which makes us hesitate over PGTA is that we almost always seem to only end up with one or two embryos from a fresh collection. My low AMH means less we seem to start with 5-8 eggs but my husband's sperm isn't great even via ICSI and I guess between my age and the inevitable drop off from day 0-5 ... we've never ended up with more than two embryos. I understand that PGTA abnormal or mosaic embryos can't be transferred and the idea of going through a fresh cycle only to then end up with nothing at all to transfer makes me feel a bit sick. However, now we're on our third miscarriage, I can see that PGTA is worth seriously considering. I can imagine the extra confidence you might have felt transferring a PGTA normal embryo, @Bkue. Huge congratulations on your baby daughter!

I do have plenty of support around me thank you, @Ellenn. I hope you do also and I wish you lots of luck on your journey.

I am fully expecting to hear again that this miscarriage was probably a non-viable embryo and that there's nothing further our IVF clinic can do / try / give me. It's so hard wanting answers and a plan which will increase success when so much of IVF is down to chance! My husband and I will certainly look into PGTA. Your comments have been really helpful. Thank you both again and all the best.

@Wren1985 I'm so sorry for your losses. It is such a hard thing to go through. Were your previous miscarriages tested? I think PGTA is worth considering if they either were untested or if they came back as abnormal.

I had my DD from my second round of ICSI then went through a further few years of treatment to have my DS. I've had every result from transfers over the years. In the end I did embryo banking and testing to have my DS alongside additional immune treatment.

Just to say that you can transfer mosaic embryos in the UK but not abnormal but then there isn't much point in transferring abnormal embryos. The evidence about embryos "correcting" is nearly all relating to mosaics. I know it is hard not getting to transfer but I suppose the way I saw it is that the only prize is a baby and if that's not going to be the outcome, it's better to find out sooner rather than later however painful. So I would rather find out at testing stage than do a failed transfer or have a loss. I know it's all awful to go through tho.

I was skeptical about immune treatment and was aware of the poor research evidence. I had assumed my loss and failures were due to age as I am in my 40s. It was only when I tested my embryos and found 2 out of 4 were normal that I started to question why my previous transfers hadn't worked. I then had a chemical with a normal embryo and decided to go all in on the immune treatment. I had my son with my final euploid embryo. Of course I can never know if that made the difference but I personally think it did.

It was also really nice being at a recurrent miscarriage clinic when I did get pregnant as I felt they were taking the risks seriously and I was getting the best possible support. I went to CRP in Epsom.

Thank you @Janefx40 for your really helpful reply. My miscarriages were untested embryos - we have not yet ventured into PGTA but are now going to look into it. Interesting that 50% of your tested embryos were euploid. Thank you for explaining about only mosaics "correcting". Yes exactly, the anxiety of possibly having nothing to transfer after PGTA is huge. However, the fear of another miscarriage also looms large and you're right that it's probably better to find out sooner rather than later if an embryo's not viable and, knowing now how complicated some miscarriages and miscarriage recoveries can be, I am starting to lean towards PGTA.

Your positive experience with immune testing is interesting. I know nothing about immunes! Do you mind me please asking you what your immune testing entailed and what your immune treatment was for your successful transfer? Are intralipids and steroids for immunity issues?

How wonderful that you now have two IVF miracles! I can certainly see the appeal of being at a recurrent miscarriage clinic.

Thank you so much for your reply and help.

@Wren1985 ive also had 3 ivf. Natural ectopic pregnancy. All early losses.
Had the miscarriage standard tests done and genetics. - showed nothing. After ectopic I went to CRP in Epsom. Showed I had high killer cells, and high inflammation markers critical in implantation which explained the early losses. I was put on injections, steroid treatment and intralipids. I also changed to gluten free diet as was having stomach issues too at the time.
Had a double transfer in August…pregnant 24 weeks with my first. I’ll be 37 when baby arrives.
so grateful to CRP and their treatment protocol.
if you have one embryo left worth just throwing everything at it and having some more tests done

Thank you @JandL2020. Huge congratulations on your pregnancy! After several losses and lots of challenges, it must feel incredible to be pregnant now. Interesting that you went to CRP in Epsom like @Janefx40. Thank you for mentioning your high killer cells and infection markers. I’m not sure whether these were included in my post second miscarriage checks but I’m certainly going to mention these to my clinic as well as intrapilids and steroids. I’m willing to try anything to increase our chances of success and avoid another miscarriage. Thank you again for your helpful reply and I wish you all the very best for your pregnancy!

@Wren1985 thank you ❤️ wish you all the best x

@JandL2020 congrats on your pregnancy and glad you also had a positive experience at CRP.

@Wren1985 as PP said CRP will test for natural killer cells as well as testing what treatment they respond to as well as thrombophilia etc as you have tested already. I did a course of Humira which I think is what made the biggest difference as I had already had steroids and intralipids in previous cycles. It is expensive especially as they will do their own tests even if you already did them elsewhere.

My IVF clinic (CRGH) had tested me for this (Chicago tests) and had also done an internal test for natural killer cells that came back normal but the immunology specialists don't put much store by internal tests as they say the results change constantly.

I was previously at ARGC who do a lot of immune work but at that time I wasn't convinced by immunology so I didn't do it.

The only IVF clinic that does full immunology work is ARGC. CRGH and the Lister do some but not Humira I don't think. Others may do a bit.

The clinics you can attend alongside your own IVF clinic are CRP in Epsom or Dr Gorgy in London but the latter is more extreme and does things like LIT that I didn't want to do. You can technically do IVF at both too I think but it's not their main expertise. London would have been more convenient (Epsom was a pain to get to) but it was worth it for the overall care and support. Gorgy is known for lack of bedside manner.

If you want to know more there is a book "is your body baby friendly" and there is a FB site called something like UK reproductive Immunology

It's a bit of a rabbi hole and very hard to know what to believe but I just know a lot of women who have had multiple miscarriages and then had success with immunology so I don't know how to square that with the research evidence!!!

Best of luck x

Rabbit hole not rabbi hole !!!

@Wren1985 have you had your thyroid levels tested?

Thank you @Sleepybunny77 and @Janefx40 for your replies. I did have my thyroid tested a year ago and it came back normal. Wow it sounds like you now really know your stuff about immunology @Janefx40! I'm looking up Humira as we speak. What you've said about different IVF clinics' approached to immunology and internal clinic immunes testing vs the approach of clinics who specialise in immunology is really interesting. Thank you for sharing all this with me so I can raise it with our consultant. Perhaps it could be the thing that makes the difference - especially if there are success stories of women who have previously had multiple miscarriages by then had IVF success with the support of immunes. I didn't realise there was so many more options than intralipids and steroids - not that I've been put on either of those yet. Thank you for giving me something specific to research and mention to our consultant. I really appreciate your helpful replies and wish you all the best.

@Wren1985 do you know the result? 4 is normal but for pregnancy it needs to be under 2.5

@Sleepybunny77 on my blood form it says TSH Thyroid Stimulating Hormone 0.80mIU/L

Hi @Wren1985 hope you are well. Wondering how your next steps went? I am in a similar position in that ICSI is our only route to conception. Like you I have one child from my first round and am currently working my way through my remaining embryos to try for a sibling. First FET failed, second worked but I miscarried at 10 weeks (development stopped at 7 weeks after the heartbeat scan). I have 3 blasts left (I guess not the best graded either) but am so reluctant to transfer and risk another miscarriage. Considering PGTA but the costs are so prohibitive. We have already spent thousands on these unsuccessful FETS but I CANNOT miscarry again, it will send me over the edge... Would love to hear of yours and others experiences with PGTA after miscarriage. Sending everyone on this awful ride a big hug.