PGS after FET miscarriage: advice please!

[Claraa2018]

We just had a very sad miscarriage at 9 weeks after seeing a heartbeat after an FET. This is our second miscarriage (the first was after a fresh cycle of IVF and a long history of infertility). We tested the remains of the first miscarriage and they came back chromosomally normal. We chose not to test the remains this time due to the high cost but our consultant thinks this one was probably normal too as the pregnancy made it this far. He/we think somehow it didn't attach well and I have endometriosis and adenoymosis. Nevertheless he thinks it could be worth PGS screening our remaining embryos to prevent more loss as at least we eliminate one factor that could cause a miscarriage in the future. We are scared that they will all come back abnormal and that we won't be allowed to use them even if they might have survived. I also wonder if we should be focussing on other likely causes of miscarriage (our consultant is skeptical about going down the immunology/steroids etc path as I've had one live birth/DC and he worries about the effectiveness/ risks of these treatments). It is such a minefield as we know some in the medical community would say the same about PGS. We are worried about more loss, finances and losing time (I just turned 39). Have others done PGS after losing normal embryos? Sorry for the long essay. We are feeling a bit lost and would love any PGS stories from others in similar situations.

I had 5 miscarriages before IVF and decided to PGS on my second round of IVF. At age 36 mine all came back abnormal or mosaic. The abnormal had to be destroyed but I was allowed to transfer a low level mosaic but it was a BFN

I personally wouldn't test blastocysts which are already frozen as they can cause damage which makes them less likely to survive another thaw

Also given that your miscarriages were chromosomally "normal" there is no evidence to suggest that testing will prove anything?

The science of PGS testing is flawed abs it's not 100% accurate. I decided not to test on my next egg collection and I'm now pregnant with twins so I'm pretty sceptical of testing now x

Hi @ivfbeenbusy, thanks very much. Congratulations on your pregnancy! That's wonderful. I'm so sorry you had 5 losses before this. This is all very tricky. Our consultant thinks that the 3 embryos we used were normal so far (one as it led to our DD and the two miscarriages). However, he thinks due to my age 40-50 percent of the embryos in total are likely to be abnormal so chromosomal problems could very well be a cause of future failure even if it wasn't the cause in the past. Both miscarriages were difficult physically and emotionally and doing unsuccessful cycles is expensive so he thinks this could spare us more upset and money. We are considering transferring two next time though our clinic tends not to recommend this. Did you do any other miscarriage tests/treatment for your successful transfer? I share your concerns about PGS especially as the embryos are already frozen (though our consultant thinks the risk to the embryos is very small).

Hi @Claraa2018 I haven’t had a miscarriage but we have both male and female issues and decided after two ivf transfers both BFN to PGS test any embryos we get. We are worried they are all abnormal but if they are we will have to face up to that and think about maybe donor eggs. If some are normal then we’ve saved ourselves heartache of transferring abnormal embryos and quicker time to getting a baby so that is a massive plus of it. It’s done very standard in US. My friend did IVF there and got 12 embryos - 6 came back abnormal 6 normal so she really saved herself heartache of transferring abnormals.

How many do you have frozen?

I did a lot of research and I do trust the process. They can generally tell exactly which chromosome is missing so its not a blanket ‘abnormal’ and there is only a 5% chance of misdiagnosis.

@ivfbeenbusy I’ve seen you on here before. I know you moved from short protocol to natural modified - was the abnormal embryo round short protocol and then your pregnancy from natural modified? I presume if you had done PGS your current pregnancy would’ve ended up PGS normal?

I’m just thinking if mine come back abnormal whether it’s be worth doing a natural modified before doing donor eggs.

@Claraa2018 have you done an ERA/ALICE/EMMA and immune testing? I would consider these tests too as if you did PGS test and then it turned out to be a lining or immunes issue you will have wasted a good PGS embryo!

@Lionoflove1, no we haven't done any of those tests. Although our clinic offers them, our consultant seems to think they are not necessary as we have one DD from an FET and got pregnant three times from IVF/FET (even if two of those failed). We have 5 remaining frozen ones (3 day 5 and 2 day 6). However, as the three we've used appear to have been 'normal', he thinks the odds are that the next ones we will transfer are likely to be abnormal and we'll lose more time that way. I have also found these miscarriages really hard to bounce back from emotionally and physically. I have also noticed that in the US, PGS seems to be much more standard. I guess my main concern is that we are testing already frozen blastocysts so there is more risk and that the screening is a big expense and there is a likelihood that all will come up abnormal as I was 37 when they were made. My consultant is already saying this could well happen and that we may have to do a fresh cycle after this. Thanks for your comments and good luck on your treatment too. x

It’s not an easy decision. I do think your consultant view is slightly odd though. If he’s saying your embryos were proven one normal and other likely normal and that you don’t have implantation issues then immune testing to me would seem like the natural next step.

I take his point about how maybe the abnormals coming up out of the batch you have but if you test and remove those, do another fresh round and get some PGS normal you still haven’t really gotten at why you’re having the miscarriages as you’ve had them with the PGS normal embryo already.

It could be worth researching whether immunes can change - ie if your immunes were fine during your first pregnancy but could be raised now. Maybe pregnancy inflamed your immune system?

I have a friend who had totally normal blood pressure then developed high blood pressure during pregnancy and is now on tablets for life. It could be that your immune profile also changed but it’s just not visible. I would maybe look into that and see if it’s possible?

But then I am throwing the kitchen sink at this is in my 4th round of ivf and can’t face into miscarriages etc if we do get pregnant so I’m doing embryo banking, PGS, immune testing and ERA/ALICE/EMMA before I do another transfer.

Hi @Lionoflove1, thank you for these thoughtful points. You are right - in fact he's saying that 3 embryos so far were likely normal (the one that led to my daughter and the two that miscarried). I must admit I am very torn and confused. I think my consultant is quite evidence-based and suspicious of some of the immune treatments as there's less evidence for them? I think he is also trying to save us money so he is focussing on what he thinks is most important. He previously didn't recommend PGS to us after one miscarriage where the remains turned out to be 'normal' even though we asked about it at the time, but now that we've had a second miscarriage, he thinks it's the right thing to do. I do wonder whether something has been off with me since my pregnancy. I also did extended breastfeeding and have been very tired with work and a young child so I feel I wasn't able to rest as much and had more stress than before. However, we felt we shouldn't wait much longer and plenty of people conceive under the same conditions. I realise you are referring to medical concerns rather than tiredness so I will raise this with the clinic. He also pointed out that we are already treating a lot of the non chromosomal reasons for miscarriage as part of their routine protocol (through thyroid, blood thinner and progesterone medication). I guess he thinks we've eliminated a lot of the reasons for miscarriage and that there is just a lot we'll never know about why they happen. It is hard for me to accept though as I keep looking for answers. I really hope you will be successful on this round. It sounds like you are giving it the best chance possible.

I moved from an old fashioned clinic to a more modern one and the consultant made a valid point that if we waited until all the new technologies were ‘proven’ ie through funded randomised controlled trials and published research then we would have missed our fertile years.

It could be worth doing immune testing and if it comes back normal fine if not you can decide what to do with the information you have on what is happening your immune system. For some treatment is blood thinner aspirin and steroids and if you’re already on blood thinner then you’ve only the steroids and aspirin to add in. Some clinics actually give this without doing the testing just in case.

If you’re very tired have you had your iron checked?

It actually drives me a bit crazy when they want to ‘save you money’ if this round works for me those extras for around 5k would have saved me 24k in 3 failed ivf cycles if they’d been done at the start - never mind I’d have my baby and my mental and physical health wouldn’t have taken such a battering.

Hi @Claraa2018 I'm so sorry for your losses. I have been in a very similar boat - have had two later first trimester miscarriages (9/10 weeks) following IVF. I am 39 too! We had one more embryo to try but decided to go back to the drawing board and do another round of stims and PGS test those embryos. My consultant reasoned the opposite - that as the pregnancies had lasted to 9/10 weeks he thought it was genetic. We got the remains of the second miscarriage tested and there was a problem there (monosomy). My clinic gives the steroids empirically, because the tests are so expensive and it's cheaper to just go on prednisolone so that might be an option for immune factors. Clotting tests are not that expensive so could try that, but I guess it's unlikely if you've carried a healthy baby to term before?

I think ultimately you have to weigh the risk of the embryos dying through the thawing and testing process, versus the risk of another miscarriage. And whether you could even consider doing another fresh cycle if the embryos didn't survive the tests. There are financial factors there too, of course. Best of luck. I'm about to start a frozen cycle shortly, so will keep my fingers crossed for us both

Thanks @Lionoflove1, I feel the same frustration as you and it's been a very difficult road. I am conscious that we are very fortunate to have one child and are really thinking of those who have not had their baby yet.

Our clinic is actually very modern as far as I can tell as it offers all of the treatments you mentioned however maybe our particular consultant just doesn't seem to be as convinced by them. He was our consultant in our first round on the NHS which led to our daughter so we were happy to go with him again at the private clinic but I'm now worried about the way forward. Strangely we had baby aspirin and blood thinner injections in our successful FET but we weren't given baby aspirin but just a higher dose of blood thinners this time. I wonder if this was a problem.

My progesterone also measured low this time although only as they have a very high target so we were told the level was not really concerning. They had us increase our progesterone with intramuscular injections until our 7 week positive scan and then they switched me back to just pessaries. Now I wonder if stopping the injections made a difference as we lost the pregnancy two weeks later. Our consultant said next time we can try an even higher dose of progesterone. I think my iron was checked in our blood tests and they didn't find anything. I think I will push for immune tests given that this hasn't been looked at at all and we seemed to have been losing normal embryos.

Hi @orangefolly, I'm so sorry for your losses. I found it really devastating this time. It is so frustrating that consultants see the same situation and take very different views especially in this area of medicine. I may actually speak to another miscarriage specialist at our clinic to get a second view.

We were very on the fence on whether to test the remains this time but as I've tested our previous one and it came up normal and I had one healthy daughter, we were advised to save our money for other tests/ treatments, particularly PGS. We would consider another fresh cycle if these don't survive. It sounds like in your case PGS made a lot of sense and may address what was wrong last time.

I think in our case clotting is unlikely to be the problem as I've delivered a baby before, take blood thinners anyway and had a scan that didn't detect anything. However, this miscarriage was so sudden and 'complete' so quickly (sorry if this is upsetting anyone), that my consultant suspects something in my uterus caused the bleeding and led it to suddenly dislocate. I really wish you a very successful cycle this time. I feel after all we've been through we deserve a good end result sooner than later.x

Hi there @Claraa2018 I’ve had three mmc between 8-9 weeks and 1 cp since summer last year. I also have one child who I got pg with quickly and no issues. I think we have secondary infertility which seems quite common.
Unfortunately, my second and third mmc the hospital corrupted one ‘product’ and didn’t get enough sample the second so I don’t actually know for sure what caused them , however , through lots of reading and from the behaviour of my hcg ( raced up extremely high very fast and then stopped doubling at 6 weeks) it seems like a genetic issue. Trisomies and monosomies are very common 8-10 weeks .
I think it’s definitely worth testing the latest mmc. Pgs normal have a 30-40 percent failure rate anyway , can be due to the environment of the womb or just the embryo runs out of steam to complete all the divisions needed to grow . I would say if the latest one is pgs normal though then the odds are it’s not the seed but the soil and you should get more testing done . I’ve found out I have a deficiency in protein c , which requires double the aspirin I was taking for the last pregnancy (150mg rather than 75) so even though you are getting treated as though you have issues perhaps you aren’t getting the right mix of drugs at the right levels . I went private and tested everything I could , including killer cells . Mine were slightly raised and were treated but the last pregnancy still failed so again I think it was a chromosome issue .
I saw it as a full MOT of my body before any future pregnancy. I’m now doing ivf with pgs . I fall pregnant quickly and naturally but have realised I have an unfussy uterus x

Thank you, @Sunshinelove8. I'm so sorry for your recurrent miscarriages and that they were in such a short time span. This sounds so hard. It sounds like you are on a great track now and have done very thorough investigations. It sounds like the unfussy uterus explanation really applies to your case (in our case we have only been able to get pregnant on IVF). How did you know your HCG was rising so fast - was it being tested that whole time?

My last miscarriage was a natural one, not an MMC (my first was a MMC and required a D and C). This one actually finished at the clinic as they rushed me in to get scanned when I reported the bleeding. I am conflicted about what to do in my case. My consultant is putting a lot of stock on me having had a successful pregnancy/healthy child in between my 2 miscarriages. I can see why we shouldn't jump the gun in looking for causes as I know I'm not in the recurrent miscarriage category of 3 miscarriages in a row and no child in between. I also think their protocols are quite thorough - my successful cycle and last miscarriage were natural FETs so my lining was monitored every day until transfer and they cancelled my previous cycle on the day of transfer as I had a bit of fluid in my uterus. However, I do worry that there are many things that we are not investigating (thank you for the point that maybe my blood thinner medicine needs to be readjusted and I do regret now that we didn't take aspirin this time).

I'm also concerned about PGS testing our remaining frozen embryos (the consultant is not concerned as they have an excellent lab and he hasn't lost any embryos this way but I think from reading that this is not as widely done).I think I'd be much more confident to PGS test a fresh batch of embryos...However, I am also conscious that if we destroy these embryos from a few years ago in the process and do a fresh cycle again, our embryos this time will be more problematic due to age.

These decisions all feel quite stressful at the moment and I'm not sure how to resolve them. It would be great to hear any stories of PGS on already frozen embryos but I have not seen any posts on this. x

Hi,
We had a miscarriage after fresh and then another after FET. Both were MMCs. PGS testing was recommended on our remaining embryos. We did that and 5 came back normal. We transferred 1 and had DC1 and then another and had DC2.

DM me if you want to ask anything in particular.
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