Karyotype after recurrent miscarriage

[PurplePansy05]

Hi All

I had 3 MCs and were under the care of an RMC. Had all the usual tests which didn't come back with anything at all. DH was also tested privately, we have no known issues.

Pregnancy tissue after my 3rd loss was genetically tested and it came back inconclusive. It wasn't a baby as such since I had a blighted ovum missed MC at 13 weeks that time.

When I spoke to my RMC consultant she advised that we should try again and that most likely this was down to bad luck and that she's very confident that I will have a successful pregnancy. I had 3 losses in less than a year so there doesn't appear to be an issue with getting pregnant, more so with staying pregnant. Anyway, she offered that if we wanted to have karyotype test (DH and I), she could refer us. This, she advised, would show whether we have a genetic predisposition to MC but it wouldn't resolve any issues as such. At no point was I advised to wait with getting pregnant - on the contrary, I was encouraged to go ahead and I did.

I am 34, currently approaching 26 weeks pregnant with my son. I had NIPT privately, all usual NHS tests and scans, some extra scans both privately and on the NHS. My son appears to be absolutely fine which was a huge surprise and relief after what we've been through.

Suddenly, few days ago I receive a letter from the genetics team inviting us to call them to arrange the testing referred to by the RMC. I though ok great, no rush with this really because I'm obviously now approaching the third trimester so seemingly this time no issues with this pregnancy. I wasn't sure if they could even test me in pregnancy. So I called them thinking we'd probably arrange it for after I give birth.

I was then told, for the first time ever, that this testing isn't only relevant to first trimester recurrent miscarriage like I was told, but it could also show genetic issues we may have that could be relevant to my current pregnancy and it could show issues with my baby. No one has provided me with full explanation but having researched this online yesterday I understand this might be to do with checking for balanced translocation. At least this seems to be the only thing that makes some kind of sense in the light of what I was told.

I am absolutely beside myself that they've contacted me now after a year since the referral and when I'm nearly 26 weeks pregnant. I am also distraught that no one has explained to me that a genetic issue could affect what I thought is a healthy pregnancy, far further along than any of my previous losses.

I really do not know what to do. For clarity, we don't have any diagnosis ourselves yet or anyone in our family regarding translocation. No one in the family has been born with unbalanced translocation that we know of either. However, my mum had 3 MCs too and my brother was born sleeping with a missed diagnosis of hydrocephalus in the 1980s.

Like I said, all NIPT and scans look absolutely fine. But I now understand they don't check for the same conditions as genetic testing does.

I will be raising a complaint about my care because I find it unacceptable and neglectful that this testing was not offered earlier on in my pregnancy.

However, it doesn't change my position now. It's too late for TFMR if a serious issue is detected. I am guessing I'd need amnio beforehand anyway and with prior history of loss that is the last thing I'd ever want tbh. I don't think I could cope with carrying this pregnancy to term if I know in advance that this baby is very ill either. We are not in a position to provide specialist care that might be needed if the baby survives anyway, but that's a separate issue.

I really do not know what to do, whether to have these tests or not. DH is thinking everything will be great and our odds are good and he dumped the responsibility for this decision on me. I've emailed my consultant yesterday but she hasn't got back to me yet. They can fit us in for an appointment on Tuesday for the tests and said the results would take 2 weeks. Ironically they'd "speed them up for me because I'm pregnant". Shame they didn't think to do that in the first trimester.

Does anyone have any words of wisdom?

I don't know what I expect, I need to get this out of my system because I'm so utterly distraught. As far as I understand translocations are rare and especially unbalanced ones are, but nevertheless they do happen and we just don't know if we're carriers or not. With the history, it would seem though that I might well be a carrier.

I just can't cope with the thought my baby might die soon or be incompatible with life after everything, for once, seemed to go fine. It's such a huge shock I am floored today. I've barely eaten, didn't sleep last night and I've been in bed most of the day thinking what on earth has just happened to us.

Thank you for reading . xx

As regards family history of MC, my understanding is that researchers would look at a range of things, for example, uterus shape, maternal/paternal age, blood clotting conditions, hormone conditions, PCOS, and as yet unidentified factors. Not JUST genetic issues.

@Dozer It's not the issue with the information that I was given now, but with the timing of the test being offered to me and the fact that no one has ever explained that potentially the same genetic issue which may have been a cause of MCs may have an impact on a far further developed pregnancy. I'm sorry, but I'm not stupid and I've done tons of reading on recurrent MC and this was not obvious to me at all so I disagree it's all clear and available. Moreover, I was actively encouraged to TTC and not to postpone after all my other tests which took months anyway, so it never crossed my mind I should perhaps wait for this particular test. I now massively regret not waiting and wish the full picture was explained to me as it should have been by the professionals.

I also understand it's a non-invasive blood test, the issue is obviously with amnio if required, I've already explained this earlier on.

And like I explained, all these other issues are in the clear, with the exception for NK cells testing....

(In the clear for me and for my mum & dad who were also tested)

@PurplePansy05 I agree. And even if not technically deemed a fault of health providers, this has left you in an unenviable situation of being heavily pregnant with major fresh worries flagged up. It is entirely natural to feel angry and upset. Xx

Ps. Did you see my previous post re. Amniocentesis risks? I realise it may not be a step you choose to take. However thought it would be helpful to be informed that risks associated are likely much lower than has been put forward.

obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.20353

Appreciate you’re worried and would’ve liked the tests much sooner.

The odds of the things you’re fearing coming to pass are low. Hopefully your midwife/current specialist can reassure on that.

My understanding is that many couples with genetic issues nonetheless ttc, then may or may not decide to have amnio during pregnancy.

The reasons for most cases of recurrent MC are never identified, so some other causes having been ruled out in your case doesn’t suggest that THIS is a cause.

Hi @SarahD19 yes, I know and understand the reasons why the risks are overstated, however I would never be able to have amnio in my position if these genetic tests showed translocation. I think that's where my head and heart is at. All I've done for 26 weeks and long before is trying to minimise the risks of losing DS and I can't even entertain this as an option, I think even if it went ok it would cause me such enormous stress until he's born that I can't even imagine going down this route. I know someone with a different history to mine may look at it completely differently and on paper the risks are of course very small, but to me they aren't acceptable. Also maybe if I had DCs already and/or if I was another few years older, I'd be approaching this differently, but that's not the case. xx

@PurplePansy05 of course. Even if risks are lower - 1/1000 or “negligible” as much of the more recent research suggests, it is still a procedure. And every procedure comes with a risk, even blood tests! It is a completely personal choice what feels right.

I know from my own experience the original higher miscarriage risk quoted to me was really unnerving so reading more about the procedure was really helpful.

@SarahD19 I think in reality, I'd choose to have genetic testing before I get pregnant, then if needed have IVF and if everything is fine, go ahead naturally.

A possible alternative would have been to try naturally and have CVS as early as possible, but I'd have to think very long and hard on that one too, tbh and not sure how acceptable this would be for me as an option.

Now I feel I couldn't do amnio or anything invasive in my circumstances.

To be clear, I am entirely for CVS/amnio if there is already an identified issue, don't get me wrong, and had this been my situation I'd be far more open to this. But now it just doesn't feel right, at this stage as well. xx

@PurplePansy05 agreed. It is personal choice whatever feels right! Sorry wasn’t meaning to seem pushy at all! You’ve stated your view and that is entirely valid in and of itself as it is only you in your circumstances who can ultimately judge what is right for you xx

No, no, you weren't pushy at all. I think it's clear from my posts that I'd rather have the full picture and when I start thinking straighter, make decisions based on that. That's why I'm so upset, because the full picture wasn't given to me by the professionals, so the more I understand the better of course. I did some reading on amnio/CVS earlier on in the pregnancy as my health board has some recommended reading, plus I read a bit more which explained why the risks stats are outdated and overstated. I was mentally prepared they may be needed if there's a clear issue with the LO and I would accept this in any pregnancy because the balance of risk shifts then IMO. xx

Yes normally Karyotyping is one of the last avenues they explore after all other issues have been ruled out. In some areas they don't test for it at all anyway, partially because most people with a translocation will eventually get a healthy baby/pregnancy just by waiting and getting through several MC, and partially because it is fairly rare even among people who have had several MC so in some areas they say it's not cost effective. I find this pretty ridiculous considering it doesn't actually cost them that much money compared to other testing, but whatever!

It's true not all people with BT opt for IVF with PGS - we didn't, although we might have looked into it if we hadn't conceived DS2 naturally. I just did not feel the risk of carrying a disabled baby to term was high enough (for me/us) to justify the whole IVF procedure and stress if we didn't need it otherwise. For some people with BT their chances of this are much higher and it's a decision which makes sense for them.

It's not something that is generally known about so I don't blame you for not knowing. I also found it really hard to find good well-evidenced info even after having the diagnosis. I've been in this "world" since 2016 really so it's accumulated info over several years. I suppose the reason they don't mention it in advance is just that they couldn't possibly tell you about every single potential condition anybody could have - it would take too long and you'd be absolutely panicked knowing every possible adverse outcome. So although it's stressful that they've now given you info that a genetic issue (which you might not have) could affect this pregnancy even though everything looks fine so far, I think this is typical clumsy NHS delivery - as it really is a very low chance and my understanding is that they have to say well yes it could affect this pregnancy, because if they tell you oh no, it's not an issue, it definitely won't, and then you were one of the tiny minority who it did, you'd understandably be upset you were previously told everything would be fine. It would be good if they would come into the 21st century and realise that with partial information, people are going to google and potentially come up with info which sounds scarier or more serious than something really is in reality.

I think speaking to the consultant and genetics team is a great idea and should really help put everything into context. It's good that you know they won't be able to tell you your personal/specific odds. And a high detail scan would not be unreasonable at all so fingers crossed they agree to this. I also found that process incredibly reassuring where the doctor was pointing out all the possible things he was checking, all chambers of the heart, different parts of the brain, stomach, nuchal fold nice and small (indicates low chance of genetic abnormalities) etc. There was a baby somewhere along the line in DH's family born with a heart defect although we don't know exactly what type. It's possible this was totally unrelated to any family translocation, but it's very reassuring to have the heart checked. But all his sisters have struggled with MC and now even one of his nieces as well.

@BertieBotts I think I mentioned on one of the previous pregnancy threads we were on that DH has a congenital heart defect. It's extremely rare (1% of the population or less) and it doesn't cause him any issues. Origin unknown. They've already checked DS over carefully for this (that's why I had a rescan at 22 weeks) and they're confident he did not inherit it. They actually don't even know if it's hereditary, it's so rare.

I definitely agree the way this information was delivered to me now was inappropriate and insufficient context has been given. I think ultimately I'm still blown away to find out that there could even be a link between recurrent MC and later genetic issue with the baby because I was told over and over again, ah now you're in the second trimester this won't be an issue, ah now you're past 24 weeks, this won't be an issue, you should be happy with your healthy pregnancy and sort of forget about the past as it's no longer relevant. My consultant and MWs told me this at every appointment.

So to be told this now is a massive WTAF moment, even if the risks aren't huge. xx

Yes I can totally understand that.

I think the chance of an issue is much lower than the 25% you mentioned - the odds of you having a BT / UBT is very very low

I had 5 miscarriages between 8 and 12 weeks. I did move on to IVF with PGS testing as I also lost my tubes to ruptured ectopics. The embryos I tested all came back with chromosome issues (I was age 36). I decided not to test anymore and transferred 2 embryos and had healthy twins.

My IVF clinic said not to bother about karyotyping - it's not offered by my NHS RMC anyway

I did do the NIPT but because they are twins we could only get results on downs/edwards/pateus

I will be raising a complaint about my care because I find it unacceptable and neglectful that this testing was not offered earlier on in my pregnancy.

being offered karyotyping on the NHS is actually very rare - it's usually only done privately, even my friend who had a TFMR for pateus had to pay privately for it

You've obviously got yourself worked up about this and I'm sorry you are stressed and I can understand given your history. Having had 3 miscarriages doesn't indicate a pre disposition to BT or UBTs otherwise all RMCs would routinely do it. The overwhelming likelihood is that they were completely unrelated - most miscarriages are actually caused by trisonomy 16

The fact you have reached 26 weeks with a healthy baby suggests the baby isn't affected at all? And the NIPT would report on a good chunk of the chromosomes that the karyotype would anyway - in fact it reports on all of them except BT/UBT and even if you did have the test it would be specific to you anyway and not the baby?

NIPT isn't usually helpful with BT because what you want to know with BT is whether your two specific chromosomes are affected, and NIPT isn't a full genetic array, it's just a screener for various specific conditions. In the future there might be a relevant NIPT for translocation carriers but at the moment the only definitive test is amnio/cvs anyway.

I wouldn't have had one at all, the only reason we did want one is DH's is on chromosome 9 and 15, which means we have a slightly elevated chance of uniparental disomy 15 aka Angelman syndrome. (or cri du chat if it was from the female side). There's no NIPT that can identify an unbalanced translocation even on chromosome 15 or 21 (downs syndrome being trisomy 21).

As an example I mean. As I can't remember offhand which other chromosomes are involved in the screened disorders.

@ivfgottwins my understanding is that three miscarriages in a row is a trigger for further investigation through the NHS. A lot of trusts DO at the very least, offer amniocentesis or CVS for this reason. Abnormalities detected in a foetus can then trigger karyotyping of parents.

Regardless of whether a complaint would be upheld, I understand one of the biggest issues here is the lack of helpful/open communication and consistent explanation for OP. She has every reason to feel upset by this and every right to complain.

Whilst I think I understand your pov here, there are many aspects of care/local authority practice, that although routine, could and should be improved. Just because something has happened routinely, doesn’t mean there is not scope for reflection and improvement (fyi I have worked in the public sector including NHS).

And as a couple of posters have pointed out, the NIPT is profoundly limited and would likely hold little bearing on the situation OP is discussing. Although it is indeed positive that there is a low risk result.

Karyotyping used to be commonly offered by RMCs and indeed it is still routinely offered if genetic testing of the pregnancy tissue indicates there may be a genetic problem or if it comes back inconclusive like mine.

Like pps said, NIPT isn't really relevant to this issue at all.

Point is, I was referred for karyotyping without a full explanation that it may have been better to wait with getting pregnant until the result is known, without proper explanation as to what it involves, what the results may show and what the consequences may be in the context of MC but also future pregnancies. Then despite being pregnant for 6 months no one offered this test, and it's a year since my referral as well. Even now the conversation I had with the geneticist scared the life out of me instead of helping. So no, I don't agree with what IVF is saying on this occasion. We ought to strive for adequate care not run lower the standards even more than they already are.

I've suddenly started feeling a bit better, I don't know why. Is this normal to flip between this overwhelming fear & worry and peace?

I don't know why but my inner voice is telling me the baby is fine. This obviously makes no sense and I don't know if I've just talked myself into this frame of mind by thinking the risks are probably very low now? I don't know if thinking this way is the right thing to do. I'm still so lost. xx

Maybe I'm just so exhausted after the last few days that I've just resigned myself to thinking what will be, will be? I really don't know. Maybe I'm actually going mad here. xx

Yes. That's good, the overwhelming fear/worry isn't a helpful headspace to be in. I can't promise that you'll feel calm every day until the end but I think once you've got there once, it's easier to feel calmer in general.

I think what can happen in these scenarios is that we perceive it almost like a threat, like we would react to seeing a big tiger coming to eat our baby. It doesn't allow you to slow down and process any information or think rationally, all you can do is react instinctively to that "danger".

Definitely I was in a very, very bad place since Friday PM. It's all still there, I can feel it, but I am so tired and maybe in denial now, maybe I'm just pushing it away because it's too much for me to deal with, I don't know.

DH and I are in awful place, didn't even celebrate our anniversary. He's left me to worry about all this on my own because he's forever the optimist, buries his head in the sand whenever it comes to any serious problems and I always have to face them head first. What an utterly shit bank holiday, and still so long before I can speak to the consultant, not to mention August. xx

This all sounds like it has been very badly handled and if you discuss it with your obstetrician they will very likely be able to reassure you. It seems crazy that based on a history of recurrent miscarriage you have been taken down a rabbit hole where possible related problems with your unborn baby have been suggested. A tiny minority of recurrent miscarriages are caused by translocations - the overwhelming chance is that yours were not. The initial test will involve a blood test for you and your partner so that your chromosomes can be checked - this should very quickly rule out a problem if you want to have it done.