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

Anyone?

No wisdom I'm sorry but didn't want to leave you hanging. Hopefully someone knowledgable will come along soon x

Thank you larry

@PurplePansy05 sorry you’re going through this. I really hope you’re ok. If it is any comfort to you, at 26 weeks if there were life threatening/serious complications, the odds are that this would be picked up. I know when under FMC the consultant explained it is very rare for third trimester complications to present - final trimester is more about growth than development.

I know maternal/paternal mosaicism and translocations can cause repeat miscarriage. However we truly know very very little about these conditions - some research even indicates we may all have low level mosaicism in some respect.

I’m not sure if my message is helpful but I didn’t just want to ignore your message. I hope you’re ok. Happy for PM if I can support at all. In the meantime, sounds like the odds are all is well and in yours and baby’s favour right now. I hope you manage to relax a bit. No stressing can change your circumstances (I know easier said than done). X

Thank you @SarahD19, I saw lots of your pisrs on this board and you're very knowledgeable in this.

You are right that translocations can be linked to recurrent MC but I read this only affects around 5% of RMC couples and for many, once the baby is tested after loss, it transpires that the MC was not actually due to translocation.

I suppose my worry now isn't in the context of MC anymore. I'm more worried that one or both of us do actually have a translocation and then as far as I understand there are 4 equally possible outcomes for my son - MC (won't happen now), he's perfectly healthy, he's healthy but with inherited balanced translocation or he's born with unbalanced translocation. It's the latter that causes me major concern, it's the what if and the fact they failed to test us earlier despite the fact the referral was in place and it was clearly obvious from my patient record that I was expecting. I really don't know what to do now. xx

*posts sorry I'm sobbing here and my spelling is atrocious.

This geneticist was very factual with me and basically said well yes the chances are good with all scans, blood tests and NIPT being fine, but they can't guarantee this as some conditions would not have been picked up at 20 week scan.

I knew that some things could of course be a surprise, but this is potentially a different scenario whereby they all knew that there may be a genetic background to my MCs but no one explained the effect this might have on a more developed pregnancy and failed to test me.

I feel absolutely awful. xx

@PurplePansy05 absolutely and it sounds as though things could have been handled better from what you’re saying. I can only imagine the anxiety and frustration... I can relate to an extent as my daughter was assessed as having Mosaic Trisomy 18 (after initially just Edwards) - I know from the research that the implications can be far reaching. Some of the research is quite a worry. However I still also consider in all likelihood the research that is available is limited and skewed. There is a reason many people get almost accidentally diagnosed with translocation/partial trisomy in later life - because for the most part they have been healthy.

I look at my daughter and she seems so healthy and strong. Obviously there are no guarantees with any pregnancy. With or without the knowledge, you may well have reached the same point... Yes you rightly feel upset that you probably should have been told things sooner. I hope you don’t mind me suggesting in some ways I query if not having that information may well have potentially been a blessing in some respects... after the experience I personally had. I have often wondered what my pregnancy might have been like if red flags weren’t raised at the start. We may have enjoyed the pregnancy more and I almost wish we never had any screening or diagnostic tests - as we wanted our baby anyway (despite what our rational brains may have thought beforehand!)

Obviously our situations are different. But as someone who was provided “hard science” and every reason to terminate my pregnancy on paper, I would not change that we have our beautiful, healthy daughter now.

I’ll be thinking of you. Sorry if this message seems a bit rambly! Hope you’re ok x

Well I can only pray my son is born healthy, either without a translocation or with a balanced one...I suppose then I may be able to look at it in a similar way. For now, the worry and uncertainty is absolutely killing me.

In some ways you're right because I felt much better up until that call yesterday which has destroyed me and I'm not enjoying a single bit of this pregnancy anymore and I know I won't. As you can imagine, my joy was already limited due to prior losses and I regret allowing myself to feel any joy at all now.

But still had someone explained things properly, we would have waited for these tests and if necessary we may have gone with IVF with PGD. But no one said anything, they've encouraged us to try again. I think it's disgraceful. Not to mention genetic testing not being offered before 24 weeks, now this is bloody beyond me too.

I don't know what to do. I really don't. I feel they've utterly screwed me over. xx

Just seen the second message. I don’t know you so hopefully not too strange to send virtual hugs. The geneticist said similar to me regarding our baby. It is scary as they do paint worst case scenarios. There are so many positives. Would requesting a third trimester scan help to reassure you maybe? Could be worth requesting. If they’re going to suggest things could have been missed, then they’ve a duty to follow up, especially when it is so stressful for you x

I promise I'm not following you around the boards this thread just came up in active and it caught my eye.

If you do end up finding out you have a translocation you'll find that there is a lot of misinformation on the Internet about it. This is partially because it is not a particularly well studied condition. But also the nature of the Internet.

My experience having been in the support group is that it absolutely does cause recurrent miscarriage for a lot of couples. It's actually thought to be one of the most common causes of recurrent miscarriage. The problem is many people have no idea they are carriers, which actually gives me hope when I'm feeling positive about it. Lots of people never know and the people who do know are the ones who have had worse experiences, and more recently, it's simply being picked up in testing more routinely.

I also wanted to reassure you that they are very much covering their backs and preparing you for the worst case scenario, which does not mean that it is a likely outcome. The reality is that every single person who is ever pregnant is at risk of less-detectable medical conditions. The only way to be totally sure would be to do a full amniocentesis or CVS with full karyotyping of every unborn baby, and of course this is not justified due to the risks of miscarriage and infection this introduces to each pregnancy. Nobody can tell you (or me or anyone else) for sure that their baby doesn't have a genetic condition. That's all they are saying. The facts are that most genetic abnormalities are either so severe that the pregnancy does not last very long - this causes the higher rate of miscarriage with a BT or as you age - or they are physically detectable on ultrasound. It is very rare to have a condition that is not apparent in one of these two ways. Of course it happens. It's not impossible. But the chances are not that much higher just because you have had miscarriages. It might be marginally higher with a BT. But again anybody in life could have a translocation and not know - most people on the support group I was on found out after a late miscarriage or amniocentesis.

For me I found it very helpful to know the specific details of DH's translocation. And by the way they did the same thing to us. Kept everything moving very very slowly so that by the time we had the info it was too late to make any decision. I don't think this was on purpose, I just didn't know how much I should have been shouting about the urgency really. I wanted to have the specialised NIPT, as you know, this time around but again by the time anybody agreed to advocate for the insurance costs, I was already over 20 weeks. I don't want to do it now. It won't make any difference anyway. But it was helpful for me to know the specifics because even though each individual translocation is so rare there isn't personalised info about it, you can gain some information by knowing for example which chromosomes are involved, where the split is, and so on. I find this kind of information as well as family history very helpful, as it helps me to put information into context. The NIPT tests only look for specific conditions which is why we wouldn't have bothered until I found one that looked for one specific condition we may have a raised chance of, but for example with the history of hydrocephalus, it's possible you may be able to have an extra ultrasound specifically to look for this, and that's the kind of information that I would be asking about.

Very happy to point you towards that FB group if you want to. They don't mind at all of you're still waiting for diagnosis or even deciding whether or not to have the karyotype done.

Thank you @SarahD19, I am consultant led and have 3rd trimester growth scans booked for 28, 32 and 36 weeks. I am minded to ask my consultant, if she reverts to me, for the 28 week one to be a high detail scan (is this what it's called? I don't actually know if this is the correct name). xx

Hi @BertieBotts, nice to chat to you again! Thanks for the comprehensive response, as always. I am trying l, in my moments of sanity, to explain to myself that most of these things probably would have been picked up as you say.

But this geneticist open a Pandora box which I've worked so, so hard to keep the lid on after my losses. Now all my concerns have spilled out and multiplied and it's hit me like a ton of bricks. I can't control this now. My mind is only focusing on the risk of negative outcomes and I can't help it. xx

Could you let me have the name of this group, please? I don't know whether to join yet or whether this will make me spiral even more, I just don't know what the right thing to do is anymore. This is going to be much harder 14/15 weeks than I could have ever imagined. I barely survived today so no idea how to face this now. xx

Hi @PurplePansy05 I’m sorry that you’re experiencing this uncertainty with your healthcare team.

The previous miscarriages could be based on a multitude of issues, not just the genetic testing that’s too if mind for you right now. It could be egg quality, your uterus and an abundance of other things.

Find solace in your blood work results and know that the healthcare system is set up to find issues, and support those who require it. They could be over cautious here ensuring they’ve covered their bases.

I’ve recently experienced an over cautious healthcare system that caused me weeks of stress and anxiety that turned out to be nothing but a healthy pregnancy.

Thinking of you through this journey. 💕

Yes I'll look it up for you. You're right it might not be right to join if you think it might make things worse. If you did I'd recommend immediately unfollowing so that you don't get all the posts appearing in your feed all the time. You'd have to choose to go in and look at them.

Is it worth talking to your midwife about how anxious this has made you feel in general? There might be some kind of support on offer there.

www.facebook.com/groups/35507179052

Congratulations on your pregnancy

To Be honest everyone I know in my RMC group who had karyotyping testing all came back normal with no issues. To actually find something wrong is incredibly incredibly rare and the doctors are right in that most miscarriages are purely just bad luck. Whilst your karyotype will most likely come back normal individually you can still have a miscarriage due to chromosome abnormalities because it's the interaction of both you and your partners dna and there is no advance test for that (even PGS testing in IVF isn't 100% accurate) - that's why I wouldn't test. Even if say one of you had a balanced or unbalanced translocation not every child you then create together is guaranteed to have it

You've had the NIPT and it's come back clear so I would rely on that more than anything

Thanks @JaiPow, I read tons about recurrent MC and am very aware. I said we had all other tests already which came back clear, with the exception for NK Cells tests which I still want to have at some point in the future and I'm already under specialist care in Coventry.

The concern isn't about another MC now at 26 weeks, as I've explained above, but about my son. I feel they were under-cautious (or rather negligent) in not inviting me for this test sooner, rather than over-cautious.

@BertieBotts Thanks lovely. I will save this but won't be joining yet. I have such a massive fear of amnio that I don't think I can go ahead with these tests. I know if they find a balanced translocation in one of us, I will want to know the full story, but I can't do this to my son if he's heslthy. I'd never, ever forgive myself if I was in this very unlucky group that suffers from loss post-amnio. I know it's extremely rare but it does happen and after losing 3 babies, I honestly would rather die myself than cause anything that increases the risk of losing him now even in the slightest. I just can't do it.

So I think I'm going to have to go through this uncertainty, somehow. No idea how because whilst up until Friday, this pregnancy was flying by and I was worried about getting everything ready quickly enough for his arrival, now every minute feels heavy and dragging and his every kick is bringing me to tears.

I'll have to speak to the MW because I can't go on. Thing is I had no consistent MW care so they don't really get me IYSWIM, plus the most recent one is from the old school of "fob them off as much as you can", so I think she'll just tell me to stop worrying because of X,Y,Z over the phone and this will be it. xx

@ivfgottwins Yes, a MC can beca result of a chromosomal issue unrelated to DH and my genetics. This can be identified after the event through genetic testing of baby. I had it done after my last loss, but like I said, it was inconclusive, meaning that it could have happened for any reason. Had it returned with a chromosomal issue, I would have been much calmer as it would likely indicate there are no genetic issues in either of us. But unfortunately that's not the case.

I know half of the children will be fine even if one of us has a translocation. But a quarter is lost to MC, and another quarter will be born sleeping, die young or be severely disabled. We are post-risk of MC, so for us the odds are effectively we still have that 25% risk at least if one of us has a translocation. This really worries me. xx

I wish they just did this test months ago or never called now until I give birth. This is the worst situation of al and very unfair.

I keep telling myself that every pregnancy can effectively have one of the four outcomes that are applicable in case of a translocation. I know most people never find out they even have it till later in life because it doesn't cause anyone any issues. I know.

But now I also know that we may be at increased risk of it which can create risk to my boy and I can't stop worrying about him. I suppose maybe if didn't have anyone in the family with similar history to mine, maybe I'd feel better, but my mum's history is so close and it's hard not to think there's a connection here. xx

@PurplePansy05 I would echo pretty much everything @BertieBotts has said. And also agree with @JaiPow and @ivfgottwins. Sometimes we can drive ourselves absolutely mad with what is unknown.

I agree asking for targeted/detailed ultrasound may help inform and hopefully reassure you too!

My experience of support groups where people have faced similar challenges, is it does give you so much information and shows how limited our understanding/research is. Often medical professionals are giving you worst case scenarios as a norm, but the realities for those living it, are very different. However I agree if it is something you are likely to become fixated upon and stress about more, then now may not be the right time.

As I’ve said, I know our experiences are very different in some respects, but if I can support at all, I am here xx.

Having seen your messages, I also agree the timing is really unfair. Hope you’re doing ok today xx

That is exactly how I felt about amnio as well. I felt like I should but I really didn't want to. Also a risk of around 1% sounded incredibly high next to the odds we were discussing which was something like 1 in 10,000 (for a specific abnormality which is severe enough to affect life but not visible on ultrasound).

I am so so glad we decided not to. And that's why we didn't opt for one this time around, even though we were offered it much earlier. It just seemed crazy to us to opt for an invasive procedure.

It's not quite the odds of 25% miscarriage / 25% born with disability - that's not been explained well to you. There's a 50% (ish) chance of creating an unbalanced embryo, but your individual odds of how many of that 50% would get to full term is completely different based on the person, and it's almost never as high as half of them - and when it is, normally the first you would hear of the possibility of translocation would be the birth of a disabled child, it would not normally be recurrent miscarriage. It's my guess that for DH for example, almost all of that 50% would result in an early miscarriage, some even before implantation, as our pattern is 6 week losses or massive gaps where we apparently don't conceive despite having periods where we conceive very quickly. If you have "big breaks" which means the chromosome is split very close to the middle of the X, causing a large loss of material when the "wrong" one is inherited, then these are normally incompatible with life and would not develop very far in the womb. The problem comes if you have the break very close to the end of the chromosome and therefore only a very small amount of genetic material would be missing - this can cause the body to "not notice" (it's not really as conscious as that) and not interrupt development.

I always think of it a bit like an ikea flatpack - if you had two boxes and two parts were swapped between the boxes, this is absolutely fine and you can still build the cupboard. But if you're building a cupboard and there's a huge part wrong like perhaps you have two doors and no cupboard back, it's simply not going to work and you'd realise very quickly and take it back to the shop - in embryo terms if there is something major duplicated/missing and the baby can't develop a nervous system or a heart or something, then it's just going to stop development there and that's when you'll have a miscarriage. But if your ikea part that's missing is something like a handle, then you might well not notice until the end and you might even think oh I can't be bothered to return the whole thing, and just live with the cupboard without a handle. That's the equivalent of an embryo that has all the right major parts, and development is not stopped but there is a (relatively) small problem in the brain which causes issues with language development after birth or causes seizures for example.

But the vast majority of conditions which are survivable have some physical markers, particularly by the 20 week scan. Even if 25% of embryos are being produced with a survivable-but-difficult genetic condition (and as I said this is an extremely high estimate, it doesn't usually split down the middle like that) it's absolutely definitely not the case that 25% of them would be undetectable until birth. And without having karyotyped you, there is no way anybody would be able to break down the unbalanced 50% into survivable / not survivable (past early pregnancy) anyway; often they are reluctant to do this even when there is a diagnosis (which is why the group is good to see what others' experiences are).

Also if you look at your history so far, you have 75% loss and 25% unknown but probably healthy pregnancy - that's really unlikely to be indicative of 50% healthy, 25% early miscarriage, 25% born with disability. It just doesn't add up/break down that way, even though the numbers are small. So I'd guess you are more likely in the category of 50% healthy, close to 50% severe problems that would miscarry early, and a tiny (much less than 1%) percentage chance to carry any baby with severe problems to term. Or as IVF says the previous losses weren't actually caused by any translocation anyway and were caused by some other issue.

But in any case the chances are NOT 25% that this baby has a severe disability, even if one of you definitely has a translocation. If that was the case, they would be urgently and strongly recommending an immediate amnio. Anything even approaching 0.2% and they do. If it was as high as 25% you'd be under enormous pressure to have it simply for the information, whether you would consider TFMR or not. The fact they are only offering it and aren't actually pushing it suggests to me that your risk is much, much lower than 1% and therefore amnio would introduce a much higher risk than it rules out.

Having said the above, I also think it is important to not be put off amniocentesis due to miscarriage risk alone if that is a factor.

I had asked for the procedure myself (at that point was told by professionals they were 99% sure baby was “incompatible with life” as rapid CVS had concluded Edwards).

The consultant highlighted that they give dated figures based on old technology and without control groups (amniocentesis and CVS is usually undertaken in higher risk groups deemed at higher risk of loss).

Most recent research indicates miscarriage risk from invasive procedures is negligible. But having said that if it still feels wrong, then absolutely trust your instincts.

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

It’s worrying, but I don’t think there was necessarily a problem with the information provided by your healthcare care provider.

Information on these tests is publicly available. Only a small proportion of people have the genetic issues tested for, even amongst the population of couples experiencing recurrent MC.

Even for those who do have things like ‘translocation’ the costly IVF/selection procedure isn’t necessarily recommended over ‘ordinary’ TTC.

‘Kareotyping’ for you and your DP is a blood test, so isn’t invasive.

When pregnant after MCs I became v anxious and upset, and found counselling really helpful for that.

Thanks @BertieBotts, that's put my mind at ease actually although it is all very complicated, isn't it. I'm going to have to re-read what you wrote as my brain is in such a state now.

I think I'll have to speak to my consultant and probably to the genetics team, but I know they won't give me our personal odds without any testing. But maybe they will be able to explain what the risks are of baby being born sleeping or severely affected that wouldn't be identifiable on scans or via NIPT before. That would help me.

I will also ask for a high detail scan, I think that's the very least they can do for me now tbh and I'll battle for it.

I think because I had so many bad experiences with the NHS, I have no trust they wrote to me now because the risk is low. I think they've genuinely missed me. The geneticist told me on the phone they didn't see my patient record and didn't know I was pregnant (!). They also send the letter out to my old address even though I updated my records immediately after the move, over 2 months ago. The letter arrived delayed by a week and only through the fact that I've set up post redirection. So I have no doubt they have no bloody idea about my history and it's not a good sign. This will be a big part of my complaint. xx