Down’s syndrome diagnosis after PGT-A testing - any experience?

[Claire12098]

Hello, after ivf I am currently in a living nightmare of having received the highest possible risk score on the combined test for T21 (greater than 1 in 2), despite my embryo being PGT-A tested and coming back normal. NT was normal but HcG was off the scale high and papp-a was low. I had convinced myself that this was just the screening false positive and was age related (just turned 40 when eggs were collected) as I could find no examples of this on any forum, however many times I searched.
However, last Friday I was devastated to learn that the nipt came back as high chance too. Today, at nearly 15 weeks, I will have cvs but seems like that is just confirmatory as it’s now something like 90-95% likely that the baby has it. I just can’t get my head around how this could be happening - I know pgta is not 100% but it’s something like 98% accurate. All I keep finding is posts where people are using pgta to avoid exactly this and others which say how rare it is for nipt to contradict a pgta test. A long shot, but has anyone had this happen to them? Also wanted to post this for balance for people considering pgta in future.

I came here for advice too when pregnant and when you say people should not be shamed you are right; so imagine how I felt reading all these uneducated comments

@yarnmum i didn’t read the comment as against Down’s syndrome, but the wouldn’t wish it on my worst enemy was in regard to the waiting for NIPT or amnio results when you know there is something wrong. Waiting to find out if your baby already has a death sentence and won’t make it to birth. My friend had a baby with Down’s syndrome, and was positive and announced it to the world but he was so sick he didn’t even make it to birth.
I am also in the camp of waiting for test results, we wouldn’t terminate for a downs diagnosis that doesn’t look incompatible with life but would for other terminal diagnosis. The waiting really is the worst thing, and something I would describe as a previous poster when it’s your one and only shot at a child after remortgaging and years of infertility and not the inability to just have more sex. This thread was for supporting those who’ve gone through PGTA and then NIPT. I have had 2 friends who have had a TFMR (not downs) and seeing what they’ve gone through I really would describe it as the previous poster described. Just unimaginable.

Ahh I see. Well that is just one reference to once case. My child is perfectly healthy and so are many many children who have Trisomy 21. Lets put it this way... if you had a child and someone described the anticipation of having a child like yours as unimaginable. Not very nice really is it. If anyone is desperate enough for a child then the child should be loved regardless. There is no such thing as a "perfect" child. Plus you can not screen or test for invisible disabilities either such as autism, adhd etc. What would happen then??? I think some research into T21 needs to be done by some people definitely

Having a child with T21 is not awful and finding out you are having a child with T21 should not be anything awful . Ways of thinking needs to be changed and these views not reinforced as there is nothing awful about it.

My DM worked with DS babies and children and thought they were the most lovely affectionate children (and they can have perfectly normal IQ). She definitely wouldn't have minded having a DS child and definitely found them a blessing.

They really are the best. It is so sad to read comments from people thinking they are not healthy, or it is a bad thing to have a baby with DS. I think views are from the medieval times; I really wish hospitals would re-educate people on what a blessing people with DS are. I feel like I have won the lottery with my child and can not believe how lucky we are

What a fascinating thread @Claire12098 and congratulations on your happy ending.

Is this a form of mosaic T21, where all the T21 cells were in the placenta? Will you have to have further tests to see whether your little boy carries any T21 cells?

I’m so glad that your little one is earthside and well, you mentioned it was your fourth child. These ladies have been through IVF & are desperate to bring any baby home and most have already suffered miscarriages along the way. No one makes this decision lightly.

Sadly some babies with T21 have comorbidities that are incompatible with life and waiting to find out if your baby is going to die really is agony.

You say on your previous post “I completely get this is just my experience and other people may not feel the same or able or in a position to continue.” Perhaps it’s worth reflecting on that again.

Please do not twist my words. I know what I said and stick by it. I am definitely pro choice. But... the use of language within this thread by posters is very outdated, offensive and upsetting to the parents of children with T21 as if their children are not worthy of life. I think the use of language and a bit of education really needs to be handled with care here and correct information provide rather than putting fear into everyone over T21 like it is a death sentence. Whilst some babies with T21 may have health problems.... so will many many other children who dont have T21

I’m sorry you feel that way, and I wish you the best of luck with your child.

I'm wondering if anyone has correlated high HCG or low PAPP-A with IVF pregnancies.

I'm currently waiting the results of my NIPT following high risk for downs.

NT 1.6mm
PAPP-A 0.52
HCG 3.31
Age 34

My pregnancy is a result of a frozen embryo transfer.

There are lots of research papers on the effect of IVF on HCG (raised values) and PAPP-A (lowered values).

Some organisations/researchers have suggested that NHS should update the data used to calculate MoM for IVF pregnancies but for some reason that has never happened. However, it is pretty well established that False Positives from the combined screening are much more likely for IVF.

Here are links to a few papers, but there are lots:

https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/uog.6254

https://pubmed.ncbi.nlm.nih.gov/19115229/

@Goldfinchesjourney thank you. This is very interesting.

When I asked the screening nurse who took my NIPT blood if IVF could have anything to do with my results, she simply said 'no'.

Like everyone in this position, the wait for results is absolutely awful :(

@crimpdad It is really frustrating as everyone knows that IVF skews the combined screening results but no one will admit it officially or even better update the data.

I don't think IVF affects NIPT results, but with very high (over 1 in 10) combined screening results NIPT is less accurate and more likely to give false negatives https://www.gov.uk/government/publications/screening-for-downs-syndrome-edwards-syndrome-and-pataus-syndrome-non-invasive-prenatal-testing-nipt/screening-for-downs-syndrome-edwards-syndrome-and-pataus-syndrome-nipt

I am not sure how IVF fits in with that data which adds in another level of worry.

If you are in the UK and haven't yet talked with ARC I thoroughly recommend giving them a call.

My combined screening result was as high as it gets and I was in complete shock given that we transferred a PGT-A Euploid and ARC really helped me to clear my head and understand the differences between all the tests.

I really hope everything works out for you x

That’s so interesting, I didn’t realise that. When I got my screening results and the NIPT the NHS docs were very skeptical about pgt testing overall and saying it wasn’t worth it.. but I wonder how many pgt tested embryos actually go on to have abnormalities - my clinic said they’d never seen it in years and years

How are you doing @Goldfinchesjourney? have you had the amnio?

@Claire12098 It is booked for Thursday so just a few more days to go, I am just trying to stay calm for now.

I still have a little bit of hope left after endlessly trawling research papers and forums.

I even found a webinar from Coopers Genomics on the evolution of PGT-A and one of their Vice Presidents Tony Gordon this was his quote about PGT-A being wrong in the case of full chromosome abnormalities:

"The thing that we’re really good at, is meiotic aneuploidies. These are full chromosome changes and that’s why we do thousands of these and it’s incredibly rare when somebody rings us up and says, for instance, ‘we have had a miscarriage, and that miscarriage has a genetic trisomy’ and we didn’t see it. So, it has an extremely low false negative. That’s good."

Hi. We’ve experienced similar: my results were:

hCG : 6.31 MoM (yes, insanely high)
papp-a 0.32 (very low)
NT 1.0mm (perfect)

this indicated 1 in 5 chance of Down syndrome. NIPT was positive. CVS postive. Excess fluid on brain and baby measured two weeks behind and more. We TFMR.

@Goldfinchesjourney Hey! how are you doing? Thinking about you, hope amnio went okay?

Thanks @ForCheekyFox.

The amino was tough a they had to do it twice in one sitting due to my anterior placenta and the first needle not being big enough. Our PCR quick results came back clear and then we had the awful 3 week wait for the full Karyotyping, however, the lab screwed up and never did the full test!!!.

Absolutely gutted as we can't (and wouldn't) do another amnio. ARC/NHS England also screwed up and their latest guidance on NIPT in cases of very high risk combined screening results is wrong as they forgot to take in to account the IVF factor so we should have never been told that NIPT wouldn't be accurate for us, and shouldn't have even had the amnio! Our Fertility Clinic had made a formal complaint to the Fetal Medical Council (or society, something like that?) about it and are changing their discharge paperwork to ensure all their patients know the issues of IVF and combined screening!

Our hospital also didn't know that the stored sample from amnio can only be used for a QUICK TEST on just ONE chromosome, not the full Karyotyping as per the paperwork we signed to agree to storing a sample. They only discovered this when they asked for the lab to correct their mistake by karyotyping the stored sample and they have been wrongly telling women it could be fully tested at a later date for years!

Overall it has been a cluster f**k, however baby has flown through all the scans, and looks healthy so that is all that really matters. Just hoping for the rest of the pregnancy to be a bit easier on us and for baby to get here safe and sound.

Ahh, I am so sorry that you had to go through all of that. I think the PCR/FISH results sound reassuring. Hope the rest of your pregnancy goes smoothly!

@Goldfinchesjourney from your understanding, how does IVF affect the combined screening results?

@crimpdad The process of IVF itself lowers PAPP-A and raises B-HCG which unfortunately are two of the main indicators looked for during Combined screening for DS (but not causes of it).

There are lots of research papers on this and in 2008 (I believe) there was talk of the NHS looking in to gathering the statistics required to add in IVF as a factor in the screening itself but that never came to pass. One of the research papers below even states that "...it is appropriate to correct for mode of conception and hence most computer software for prenatal risk calculation is programmed to correct IVF/ICSI with a predefined correction factor. " This is unfortunately not the case in the UK.

In our area IVF and PGTA are not recorded at all in the combined screening notes. I had specifically told our midwife that it was a tested embryo but had not realised that this very important piece of information is not logged anywhere so when we got given our very high result it took me 24 hours to realise that they had no idea baby was from IVF let alone a tested Euploid embryo and therefore at low risk of DS due to PGTA accuracy. Once the screening department was informed of this NIPT was recommended over invasive, but unfortunately ARC's advice was different and led us down the amnio path (which is once again because the latest NHS England advice has failed to recognose that IVF pregnancies skew the CS results).

After months of research I have found zero firsthand, or documented, cases of a PGTA Euploid having a type of DS, including mosaic DS but I did find lots of cases of combined screening being wrong and every expert we talked to agreed that CS is just not accurate for IVF, the false positive rate is over 15% for IVF compared to around 4% for natural pregnancies, but it is the elephant in the room that doesn't seem to be recognised by the NHS.

There are lots of papers about it but here are links to some of them. Hope that helps:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633581/

https://pubmed.ncbi.nlm.nih.gov/31037917/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9878858/

https://academic.oup.com/humupd/article/18/4/350/664636

Thanks, the results and scan have all been very reassuring.

The lack of knowledge within the NHS is shocking, it feels like the info is out there and in one 'book' but they only read one,different, chapter each and have never bothered to ask for the rest of the book to read.

Once again it is a case of them never really bothering to invest in studying the female body which is something we have found the whole way through loss, infertility, IVF and now pregnancy.

I have put it all behind me for now and I am slowly letting excitement creep in after 4 months of awfulness, baby is thriving and that is all I ever cared about x

I know this is an old thread and I really hope everyone is well and babies doing good. So I have had PGT-a testing too and interestingly, after a letter from my IVF clinic to my medical team, they decided not to do the twelve week screening for downs because of the risk of getting a false test result. They felt as the embryo has already been screened, it would be sufficient and prevent stress over false results and invasive procedures. I'm guessing they have to check NT at the ultrasound as it also is a marker for other things - I need to check but have made an assumption came back fine. Thought I'd share my experience.

Gosh, I just read this and now appreciate why my clinic sent this letter to my medical team and grateful my team took it seriously and didn't just follow routine. Gosh how much anxiousness that may have led for people that was unnecessary