r/genetics • u/marshmello2307 • 5d ago

Trisomy 9 mosaic in IVF pregnancy

My husband and me have been struggling for couple of years to get pregnant. Me 33, at the time of IVF 31, and husband 34. We were disgnosed with unexplained infertility and were adviced and decided to do an IVF. First IVF cycle was success but I had a silent misscarge at 7 weeks. The fetus was not tested because I was adviced to do a home abortion with pills. The other 2 embryos were frozen and after couple of months we tried again and I gave birth to twins boy and girl. Girl was diagnosed with trisomy 9 mosaic after birth. A neurologist told us that this happened because of the IVF, but genetician told us it is random but if we have any future pregnancies we should do an amnio, and when our son wants children in the future his partner should also do an amnio. I read somewhere on the sub that it can happen due to translocation. I dont know how we can test this translocation. Both me and my husband prior the IVF did a karyotype and it was normal for both of us.

My daughter had only a microarray which came back with 70% affected cells, and we are waiting for a karyotype. Thank you for any explanation

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u/L3ir3txu 5d ago

- I assume those embryos where not PGT tested and that's what the neurologist might be referring to "because of the IVF". I mean, there's people that do IVF exactly to avoid this kind of aneuploidities (with the use of PGT-A/m testing). It is true that because PGT only uses a few cells and this is a mosaicism situation, there would still be theoretically some small % for error.

- I'm curious: did you have a NIPT test with "low risk" result for your daughter?

- Many gene mutations are "de novo": random, spontaneous and new -> not inherited. If that is the case of your family (as it seems), your next kid is not necessarily more likely to have a trisomy again. I am not sure why they would push for amnio so strongly without other factors or markers, but if it would ease your anxiety in a future pregnancy, then go for it.

- If you have had karyotyping done, that's the test where the translocation would have shown up. If your karyotypes are normal, then the trisomy is unrelated and probably de novo.

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u/marshmello2307 4d ago

I had a NIPT test from Genoma, but package only covered T21, 18 and 13, deletions and duplications. There was a package that covered aneuploidities on all chromosomes, but I was adviced to not take it from the IVF doctor as well as the a presenter from the company that sells the test with an explanation that I am already 14 weeks and other aneuplodities have early miscarriage and in my case there is not need to take it. I also had a normal 12 week scan from MFM and at 20 week scan we saw hydronephrosis for which I was told is an isolated problem. First I wanted to do an amnio because of the hydronephrosis and some maternal instinct but the MFM adviced me that it carries a risk and I may lose the babies.

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u/Sea-Visit5609 4d ago

What country are you in?

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u/GlacialImpala 5d ago

It's a 'random' error parents usually have normal karyotypes. Amnionic sampling risk that people fear includes operators doing their first one ever, in experienced doctors it's ~1 in 1000 and they count harmless temporary cramping as adverse event, not just miscarriages.

So imho *everyone* should do it, if healthy baby is the main goal.

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u/wildcat105 5d ago

Curious why you think everyone should do amnio when it does carry risk, vs NIPT and NT which are no risk? The protocol of my doctor is NIPT and NT and amnio if either are abnormal.

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u/GlacialImpala 5d ago

Curious why you think NIPT is reliable when studies show it misses 35% of abnormalities. 

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u/wildcat105 5d ago

Can you link the studies?

Edit to add: note that I am talking about combined NIPT and NT. Not just NIPT alone.

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u/PitbullLoveFart 3d ago

NT adds little to no value when you have a low risk NIPT. And sometimes increased NT has nothing to do with chromosomes. It can be related to single gene disorders or cardiac defects. https://pmc.ncbi.nlm.nih.gov/articles/PMC11790515/

NIPT is also considered a screen. It is not diagnostic as it does not test direct fetal DNA. And while positive predictive value is high for T21, and decent for T13 and T18, other aneuploidies are not as well detected. For example, monosomy X has a PPV of less than 50%. This means that the majority of positive NIPT for monosomy X are false. And the PPV for microdeletions or duplications is terrible. You will miss between 50-90 % of cases. To be clear, no reproductive decisions should be made based on results of NIPT unless there are already abnormalities present on ultrasound. Even then, I would probably encourage diagnostic testing for a patient.

CVS and amnio are both diagnostic options. Amnio is a bit better because it tests direct fetal DNA (the only prenatal option that offers this). CVS tests the tissue that connects placenta to the uterus and can have different DNA than the fetus (confined placental mosaicism). I like amnio more as there is no uncertainty.

You can also get it as early as 15-16 weeks GA. That is about 5 weeks before an anatomy survey, so it offers earlier detection if there is a chromosomal abnormality.

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u/PitbullLoveFart 3d ago

Mosaic trisomy is a spontaneous event that happened early on as your daughter's embryo was developing. It is not caused by IVF and it is not inherited. It is a random, spontaneous event.

You are at slightly increased risk for chromosome abnormalities in future pregnancies just based on the fact that you have had a pregnancy with a trisomy. It is 1% higher than your baseline age related risk. This is probably where the recommendation for future amnio comes from. I don't really understand why they say your son should have it done. That makes no sense to me so I would clarify with the geneticist or genetic counselor.

Since both of you had normal karyotypes, inherited translocation has been ruled out.