Sunday, September 23, 2012

Aneuploidy as a cause of recurrent miscarriage

My RE sent me a study on aneuploidy (=abnormality in chromosome number) as a cause in recurrent pregnancy loss, and it was a fascinating, yet difficult to grasp read, as far as significance went.

They started with this statistic -- the prevalence of fetal aneuploidy in women in sporadic miscarriage (ie have loss(es) interspersed between live births) is around 76%. In women with recurrent loss, it is much lower-- around 50%.  This means that with recurrent loss, there is possibly greater contribution of factors other than a genetic abnormality in the embryo. Yet, fetal chromosmal abnormality still prevails as an important cause---around 50%.

They then subdivided by the patients based on presumed issue, such as as anti-phopholipid syndrome (APS), uterine abnormalities, abnormal karyotype in either partner, hypothyroidism/Diabetes/PCOS and then looked at incidence of fetal chromosomal abnormalities.

As expected, when either parent had a abnormal karyotype, they produced a very high number (over 75%) of aneuploid embryos.The APS and hypothyroidism/Diabetes/PCOS groups held steady with around 50 % of examined embryos being aneuploid. The uterine abnormality group had a much lower percentage of aneuploidy, around 17%.

The point the authors made conclusively- aneuploidy is a significant, but not sole,contributor to pregnancy loss, even of the recurrent variety.  But here is the question I want answered---do certain conditions or gene mutations predispose to a higher rate of aneuploidy?We all know advanced maternal age increases aneuploidy. However, the average age of women in this study was 32 years.  What are the other factors?  Does PCOS, for example, make the mother more prone to producing aneuploid eggs? Or do they just have 2 separate issues (the second of which-- the cause of the aneupolidy) is unknown?

I've done many pubmed searches trying to link issues found in me (such  PCOS, PAI4G and the MTHFR C677T) mutations and increased aneuploidy.  Turns out, there have been people trying to study the same.

The only semi-tangible thing to show up is the folate connection. The MTHFR 1298C mutation (but not the C677T) mutation has a link to an increased incidence of fetal aneuploidy. Interestingly, multiple other studies have reported the same, they see an association with the 1298C but not the C677T mutation and various single chromosome aneuploidies.

Furthermore, many, many studies show that low folate levels increases chromosomal abnormalities in cells of the immune system.  But what about germ (sperm and egg) cells?

A smart study looked at the effect of folate supplementation on aneuploidy in sperm (something that is so easily studied!), and basically found that increased folate intake decreased sperm aneuploidy. 2 important things: folic acid could possibly decrease risk of aneuploidy in eggs as well, and women, make your husbands take that 5 mg dose!

BUT--- whatever the road to it, aneupoidy is a major contributor to pregnancy loss. One statistic that knocked the carpet out under me was the finding that 40% of all IVF-generated embryos (even in younger women) are aneuploid. Is this true even of the natural process?  Is that why so few natural tries end in a clinical pregnancy?

I was recently pointed me to this study by a couple of people (thank you!)---Super-fertility’ may explain some miscarriages, BBC News has reported. It says that the wombs of some women are ‘too good at letting embryos implant’, even those that are of poor quality and so which should be rejected.   

Basically, if you take the assumption that the natural rate of aneuploidy is as high as that in IVF, and combine it with the above study, then, well, that would explain a lot, including what happened with me. Heck, maybe my aneuploidy rate is even higher than 40%, but my uterus is a champ at implanting any and all comers.  Or not. Who the heck knows?


  1. This is so so so interesting to me. Thank you for posting. I feel the same way, my uterine septum problemo, combined with and my ability to now get pregnant very easily puts me in this same exact place. Ugh. One of these times is bound too work again.

  2. Yes, I remember reading something like 60% of all embryos are aneuploid.  And that superfertility study is interesting; completely anecdotally I noticed years ago that many women I knew on SMC boards who had recurrent chemical pregnancies or relatively early miscarriages also got pregnant SUPER easily, like pretty  much every cycle they tried, which is much higher than a statistical average for IUIs.

  3. Who the heck knows is right...I wish there were clear cut answers.

  4. oh Jay, I relish in your gigantic brain and your unquenchable thirst for knowledge. I hope that your searches lead you to the answers you are looking for.
    I found the British study fascinating when I heard of it. The data you share here is also really interesting. 40% seems so high, but that's in women who are doing IVF - i.e. for whom there was a problem to begin with. The rate of m/c in the general population is lower than that, and includes other causes than genetic abnormalities in the embryo.