Medical Research

What Mosaicism Means for Live Birth Rates

In the past few years some PGS technologies have become capable of detecting mosaicism in embryos -- meaning embryos can be classified not only as normal or abnormal, but also as mosaic, which has represented a grey area in between. There has been debate raging as to what should happen with these embryos if a patient only has mosaic embryos to choose from -- should they be transferred? Would they result in healthy babies? Should we distinguish even further between different types of mosaic embryos when selecting what to transfer?

What’s New


A new study published in Fertility & Sterility gives us more data on the reproductive potential of mosaic embryos overall, going even deeper to show us the potential based on the level of mosaicism detected by PGS. In the study, 77 women who had no euploid embryos available transferred embryos that PGS diagnosed with different levels of mosaicism, and outcomes were tracked against transfers of euploid embryos.

What The Study Showed


When compared to euploid embryos, mosaic embryos had significantly lower live birth rates: mosaics delivered live births 30.8% of the time vs. 46.6% for euploid embryos. While that’s a meaningful difference, it’s important to note that a 30.8% live birth rate is high, especially for a class of embryos that used to be lumped into the “abnormal” category.

Possibly more interesting is that amongst mosaic embryos comprised of mostly normal cells (at least 50% of cells were normal), there was only a small difference in live birth rate compared to euploid embryos -- “low grade” mosaics had a 42.2% live birth rate, while normal embryos had 46.6%. Embryos with a higher percentage of abnormal cells (more than 50% aneuploid) had a much lower 15.2% live birth rate.

Importantly, none of the babies born had evidence of mosaicism at birth.

It’s also worth noting that there was not a meaningful difference in the miscarriage rate for mosaic embryos (whether or not they had high levels of mosaicism) and euploid embryos.

Our Take


Patients undergoing PGS testing should do their best up front to understand how their clinic and lab will report (or not report) mosaic results. There are more details on this in our PGS course. The live birth numbers, particularly for mosaics with less than 50% abnormal cells, are higher than the field had previously hypothesized, and could meaningfully change how PGS results are interpreted and how transfer decisions are made.

Study’s Limitations


While the results of this study are certainly helpful as we come to understand how to handle mosaic embryos, it’s by no means perfect.

Even though the findings were statistically significant, it was still based on a relatively small sample size of 77 women transferring mosaic embryos. And embryos of a different chromosomal makeup than the ones transferred in the study could have different outcomes -- just because all the babies here were born healthy doesn’t mean that all mosaics are safe to transfer. Patients should always meet with a genetics counselor ahead of transfer and consider doing an amniocentesis for diagnosis during pregnancy. Along similar lines, this study does not include a long term follow up on the health of the children born.

Finally, during the first part of this study, cells were analyzed using array-CGH technology, but then they switched to Next Generation Sequencing (NGS) technology. This matters because each technology differs in its ability to detect mosaicism, so you can’t assume that your reference lab uses a technology that an detect mosaicism to the same extent.