Mosaic embryos – they sound very exotic. But what exactly are they? Alka Goyal, PhD, HCLD/CC is the Director of Laboratories at GENESIS. Read on for her explanation and what it could mean for you.

Genetic Testing

Over the years PGT- A (preimplantation genetic testing for aneuploidy) has been seen to improve pregnancy outcomes in couples going through IVF.  It involves removing a sample of cells (biopsy) from the part of the embryo that makes the placenta (trophectoderm). The sample is then tested to determine the genetic health of the embryo. The test results help in the selection of the embryo which would have the highest chance for a normal pregnancy.

Up until recently the result would either show that the embryo was euploid (normal) or aneuploid (abnormal). Euploid embryos are normal embryos as they have the correct number of chromosomes. They are less likely to be rejected by the uterus and have a higher likelihood of resulting in a pregnancy. On the other hand, aneuploid embryos are abnormal. They have an incorrect number of chromosomes and are less likely to implant.

However the development of newer and more sensitive techniques like NGS (Next Generation sequencing) has led to a third category of results, which are mosaic embryos.

Mosaic embryos have a mixture of both abnormal and normal cells in the embryo in different proportions. In aneuploid embryos the abnormalities originate from the sperm or the egg and occur before fertilization. However in mosaic embryos the abnormalities develop after fertilization during cell division and growth of the embryo.

How common are Mosaic embryos?

Mosaic embryos are not a new phenomenon. It is estimated that roughly 20% of all embryos are mosaic in nature. However, earlier technology was unable to detect them with such precision, sensitivity and reliability.

NGS is such a sensitive and powerful technique that it has the capability of detecting the percentage of mosaicism and quantifying its level. Embryos are categorized as low level or high level mosaics depending on the percentage of abnormal cells present in the biopsy sample.

The challenge to physicians is how to interpret these results and counsel the patient about whether they are transfer worthy.

Although the origin of mosaicism is mitotic – that is, a mutation occurs during cell division during the growth of the embryos – there have been various other theories, too. These include statistical variation, amplification bias, contamination, variation in biopsy techniques, stimulation protocols and lab conditions.

What happens if you transfer a mosaic embryo?

A recently published study of 1,000 mosaic embryos transfers, found that those that progressed to a late-term pregnancy and full term birth had similar odds of being born without any discernible genetic differences as normal embryos.

There is not enough data regarding the health of the pregnancies and children born after the transfer of embryos with mosaic results. However, the data seem to be reassuring. Embryos have either failed to implant, or have miscarried, or have resulted in a live birth with no apparent abnormal phenotype. This has led to an acceptance by physicians of transferring mosaic embryos in the hope that the mosaic diagnosis is either due to an analytical error, that the embryo will self-correct, fail to implant or miscarry in case something is grossly wrong.

In some cases, doctors believe those abnormal cells can self-correct or be pushed to the placenta, leaving the embryo healthy.

Low level mosaic embryos have a higher implantation rate according to some studies. However, a committee of the American Society for Reproductive Medicine found earlier this year that they didn’t have enough information to form an opinion on what percentage of normal cells is needed to be recommended for use. Thus, there is no evidence based classification system for prioritizing embryos.

However this data has limitations as mosaicism may go unrecognized in the neonatal period. There have been no formal studies to evaluate or document the health of the newborns once delivery has occurred.

For patients with no remaining euploid embryos, consideration may be given to the transfer of a low level mosaic embryo after a consultation with a genetic counselor. At this time, we are not transferring high level mosaic or abnormal embryos. This is because of their increased risk of possible birth disorders and miscarriage, along with a lower implantation rate. However a low level mosaic embryo transfer will be considered in special circumstances, after a consult with your physician and a genetic counselor.

References:

Science Direct

Original post September 20, 2021
Updated July 22, 2023