Mosaicism in Human Embryos: What Do We Know?

Abstract

Preimplantation Genetic Testing for Aneuploidy (PGT-A) involves performing aneuploidy testing on the small number of cells biopsied from a preimplantation embryo. It is well established that aneuploidy is a common cause of implantation failure and miscarriage. In an ideal world, a measure of the chromosome status of the cells from the embryo would produce a highly specific result that would predict the fate of that embryo. One of the difficulties with PGT-A however, has been putative chromosomal mosaicism present in a proportion of tested embryos. Chromosome mosaicism became more widely reported following the use of Next Generation Sequencing (NGS) as a tool for performing PGT-A. This was due to the higher dynamic range of the NGS profiles that made mosaicism in the trophectoderm biopsy more visible. Around this same time the first study was published that followed the transfer of 18 mosaic embryos, resulting in the birth of six healthy babies (Greco et al 2015). Since then, several publications have described the results of mosaic embryo transfers, including the work by Viotti et al 2021 which summarised the results of transferring 1000 mosaic embryos. These studies have the common theme that a mosaic embryo result does not clearly predict a negative pregnancy outcome, unlike a uniform aneuploid result. However, it may predict a reduced chance of pregnancy, and an increased chance of miscarriage, depending on the type of mosaicism. Reassuringly, a mosaic result in an embryo also does not seem to indicate a higher chance of having a baby with an abnormality than euploid embryos. Chromosomally mosaic embryos should not be discarded and should be considered for use with appropriate counselling of the patients.