Mosaicism: detection and clinical outcomes

Abstract

Introduction It has been proposed that selecting euploid blastocysts to transfer via preimplantation genetic testing for aneuploidy (PGT-A) with the use of comprehensive chromosome screening (CCS) methods, could lead to significant improvements in IVF outcomes. However, questions have been raised related to the implantation potential of mosaic embryos, composed of a mixture of normal and chromosomally abnormal cells. The main aim of this study was to examine the developmental ability of mosaic blastocysts. Materials and methods Blastocysts were biopsied and processed with the use of NGS, followed by frozen embryo transfer. Trophectoderm (TE) biopsies were classified as mosaic if they had 20%–80% abnormal cells. Results Different aneuploidy types, including some complex forms, were capable of persisting to the blastocyst stage. Euploidy rates decreased dramatically with advancing female age, whereas uniform aneuploidy increased. Moreover, the transfer of mosaic diploid aneuploid blastocysts was associated with higher miscarriage and lower implantation rates, compared to embryos in which only euploid cells were detected in the TE biopsy. Conclusions Extensive analysis of the chromosome constitution of human blastocysts suggested that a significant proportion are chromosomally normal in every cell. These findings do not support the notion that mosaic chromosome abnormalities are a natural part of embryo development. Blastocysts with uniform aneuploidy present in the biopsied TE sample and, to a lesser extent, those with mosaic abnormalities were associated with poorer clinical outcomes, compared to euploid embryos.