Genetic screening revealed widespread mosaicism in human early embryos

Abstract Pre-implantation Genetic Testing for Aneuploidy (PGT-A) is widely used in half of in vitro fertilization (IVF) cycles, leading to the unwarranted disposal of embryos with pregnancy potential. Due to the limited understanding of genetics of human embryo, current PGT-A is built on biologically uncertain assumptions and on unvalidated guidelines1. Here, we sequenced all single cells (1,072) from 20 human blastocysts and analyzed 13,897 single cells from post-implantation embryos as well as fetal organs. Unexpectedly, all blastocysts contained mitotic aneuploid cells and showed about 25% aneuploidy rate per embryo. Among the 20 blastocysts, 70% (14/20) contained chromosome ‘complementary’ cells, suggesting the possible underestimation of mosaicism in traditional PGT-A. All the post-implantation embryos and fetal organs were mosaic, and over 80% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings showed all human embryos are naturally aneuploid-mosaic and this may provide guidance to the implementation of PGT-A in clinical practice.