Abstract
SummaryChromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.
Highlights
Aneuploidy in human conceptions is the leading cause of embryo implantation failure, pregnancy loss, and congenital disorders in live-born infants
Our findings show that in the majority of cases where mosaicism is detected in TE biopsies, this is due to a few aneuploid cells that originate from the trophectoderm tissue and give rise to a low- to medium-grade mosaicism configuration
Incidence and prevalence of chromosomal mosaicism on blastocyst-stage human embryos To shed light on the incidence and prevalence of chromosomal mosaicism in human preimplantation embryos, we first analyzed a large historical dataset of 6,766 embryos, where a clinical trophectoderm biopsy had been processed with next-generation sequencing (NGS) technology
Summary
Aneuploidy in human conceptions is the leading cause of embryo implantation failure, pregnancy loss, and congenital disorders in live-born infants. Recent large genome-wide non-invasive prenatal screening (NIPS) studies performed at 12 weeks of gestation have shown that the presence of confined placental mosaicism (CPM) explains a significant fraction of falsepositive cases of rare autosomal trisomies (RATs).[4,5] Yet, the prevalence of chromosomal mosaicism in human pregnancies is reported in fewer than 0.3% of prenatal tests (e.g., by amniocentesis or by NIPS).[6] On the basis of experiments in murine models, the sharp drop in mosaicism between pre- and post-implantation stages has been explained by the selective elimination of aneuploid cells through competitive growth of euploid cells or apoptosis of the abnormal cellular clones.[7,8] In humans, the prevalence and developmental potential of mosaic embryos consisting of both diploid and aneuploid cells remain the subject of intense debate.[9] This is largely due to a paucity of studies that have assessed mosaicism across the whole embryo; as a result, our understanding of the distribution of aneuploid cells is limited. One major clinical impact of this shortcoming has been that fewer than 3% of mosaic embryos are being used in in babies born after in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
