Chromosomal mosaicism in human blastocysts: the ultimate challenge of preimplantation genetic testing?

AbstractSTUDY QUESTIONTo what extent does a trophectoderm (TE) biopsy reliably reflect the chromosomal constitution of the inner cell mass (ICM) in human blastocysts?SUMMARY ANSWERConcordance between TE and ICM was established in 62.1% of the embryos analysed.WHAT IS KNOWN ALREADYNext generation sequencing (NGS) platforms have recently been optimised for preimplantation genetic testing for aneuploidies (PGT-A). However, higher sensitivity has led to an increase in reports of chromosomal mosaicism within a single TE biopsy. This has raised substantial controversy surrounding the prevalence of mosaicism in human blastocysts and the clinical implications of heterogeneity between the TE and ICM.STUDY DESIGN, SIZE, DURATIONTo define the distribution and rate of mosaicism in human blastocysts, we assessed chromosomal profiles of the ICM and multiple TE portions obtained from the same embryo. We evaluated donated embryos with an unknown chromosomal profile (n = 34), as well as PGT-A blastocysts, previously diagnosed as abnormal or mosaic (n = 24). Our intra-embryo comparison included a total of 232 samples, obtained from 58 embryos.PARTICIPANTS/MATERIALS, SETTING, METHODSFour embryo samples, including the ICM and three distinct TE portions, were acquired from good quality blastocysts by micromanipulation. Whole genome amplification (WGA), followed by NGS was performed on all embryo segments. Profiles were compared between samples from the same embryo, while the results from preteste...
Source: Human Reproduction - Category: Reproduction Medicine Source Type: research