Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro

TLDR

The study used FISH on a single nucleated cell from 143 day‑3 embryos to detect aneuploidy of chromosomes X, Y, 13, 16, 18, and 21. Half of the day‑3 embryos were aneuploid, and these were less likely to reach the blastocyst stage (59 % vs 34 % for euploid), yet 40 % of resulting blastocysts remained aneuploid with a high incidence of mosaicism in the inner cell mass, showing strong concordance for trisomies and complex abnormalities but weaker concordance for monosomies and haploidy, and an increased proportion of ICM cells in haploid or complex cases.

Abstract

In all, 143 human embryos obtained 3 days (day 3) after insemination or intracytoplasmic sperm injection (ICSI) were biopsied and a single nucleated cell removed for identification of aneuploidy by fluorescent in-situ hybridization (FISH) for chromosomes X, Y, 13, 16, 18 and 21. Fifty-one per cent of embryos were aneuploid and significantly more aneuploid embryos blocked in further development to morulae and blastocysts than euploid embryos (59 versus 34%; P < 0.001). Chromosomal analysis of the generated blastocysts revealed 40% were aneuploid (16 of 40 generated blastocysts). Re-examination of cells by FISH for the same chromosome probes of the inner cell mass (ICM) of expanded and hatching blastocysts derived from the aneuploid embryos revealed a high incidence of mosaicism of ICM cell lineages that were usually predictable from observations of day 3 single-cell biopsies. These data would not support the hypothesis of a preferential allocation of euploid cells to the ICM and aneuploid cells to the trophectoderm. A high concordance between day 3 aneuploidy diagnosis and ICM cell lineages was observed with trisomies (97%), and multiple complex chromosome numerical abnormalities (100%). A reduced concordance was observed with monosomies (65%) and haploidy (18%). Concomitantly, the proportion of ICM cell lineages was increased in blastocysts whose chromosomal condition was diagnosed as haploid (21%) or with complex numerical abnormalities (50%).