Chromosomal mosaicism throughout human preimplantation development in vitro: incidence, type, and relevance to embryo outcome

TLDR

Chromosomal mosaicism is common in in‑vitro fertilized embryos, with many cleavage‑stage embryos containing both normal and abnormal cells. The study aimed to map mosaicism across cleavage stages and assess its impact on preimplantation development. Researchers analyzed 216 normally fertilized embryos using multi‑colour FISH probes for nine chromosomes to detect chromosomal abnormalities. Mosaicism was found in 48.1% of embryos, increasing from 15.2% at 2–4 cells to 58.1% at morula and reaching 90.9% at blastocyst (mostly diploid/polyploid), with arrested mosaics exhibiting more chaotic abnormalities and higher abnormal cell proportions, suggesting that extensive chromosomal imbalances hinder blastocyst formation.

Abstract

BACKGROUND: A large percentage of in-vitro generated cleavage stage human embryos are chromosomally mosaic, consisting of both normal (diploid) and abnormal (non-diploid) cells. The present study characterized mosaicism at each stage of cleavage division and examined its effect on preimplantation development in vitro. METHODS: A total of 216 normally fertilized (two-pronucleate) embryos which were not selected for transfer to the patients were analysed for chromosomal abnormalities using multi-colour fluorescence in-situ hybridization DNA probes specific for three to five of nine different chromosomes (X, Y, 2, 7, 13, 16, 18, 21, 22). RESULTS: Overall, 48.1% of embryos were mosaic. The frequency of mosaic embryos increased from 15.2 to 49.4 to 58.1%, from the 2–4-cell to 5–8-cell to morula stages respectively, and the types of non-diploid cells detected were mostly aneuploid or chaotic. The incidence of mosaicism at the blastocyst stage was 90.9%; however, most of the mosaicism comprised diploid and polyploid cells. Arrested mosaic embryos had a higher incidence of chaotic abnormalities, and higher proportions of abnormal cells compared with the non-arrested group. CONCLUSIONS: Post-zygotic errors leading to mosaicism may occur, and persist throughout preimplantation development in vitro. Our results suggest that mosaicism involving multiple chromosomal imbalances and/or imbalances affecting a high proportion of cells in an embryo appear to impair development to the blastocyst stage.