Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage

TLDR

Previous studies have demonstrated that aneuploidy in human embryos is surprisingly frequent, with 50–80 % of cleavage‑stage embryos carrying abnormal chromosome numbers. The study aims to determine whether blastomere behavior during the first two cleavage divisions reflects embryo ploidy. The authors used non‑invasive time‑lapse imaging together with karyotypic reconstruction of all blastomeres in four‑cell embryos. They found that euploid embryos exhibit precise cell‑cycle timing to the four‑cell stage, whereas only 30 % of aneuploid embryos fall within normal timing windows, and that blastomere cycle and fragmentation parameters can diagnose ploidy, enabling automated tracking and potentially reducing transfer of embryos prone to miscarriage.

Abstract

Previous studies have demonstrated that aneuploidy in human embryos is surprisingly frequent with 50-80% of cleavage-stage human embryos carrying an abnormal chromosome number. Here we combine non-invasive time-lapse imaging with karyotypic reconstruction of all blastomeres in four-cell human embryos to address the hypothesis that blastomere behaviour may reflect ploidy during the first two cleavage divisions. We demonstrate that precise cell cycle parameter timing is observed in all euploid embryos to the four-cell stage, whereas only 30% of aneuploid embryos exhibit parameter values within normal timing windows. Further, we observe that the generation of human embryonic aneuploidy is complex with contribution from chromosome-containing fragments/micronuclei that frequently emerge and may persist or become reabsorbed during interphase. These findings suggest that cell cycle and fragmentation parameters of individual blastomeres are diagnostic of ploidy, amenable to automated tracking algorithms, and likely of clinical relevance in reducing transfer of embryos prone to miscarriage.