The genetics of preimplantation embryonic arrest: the role of aneuploidies.

Abstract

Purpose of the review: Aneuploidy is a major cause of embryonic arrest. While meiotic aneuploidies, especially maternal, are a well-documented cause of embryo and fetal arrest, increasing evidence highlights the crucial role played by mitotic aneuploidies. This review explores the molecular and cellular pathways underlying these abnormalities, focusing on abnormal cleavage, chromatin cohesion, spindle stability, maternal effect genes, and mitochondria.

Recent findings: Approximately half of human embryos cease development in vitro or shortly after transfer to the uterus. Genetic investigation of these embryos has highlighted that 90% of these exhibit aneuploidies. Surprisingly, most of these arise from errors during the early mitotic divisions of preimplantation embryos. These findings strongly correlate with disruptions of early cleavage possibly due to faulty spindle assembly or mitochondrial dysfunction during the in-vitro development. Moreover, maternal effects, such as faulty meiotic recombination and variants in maternal effect genes involved in the subcortical maternal complex, may further predispose the embryo to high rates of chromosomal imbalance.

Summary: Meiotic and mitotic aneuploidies play a significant role in embryo arrest, yet their molecular and cellular origin are not well understood. Investigating these pathways may lead to interventions that could be developed to improve success rates with IVF or even fertility rates in general.