PREIMPLANTATION GENETIC TESTING: Chromosome abnormalities in human embryos

Abstract

Aneuploidy is a frequent event in human embryos, and its incidence is higher in oocytes and embryos from women of advanced maternal age. Aneuploidy may also be a contributing factor in infertile populations, such as couples with recurrent miscarriages, repetitive implantation failure, or male infertility. For these reasons, preimplantation genetic testing for aneuploidy (PGT-A) has been proposed to prevent miscarriages and increase live birth rates in infertile couples undergoing in vitro fertilisation. Next-generation sequencing is currently being applied for the detection of aneuploidies in human embryos, including whole chromosome aneuploidies, segmental aneuploidies, uniform, and mosaic aneuploidies. More recently, this technology has been incorporated for the analysis of the cell-free DNA secreted by the embryo to the culture media. Chromosome abnormalities mostly originate in female meiosis. Recombination between homologous chromosomes is a critical event that occurs in the foetal ovary. The importance of altered recombination pertains to paternally as well as maternally derived trisomies, but as most aneuploidy arises during oogenesis, the female is at greater risk. For males, sperm concentration is associated with a higher risk of aneuploid sperm and thus aneuploid embryos. Mitosis errors can occur at all stages of early embryo development that result in chromosomally distinct cell populations. The clinical impact of mosaicism depends on the mosaicism type, location, and number of aneuploid cells. Transfer of mosaic embryos has been proposed when no euploid embryos are available in the PGT-A cycle.