Preimplantation genetic testing for meiotic aneuploidy in trophectoderm biopsies - is it time to change our approach?

Direct evidence from live cell imaging and single-cell sequencing of disaggregated cells that mitotic abnormalities continue to occur in the trophectoderm at the blastocyst stage, resulting in clones of aneuploid cells, has important implications for preimplantation genetic testing (PGT) for aneuploidies. Here we argue that, to improve accuracy and minimize the deselection of potentially viable embryos with only mitotic aneuploidies of unknown clinical significance, the use of methods that, up until now, have only been used for PGT for monogenic/single-gene defects could provide the answer. Genome-wide single-nucleotide polymorphism parental haplotyping (karyomapping) is a universal linkage-based method for tracking the inheritance of disease genes. However, the same method can be used for molecular karyotyping to identify meiotic trisomies and monosomies or segmental deletions by the presence of dual parental haplotypes, or absence of parental haplotypes, respectively. Combined with parental intensity analysis to detect mitotic aneuploidies with normal biparental inheritance, this allows meiotic and mitotic, whole and segmental chromosome aneuploidies to be identified. This provides the opportunity to prioritize the deselection of embryos with meiotic aneuploidies affecting the whole embryo while considering those with only mitotic aneuploidies for transfer, with appropriate genetic counselling.