Combined SNP parental haplotyping and intensity analysis identifies meiotic and mitotic aneuploidies and frequent segmental aneuploidies in preimplantation human embryos

Abstract Genome-wide single nucleotide polymorphism (SNP) genotyping using microarrays and karyomapping (parental haplotyping) is a universal linkage-based method for preimplantation genetic testing of monogenic disease (PGT-M) and identification of chromosome aneuploidies, including meiotic trisomies, monosomies and deletions. Following IVF, embryos are biopsied at the blastocyst stage and several trophectoderm cells removed. Both parents, a close relative of known disease status and the biopsy samples are genotyped and parental haplotypes analysed. Here we extended the method by combining parental haplotyping with SNP intensity analysis. This enables identification of meiotic and mitotic, whole and segmental aneuploidies at high resolution. In 342 cycles of PGT-M in couples with a mean maternal age of 32.9±4.2 (SD), 37% (471/1270) of the biopsy samples were identified as aneuploid with an almost equal number of meiotic and mitotic aneuploidies. Meiotic aneuploidies were predominantly whole chromosome aneuploidies of maternal origin and increased with maternal age. Mitotic aneuploidies (with normal parental haplotype patterns) were mainly segmental imbalances. For PGT of aneuploidies (PGT-A) in infertile couples, identifying meiotic aneuploidies, which are almost all non-viable, provides a valuable option to avoid the discard of embryos with only mitotic aneuploidies of unknown clinical outcome.