69 Parental aneuploidy determines type of chromosome error

Unlike other mammalian species, as women age their oocytes are at high risk for chromosome aneuploidy errors (gain or loss of a chromosome), which are directly associated with reproductive failure. The aim of this study was to explore this phenomenon further and investigate whether the parent of origin has an impact on the type of chromosome error. This was a retrospective analysis of de-identified pre-implantation genetic testing (PGT-A) data that included embryonic origin of aneuploidy screening (n = 66). Aliquots of whole-genome amplified DNA generated from trophectoderm biopsies, alongside parental DNA, were used for SNP analysis using the HumanKaryomap-12 Beadchip (Illumina) to determine origin of aneuploidy and recombination events (n = 455 embryo biopsies). Upon identification of origin of error, statistical analysis was calculated using chi-squared probability distribution to analyse categorical data, with significance at P < 0.05 to elucidate the distribution of the three categories of chromosomes (metacentric: chromosomes 1, 3, 16, 19, 20; subcentric: chromosomes 2, 4–12, 17, 18, X; or acrocentric: chromosomes 13, 14, 15, 21, 22, Y). As expected, a larger proportion of embryo aneuploidy was associated with maternal origin (mean age = 39.2; n = 366; 80%) compared to paternal (mean age = 41; n = 89; 20%; P = 0.0019). Maternally derived aneuploidy was found to be more prevalent in errors from acrocentric chromosomes (meta = 27.6%; sub = 31.4%; acro = 41.0%; P < 0.001). However, most of paternally derived aneuploidy was found in subcentric chromosomes (meta = 13.5%; sub = 65.2%; acro = 21.3%; P < 0.001). Additionally, a reduced number of recombination events was observed in the chromosome of error for both parents of origin (maternally derived = 0.3 events on the maternal chromosome vs 3.4 on the paternal, P < 0.0001; paternally derived = 1.0 events on the paternal chromosome vs 1.5 on the maternal, P = 0.0015). Segmental aneuploidies were found to be largely associated with paternal inheritance compared to those that were maternally derived (28% vs 2%; P < 0.001). Likewise, errors in sex chromosomes were inherited from the paternal sperm gamete with significantly greater frequency than from the oocyte (14.6% vs 2.7%; P < 0.001). This study found that maternally inherited embryonic aneuploidy largely occurred in metacentric chromosomes, whereas paternally derived aneuploidy was more common in the subcentric chromosomes. Additionally, segmental and sex chromosome aneuploidies are almost exclusively derived from the paternal gamete. Further understanding of the mechanisms underlying aneuploidy and how they differ depending on the origin and which parental gametes, could assist in improving reproductive success for infertility patients.