Abstract
Triploid and haploid conceptions are not viable and are a common occurrence in humans, where they account for 10% of all pregnancy losses. Despite the parent of origin being important in the etiology of the pregnancy, our knowledge of their causes is limited, especially at the point of conception. Using a dataset of 96,660 biopsies and a validation dataset of 44,324 from human blastocyst embryos generated by intracytoplasmic sperm injection, we estimate that 1.1% of human conceptions (n = 1,063) contain extra or missing chromosome sets in zygotes. In our cohort of intracytoplasmic-sperm-injection-derived embryos, where the risk of polyspermy is inherently lower compared to natural conception, we identify for the first time a maternal age effect, with a 1.046-per-year increased risk in triploidy/haploidy (p < 0.001). In 0.03% of couples, we identified three or more triploid/haploid embryos, suggesting a personal risk effect (p = 0.03). Genotype analysis of 41 triploid embryo biopsies and their parents shows that around one-third of maternal triploid conceptions originate in meiosis I and two-thirds in meiosis II. Seven of these embryos are inferred to have entirely failed to initiate meiotic recombination genome wide, a surprising finding suggesting that human oocytes with pervasive meiotic recombination failure that are formed during fetal development are capable of ovulation in adult life. Finally, we identify a type of genome-wide maternal isodiploidy (two maternal chromosome sets) in 0.05% of embryos (41/74,009). Collectively, our findings shed light on the biology of meiosis and the formation of human oocytes with the number of chromosome sets.