{"doi":"10.1016/j.ajhg.2025.09.014","title":"Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans","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.","journal":"The American Journal of Human Genetics","year":2025,"id":535040,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9383,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991662,"name":"Christian S. 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Whitehead","orcid":null,"position":10,"is_corresponding":false},{"id":1418187,"name":"Pavan Gill","orcid":"0000-0001-8545-1713","position":11,"is_corresponding":false},{"id":1418644,"name":"Emily Mounts","orcid":null,"position":12,"is_corresponding":false},{"id":1418188,"name":"D Babariya","orcid":"0000-0002-8263-0502","position":13,"is_corresponding":false},{"id":1418189,"name":"Laura Rienzi","orcid":"0000-0001-8104-3958","position":14,"is_corresponding":false},{"id":1418190,"name":"Filippo Maria Ubaldi","orcid":"0000-0002-6894-2147","position":15,"is_corresponding":false},{"id":584770,"name":"Juan A. García-Velasco","orcid":"0000-0003-1005-8727","position":16,"is_corresponding":false},{"id":1418191,"name":"António Pellicer","orcid":"0000-0002-8254-863X","position":17,"is_corresponding":false},{"id":289878,"name":"Shai Carmi","orcid":"0000-0002-0188-2610","position":18,"is_corresponding":false},{"id":57605,"name":"Eva R. 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