{"doi":"10.1093/humrep/deac196","title":"The risks of birth defects and childhood cancer with conception by assisted reproductive technology","abstract":"STUDY QUESTION: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer? SUMMARY ANSWER: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects. WHAT IS KNOWN ALREADY: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved. STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% ","journal":"Human Reproduction","year":2022,"id":244438,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":276546,"name":"Morton B. Brown","orcid":null,"position":1,"is_corresponding":false},{"id":276547,"name":"Ethan Wantman","orcid":null,"position":2,"is_corresponding":false},{"id":390441,"name":"Maria J. Schymura","orcid":"0000-0003-0587-8667","position":3,"is_corresponding":false},{"id":275140,"name":"Marilyn L. Browne","orcid":"0000-0002-1872-2787","position":4,"is_corresponding":false},{"id":275141,"name":"Sarah C. Fisher","orcid":"0000-0002-4702-1007","position":5,"is_corresponding":false},{"id":275139,"name":"Nina Forestieri","orcid":"0000-0001-7894-0279","position":6,"is_corresponding":false},{"id":877772,"name":"Chandrika Rao","orcid":"0000-0001-7950-097X","position":7,"is_corresponding":false},{"id":275144,"name":"Hazel B. Nichols","orcid":"0000-0003-0972-1560","position":8,"is_corresponding":false},{"id":275142,"name":"Mahsa M. Yazdy","orcid":"0000-0002-7415-5350","position":9,"is_corresponding":false},{"id":543122,"name":"Susan T. Gershman","orcid":null,"position":10,"is_corresponding":false},{"id":756127,"name":"Caitlin R. Sacha","orcid":"0000-0003-2170-1976","position":11,"is_corresponding":false},{"id":878165,"name":"Melanie Williams","orcid":null,"position":12,"is_corresponding":false},{"id":276548,"name":"Mary K. Ethen","orcid":null,"position":13,"is_corresponding":false},{"id":268650,"name":"Mark A. Canfield","orcid":"0000-0001-8827-1881","position":14,"is_corresponding":false},{"id":276549,"name":"Kevin J. Doody","orcid":null,"position":15,"is_corresponding":false},{"id":232339,"name":"Michael L. Eisenberg","orcid":"0000-0001-5482-0141","position":16,"is_corresponding":false},{"id":247246,"name":"Valerie L. Baker","orcid":"0000-0003-1762-7339","position":17,"is_corresponding":false},{"id":533362,"name":"Carrie Williams","orcid":"0000-0003-2705-7712","position":18,"is_corresponding":false},{"id":533361,"name":"Alastair Sutcliffe","orcid":"0000-0001-8542-6155","position":19,"is_corresponding":false},{"id":240622,"name":"Melissa A. Richard","orcid":"0000-0003-0129-9860","position":20,"is_corresponding":false},{"id":247448,"name":"Philip J. Lupo","orcid":"0000-0003-0978-5863","position":21,"is_corresponding":false},{"id":275138,"name":"Barbara Luke","orcid":"0000-0002-0405-8133","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:23:25.718788Z","pmid":"36112004","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}