{"doi":"10.1093/humrep/deaa272","title":"The risk of birth defects with conception by ART","abstract":"STUDY QUESTION: What is the association between ART conception and treatment parameters and the risk of birth defects? SUMMARY ANSWER: Compared to naturally conceived singleton infants, the risk of a major nonchromosomal defect among ART singletons conceived with autologous oocytes and fresh embryos without use of ICSI was increased by 18%, with increases of 42% and 30% for use of ICSI with and without male factor diagnosis, respectively. WHAT IS KNOWN ALREADY: Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects but have been limited by small sample size and inadequate statistical power, failure to differentiate results by plurality, differences in birth defect definitions and 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 2015 that resulted in live births from 1 September 2004 to 31 December 2016 in Massachusetts and North Carolina and from 1 September 2004 to 31 December 2015 for Texas and New York: these were large and ethnically diverse States, with birth defect registries utilizing the same case definitions and data collected, and with high numbers of ART births annually. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Naturally conceived ART siblings were identified through the mother's information. Non-ART children were classified as being born to women who conceived with ovulation induction (OI)/IUI when there was an indication of infertility treatment on the birth certificate, but 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 135 051 ART children (78 362 singletons and 56 689 twins), 23 647 naturally conceived ART siblings (22 301 singletons and 1346 twins) and 9396 children born to women treated with OI/IUI (6597 singletons and 2799 twins) and 1 067 922 naturally conceived children (1 037 757 singletons and 30 165 twins). 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). Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CI to evaluate the risk of birth defects due to conception with ART (using autologous oocytes and fresh embryos), and with and without the use of ICSI in the absence or presence of male factor infertility, with naturally conceived children as the reference. Analyses within the ART group were stratified by combinations of oocyte source (autologous, donor) and embryo state (fresh, thawed), with births from autologous oocytes and fresh embryos as the reference. Analyses limited to fresh embryos were stratified by oocyte source (autologous, donor) and the use of ICSI. Triplets and higher-order multiples were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 998 singleton children (1.9%) and 3037 twin children (3.3%) had a major birth defect. Compared to naturally conceived children, ART singletons (conceived from autologous oocytes, fresh embryos without the use of ICSI) had increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% 1.05, 1.32), cardiovascular defects (AOR 1.20, 95% CI 1.03, 1.40), and any birth defect (AOR 1.18, 95% CI 1.09, 1.27). Compared to naturally conceived children, ART s","journal":"Human Reproduction","year":2020,"id":53797,"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":112,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","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":275139,"name":"Nina Forestieri","orcid":"0000-0001-7894-0279","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":275142,"name":"Mahsa M. Yazdy","orcid":"0000-0002-7415-5350","position":6,"is_corresponding":false},{"id":276548,"name":"Mary K. Ethen","orcid":null,"position":7,"is_corresponding":false},{"id":268650,"name":"Mark A. Canfield","orcid":"0000-0001-8827-1881","position":8,"is_corresponding":false},{"id":275143,"name":"Stephanie Watkins","orcid":"0000-0001-7623-4661","position":9,"is_corresponding":false},{"id":275144,"name":"Hazel B. Nichols","orcid":"0000-0003-0972-1560","position":10,"is_corresponding":false},{"id":275145,"name":"Leslie V. Farland","orcid":"0000-0001-7455-8531","position":11,"is_corresponding":false},{"id":275146,"name":"Sergio Oehninger","orcid":"0000-0001-9472-6010","position":12,"is_corresponding":false},{"id":276549,"name":"Kevin J. Doody","orcid":null,"position":13,"is_corresponding":false},{"id":232339,"name":"Michael L. Eisenberg","orcid":"0000-0001-5482-0141","position":14,"is_corresponding":false},{"id":247246,"name":"Valerie L. Baker","orcid":"0000-0003-1762-7339","position":15,"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":"2026-07-18T20:45:25.145885Z","pmid":"33251542","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":[]}