Childhood Cancer Risk After Assisted Reproductive Technology.
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IMPORTANCE: Childhood cancer risk after assisted reproductive technology (ART) remains uncertain, particularly by procedure and cancer type. OBJECTIVE: To examine associations between ART and childhood cancer overall and by ART modality and cancer type. DESIGN, SETTING, AND POPULATION: Nationwide Danish cohort of 1 086 136 live-born children from 1996 to 2012, of whom 37 228 (3.4%) were conceived using ART, with follow-up through 2023. EXPOSURES: Maternal ART, classified as in vitro fertilization (IVF), intracytoplasmic sperm injection, or frozen embryo transfer. MAIN OUTCOMES AND MEASURES: Incident childhood cancer. Cox proportional hazards models estimated hazard ratios (HRs); Poisson models estimated incidence rates. Non-ART births were the primary reference; secondary analyses used children of women with a history of infertility and children conceived using IVF as reference groups. RESULTS: During a median follow-up of 20 years, 3736 cancers occurred. Compared with non-ART births (incidence rate, 18.3 per 100 000 person-years), children conceived using ART had higher cancer incidence (incidence rate, 23.6 per 100 000; HR, 1.26 [95% CI, 1.07-1.48]). Rates were higher after frozen embryo transfer (incidence rate, 41.1 per 100 000; HR, 2.18 [95% CI, 1.45-3.29]) and intracytoplasmic sperm injection (incidence rate, 27.9 per 100 000; HR, 1.48 [95% CI, 1.16-1.89]) but not IVF (incidence rate, 18.5 per 100 000; HR, 1.01 [95% CI, 0.79-1.28]). Frozen embryo transfer was associated with leukemia (incidence rate, 11.1 per 100 000; HR, 2.36 [95% CI, 1.06-5.28]), lymphomas (HR, 3.03 [95% CI, 1.13-8.12]), and soft tissue sarcomas (HR, 7.63 [95% CI, 2.82-20.62]); intracytoplasmic sperm injection was associated with lymphomas (incidence rate, 4.6 per 100 000; HR, 1.94 [95% CI, 1.07-3.54]), soft tissue sarcomas (incidence rate, 3.3 per 100 000; HR, 3.28 [95% CI, 1.54-7.00]), and central nervous system neoplasms (incidence rate, 8.2 per 100 000; HR, 1.63 [95% CI, 1.04-2.57]); no associations were observed for IVF. Findings were similar in secondary analyses using children of women with a history of infertility and children conceived using IVF as reference groups. CONCLUSIONS AND RELEVANCE: ART, particularly frozen embryo transfer and intracytoplasmic sperm injection, was associated with increased childhood cancer risk, but absolute risks were low. The consistent results in secondary analyses of children with maternal infertility history or conceived via IVF suggest that procedure-related, rather than infertility-related, factors warrant further investigation.