Cancer Incidence in Women After Medically Assisted Reproduction.
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IMPORTANCE: High-quality evidence on cancer occurrence for women who have used medically assisted reproduction (MAR) is required to guide care. OBJECTIVE: To compare cancer incidence in MAR-exposed women with the general population of women. DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study of Australian women. MAR treatments, pregnancies, incident cancers, and deaths were ascertained using linkage between population-based administrative health datasets and statutory registries. Women aged 18 to 55 years who used MAR from 1991 to 2018 were identified and analyzed from April to November 2024. EXPOSURES: Three MAR cohorts were created: assisted reproductive therapy (ART), intrauterine insemination with ovarian stimulation (IUI/OS), and ovulation induction using clomiphene citrate (clomiphene citrate). MAIN OUTCOMES AND MEASURES: Cancer incidence among MAR-exposed women was compared with the age-, jurisdiction-, and calendar year-matched general population. The main outcomes were cancer standardized incidence ratios (SIRs) and rate differences. RESULTS: A total of 417 984 MAR-exposed women were included, with 274 676 (65.7%) having ever used ART (median [IQR] age, 34 [31-38] years; median [IQR] follow-up time, 9.42 [5.08-15.42] years), 120 739 (28.9%) having ever used IUI/OS (median [IQR] age, 34 [30-38] years; median [IQR] follow-up time, 11.67 [6.25-18.42] years), and 175 510 (42.0%) having ever used clomiphene citrate (median [IQR] age, 32 [28-36] years; median [IQR] follow-up time, 9.42 [5.42-13.58] years). The overall incidence of invasive cancer was comparable with the general population for the ART (SIR, 1.00; 95% CI, 0.98-1.02) and IUI/OS (SIR, 0.99; 95% CI, 0.97-1.02) cohorts and slightly elevated for the clomiphene citrate cohort (SIR, 1.04; 95% CI, 1.00-1.07). For all cohorts, incidence of uterine cancer (SIRs, 1.23-1.83) and in situ and invasive melanoma (SIRs, 1.07-1.15) were elevated, and incidence of cervical cancer (SIRs, 0.52-0.61) and cancer of the trachea, bronchus, and lung (SIRs, 0.62-0.70) were lower. Ovarian cancer incidence was elevated for the ART (SIR, 1.23; 95% CI, 1.10-1.37) and IUI/OS (SIR, 1.18; 95% CI, 1.01-1.37) cohorts. In situ breast cancer incidence was elevated for the ART cohort only (SIR, 1.24; 95% CI, 1.12-1.38). Incidence of invasive breast cancer was not elevated. Rate differences for invasive cancers with elevated incidence were all small (<1 to 6.51 cases per 100 000 person-years). CONCLUSIONS AND RELEVANCE: In this cohort study of cancer incidence in women who received MAR, the overall incidence of cancer was comparable with that of the general population. The incidence of certain cancers appeared elevated; however, the excess numbers of these cancers were small, and there was reduced incidence of other cancers. Causation cannot be inferred from this descriptive evidence, but findings may guide women and their health care practitioners.