Cancer Incidence in Women After Medically Assisted Reproduction

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 (