TOPLINE:

Women who used medically assisted reproduction (MAR) in Australia had comparable overall cancer incidence to the general population, though certain hormone-sensitive cancers showed elevated rates. Among 417,984 MAR-exposed women followed for a median of 9-12 years, uterine cancer incidence was elevated across all treatment types, with standardized incidence ratios (SIRs) ranging from 1.23 to 1.83, while cervical cancer and lung cancer incidence were reduced by more than one third.

METHODOLOGY:

• There has been longstanding concern that ovarian and other hormone-sensitive cancers are more common in women exposed to MAR, potentially due to fertility medications and repeated puncture of ovarian follicles during in vitro fertilization. Population-based studies indicate ovarian cancer may be more common and cervical cancer less common in women exposed to assisted reproductive therapy (ART) compared with the general population, though findings for other cancers are mixed.
• Researchers conducted a population-based cohort study of 417,984 Australian women aged 18-55 years who used MAR from 1991 to 2018, with data analyzed from April to November 2024.
• Three MAR cohorts were created: 274,676 women (65.7%) who used ART, 120,739 women (28.9%) who used intrauterine insemination with ovarian stimulation (IUI/OS), and 175,510 women (42.0%) who used ovulation induction with clomiphene citrate.
• MAR treatments, pregnancies, incident cancers, and deaths were ascertained using linkage between population-based administrative health datasets and statutory registries in Australia.
• Median follow-up time was 9.42 years (interquartile range [IQR], 5.08-15.42 years) for the ART cohort, 11.67 years (IQR, 6.25-18.42 years) for the IUI/OS cohort, and 9.42 years (IQR, 5.42-13.58 years) for the clomiphene citrate cohort.
• Cancer incidence among MAR-exposed women was compared with the age-, jurisdiction-, and calendar year-matched general population, with main outcomes being cancer SIRs and rate differences.

TAKEAWAY:

• Overall invasive cancer incidence was comparable to the general population for the ART cohort (standardized incidence ratio [SIR], 1.00) and IUI/OS cohort (SIR, 0.99) and slightly elevated for the clomiphene citrate cohort (SIR, 1.04).
• Uterine cancer incidence was elevated across all MAR cohorts, with the highest elevation in the clomiphene citrate cohort (SIR, 1.83; 95% CI, 1.60-2.07), followed by the IUI/OS cohort (SIR, 1.32; 95% CI, 1.17-1.49) and ART cohort (SIR, 1.23; 95% CI, 1.12-1.34).
• Ovarian cancer incidence was elevated for the ART cohort (SIR, 1.23; 95% CI, 1.10-1.37) and IUI/OS cohort (SIR, 1.18; 95% CI, 1.01-1.37), with the excess appearing restricted to endometrioid and serous subtypes.
• Cervical cancer incidence reduced across all MAR cohorts, with SIRs ranging from 0.52 to 0.61 (ART: SIR, 0.61), and lung cancer incidence also decreased (ART: SIR, 0.70).

IN PRACTICE:

“Causation cannot be inferred from this descriptive evidence, but findings may guide women and their health care practitioners,” wrote the authors of the study.

SOURCE:

The study was led by Claire Melissa Vajdic, PhD, Kirby Institute, University of New South Wales, Sydney, Australia. It was published online on March 10 in JAMA Network Open.

LIMITATIONS:

According to the authors, the study was unable to assess cancer incidence by stage, cancer incidence compared with infertile women unexposed to MAR, or cause-specific cancer mortality. There was no person-level national data on the indication for fertility treatment, adiposity, breastfeeding, skin type, or smoking. Multiple testing may have increased the risk for chance findings in stratified analyses, and SIR estimates in many strata had low precision due to small numbers of observed cancers. Additionally, the follow-up duration was relatively short, and most women were younger than 50 years at the end of follow-up. The comparator population was the general population of women matched only for age, calendar year, and state of residence, which limits causal inference.

DISCLOSURES:

This study was funded by grant APP1164852 from the National Health and Medical Research Council (NHMRC). Vajdic disclosed receiving grants from NHMRC awarded to her institution during the conduct of the study. Adrian Raymond Walker, PhD, disclosed being employed by University of New South Wales, Sydney, during the conduct of the study. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.