Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology

J Natl Cancer Inst. 2021 Jun 1;113(6):699-709. doi: 10.1093/jnci/djaa163.


Background: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.

Methods: This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided.

Results: After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time.

Conclusions: Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Cohort Studies
  • Female
  • Humans
  • Ovarian Neoplasms* / epidemiology
  • Ovarian Neoplasms* / etiology
  • Ovarian Neoplasms* / pathology
  • Ovulation Induction / adverse effects
  • Pregnancy
  • Reproductive Techniques, Assisted* / adverse effects