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

Mandy Spaan, Alexandra W van den Belt-Dusebout, Cornelis B Lambalk, Hester H van Boven, Roel Schats, Marian Kortman, Frank J M Broekmans, Joop S E Laven, Evert J P van Santbrink, Didi D M Braat, Lucette A J van der Westerlaken, Ben J Cohlen, Astrid E P Cantineau, Jesper M J Smeenk, Minouche M van Rumste, Mariëtte Goddijn, Ron J T van Golde, Paul A M Meeuwissen, Carl J C M Hamilton, Gabriële M OuwensMiranda A Gerritsma, Michael Schaapveld, Curt W Burger, Flora E van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article number163
Pages (from-to)699-709
Number of pages11
JournalJournal of the National Cancer Institute
Issue number6
Early online date17 Nov 2020
Publication statusPublished - Jun 2021




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