TY - JOUR
T1 - Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology
AU - Spaan, Mandy
AU - Van Den Belt-Dusebout, Alexandra W.
AU - Lambalk, Cornelis B.
AU - Van Boven, Hester H.
AU - Schats, Roel
AU - Kortman, Marian
AU - Broekmans, Frank J.M.
AU - Laven, Joop S.E.
AU - Van Santbrink, Evert J.P.
AU - Braat, Didi D.M.
AU - Van Der Westerlaken, Lucette A.J.
AU - Cohlen, Ben J.
AU - Cantineau, Astrid E.P.
AU - Smeenk, Jesper M.J.
AU - Van Rumste, Minouche M.
AU - Goddijn, Mariëtte
AU - Van Golde, Ron J.T.
AU - Meeuwissen, Paul A.M.
AU - Hamilton, Carl J.C.M.
AU - Ouwens, Gabriële M.
AU - Gerritsma, Miranda A.
AU - Schaapveld, Michael
AU - Burger, Curt W.
AU - Van Leeuwen, Flora E.
N1 - Funding:
This work was supported by grants from the Dutch Cancer
Society (NKI 2006-3631).
Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107390900&partnerID=8YFLogxK
U2 - 10.1093/jnci/djaa163
DO - 10.1093/jnci/djaa163
M3 - Article
C2 - 33769500
AN - SCOPUS:85107390900
SN - 0027-8874
VL - 113
SP - 699
EP - 709
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 6
ER -
