O-152 Benign epithelial ovarian tumors following use of fertility drugs: a register-based cohort study from Denmark
Authors: Gottschau M , Frederiksen K , Lima C , Frandsen Brown , Hargreave M , Nøhr B , Kjær S K , Jensen A 
Published: June 2023

Study question

Is use of fertility drugs associated with an increased risk of benign epithelial ovarian tumors among women with infertility?

Summary answer

Among women with infertility, use of fertility drugs is not associated with an increased risk of benign epithelial ovarian tumors.

What is known already

Benign epithelial ovarian tumors are the most common neoplasms in the ovaries. These benign tumors share some of the same risk factors, which are associated with ovarian cancer. The general understanding of the pathogenesis and etiology of ovarian cancer is sparse; therefore, knowledge on factors influencing development of benign epithelial ovarian tumors—and hence likely ovarian cancer—is warranted. Previous studies on the association between fertility treatment and ovarian cancer are conflicting, whereas no previous study has examined the association between use of fertility drugs and benign epithelial ovarian tumors.

Study design, size, duration

Retrospective register-based cohort study of nearly 145,000 women included in the Danish Infertility Cohort during 1995–2017 at age 20–45 years. Women were followed from one year after infertility diagnosis until first benign epithelial ovarian tumor or one of the censoring criteria: borderline ovarian tumor, ovarian cancer, oophorectomy, emigration, death or end of follow-up (December 31, 2018).

Participants/materials, setting, methods

Using the Aalen-Johansen estimator, we determined 10-year cumulative risks of benign epithelial ovarian tumors among approximately 25,000 women who used fertility drugs (defined within one year after infertility diagnosis: clomiphene citrate, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone [GnRH] receptor modulators, and progesterone) compared with women diagnosed with infertility and no drug use. Additionally, we used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Main results and the role of chance

Our results showed that the crude 10-year cumulative risk of benign epithelial ovarian tumors were 0.32% (95% CI: 0.29%–0.36%) for women who used any fertility drug compared with 0.49% (95% CI: 0.40%–0.60%) in women with no use of fertility drugs (risk difference: -0.17% [95% CI: -0.28–(-0.07)]). When adjusted for age, calendar period of infertility diagnosis, educational level, parity, obesity, polycystic ovary syndrome, and origin of infertility information, the HR for use of any fertility drug was 0.73 (95% CI 0.55–0.96). In general, the 10-year risk differences as well as the HRs for each drug evaluated separately were similar to the results for use of any drug. Lastly, we tested the robustness of our results by various pre-defined secondary analyses, and this did not change our results.

Limitations, reasons for caution

We did not include information on number of cycles and treatment regimens as these are only partly available in the registers.

Wider implications of the findings

Among women with infertility, we observe a lower relative risk of benign epithelial ovarian tumors for women treated with fertility drugs compared with women who did not use fertility drugs. However, this finding translates into a small decrease in absolute risk, which does not appear to have any clinical relevance.

Trial registration number

Not applicable