Objective: To review critically the published data regarding the proposed association of ovulation induction, infertility, and an increased risk of ovarian cancer.
Design: A medline search was conducted to identify all case reports, epidemiologic studies, and clinical investigations containing data relevant to infertility, treatment of infertility, and the associated risk of ovarian cancer. Additional sources were obtained from reference lists of original research and review articles. Particular emphasis was placed on the most recently published reports examining these associations.
Results: Four case-control studies and three retrospective cohort studies, as well as a large meta-analysis of three additional case-control studies were identified as presenting the most pertinent clinical data.
Conclusion: Currently available data in the literature suggest that an association between ovulation induction and ovarian cancer does not indicate necessarily a causal effect. Infertility alone is an independent risk factor for the development of ovarian cancer. Nulliparous women with refractory infertility may harbor a particularly high risk of ovarian cancer, irrespective of their use of fertility drugs. Furthermore, the apparent association between fertility drug use and ovarian cancer may arise because these women are the most likely to have used ovulation-stimulating agents as part of their infertility treatment. Close clinical surveillance of patients before, during, and after treatment of infertility is warranted.