Cancer risk associated with subfertility and ovulation induction: a review

Objective: Over the past decades the use of fertility drugs (FDs) has great ly increased. Recently, the possible association between the use of FDs and risk of cancer has aroused great concern. In this paper, we critically rev iew the available epidemiologic studies. Methods: We identified papers published between 1966 and 1999 that examined FDs and specific causes of subfertility in relation to the risks of cancer s of the ovary, breast, endometrium and thyroid, and melanoma. Results: Although present insights into the pathogenesis of hormone-related malignancies suggest a possible association between the use of FDs and the risk of specific cancers, this has not been convincingly demonstrated in e pidemiologic studies. With regard to cancer risk in relation to the cause o f subfertility, the only consistent association observed is an increased ri sk of endometrial cancer for women with subfertility due to hormonal disord ers. While positive findings in some studies on FDs and ovarian cancer risk have aroused serious concern, the associations observed in most of these r eports appear to be due to bias or chance rather than being causal. The mos t important sources of bias are inadequate confounder control for both pari ty and causes of subfertility. Conclusions: To discriminate between the possible carcinogenic effects of v arious ovulation induction regimens, subfertility disorders, and reproducti ve characteristics associated with subfertility, future studies should incl ude large populations of subfertile women with sufficient follow-up time. I n such cohort studies the cause of subfertility should be measured adequate ly (based on medical records) and information about reproductive characteri stics should be collected for all cohort members. Such studies should also include a group of subfertile women with an indication for FD use but not s o treated.