Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies

Controversy surrounds the relations among infertility, fertility drug use, and the risk of ovarian cancer. The authors pooled interview data on infertility and fertility drug use from eight case-control studies conducted between 1989 and 1999 in the United States, Denmark, Canada, and Australia. Odds ratios and 95% confidence intervals were calculated, adjusting for age, race, family history of ovarian cancer, duration of oral contraception use, tubal ligation, gravidity, education, and site. Included in the analysis were 5,207 cases and 7,705 controls. Among nulligravid women, attempts for more than 5 years to become pregnant compared with attempts for less than 1 year increased the risk of ovarian cancer 2.67-fold (95% confidence interval (CI): 1.91, 3.74). Among nulliparous, subfertile women, neither any fertility drug use (odds ratio (OR) = 1.60, 95% CI: 0.90, 2.87) nor more than 12 months of use (OR = 1.54, 95% CI: 0.45, 5.27) was associated with ovarian cancer. Fertility drug use in nulligravid women was associated with borderline serous tumors (OR = 2.43, 95% CI: 1.01, 5.88) but not with any invasive histologic subtypes. Endometriosis (OR = 1.73, 95% CI: 1.10, 2.71) and unknown cause of infertility (OR = 1.19, 95% CI: 1.00, 1.40) increased cancer risk. These data suggest a role for specific biologic causes of infertility, but not for fertility drugs in overall risk for ovarian cancer.