Subfertility, use of fertility treatments and BRCA mutation status and the risk of ovarian cancer

Purpose: The objective of the study is to evaluate the possible association between history of subfertility, fertility treatments, BRCA mutations and the risk of ovarian cancer.

Methods: This Israeli National Case-Control study included 1269 consecutive ovarian cancer cases and 2111 individually matched healthy controls. All participants were interviewed and molecular analysis of BRCA mutations were performed to 896 cases. The main outcome measure was reported history of subfertility and exposure to fertility treatments.

Results: The rate of reported subfertility was 15.1% and 14.3% in ovarian cancer cases and controls, respectively. However, subfertility was more prevalent in cases with borderline ovarian cancer (but not for invasive ovarian cancer cases) than controls. Multivariate conditional logistic regression revealed that the risk of borderline ovarian cancer was elevated in both women treated for subfertility and those that were not treated for subfertility, (OR = 1.74; 95% CI 0.9-3.36 and OR = 1.79; 95% CI 0.98-3.26, respectively). In non-carriers of BRCA1/2 mutations, fertility treatments were associated with a decreased risk of invasive ovarian cancer while a significant increased risk of borderline ovarian cancer was observed (OR = 2.92, 95%CI 1.67-5.10).

Conclusions: Reported subfertility and exposure to fertility treatments were associated with borderline but not with invasive ovarian tumors. This association was more prominent in women who are non-carriers of a BRCA mutation.