Fertility drug use and risk of ovarian tumors: a debated clinical challenge.

Infertility itself increases the incidence of ovarian carcinoma, while the potential additional risk associated with the use of fertility drugs is still debated. In 1992, the cumulative analysis of 12 US case-control studies revealed that women who received ovulation-inducing drugs had approximately three-fold higher incidence of invasive ovarian carcinoma. Other investigations reported a lower increase of the risk of invasive carcinoma or borderline tumor of the ovary in women treated with these agents. Conversely, several other case-control or cohort studies failed to detect a significant correlation between fertility drug use and ovarian tumor risk in either parous or nulliparous women compared with untreated infertile women. Moreover neither the number of treatment cycles nor the type of drug used was associated with an increased risk in most studies. Incessant ovulation and excessive gonadotropin secretion have been long considered to play a major role in the development of ovarian carcinoma, and therefore fertility drugs, which raise the serum levels of gonadotropins and increase the chances of multiple ovulations, have been retained as a risk factor for this malignancy, However, the large majority of literature data as well as the new hypotheses on ovarian carcinogenesis appear to exclude a relevant impact of fertility drug use on the risk of ovarian tumors, and especially of high-grade invasive epithelial ovarian cancers.