Ovarian cancer :

The use of fertility drugs has been associated with neoplasia, particularly borderline ovarian tumors, in some but not all, studies .Studies to date have focused on clomiphene and gonadotropin therapy.

In one series, the risk appeared to be only in women who had undergone more than 12 cycles of clomiphene citrate therapy .

The apparent association between fertility drug use and epithelial ovarian cancer appears to be related to the fact that these drugs are more likely to be used in infertile women, who are known to be at higher risk of developing ovarian cancer, irrespective of their use of fertility drugs .

Because of the observations that pregnancy rates are low after six cycles of treatment, and that 12 or more cycles may increase the risk of ovarian neoplasms , the American College of Obstetricians and Gynecologists has suggested that clomiphene treatment be limited to fewer than 12 cycles, and that the number of gonadotropin cycles be minimized as well .

Breast cancer  There does not appear to be an increased

risk of breast cancer in women treated with fertility drugs.

However, interpretation of the available data is limited by several factors, such as survey information, small subgroup numbers, lack of evaluation by drug type/dose or cause of infertility, and confounding by the presence of other risk factors for breast cancer.

One relatively large case-control study showed that infertile women with breast cancer were more likely to have been treated with human menopausal gonadotropin (hMG) for more than six cycles than infertile women without breast cancer; no increased risk was noted for clomiphene citrate. However, this study was subject to many of the limitations noted above.

Women taking infertility drugs can be reassured that these drugs probably do not increase their risk of breast cancer, although it is not clear whether some subgroups may be at increased risk. Further investigation is required.

Uterine cancer In a retrospective, cohort study, neither

clomiphene nor gonadotropin use appeared to be associated with an increased risk of melanoma, thyroid, cervical, or colon cancers .

In contrast, the same investigators reported that clomiphene use may be associated with a greater risk of endometrial cancer. However, one explanation for these findings is that infertile women who used clomiphene were more likely to have underlying chronic anovulation, which is a strong risk factor for development of endometrial cancer, than infertile women not exposed to clomiphene.

Other ovulation induction therapies (including pulsatile GnRH, and dopamine agonists) have not been linked to ovarian or breast cancer risk.