Ovulation induction in women with infertility: a new indication for aromatase inhibitors

The third-generation aromatase inhibitors were initially introduced to treat postmenopausal breast cancer. We now realize that many other potential indications for aromatase inhibitors exist, especially in the field of gynecology. Preliminary data were suggestive that aromatase inhibitors could be used to treat endometriosis and uterine leiomyomata and induce or augment ovulation. Aromatase inhibitors promote ovulation, most likely by increasing endogenous FSH production owing to decreased estrogen biosynthesis in the ovary and extraovarian tissues, including the brain. Aromatase inhibitors differ from the estrogen antagonist clomiphene citrate in that they do not exert a direct unfavorable effect on endometrial growth and development during the menstrual cycle. Healey et al. (1) report important findings on the effects of the addition of an aromatase inhibitor to gonadotropin injections for superovulation. A relatively large number of patients and a control group were studied, and several clinically useful outcomes including pregnancy rates were reported. The addition of letrozole to an ovulation induction regimen using injectable gonadotropins in a mixed population of patients with infertility does not seem to offer any benefits over gonadotropin-only cycles, because the decreased gonadotropin dose (the only apparent benefit) was offset by increased complexity of the treatment. Further randomized clinical trials using a similar design and patient sample may not provide clinically useful data. On the other hand, optimization of this regimen (gonadotropin plus aromatase inhibitor) in poor responders may offer an alternative in this subset of women (2). From the existing literature, it appears that use of an aromatase inhibitor alone to induce or augment ovulation will continue to be an exciting area of research future (3, 4). In particular, the dosing and timing of administration (late luteal versus early follicular) of an aromatase inhibitor for ovulation induction should be optimized. Defining the hormonal profiles of the women who will benefit the most from aromatase inhibition may further increase the success of treatment. In summary, Healey et al. (1) should be congratulated for conducting this interesting work. Carefully designed randomized studies on the use of aromatase inhibitors for ovulation induction or augmentation are warranted.