Aromatase inhibitors for the treatment of infertility

Ovarian stimulation during infertility treatment is used either alone or in conjunction with intrauterine insemination and assisted reproductive technologies. At the present time, the two main medications used for ovarian stimulation include an oral antioestrogen, clomiphene citrate and injectable gonadotrophins. In spite of the high ovulation rate, the use of clomiphene citrate is associated with adverse side effects and low pregnancy rates. In clomiphene citrate failures, gonadotrophin injections are generally the next treatment option but, especially in polycystic ovarian syndrome, are associated with increased risk of severe ovarian hyperstimulation syndrome and high multiple pregnancies. Therefore, an effective oral treatment that could be used without risk of ovarian hyperstimulation syndrome and with minimal monitoring is preferred. It was hypothesised that aromatase inhibitors can be administered early in the follicular phase to induce ovulation by releasing the hypothalamus and/or pituitary from oestrogen negative feedback. The success of aromatase inhibitors in induction and augmentation of ovulation has been reported. In addition, increased intraovarian androgen levels may synergise with central effects of decreased oestrogen to enhance ovarian response to gonadotrophin stimulation. This increased sensitivity to follicle-stimulating hormone may be especially useful in poor responders. The potential future applications for aromatase inhibitors in infertility management are also discussed.