Direct ovarian effects and safety aspects of GnRH agonists and antagonists

The wide application of gonadotrophin-releasing hormone (GnRH) analogues in assisted reproduction has raised concerns about their potential extra-pituitary actions. Although data from animal studies support the presence of ovarian GnRH receptors and of direct ovarian effects of GnRH analogues, this has not been unequivocally demonstrated in humans. Available evidence suggests, however, the existence of GnRH receptors in human granulosa-luteal cells, while the majority of the studies performed showed that progesterone is inhibited by GnRH agonists in vitro. On the other hand, no difference seems to exist between agonists and antagonists in terms of granulosa-luteal cell steroidogenesis under basal conditions. So far, no studies have suggested an adverse effect of GnRH analogues on the developing human follicle. Moreover, the physiological significance of a direct in-vitro ovarian effect of GnRH analogues remains to be established.