Pulsatile gonadotropin-releasing hormone therapy for ovulatory disorders

Pulsatile GnRH remains a physiologic method of inducing ovulation that is effective and safer than other parenteral preparations. Its lower rate of acceptance in the United States stands in curious contrast to its widespread usage in other countries as a second-line (postclomiphene) technique of choice for ovulation induction. In a high-technology era such as ours, women who may benefit from pulsatile GnRH therapy should not be forgotten. By far the most favorable results are obtained in women with primary or secondary hypothalamic amenorrhea. In such women, pregnancy rates appear comparable to those achieved with exogenous gonadotropins with a much lower risk of multiple pregnancy and ovarian hyperstimulation. These positive aspects, combined with the decreased need for clinical monitoring and the increased sense of control imparted to the patient, lead to the conclusion that women with uncomplicated hypothalamic-pituitary disorders are the ideal patient group to consider for therapy. The application of pulsatile GnRH therapy to other groups of women relies on limited data. By all means, women with polycystic ovarian syndrome who have not ovulated or conceived after other forms of treatment should be considered because reasonable pregnancy salvage can be obtained. We have noted a first-cycle successful pregnancy after failure of exogenous gonadotropins, with or without a superimposed GnRH agonist, and even in vitro fertilization with multiple embryo transfers. Before such invasive, high-technology procedures are entertained, it would appear prudent to consider this simple alternative in women with an overactive hypothalamic-pituitary axis, as seen in polycystic ovarian syndrome. Other ovulatory defects also may be amenable to treatment with pulsatile GnRH, but their practical usefulness will await further clinical study.