Ovulation induction in clomiphene nonresponsive patients: the place of pulsatile gonadotropin-releasing hormone in clinical practice.

Seventy-three treatment courses of pulsatile gonadotropin-releasing hormone (GnRH) were given to 19 patients with clomiphene nonresponsive anovulatory infertility. Fifty cycles were given by the subcutaneous route, and 23 were given intravenously. Doses varied between 1 and 40 micrograms per pulse given at 60- or 90-minute intervals. Luteal support was either by continuation of the pulsatile GnRH or by human chorionic gonadotropin injections. In 16 cycles, potentially fertile ovulation occurred, and three pregnancies resulted, of which one continues normally. Only one of the three pregnancies occurred during intravenous GnRH treatment, and it is likely that this patient would have responded to subcutaneous treatment. The optimum dosage to induce ovulation ranged between 10 and 20 micrograms per pulse at a frequency of 60 to 90 minutes. Those patients who responded to treatment were all of normal or low body weight for their age and frame. Conversely, those who failed to respond to pulsatile GnRH with ovulation were obese except for one patient with the polycystic ovary syndrome. Because pulsatile GnRH treatment is simple and potentially safe to administer, a therapeutic trial is indicated in patients of low to normal body weight who fail to respond to clomiphene. Where patients are responsive to pulsatile GnRH, the ovulations produced are likely to be fertile, possibly because of the endogenous nature of the ovulatory luteinizing hormone surge.