Ovulation induction using s.c. pulsatile gonadotrophin-releasing hormone: effectiveness of different pulse frequencies

Abstract

To determine the ovarian response to a fixed dose of gonadotrophin-releasing hormone (GnRH) administered s.c. at four different pulse frequencies, 20 patients with hypothalamic amenorrhoea were treated over 41 cycles using a dose of 20 ng/kg/pulse. These patients were randomly assigned to receive GnRH at pulse frequencies of 60, 90, 120 or 180 min. GnRH was administered s.c. using portable infusion pumps. Subjects were paid volunteers with a diagnosis of hypothalamic amenorrhoea. All patients had low to less than detectable serum concentrations of luteinizing hormone and follicle stimulating hormone on 8 h serial sampling, and normal serum concentrations of prolactin and androgen, including androstenedione, testosterone and dihydroepiandrosterone sulphate. Six of the 20 patients were enrolled in the protocol to achieve a pregnancy, while 14 were volunteers using a barrier method of contraception. Highest ovulation rates were achieved using pulse frequencies of 90 and 120 min (60 and 88% of cycles respectively). Ovulation occurred significantly less often with frequencies of 60 and 180 min (12 and 38% respectively; P </= 0.05). Pregnancy was achieved in four of the six patients who desired a pregnancy at pulse frequencies of 90 (three out of three) and 120 (one out of one) min. No pregnancies occurred at pulse frequencies of 60 (none out of one) and 180 (none out of one) min. When ovulatory cycles were considered, oestradiol concentrations were not different among pulse frequencies but varied significantly between ovulatory and anovulatory cycles. Integrated luteal progesterone concentrations for 90 and 120 min frequencies (118.26 +/- 25.89 and 125.15 +/- 32. 10 ng/ml/luteal phase respectively) were significantly higher than for 60 and 180 min (80.1 +/- 48.2 and 42.75 +/- 26.48 ng/ml/luteal phase respectively). Ovulation may be induced by a broad range of pulse frequencies. Pulse frequencies of 90 or 120 min for s.c. GnRH appear to induce more reliably the sequence of follicular development, ovulation and normal luteal function than frequencies of either 60 or 180 min. Significantly higher ovulation rates occurred at 90 and 120 min by s.c. administered GnRH.