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

To determine the ovarian response to a fixed dose of gonadotrophin-releasinghormone (GnRH) administered s.c. at four different pulse frequencies,20 patients with hypothalamic amenorrhoea were treated over41 cycles using a dose of 200 ng/kg/pulse. These patients wererandomly assigned to receive GnRH at pulse frequencies of 60,90, 120 or 180 min. GnRH was administered s.c using portableinfusion pumps. Subjects were paid volunteers with a diagnosisof hypothalamic amenorrhoea. All patients had low to less thandetectable serum concentrations of luteinizing hormone and folliclestimulating hormone on 8 h serial sampling, and normal serumconcentrations of prolactin and androgen, including andro-stenedione,testosterone and dihydroepiandrosterone sulphate. Six of the20 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 frequenciesof 90 and 120 min (60 and 88% of cycles respectively). Ovulationoccurred significantly less often with frequencies of 60 and180 min (12 and 38% respectively; P 0.05). Pregnancy was achievedin four of the six patients who desired a pregnancy at pulsefrequencies of 90 (three out of three) and 120 (one out of one)min. No pregnancies occurred at pulse frequencies of 60 (noneout of one) and 180 (none out of one) min. When ovulatory cycleswere considered, oestradiol concentrations were not differentamong pulse frequencies but varied significantly between ovulatoryand anovulatory cycles. Integrated luteal progesterone concentrationsfor 90 and 120 min frequencies (118.26 25.89 and 125.15 32.10 ng/ml/luteal phase respectively) were significantly higherthan for 60 and 180 min (80.1 48.2 and 42.75 26.48 ng/ml/lutealphase respectively). Ovulation may be induced by a broad rangeof pulse frequencies. Pulse frequencies of 90 or 120 min fors.c GnRH appear to induce more reliably the sequence of folliculardevelopment, ovulation and normal luteal function than frequenciesof either 60 or 180 min. Significantly higher ovulation ratesoccurred at 90 and 120 min by s.c administered GnRH.