OVULATION INDUCTION USING SC PULSATILE GONADOTROPIN-RELEASING-HORMONE- EFFECTIVENESS OF DIFFERENT PULSE FREQUENCIES

To determine the ovarian response to a fixed dose of gonadotrophin-rel easing hormone (GnRH) administered s.c. at four different pulse freque ncies, 20 patients with hypothalamic amenorrhoea were treated over 41 cycles using a dose of 200 ng/kg/pulse. These patients were randomly a ssigned to receive GnRH at pulse frequencies of 60, 90, 120 or 180 min , GnRH was administered s.c. using portable infusion pumps, Subjects w ere paid volunteers with a diagnosis of hypothalamic amenorrhoea, All patients had low to less than detectable serum concentrations of lutei nizing hormone and follicle stimulating hormone on 8 h serial sampling , and normal serum concentrations of prolactin and androgen, including androstenedione, testosterone and dihydroepiandrosterone sulphate, Si x of the 20 patients were enrolled in the protocol to achieve a pregna ncy, while 14 were volunteers using a barrier method of contraception, Highest ovulation rates were achieved using pulse frequencies of 90 a nd 120 min (60 and 88% of cycles respectively), Ovulation occurred sig nificantly less often with frequencies of 60 and 180 min (12 and 38% r espectively; P less than or equal to 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 pregnancie s occurred at pulse frequencies of 60 (none out of one) and 180 (none out of one) min, When ovulatory cycles were considered, oestradiol con centrations were not different among pulse frequencies but varied sign ificantly 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 sign ificantly 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 f or 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 a t 90 and 120 min by s.c. administered GnRH.