A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome. Pulsatile gonadotrophin releasing hormone stimulation after medium-term pituitary suppression in polycystic ovary syndrome. Initial experiences with subcutaneous pulsatile human menopausal gonadotropin administration: successful induction of ovulation in patients with polycystic ovarian disease.
OBJECTIVE: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC). DESIGN: Subgroup analysis within a randomized, controlled, multicenter study. SETTING: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands. PATIENT(s): Twenty-eight infertile patients with PCOS. INTERVENTIONs): Patients were randomly assigned to pulsatile IV GnRH (10-20 microgram/90 min) after GnRH-a down-regulation or CC (50-150 mg; cycle days 3-7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E(2), LH, and FSH. Serum P and sonography confirmed ovulation. MAIN OUTCOME MEASURE(s): Serum concentrations of E(2), LH, and FSH were assessed before treatment was started and after each ovarian sonography. RESULT(s): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E(2), LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group. CONCLUSION(s): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion. Ovulation induction in the polycystic ovary syndrome with pulsatile gonadotrophin releasing hormone (GnRH) in the recovery phase after treatment with a GnRH agonist (GnRHa) during 6-8 weeks has been reported to improve ovulation and pregnancy rates and to normalize follicular phase luteinizing hormone (LH) levels. We studied the results of stimulation with pulsatile GnRH after a shorter 'medium-term' period of 3 weeks of treatment with a GnRHa by comparing a cycle without GnRHa pre-treatment with a cycle with GnRHa (post-GnRHa) pre-treatment in 12 patients. We could prove no significant clinical improvement in post-GnRHa cycles. Ovulation rates were similar. However, in the post-GnRHa cycles, two ongoing pregnancies were observed versus one spontaneous abortion in the cycles without GnRHa pre-treatment. This observation might be explained by the fact that follicular phase LH levels in post-GnRHa cycles were significantly decreased. Human menopausal gonadotropin (hMG) was administered to 10 patients with polycystic ovarian disease (PCOD) who had failed to ovulate in response to clomiphene citrate. Five patients (group 1) were treated with intramuscular hMG injections daily, on an individually adjusted regimen. Five others (group 2) were stimulated with subcutaneous hMG in a pulsatile fashion by means of a portable infusion minipump. The pulse doses ranged between 3.5 and 7.7 IU FSH per pulse at a constant frequency of 90 minutes. Sixteen of 18 treatment cycles were ovulatory, 9 under intramuscular, and 7 under subcutaneous treatment. A total of two patients conceived with singleton pregnancies, one in each treatment group. Neither ovarian hyperstimulation nor complications of injections were noted. The amount of subcutaneous hMG required to achieve ovulation was significantly less (46.5%; P less than .001) than that needed with intramuscular administration. However, there were no differences in the duration of stimulation periods, the lengths of luteal phases, or serum E2 and gonadotropin levels between the groups. In conclusion, pulsatile subcutaneous hMG administration may be an alternative delivery mode for patients with PCOD.
The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.