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. Ovulation induction in polycystic ovarian disease by pure FSH (Metrodin). A comparison between chronic low-dose pulsatile administration and i.m. injections. Use of combined exogenous gonadotropins and pulsatile gonadotropin-releasing hormone in patients with polycystic ovarian disease. [Treatment of refractory polycystic ovary syndrome by bushen huoxue method combined with ultrasound-guided follicle aspiration]. Treatment of clomiphene citrate-resistant polycystic ovarian syndrome with pure follicle-stimulating hormone or human menopausal gonadotropin. Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation.
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. A randomized cross-over study was performed to assess the value of pulsatile versus i.m. administration of pure FSH in polycystic ovarian disease. All patients admitted to the study had failed to respond to treatment with clomiphene citrate, while four had also been unsuccessfully treated with i.m. Pergonal. Sixteen cycles with i.m. FSH and 15 cycles with pulsatile s.c. FSH were analysed. The results showed no statistically significant differences in the dosage, the rate of ovulation or pregnancy rate. Hyperstimulation occurred in 30% of both the treatment groups. It is concluded that chronic low-dose pulsatile administration of pure FSH (Metrodin, Serono) has no advantage over chronic low-dose i.m. administration. We previously tested a combined regimen based on the administration of gonadotropin in the early follicular phase followed by pulsatile gonadotropin-releasing hormone (GnRH) until complete follicular maturation in patients suffering from polycystic ovarian disease. Despite good clinical results, a high rate of premature luteinization was observed with this approach. We therefore evaluated in this study whether starting pulsatile GnRH therapy before gonadotropin administration might reduce premature luteinization. Eight women underwent induction of ovulation with both combined therapy and pure exogenous follicle-stimulating hormone alone using a crossover scheme. No premature luteinization and a single follicular growth were recorded with the modified combined regimen. Clinical results (8/8 versus 3/7 ovulatory cycles; 3/8 versus 1/7 pregnancies) favor the combined approach over gonadotropin alone. To observe the clinical effect of traditional Chinese medicine Bushen Houxue (BSHX) method combined with ultrasound-guided follicle aspiration (MFA) in treating refractory polycystic ovary syndrome (PCOS).
                Forty-four patients with PCOS were randomly assigned to two groups by randomizing digital table, 20 in the observation group and 24 in the control group. MFA was performed on both groups, and the decoction of BSHX, which consisted of dodder seed 20 g, prepared rehmannia root 10 g, mulberry mistletoe 20 g, epimedium 15 g, psoralea fruit 10 g, solomonseal rhizome 10 g, honeylocust thorn 15 g, peach kernel 10 g, pleione bulbocodioides 10 g, red sage root 20 g, and licorice root 6 g, was given to the observation group one dose every day for 14 days every menstrual cycle. Changes of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were determined before and after MFA. The impacts on quantity of HMG used, number of sinus follicle, mature follicle, incidence of ovarian hyperstimulating syndrome (OHSS), luteinized unrupture follicular syndrome (LUFS) and pregnance rate were also observed.
                MFA had been performed for 42 cycles in the observation group and 56 cycles in the control group. Levels of T, LH and LH/FSH ratio markedly reduced after aspiration, showing significant difference as compared with those of before treatment in both groups (P < 0.01), and difference of LH/FSH between groups was of statistical significance (P <0.01). In the observation group, 18 patients (90.0%) had their sinus follicle decreased to < 10 after MFA, while in the control group, it reached to <10 in 22 patients (91.70%), all were different to those before treatment (P <0.01). In the observation group, the quantity of HMG used for promoting ovulation was (585.0 +/- 195.0) IU, number of mature follicle at the day of HCG injection was 1.1 +/- 0.3, while in the control group, the corresponding data were (1470.0 +/- 532.5) IU and 3.1 +/- 1.4, all with significant difference between groups (P <0.01). None of OHSS and 1 case of LUFS occurred in the former group, while 1 mild OHSS and 2 LUFS in the latter. After ovulation promoting therapy and in the 3-month secutive follow-up period, pregnancy was found in 8 out of the 18 patients in the observation group (one twins and 7 single), with the pregnancy rate of 44.4%; while in the control group, 7 in 22 (2 twins and 5 single) was found, the pregnancy rate being 31.8%.
                BSHX method combined with MFA is a safe and effective treatment for refractory PCOS, with few trauma. The combined usage of Chinese herbal medicine could significantly reduce dosage of HMG used for promoting follicle and the production of multiple mature follicles, thus to avoid the risk of OHSS. Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%. Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients.
                Part I of the study was an observational pilot study to evaluate the hormonal change as a result of the Diane/cetrorelix protocol (n = 26). Part II of the study was a prospective randomized study comparing the Diane/cetrorelix protocol (n = 25) and the GnRH agonist long protocol (n = 24). In the Diane/cetrorelix protocol, patients were pre-treated with three cycles of Diane-35, followed by 0.25 mg of cetrorelix on cycle day 3. From day 4, cetrorelix and gonadotrophin were administered concomitantly until the day of HCG injection.
                Serum LH, estradiol and testosterone levels were suppressed comparably in both protocols at the start of gonadotrophin administration. Serum LH was suppressed at constant levels without a premature LH surge in the Diane/cetrorelix protocol. The clinical results for both protocols were comparable, with significantly fewer days of injection, lower amounts of gonadotrophin used and lower estradiol levels on the day of HCG injection following the Diane/cetrorelix protocol. Furthermore, there was no significant difference in clinical pregnancy outcome between the two stimulation protocols.
                The Diane/cetrorelix protocol has a similar pregnancy outcome to the GnRH agonist long protocol for women with PCOS undergoing IVF treatment. To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH).
                A prospective randomized trial.
                The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France.
                One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period.
                Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression.
                Response to COH, pregnancy rate (PR), tolerance.
                In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups.
                We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.
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.