Ovulation induction in polycystic ovary syndrome with urinary follicle-stimulating hormone or human menopausal gonadotropin

In patients with polycystic ovarian disease (PCOD) ovulation was induced with a combination of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) or with urinary follicle-stimulating hormone (uFSH; Metrodin, Serono Laboratories, Inc., Randolph, MA) alone. hMG/hCG and uFSH resulted in comparable rates of ovulation and conception in patients with PCOD. The incidence of hyperstimulation and the potential for multiple births appeared lower with uFSH. The fact that endogenous ovulation did not occur in hMG patients who had hCG withheld or in 3 of the 11 uFSH patients who had preovulatory levels of estradiol and follicles greater than 15 mm may imply that these similarly derived gonadotropins in some instances block endogenous ovulation.     

Induction of ovulation in polycystic ovary: human menopausal gonadotropin or human urinary follicle stimulating hormone?

One group of 21 and one group of 22 anovulatory women with polycystic ovaries (PCO) underwent induction of ovulation with human urinary follicle stimulating hormone (HU-FSH)/human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG)/HCG, respectively. No statistically significant differences in ovulation rate were found between patients treated with HU-FSH (95.2%) and those treated with HMG (100%). Eight (38.1%) and 11 (50.0%) patients conceived, six (28.5%) and eight (36.3%) delivered, and two (9.5%) and three (13.6%) aborted with HU-FSH and HMG, respectively. No multiple pregnancies occurred. Serum 17 beta-estradiol (E2) levels and the number of maturing follicles prior to HCG injection were significantly higher with HU-FSH than HMG, while there were no differences in the diameter of the dominant follicle before HCG. Ovarian hyperstimulations were discovered more frequently after HU-FSH/HCG (40%) than HMG/HCG treatments (22.2%). These data do not confirm an effective advantage in the use of HU-FSH in ovulation induction in cases of PCO.     

Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients.

OBJECTIVE: To compare ovarian performance and hormonal levels, after ovulation induction, in patients with isolated hypogonadotropic hypogonadism, using two different gonadotropin drugs. DESIGN: Patients were treated during consecutive cycles, using the same stimulation protocol, with human menopausal gonadotropin (hMG) in the first treatment cycle and purified follicle-stimulating hormone (FSH) in the second one. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Nine patients with isolated hypogonadotropic hypogonadism. MAIN OUTCOME MEASURE: Duration of stimulation, number of leading follicles, serum estradiol (E2) concentration and endometrial thickness at the time of human chorionic gonadotropin administration, and the occurrence of ovulation. RESULTS: Compared with hMG, treatment with purified FSH required significantly more ampules of drug (P less than 0.04) but resulted in a significant reduction in the number of leading follicles (P less than 0.05), serum E2 concentrations (P less than 0.002), endometrial thickness (P less than 0.02) and the occurrence of ovulation (P less than 0.05). CONCLUSION: This study in isolated hypogonadotropic hypogonadism patients is consistent with the two-cell two-gonadotropin hypothesis, that both gonadotropins are required to accommodate their synergistic action for appropriate steroidogenesis. In treating this group of patients, the superior efficacy of hMG compared with purified FSH preparation is beyond question.     

Comparison between human urinary follicle-stimulating hormone and human menopausal gonadotropin treatment in polycystic ovary

Five infertile patients with polycystic ovarian disease were treated to induce ovulation with pure human urinary follicle-stimulating hormone and human menopausal gonadotropin consisting of follicle-stimulating hormone and luteinizing hormone in 1:1 ratio. No substantial differences were seen between the two types of treatment regarding plasma values of follicle-stimulating hormone, prolactin, testosterone, dihydrotestosterone, progesterone, and 17-hydroxyprogesterone. Estrone, estradiol, and androstenedione values were higher during human urinary follicle-stimulating hormone treatments. Luteinizing hormone levels dropped in both treatments, but the fall was greater during human urinary follicle-stimulating hormone. No real differences were observed concerning number of ovulations, length of treatments, and follicle-stimulating hormone amounts administered; no hyperstimulations were observed. These data do not confirm the observation that more controlled responses of the ovaries can be elicited when low luteinizing hormone gonadotropin preparations are used.     

Transient hyperprolactinaemia in human menopausal gonadotropin induction of ovulation

In 20 anovulatory patients who were normoprolactinaemic, 12 developed transient hyperprolactinaemia when they were treated with human menopausal gonadotropin (hMG) for induction of ovulation. The hyperprolactinaemia was probably due to the increased oestrogen production effect on some susceptible patients. The pregnancy rate was found to be lower in those who developed this condition. The dosage of hMG required was found to be significantly higher in this group. The importance of recognizing this transient hyperprolactinaemia and the probably role of Bromocriptine are discussed. Further study is suggested.     

Ovulation induction in the new millennium: Recombinant follicle-stimulating hormone versus human menopausal gonadotropin

The renewed interest in luteinizing hormone (LH), together with limited and decreasing health resources, make essential the comparison of high-cost, recombinant follicle-stimulating hormone (rFSH) preparations (devoid of LH) and human menopausal gonadotropin (hMG) in terms of clinical efficacy. All published, randomized controlled trials (RCTs) comparing rFSH versus hMG under different protocols of stimulation were examined. Eight true RCTs were included in this meta-analysis, recruiting 2031 participants. Data for ongoing pregnancy/live birth rate, clinical pregnancy rate, miscarriage rate, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) were extracted, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with the use of a fixed-effects model. Data for the meta-analysis were combined using RevMan software (using the Mantel–Haenszel method). Pooling the results of these RCTs showed no significant difference between rFSH and hMG regarding the different outcomes: ongoing pregnancy/live birth rate, OR 1.18 (95% CI 0.93–1.50); clinical pregnancy rate, OR 1.2 (95% CI 0.99–1.47), miscarriage rate, OR 1.2 (95% CI 0.70–2.16); multiple pregnancy rate, OR 1.35 (95% CI 0.96–1.90); incidence of moderate/severe OHSS, OR 1.79 (95% CI 0.74–4.33). However, there was significant reduction in the amount of gonadotropins in favor of hMG over rFSH. There was no significant heterogeneity of treatment effect across the trials. In conclusion, there is no clinically significant difference between hMG and rFSH in in vitro fertilization/intracytoplasmic sperm injection cycles. Decision-makers should establish their choice of one drug over the other based on the most up-to-date evidence available.     

Comparison of intermediate-dose purified urinary follicle-stimulating hormone with and without human chorionic gonadotropin for ovulation induction in polycystic ovarian disease

Urinary FSH is capable of inducing ovulation in PCOD. The duration of treatment can be reduced by administering an intermediate dose. However, it appears that prospective monitoring with E2 assays and ultrasound, combined with hCG, is required to optimize outcome and minimize complications. Studies comparing urinary FSH with similar doses of hMG with and without hCG are needed to determine the most effective form of gonadotropin therapy in PCOD.     

Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in polycystic ovarian syndrome

A randomized, double-blind, crossover study was carried out to compare purified urinary follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for ovarian stimulation in polycystic ovarian syndrome (PCOS). Twelve patients were stimulated with FSH and hMG in three alternate cycles. FSH, luteinizing hormone (LH), estradiol, dihydroepiandrosterone sulphate, free and total testosterone, delta 5-androstenedione, sex hormone binding globulin, and ovarian volume were monitored during the stimulation. There was no difference between the dose of FSH and hMG necessary to induce preovulatory follicles in the individual patients. The mean increase of ovarian volume during stimulation with FSH and hMG was 120% and 129% respectively (no significant difference). Two patients became pregnant in the first cycle. Two other patients had delayed bleeding and positive serum-human chorionic gonadotropin. No significant difference was found in the endocrine changes during the two different stimulation methods. The LH/FSH ratio was normalized after a few days of treatment regardless of the type of stimulation. The size of the material does not permit a comparison of the efficacy of the two treatment schedules. Our clinical and ultrasonic observations do not support the theory that treatment of infertility in PCOS with FSH is more safe than with hMG.     

The combination of follicle-stimulating hormone and human menopausal gonadotropin for the induction of multiple follicular maturation for in vitro fertilization

One hundred fifty-one cycles in 134 consecutive patients were stimulated with 150 IU of human urinary follicle-stimulating hormone (FSH) and 150 IU of human menopausal gonadotropin (hMG) on cycle days 3 and 4 and then with 150 IU of hMG daily for the purpose of multiple follicular development for in vitro fertilization (IVF). Seventy-three patients did not have a prior IVF attempt, and 61 patients in 78 cycles had prior IVF attempts at least once with their previous cycles stimulated with the same method and/or hMG and/or FSH. There was an average of three preovulatory oocytes retrieved per laparoscopy and a pregnancy rate of 27% per transfer cycle. The results were equally favorable in "new" and "old" patient cycles. The pregnancy rate increased with the transfer of two or more conceptuses of preovulatory origin. The multiple pregnancy rate, but not the abortion rate, increased with increased numbers of conceptuses transferred.     

Ovulation induction in the new millennium: recombinant follicle-stimulating hormone versus human menopausal gonadotropin.

The renewed interest in luteinizing hormone (LH), together with limited and decreasing health resources, make essential the comparison of high-cost, recombinant follicle-stimulating hormone (rFSH) preparations (devoid of LH) and human menopausal gonadotropin (hMG) in terms of clinical efficacy. All published, randomized controlled trials (RCTs) comparing rFSH versus hMG under different protocols of stimulation were examined. Eight true RCTs were included in this meta-analysis, recruiting 2031 participants. Data for ongoing pregnancy/live birth rate, clinical pregnancy rate, miscarriage rate, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) were extracted, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with the use of a fixed-effects model. Data for the meta-analysis were combined using RevMan software (using the Mantel-Haenszel method). Pooling the results of these RCTs showed no significant difference between rFSH and hMG regarding the different outcomes: ongoing pregnancy/live birth rate, OR 1.18 (95% CI 0.93-1.50); clinical pregnancy rate, OR 1.2 (95% CI 0.99-1.47), miscarriage rate, OR 1.2 (95% CI 0.70-2.16); multiple pregnancy rate, OR 1.35 (95% CI 0.96-1.90); incidence of moderate/severe OHSS, OR 1.79 (95% CI 0.74-4.33). However, there was significant reduction in the amount of gonadotropins in favor of hMG over rFSH. There was no significant heterogeneity of treatment effect across the trials. In conclusion, there is no clinically significant difference between hMG and rFSH in in vitro fertilization/intracytoplasmic sperm injection cycles. Decision-makers should establish their choice of one drug over the other based on the most up-to-date evidence available.     

Ovarian hyperstimulation syndrome following ovulation induction with human menopausal gonadotropin

Twenty-seven anovulatory women who had episode(s) of ovarian hyperstimulation during ovulation induction with hMG were studied. Twenty-nine of the total 89 treatment cycles were complicated by ovarian hyperstimulation. Twenty-four-hour urinary estrogen concentrations 3 days prior to hCG administration were significantly higher in the hyperstimulated (H) than in the nonhyperstimulated cycles (NH). Patients who had progesterone withdrawal bleeding (Group I) were more prone to be hyperstimulated in the first treatment cycle than patients who had no progesterone withdrawal bleeding (Group II). In all instances, the syndrome resolved spontaneously with time. The pregnancy rate of H was threefold NH. It is concluded that hyperstimulation in patients who had evidence of endogenous estrogen activity as demonstrated by progesterone withdrawal bleeding tend to occur in the first treatment cycle. Strict monitoring decreased the incidence of severe hyperstimulation. A minimal amount of hyperstimulation might be beneficial to improve the pregnancy rate.     

Influence of weight in the induction of ovulation with human menopausal gonadotropin and human chorionic gonadotropin

Patients failing to ovulate and conceive on clomiphene citrate (CC) or CC plus human chorionic gonadotropin (hCG) or patients with pituitary gonadotropin deficiency are candidates for human menopausal gonadotropin (hMG) plus hCG therapy. The duration and number of ampules needed to stimulate ovarian response leading to ovulation and/or pregnancy vary individually. Seventy-one patients who had complete follow-up evaluation and accurately documented body weights at the time of therapy were considered for the study. Of these 71 patients, 41 (57.3%) conceived in 293 cycles. The average number of ampules of hMG used by patients with 10% to 20% below ideal body weight (IBW) was 13.9 +/- 6.3 (mean +/- standard deviation [SD]). The average number of ampules used by patients with normal +/- 10% IBW was 14.2 +/- 3.5. Patients who were overweight by 10% to 25% used 15.3 +/- 5.4 ampules, and patients overweight by greater than or equal to 25% used 20.9 +/- 5.6 ampules of hMG. Eleven patients with severe hypothalamic chronic anovulation needed an average of 20.6 +/- 6.2 ampules. The data reveal a direct relationship between IBW and the amount of hMG needed to induce ovulation and/or pregnancy; however, in the presence of chronic hypoestrogenic conditions, it is expected that these patients will need higher amounts of hMG, regardless of body weight.     

A pharmacodynamic comparison of human urinary follicle-stimulating hormone and human menopausal gonadotropin in normal women and polycystic ovary syndrome

We performed a pharmacodynamic comparison of human urinary follicle-stimulating hormone (hFSH) and human menopausal gonadotropin (hMG) to characterize differences in the bioavailability of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as to compare estrogen responses in normal women and those with polycystic ovary syndrome (PCOS). Ten women with PCOS and ten normal ovulatory controls were randomized to receive a single dose (2 ampules) of either hFSH or hMG. Serum LH decreased significantly following hFSH with responses occurring earlier in controls (24.5 +/- 10.9% after 30 minutes) than in PCOS patients (27.3 +/- 7.5% after 18 hours). After hMG, LH increased only in controls (33.8 +/- 16.3%). An FSH increment following hFSH was observed in both PCOS patients (54.7 +/- 24.8%) and controls (74.6 +/- 36.8%), with peak responses at 6 and 4 hours, respectively. However, after hMG, FSH increased only in controls. The LH/FSH ratio after hFSH decreased, with the nadir at 18 hours (1.438 +/- 0.183) being similar to baseline LH/FSH ratios of controls (1.433 +/- 0.341). Serum estradiol (E2) increased following hMG, with peak responses after 18 hours, in both PCOS patients (75.4 +/- 28.6%) and controls (88.5 +/- 32.5%). The peak E2 response to hFSH was observed to be earlier in PCOS patients (147 +/- 34%), occurring after 12 hours, compared with controls (58 +/- 29% after 18 hours).     

Equivalency of human menopausal gonadotropin and follicle-stimulating hormone stimulation after gonadotropin-releasing hormone agonist suppression

This study compares the use of human menopausal gonadotropin (hMG) versus follicle-stimulating hormone (FSH), after gonadotropin-releasing hormone agonist (GnRH-a) suppression for in vitro fertilization. Thirty-seven patients were randomized to ovarian stimulation with either hMG or pure FSH. The GnRH-a leuprolide acetate was administered to all patients beginning in the midluteal phase of the prior cycle and continuing until the day of human chorionic gonadotropin (hCG) administration. There were no significant differences between hMG and FSH cycles with regard to the day of hCG administration, mean peak estradiol levels, number of ampules of medication used, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that there is no significant difference between hMG and FSH stimulation when used in conjunction with GnRH-a.     

Sequential use of clomiphene citrate and human menopausal gonadotropin in ovulation induction.

In an effort to diminish the incidence of multiple pregnancy, ovarian hyper-stimulation syndrome, and the excessive cost of human menopausal gonadotropin (HMG) administration, a sequence of Clomid-HMG-human chorionic gonadotropin (HCG) was used in 80 patients with infertility due to prolonged amenorrhea. Criteria for this therapeutic regimen were: (1) normal seminal fluid analysis and postcoital test; (2) lack of withdrawal bleeding from progesterone following amenorrhea of more than 6 months' duration; (3) normal x-ray of the sella turcica and visual fields; (4) low serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels; (5) normal endoscopic examination; and (6) lack of response to clomiphene in excessive dose (200 mg daily for 5 days) or prolonged dose (100 mg daily for 10 days) with or without HCG, or apparent ovulatory response to the above sequence for five or six consecutive cycles without pregnancy. Clomiphene was administered in a dose of 100 mg daily for 7 days. HMG was then given in the following manner: two ampules daily for 4 days, then one ampule daily for 2 days (75 IU of FSH and 75 IU of LH/ampule). After a 24-hour interval without treatment, 10,000 IU of HCG were given and 2000 IU of HCG 4 days later. Twenty-three pregnancies occurred in 80 patients. However, 15 of the first 25 patients became pregnant--in these patients the only abnormality noted was lack of ovulation. Six additional pregnancies occurred subsequent to one or more unsuccessful cycles. Multiple pregnancies occurred in only two patients (twins delivered at 32 weeks in one and an abortion of five fetuses at 20 weeks in another). However, multiple pregnancy did not occur in any patient whose urinary estrogen level was monitored and in whom the level was 100 mug or less when the HCG was given. The ovarian hyperstimulation syndrome did not occur in any patient.     

Induction of ovulation in amenorrheic patients with gonadotropin-releasing hormone and human menopausal gonadotropin

In five hypothalamic amenorrhea patients who underwent chronic intermittent gonadotropin-releasing hormone (GnRH) therapy for induction of ovulation, small doses (2 to 4 ampules/day) of human menopausal gonadotropin (hMG) were administered 9 to 32 days after the start of GnRH treatment. In seven treatment cycles, the addition of hMG initiated a sudden rise of 17 beta-estradiol concentrations, followed by a luteinizing hormone and follicle-stimulating hormone surge and ultrasonographic evidences of ovulation. Four of five patients conceived (singleton pregnancies) after the first or second treatment course. There were no clinical signs of ovarian hyperstimulation. Combined therapy of GnRH and hMG may be useful, therefore, for the treatment of hypothalamic amenorrhea patients who demonstrate prolonged follicular phases or luteinized unruptured follicle syndrome under chronic treatment with pulsatile GnRH alone.     

Down-regulation of testicular follicle-stimulating hormone receptors by human menopausal gonadotropin in infertile men

We measured testicular FSH receptors in 27 infertile men before, or 1, 3, 5, 7, or 14 days after a single administration of 150 IU of hMG. The administration of hMG reduced Bmax for FSH receptors to about 50% of that in the preadministration testes for 5 days. From the seventh day, Bmax of FSH receptors began to increase and returned to the preadministration level 14 days after the administration.