Comparison of pulsatile subcutaneous gonadotropin-releasing hormone and exogenous gonadotropins in the treatment of men with isolated hypogonadotropic hypogonadism

Eight men with isolated hypogonadotropic hypogonadism were treated with pulsatile gonadotropin-releasing hormone (GnRH) after maximal testicular growth and function had already been achieved with human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG). Only four subjects could normalize plasma testosterone (T) levels (group A). After 18 months of GnRH therapy, testicular size of group A increased by 53% (P less than 0.01) over that previously attained with exogenous gonadotropins. However, despite further testicular growth, two men who were previously azoospermic on hCG/hMG remained so on GnRH. In the other two patients, total sperm count increased minimally. Thus, pulsatile gonadotropin levels achieved with GnRH are more effective in stimulating testicular growth, but not necessarily sperm output, than are stable gonadotropin concentrations obtained with hCG/hMG.     

Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin

The purpose of this study was to analyze follicular fluid (FF) samples for steroid levels from stimulated and unstimulated cycles triggered with human chorionic gonadotropin (hCG) and to assess the influence of controlled ovarian hyperstimulation and luteinizing hormone/hCG on these levels. Spontaneous ovulatory cycles were monitored with serial ultrasound examinations, and hCG 10,000 IU was given when the lead follicle was mature. Fourteen FF samples yielding fertilizable oocytes were compared with 13 FF samples from controlled ovarian hyperstimulation cycles. Progesterone (P) was higher in controlled ovarian hyperstimulation than in unstimulated cycles (9.0 +/- 1.2 micrograms/mL versus 4.4 +/- 0.6 microgram/mL; mean +/- SEM), whereas estradiol (E2) was lower (0.8 +/- 0.1 microgram/mL versus 1.3 +/- 0.2 microgram/mL), resulting in a higher P:E2 ratio (15.5 +/- 3.3 versus 4.4 +/- 0.7). Androstenedione (A), testosterone (T), and T:E2 ratios were all higher in unstimulated than controlled ovarian hyperstimulation cycles. We conclude that controlled ovarian hyperstimulation is associated with increased FF P, decreased FF E2, T, and A levels, and decreased T:E2 ratios, suggesting altered steroidogenesis and enhanced follicular aromatase activity.     

Elevated serum estradiol associated with increased androstenedione-testosterone ratio in adolescent males with varicocele and gynecomastia

OBJECTIVE: To investigate the testicular function in adolescents with pubertal gynecomastia associated with varicocele before and after varicocelectomy. DESIGN AND PATIENTS: We have studied six male adolescents 15 to 19 years of age with bilateral gynecomastia. They were selected among other adolescents with gynecomastia because of the presence of visible varicoceles. All of them had normal physical examination and secondary sexual characteristics. This was prospective study of 3 months' duration. All the patients that were included finished the study. SETTING: All the patients were evaluated in the Endocrine Clinic of Winthrop-University Hospital, a tertiary care unit. INTERVENTION: Serum testosterone (T), androstenedione (A), and estradiol (E2) responses to the administration of human chorionic gonadotropin (hCG) 2,000 IU for 3 consecutive days before and 3 months after varicocelectomy were determined. RESULTS: Varicocelectomy did not cause any significant changes in the basal (pre-hCG) levels of the steroid. However, the increase in T levels achieved with hCG was significantly (P less than 0.005) higher after varicocelectomy (before T, 925 +/- 212 ng%; after T, 1,649 +/- 406 ng%). Simultaneously, the stimulated levels of E2 and A were significantly lower (P less than 0.005) after varicocelectomy (E2, 62 +/- 12 pg/mL; A, 326 ng% +/- 80 ng%) than before (E2, 106 +/- 13 pg/mL; A, 580 ng% +/- 95 ng%). CONCLUSION: The reciprocal effect on the levels of T and its immediate precursor, A, suggests an impairment of the 17-ketoreductase enzyme activity. The increased levels of E2 after hCG and its normalization after varicocelectomy suggests that varicoceles may play a pathogenetic role in the development of gynecomastia.     

Luteal dysfunction in ovulation induction: the role of repetitive human chorionic gonadotropin supplementation during the luteal phase

Several studies have indicated that ovulation induction with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) or clomiphene citrate (CC) is associated with luteal phase defect. To assess the efficiency of luteal support by hCG to an infertile population undergoing ovulation induction, with CC/hCG or hMG/hCG, we have randomly administered 2500 IU hCG intramuscularly on days 3, 6, and 9 after ovulation induction by 10,000 IU of hCG to 74 patients on 265 treatment cycles. As controls served 357 ovulation induction cycles in the same 74 patients. The treatment cycles were randomly alternated with control cycles so that each patient served as her own control. However, the mean +/- standard deviation (SD) midluteal P was 38.1 +/- 10.8 ng/ml in the study group versus 15.7 +/- 10.5 ng/ml in the control group (P less than 0.001). Luteal phase length was 15.4 +/- 1.5 days in the treatment group versus 12.1 +/- 1.7 in the control group (P less than 0.01). In the treatment group, 64.8% of the patients achieved pregnancy (27% pregnancies/treatment cycle) versus 47.3% in the control group (11.5% pregnancies/control cycle) (P less than 0.01). The pregnancy wastage rates (including abortions and "chemical" pregnancies) were 30.6% in the treatment group versus 56% in the control group (P less than 0.01). We conclude that repetitive hCG administration may be an efficient luteal support in infertile patients undergoing ovulation induction.     

Ovarian stimulation for in vitro fertilization and embryo transfer, human menopausal gonadotropin versus pure human follicle stimulating hormone: a randomized prospective study

A randomized, prospective study was conducted to compare ovarian stimulation with human menopausal gonadotropin (hMG) and human follicle-stimulating hormone (hFSH) in an in vitro fertilization and embryo transfer (IVF-ET) program. Minimal inclusion criteria included age less than or equal to 37, tubal infertility, regular menstrual cycles before IVF, and a normal semen analysis. Equivalent doses (225 IU/day) of either hMG (N = 20) or hFSH (N = 20) were administered, and the patients followed by serum estradiol (E2) levels and pelvic ultrasound. Parameters related to the ovarian response to therapy, the number and quality of ova recovered, and the cycle outcome were compared in the two groups using the Student's t-test and chi-square analysis. No difference was detected between the groups in peak E2 levels (828 +/- 78 versus 819 +/- 79 in the hMG and hFSH groups, respectively), day of human chorionic gonadotropin (hCG) administration (9.3 +/- 0.3 versus 9.7 +/- 1.01), occurrence of spontaneous luteinizing hormone (LH) surge (44% versus 27%, P greater than 0.05, chi square analysis), average number of ova recovered (5.0 +/- 0.7 versus 5.6 +/- 1), ova maturation (7.5% versus 12.7% rate of immature ova), rate of normal and abnormal fertilization (9.2% versus 8.1% polyspermic fertilization), cleavage stage at transfer (3.6 +/- 0.4 versus 3.4 +/- 0.7 cells per embryos), the number of embryos transferred (2.5 +/- 0.3 versus 2.6 +/- 0.3), or the occurrence of pregnancy (1 in the hMG group and 2 in the hFSH group).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal therapy and pubertal development in boys with selective hypogonadotropic hypogonadism

The authors have compared the effects of treatment with weekly injections of human chorionic gonadotropin (hCG) with those of monthly testosterone (T) injections in males with hypogonadotropic hypogonadism. There was no significant difference in pubertal development as measured by progression through the Tanner stages, final height, or bone age, with the two treatment regimens. The final testicular volume in patients treated with 5,000 U/week of hCG (14.0 +/- 2.0 ml) was significantly greater than that in patients treated with 250-mg monthly T injections (4.3 +/- 1.8 ml) (P less than 0.01). This study shows that weekly injections of hCG are effective in achieving virilization in hypogonadotropic hypogonadic males, leading to a greater testicular growth than T preparations. Therefore, hCG treatment may have an advantageous effect on the eventual induction of fertility with human menopausal gonadotropin.     

Episodic luteinizing hormone release in idiopathic oligospermia

The pathophysiology of idiopathic oligospermia (IO) is not fully understood. As some males with IO, particularly those with low normal testosterone (T), may respond favorably to human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG), aberration in gonadotropin release may be implied in these subjects. Therefore, episodic luteinizing hormone (LH) was studied in five males with IO and normal T and compared to six normal control males. Blood samples were obtained every 20 minutes, commencing at 8 A.M. over a period of six to eight hours and assayed for FSH and LH. T was determined at 0, 100, 180, 300, 360, and 480 minutes. Mean LH of 44.6 +/- 4.8 ng/mL (mean + standard error of the mean) in IO was higher than the mean LH of 32.2 + 3.1 ng/mL in the control group (P less than .025). Mean FSH of 204.2 +/- 20.3 ng/mL in IO was higher than mean FSH of 143.1 +/- 22.0 ng/mL in the control group (P less than .05). Mean T of 430 + 56 ng/dL in IO was comparable to 471 +/- 59.2 in the control group. The frequency of LH pulses was similar in both groups. The mean pulse amplitude of LH, 27 +/- 5.5 ng/mL, in IO was significantly higher than in the control group (15 +/- 2.2 ng/mL) (P less than .05). Although a central mechanism cannot be excluded, our data support a possible abnormality in testicular function in some males with IO.     

Hormonal secretions in singleton pregnancies arising from the implantation of fresh or frozen embryos after oocyte donation in women with ovarian failure.

OBJECTIVE: To determine whether levels of human chorionic gonadotropin (hCG), 17 beta-estradiol (E2), and progesterone (P) are different in the peri-implantation phase of fresh versus frozen embryos. DESIGN: Hormonal secretions were measured on days 9 and 11 after implantation and at 4, 5, and 6 weeks gestation. PATIENTS: Thirty-one pregnancies were achieved in 65 patients with ovarian failure. Seventeen singleton pregnancies developed after implantation of 4 frozen and 13 fresh embryos. RESULTS: Human chorionic gonadotropin and E2, contrary to P, were higher in cases of fresh embryos from the 9th day after transfer to the 5th week at which time they become statistically significant (respectively, for hCG and E2, 5,800.3 +/- 332.3 versus 2,027.3 +/- 916.3 [mean +/- SD] mIU/mL for hCG and 562.3 +/- 215 versus 291 +/- 152 pg/mL for E2). CONCLUSIONS: This difference might be explained by either the higher number of fresh embryo replaced or by the fact that the number of blastomeres and also their metabolic activity could be reduced after freezing and thawing.     

Subcutaneous gonadotropin therapy in male patients with hypogonadotropic hypogonadism

OBJECTIVE: The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism. DESIGN: Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively. SETTING: The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology. PATIENTS: Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmann's syndrome in prepubertal or early pubertal stages. INTERVENTIONS: Human chorionic gonadotropin and hMG were administered SC in individual dosages. MAIN OUTCOME MEASURES: Increase of serum testosterone (T), testicular volume, semen volume, and sperm count were evaluated. RESULTS: Normalization of serum T and complete sexual maturation was achieved in all patients. Spermatogenesis was induced in all but two patients. Seven patients showed normal findings in semen volume and sperm count, and two patients had semen quality close to normal. In five patients sperm count remained less than 10 x 10(6)/mL. CONCLUSIONS: The results obtained by SC gonadotropin replacement prove this mode of administration to be effective in stimulating steroidogenesis and spermatogenesis in hypogonadotropic males.     

A long-acting gonadotropin-releasing hormone agonist inhibits the growth of a human ovarian epithelial carcinoma (BG-1) heterotransplanted in the nude mouse

Human ovarian epithelial carcinoma (BG-1) was heterotransplanted in female nude athymic mice and growth was evaluated in intact, surgically castrated, and gonadotropin-releasing hormone (GnRH) agonist (Lupron-SR)-treated mice. Tumor volume was represented as percent of tumor volume on day 0 and measured every other day from the administration of drug and/or the attainment of a minimum tumor volume of 0.5 cm3 on each side of the animal. Tumors in surgically castrated mice had significantly accelerated growth compared with control tumors grown in intact mice (1810 +/- 247.2 versus 1253.6 +/- 44.6%, respectively; P less than .05). Treatment with GnRH agonist significantly reduced tumor growth in intact mice at days 16, 18, and 20 compared with normal control tumors and placebo-treated tumors in intact mice (P less than .02). Gonadotropin levels in pooled serum of mice were reduced from normal levels with GnRH agonist treatment (control: mLH 16.9 +/- 2.2 ng/mL, mFSH 6.6 +/- 0.3 ng/mL; GnRH agonist-treated: mLH 9.3 +/- 1.8 ng/mL, mFSH 4.9 +/- 0.7 ng/mL; surgically castrated: mLH 32.2 +/- 2.7 ng/mL, mFSH 19.4 +/- 0.5 ng/mL). This human tumor model appears responsive to gonadotropins as evidenced by the ability of a GnRH agonist to inhibit growth of BG-1. These results suggest that GnRH agonist therapy may be a useful adjuvant in the treatment of human ovarian epithelial carcinoma.     

Ovarian responses to menopausal gonadotropins in groups of patients with differing basal growth hormone levels.

OBJECTIVE: To investigate the relationship between endogenous serum levels of human growth hormone (hGH) and ovarian response to human menopausal gonadotropins (hMG). DESIGN: Retrospective analysis of patient response to hMG. SETTING: Center for assisted reproductive technology. PATIENTS: Eighty women who had undergone controlled ovarian hyperstimulation with hMG. Basal levels of hGH in sera from 40 of these patients were less than 5.0 microIU/mL (low hGH), values for the remaining 40 were greater than 5.0 microIU/mL (high hGH). Levels of hGH in day 2 sera were analyzed against numbers of oocytes recovered in an additional 182 patients. MAIN OUTCOME MEASURES: Serum estradiol (E2) levels and numbers of oocytes recovered at oocyte pick-up. RESULTS: Average (+/- SE) levels of hGH in sera of high-hGH and low-hGH patients were 10.2 +/- 0.6 and 2.47 +/- 0.3 microIU/mL, respectively (P less than 0.05). Respective peripheral levels of insulin-like growth factor-I were 105.3 +/- 2.9 and 97.2 +/- 2.8 ng/mL. Levels of E2 in serum of high-hGH patients exceeded respective (P less than 0.05) low-hGH values throughout folliculogenesis, and more oocytes were recovered from high-hGH patients (8.1 +/- 0.9 versus 4.7 +/- 0.5 for low-hGH patients; P less than 0.05). Serum progesterone values did not differ. Higher day 2 hGH levels were associated with higher numbers of oocytes recovered after controlled ovarian hyperstimulation. CONCLUSIONS: The present findings indicate that endogenous hGH may augment gonadotropins during follicle recruitment and during multiple folliculogenesis in women. The phase of maximum ovarian sensitivity to hGH/gonadotropin synergism and the nature of synergism remain unclear.     

Use of micro-dose human chorionic gonadotropin (hCG) after clomiphene citrate (CC) to complete folliculogenesis in previous CC-resistant anovulation

OBJECTIVE: The purpose of this study was to compare the effectiveness of low-dose human chorionic gonadotropin (hCG) in the late follicular phase to induce ovulation and its endocrine response in patients who had previously failed to ovulate on clomiphene citrate (CC) alone. DESIGN: A total of 67 patients from a private tertiary infertility clinic, who had produced a dominant follicle 12 mm or larger but 20 mm or smaller on a prior CC cycle at 100 mg but had failed to ovulate, were prospectively randomly assigned to groups. Group 1 repeated the 100 mg dose of CC but started a 200 IU hCG intramuscular injection daily when the largest follicle was 12 mm or larger mean diameter. Group 2 received a 150 mg dose of CC and both groups were monitored with transvaginal ultrasound and serum levels of E 2 , P 4 , and testosterone. Ultrasound measurements of follicle number and growth, ovulation, pregnancy rates, and serum hormonal levels were recorded and compared between the 2 groups. Analysis of variance and Student t test were used for statistical significance. RESULTS: The low-dose hCG group had significantly higher percentage of ovulatory cycles (57% vs 7% P < .001), peak E 2 levels (378 pg/mL vs 125 pg/mL P < .01), and pregnancy rates (18% vs 0% P < .001). This group showed no evidence of premature leutinization from the hCG with preovulatory P 4 levels less than 1.0 ng/mL and a slight increase in androgen levels. CONCLUSION: The use of micro-dose hCG after CC in the late follicular phase results in continued follicle growth, increased E 2 levels, ovulation, and pregnancies. This treatment offers an efficient and cost-effective alternative before gonadotropin therapy for this type of patient.     

Effect of growth hormone administration on human ovarian function and steroidogenic gene expression in granulosa-luteal cells.

OBJECTIVE: To study the effect of growth hormone (GH) in combination with an ultrashort-term gonadotropin-releasing hormone analogue/human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) regimen in ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized placebo-controlled study. SETTING: University-based IVF program. PATIENTS: Fifty-four normally cycling women (27 control and 27 GH-treated) participated in this study. INTERVENTIONS: Human recombinant GH (24 IU)/placebo was given intramuscularly on alternate days starting on cycle day 4 until the day of last hMG injection. RESULTS: Serum estradiol (E2) and progesterone (P) concentrations were slightly lower in the GH group than in the placebo group on the day of hCG injection and 1 day thereafter (P < 0.01 to 0.001). Serum luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone (T), and sex hormone-binding globulin did not differ between the groups. The follicular fluid (FF) concentration of T was higher in the GH group than in the placebo group (15.9 +/- 6.0 nmol/L versus 10.2 +/- 4.9 nmol/L, P < 0.005), and no differences were observed in the FF concentrations of E2, P, and insulin-like growth factor I between the groups. In granulosa cells isolated from patients who received GH treatment, the levels of 3 beta-hydroxysteroid dehydrogenase and aromatase messenger ribonucleic acid were significantly higher than in the patients receiving placebo. The number of hMG ampules needed for follicular development and the number of follicles and oocytes recovered were similar in both groups. CONCLUSIONS: These results indicate that GH administration modifies ovarian steroidogenic response to gonadotropins in IVF patients, suggesting a role for GH in the regulation of human ovarian function.     

Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist

OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome.     

Suppression of corpus luteum function by the gonadotropin-releasing hormone antagonist Nal-Glu: effect of the dose and timing of human chorionic gonadotropin administration

OBJECTIVE: To assess the effect of gonadotropin-releasing hormone antagonist Nal-Glu administration in the luteal phase and the potential rescue by exogenous human chorionic gonadotropin (hCG) of corpus luteum (CL) after antagonist treatment. DESIGN: We studied the dose of Nal-Glu required for luteolysis and subsequently we coadministered low doses of hCG for 3 consecutive days either simultaneously to Nal-Glu administration (n = 5), or 48 (n = 5), or 72 hours (n = 5) later. Six additional participants received pharmacological doses of hCG 48 hours after the luteolytic dose of Nal-Glu. SETTING: Participants were studied in Clinique Endocrinologique, Nantes, and in Service d'Endocrinologie, H?pital Bicêtre, Le Kremlin Bicetre, France. PARTICIPANTS: Twenty-nine normal young women (ages 20 to 35) were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Measurements of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, Progesterone (P) levels were performed by radioimmunoassay before, during, and after the various treatment regimens. RESULTS: Complete luteolysis occurred in women who received 10 mg of Nal-Glu daily on days 4 and 5 after the LH surge. The coadministration of Nal-Glu and hCG overrode the effect of the antagonist (P = 48.8 +/- 22.5 versus 60.8 +/- 3.1 nmol/L in controls treated with hCG alone [NS]). When hCG treatment was started 48 hours after Nal-Glu, a partial luteolysis occurred (P = 33.8 +/- 10.9 versus 117 +/- 12.9 nmol/L, P less than 0.01). When hCG was started 72 hours after Nal-Glu, a complete luteolysis occurred (P = 5.8 +/- 2.05 versus 36.2 +/- 0.6 nmol/L, P less than 0.01). Higher doses of hCG (1,500 or 5,000 IU) administered 72 hours after Nal-Glu resulted in a significant rescue of CL function (P = 37.7 +/- 4.8 and P = 43.8 +/- 22.2 versus 74.5 +/- 19.8 and 130.2 +/- 14.3 nmol/L, P less than 0.05), respectively. CONCLUSIONS: These results confirm the LH dependence of CL function. The suppression of CL LH support for 72 hours induced a compromise of the CL nonreversible by low doses of hCG mimicking early pregnancy but reversible with pharmacological doses.     

Preferred treatment of infertile women older than 37 years of age who demonstrate premature luteinization in the first evaluation cycle

OBJECTIVE: To evaluate the efficacy of various treatments in abolishing premature luteinization in infertile women over 37 years old who are undergoing ovulation induction. DESIGN: Prospective, nonrandomized study. SETTING: Tertiary care medical clinic. PATIENT(S): Seventeen infertile women >37 years old in whom premature luteinization was detected during their evaluation (pretreatment) cycle. INTERVENTION(S): The patients underwent three consecutive treatment cycles with clomiphene citrate (group A), hMG (group B), and a GnRH agonist plus hMG (group C). MAIN OUTCOME MEASURE(S): Premature luteinization, defined as a progesterone/E2 ratio of >1 on the day of hCG administration. RESULT(S): Fifteen (88%) of the 17 patients in group A and 13 (76%) of the 17 patients in group B demonstrated premature luteinization. In contrast, only 1 (6%) of the 17 patients in group C had a progesterone/E2 ratio of >1 on the day of hCG administration. The mean (+/-SD) E2 level on the day of hCG administration was significantly higher in group C (1.236 +/- 772.7 pg/mL) than in group A (214.02 +/- 104.46 pg/mL) or group B (412.5 +/- 337 pg/mL). CONCLUSION(S): Pituitary desensitization with a GnRH agonist in conjunction with hMG may be of benefit for older infertile women who demonstrate early luteinization in their first evaluation cycle.     

Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone

OBJECTIVE: To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG. DESIGN: Controlled, prospective, randomized comparison of fixed gonadotropin regimens. SETTING: Academic research institution. PATIENT(S): Fifty infertile patients who were candidates for IUI. INTERVENTION(S): Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen). MAIN OUTCOME MEASURES: Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications.Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ. CONCLUSION: The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.     

Cocaine impairs ovarian response to exogenous gonadotropins in nonhuman primates.

OBJECTIVE: Determine whether cocaine directly impairs ovarian steroid production and ovulation. METHODS: Normally cycling adult female rhesus monkeys received daily intravenous normal saline (control; n = 8) or cocaine (4 mg/kg; n = 8) through the follicular phase. Monkeys were injected daily with human menopausal gonadotropin (hMG; Pergonal) at a dose of 6 IU/kg intramuscularly beginning on cycle day 2. Daily blood samples were obtained, and serum estradiol (E(2)) and progesterone (P(4)) were measured by radioimmunoassay. When serum levels of E(2) declined, plateaued, or exceeded 600 pg/mL, laparoscopy was performed to count the number of follicles. If no new corpus luteum was present, monkeys were injected intramuscularly with 1000 IU of hCG. Laparoscopy was repeated 2 days later to document the number of ovulatory stigma. RESULTS: During ovarian stimulation, cocaine-treated monkeys required an average additional 1.5 days of hMG injections (P =.01), and this resulted in a greater total dose of hMG compared with control monkeys (351 +/- 16 IU versus 297 +/- 15 IU [mean +/- standard error of the mean], P =.03). For spontaneous and hCG-triggered ovulation, the number of ovulatory stigma was significantly lower (P <.003) in the cocaine-treated versus control monkeys (16 versus 31). Peak E(2) levels were significantly (P =.05) lower in cocaine-treated monkeys compared with controls. Luteal phase P(4) levels were lower in the cocaine-treated monkeys, but the difference was not statistically significant when compared with controls. CONCLUSION: Cocaine impaired ovarian responsiveness to exogenous gonadotropins and decreased ovulatory stigma in nonhuman primates. These findings suggest that cocaine has direct ovarian effects.     

Follicular fluid vascular endothelial growth factor concentrations are increased during GnRH antagonist/FSH ovarian stimulation cycles

BACKGROUND: The aim of this study was to investigate the effect of GnRH antagonists (GnRH-ant) on follicular fluid vascular endothelial growth factor (FF VEGF). METHODS: Sixty women undergoing assisted reproduction were randomised (computer-generated randomisation list) and assigned to two different GnRH analogue regimens: GnRH agonist (GnRH-a) (Group A; n = 30) and GnRH-ant (Group B; n = 30). RESULTS: Mean (+/-S.D.) FF VEGF concentrations were 1598+/-612 pg/mL and 2906+/-1558 pg/mL for Groups A and B, respectively (p < 0.001). In the women treated with GnRH-ant, we found a statistically significant reduction in serum LH levels (1.72+/-0.74 IU/L in Group A versus 0.93+/-0.43 IU/L in Group B, p < 0.001), in serum oestradiol (E2) levels (1562.1+/-410.7 pg/mL in Group A versus 1214.67+/-779.9 pg/mL in Group B, p < 0.05), in FF E2 levels (1146+/-593 ng/mL in Group A versus 621+/-435 ng/mL in Group B, p < 0.05), and in FF androstenedione levels (136+/-55 ng/mL in Group A versus 78+/-31 ng/mL in Group B, p < 0.001), as well as a reduction in the number of pregnancies, though not statistically significant (23.3% in Group A versus 16.6% in Group B). CONCLUSION: The increase in FF VEGF levels in women treated with GnRH-ant might be explained by a suppression of LH and E2 levels.     

Serum progesterone at human chorionic gonadotropin injection significantly correlate with female age

AIM: In in vitro fertilization-embryo transfer (IVF-ET) higher age and low responses are associated with accelerated luteinization of mature follicles rather than diminished responsiveness. The aim of this study was to determine whether an elevated serum progesterone (P) on the day of human chorionic gonadotropin (hCG) administration during gonadotropin stimulation for IVF-ET is associated with age. METHODS: E2 (17beta estradiol) and P concentrations on the day of hCG administration, number and quality of oocytes and embryos, and clinical pregnancies were retrospectively analyzed in 460 women undergoing IVF-ET. We evaluated patients according to age; the 25-30 age group (n=140), the 31-35 age group (n=100), the 36-40 (n=90), and the 41-45 age group (n=130). RESULTS: In the 25-30 age group (n=140) P was 0.67+/-0.3 ng/mL, in the 31-35 age group (n=100) P was 0.87+/-0.2 ng/mL, in the 36-40 age group (n=90) P was 0.95+/-0.2 ng/mL, in the 41-45 age group (n=130) P was 1+/-0.2 ng/mL. The difference between the 25-30 age group and the 41-45 age group was statistically significant (P<0.05). CONCLUSIONS: Periovulatory levels of serum P vary according to ovarian response to controlled ovarian hyperstimulation. Periovulatory P may reflect inadequate steroidogenesis. In women stimulated with recombinant follicle stimulating hormone for IVF, the serum P on the day of hCG administration increases with age.