Michael C. Edelstein

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.

Studies on the in vitro spermicidal activity of synthetic magainins.

2 synthetic magainins--A and G-- have been shown through transmission electron microscopy to have spermicidal activity. Magainins a class of peptides isolated from the skin of the African clawed frog. I have been demonstrated to have wide spectrum in vitro antimicrobial activity. In this study semen sample collected from 7 healthy volunteers were diluted with magainins A and G and then examined for spermiostatic activity. Sperm diluted only with saline were used as a control. Sperm assays indicated the potency of magainin A to be significantly greater than that of magainin G. Magainin A demonstrated spermiostatic activity at concentrations of 0.024-0.095 mg/mL compared to concentrations of 0.095-0.380 mg/mL for magainin G. A similar pattern was identified in the concentration of peptide required to inhibit sperm motility. Magainin A inhibited sperm motility when diluted in seminal plasma at concentrations of 0.77-1.54 mg/mL while 1.54-3.08 mg/mL of magainin G were required to produce this effect. In the transmission electron microscopic studies magainin-treated sperm cells incubated with either peptide consistently demonstrated denudation of the outer plasma membrane and partial disappearance of the acrosome while sperm incubated in saline remained unaltered. It is hypothesized that magainins exert their spermicidal activity by disrupting the outer plasma membrane. The contraceptive potential of synthetic magainins should be explored through animal studies that measure the in vivo effects of seminal fluid and vaginal secretions on magainin activity and the effects of these agents on vaginal and cervical mucosa.

Ovarian stimulation for in vitro fertilization in low-responder patients using pulsatile intravenous follicle stimulating hormone

There is a subset of patients who fail to respond adequately to exogenous gonadotropin stimulation for in vitro fertilization (IVF). In this study, six such low-responder patients who had inadequate stimulations with high-dose intramuscular (im) follicle stimulating hormone (FSH) were treated in a subsequent cycle with pulsatile intravenous (iv) FSH. A paired analysis was performed to compare the cycles using high-dose im FSH with those using pulsatile iv FSH. Trough serum FSH levels were significantly higher with pulsatile iv FSH. No significant difference was noted in the stimulation characteristics or the number or quality of oocytes retrieved and embryos transferred. No pregnancies occurred in either group. While pulsatile iv administration of gonadotropin increases serum FSH levels, it does not appear to have a major impact on follicular stimulation or outcome in low-responder patients undergoing IVF.

Ovarian stimulation for in vitro fertilization using pure follicle-stimulating hormone with and without gonadotropin-releasing hormone agonist in high-responder patients.

There is a distinct pattern of response to gonadotropin stimulation in some patients marked by high peak estradiol (E2) levels, multifollicular ovarians response, and elevated basal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios. We reviewed the stimulation profiles of five such high-responder patients who failed to conceive during in vitro fertilization with ovarian stimulation using pure FSH. All patients had baseline LH/FSH >1.5 and peak E2>800 pg/ml. One cycle was canceled prior to hCG administration because of marked ovarian response (E2>2500 pg/ml, multiple small follicles). In a subsequent cycle, all patients were pretreated with the gonadotropin releasing-hormone agonist (GnRHa) leuprolide acetete for 10–14 days prior to initiation of FSH for ovarian stimulation. Leuprolide was continued until the day of hCG administration. During cycles using GnRHa, there was a statistically significant decrease (P <0.05) in serum FSH on day 3 (<5 vs 8.3 mIU/ml), serum E2 on day 3 (14.6 vs 34.6 pg/ml), and peak serum E2 (1197.6 vs 1923.0 pg/ml). Patients during cycles with GnRHa had a greater number of preovulatory (8.6 vs 3.0) and total (12.4 vs 6.0) oocytes retrieved (P<0.05). The fertilization rate of preovulatory oocytes was also higher during cycles using GnRHa (83 vs 64%). Two pregnancies occurred in the cycles pretreated with GnRHa. These preliminary data indicate that in high-responder patients, a combination of GnRHa and pure FSH results in lower E2 levels during the stimulation cycle and a greater number of total and mature oocytes retrieved and fertilized.

Antide bioavailability : single dose administration for suppression of testosterone and inhibin in male monkeys

The pharmacokinetics and pharmacodynamics of a single sc injection of Antide on testosterone (T) and inhibin secretion in intact male cynomolgus monkeys were examined. Fifteen primates were randomized to three groups receiving: propylene glycol and water vehicle, 3 mg/kg Antide, and 10 mg/kg of Antide. Antide at the 10 mg/kg dose caused long-term suppression of T ranging from 24-56 days. At the 3 mg/kg dose, suppression of T was of shorter duration. Serum Antide levels were significantly greater in the 10 mg/kg group than the 3 mg/kg group (p less than 0.02), both initially and through 35 days post-treatment. The duration of testosterone inhibition and sustained Antide levels were significantly correlated (p less than 0.01). Inhibin concentrations followed the same general pattern as testosterone reaching a nadir on day 21 post-treatment before subsequent recovery. The prolonged suppressive effect of Antide on T without detectable side effects makes this compound an excellent candidate for clinical evaluation.

Studies on the in Vitro Spermicidal Activity of Synthetic Magainins

Two synthetic magainins A and G are shown to have spermicidal activity. Transmission electron microscopic micrographs show that both magainins alter the plasma membranes of sperm and that these actions are rapid. Further studies will better delineate the contraceptive potential of synthetic magainins.

Progesterone levels on the day of human chorionic gonadotropin administration in cycles with gonadotropin-releasing hormone agonist suppression are not predictive of pregnancy outcome

Luteinizing hormone bioactivity and variable responses to clorniphene citrate in chronic anovulation Prough SG; Aksel S; Yeoman R Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of South Alabama, CC/C& Mobile, AL 36688. USA FERTIL STERIL 1990 5415 (799-804) In I8 women with infertility and chronic anovulation with normal gonadotropins, three different responses were observed to increasing doses (250 to 750 mg) of clomiphene citrate (CC). Follicle development and ovulation in 8. follicle development but no ovulation without human chorionic gonadotropin (hCG) in 6, and no response to CC in 4. Serum concentrations of bioactive luteinizing hormone (bioactive-LH), immunoactive (immunoactive-LH), follicle-stimulating hormone. and estradiol (Ez) were measured and follicle growth was assessed by daily ultrasound. Findings were compared with 8 normal ovulatory controls. Folliculogenesis on CC therapy, based on our data, was 78%; however, only 44% ovulated spontaneously, 34% required hCG for follicle rupture. There were no apparent hormonal indicators to predict responders from nonresponders. The absence of an LH surge in the presence of follicles and sustained high Ez concentrations in 34% of patients may be associated with a decreased E2 sensitivity at the hypothalamic-pituitary level. Ultrasound easily identified patients who responded to CC with folliculogenesis but did not initiate an LH surge. Follicle rupture was achieved promptly by hCG administration.