Objective: To report an unusual case of idiopathic zygotic polypronuclei.Design: Case report.Setting: Major urban infertility referral center.Patient(s): A 34-year-old woman with unexplained infertility.Intervention(s): The patient underwent two cycles of controlled hyperstimulation and oocyte retrieval followed by in vitro insemination and intracytoplasmic sperm injection (ICSI).Main Outcome Measure(s): Pregnancy and delivery of a normal infant following transfer of a single preembryo from an ICSI cycle in which only one zygote showed a normal pronuclear number (2PN) and 12 zygotes appeared polypronucleated (greater than or equal to3PN).Result(s): On the first IVF cycle, 23 oocytes were retrieved and inseminated with 240 X 1 03 motile sperm/mL, after which two zygotes showed a normal pronuclear number and 20 zygotes appeared polyploid with three to seven pronuclei. Transfer of two poor-quality day-3 preembryos following assisted hatching did not achieve pregnancy. On the subsequent ICSI cycle, 33 oocytes were retrieved, and 17 mature oocytes were subjected to ICSI, after which only one zygote showed 2PN and 12 zygotes appeared polyploid with three to eight pronuclei. The normally fertilized zygote developed into a poor-quality, day-3 embryo and was subjected to assisted hatching. Transfer of this preembryo resulted in an uneventful pregnancy and birth of a normal infant.Conclusion(s): Mechanisms other than polyspermia may result in polypronuclear development in some patients. (C)2004 by American Society for Reproductive Medicine.
Objectives: After failure of an IVF cycle, both the couple and IVF center seek to evaluate the failed cycle in an effort to determine why the cycle did not result in success and which if any variables might be changed to enhance the chances for success in a subsequent cycle. The purpose of this study was to determine which, if any, IVF variables were predictive of success in IVF cycles that follow a first cycle failure. Design: Prospective historical study. Materials and Methods: Women undergoing their first and second IVF cycle between January 1997 and December 1999 were evaluated. Only patients who had an unsuccessful first IVF cycle, defined as a negative pregnancy test, were included in the study. For analysis, patients were divided into two groups. All of the women in group A, had both an unsuccessful first and second IVF cycle. All of the women in group B, had an unsuccessful first cycle and a successful second cycle. Success was defined as a gestational sac with fetal cardiac activity. Both ICSI and non-ICSI cycles were included. All cycles had day 3 uterine embryo transfers. The main variables of interest included the number of days between cycles, the number of oocytes retrieved, the number of oocytes fertilized, the number of embryos transferred and the quality of embryos transferred. Differences between variables from the first and second IVF cycles were compared both within and between groups. A chi square test was used to evaluate differences between categorical variables and a t test was used to evaluate differences between continuous variables (α = 0.05). Results: A total of 180 cycles were evaluated. Of these cycles, 96 cycles (48 women) were included in group A, and 84 cycles (42 women) were included in group B. There were no differences between groups with regard to the number of days between procedures (176 versus 186). The quality of embryos did not change from cycle 1 to cycle 2 in either group. Both groups had a significantly higher number of oocytes retrieved in the second cycle as compared to the first cycle. Group B on average had a greater number of oocytes retrieved (2.69 versus 1.21), oocytes fertilized (1.48 versus 0.42) and embryos transferred (0.88 versus −0.10) as compared to group A. Conclusions: These data suggest that the number of oocytes retrieved, the number of oocytes fertilized and the number of embryos transferred, but not the quality of embryos transferred are associated with successful second IVF cycles.
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 < 0.02), both initially and through 35 days post-treatment. The duration of testosterone inhibition and sustained Antide levels were significantly correlated (p < 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.
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.
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.
Between September 1987 and August 1989, all patients and their spouses entering our in vitro fertilization (IVF) program were screened for the human immunodeficiency virus (HIV) using the enzyme-linked immunosorbent assay (ELISA). Of 848 patients and 848 spouses tested, all but 4 patients and 1 husband tested negative. Of those who tested positive on repeat testing with ELISA, only one was positive on Western blotting (HIV prevalence, 0.59 per 1000). During this same time period 1187 samples of human cord blood were used to make tissue culture medium for the IVF embryology laboratory. One sample was discarded because of positive HIV on ELISA and Western blotting; two other samples were discarded because of positivity to the hepatitis B surface antigen. While we believe that routine HIV screening of IVF patients and their spouses is indicated, this population is of low risk for HIV positivity. Furthermore, continued screening of human sera used to make tissue culture media for IVF is mandatory.
This study was designed to find the minimal single dose of Antide (Nal-Lys GnRH antagonist) that would provide long-term inhibition of serum testosterone levels in adult male monkeys. At 3 mg/kg (sc), Antide blocked testosterone secretion for only a few days. However, when the dose of Antide was raised to 10 mg/kg, some of the males manifested testosterone inhibition lasting more than 60 days, while shorter durations of action were found in others. These preliminary findings increase our interest in studying Antide as a potential male contraceptive agent, when combined with androgen replacement therapy, as well as for therapeutic applications in men having prostatic carcinoma. Importantly, Antide lacks the sometimes deleterious "flare" effect known to occur when GnRH agonists are used to treat these patients.
In in vitro fertilization (IVF) cycles using gonadotropin-releasing hormone agonist (GnRH-a) suppression, we investigated whether an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration indicates premature luteinization and is associated with a lower pregnancy rate. We retrospectively studied 101 patients treated with the GnRH-a leuprolide acetate, begun in the luteal phase of the prior menstrual cycle and continued until the day of hCG administration. On the day of hCG, 72 patients had P less than 0.9 ng/mL and 29 had less than or equal to 0.9 ng/mL. Patients in the high P group had a significantly greater estradiol level on the day of hCG. No significant difference in clinical pregnancy rates or ongoing pregnancy rates occurred between the low P and high P groups. We conclude that in IVF cycles pretreated with GnRH-a, P levels on the day of hCG are not predictive of conceiving in that cycle.
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.
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.
Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania