Bobby W. Webster

Concurrent ganirelix and follitropin beta therapy is an effective and safe regimen for ovulation induction in women with polycystic ovary syndrome

OBJECTIVE To evaluate controlled ovarian stimulation cycles using the GnRH antagonist ganirelix in combination with the recombinant FSH, follitropin-beta, in women with polycystic ovary syndrome (PCOS). DESIGN Prospective, nonrandomized clinical study. SETTING Hospital-based infertility practice. PATIENT(S) Twenty women with PCOS planning to undergo ovarian stimulation. INTERVENTION(S) Fasting glucose and insulin levels were used to calculate insulin resistance ratios (FG/I). After pretreatment with oral contraceptives, serum LH levels were determined, and 250 microg ganirelix was administered on cycle day 2. Upon suppression of LH, concurrent ganirelix and follitropin-beta therapy (morning ganirelix and evening follitropin-beta) was started and continued until the day of hCG. MAIN OUTCOME MEASURES Days of stimulation, dose of follitropin-beta, pregnancy, and ongoing pregnancy were compared based on FG/I ratios. RESULTS One dose of ganirelix effectively suppressed LH levels in all patients. All patients ovulated as documented by a rise in progesterone. Significant differences were observed between the insulin-resistant and non-insulin-resistant groups for both days of stimulation and dose of follitropin-beta. The overall clinical pregnancy rate was 44.4%, with an ongoing pregnancy rate of 27.8%. CONCLUSIONS In this preliminary study, we demonstrate the effectiveness of a concurrent ganirelix and follitropin-beta therapy for ovarian stimulation in women with PCOS.

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.

Polyspermy: effect of varying stimulation protocols and inseminating sperm concentrations

Results from 198 cycles of in vitro fertilization (IVF) were examined to identify factors in the subsequent development of polyspermy. Polyspermy occurred in 24 of 235 fertilized oocytes and was equally likely in mature and immature oocytes. No significant difference in polyspermy was demonstrated between the stimulation protocol using human menopausal gonadotropin (hMG) and those using clomiphene citrate (CC) or combined hMG/CC. The incidence of polyspermy was no different after insemination of oocytes with concentrations of progressively motile sperm ranging from 250,000 to 500,000. Although polyspermy continues to be a problem in IVF, we have been unable to identify possible predisposing mechanisms for its development.

Selection of superior stimulation protocols for follicular development in a program for in vitro fertilization

Classification of stimulated controlled follicular development cycles in programs for in vitro fertilization by the likelihood of culminating in a pregnancy would allow for increased efficacy in patient management and the distribution of care provider services. Analysis of human menopausal gonadotropin stimulations by the estradiol (E2) patterns identified trends suggesting superiority of one pattern, but no statistically significant difference was identified. Similarly, trends were identified in the Norfolk data for the height and pattern of E2 response, but no statistical significance was identified. While these observations may become significant with larger numbers, until that time, criteria for altering patient management based on the rise of follicular phase E2 levels should be reconsidered.

Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer

Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol.

Correlation of human sperm motility characteristics with an in vitro cervical mucus penetration test**Supported by the Women’s Research Institute, Wichita, Kansas.

Semen analysis was performed on 226 ejaculates by an integrated microcomputerized system employing the multiple-exposure photography (MEP) method. Mucus penetration tests were performed in vitro using commercial preparations of bovine cervical mucus. A highly significant (P less than 0.001) correlation between mucus penetration distance and sperm count (r = 0.582), motility (r = 0.357), velocity (r = 0.569), motile density (r = 0.582), motility index (r = 0.467), and morphology (r = 0.383) was observed. Increased percentages of immature germ cells (r = -0.318) and bent-tailed sperm (r = -0.221) were the most strongly correlated with mucus penetration. Approximately 10% to 15% of patients with otherwise normal semen parameters displayed poor penetration of mucus. Conversely, 5% to 40% of patients with abnormal semen parameters displayed excellent penetration of the mucus. Motile density and velocity demonstrated the strongest relationship with the outcome of the mucus penetration test. These results suggest that a significant subpopulation of patients can be identified as having inadequate (or adequate) penetration of mucus with otherwise normal (or abnormal) motility characteristics.

Variation in the biologic and biochemical characteristics of human menopausal gonadotropin**Presented at the Forty-Third Annual Meeting of The American Fertility Society, September 28 to 30, 1987, Reno, Nevada, and awarded the Associate Member’s Forum Prize Paper.††Supported in part by the Wesley Medical Research Institutes and the Women’s Research Institute, Wichita, Kansas.

Lot differences in the biopotency of human menopausal gonadotropin (hMG) were evaluated and the potential biochemical basis was investigated. The in vivo biopotency of hMG was assessed by a unique bioassay that evaluates the number of ova shed in the cyclic hamster in response to hMG administration. Significant variation in hMG lots was observed using this assay. When subjected to chromatofocusing, hMG displayed five immunoreactive follicle-stimulating hormone (FSH) isohormones and nine luteinizing hormone (LH) isohormones. The relative distribution of FSH, but not LH isohormones, was slightly but significantly different between the lots tested. These data indicate that significant differences exist in the ability of commercially available hMG to stimulate follicular development and ovulation. The biochemical basis for these differences in in vivo biopotency remains to be elucidated.