Charles E. Miller

Endometrin for luteal phase support in a randomized, controlled, open-label, prospective in-vitro fertilization trial using a combination of Menopur and Bravelle for controlled ovarian hyperstimulation

OBJECTIVE To assess the efficacy and safety of a vaginal progesterone (P(4)) insert (Endometrin) for luteal support for assisted reproductive technology (ART). DESIGN Multicenter, randomized, open-label (assessor-blinded) phase III clinical trial. SETTING Twenty-five U.S. ART centers. PATIENT(S) A total of 1,211 ART patients randomized to three groups: Endometrin 100 mg twice daily (n = 404), Endometrin 100 mg three times daily (n = 404), and P(4) 90 mg 8% gel daily (n = 403). INTERVENTION(S) In vitro fertilization and ET were performed according to site-specific protocols. The day after oocyte retrieval, Endometrin or vaginal P(4) gel was begun for luteal support and continued for up to 10 weeks of pregnancy. MAIN OUTCOME MEASURE(S) Biochemical, clinical, and ongoing pregnancy and live birth rates. RESULT(S) Pregnancy rates were high and similar in all treatment groups, with biochemical rates exceeding 50%, clinical and ongoing rates >or=40%, and live birth rates at 35%-38%. The adverse event profiles were similar across groups. CONCLUSION(S) Pregnancy rates and live birth rates for Endometrin (twice daily and three times daily) were high and similar to those for P(4) gel. The adverse event profiles for both were similar to that for P(4) gel and primarily due to IVF stimulation and oocyte retrieval. Endometrin was safe and well tolerated.

Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate

OBJECTIVE To determine the effect on pregnancy rate (PR) of low-dose glucocorticoid treatment in cycles without micromanipulation. DESIGN Randomized, prospective, double-blinded, placebo-controlled trial. SETTING One university-based tertiary infertility center and two private infertility centers. PATIENTS All patients receiving standard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study. Patients having micromanipulation were excluded from this study. INTERVENTIONS Participating patients were randomized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion. Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days. Cryopreservation and stimulation cycles were managed according to pre-established protocols for all patients. A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound. RESULTS A total of 206 stimulation patients and 61 cryopreservation patients were randomized and had an ET. Patient characteristics were similar between groups. The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9% versus 40.8% and 12.8% versus 11.7% for stimulation cycles and 30.3% versus 25% and 9.9% versus 7.4% for cryopreservation cycles, respectively. None of these differences were statistically significant. CONCLUSIONS Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates.

Gynecologic use of Sepraspray Adhesion Barrier for reduction of adhesion development after laparoscopic myomectomy: a pilot study

OBJECTIVE To assess the safety and efficacy of Sepraspray Adhesion Barrier (a modified hyaluronic acid and carboxymethylcellulose powder) after laparoscopic surgery, in view of both the high efficacy of Seprafilm Adhesion Barrier in reducing postoperative adhesions after open surgical procedures and the difficulty with laparoscopic delivery. DESIGN Multicenter, randomized, reviewer-blinded trial. SETTING Reproductive endocrinology and infertility clinics. PATIENT(S) Women undergoing laparoscopic myomectomy for indications including infertility. INTERVENTION(S) Randomization to treatment with (n = 21) or without (n = 20) Sepraspray Adhesion Barrier. MAIN OUTCOME MEASURE(S) Postoperative adhesions development was assessed at early second-look laparoscopy. Adhesions were scored using the modified American Fertility Society scoring system. RESULT(S) Surgical procedure duration length was 99 versus 102 minutes in the control versus Sepraspray Adhesion Barrier groups, respectively, with the median number of fibroids removed being two in each group and corresponding fibroid weights of 134 ± 103 versus 113 ± 161 g, respectively. Adhesions scores increased in both the control and Sepraspray Adhesion Barrier groups, with larger although nonstatistically significant increases noted in control subjects when evaluating for the anterior uterus, the posterior uterus, and the entire uterus. CONCLUSION(S) Laparoscopic application of Sepraspray Adhesion Barrier after myomectomy in this pilot study was associated with a trend toward a reduction in postoperative adhesion development, as well as an encouraging safety profile. Further evaluation is warranted. CLINICAL TRIAL NUMBER Sepraspray Adhesion Barrier #NCT00624930.

Pituitary follicle-stimulating hormone heterogeneity: assessment of biologic activities of each follicle-stimulating hormone form**Supported by NIH grant R01-14742.

The multiple species of follicle-stimulating hormone (FSH) present within pituitary tissue were separated by the technique of polyacrylamide gel isoelectric focusing. The ability of each FSH species to stimulate the secretion of plasminogen activator from cultured granulosa cells was tested (FSH in vitro bioassay). A wide range of biologic/radioimmunologic FSH activity was observed when FSH species were compared. As the isoelectric point of the FSH molecule declined, so did the biologic activity. A second series of studies was performed to determine which forms of FSH were secreted by pituitary tissue in vitro. All of the forms of FSH present in pituitary tissue were secreted into culture medium. However, the relative proportions of FSH forms in the pituitary and medium were not always similar. Exposure of pituitary tissue to luteinizing hormone-releasing hormone elicited an increase in the relative proportion of the more biologically active forms of FSH that were secreted. These studies suggest that the hormonal milieu surrounding the pituitary affects not only the quantity but also the potency of the FSH signal emitted. Thus, the basis for observed differences between biologic and immunologic FSH activities observed during some endocrine states may be the result of preferential secretion of certain FSH species.