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.

Expression of L-selectin ligand MECA-79 as a predictive marker of human uterine receptivity.

PROBLEM: Patients with repeated implantation failure (RIF) represent a subgroup of couples who suffer from unexplained infertility. Human blastocysts utilize L-selectin to initiate implantation by binding to endometrial ligands composed of oligosaccharide moieties on the surface glycoproteins. The absence of these ligands could lead to recurrent implantation failure (RIF) in some of these couples. METHODS: Twenty fertile women and 20 patients with RIF were tested for the presence of the L-selectin ligands by immunohistochemistry. Endometrial biopsies were obtained on the sixth day post ovulation. After fixation, they were dated according to Noyes. Immunolocalization was performed using the MECA-79 antibody which is directed against ligands of L-selectin. RESULTS: The fertile group all showed the presence of the L-selectin ligand. Of those with RIF, five were negative for the ligand and never, despite an average of five successive embryo transfers, became pregnant. Fifteen RIF patients were positive for the L-selectin ligand, of whom ten subsequently conceived. As a screening test for RIF patients who lack the ligand, the predictive value was 100% with a sensitivity of 50% and specificity of 100%. The positive predictive value was 100% and negative predictive value is 87%. CONCLUSIONS: L-selectin and its ligands play a vital role for early human implantation. Screening for the absence of the ligand may help many patients with RIF to avoid undergoing repeated failed treatment cycles.

Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface.

Trophoblast adhesion to the uterine wall is the requisite first step of implantation and, subsequently, placentation. At the maternal-fetal interface, we investigated the expression of selectin adhesion systems that enable leukocyte capture from the bloodstream. On the maternal side, human uterine epithelial cells up-regulated selectin oligosaccharide-based ligands during the window of receptivity. On the fetal side, human trophoblasts expressed L-selectin. This ligand-receptor system was functional, because beads coated with the selectin ligand 6-sulfo sLe(x) bound to trophoblasts, and trophoblasts bound to ligand-expressing uterine luminal epithelium in tissue sections. These results suggest that trophoblast L-selectin mediates interactions with the uterus and that this adhesion mechanism may be critical to establishing human pregnancy.