Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo

Objective: To investigate whether the deleterious effect of E-2 on embryonic implantation is due to a direct effect on the endometrium, on the embryo, or both. Design: Prospective, controlled in vitro study. Setting: Tertiary infertility center. Patient(s): Fertile patients in the luteal phase with histologically normal endometrium who were attending the infertility clinic as oocyte donors (n = 14). Intervention(s): E-2 dose-response (0, 10(-8), 10(-7), 10(-6), 10(-5), and 10(-4) M) and time course (day 2 vs. day 5) experiments were per-formed in an in vitro embryo adhesion assay composed of human polarized endometrial epithelial cells obtained from fertile patients and mouse embryos. Main Outcome Measure(s): Blastocyst formation rate and embryo adhesion rate. Results: Monolayers of polarized endometrial epithelial cells expressed ER alpha at the mRNA level. The E-2 dose response of blastocysts with polarized endometrial epithelial cells (n = 235) demonstrated a progressive reduction in embryonic adhesion that was statistically significant at 10(-6) M. When polarized endometrial epithelial cells were treated alone with increasing doses of E-2 for 3 days and E-2 was then removed and blastocysts added (n = 410), embryonic adhesion was not significantly reduced, except at 10(-4) M. When 2-day mouse embryos (n = 609) were treated with increasing E-2 concentrations until day 5, the rate of M, and embryonic adhesion decreased blastocyst formation significantly decreased at a concentration greater than or equal to 10(-6) when blastocysts (n = 400) were obtained at a concentration greater than or equal to 10(-7) M. Time course experiments of embryos cultured for 2 days with polarized endometrial epithelial cells (n = 426) showed that the adhesion rate was higher at E-2 levels of 10(-7), 10(-6) and 10(-5) M compared with embryos cultured for 5 days (n = 495). Conclusion(s): High E-2 levels are deleterious to embryo adhesion in vitro, mainly because they have a direct toxic effect on the embryo that may occur at the cleavage stage. (C) 2001 by American Society for Reproductive Medicine.