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.


METHODS
Prospective, controlled in vitro study.


METHODS
Tertiary infertility center.


METHODS
Fertile patients in the luteal phase with histologically normal endometrium who were attending the infertility clinic as oocyte donors (n = 14).


METHODS
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 performed in an in vitro embryo adhesion assay composed of human polarized endometrial epithelial cells obtained from fertile patients and mouse embryos.


METHODS
Blastocyst formation rate and embryo adhesion rate.


RESULTS
Monolayers of polarized endometrial epithelial cells expressed ERalpha 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 blastocyst formation significantly decreased at a concentration >or= 10(-6) M, and embryonic adhesion decreased when blastocysts (n = 400) were obtained at a concentration >or= 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).


CONCLUSIONS
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.
Valbuena
D
D
Instituto Valenciano de Infertilidad Foundation (FIVIER), Valencia, Spain.
Martin
J
J
de Pablo
J L
JL
Remohí
J
J
Pellicer
A
A
Simón
C
C
D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects*; D004622:Embryo, Mammalian / Q000187:drug effects*; D004717:Endometrium / Q000166:cytology; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018587:Oocyte Donation; D011446:Prospective Studies; D013997:Time Factors
D004958:Estradiol