Ovarian stimulation modulates steroid receptor expression and spheroid attachment in peri-implantation endometria: studies on natural and stimulated cycles

ObjectiveTo compare the effect of high serum E2 levels on endometrial steroid receptors in gonadotropin-stimulated cycles (hCG + 7) and natural cycles (LH + 7), and to study its effect on spheroid attachment.DesignObservational.SettingUniversity hospital.Patient(s)Infertile patient with normal menstrual cycles undergoing IVF treatment.Intervention(s)Gonadotropin stimulation and endometrial biopsy; trophoblast spheroid (embryo surrogate, Jeg-3)–endometrial cell (Ishikawa) coculture assay.Main Outcome Measure(s)Steroid receptor expression by quantitative polymerase chain reaction and immunohistochemistry; spheroid attachment rate.Result(s)Endometrial biopsies from natural (n = 12) and stimulated (n = 23) cycles were obtained. The expression of estrogen receptor α (ERα) but not ERβ or progesterone receptor (PR) transcript was significantly reduced in stimulated cycles compared with natural cycles. Glucocorticoid receptor (GR) transcript was significantly increased in the excessive responders of the stimulated cycle. There was no difference in ERα immunoreactivity in endometrial stroma, but a higher immunoreactivity was seen in endometrial glands of stimulated cycles. The endometrium of stimulated cycles had a lower expression of PR protein in glands, but a higher expression in stroma. Although no GR protein was detected in glands, GR protein expression was significantly up-regulated in stroma of the stimulated cycles. Endometrial cells treated with high steroid concentrations had a reduced spheroid attachment rate compared with the controls.Conclusion(s)High serum E2 level affects the expression of steroid receptors in the endometrial cells and suppresses spheroid attachment.