Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clorniphene citrate
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\Objective: To assess the effect of clomiphene citrate (CC) on endometrial epithelial integrins and P receptors (PR) during the window of implantation. Design: Controlled, prospective, clinical study. Setting: Teaching hospital and university research laboratory. Patient(s): Thirty-one fertile, normo-ovulatory women participated in this trial. Thirteen women exhibited a CC-stimulated cycle with 50 mg on days 5-9, and 18 women with spontaneous menstrual cycles served as controls. Intervention(s): Endometrial biopsies in the midluteal phase. Main Outcome Measure(s): Immunohistochemical determination and endometrial cellular localization of alpha(1), alpha v, beta(3), and alpha(4) epithelial integrins and PR during the window of implantation. The staining intensity was assessed by a semiquantitative index (HSCORE) and compared by nonparametric Mann-Whitney test. Result(s): Higher plasma levels of P and E-2 and delayed histologic dating of the endometrium (38%) were features of CC-treated women. In addition, a low epithelial beta(3) integrin expression and persistent PR were observed in glandular epithelial cells of "out-of-phase" endometrial biopsies from CC-treated women. In contrast, in "in-phase" biopsies, neither epithelial PR nor beta(3) integrin were different from spontaneous control cycles. There was no difference in the expression of alpha(1), alpha v, and alpha(4) between the groups studied. Conclusion(s): The administration of clorniphene produces aberrant endometrial beta(3), integrin expression in conjunction with a failure in the down-regulation of PR during the window of implantation in a significant number of normo-ovulatory women, notwithstanding the higher plasma P levels. Therefore, CC might affect the expression of endometrial receptivity markers.