Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clomiphene citrate

To assess the effect of clomiphene citrate (CC) on endometrial epithelial integrins and P receptors (PR) during the window of implantation. Controlled, prospective, clinical study. Teaching hospital and university research laboratory. 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. Endometrial biopsies in the midluteal phase. Immunohistochemical determination and endometrial cellular localization of α 1, αv, β 3, and α 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. 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 β 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 β 3 integrin were different from spontaneous control cycles. There was no difference in the expression of α 1, αv, and α 4 between the groups studied. The administration of clomiphene produces aberrant endometrial β 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.