Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation

Objective: To compare the expression of endometrial P receptors (PR) levels with markers of endometrial receptivity during the window of implantation. Design: Prospective, controlled study to examine endometrial PR and three cycle-specific integrins in endometrial biopsies obtained during the window of implantation. Setting: An academic teaching hospital. Patients: One hundred seventy-five endometrial biopsies from regularly cycling women with luteal phase defect (LPD; group 1; n = 80), medically treated LPD (group 2; n = 16), minimal and mild endometriosis with aberrant alpha v beta 3 expression (group 3; n = 21), fertile controls (group 4; n = 26), and infertile controls (group 5; n = 32). Main Outcome Measure: Immunohistochemical staining intensity of each antigen using the semi-quantitative grading system (HSCORE), compared using analysis of variance with Scheffe's correction. Results: Among the five groups studied, nuclear PR expression was significantly elevated in glandular epithelial cells from tissue samples with histologic delay greater than or equal to 3 days consistent with luteal phase deficiency (LPD; group 1). Failure of PR down-regulation was associated with aberrant alpha v beta 3 integrin expression. Medical correction of LPD was associated with return of normal endometrial histology, normal integrin expression, and the loss of epithelial PR, similar to controls. The other two cycle-dependent integrin markers, alpha 1 beta 1 and alpha 4 beta 1, were not different between groups. In women with aberrant alpha v beta 3 and ''in phase'' endometrium, epithelial PR expression was not different from controls. Conclusions: The establishment of normal endometrial receptivity appears to be tightly associated with the down-regulation of epithelial PR. Histologic delay, consistent with LPD, is associated with a failure of PR down-regulation and the lack, of normal markers of endometrial receptivity. Occult uterine receptivity defects (aberrant beta 3 expression in otherwise normal histology) are regulated differently, suggesting alternate mechanisms also exist which influence endometrial receptivity.