ENDOMETRIAL PROGESTERONE RECEPTORS AND MARKERS OF UTERINE RECEPTIVITYIN THE WINDOW OF IMPLANTATION

Objective: To compare the expression of endometrial P receptors (PR) l evels with markers of endometrial receptivity during the window of imp lantation. Design: Prospective, controlled study to examine endometria l PR and three cycle-specific integrins in endometrial biopsies obtain ed during the window of implantation. Setting: An academic teaching ho spital. Patients: One hundred seventy-five endometrial biopsies from r egularly cycling women with luteal phase defect (LPD; group 1; n = 80) , medically treated LPD (group 2; n = 16), minimal and mild endometrio sis 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 t he five groups studied, nuclear PR expression was significantly elevat ed in glandular epithelial cells from tissue samples with histologic d elay greater than or equal to 3 days consistent with luteal phase defi ciency (LPD; group 1). Failure of PR down-regulation was associated wi th 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 contro ls. The other two cycle-dependent integrin markers, alpha 1 beta 1 and alpha 4 beta 1, were not different between groups. In women with aber rant alpha v beta 3 and ''in phase'' endometrium, epithelial PR expres sion was not different from controls. Conclusions: The establishment o f normal endometrial receptivity appears to be tightly associated with the down-regulation of epithelial PR. Histologic delay, consistent wi th LPD, is associated with a failure of PR down-regulation and the lac k, of normal markers of endometrial receptivity. Occult uterine recept ivity defects (aberrant beta 3 expression in otherwise normal histolog y) are regulated differently, suggesting alternate mechanisms also exi st which influence endometrial receptivity.