INTEGRINS AS MARKERS OF UTERINE RECEPTIVITY IN WOMEN WITH PRIMARY UNEXPLAINED INFERTILITY

Objective: To assess uterine receptivity in women with unexplained infertility Design: Prospective, controlled study design. Patients: Eighty-seven nulliparous women with unexplained infertility and 32 fertile and infer the parous controls. Main Outcome Measure: Immunohistochemical staining for alpha 1, alpha 4, and beta 3 integrin subunits in endometrial biopsies obtained during the window of implantation (days 20 to 24), using the semiquantitative HSCORE by two observers in a blinded fashion. Results: All endometrial biopsies from parous controls contained positive immunostaining for the alpha 1, and beta 3 integrin subunits in glandular epithelium. Some samples from parous controls were missing the alpha 4 subunit. In contrast, compared with parous controls, biopsies from women with unexplained infertility had reduced significantly beta 3 expression, with similar expression of alpha 1 and alpha 4. Two distinct defects in integrin expression were identified: ''out-of-phase'' samples that lacked beta 3 because of histologic lag (type I defects) and ''in-phase'' endometrium that still failed to express this integrin (type II defects). These subclassifications accounted for 26% and 39% of the total unexplained infertility group, respectively. Conclusions: Abnormal endometrial integrin expression was a frequent finding in women with unexplained infertility. These data suggest that defective uterine receptivity may be an unrecognized cause of infertility in this population of women.