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Background  The pathophysiology of recurrent pregnancy loss (RPL) is still unknown in 50% of the cases. Herein we measure the expression of beta3 integrin subunit, a well-known implantation marker, in women with or without RPL and correlate it with the histological dating of the endometrial tissue.    Methods  LH-timed endometrial biopsies were obtained from cases (RPL; n = 21, age 33.9+/-4.7) and healthy controls (n = 29; age 29.8+/-4.1) during the mid-secretory phase (post ovulatory day: 8 to 10). Endometrial samples were timed histologically according to Noyes’ criteria and underwent immunohistochemical staining for beta3 integrin expression. For statistical analysis the semi-quantitative HSCORE was assessed. Type I (beta3 negative in an out-of-phase endometrium) and Type II defect (beta3 negative in an in-phase endometrium) were also analysed. Statistical analysis was done with Student  t -test, Mann Whitney  U  test, ANCOVA and  chi  square for trend. Significance was set as  P  < 0.05.    Results  The mean (SD) age in controls was lower compared to cases [(29.8 (4.1)  vs.  33.9 (4.7) –  P  = 0.001; Student  t -test)]. The median (range) expression of beta3 integrin in controls and cases was 1.94 (0 to 3.5)  vs.  0.82 (0 to 3.6), respectively ( P  = 0.001; Mann Whitney  U  test). Significance was still significant after adjusting for age ( P =  0.03;ANCOVA). The normal positive staining > =0.7 of beta3 integrin subunit and in-phase endometrium was seen in 24 out of 29 (82.8%) controls, but in only 6 out of 21 (28.6%) of cases with RPL; Type I and II defects were seen in 10.3 and 6.9% of controls, while present in 52.4 and 19.1% of cases, respectively ( P  = 0.0005;  chi- square).    Conclusions  Women with unexplained RPL had significantly reduced integrin expression compared to controls. Our findings underline the need for further molecular analysis of endometrial tissue in affected women.

Endometrial beta3 Integrin profile reflects endometrial receptivity defects in women with unexplained recurrent pregnancy loss