The Correlative Factors Of Affecting Endometrial Receptivity

Objective: To study serum estradiol (E2), progesterone (P) and the endometrial expressions of estrogen receptor (ER), progesterone receptor (PR), integrin α_vβ₃, leukemia inhibitory factor (LIF), vascular endothelial growth factor (VEGF) in women undergoing in vitro fertilization-embryo transfer (IVF-ET); to elucidate the relationship of E₂, P and integrin α_vβ₃, LIF, VEGF and to assess whether they could be used to predict subsequent treatment success.Materials and methods: The endometrium tissue samples and serum samples were obtained from 40 patients undergoing IVF-ET in the Reproductive Medical Center, the Second Affiliated Hospital of Zhengzhou University in the window of implantation (mid-luteal). The serum E₂ and P level was measured by radioimmunoassay. The endometrial ER, PR, integrin α_vβ₃, LIF, VEGF were detected by immunohistochemistry using monoclonal or polyclonal antibody and semi-quantified by using the H-SCORE. Forty patients were divided into two groups: the pregnancy group (16 patients) and non-pregnancy group (24 patients). The data were analyzed by SPSS10.0 for windows. Comparison of the average in the two groupswas performed by t-test (a =0.05). Relationship between two variables was performed by correlativity analysis (a =0.05). Results:1. The mean age of the two groups respectively were 32.56 + 3.16 years old and 32.92+4.98 years old. There was no significant difference in the two groups (P> 0.05).2. There was no significant difference in mean serum E2 level during the window of implantation (mid-luteal) (116.60 + 30.97 vs. 110.85 + 34.04, P>0.05). The serum P level during the window of implantation was higher in pregnancy group than that in the non-pregnancy group (17.80 + 6.08 vs.14.12+4.74, P<0.05).3. The endometrial ER staining was located in the nucleus during the window of implantation. The ER immunostaining intensity in glandular epithelial, luminal epithelium and stromal was strong. But there was no significant difference in the two groups (1.36+0.41 vs. 1.31+0.32, P>0.05; 1.49 + 0.56 vs.1.41 +0.40, P>0.05; 1.26 + 0.41 vs.l.20 + 0.40,P>0.05).4. The endometrial PR staining was located in the nucleus during the window of implantation. The endometrial luminal epithelial and glandular epithelial PR score in non-pregnancy group was significantly higher than that in the pregnancy group (2.61 + 0.54 vs. 0.65 + 0.31, P<0.05; 2.30 + 0.40 vs. 0.55 + 0.35, P<0.05). The endometrial stromal PR score in non-pregnancy group was significantly lower than that in the pregnancy group (2.42 + 0.71 vs.2.95 + 0.48, P<0.05).5. The integrin otvfo was present in endometrial cytoplasm during the window of implantation. The immunostaining intensity of glandular was stronger than that of luminal epithelial. The luminal epithelial and glandular immunostaining integrin avfo score was higher in pregnancy group than that in non-pregnancy group (1.53 + 0.28 vs.l.12 + 0.24, P<0.05; 1.73 + 0.18 vs.1.50 + 0.23, P <0.05). The correlative analysis of integrin ctvfo in endometrial luminal epithelial and glandular epithelial immunostaing with serum P level shows statistical correlation in two groups (glandular epithelial r=0.678, P<0.01; luminal epithelial r=0.711, P<0.01). Thecorrelative analysis of integrin ovft in endometrial luminal epithelial and glandular epithelial immunostaing with serum E2 level shows no statistical correlation in two groups (glandular epithelial r=-0.007, P>0.05; luminal epithelial r=0.011, P>0.05).6. The LIF was present in endometrial cytoplasm during the window of implantation. The immunostaining intensity of luminal epithelial was stronger than that of glandular. The luminal epithelial and glandular immunostaining LIF score was higher in pregnancy group than that in non-pregnancy group (1.56±0.41 vs.l.31± 0.32, P<0.05; 1.45 + 0.31 vs.l.15 + 0.37, P<0.05). The correlative analysis of LIF in endometrial luminal epithelial and glandular epithelial immunostaing with serum P level shows statistical correlation in two groups (glandular epithelial r=0.589, P< 0.01; luminal epithelial r=0.553, P<0.01). The correlative analysis of LIF in endometrial luminal epithelial and glandular epithelial immunostamg with serum E2 level shows no statistical correlation in two groups (glandular epithelial r=0.172, P> 0.05; luminal epithelial r=0.074, P>0.05).7. The VEGF was present in endometrial cytoplasm during the window of implantation. The immunostaining intensity of glandular was stronger than that of luminal epithelial. The luminal epithelial and glandular immunostaining VEGF score was higher in pregnancy group than that in non-pregnancy group (1.35 + 0.30 vs.l.12 ±0.24, P<0.05; 1.49±0.27 vs.1.28+0.28, P<0.05). The correlative analysis of VEGF in endometrial luminal epithelial and glandular epithelial immunostaing with serum E2 level shows statistical correlation in two groups (glandular epithelial r=0.524, P<0.01; luminal epithelial r=0.491, P<0.01). The correlative analysis of VEGF in endometrial luminal epithelial and glandular epithelial immunostaing with serum P level shows no statistical correlation in two groups (glandular epithelial r=0.271, P>0.05; luminal epithelial r=0.306, P>0.05).Conclusion:1. The serum estradiol level in the window of implantation would not affect the endometrial receptivity. But the decreased serum progesterone level in the window of implantation maybe impairs endometrial receptivity. The serum progesterone levelcan be used as one of the indexes to predict subsequent treatment success.2. The failure of down-regulation of the endometrial luminal epithelial, glandular epithelial PR and the decreased stromal PR may be the mechanism of the diminished endometrial receptivity. The immunostaining of the endometrial luminal epithelial, glandular epithelial and stromal ER in the window of implantation would not correlate to endometrial receptivity.3. The immunostaining of endometrial integrin ovft, LIF, VEGF in the window of implantation were positive. The high expressions of integrin otvfo, LIF, VEGF in the window of implantation may be one of the important factors that affect on the early blastocyst implantation.4. The endometrial expression of integrin ovft, LIF, VEGF could be used to predict subsequent treatment success.5. The expression of integrin ov/33 and LIF in endometrium is induced by serum progesterone level. The variation of integrin avfo and LIF expression in endometrium shows significant correlations with serum progesterone. The variation of VEGF expression in endometrium shows significant correlations with serum estradiol.