Hypoxia inducible factor and microvessels in peri-implantation endometrium of women with recurrent miscarriage

Objective: To compare the expression of hypoxia inducible factor 1 alpha (HIF1 alpha) and micro-blood vessels in endometrium around the time of embryo implantation in women with recurrent miscarriage and fertile controls. Design: Retrospective study. Setting: University hospitals. Patient(s): Sixty women: 24 with recurrent miscarriage and 36 with proven fertility. Intervention(s): Endometrial biopsy samples obtained precisely 7 days after luteinization hormone (LH) surge in a natural cycle. Main Outcome Measure(s): Immunohistochemical analysis to determine expression of HIF1 alpha and micro-blood vessels as identified by von Willebrand factor (vWF) in endometrium; semiquantitative analysis using H-score analysis of staining intensity for HIF1 alpha in the luminal epithelium, glandular epithelium, and stroma, separately; number, diameter, and volume of vWF-positive endometrial micro-vessels as counted by Image J software. Result(s): The luminal epithelial and stromal expression of HIF1 alpha in women with recurrent miscarriage was higher than found in the fertile controls, with the change in the luminal epithelium reaching the highest statistical significance. There was no statistically significant difference in HIF1 alpha expression in glandular epithelium between the two groups. An increased number as well as volume of micro-blood vessels was observed in women with recurrent miscarriage although the mean diameter of the micro-blood vessels did not statistically significantly differ between the two groups. Conclusion(s): We have found an aberrant expression of HIF1 alpha and micro-vessel number and volume in the peri-implantation endometrium of women with recurrent miscarriage, suggesting that altered hypoxia and vascularization status may account for the endometrial contribution to recurrent miscarriage. (C) 2016 by American Society for Reproductive Medicine.)