Endometrial injury increases expression of hypoxia-inducible factor and angiogenesis in the endometrium of women with recurrent implantation failure

Research question: The aim of this study was to compare expression of hypoxia-inducible factor 1-alpha (HIF-1 alpha), angiogenesis and apoptosis in endometrial tissue near the implantation window of women with recurrent implantation failure (RIF) and in fertile control women, and to describe possible mechanisms of endometrial injury. Design: A controlled clinical study was conducted. Endometrial tissue specimens were obtained from 20 women undergoing IVF who had had at least three previous failed treatment cycles; normal endometrial specimens were obtained from 10 fertile control women. Results: HIF-1 alpha expression was down-regulated in the endometrium of women with RIF compared with that of control women. In addition, micro-vessel density (MVD) was much lower in the endometrium of women with RIF than in that of the control women. Apoptosis was significantly reduced in the endometrium of the RIF group compared with the control group. Endometrial injury increased HIF-1 alpha expression and MVD in endometrial samples of the RIF group, but apoptosis was not significantly altered. Conclusions: HIF-1 alpha expression, MVD and endometrial apoptosis were reduced in the peri-implantation endometrium of women with RIF. This suggests that altered endometrial HIF-1 alpha expression and angiogenesis may contribute to implantation failure.