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Serum cytokine profile and T helper (Th)1/Th2 cell balance are related to the success of embryo implantation, although not yet firmly linked to recurrent implantation failure (RIF), a repeated failure to achieve clinical pregnancy following multiple high-quality embryo transfer. In this prospective study, comprehensive bioinfomatic analysis and logistic regression analysis were used to compare the serum cytokine profiles of 41 RIF patients with those of 29 subjects with first-cycle successful pregnancy in the mid-luteal phase and to assess the alterations of cytokine profiles in patients with clinical pregnancy at five weeks post-transplantation. We found several elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and increased Th1/Th2 cytokine ratios in RIF patients compared to control subjects. Specifically, the receiver operating characteristic (ROC) curve generated using multiple indicators provides a high predictive value for diagnosing RIF (area under the curve [AUC] = 0.94, 95% confidence interval [CI] 0.87-1.00, P < 0.0001), with a sensitivity of 96.55% and a specificity of 87.50%. Meanwhile, at five weeks post-transplantation, patients in both groups diagnosed with clinical pregnancy exhibited increased levels of several cytokines compared with pre-pregnancy levels, and a gradual shift in Th1/Th2 balance toward Th2. These findings suggest that inflammatory serum cytokines and the predominance of Th1 cells likely contribute to RIF and possibly reflect the immune environment at the maternal-fetal interface, suggesting their value as outcome indicators in assisted reproductive therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Guo, Yang, Li, Yan, Deng, Dai and Li.)

Research Question: The aim of this study was to compare expression of hypoxia-inducible factor 1-alpha (HIF-1α), 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-1α 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-1α expression and MVD in endometrial samples of the RIF group, but apoptosis was not significantly altered., Conclusions: HIF-1α expression, MVD and endometrial apoptosis were reduced in the peri-implantation endometrium of women with RIF. This suggests that altered endometrial HIF-1α expression and angiogenesis may contribute to implantation failure., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)