SummaryRecurrent implantation failure (RIF) is considered to be one of the major limiting factors of assisted reproductive technology (ART) programme success. The current study focused on the investigation of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), cytokines and cell adhesion molecules in peripheral blood (PB) and follicular fluid (FF) obtained from 44 women aged between 25 and 39 years old and undergoing intracytoplasmic sperm injection (ICSI). These women were divided into two groups: 22 RIF women with embryo implantation failures after the transfer of at least four fresh or frozen–thawed good quality embryos in a minimum of three ICSI cycles, and 22 ICSI success women (controls) who achieved a clinical pregnancy at their first ICSI attempt. The PB and FF samples were obtained from each patient on the day of oocyte retrieval. MMP-1, -2, -3, -7, -9, TIMP-1, -2, vascular endothelial growth factor (VEGF), leukaemia inhibitory factor (LIF), vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecules 1 (ICAM1) were analyzed using enzyme-linked immunosorbent assay of PB and FF. Our results showed significant decreases in PB MMP-7 and PB VEGF in the RIF group compared with controls [281.11 (33–614) pg/ml vs 119.92 (27–441) pg/ml; P-value = 0.030] and [82.54 (25.94–210.20) pg/ml vs 30.93 (13.62–193.33) pg/ml; P-value = 0.022; respectively]. Receiver operating characteristic (ROC) curve analysis showed informative area under the curve values for PB MMP-7, as well as for PB VEGF, making them able to be proposed as biomarkers of the RIF. Therefore, circulating MMP-7 and VEGF seem to play an interesting role in embryo implantation in in vitro fertilization (IVF)/ICSI cycles and could be proposed as circulating biomarkers of the RIF. These results could be helpful for clinicians and patients to choose the best rescue strategy and treatment to minimize implantation failure in women undergoing IVF/ICSI procedures after the first attempt.

中文翻译：

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循环 MMP-7 和 VEGF 作为复发性植入失败的潜在预测生物标志物

摘要复发性植入失败 (RIF) 被认为是辅助生殖技术 (ART) 计划成功的主要限制因素之一。目前的研究侧重于调查来自 44 名 25 至 39 岁女性的外周血 (PB) 和卵泡液 (FF) 中的基质金属蛋白酶 (MMP)、MMP 组织抑制剂 (TIMP)、细胞因子和细胞粘附分子并接受胞浆内精子注射（ICSI）。这些女性被分为两组：在至少三个 ICSI 周期内移植至少四个新鲜或冷冻解冻的优质胚胎后胚胎植入失败的 22 名 RIF 女性，以及 22 名获得临床试验的 ICSI 成功女性（对照组）在他们第一次尝试 ICSI 时怀孕。在取卵当天从每位患者获得 PB 和 FF 样本。MMP-1、-2、-3、-7、-9、TIMP-1、-2、血管内皮生长因子（VEGF）、白血病抑制因子（LIF）、血管细胞粘附分子1（VCAM1）和细胞间粘附分子使用 PB 和 FF 的酶联免疫吸附试验分析 1 (ICAM1)。我们的结果显示，与对照组相比，RIF 组的 PB MMP-7 和 PB VEGF 显着降低 [281.11 (33–614) pg/ml 对比 119.92 (27–441) pg/ml；磷-值 = 0.030] 和 [82.54 (25.94–210.20) pg/ml 对比 30.93 (13.62–193.33) pg/ml；磷-值 = 0.022；分别]。接受者操作特征 (ROC) 曲线分析显示 PB MMP-7 以及 PB VEGF 的曲线值下方的信息区域，使其能够被提议作为 RIF 的生物标志物。因此，循环 MMP-7 和 VEGF 似乎在体外受精（IVF）/ICSI 周期，并且可以被提议作为 RIF 的循环生物标志物。这些结果可能有助于临床医生和患者选择最佳的抢救策略和治疗方法，以最大限度地减少第一次尝试后接受 IVF/ICSI 手术的女性的植入失败。