Metrnl在子宫内膜容受性调控中的作用及其表达异常与反复种植失败的关联

Role of Metrnl in regulation of endometrial receptivity and the association between its abnormal expression and repeated implantation failure

摘要:

目的 分析镍纹样蛋白（Metrnl）表达与不孕症患者子宫内膜受容性及反复种植失败（RIF）的关联。方法 本文为回顾性研究，选取2020年10月至2022年12月黄河三门峡医院收治的113例不孕症患者，所有患者均采用体外受精/卵细胞浆内单精子注射-胚胎移植（IVF/ICSI-ET）进行辅助生殖（ART）治疗，根据ART治疗结果，将种植成功的60例患者列为成功组，将RIF的53例患者列为失败组，检测并对比两组患者的子宫内膜受容性相关指标及Metrnl表达情况，经Spearman相关性系数验证Metrnl表达与子宫内膜受容性的相关性，通过绘制受试者工作特征（ROC）曲线并参考线下面积（AUC）验证Metrnl表达对不孕症患者RIF结局的预测效能。结果 经检测，失败组的子宫内膜厚度为（10.25±3.41）mm，子宫内膜容积为（4.14±2.26）mL，均低于成功组［（12.33±3.24）mm、（5.77±2.38）mL］，子宫内膜血流阻力指数（RI）为（2.44±0.75），高于成功组（1.88±0.27）（P<0.05）。经检测，失败组的胎盘蛋白14（PP14）表达水平为（23.44±5.28）μg/L，半乳糖凝集素-1（GAL-1）表达评分为（4.15±1.26）分，骨桥蛋白（OPN）分子表达量为（38.24±10.46）kDa，均低于成功组［（26.25±5.16）μg/L、（5.44±1.76）分、（45.33±10.37）kDa］（P<0.05）。失败组的Metrnl表达水平为（95.25±20.61）pg/mL，高于成功组（78.24±20.16）pg/mL（P<0.05）。经Spearman相关性系数检验，Metrnl表达与子宫内膜厚度、子宫内膜容积、PP14、GAL-1、OPN负相关，与RI正相关。经ROC曲线验证，Metrnl高表达对不孕症患者RIF的预测灵敏度为80.25%、特异度为78.33%，截断值为90.45 pg/mL，AUC值为0.855。结论 Metrnl表达水平与子宫内膜受容性密切相关，高表达Metrnl为导致不孕症患者RIF结局的危险因素，当Metrnl表达≥90.27 pg/mL，不孕症患者更易出现RIF。

关键词:不孕症;反复种植失败;镍纹样蛋白;子宫内膜受容性;相关性分析

Abstract:

Objective To analyze the association between Metrnl expression and endometrial receptivity and repeated implantation failure (RIF) in infertility patients.Methods This article is a retrospective study, with cases included from October 2020 to December 2022. The study subjects were 113 infertile patients, all of whom were treated with in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) for assisted reproductive technology (ART). Based on the results of ART treatment, 60 patients with successful implantation were classified as the success group, and 53 patients with RIF were classified as the failure group. The endometrial receptivity related indicators and Metrnl expression of the two groups of patients were tested and compared. The correlation between Metrnl expression and endometrial receptivity was verified by Spearman correlation coefficient, and the predictive efficacy of Metrnl expression on RIF outcomes in infertile patients was verified by plotting receiver operating characteristic (ROC) curve and referencing the area under the curve (AUC).Results After testing, the endometrial thickness and volume of the failed group were 10.25±3.41 mm and 4.14±2.26 mL, respectively, which were lower than those of the successful group (12.33±3.24 mm and 5.77±2.38 mL). Endometrial blood flow resistance index (RI) of the failed group was 2.44±0.75, which was higher than that of the successful group (1.88±0.27) (P<0.05). After testing, the expression level of PP14 was 23.44±5.28 μg/L, GAL-1 expression score was 4.15±1.26 points, and OPN molecular expression level was 38.24±10.46 kDa in the failed group, which were lower than those in the successful group (26.25±5.16 μg/L, 5.44±1.76 points, and 45.33±10.37 kDa (P<0.05). The expression level of Metrnl in the failed group was 95.25±20.61 pg/mL, which was higher than that in the successful group (78.24±20.16 pg/mL (P<0.05). After Spearman correlation coefficient test, the expression of Metrnl was negatively correlated with endometrial thickness, endometrial volume, PP14, GAL-1, OPN, and positively correlated with RI. The ROC curve showed that the sensitivity, specificity, cut-off value and AUC value of Metrnl high expression for predicting RIF in infertile patients were 80.25%,78.33%, 90.45 pg/mL and 0.855 respectively.Conclusion The expression level of Metrnl is closely related to endometrial receptivity, and high expression of Metrnl is a risk factor for RIF outcomes in infertile patients. When Metrnl expression is not lower than 90.27 pg/mL, infertile patients are more likely to develop RIF.

Key words:infertility;repeated planting failure;Nickel like secretory protein;endometrial receptivity;correlation analysis