Changes of peripheral blood miR-145 level and its effect on PAI-1 in patients with repeated implantation failure
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摘要:
目的 探讨反复种植失败患者取卵前、胚胎移植前血清miR-145水平变化及对纤溶酶原激活物抑制因子-1(PAI-1)的影响。 方法 选取2021年1月—2022年6月湖南省郴州市第一人民医院生殖医学中心胚胎反复种植失败(RIF)患者71例为观察组，妊娠成功者551例为对照组。分析miR-145与PAI-1相关性、miR-145与RIF的独立关系，miR-145对RIF的评估价值。 结果 取卵前、胚胎移植前观察组血清miR-145[(1.09±0.13)ng/mL vs.(0.98±0.14)ng/mL，F=8.419，P=0.004；(1.19±0.16)ng/mL vs.(1.01±0.18)ng/mL，F=58.184，P＜0.001]、PAI-1[(21.36±6.28)ng/mL vs.(15.09±7.16)ng/mL，F=6.463，P=0.017；(25.36±6.18)ng/mL vs.(17.32±6.99)ng/mL，F=78.536，P＜0.001]水平高于对照组；观察组取卵前、胚胎移植前miR-145与PAI-1均呈正相关关系(r=0.725，P＜0.001；r=0.671，P＜0.001)；取卵前、胚胎移植前miR-145均与RIF独立相关(P＜0.05)；取卵前、胚胎移植前miR-145评估RIF的AUC值分别为0.690、0.774。 结论 RIF不孕症患者miR-145呈异常高表达，其可能通过靶向调节PAI-1表达降低子宫内膜容受性，参与RIF的发生过程。 -
关键词:
- 反复种植失败 /
- miR-145 /
- 纤溶酶原激活物抑制因子-1 /
- 体外受精-胚胎移植
Abstract:Objective To investigate the changes of serum miR-145 levels and their impact on plasminogen activator inhibitor 1 (PAI-1) in patients with repeated implantation failure before egg retrieval and embryo transfer. Methods A total of 71 cases of repeated implantation failure (RIF) in the Reproductive Medicine Center of the First People's Hospital of chenzhou were included in the observation group, and 551 cases of successful pregnancy were included in the control group. The correlation between miR-145 and PAI-1, the independent relationship between miR-145 and RIF, and the evaluation value of miR-145 on RIF were analyzed. Results The levels of miR-145 [(1.09±0.13)ng/mL vs. (0.98±0.14) ng/mL, F=8.419, P=0.004; (1.19±0.16) ng/mL vs. (1.01±0.18) ng/mL, F=58.184, P<0.001] and PAI-1 [(21.36±6.28) ng/mL vs. (15.09±7.16) ng/mL, F=6.463, P=0.017; (25.36±6.18) ng/mL vs.(17.32±6.99) ng/mL, F=78.536, P<0.001] in the observation group were higher than those in the control group before egg retrieval and embryo transfer. There was a positive correlation between miR-145 and PAI-1 in the observation group before egg retrieval and embryo transfer (r=0.725, P<0.001; r=0.671, P<0.001). miR-145 was independently correlated with RIF before egg retrieval and embryo transfer (P<0.05). The AUC values of RIF evaluated by miR-145 before egg retrieval and embryo transfer were 0.690 and 0.774, respectively. Conclusion Patients with RIF infertility have abnormally high expression of miR-145, and it may reduce endometrial receptivity by targeting PAI-1 expression, thus participating in the process of RIF. -
图 1 取卵前和胚胎移植前miR-145水平评估RIF的ROC曲线
Figure 1. ROC curves of RIF evaluated by miR 145 levels before egg retrieval and embryo transfer
表 1 2组不孕症患者临床资料比较
Table 1. Comparison of clinical data of two groups of infertility patients
项目 观察组(71例) 对照组(551例) 统计量 P值 年龄(x±s，岁) 32.06±3.18 30.14±2.92 5.161a < 0.001 配偶年龄(x±s，岁) 35.26±6.72 34.19±7.03 1.213a 0.226 不孕年限(x±s，年) 4.31±1.05 3.70±1.13 4.315a < 0.001 体重指数[例(%)] <18.5 17(23.94) 63(11.43) 8.783b 0.003 18.5~<25.0 34(47.89) 303(54.99) 1.278b 0.258 25.0~<30.0 20(28.17) 185(33.58) 0.832b 0.362 吸烟史[例(%)] 6(8.45) 46(8.35) 0.001b 0.977 饮酒史[例(%)] 9(12.68) 59(10.71) 0.250b 0.617 不孕类型[例(%)] 10.242b 0.001 原发性 21(29.58) 274(49.73) 继发性 50(70.42) 277(50.27) 人工流产次数[例(%)] 2.707c 0.007 0次 50(70.42) 459(83.30) 1次 15(21.13) 72(13.07) 2次 6(8.45) 20(3.63) 宫腔镜检查异常[例(%)] 20(28.17) 387(70.24) 49.210b < 0.001 女方染色体核型异常[例(%)] 3(4.23) 15(2.72) 0.112b 0.738 男方染色体核型异常[例(%)] 7(9.86) 51(9.26) 0.027b 0.869 SAS评分(x±s，分) 68.98±6.73 64.86±7.02 4.676a < 0.001 SDS评分(x±s，分) 63.25±5.44 60.05±5.18 4.871a < 0.001 AMH(x±s，ng/mL) 4.02±1.89 5.12±2.01 4.369a < 0.001 FSH(x±s，IU/L) 6.91±1.04 6.40±1.11 3.669a < 0.001 LH(x±s，IU/L) 5.59±2.13 5.71±2.30 0.417a 0.677 雌二醇(x±s，pg/mL) 43.26±18.28 45.61±20.01 0.940a 0.348 孕酮(x±s，ng/mL) 0.42±0.16 0.39±0.15 1.574a 0.116 睾酮(x±s，ng/mL) 0.34±0.13 0.37±0.15 1.609a 0.108 PRL(x±s，ng/mL) 19.67±6.32 18.56±7.04 1.264a 0.207 移植日内膜厚度(x±s，mm) 10.01±2.02 10.79±2.11 2.946a 0.003 移植日宫腔深度(x±s，cm) 8.09±0.57 7.99±0.61 1.310a 0.191 注：a为t值，b为χ2值, c为Z值。 
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表 2 2组不孕症患者取卵前、胚胎移植前血清miR-145、PAI-1水平比较(x±s)
Table 2. Comparison of serum miR-145 and PAI-1 levels between two groups of infertility patients before egg retrieval and embryo transfer (x±s)
组别 例数 miR-145 PAI-1(ng/mL) 取卵前 胚胎移植前 取卵前 胚胎移植前 观察组 71 1.09±0.13 1.19±0.16 21.36±6.28 25.36±6.18 对照组 551 0.98±0.14 1.01±0.18 15.09±7.16 17.32±6.99 F值 8.419 58.184 6.463 78.536 P值 0.004 < 0.001 0.017 < 0.001
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表 3 Logistic回归模型分析miR-145与RIF发生的独立关系
Table 3. Logistic regression model analysis of the independent relationship between miR-145 and RIF
因素 B SE Wald χ2 P值 OR值 95% CI 模型1 取卵前 Q2 0.750 0.319 5.535 0.041 2.118 1.352~3.318 Q3 0.790 0.334 5.594 0.037 2.203 1.427~3.402 Q4 0.880 0.327 7.241 0.025 2.411 1.609~3.612 胚胎移植前 Q2 0.780 0.324 5.793 0.039 2.181 1.393~3.415 Q3 0.870 0.335 6.741 0.030 2.386 1.505~3.784 Q4 0.969 0.332 8.512 0.013 2.634 1.693~4.099 模型2 取卵前 Q2 0.805 0.329 5.984 0.035 2.236 1.428~3.502 Q3 0.897 0.318 7.960 0.021 2.453 1.521~3.955 Q4 1.053 0.336 9.822 0.002 2.866 1.973~4.164 胚胎移植前 Q2 0.917 0.322 8.106 0.018 2.501 1.699~3.682 Q3 1.011 0.338 8.938 0.010 2.747 1.872~4.031 Q4 1.083 0.321 11.388 < 0.001 2.954 2.043~4.272 模型3 取卵前 Q2 0.988 0.319 9.595 0.006 2.686 1.882~3.834 Q3 1.062 0.320 11.016 < 0.001 2.892 2.038~4.105 Q4 1.153 0.324 12.662 < 0.001 3.167 2.220~4.519 胚胎移植前 Q2 1.014 0.327 9.625 0.004 2.758 1.915~3.972 Q3 1.135 0.341 11.069 < 0.001 3.110 2.139~4.521 Q4 1.224 0.332 13.588 < 0.001 3.400 2.407~4.803 注：模型1无调整混杂因素；模型2调整年龄、不孕年限、体重指数、不孕类型、宫腔镜检查异常、SAS评分、SDS评分；模型3调整年龄、不孕年限、体重指数、不孕类型、宫腔镜检查异常、SAS评分、SDS评分、FSH、AMH、移植日内膜厚度。均以Q1为参照。
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表 4 取卵前和胚胎移植前miR-145水平对RIF的评估价值
Table 4. Assessment value of miR-145 levels on RIF before egg retrieval and embryo transfer
指标 AUC 95% CI Z值 P值 Cut-off值 Youden指数 灵敏度(%) 特异度(%) 取卵前miR-145 0.690 0.652~0.727 5.843 < 0.001 >1.02 0.319 71.83 60.07 胚胎移植前miR-145 0.774 0.739~0.806 9.776 < 0.001 >1.06 0.428 78.87 63.88
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