生殖医学杂志

目的 探讨血清白细胞介素-6(IL-6)/Janus激酶-2(JAK2)/转录激活蛋白3(STAT3)信号通路水平与早发性卵巢功能不全（POI）患者卵巢反应性及体外受精-胚胎移植（IVF-ET）妊娠结局的关系。方法 选取2021年1月至2024年8月在邢台市中心医院行IVF-ET助孕的POI患者196例（POI组），另按照2∶1比例选取同期接受体检的健康女性98例为对照组。采用酶联免疫吸附法检测两组研究对象的血清IL-6、JAK2、STAT3水平。POI患者再根据助孕过程中卵巢反应性分为高反应组（26例）、正常反应组（58例）和低反应组（112例），以及根据IVF-ET妊娠结局分为不良结局组（112例）和良好结局组（84例），通过Pearson相关分析POI患者血清IL-6、JAK2、STAT3水平的相关性，采用多因素Logistic回归分析血清IL-6/JAK2/STAT3信号通路水平与POI患者IVF-ET妊娠结局的关系，并利用接收者操作特征（ROC）曲线分析血清IL-6/JAK2/STAT3信号通路水平对POI患者IVF-ET妊娠结局不良的预测能效。结果 （1）与对照组比较，POI组血清IL-6、JAK2、STAT3水平均显著升高（P<0.001）;POI患者血清IL-6、JAK2、STAT3水平呈两两相关（P<0.001）。（2）POI患者卵巢高反应组、正常反应组、低反应组的血清IL-6、JAK2、STAT3水平均依次显著升高（P<0.001）;196例POI患者IVF-ET妊娠结局不良率为57.14%(112/196),FSH水平升高、卵巢低反应性异常、IL-6水平升高、JAK2水平升高、STAT3水平升高为POI患者IVF-ET妊娠结局不良的独立危险因素（P<0.05），而AMH升高为独立保护因素（P<0.05）。（3）血清IL-6/JAK2/STAT3信号通路水平联合预测POI患者IVF-ET妊娠结局不良的曲线下面积（AUC）为0.931，大于血清IL-6、JAK2、STAT3单独预测的AUC（分别为0.771、0.785、0.790,P<0.001），其敏感度为0.866、特异度为0.857。结论 血清IL-6/JAK2/STAT3信号通路水平升高与POI患者卵巢反应性降低及IVF-ET妊娠结局不良有关，血清IL-6/JAK2/STAT3信号通路水平联合对IVF-ET妊娠结局不良具有较高的预测能效。

Objectives: To investigate the relationships among serum interleukin-6(IL-6)/Janus kinase-2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway levels and ovarian response and pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)in patients with premature ovarian insufficiency(POI).Methods:A total of 196 POI patients who underwent IVF-ET at Xingtai Central Hospital from January 2021 to August 2024 were selected as the POI group,and 98 healthy women who underwent physical examinations during the same period were selected as the control group in a 2∶1 ratio.Serum IL-6,JAK2 and STAT3 levels in two groups were measured by enzyme-linked immunosorbent assay.POI patients were further divided into high response group(26 cases),normal response group(58 cases)and low response group(112 cases)based on ovarian responsiveness during assisted reproduction.According to the pregnancy outcomes of IVF-ET,the patients were divided into adverse outcome group(112 cases)and good outcome group(84 cases).Correlation analyses of serum IL-6,JAK2 and STAT3 levels in POI patients were conducted using Pearson correlation coefficient.The relationship between serum IL-6/JAK2/STAT3 signaling pathway levels and IVF-ET pregnancy outcomes in POI patients were analyzed by multivariate logistic regression.The predictive efficiency of the serum IL-6/JAK2/STAT3 signaling pathway levels for poor IVF-ET pregnancy outcomes in POI patients was analyzed by receiver operating characteristic(ROC)curve.Results:Compared with the control group,serum levels of IL-6,JAK2 and STAT3 were significantly increased in the POI group(P<0.001).The serum levels of IL-6,JAK2 and STAT3 of POI patients showed pairwise correlations(P<0.001).The serum levels of IL-6,JAK2 and STAT3 were all gradually increased from the low to high response group(P<0.001).The poor IVF-ET pregnancy outcome rate in196 POI patients was 57.14%(112/196).The elevated FSH level,abnormal ovarian hyporesponsiveness,the increase of IL-6 level,JAK2 level and STAT3 level were independent risk factors for poor IVF-ET pregnancy outcomes in POI patients,while the elevated anti-Müllerian hormone(AMH) was an independent protective factor(P<0.05).The area under the ROC curve for predicting poor IVF-ET pregnancy outcomes using the combined IL-6/JAK2/STAT3 signaling pathway in POI patients was 0.931,which was higher than that predicted by serum IL-6,JAK2,STAT3 levels alone(0.771,0.785,0.790,respectively,P<0.001),with the sensitivity of 0.866 and the specificity of 0.857.Conclusions:The increase of serum IL-6/JAK2/STAT3 signaling pathway levels were associated with decreased ovarian response and poor IVF-ET pregnancy outcomes in POI patients.The combination of serum IL-6/JAK2/STAT3 signaling pathway levels showed a high predictive power for adverse pregnancy outcomes in IVF-ET.