探讨胚胎移植后第14天接受辅助生殖技术（ART）的不孕妇女血清相关指标（炎性细胞因子和必需微量元素水平）与流产风险的关系。开发并建立多变量预测妊娠结局的算法模型。根据嵌套的病例对照研究设计，这项研究共包括100例流产病例和100例活产对照组，两组妇女均不育，并接受了体外受精（IVF）。进行妊娠试验，血清中五种必需微量元素（钒（V），铜(Cu),锌(Zn),硒（Se）和钼（Mo）和五种炎症细胞因子（白细胞介素-1β（IL-1β），在胚胎移植后第14天测量参与者的IL-6，IL-8，IL-10和肿瘤坏死因子-α（TNF-α）。采用多重磁珠酶免疫分析仪测定血清中5种炎性细胞因子的含量;采用电感耦合等离子体质谱(ICP-MS)同时测定血清中5种元素的浓度。采用logistic回归分析这些血清指标与接受ART治疗的妇女流产风险的关系,建立了基于这些指标的妊娠结局预测模型。活产组不孕妇女IL-10、IL-1β和TNF-α水平明显高于流产组(p=0.009,p<0.001,p=0.006),和V的水平，Cu,活产组不孕妇女的Zn和Se也明显高于流产组(均p<0.001)。通过逻辑回归分析，我们发现IL-1β的血清水平,TNF-α,V,Cu,锌和硒与流产风险显著负相关。根据logistic回归分析结果生成不同的组合预测模型,和IL-1β的组合，Cu和Zn具有最好的预测性能。曲线下面积（AUC）为0.776，模型的敏感性为60％，特异性为84％。总之,胚胎移植后第14天接受ART的女性血清相关指标，包括炎症细胞因子如IL-1β和TNF-α和必需的微量金属元素如V,Cu,Zn和Se，与流产风险呈负相关。建立了预测接受ART的妇女妊娠结局的多变量算法模型,这表明IL-1β，Cu和Zn可以协同预测妊娠结局。
To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nested
case-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1β and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1β, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1β, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion, the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1β and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1β, Cu and Zn might synergistically predict pregnancy outcome.
