目的 探讨移植前血清成纤维细胞生长因子21（FGF-21）、抗苗勒管激素（AMH）及神经纤毛蛋白-1（NRP-1）在体外受精-胚胎移植（IVF-ET）术后孕6周胎停育中的预测价值，并基于血清生化指标构建早期预测模型。 方法 本研究采用前瞻性设计，连续纳入2022年9月至2024年9月期间在医院接受IVF-ET助孕并确诊为临床妊娠的322例患者，按7∶3比例将患者分为建模集（n = 225）和验证集（n = 97）。根据孕6周超声结果将建模集患者分为胎停组（n = 59）与持续妊娠组（n = 166）。采集患者基础临床资料及移植前血清FGF-21、AMH、NRP-1水平，采用多因素logistic回归分析筛选胎停育的独立影响因素，并构建预测模型。通过ROC曲线、Hosmer-Lemeshow拟合优度检验及Bootstrap重抽样方法对建模集和验证集模型的判别力、拟合度及稳定性进行评估。 结果 单因素分析显示，FSH/LH比值、窦卵泡数及获卵数与孕6周胎停育显著相关（P < 0.001）。胎停组患者移植前血清FGF-21水平明显升高，而AMH和NRP-1水平显著降低（P < 0.001）。Logistic回归分析结果显示，在控制年龄、BMI等与生殖结局相关的已知混杂因素后，FSH/LH < 1.8（OR = 1.629，P = 0.002）及移植前FGF-21水平升高（OR = 1.338，P = 0.002）仍是胎停育的独立危险因素，而移植前AMH（OR = 0.741，P = 0.010）及NRP-1水平（OR = 0.874，P = 0.007）较高则为保护因素。分层分析显示，在FSH/LH ≥ 1.8的患者中，FGF-21水平显著升高，而AMH及NRP-1水平均显著降低（P < 0.001）。交互作用分析提示，FSH/LH比值对3项指标与胎停育风险的关联均具有显著调节作用（P_交互 < 0.05）。在FSH/LH较高的亚组中，FGF-21的风险效应增强，AMH及NRP-1的保护效应亦更显著。本研究构建的建模集和验证集联合预测模型C-index 值分别为0.869（95%CI：0.826 ~ 0.926）和0.835（95%CI：0.811 ~ 0.907），其预测IVT-ET术后孕6周胎停育的AUC为0.934（建模集）和0.909（验证集）均显著优于单一指标（FGF-21、AMH、NRP-1的AUC分别为0.867、0.881、0.853）（Z = 2.024、1.831，P < 0.001），且DCA曲线提示该模型在0.1~0.4的阈值范围内均提供正向临床净收益，应用价值较高。 结论 移植前血清FGF-21升高、AMH及NRP-1降低与IVF-ET术后孕6周胎停育密切相关。本研究构建的联合预测模型表现出良好的准确性与稳定性，具备较高的临床应用价值。

Objective To investigate the predictive value of pre-transfer serum fibroblast growth factor 21 （FGF-21）， anti-Müllerian hormone （AMH）， and neuropilin-1 （NRP-1） for early pregnancy loss at 6 weeks following in vitro fertilization-embryo transfer （IVF-ET）， and to establish an early predictive model based on serum biochemical markers. Methods This prospective study consecutively enrolled 322 women who achieved clinical pregnancy after IVF-ET at our center between September 2022 and September 2024. Participants were randomly divided into a modeling cohort （n = 225） and a validation cohort （n = 97） at a 7：3 ratio. According to ultrasound findings at 6 weeks of gestation， patients in the modeling cohort were classified into an early pregnancy loss group （n = 59） and an ongoing pregnancy group （n = 166）. Baseline clinical characteristics and pre-transfer serum levels of FGF-21， AMH， and NRP-1 were collected. Multivariate logistic regression was applied to identify independent risk factors for early pregnancy loss and to construct a predictive model. Model discrimination， calibration， and stability were evaluated using receiver operating characteristic （ROC） curves， the Hosmer-Lemeshow goodness-of-fit test， and bootstrap resampling in both cohorts. Results Univariate analysis revealed that the FSH/LH ratio， antral follicle count， and number of retrieved oocytes were significantly associated with early pregnancy loss （P < 0.001）. Compared with the ongoing pregnancy group， women with early loss showed significantly elevated pre-transfer serum FGF-21 levels， whereas AMH and NRP-1 levels were markedly reduced （P < 0.001）. Multivariate logistic regression demonstrated that an FSH/LH ratio < 1.8 （OR = 1.629， P = 0.002） and higher FGF-21 levels （OR = 1.338， P = 0.002） were independent risk factors， while higher AMH （OR = 0.741， P = 0.010） and NRP-1 levels （OR = 0.874， P = 0.007） were protective. Stratified analysis indicated that among patients with FSH/LH ≥ 1.8， FGF-21 levels were significantly higher and AMH and NRP-1 levels significantly lower （all P < 0.001）. Interaction analysis further suggested that the FSH/LH ratio significantly modified the associations between these biomarkers and pregnancy loss risk （P for interaction < 0.05）. Specifically， in the higher FSH/LH subgroup， the risk effect of FGF-21 was amplified， while the protective effects of AMH and NRP-1 were more pronounced. The combined predictive model achieved C-indices of 0.869 （95%CI： 0.826 ~ 0.926） in the modeling cohort and 0.835 （95%CI： 0.811 ~ 0.907） in the validation cohort. Its AUC for predicting early pregnancy loss was 0.934 in the modeling cohort and 0.909 in the validation cohort， both significantly outperforming individual markers （AUCs： FGF-21 = 0.867， AMH = 0.881， NRP-1 = 0.853； Z = 2.024， 1.831； P < 0.001）. Decision curve analysis showed that the model provided consistent net clinical benefit across threshold probabilities of 0.1 ~ 0.4， underscoring its clinical utility. Conclusions Elevated pre-transfer serum FGF-21 and reduced AMH and NRP-1 levels are strongly associated with early pregnancy loss at 6 weeks after IVF-ET. The predictive model developed in this study demonstrates robust accuracy and stability， offering substantial clinical application value for early risk stratification.