Yang Jingwei, Gao Jing, Zhou Danni, Ye Hong, Huang Guoning, Lian Xuemei, Zhang Xiaodong
Chongqing Key Laboratory of Human Embryo Engineering, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Clinical Research Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Chongqing, China.
Int J Gynaecol Obstet. 2025 Feb;168(2):663-672. doi: 10.1002/ijgo.15878. Epub 2024 Aug 22.
The aim of the present study was to investigate the incidence of intrahepatic cholestasis of pregnancy (ICP) as well as neonatal outcomes between conception via in vitro fertilization (IVF) compared with spontaneous conception (SC) and screen the risk factors of ICP in IVF.
This retrospective cohort study included 4467 puerperae who conceived via IVF, and 28 336 puerperae who conceived spontaneously and linked the information from neonates. The general linear model (GLM), multivariate logistic regression analysis, a forest plot, and nomogram were used to assess impact factors and risk prediction.
Logistic analysis adjusted for confounders revealed significant differences in the ICP rate of singleton delivery (4.24% vs 3.41%, adjusted OR [aOR] = 1.26; 95% confidence interval [CI] 1.03-1.53, P = 0.025) and in groups with total bile acids (TBA) ≥40 and <100 μmol/L (14.77% vs 10.39%, aOR = 1.31; 95% CI: 1.06-1.63, P = 0.023) between IVF and SC. When we divided newborns into singleton and twins delivery, the GLM revealed a higher rate with Apgar score <7 (13.44% vs 3.87%, aOR = 3.85; 95% CI: 2.07-7.17, P < 0.001) and fetal distress for IVF in comparison with SC (19.32% vs 5.55%, OR = 3.48; 95% CI: 2.39-6.95, P < 0.001) in the singleton group. In multivariate logistic regression analysis, body mass index (BMI) (aOR = 1.29; P = 0.031), number of embryo transfers (ET) (single ET vs double ET, aOR = 2.82; P < 0.001), E level on the ET day (aOR = 2.79; P = 0.011), fresh ET which compared with frozen ET (FET) (aOR = 1.45; P = 0.014), embryo stage (cleavage embryo vs blastocyst, aOR = 1.75; P = 0.009) and severe ovarian hyperstimulation syndrome (OHSS) which compared with non-OHSS (aOR = 3.73; P = 0.006) were independent predictors of ICP. These predictive factors in the logistic regression model were integrated into the nomogram (C-index = 0.735; 95% CI: 0.702-0.764); for each patient, higher total points indicated a higher risk of ICP.
We observed that the ICP rate of singleton delivery was higher in IVF than in SC. In ICP patients, there were higher rates of neonatal Apgar score <7 and fetal distress in IVF than SC and found the predictors of ICP in IVF.
本研究旨在调查体外受精(IVF)受孕与自然受孕(SC)相比,妊娠肝内胆汁淤积症(ICP)的发生率以及新生儿结局,并筛查IVF中ICP的危险因素。
这项回顾性队列研究纳入了4467例通过IVF受孕的产妇以及28336例自然受孕的产妇,并关联了新生儿的信息。采用一般线性模型(GLM)、多因素逻辑回归分析、森林图和列线图来评估影响因素和风险预测。
经混杂因素调整后的逻辑分析显示,单胎分娩的ICP发生率(4.24%对3.41%,调整后比值比[aOR]=1.26;95%置信区间[CI]1.03 - 1.53,P=0.025)以及总胆汁酸(TBA)≥40且<100μmol/L组(14.77%对10.39%,aOR=1.31;95%CI:1.06 - 1.63,P=0.023)在IVF和SC之间存在显著差异。当我们将新生儿分为单胎和双胎分娩时,GLM显示与SC相比,IVF中单胎组阿氏评分<7的发生率更高(13.44%对3.87%,aOR=3.85;95%CI:2.07 - 7.17,P<0.001)以及胎儿窘迫发生率更高(19.32%对5.55%,OR=3.48;95%CI:2.39 - 6.95,P<0.001)。在多因素逻辑回归分析中,体重指数(BMI)(aOR=1.29;P=0.031)、胚胎移植次数(ET)(单次ET对双次ET,aOR=2.82;P<0.001)、ET日的E水平(aOR=2.79;P=0.011)、新鲜ET与冷冻ET(FET)相比(aOR=1.45;P=0.014)、胚胎阶段(卵裂期胚胎对囊胚,aOR=1.75;P=0.009)以及重度卵巢过度刺激综合征(OHSS)与非OHSS相比(aOR=3.73;P=0.006)是ICP的独立预测因素。逻辑回归模型中的这些预测因素被整合到列线图中(C指数=0.735;95%CI:0.702 - 0.764);对于每位患者,总分越高表明ICP风险越高。
我们观察到IVF中单胎分娩的ICP发生率高于SC。在ICP患者中,IVF中新生儿阿氏评分<7和胎儿窘迫的发生率高于SC,并发现了IVF中ICP的预测因素。