Comparing risk factors and neonatal outcomes in women with intrahepatic cholestasis of pregnancy between assisted reproductive technology and spontaneous conception.

Objective: 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.

Methods: 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.

Results: 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), E₂ 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.

Conclusion: 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.