Intrahepatic cholestasis of pregnancy and neonatal outcomes in assisted reproductive technology versus spontaneous conception: a prediction nomogram-based study

Abstract

Background There are a limited number of studies comparing intrahepatic cholestasis of pregnancy (ICP) and neonatal outcomes in puerperae who spontaneously conceived (SC) and those who conceived via in vitro fertilization (IVF). We aimed to investigate the incidence of intrahepatic cholestasis of pregnancy (ICP) as well as neonatal outcomes between conception via IVF compared with spontaneous conception and screen the risk factors of ICP in IVF. Methods A retrospective cohort study included 4,467 puerperae who conceived via IVF, and 28,336 puerperae who conceived spontaneously and linked the information from neonates. Cochran–Mantel–Haenszel (CMH) analysis and a general linear model (GLM) were used to control bias. We compared the related serum-derived indicators and neonatal outcomes of ICP patients with IVF and SC. 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 = 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 transferred (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. And 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.