O-151 Intrahepatic cholestasis of pregnancy and relevant neonatal outcomes in IVF versus spontaneous conception: a prediction nomogram-based study
Authors: Yang J , Zhang X , Huang G , Ye H 
Published: June 2023

Abstract

Study question
Does the incidence of intrahepatic cholestasis of pregnancy (ICP) differ in spontaneous conception(SC) versus in vitro fertilization (IVF) conception?

Summary answer
We observed that the ICP rate was higher in IVF than in SC, and first built a prediction nomogram to find the predictors of ICP.

What is known already
There are limited clinical studies comparing intrahepatic cholestasis of pregnancy(ICP) and neonatal outcomes in puerperae who spontaneously conceived and those who conceived via assisted reproductive technology. Several studies comparing the maternal, laboratory, and perinatal characteristics of in-vitro fertilization(IVF) and spontaneous pregnancies concerning ICP show that IVF treatment has an increased risk of ICP in singleton and multiple deliveries. However, given that it is difficult to collect big data, most research on IVF patients with ICP involve small sample size or case reports.

Study design, size, duration
This was a retrospective real-world data study that linked the information from puerperae and neonates. We included 4,467 puerperae who conceived via ART, and 28,336 puerperae who conceived spontaneously.

Participants/materials, setting, methods
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 in vitro fertilization (IVF) and SC. Multivariate logistic regression analysis, a forest plot, and nomogram were used to assess impact factors and risk prediction.

Main results and the role of chance
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 &lt;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 &lt;7 (13.44% vs. 3.87%; aOR=3.85 [95% CI: 2.07–7.17], P &lt;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 &lt;0.001) in the singleton group. In multivariate logistic regression analysis, five factors were independent predictors of ICP: body mass index (BMI) (aOR=1.75 [95% CI 1.03–2.13], P=0.036), number of embryo transferred (ET) (single ET vs. double ET: aOR=4.82 [95% CI 3.83–6.05], P&lt;0.001), E2 level on the ET day (aOR=2.79 [95% CI 1.79–4.05], P=0.011), fresh ET which compared with frozen ET (FET) (aOR=1.40 [95% CI 1.09–1.80], P=0.008), and severe ovarian hyperstimulation syndrome which compared with non-OHSS (aOR=3.97 [95% CI 1.79–8.80], P&lt;0.001). 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.

Limitations, reasons for caution
The limitations of this study include its retrospective nature, and the balance in baseline characteristics between IVF and SC measured using statistical methods.

Wider implications of the findings
Our results provide evidence for the incidence of ICP between spontaneously conceived and those who conceived via IVF, and found predictors of ICP in IVF treatment. It could assist physicians in making clinical decisions avoiding risk factors during IVF, and taking preventive countermeasures for patients.

Trial registration number
not applicable