Placental Oxidative Stress and eNOS Alterations in Intrahepatic Cholestasis of Pregnancy Following ICSI

<b>Background:</b> Pregnancies following in vitro fertilization (IVF) are associated with higher rates of intrahepatic cholestasis of pregnancy (ICP) compared to spontaneous conceptions. This study aimed to investigate oxidative stress biomarkers, endothelial nitric oxide synthase (eNOS) expression, and placental histopathology in ICP women undergoing intracytoplasmic sperm injection (ICSI). <b>Methods:</b> Placental samples from four groups-healthy spontaneous conception (non-ICP-SC, n = 7), ICP spontaneous conception (ICP-SC, n = 7), healthy ICSI (non-ICP-ICSI, n = 7), and ICP-ICSI (n = 7)-were analyzed. eNOS immunostaining, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and syncytial knots were evaluated. <b>Results:</b> The ICP ICSI group had the highest TAS and lowest eNOS levels (p < 0.05). Non-ICP-ICSI showed higher TOS and syncytial knots compared to non-ICP-SC (p = 0.026, p = 0.01). eNOS expression was lower in ICP-ICSI versus ICP-SC (p = 0.021). <b>Conclusion:</b> These findings suggest that ICP-ICSI placentas experience increased oxidative stress and decreased eNOS expression. ICSI may affect placental oxidative balance regardless of ICP status.