Claims-defined hepatic steatosis compatible with MASLD and reproductive outcomes after the first observed embryo transfer: a Korean nationwide cohort study

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly prevalent among women of reproductive age; however, its association with reproductive outcomes after in vitro fertilization (IVF) remains insufficiently characterized in population-level data. We evaluated pre-index claims-defined hepatic steatosis compatible with MASLD as the primary exposure of interest in relation to first claims-identified pregnancy and time to first claims-identified live birth after the first observed embryo transfer (ET). Inflammatory bowel disease, irritable bowel syndrome, and autoimmune hepatobiliary disease were included as gastrointestinal and hepatic comparators. We conducted a retrospective cohort study using Korean National Health Insurance Service claims data from 2017 to 2024. Among 601,664 women with an infertility diagnosis (ICD-10 N97), 122,134 underwent a first observed ET between 2019 and 2023 after predefined exclusions. Exposures were ascertained from pre-index claims using disease-specific ascertainment windows. The co-primary outcomes were first claims-identified pregnancy and time to first claims-identified live birth after the index ET. Claims-defined pregnancy loss was a secondary outcome among women with a first claims-identified pregnancy. Associations were analyzed using inverse probability of treatment weighting (IPTW)-adjusted Cox and logistic regression models, with false discovery rate (FDR) correction and E-value analyses. Among 122,134 women (mean age, 36.4 ± 4.2 years), 82.1% had a first claims-identified pregnancy and 62.7% had a claims-identified live birth during follow-up. After IPTW adjustment, claims-defined hepatic steatosis compatible with MASLD was associated with a modestly lower hazard of first claims-identified pregnancy (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.88–0.98; FDR q = 0.049) and first live birth during follow-up (HR 0.88; 95% CI 0.82–0.94; FDR q = 0.0006). It was not associated with claims-defined pregnancy loss among women with a first claims-identified pregnancy. Pre-index claims-defined hepatic steatosis compatible with MASLD was associated with modestly lower hazards of first claims-identified pregnancy and first live birth during follow-up. Because body mass index, ovarian-reserve markers, clearly separated ovarian phenotypes, male-factor information, and cycle-level characteristics were unavailable, MASLD-compatible hepatic steatosis may represent a broader metabolic–reproductive phenotype rather than an independent hepatic effect. Given the modest E-values, these findings are hypothesis-generating and should not be interpreted causally or used alone to guide individual IVF counseling or treatment decisions.