Association between nonalcoholic fatty liver disease and infertility in reproductive-aged females

Context : Findings from observational studies indicate association between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome. However, the relationship between NAFLD and female infertility remains unclear. Objective : This study aimed to evaluate the associations between NAFLD and female infertility at the phenotypic and genetic levels. Methods : Cross-sectional analysis using the 2013-2018 and 2017-2020 (pre-pandemic) National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI), median value of controlled attenuation parameter (CAP)and liver stiffness measurement (LSM). Multivariable logistic regression and subgroup analyses were used to examine the observational associations of NAFLD related indicesand female infertility. Subgroup analyses were used to explore whether the relationship between female infertility and HSI values was influenced by potential confounders. A bidirectional, two-sample Mendelian randomization analysis was used to determine the potential causal relationship between NAFLD and female infertility. Results : Higher HSI was associated with progressively higher odds of infertility in women. Increasing CAP and LSM value were positively associated with an increased risk of female infertility. There was an interaction between age and NAFLD indices in relation to the prevalence of female infertility. In MR analyses, the IVW method showed no genetically causal relationship between NAFLD and female infertility. Conclusion : Reproductive-aged women with NAFLD may have higher prevalence of infertility in the U.S. however, findings from MR analysis did not indicate a causal relationship between NAFLD and female infertility.