HOMA-IR partially mediates the association between percent appendicular skeletal muscle mass and IVF/ICSI outcomes

BACKGROUND: Skeletal muscle mass contributes to metabolic health, particularly in relation to insulin sensitivity, and both skeletal muscle mass and metabolic health may influence outcomes after assisted reproductive technology (ART). However, whether insulin sensitivity partially explains the association between skeletal muscle mass and ART outcomes remains unclear. This study aimed to investigate the association between the percentage of appendicular skeletal muscle mass (PASM) and outcomes from in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and to explore whether insulin resistance, assessed by HOMA-IR, partially mediates this association. METHODS: This retrospective study included 990 patients who underwent IVF/ICSI at Nanjing Medical University from April 2022 to April 2023. PASM was measured by bioelectrical impedance analysis (BIA) and analysed both as quartiles and as a continuous variable. Insulin sensitivity was assessed using the homeostatic model assessment of insulin resistance (HOMA‑IR). We employed Spearman's correlation analysis, multivariate regression, restricted cubic spline (RCS) models, and mediation analysis with adjustment for relevant confounders. RESULTS: Unadjusted comparisons showed only non-significant increasing trends across PASM quartiles, whereas adjusted regression analyses indicated more favourable laboratory outcomes in higher PASM quartiles. Each 1-unit increase in PASM was associated with the number of oocytes retrieved (Beta = 0.29), available embryos (Beta = 0.25) and blastocysts (Beta = 0.21), as well as higher available embryo rate (Beta = 1.49) and blastocyst formation rate (Beta = 1.52). PASM was positively linked to cumulative clinical pregnancy rate (CCPR) (OR = 1.30). Higher PASM was inversely associated with HOMA‑IR and insulin resistance (IR) prevalence; elevated HOMA‑IR was independently associated with poorer embryology laboratory indicators (P < 0.05). Mediation analysis suggested that HOMA-IR modestly mediated 5.5%, 5.9%, and 7.3% of the associations between PASM and the number of oocytes retrieved, available embryos and blastocysts, respectively. CONCLUSIONS: Higher PASM was associated with more favourable embryology laboratory indicators and higher pregnancy success after IVF/ICSI, with HOMA-IR showing partial and modest mediation. Interventions targeting skeletal muscle mass may represent a potential strategy for optimizing assisted reproduction outcomes, pending confirmation in prospective studies.