Localized Depletion of Seminal HDL-C Despite Preserved Systemic Lipid Profiles in Men with Impaired Semen Parameters: A Prospective Cross-Sectional Study.

BACKGROUND

Lipid homeostasis is essential for sperm membrane integrity, capacitation, and fertilizing competence. However, whether lipid alterations associated with oligoasthenoteratozoospermia (OAT) reflect systemic dyslipidemia or a disturbance localized to the seminal compartment remains unclear. This study investigated serum high-density lipoprotein (HDL) subfractions and seminal lipid concentrations in men with OAT.

METHODS

In this prospective cross-sectional study, 99 men were included: 49 men clinically classified as having OAT and 50 men with normozoospermia. Conventional semen analysis was performed according to the WHO 2021 manual. Serum HDL subfractions were analyzed using the Lipoprint HDL system, which classifies HDL into 10 subfractions and 3 major groups (large, intermediate, and small HDL). Seminal plasma total cholesterol and high-density lipoprotein cholesterol (HDL-C) were measured using enzymatic colorimetric and fluorometric assays, respectively. Correlations between lipid parameters and semen quality indices were assessed using Spearman's rank analysis.

RESULTS

Baseline demographic and systemic metabolic characteristics were comparable between groups. Men with OAT had significantly higher FSH and estradiol levels and markedly impaired semen parameters, including sperm concentration, total sperm count, total motile sperm count, motility, and morphology. No significant differences were observed in serum HDL subfractions 1-10 or in large, intermediate, and small HDL concentrations between groups. In contrast, seminal total cholesterol was significantly lower in the OAT group (p = 0.048), and seminal HDL-C was markedly reduced (p < 0.001). Seminal HDL-C showed weak-to-moderate positive correlations with sperm concentration (ρ = 0.407), rapid progressive motility (ρ = 0.417), slow progressive motility (ρ = 0.418), total motile sperm count (ρ = 0.379), and normal morphology (ρ = 0.344) (all p < 0.001).

CONCLUSIONS

OAT is characterized by a compartmentalized lipid alteration marked by preserved systemic HDL subfraction profiles but depleted seminal HDL-C. These findings suggest that local seminal lipid homeostasis may be more closely related to sperm quality than circulating HDL-related measures and support seminal HDL-C as a candidate local metabolic indicator in male infertility.