Phenotype-associated immune-hematological profiles in men undergoing semen analysis: a real-world laboratory study

Male reproductive dysfunction reflects the interaction of endocrine, metabolic, genetic, environmental, oxidative, and immune-related factors. Although semen analysis remains the principal laboratory assessment, it is largely descriptive and provides limited insight into the systemic biological context in which semen abnormalities arise. Complete blood count (CBC)-derived inflammatory indices may offer a practical, low-cost approach to characterizing this context, but their relationship with semen-analysis phenotypes remains unclear.

To examine whether conventional haematological variables and leukocyte-derived immune-inflammatory indices differ across semen-analysis phenotypes and whether these markers are related to individual semen parameters.

This retrospective cross-sectional study analysed anonymised semen-analysis and complete blood count data from Royal Diagnostics Medical Laboratory, Riyadh, Saudi Arabia, collected between February and May 2025. The final analytical cohort comprised 245 matched records. Conventional haematological parameters, leukocyte percentages, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were compared across the principal semen phenotypes. Correlation analyses and exploratory logistic regression models were used to assess parameter-level associations and predictive performance.

Normozoospermia was the most common phenotype (49.8%), followed by asthenozoospermia (31.4%). Conventional haematological parameters were broadly comparable across phenotype groups. In contrast, neutrophil percentage (p = 0.013), lymphocyte percentage (p = 0.007), and NLR (p = 0.008) differed significantly across the principal semen phenotypes. The pattern of variation was heterogeneous rather than progressively graded across groups. PLR and SII did not differ significantly. Immune-inflammatory markers showed no meaningful correlations with sperm concentration, progressive motility, or morphology, and exploratory regression models found no independent predictive effects.  Conclusions: Leukocyte-derived inflammatory markers varied across semen-analysis phenotypes, whereas conventional haematological parameters remained broadly comparable. However, these markers showed no meaningful correlations with individual semen parameters and no independent predictive value in exploratory models. They should therefore be interpreted as descriptive indicators of immune-haematological context rather than diagnostic biomarkers of semen quality or male infertility.