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Abstract
Are 155 circulating metabolic measures relevant to lifestyle and metabolic health associated with sperm parameters (as measured by concentration, motility and total motile sperm count (TMSC))? An extensive range of metabolites were not associated with semen parameters, however, several metabolites exhibited differential direction of associations with the odds of a low TMSC and warrant replication. Robust identification of additional modifiable and non-modifiable risk factors for poor semen quality have had limited success. An alternative approach to identify risk factors for an abnormal semen analysis would be to examine circulating metabolites by means of a high throughput cost efficient NMR platform, which may provide insights into downstream factors as well as more upstream exposures. Cross-sectional study of 325 men prospectively recruited between 1 April 2017 and 31 March 2019. Men intending to undergo assisted conception at a University Hospital, had a detailed demographic, lifestyle, fertility and medical history and semen analysis. Non-fasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis and inflammatory markers) were quantified by NMR spectroscopy. Multivariable linear and logistic regression were used to examine the associations of serum metabolic profiles (exposures), with functional sperm concentration, motility and TMSC (outcomes) with adjustment for confounders. Participants were mean 37.2 (SD 5.7) years and had a median sperm concentration of 35 million/ml (IQR 15, 69 million/ml) and median motility of 53% (IQR 42,67). 76% of men had a TMSC >15 Million, 10% 5-15 Million and 14% <5 Million. In both univariate and confounder adjusted analyses an extensive range of lipids and lipoproteins, glycolysis related metabolites, amino acids, ketone bodies, creatinine or albumin, did not show strong statistical evidence of associated with sperm concentration, motility, or the odds of having a reduced or low TMSC (all PBonferroni > 0.0029). Sperm parameters were measured on a single sample, in accordance with recent WHO guidance, and by non-automated techniques which may have introduced random measurement error that could have attenuated to the null. This study provides preliminary data on a range of metabolic pathways and their association with semen parameters. The differential direction of associations with sperm motility and potentially of important clinical effect sizes warrant further exploration and replication in a larger prospective study.
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