Urinary haloacetic acid concentrations and asthenozoospermia risk: a case–control study in China

Men with higher urinary concentrations of two haloacetic acids had higher odds of asthenozoospermia in an age-matched case–control study conducted within a Chinese cohort. The study analyzed 135 men with asthenozoospermia and 270 controls who were undergoing assisted reproductive technology treatment. Higher urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were each associated with increased odds of the condition, while simultaneous high exposure to both compounds was associated with a 2.62-fold increase in odds compared with low exposure to both.

These results show associations, not proof that exposure caused asthenozoospermia. The researchers used repeated urinary measurements to improve exposure assessment and focused on DCAA and TCAA, the predominant haloacetic acids examined in the study. Conditional logistic regression was used to evaluate associations between urinary concentrations and asthenozoospermia, while interaction analyses assessed whether joint exposure was associated with risk beyond the individual effects of the two compounds.

The case–control sample was nested within the TREE cohort and matched cases and controls by age. For DCAA, men in the highest urinary concentration quartile had 2.05 times the odds of asthenozoospermia compared with men in the lowest quartile. The 95% confidence interval was 1.10 to 3.83, and the reported P value for trend across quartiles was 0.04.

For TCAA, the highest quartile had 2.13 times the odds of asthenozoospermia relative to the lowest quartile, with a 95% confidence interval of 1.11 to 4.09 and a reported P value for trend of 0.05. The confidence intervals quantify uncertainty around these estimates, while the sample size limits the precision of the exposure-response estimates. Joint exposure produced the strongest reported association.

Participants with high concentrations of both DCAA and TCAA had 2.62 times the odds of asthenozoospermia compared with participants classified as having low concentrations of both compounds; the 95% confidence interval was 1.48 to 4.69. The analysis found evidence of a multiplicative interaction between the two biomarkers, with a P value of 0.01. The study also reported evidence of an additive interaction.

The relative excess risk due to interaction was 1.98, with a 95% confidence interval of 0.61 to 4.40, and the attributed proportion due to interaction was 0.76, with a 95% confidence interval of 0.29 to 1.04. The authors characterized the co-exposure findings as suggesting an additive effect. Haloacetic acids are disinfection byproducts formed during drinking-water treatment, and the study describes exposure to these contaminants as widespread and unavoidable.

The results provide human evidence that urinary DCAA and TCAA concentrations are individually associated with higher odds of asthenozoospermia among men receiving assisted reproductive technology treatment. The joint-exposure analysis supports the importance of evaluating both biomarkers when assessing male reproductive risks associated with these disinfection byproducts. Several features limit how the findings should be interpreted.

The work was observational and therefore cannot establish causation. Participants were men undergoing fertility treatment, so the results describe associations within this clinical population rather than the entire population. The case–control design also leaves possible differences between cases and controls as an alternative explanation, even though the analysis matched participants by age and used repeated exposure measurements.

The reported confidence intervals and interaction estimates show that the size and precision of the associations varied across analyses. The researchers said the findings highlight the importance of assessing the joint effects of the two urinary biomarkers on male reproduction. They also emphasized the value of reducing haloacetic acid levels in drinking water and suggested that the results may inform public-health strategies and clinical decision-making.

Subject of Research: Associations between urinary DCAA and TCAA and asthenozoospermia risk in Chinese men receiving fertility treatment

Article Title: Urinary haloacetic acid concentrations and asthenozoospermia risk: a case–control study in China

Article References: Ge, L., Zhang, M., Deng, Y.-L., Liu, X.-Y., Zeng, J.-Y., Zhu, J.-Q., Liu, P.-H., Miao, Y., Li, Y.-J., Liu, A.-X., Liu, C.-J., & Zeng, Q. (2026). Urinary haloacetic acid concentrations and asthenozoospermia risk: a case–control study in China. Journal of Exposure Science & Environmental Epidemiology. https://doi.org/10.1038/s41370-026-00997-x

Image Credits: AI Generated

DOI: 10.1038/s41370-026-00997-x

Keywords: haloacetic acids, asthenozoospermia, male reproductive health, disinfection byproducts, DCAA, TCAA, urinary biomarkers, case–control study, China, assisted reproductive technology, Urinary, haloacetic