The relationship between semen factors and unexplained recurrent spontaneous abortion.

Abstract Background The male factor may contribute to unexplained recurrent spontaneous abortion (URSA). The relationship between semen factors and URSA is largely unknown. The analysis of metabolomics which is broadly acknowledged as the omics closest to the phenotype is suitable for providing assistance in the semen parameters analysis. Methods We conducted a study including couples with URSA and controls which was next combined with a meta-analysis, and finally the study included 2352 subjects on semen parameters and URSA. Metabolomics analysis was conducted to detect semen metabolic factors related to URSA in total of 106 samples including seminal plasma and sperm cells. Results The URSA group had significantly lower total sperm count, sperm concentration, motility and normal morphology percentage. Meta-analysis next showed consistent findings. Metabolomics revealed that 4 metabolites and one pathway and 8 metabolites and one pathway were significantly associated with URSA in sperm and seminal plasma, respectively. The combination of ascorbic acid and guanine in seminal plasma and hexadecanedioic acid and pyroglutamic acid in sperm showed ability for URSA prediction. Conclusion We provided novel insights into semen indices in relation to URSA. Lower sperm number and quality might increase the risk of URSA, and oxidative stress and hormone metabolism in sperm as well as nucleic acid synthesis and oxidative stress in seminal plasma were related to URSA.