Association of the Human Semen DNA Virome with Successful In Vitro Fertilization

ABSTRACT Objective To comprehensively characterize the DNA virome in semen samples collected for in vitro fertilization. Design A descriptive clinical study. Setting Single academic fertility center. Patients 24 male partners from couples undergoing in vitro fertilization (IVF). Interventions Couples were randomized to receive 1 g of azithromycin (standard of care) or no azithromycin at the time of baseline IVF assessment. Semen samples were collected at the time of the female partners’ egg retrieval, and 100 μL of sample was used for virome analysis. Main Outcome Measures Detection of viruses by ViroCap enrichment of viral nucleic acid and sequencing. Association between the virome, semen parameters, and pregnancy outcomes. Results We detected viruses in 58% of the subjects. Viruses included polyomaviruses, papillomaviruses, herpesviruses, and anelloviruses. Viromes detected in semen had little overlap with the viromes detected in vaginal samples from their female partners collected at time of embryo transfer, which were analyzed in a previous study. Lower viral diversity in semen samples was positively associated with pregnancy (P=0.03, Hodges-Lehmann estimate of difference 1; 95% CI 2 to 0.00003). There was no association between viral diversity and sperm concentration, motility or fertilization rates. Conclusion This comprehensive characterization of the DNA virome in semen reveals an association between virome diversity and pregnancy in couples undergoing IVF. However, no association was found with specific semen parameters or fertilization rates, suggesting viral exposure may negatively affect pregnancy after fertilization. Future studies should be undertaken to evaluate associations between the semen virome with IVF outcomes in larger cohort.