Epigenetic sperm quality testing for predicting fertility treatment success: a real-world and multi-site analysis

Abstract

Purpose: Infertility affects 1 in 6 couples, yet male fertility assessments often rely on semen analysis alone, which has limited predictive value for treatment success. This study evaluates an epigenetic tool for assessing sperm quality, aiming to provide a more comprehensive view of male fertility and improve personalized treatment strategies. Methods: De-identified pregnancy outcomes from 537 couples treated at 10 US fertility clinics were analyzed. Partner ages, total motile sperm count, treatment type, and sperm epigenetic quality were considered to assess associations with fertility treatment outcomes. Results: Men with abnormal sperm epigenetic profiles had significantly lower pregnancy success rates with intrauterine insemination (IUI) compared to those with normal profiles, despite similar sperm motility and concentration. In contrast, pregnancy rates did not differ between abnormal and normal profiles among couples undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), suggesting that ICSI may overcome sperm epigenetic quality issues. Conclusion: This real-world analysis was limited by the availability of detailed clinical and phenotypic data, which may introduce potential confounders. Nevertheless, the findings highlight the clinical value of epigenetic sperm assessment as part of male fertility evaluation and support its potential to guide more effective, personalized fertility treatment pathways.