Introduction: New technology and diagnostics are needed for better assessment of male infertility. The mainstay of male factor infertility diagnosis is the standard semen analysis that has changed very little over the last several decades and has been shown to have limited predictive value. Here we present results on the analysis of men seeking fertility care using a newly available epigenetic sperm quality test (SpermQT). Methods: SpermQT is a newly developed assessment of sperm quality that identifies male factor infertility missed by the standard semen analysis. SpermQT results are highly predictive of pregnancy in individuals undergoing IUI. Specifically, SpermQT looks at DNA methylation profiles of 1233 promoters and calculates deviations in these profiles away from a healthy state. The accumulation of gene promoters that differ from the defined healthy state is associated with poorer fertility outcomes. SpermQT was run on 157 semen samples from consented patients at a single academic center. Semen parameters, hormones, medications, health history, fertility treatments, and outcomes were compared to the SpermQT result for each sample, with pregnancy and live birth data continually being collected. Results: In the 157 samples analyzed, 17% had a Poor SpermQT results (N=26). Of the 17% with a Poor result, 92% had normal semen. Additionally, there was no significant relation between SpermQT, age (r2=0.0008), DFI (r2=0.00005), and BMI (r2=0.002). Men on antioxidant treatment tended to have fewer unstable promoters (p=0.06) compared to those not on antioxidant treatment, while men with a history of THT (N=20) have more unstable promoters (p=0.02) than those without (N=1-6). Only 12 men in the study had pregnancy outcomes associated with IUI. Within these 12, individuals with a pregnancy from IUI had an average of 5.6 unstable promoters (std 3.5) while individuals unable to achieve pregnancy had an average of 19.8 unstable promoters (std 19.8). No statistical differences was identified in the number of unstable promoters between men with or without a pregnancy who underwent IVF-ICSI (p=0.4). Conclusions: Here we support earlier findings that SpermQT identifies men who would be missed by standard laboratory techniques as the number of unstable promoters in SpermQT is not correlated with semen parameters, age, and BMI. Early data indicates that men unable to conceive with IUI have a dominance of unstable promoters; however, more outcomes data is needed to verify these early results. Using these data, SpermQT can direct clinicians the most effective treatment. SOURCE OF Funding: NSF - SBIR
