Phosphatidylserine-Positive Live Sperm as a Biomarker of Fertility Status: Evidence from Patients Undergoing Varicocele Treatment

Purpose: Phosphatidylserine exposed on live and motile sperm is necessary for sperm:egg fusion, and emerging data suggest it is a biomarker for fertilization competent sperm. Men with varicocele often display infertility, and one of the known causes is poor sperm quality. Here, we sought to determine whether the percentage of phosphatidylserine-positive live sperm (PS + live sperm) could serve as a reliable indicator of male fertility. Materials and Methods: Semen samples from cryo-banked pregnancy-proven donors, from self-identified pregnancy-reported donors, and from men seeking infertility treatment for varicocele were analyzed for phosphatidylserine exposure on live sperm. Semen samples were also analyzed premicrosurgical and postmicrosurgical varicocele repair to determine whether varicocele repair led to a change in the percentage of PS + live sperm. Results: Semen samples from “pregnancy-proven” donors (n = 31) had 82% ± 2% PS + live sperm and samples from “self-identified pregnancy-reported” donors (n = 34) had 87% ± 1%. Men presenting with a varicocele (n = 80) had significantly lower PS + live sperm with 68% ± 3%. PS + live sperm correlated with reported pregnancies in patients with varicocele, whereas total motile sperm count did not. Varicocele repair (n = 10) led to a significant increase in PS + live sperm, and 2 of the patients reported pregnancies after varicocele repair. Conclusions: These results suggest that the percentage of PS + live sperm in an ejaculate correlates with male fertility status and could help in guiding treatment options for patients with varicoceles.