Predictive value of oxidative stress testing in semen for sperm DNA fragmentation assessed by sperm chromatin dispersion test

Background: Although standard semen analysis is a cornerstone of male infertility investiation, it has significant limitations. Seminal oxidative stress and DNA damage have shown potential to better predict male fertility potential and provide improved diagnostic and management strategies.

Objective: The aim of this study was to investigate whether seminal oxidation-reduction potential (ORP), a new parameter to measure oxidative stress directly, can accurately predict the percentage of sperm DNA fragmentation (SDF) and thereby serve as a surrogate marker in the evaluation of male infertility.

Materials and methods: ORP was evaluated in 3968 patients using the MiOXSYS system and SDF in 1147 patients using the Halosperm G2 test kit. Both parameters were analyzed in 1068 patients, along with seminal analysis, according to WHO guidelines 2010 (5th edition).

Results: SDF correlated positively with seminal ORP normalized for sperm concentration (n = 1068; r = .218; P < .0001) as well as with ORP normalized for the motile sperm concentration (motORP; n = 1068; r = .387; P < .0001). MotORP can significantly (P < .0001) better predict SDF than ORP normalized for the sperm concentration (area under the curve (AUC): 0.719 vs 0.623) (specificity: 71.5%; sensitivity: 61.9%; PPV: 47.1%; NPV: 82.1%). Moreover, motORP can significantly (P < .0001) better predict (AUC: 0.826 vs 0.771) normozoospermia with high sensitivity (82.75%) and specificity (68.5%).

Discussion: Unlike other oxidative stress (OS) markers, ORP provides a global vision of the redox balance in semen. Moreover, SDF can also be induced by mechanisms different from OS, which could explain why its predictive power was low. The higher predictive power of motORP reflects the impact of seminal ROS on motility rather than inherent DNA breaks present in immature and aborted apoptotic spermatozoa.

Conclusion: The evaluation of motORP seems a more promising parameter than ORP normalized for sperm concentration for the prediction of SDF and normozoospermia. However, even if ORP and SDF are inter-related, they measure independent sperm functions and one test cannot replace the other in the evaluation of sperm function defects.