Comment on “Multiantioxidant therapy in varicocele: the value of oxidative stress markers and testicular hemodynamics”
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We read the article by Rochdi et al. [1] with great interest. In this prospective study, the authors investigated the role of oxidative stress (OS) in the pathogenesis of male infertility, including varicocele, and evaluated the therapeutic potential of multiantioxidant supplementation in oligoasthenozoospermic patients with varying grades of varicocele. Serum and semen samples were collected at baseline and after 6 months of treatment, with assessments of sperm DNA damage, reproductive hormone levels, and pregnancy outcomes. Antioxidant therapy was associated with significant improvements in semen parameters, including sperm count, motility, and morphology, as well as enhanced sperm DNA integrity across patient groups. Pregnancy rates following intrauterine insemination were highest among patients with grade 0 and grade 1 varicocele (11% and 9%, respectively), with additional spontaneous pregnancies observed in these groups (6% and 3%). In contrast, patients with higher-grade varicocele (grades 2 and 3) did not demonstrate significant improvements in pregnancy rates. Collectively, these findings indicate that multiantioxidant therapy may confer meaningful benefits in low-grade varicocele, supporting its role as a potentially valuable adjuvant in the management of varicocele-associated infertility.
In line with this topic, we have also conducted prospective research in recent years [2]. Specifically, we evaluated the impact of clinical varicocele on testicular microcirculation using spectral Doppler analysis and examined correlations between Doppler ultrasonographic findings and semen parameters. Varicocele grades were determined sonographically, and spectral Doppler indices—including peak systolic velocity (PSV), end-diastolic velocity (EDV), resistivity index (RI), and pulsatility index (PI)—were measured from capsular and intratesticular branches of the testicular arteries in conjunction with semen analysis. Although no significant associations were identified between RI, PI, or EDV and semen parameters such as sperm count, motility, volume, or morphology, PSV demonstrated a significant correlation with sperm count in both unilateral and bilateral varicocele cases. Based on these findings, we suggest that spectral Doppler analysis represents a useful noninvasive method for assessing testicular hemodynamics in patients with varicocele, with PSV emerging as a potentially informative indicator of sperm count.
It is well established that patients with varicocele exhibit elevated levels of OS, reduced total sperm count and motility, abnormal sperm morphology, and increased sperm DNA fragmentation. Identification of objective biomarkers of OS may therefore facilitate more reliable prediction of semen analysis parameters in this population. In this context, assessment of PSV in capsular and intratesticular arteries may also serve as a valuable noninvasive indicator for monitoring the response to antioxidant therapy. Such an approach could further assist in determining the optimal duration of antioxidant supplementation required to achieve sustained therapeutic effects. Among proposed OS biomarkers, thiol–disulfide homeostasis has attracted increasing attention [3]. Infertile men with varicocele have been reported to exhibit significantly higher disulfide concentrations and elevated disulfide/native thiol, disulfide/total thiol, and native/total thiol ratios compared with fertile men with varicocele and fertile controls. Notably, excessive OS has also been detected in the plasma of patients with varicocele who exhibit normospermia. We further evaluated this OS marker in men undergoing transrectal ultrasound-guided prostate biopsy [4], in whom we observed statistically significant alterations in thiol levels, indicating that the procedure itself is associated with the induction of OS.
In conclusion, as emphasized by Rochdi et al. [1], higher varicocele grades are associated with poorer semen parameters. Antioxidant treatment therefore represents a viable option for improving semen quality in selected patients with varicocele. In infertile men diagnosed with varicocele, assessment of capsular and intratesticular PSV in conjunction with varicocele grade may provide clinicians with valuable insight into testicular OS and its relationship with semen parameters. Moreover, incorporation of OS markers such as thiol–disulfide homeostasis at baseline and during follow-up, together with PSV measurements, may enable a more comprehensive evaluation of testicular response to multiantioxidant therapy and its effects on semen quality. Periodic assessment of these parameters throughout antioxidant treatment may allow early detection of alterations in testicular parenchymal status before corresponding changes in semen parameters become apparent, thereby supporting more timely evaluation of therapeutic efficacy. Such an approach may offer meaningful advantages in clinical decision-making and treatment planning. Assuming that multiantioxidant therapy demonstrates greater efficacy in low-grade varicocele, in cases of high-grade varicocele accompanied by reduced PSV values, early microsurgical varicocelectomy may represent a more appropriate intervention than initiation of antioxidant therapy, in order to avoid unnecessary delays in definitive treatment.
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Conflict of interest
No potential conflict of interest relevant to this article was reported.