Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis

My Viewpoint on the Effects of Varicocele Repair on SDF and OS

Dr. Fahmi Bahar responds to questions from Ashok

Q1. How might the reduction in oxidative stress markers like MDA influence male reproductive health post-VR?

Dr. Bahar: As we all know, it is estimated that one of the adverse effects of varicocele is the generation of oxidative stress, which can affect the quality and quantity of sperm. One common marker used in this regard is Malondialdehyde (MDA), where varicocelectomy can decrease MDA levels, thus resulting in better male reproductive health post-operation.

Q2. Does varicocele grade or severity influence the outcomes of VR in terms of SDF and MDA levels?

Dr. Bahar: Based on the clinical experience I encounter daily, generally, the more severe the degree of varicocele a person has, the better the improvement in parameters postoperation, and the decrease in the percentage of SDF (sperm DNA fragmentation) and MDA levels will be. As long as it is estimated that varicocele is indeed the only sole cause in those patients.

Q3. What are the clinical implications of the high heterogeneity observed in studies analyzing SDF and MDA levels post-VR?

Dr. Bahar: In this SRMA (Systematic Review and Meta-Analysis), a high heterogeneity index (above 50%) was found, thus a random-effects model approach was employed. Additionally, meta-regression and subgroup analysis were used, indicating the significance of Varicocelectomy in reducing SDF and MDA levels.

Q4. How could the findings from this study affect current guidelines on the management of varicoceles in infertile men?

Dr. Bahar: The findings of this study can serve as a reference for professional organizations to include the assessment of SDF and MDA levels as routine examinations in cases of varicocele. Subsequently, they may recommend varicocelectomy if increased levels of MDA and SDF are found.

Q5. Is there evidence to support routine SDF testing in men with palpable varicoceles before considering VR?

Dr. Bahar: According to the results of this study, which found a decrease in SDF levels before and after varicocelectomy, the assessment of SDF can be suggested as a routine examination for men with palpable varicocele to strengthen the indication for surgical intervention.

Fahmi Bahar, MD: Short Biography

Fahmi Bahar, MD Andrologist,

Andrology Section Siloam Palembang Hospital Jakarta, Indonesia

E-mail: dr.fbw.st@gmail.com

ORCID ID: https://orcid.org/0000-0002- 7027-9436

My Viewpoint on the Effects of Varicocele Repair on SDF and OS

Dr. Gianmaria Salvio responds to questions from Ashok

Q1. How significant is the reduction in sperm DNA fragmentation (SDF) after varicocele repair (VR) in infertile men with clinical varicocele?

Dr. Salvio: The reduction in SDF after varicocelectomy certainly appears to be statistically significant, but its clinical significance needs to be demonstrated. VR is accompanied by an average reduction of about 1% in SDF (SMD -1.125, 95 % confidence interval [CI] -1.410, - 0.840; p<0.0001), but it should be kept in mind that the magnitude of the effect may be affected both by the technique used for VR (non-surgical approaches might result in better results than surgical approaches) and by the method of measuring DNA fragmentation. It has also been observed from previous meta-analyses that infertile subjects have higher levels of SDF than fertile controls, but it is not known what minimum improvement is sufficient to achieve an increase in pregnancy rate. Therefore, no firm conclusions can yet be drawn, although the present study suggests that VR may indeed result in a benefit in terms of sperm DNA quality.

Q2. What changes in seminal malondialdehyde (MDA) levels are observed after VR, and what does this indicate about oxidative stress in these patients?

Dr. Salvio: VR is accompanied by a significant reduction in seminal MDA levels. It is derived from peroxidation of polyunsaturated fatty acids and its expression correlates directly with the oxidative state of the medium in which it is measured. Specifically, the reduction in seminal MDA suggests an important VR-related oxidative stress reduction effect, which may accompany improved fertility, as suggested by the observation that most infertility risk factors act through increased oxidative stress on spermatozoa.

Q3. Are the improvements in SDF and MDA levels after VR consistent across different surgical techniques?

Dr. Salvio: The effects of VR on MDA levels were analyzed in a total of 6 studies: surgical approaches (microsurgery in all) were evaluated in 4 studies and nonsurgical approaches in 2 studies. Although the small number of studies does not allow for subgroup analysis, the effect of VR appears overall positive and does not appear to be significantly different among the different types of procedures.

Q4. How does the effectiveness of microsurgical varicocele repair compare to nonmicrosurgical inguinal approaches in reducing SDF?

Dr. Salvio: From the present study, it appears that nonsurgical approaches may lead to a more pronounced decrease in SDF levels. By the way, it should be kept in mind that nonsurgical approaches were considered in only 4 studies, whereas micro-surgical approaches were evaluated in 13 studies. Therefore, no firm conclusions can be drawn.

Q5. What are the implications of these findings for the future management of male infertility associated with varicocele?

Dr. Salvio: The present meta-analysis confirms the beneficial effects of VR in infertile men. Since SDF and oxidative stress seem to play a pivotal role in male infertility (especially in idiopathic male infertility), but no clear cut-offs for normal or pathological SDF and MDA are currently available, more studies are needed to establish the ideal goal of improvement that should be reached to obtain clinical benefits and to improve pregnancy rate and live birth rate in infertile couples.

Gianmaria Salvio, MD: Short Biography

My Viewpoint on the Effects of Varicocele Repair on SDF and OS

Dr. Murat Gul responds to questions from Ashok

Q1. What role do seminal oxidative stress markers play in evaluating the success of VR?

Dr. Gul: Seminal oxidative stress markers like malondialdehyde (MDA) levels can provide valuable insights into the success of varicocele repair (VR) in improving sperm quality. A systematic review and meta-analysis found that VR significantly reduced seminal MDA levels in infertile men with clinical varicocele, indicating reduced oxidative stress2. However, the search results do not directly address the role of oxidative stress markers in evaluating VR outcomes.

Q2. How might these findings influence the decision-making process for urologists treating men with infertility related to varicocele?

Dr. Gul: The findings that VR improves conventional semen parameters like sperm concentration, motility, and morphology in infertile men with varicocele12 can influence urologists' decision-making process. The significant improvements in semen quality provide evidence to support VR as a treatment option for male infertility related to varicocele. However, the search results do not discuss how these findings specifically impact urologists' decision-making.

Q3. Given the reductions in SDF and MDA, should VR be considered a preventive strategy for future fertility issues in men diagnosed with varicocele?

Dr. Gul: The search results do not directly address whether VR should be considered a preventive strategy for future fertility issues in men diagnosed with varicocele. While VR reduces sperm DNA fragmentation and oxidative stress markers2, more research is needed to determine if these improvements translate to preventing future fertility problems in men with varicocele.

Q4. Are there specific patient profiles (e.g., age, duration of infertility, varicocele severity) that particularly benefit from VR in terms of improvements in sperm quality?

Dr. Gul: The search results do not provide specific patient profiles that particularly benefit from VR in terms of sperm quality improvements. The meta-analyses included infertile men with clinical varicocele but did not stratify results based on age, duration of infertility, or varicocele severity. Further research is needed to identify patient characteristics that predict the greatest improvements in sperm parameters following VR.

Q5. What further research is needed to clarify the mechanisms by which VR improves sperm parameters and oxidative stress markers in men with varicocele?

Dr. Gul: To clarify the mechanisms by which VR improves sperm parameters and oxidative stress markers, future research should investigate:

• The time course of changes in semen quality and oxidative stress after VR
• The relationship between improvements in specific semen parameters and oxidative stress markers
• The impact of VR on other markers of sperm function and DNA integrity
• The role of varicocele grade and duration in modulating the effects of VR on sperm and oxidative stress
• In summary, while VR significantly improves conventional semen parameters and reduces oxidative stress in infertile men with varicocele, more research is needed to fully elucidate the mechanisms and identify patient profiles most likely to benefit from this treatment
  

Murat Gul, MD: Short Biography