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

Rossella Cannarella, Rupin Shah, Ramadan Saleh, Florence Boitrelle, Taha Abo Almagd Abdel Meguid Hamoda, Rajender Singh, Gianmaria Salvio, Tuncay Toprak, Marco Falcone, Murat Gul, Fotios Dimitriadis, Amarnath Rambhatla, Giorgio I. Russo, Edmund Ko, Armand Zini, Parviz Kavoussi, Nguyen Ho Vinh Phuoc, Hussein Kandil, Ramy Abou Ghayda, Ponco BirowoNazim Gherabi, Erman Ceyhan, Jie Dong, Vineet Malhotra, Damayanthi Durairajanayagam, Bircan Kolbasi, Fahmi Bahar, Gokhan Calik, Selahittin Çayan, Germar Michael Pinggera, Aldo E. Calogero, Osvaldo Rajmil, Taymour Mostafa, Widi Atmoko, Ahmed M. Harraz, Tan V. Le, Jean de la Rosette, Lukman Hakim, Edoardo Pescatori, Oleg Sergeyev, Ayman Rashed, Pallavi Saini, Ashok Agarwal

Research output: Contribution to journalArticlepeer-review


Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). How­ever, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I2=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogene­ity (I2=93.7%). Conclusions: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Original languageEnglish
Pages (from-to)321-337
Number of pages17
JournalWorld Journal of Men's Health
Issue number2
Publication statusPublished - Apr 2024


  • DNA fragmentation
  • Infertility
  • male
  • Malondialdehyde
  • Varicocele


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