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. 2024 Apr;42(2):321-337.
doi: 10.5534/wjmh.230235. Epub 2024 Jan 2.

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  1   2   3 , Rupin Shah  1   3   4 , Ramadan Saleh  3   5 , Florence Boitrelle  3   6   7 , Taha Abo-Almagd Abdel-Meguid Hamoda  3   8   9 , Rajender Singh  3   10 , Gianmaria Salvio  3   11 , Tuncay Toprak  3   12 , Marco Falcone  3   13 , Murat Gul  3   14 , Fotios Dimitriadis  3   15 , Amarnath Rambhatla  3   16 , Giorgio I Russo  3   17 , Edmund Ko  3   18 , Armand Zini  3   19 , Parviz Kavoussi  3   20 , Nguyen Ho Vinh Phuoc  3   21   22 , Hussein Kandil  3   23 , Ramy Abou Ghayda  3   24 , Ponco Birowo  3   25 , Nazim Gherabi  3   26 , Erman Ceyhan  3   27 , Jie Dong  3   28 , Vineet Malhotra  3   29 , Damayanthi Durairajanayagam  3   30 , Bircan Kolbasi  3   31 , Fahmi Bahar  3   32 , Gokhan Calik  3   33 , Selahittin Çayan  3   34 , Germar-Michael Pinggera  3   35 , Aldo E Calogero  2   3 , Osvaldo Rajmil  3   36   37 , Taymour Mostafa  3   38 , Widi Atmoko  3   25 , Ahmed M Harraz  3   39   40   41 , Tan V Le  3   21   22 , Jean de la Rosette  3   42 , Lukman Hakim  3   43 , Edoardo Pescatori  3   44 , Oleg Sergeyev  3   45   46 , Ayman Rashed  3   47 , Pallavi Saini  3   10 , Ashok Agarwal  3   48
Affiliations

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 et al. World J Mens Health. 2024 Apr.

Abstract

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.

Keywords: DNA fragmentation; Infertility, male; Malondialdehyde; Varicocele.

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Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) flow-chart for inclusion/exclusion of studies.
Fig. 2
Fig. 2. Forest plot of the sperm DNA fragmentation in infertile patients after varicocele repair compared to before varicocele repair. 95% CI: 95% confidence interval.
Fig. 3
Fig. 3. Forest plot of the sperm DNA fragmentation in infertile patients after varicocele repair compared to before varicocele repair using microsurgical treatment. 95% CI: 95% confidence interval.
Fig. 4
Fig. 4. Forest plot of the sperm DNA fragmentation in infertile patients after varicocele repair compared to before varicocele repair using non-microsurgical inguinal treatment. 95% CI: 95% confidence interval.
Fig. 5
Fig. 5. Forest plot of the sperm DNA fragmentation in infertile patients after varicocele repair compared to before varicocele repair using SCD. 95% CI: 95% confidence interval.
Fig. 6
Fig. 6. Forest plot of the sperm DNA fragmentation in infertile patients after varicocele repair compared to before varicocele repair using SCSA. 95% CI: 95% confidence interval.
Fig. 7
Fig. 7. Forest plot of the sperm DNA fragmentation in infertile patients after varicocele repair compared to before varicocele repair using TUNEL. 95% CI: 95% confidence interval.
Fig. 8
Fig. 8. Forest plot of the sperm DNA fragmentation (SDF) in infertile patients after varicocele repair compared to before varicocele repair using a not specified methods for analysis of SDF. 95% CI: 95% confidence interval.
Fig. 9
Fig. 9. Forest plot of seminal malondialdehyde level in infertile patients after varicocele repair compared to before varicocele repair. 95% CI: 95% confidence interval.
Fig. 10
Fig. 10. Metaregression showing the influence of pre-treatment sperm DNA fragmentation (SDF) levels (moderator) on the standard difference of the mean of SDF after varicocelectomy. The size of the circles indicates the studies’ sample sizes. The red line represents linear predictions for the standard mean difference of SDF change after varicocelectomy as a function of the mean absolute increase in preoperative SDF levels. The curved lines indicate the 95% confidence interval lines around the regression line.
Fig. 11
Fig. 11. Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis. SRMA: systematic review and meta-analysis, SDF: sperm DNA fragmentation, MDA: malondialdehyde, VR: varicocele repair, 8OHDG: 8-hydroxydeoxyguanosine.
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References

    1. Centers for Disease Control and Prevention (CDC) National public health action plan for the detection, prevention, and management of infertility. CDC; 2014.
    1. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22:1506–1512. Erratum in: Hum Reprod 2007;22:2800. - PubMed
    1. Martinez G, Daniels K, Chandra A. Fertility of men and women aged 15-44 years in the United States: national survey of family growth, 2006-2010. Natl Health Stat Report. 2012;51:1–28. - PubMed
    1. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13:37. - PMC - PubMed
    1. Snow-Lisy D, Sabanegh E., Jr What does the clinician need from an andrology laboratory? Front Biosci (Elite Ed) 2013;5:289–304. - PubMed