Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis

Giorgio Ivan Russo; Ramadan Saleh; Federica Finocchi; Almas Ramadhani Juma; Damayanthi Durairajanayagam; Oguzhan Kahraman; Emrullah Söğütdelen; Ioannis Sokolakis; Ranjit B Vishwakarma; Fahmi Bahar; Ahmed M Harraz; Parviz Kavoussi; Widi Atmoko; Eric Chung; Naveen Kumar; Wael Zohdy; Amarnath Rambhatla; Mohamed Arafa; Nguyen Ho Vinh Phuoc; Gianmaria Salvio; Aldo E Calogero; Tuncay Toprak; Germar-Michael Pinggera; Rossella Cannarella; Giovanni Colpi; Taha Abo-Almagd Abdel-Meguid Hamoda; Rupin Shah; Ashok Agarwal

doi:10.5534/wjmh.230260

Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis

World J Mens Health. 2024 Jul;42(3):563-573. doi: 10.5534/wjmh.230260. Epub 2024 Feb 7.

Authors

Giorgio Ivan Russo^{1

2}, Ramadan Saleh^{2

3

4}, Federica Finocchi^{2

5}, Almas Ramadhani Juma^{2

6}, Damayanthi Durairajanayagam^{2

7}, Oguzhan Kahraman^{2

8}, Emrullah Söğütdelen^{2

9}, Ioannis Sokolakis^{2

10}, Ranjit B Vishwakarma^{2

11}, Fahmi Bahar^{2

12

13}, Ahmed M Harraz^{2

14

15

16}, Parviz Kavoussi^{2

17}, Widi Atmoko^{2

18}, Eric Chung^{2

19}, Naveen Kumar^{2

20}, Wael Zohdy^{2

21}, Amarnath Rambhatla^{2

22}, Mohamed Arafa^{2

21

23

24}, Nguyen Ho Vinh Phuoc^{2

25

26}, Gianmaria Salvio^{2

3}, Aldo E Calogero^{2

27}, Tuncay Toprak^{2

28}, Germar-Michael Pinggera^{2

29}, Rossella Cannarella^{2

27

30}, Giovanni Colpi^{2

31}, Taha Abo-Almagd Abdel-Meguid Hamoda^{2

32

33}, Rupin Shah^{2

11}, Ashok Agarwal^{2

34}

Affiliations

¹ Urology Section, Department of Surgery, University of Catania, Catania, Italy.
² Global Andrology Forum, Moreland Hills, OH, USA.
³ Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Ajyal IVF Center, Ajyal Hospital, Sohag, Egypt.
⁵ Division of Endocrinology, Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, Ancona, Italy.
⁶ Department of Reproductive Health and Biology, Kenya Institute of Primate Research, Nairobi, Kenya.
⁷ Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
⁸ Department of Urology, Faculty of Medicine, Baskent University, Konya, Turkey.
⁹ Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey.
¹⁰ 2nd Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹¹ Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India.
¹² Andrology Section, Faculty of Medicine, Universitas Muhammadiyah Palembang, Palembang, Indonesia.
¹³ Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia.
¹⁴ Department of Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
¹⁵ Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait.
¹⁶ Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait.
¹⁷ Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA.
¹⁸ Department of Urology, Faculty of Medicine, Universitas Indonesia Dr. Ciptomangunkusumo Hospital, Jakarta, Indonesia.
¹⁹ Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia.
²⁰ Department of Urology, All India Institute of Medical Sciences (AIIMS), Patna, India.
²¹ Department of Andrology and STDs, Cairo University, Cairo, Egypt.
²² Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA.
²³ Department of Urology, Hamad Medical Corporation, Doha, Qatar.
²⁴ Department of Urology, Weill Cornell Medical-Qatar Doha, Doha, Qatar.
²⁵ Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
²⁶ Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam.
²⁷ Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
²⁸ Department of Urology, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.
²⁹ Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
³⁰ Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
³¹ Andrology & IVF Center, Next Fertility Procrea, Lugano, Switzerland.
³² Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia.
³³ Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt.
³⁴ Cleveland Clinic Foundation, Cleveland, OH, USA. [email protected].

Abstract

Purpose: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele.

Materials and methods: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×10⁶), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist.

Results: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high.

Conclusions: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Keywords: Infertility; Oxidative stress; Reactive oxygen species; Spermatozoa; Varicocele.