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

Contributors: Oğuzhan Kahraman, MD (Turkey), Emrullah Sogutdelen, MD (Turkey) and Ranjit Vishwakarma, MBBS, DNB (India)

Commentary:

Varicocele is recognized as the most common correctable cause of male infertility. The mechanism by which varicocele contributes to infertility remains a subject of debate. Testicular tissue is highly prone to oxidative stress as it consumes a significant amount of oxygen. Reactive oxygen species (ROS) are known to cause harm to cellular structures and deoxyribonucleic acid (DNA).

Russo et al. conducted a systematic review and meta-analysis (SRMA) to explore the impact of varicocele on testicular oxidative stress markers and sperm parameters in experimental animal models with and without varicocele. An extensive literature review spanning the last 20 years was performed using the PubMed and Scopus databases. Out of 76 articles identified, only six met the criteria for inclusion in the current SRMA. Despite the heterogeneity of the data, findings indicated that levels of Malondialdehyde (MDA) and sperm DNA fragmentation (SDF) were significantly elevated, while sperm vitality and motility were notably reduced in animal models with varicocele.

The SRMA highlighted that, although based on a limited number of studies, there is high-quality evidence suggesting that ROS, leading to increased lipid peroxidation and elevated MDA levels—a marker of this process—are heightened in animal models with varicocele. The escalation in oxidative stress may result in DNA damage and adversely affect sperm motility and vitality.

There is an ongoing debate on varicocele repair in male infertility. In daily practice, only patients with clinical varicocele and abnormal sperm parameters are treated. Varicocelectomy may reverse sperm DNA damage and improve sperm parameters. Greater improvement is seen in higher-grade varicoceles. There is a controversy in the treatment of varicocele patients with elevated SDF and normal sperm parameters. If the female ovarian reserve is good, after discussing the possible delay for assisted reproductive techniques, varicocelectomy is advised.



The current literature reveals a gap in evidence concerning the relationship between the duration of varicocele, the associated level of oxidative stress, and changes in sperm parameters. Additionally, there is a notable scarcity of data on pregnancy and live birth rates, which are essential outcomes in fertility research.