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Alpha-lipoic acid improves sperm motility in infertile men after varicocelectomy: a triple-blind randomized controlled trial
BIOGRAPHY Mohammad H. Nasr-Esfahani Ph.D. (Camb) is currently an Academic Member of the Royan Institute, Head of the Royan Institute for Biotechnology, and Laboratory Director of the Isfahan Fertility and Infertility Centre, Isfahan, Iran. His main research areas are male infertility, stem cells, animal cloning, and recombinant protein.
Behzad Abbasi, Newsha Molavi, Marziyeh Tavalaee, Homayoun Abbasi, Mohammad H. Nasr-Esfahani
KEY MESSAGE
*An 80-day course of alpha-lipoic acid (ALA) medication after microsurgical repair improves sperm motility and progressive motility in men with a varicocele. Thus, ALA supplementation could be considered as an adjunct therapy to varicocelectomy.
ABSTRACT
Research question: Does supplementation with alpha-lipoic acid (ALA) enhance sperm parameters and/or the status of sperm lipid peroxidation and DNA fragmentation in men who have undergone microsurgical repair of a varicocele?
Design: Individuals with a varicocele who had undergone varicocelectomy were divided into two groups receiving either 600 mg of ALA or an identical placebo for 80 days. Semen samples obtained from the participants before surgery and after completion of the course of medication were analyzed and compared. Participants, clinicians, and data analysts were blinded to the randomization sequence.
Results: In the ALA group, total motility (P = 0.01) and progressive motility (P = 0.002) of the spermatozoa were significantly higher compared with the placebo group after surgery. Sperm lipid peroxidation and DNA damage (assessed by sperm chromatin structure assay) showed significant decreases in both the ALA and placebo groups (P ≤ 0.02) after treatment.
Conclusions: An 80-day course of ALA medication after surgical repair improves total motility and progressive motility of the spermatozoa in individuals with a varicocele.
Introduction
The term ‘infertility’ depicts the failure to conceive after a minimum of 12 months of regular unprotected intercourse and affects 10% of the couples of reproductive age. A male etiology contributes to as many as half of all cases of infertility (Winters and Walsh, 2014): classically, an impairment on sperm analysis implies male infertility (WHO, 2010). While the environment, physiological alterations, and genetics have long been acknowledged to affect male fertility status, the exact underlying molecular mechanisms are not well recognized (Coutton et al.,2016). However, the evidence indicates that oxidative stress plays a substantial role in approximately 50% of cases. Oxidative stress arises as a result of an imbalance between oxidizing agents and reductant molecules due to the overproduction of oxidants, namely reactive oxygen species (ROS) (Agarwal et al., 2018; Scott et al.). ROS, naturally produced through normal cellular metabolism, serve as signaling molecules and promote sperm penetration into the oocyte at physiological levels; some studies have shown that incubation of spermatozoa with particular types of ROS upholds capacitation, acrosome reaction, hyperactivation, and fusion to the zona pellucida (de Lamirande et al., 1997).
Morphologically abnormal spermatozoa and seminal leukocytes are the principal suppliers of excessive ROS in human semen, the main aetiologies being considered to be mitochondrial dysfunction and a provoked myeloperoxidase system, respectively (Lobascio et al., 2015). In the seminal plasma, antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase work hand in hand with antioxidant compounds, namely ascorbic acid (vitamin C), tocopherol (vitamin E), and glutathione, in order to maintain optimal oxidative homeostasis (Agarwal et al., 2005).
Varicocele – defined as aberrant dilation/ elongation of the pampiniform venous plexus of the spermatic cord – is the most common treatable cause of male infertility. Its prevalence ranges between 15% and 20% in the normal adult male population. It is estimated that 30% and 70–85% of men with primary and secondary male factor infertility, respectively, manifest variable degrees of varicocele (Alsaikhan et al., 2016). The physiopathology of varicocele is not well-understood. However, the spermatic veins tend to dilate, supposedly as a consequence of structural defects, leading to incompetency followed by a backflow of hazardous components of venous blood to the testicles, as well as the production of higher mean temperatures (McClure and Hricak, 1986; Miyaoka and Esteves, 2012).
Studies have shown that men with a varicocele show higher concentrations of oxidative stress markers. The abundance of polyunsaturated fatty acids subjects the human sperm membrane to lipid peroxidation, which is a major consequence of seminal oxidative stress, leading to defects in the morphology and functionality of the sperm membrane (Alaa Hamada, 2016). Additionally, elevated concentrations of ROS decrease intracellular pH, which unbalances the relationship between total antioxidant capacity and ROS production, as ROSscavenging enzymes work optimally in mildly alkaline environments (Alaa Hamada, 2016). Besides damaging multiple cell organelles, the resultant thermal/oxidative stress may harm sperm chromatin; however, the situation is shown to be reversible following surgical repair (Telli et al., 2015; Zaazaa et al., 2018).
CONCLUSION
An 80-day course of ALA medication after surgery improves semen quality in individuals with varicocele. In this study, mean sperm motility and progressive motility significantly improved after the participants took ALA for approximately 3 months. Additional ALA treatment after surgical repair of varicocele could thus enhance sperm quality more efficiently than treatment with surgery alone. ALA supplementation could therefore be considered as an adjunct therapy to varicocelectomy. More extensive trials are needed to further investigate this association and the mechanisms involved.
BIOGRAPHY Mohammad H. Nasr-Esfahani Ph.D. (Camb) is currently an Academic Member of the Royan Institute, Head of the Royan Institute for Biotechnology, and Laboratory Director of the Isfahan Fertility and Infertility Centre, Isfahan, Iran. His main research areas are male infertility, stem cells, animal cloning, and recombinant protein.
Behzad Abbasi, Newsha Molavi, Marziyeh Tavalaee, Homayoun Abbasi, Mohammad H. Nasr-Esfahani
KEY MESSAGE
*An 80-day course of alpha-lipoic acid (ALA) medication after microsurgical repair improves sperm motility and progressive motility in men with a varicocele. Thus, ALA supplementation could be considered as an adjunct therapy to varicocelectomy.
ABSTRACT
Research question: Does supplementation with alpha-lipoic acid (ALA) enhance sperm parameters and/or the status of sperm lipid peroxidation and DNA fragmentation in men who have undergone microsurgical repair of a varicocele?
Design: Individuals with a varicocele who had undergone varicocelectomy were divided into two groups receiving either 600 mg of ALA or an identical placebo for 80 days. Semen samples obtained from the participants before surgery and after completion of the course of medication were analyzed and compared. Participants, clinicians, and data analysts were blinded to the randomization sequence.
Results: In the ALA group, total motility (P = 0.01) and progressive motility (P = 0.002) of the spermatozoa were significantly higher compared with the placebo group after surgery. Sperm lipid peroxidation and DNA damage (assessed by sperm chromatin structure assay) showed significant decreases in both the ALA and placebo groups (P ≤ 0.02) after treatment.
Conclusions: An 80-day course of ALA medication after surgical repair improves total motility and progressive motility of the spermatozoa in individuals with a varicocele.
Introduction
The term ‘infertility’ depicts the failure to conceive after a minimum of 12 months of regular unprotected intercourse and affects 10% of the couples of reproductive age. A male etiology contributes to as many as half of all cases of infertility (Winters and Walsh, 2014): classically, an impairment on sperm analysis implies male infertility (WHO, 2010). While the environment, physiological alterations, and genetics have long been acknowledged to affect male fertility status, the exact underlying molecular mechanisms are not well recognized (Coutton et al.,2016). However, the evidence indicates that oxidative stress plays a substantial role in approximately 50% of cases. Oxidative stress arises as a result of an imbalance between oxidizing agents and reductant molecules due to the overproduction of oxidants, namely reactive oxygen species (ROS) (Agarwal et al., 2018; Scott et al.). ROS, naturally produced through normal cellular metabolism, serve as signaling molecules and promote sperm penetration into the oocyte at physiological levels; some studies have shown that incubation of spermatozoa with particular types of ROS upholds capacitation, acrosome reaction, hyperactivation, and fusion to the zona pellucida (de Lamirande et al., 1997).
Morphologically abnormal spermatozoa and seminal leukocytes are the principal suppliers of excessive ROS in human semen, the main aetiologies being considered to be mitochondrial dysfunction and a provoked myeloperoxidase system, respectively (Lobascio et al., 2015). In the seminal plasma, antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase work hand in hand with antioxidant compounds, namely ascorbic acid (vitamin C), tocopherol (vitamin E), and glutathione, in order to maintain optimal oxidative homeostasis (Agarwal et al., 2005).
Varicocele – defined as aberrant dilation/ elongation of the pampiniform venous plexus of the spermatic cord – is the most common treatable cause of male infertility. Its prevalence ranges between 15% and 20% in the normal adult male population. It is estimated that 30% and 70–85% of men with primary and secondary male factor infertility, respectively, manifest variable degrees of varicocele (Alsaikhan et al., 2016). The physiopathology of varicocele is not well-understood. However, the spermatic veins tend to dilate, supposedly as a consequence of structural defects, leading to incompetency followed by a backflow of hazardous components of venous blood to the testicles, as well as the production of higher mean temperatures (McClure and Hricak, 1986; Miyaoka and Esteves, 2012).
Studies have shown that men with a varicocele show higher concentrations of oxidative stress markers. The abundance of polyunsaturated fatty acids subjects the human sperm membrane to lipid peroxidation, which is a major consequence of seminal oxidative stress, leading to defects in the morphology and functionality of the sperm membrane (Alaa Hamada, 2016). Additionally, elevated concentrations of ROS decrease intracellular pH, which unbalances the relationship between total antioxidant capacity and ROS production, as ROSscavenging enzymes work optimally in mildly alkaline environments (Alaa Hamada, 2016). Besides damaging multiple cell organelles, the resultant thermal/oxidative stress may harm sperm chromatin; however, the situation is shown to be reversible following surgical repair (Telli et al., 2015; Zaazaa et al., 2018).
CONCLUSION
An 80-day course of ALA medication after surgery improves semen quality in individuals with varicocele. In this study, mean sperm motility and progressive motility significantly improved after the participants took ALA for approximately 3 months. Additional ALA treatment after surgical repair of varicocele could thus enhance sperm quality more efficiently than treatment with surgery alone. ALA supplementation could therefore be considered as an adjunct therapy to varicocelectomy. More extensive trials are needed to further investigate this association and the mechanisms involved.
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