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      A Preliminary Study: N-acetyl-L-cysteine Improves Semen Quality following Varicocelectomy

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          Abstract

          Background

          Surgery is considered the primary treatment for male infertility from clinical varicocele. One of the main events associated with varicocele is excessive production of reactive oxygen species (ROS). N-acetyl-L-cysteine (NAC), an antioxidant that scavenges free radicals, is considered a supplement to alleviate glutathione (GSH) depletion during oxidative stress. Despite beneficial effects of NAC in other pathological events, there is no report on the effect of NAC in individuals with varicocele. Therefore, the aim of this study is to evaluate the outcome of NAC on semen quality, protamine content, DNA damage, oxidative stress and fertility following varicocelectomy.

          Materials and Methods

          This prospective clinical trial included 35 infertile men with varicocele randomly divided into control (n=20) and NAC (n=15) groups. We assessed semen parameters, protamine content [chromomycin A3 (CMA3)], DNA integrity [terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL)] and oxidative stress [2', 7'-dichlorodihydrofluorescein-diacetate (DCFH-DA)] before and three months after varicocelectomy.

          Results

          Percentage of abnormal semen parameters, protamine deficiency, DNA fragmentation and oxidative stress were significantly decreased in both groups compared to before surgery. We calculated the percentage of improvement in these parameters compared to before surgery for each group, then compared the results between the groups. Only percentage of protamine deficiency and DNA fragmentation significantly differed between the NAC and control groups.

          Conclusion

          The results of this study, for the first time, revealed that NAC improved chromatin integrity and pregnancy rate when administered as adjunct therapy post-varico- celectomy (Registeration Number: IRCT201508177223N5).

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          Most cited references29

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          Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria.

          DNA damage in human spermatozoa is known to be associated with a variety of adverse clinical outcomes affecting both reproductive efficiency and the health and wellbeing of the offspring. However, the origin of this damage, its biochemical nature and strategies for its amelioration, still await resolution. Using novel methods to simultaneously assess DNA fragmentation (modified TUNEL assay), DNA-base adduct formation (8-hydroxy-2'-deoxyguanosine [8OHdG]) and cell vitality, spermatozoa from a cohort of 50 assisted conception patients were examined and compared with a group of donors. Receiver operating characteristic (ROC) curve analysis was then used to examine the frequency distribution of the data and to determine optimized thresholds for identifying patients exhibiting abnormally high levels of DNA damage. 8OHdG formation and DNA fragmentation were highly correlated with each other and frequently associated with cell death. Percoll centrifugation improved sperm quality but, unexpectedly, increased 8OHdG formation in live cells, as did sperm fractionation using Puresperm gradients. ROC analysis indicated that the frequency distribution of 8OHdG and DNA fragmentation data were significantly different between patients and donors (P < 0.001), permitting the development of thresholds that would allow the accurate diagnosis of DNA damage in the male germ line. The aetiology of DNA damage in spermatozoa involves a cascade of changes that progress from the induction of oxidative stress and oxidized DNA base adduct formation to DNA fragmentation and cell death. Preparation of spermatozoa on discontinuous density gradients aggravates the problem by stimulating the formation of 8OHdG in live cells. However, the development of novel methods and optimized thresholds for diagnosing oxidative DNA damage in human spermatozoa should assist in the clinical management of this pathology.
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            Insight into oxidative stress in varicocele-associated male infertility: part 1.

            Varicocele is recognized as the leading cause of male infertility because it can impair spermatogenesis through several distinct pathophysiological mechanisms. Current evidence supports oxidative stress as a key element in the pathophysiology of varicocele-related infertility, although these mechanisms have not yet been fully described. Measurement of the reactive oxygen species and other markers of oxidative stress, including the levels of the antioxidant enzymes catalase and superoxide dismutase, can provide valuable information on the extent of oxidative stress and might guide therapeutic management strategies. The testis can respond to varicocele-associated cell stressors, such as heat stress, ischaemia or production of vasodilators (for example, nitric oxide) at the expense of the generation of excessive reactive oxygen species. These responses have their own implications in exacerbating the underlying oxidative stress and on the subsequent infertility.
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              The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization.

              To assess the role of varicocele in male infertility. Data analysis of a large population of couples who were systematically investigated for infertility. Couples were recruited in 34 World Health Organization collaborating centers in 24 countries. Nine thousand thirty-four men presenting as partner of infertile couples. None. Physical findings, semen characteristics, coincidental pathology, and spontaneous pregnancies. Varicocele was found in 25.4% of men with abnormal semen, compared with 11.7% of men with normal semen. It was accompanied by decreased testicular volume, impaired sperm quality, and decline of Leydig cell secretion. Spontaneous pregnancies were as frequent in couples in whom the men did or did not have varicocele. Varicocele is clearly associated with impairment of testicular function and infertility.
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                Author and article information

                Journal
                Int J Fertil Steril
                Int J Fertil Steril
                Royan Institute
                International Journal of Fertility & Sterility
                Royan Institute
                2008-076X
                2008-0778
                Apr-Jun 2016
                5 April 2016
                : 10
                : 1
                : 120-126
                Affiliations
                [1 ]Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
                [2 ]Department of Biology, Flavarjan Branch, Islamic Azad University, Flavarjan, Isfahan, Iran
                [3 ]Isfahan Fertility and Infertility Center, Isfahan, Iran
                Author notes
                [*Corresponding Address: ]P.O.Box: 8165131378Department of Reproductive BiotechnologyReproductive Biomedicine Research CenterRoyan Institute for Biotechnology ACECRIsfahanIran Email: mh.nasr-esfahani@ 123456royaninstitute.org
                Article
                Int-J-Fertil-Steril-10-120
                4845522
                27123209
                9e515a28-ca33-471b-806b-a0ecc713c606
                Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 January 2014
                : 20 April 2014
                Categories
                Original Article
                Andrology
                Cellular and Molecular Biology
                Custom metadata
                Barekat F, Tavalaee M, Deemeh MR, Bahareinian M, Azadi L, Abbasi H, Rozbahani Sh, Nasr Esfahani MH. A pre- liminary study: N-acetyl-L-cysteine improves semen quality following varicocelectomy. Int J Fertil Steril. 2016; 10(1): 120-126.

                dna fragmentation,protamines,oxidative stress,varicocele,nac

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