Advertisement

Varicocele and Oxidative Stress

  • Armand Zini
  • Naif Al-hathal
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

A varicocele is an abnormal dilatation of the pampiniform plexus within the spermatic cord. It is the most common male infertility factor, with multiple potential etiologies involved in its development. However, despite ongoing extensive research on varicoceles, the exact mechanism(s) by which varicocele influences male fertility is not known. Recent studies have shown that infertile men with varicocele have higher levels of seminal oxidative stress (OS) markers, and/or lower seminal antioxidant levels, than do fertile men and infertile men without varicocele. The abnormally high levels of seminal OS biomarkers (e.g., reactive oxygen species, malonaldehyde) in infertile men with varicocele is clinically relevant as these markers have been associated with poor sperm function and reduced fertility potential. In addition, infertile patients with varicocele possess high levels of sperm DNA damage and the mechanism of varicocele-induced sperm DNA damage is believed to be at least in part due to OS. The observed improvement in seminal OS and sperm DNA damage after varicocele repair supports the premise that varicocele can induce seminal OS.

Keywords

Varicocele Oxidative stress Mechanisms of disease Pathophysiology of varicocele Varicocelectomy DNA damage 

References

  1. 1.
    Naughton CK, Nangia AK, Agarwal A. Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001;7(5):473–81.PubMedGoogle Scholar
  2. 2.
    Shafik A, Bedeir GA. Venous tension patterns in cord veins. I: in normal and varicocele individuals. J Urol. 1980;123(3):383–5.PubMedGoogle Scholar
  3. 3.
    Ahlberg NE, Bartley O, Chidekel N. Right and left gonadal veins. An anatomical and statistical study. Acta Radiol Diagn (Stockh). 1966;4(6):593–601.Google Scholar
  4. 4.
    Comhaire F, Monteyne R, Kunnen M. The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of “subclinical” varicocele. Fertil Steril. 1976;27(6):694–8.PubMedGoogle Scholar
  5. 5.
    Zorgniotti AW, Macleod J. Studies in temperature, human semen quality, and varicocele. Fertil Steril. 1973;24(11):854–63.PubMedGoogle Scholar
  6. 6.
    Goldstein M, Eid JF. Elevation of intratesticular and scrotal skin surface temperature in men with varicocele. J Urol. 1989;142(3):743–5.PubMedGoogle Scholar
  7. 7.
    Mieusset R, et al. Association of scrotal hyperthermia with impaired spermatogenesis in infertile men. Fertil Steril. 1987;48(6):1006–11.PubMedGoogle Scholar
  8. 8.
    Jung A, Eberl M, Schill WB. Improvement of semen quality by nocturnal scrotal cooling and moderate behavioural change to reduce genital heat stress in men with oligoasthenoteratozoospermia. Reproduction. 2001;121(4):595–603.PubMedGoogle Scholar
  9. 9.
    Comhaire F, Vermeulen A. Varicocele sterility: cortisol and catecholamines. Fertil Steril. 1974;25(1):88–95.PubMedGoogle Scholar
  10. 10.
    Ito H, et al. Internal spermatic vein prostaglandins in varicocele patients. Fertil Steril. 1982;37(2):218–22.PubMedGoogle Scholar
  11. 11.
    Ozbek E, et al. The role of adrenomedullin in varicocele and impotence. BJU Int. 2000;86(6):694–8.PubMedGoogle Scholar
  12. 12.
    Kilinc F, et al. Experimental varicocele induces hypoxia inducible factor-1alpha, vascular endothelial growth factor expression and angiogenesis in the rat testis. J Urol. 2004;172(3):1188–91.PubMedGoogle Scholar
  13. 13.
    Lee JD, Jeng SY, Lee TH. Increased expression of hypoxia-inducible factor-1alpha in the internal spermatic vein of patients with varicocele. J Urol. 2006;175(3 Pt 1):1045–8; discussion 1048.Google Scholar
  14. 14.
    Guzick DS, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2001;345(19):1388–93.PubMedGoogle Scholar
  15. 15.
    ESHRE Capri Workshop Group. Social determinants of human reproduction. Hum Reprod. 2001;16(7):1518–26.Google Scholar
  16. 16.
    Akbay E, et al. The prevalence of varicocele and varicocele-related testicular atrophy in Turkish children and adolescents. BJU Int. 2000;86(4):490–3.PubMedGoogle Scholar
  17. 17.
    Laven JS, et al. Effects of varicocele treatment in adolescents: a randomized study. Fertil Steril. 1992;58(4):756–62.PubMedGoogle Scholar
  18. 18.
    Lipshultz LI, Corriere Jr JN. Progressive testicular atrophy in the varicocele patient. J Urol. 1977;117(2):175–6.PubMedGoogle Scholar
  19. 19.
    Pinto KJ, Kroovand RL, Jarow JP. Varicocele related testicular atrophy and its predictive effect upon fertility. J Urol. 1994;152(2 Pt 2):788–90.PubMedGoogle Scholar
  20. 20.
    Sigman M, Jarow JP. Ipsilateral testicular hypotrophy is associated with decreased sperm counts in infertile men with varicoceles. J Urol. 1997;158(2):605–7.PubMedGoogle Scholar
  21. 21.
    World Health Organization. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril. 1992;57(6):1289–93.Google Scholar
  22. 22.
    Zini A, et al. The influence of clinical and subclinical varicocele on testicular volume. Fertil Steril. 1997;68(4):671–4.PubMedGoogle Scholar
  23. 23.
    Zini A, et al. Loss of left testicular volume in men with clinical left varicocele: correlation with grade of varicocele. Arch Androl. 1998;41(1):37–41.PubMedGoogle Scholar
  24. 24.
    Alukal JP, et al. Testicular hypotrophy does not correlate with grade of adolescent varicocele. J Urol. 2005;174(6):2367–70; discussion 2370.Google Scholar
  25. 25.
    Diamond DA, et al. Relationship of varicocele grade and testicular hypotrophy to semen parameters in adolescents. J Urol. 2007;178(4 Pt 2):1584–8.PubMedGoogle Scholar
  26. 26.
    Dubin L, Hotchkiss RS. Testis biopsy in subfertile men with varicocele. Fertil Steril. 1969;20(1):51–7.PubMedGoogle Scholar
  27. 27.
    Comhaire F, Vermeulen A. Plasma testosterone in patients with varicocele and sexual inadequacy. J Clin Endocrinol Metab. 1975;40(5):824–9.PubMedGoogle Scholar
  28. 28.
    Johnsen SG, Agger P. Quantitative evaluation of testicular biopsies before and after operation for varicocele. Fertil Steril. 1978;29(1):58–63.PubMedGoogle Scholar
  29. 29.
    Hudson RW. The endocrinology of varicoceles. Fertil Steril. 1988;49(2):199–208.PubMedGoogle Scholar
  30. 30.
    Agger P, Johnsen SG. Quantitative evaluation of testicular biopsies in varicocele. Fertil Steril. 1978;29(1):52–7.PubMedGoogle Scholar
  31. 31.
    Ibrahim AA, et al. Bilateral testicular biopsy in men with varicocele. Fertil Steril. 1977;28(6):663–7.PubMedGoogle Scholar
  32. 32.
    Santoro G, Romeo C. Normal and varicocele testis in adolescents. Asian J Androl. 2001;3(4):259–62.PubMedGoogle Scholar
  33. 33.
    Lue YH, et al. Mild testicular hyperthermia induces profound transitional spermatogenic suppression through increased germ cell apoptosis in adult cynomolgus monkeys (Macaca fascicularis). J Androl. 2002;23(6):799–805.PubMedGoogle Scholar
  34. 34.
    MacLeod J. Seminal cytology in the presence of varicocele. Fertil Steril. 1965;16(6):735–57.PubMedGoogle Scholar
  35. 35.
    Ayodeji O, Baker HW. Is there a specific abnormality of sperm morphology in men with varicoceles? Fertil Steril. 1986;45(6):839–42.PubMedGoogle Scholar
  36. 36.
    Johnson DE, Pohl DR, Rivera-Correa H. Varicocele: an innocuous condition? South Med J. 1970;63(1):34–6.PubMedGoogle Scholar
  37. 37.
    Zargooshi J. Sperm count and sperm motility in incidental high-grade varicocele. Fertil Steril. 2007;88(5):1470–3.PubMedGoogle Scholar
  38. 38.
    Chehval MJ, Purcell MH. Deterioration of semen parameters over time in men with untreated varicocele: evidence of progressive testicular damage. Fertil Steril. 1992;57(1):174–7.PubMedGoogle Scholar
  39. 39.
    Lund L, Larsen SB. A follow-up study of semen quality and fertility in men with varicocele testis and in control subjects. Br J Urol. 1998;82(5):682–6.PubMedGoogle Scholar
  40. 40.
    Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet. 2009;26(8):427–32.PubMedGoogle Scholar
  41. 41.
    Aitken RJ, et al. Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria. Hum Reprod. 2010;25(10):2415–26.PubMedGoogle Scholar
  42. 42.
    Fraga CG, et al. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA. 1991;88(24):11003–6.PubMedGoogle Scholar
  43. 43.
    Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992;57(2):409–16.PubMedGoogle Scholar
  44. 44.
    Aitken RJ, Clarkson JS. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil. 1987;81(2):459–69.PubMedGoogle Scholar
  45. 45.
    de Lamirande E, Gagnon C. Reactive oxygen species and human spermatozoa. II. Depletion of adenosine triphosphate plays an important role in the inhibition of sperm motility. J Androl. 1992;13(5):379–86.PubMedGoogle Scholar
  46. 46.
    de Lamirande E, Gagnon C. Reactive oxygen species and human spermatozoa. I: effects on the motility of intact spermatozoa and on sperm axonemes. J Androl. 1992;13(5):368–78.PubMedGoogle Scholar
  47. 47.
    Zini A, Garrels K, Phang D. Antioxidant activity in the semen of fertile and infertile men. Urology. 2000;55(6):922–6.PubMedGoogle Scholar
  48. 48.
    Yang MH, Schaich KM. Factors affecting DNA damage caused by lipid hydroperoxides and aldehydes. Free Radic Biol Med. 1996;20(2):225–36.PubMedGoogle Scholar
  49. 49.
    Lewis SE, Aitken RJ. DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res. 2005;322(1):33–41.PubMedGoogle Scholar
  50. 50.
    Alvarez JG, et al. Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J Androl. 1987;8(5):338–48.PubMedGoogle Scholar
  51. 51.
    Twigg J, et al. Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod. 1998;13(6):1429–36.PubMedGoogle Scholar
  52. 52.
    Weese DL, et al. Stimulated reactive oxygen species generation in the spermatozoa of infertile men. J Urol. 1993;149(1):64–7.PubMedGoogle Scholar
  53. 53.
    Hendin BN, et al. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol. 1999;161(6):1831–4.PubMedGoogle Scholar
  54. 54.
    Sharma RK, et al. The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility. Hum Reprod. 1999;14(11):2801–7.PubMedGoogle Scholar
  55. 55.
    Pasqualotto FF, et al. Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil Steril. 2000;73(3):459–64.PubMedGoogle Scholar
  56. 56.
    Pasqualotto FF, et al. Oxidative stress in normospermic men undergoing infertility evaluation. J Androl. 2001;22(2):316–22.PubMedGoogle Scholar
  57. 57.
    Allamaneni SS, et al. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil Steril. 2004;82(6):1684–6.PubMedGoogle Scholar
  58. 58.
    Hurtado de Catalfo GE, et al. Oxidative stress biomarkers and hormonal profile in human patients undergoing varicocelectomy. Int J Androl. 2007;30(6):519–30.PubMedGoogle Scholar
  59. 59.
    Pasqualotto FF, et al. Semen quality and oxidative stress scores in fertile and infertile patients with varicocele. Fertil Steril. 2008;89(3):602–7.PubMedGoogle Scholar
  60. 60.
    Sakamoto Y, et al. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008;101(12):1547–52.PubMedGoogle Scholar
  61. 61.
    Cocuzza M, et al. Impact of clinical varicocele and testis size on seminal reactive oxygen species levels in a fertile population: a prospective controlled study. Fertil Steril. 2008;90(4):1103–8.PubMedGoogle Scholar
  62. 62.
    Mostafa T, et al. Seminal reactive oxygen species-antioxidant relationship in fertile males with and without varicocele. Andrologia. 2009;41(2):125–9.PubMedGoogle Scholar
  63. 63.
    Ishikawa T, et al. Increased testicular 8-hydroxy-2’-deoxyguanosine in patients with varicocele. BJU Int. 2007;100(4):863–6.PubMedGoogle Scholar
  64. 64.
    Shiraishi K, Naito K. Generation of 4-hydroxy-2-nonenal modified proteins in testes predicts improvement in spermatogenesis after varicocelectomy. Fertil Steril. 2006;86(1):233–5.PubMedGoogle Scholar
  65. 65.
    Chen SS, Chang LS, Wei YH. Oxidative damage to proteins and decrease of antioxidant capacity in patients with varicocele. Free Radic Biol Med. 2001;30(11):1328–34.PubMedGoogle Scholar
  66. 66.
    Mostafa T, et al. Reactive oxygen species and antioxidants relationship in the internal spermatic vein blood of infertile men with varicocele. Asian J Androl. 2006;8(4):451–4.PubMedGoogle Scholar
  67. 67.
    Romeo C, et al. Nitric oxide production is increased in the spermatic veins of adolescents with left idiophatic varicocele. J Pediatr Surg. 2001;36(2):389–93.PubMedGoogle Scholar
  68. 68.
    Turkyilmaz Z, et al. Increased nitric oxide is accompanied by lipid oxidation in adolescent varicocele. Int J Androl. 2004;27(3):183–7.PubMedGoogle Scholar
  69. 69.
    Moskovtsev SI, et al. Cause-specific treatment in patients with high sperm DNA damage resulted in significant DNA improvement. Syst Biol Reprod Med. 2009;55(2):109–15.PubMedGoogle Scholar
  70. 70.
    Oliva A, Dotta A, Multigner L. Pentoxifylline and antioxidants improve sperm quality in male patients with varicocele. Fertil Steril. 2009;91(4 Suppl):1536–9.PubMedGoogle Scholar
  71. 71.
    Paradiso Galatioto G, et al. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele. World J Urol. 2008;26(1):97–102.PubMedGoogle Scholar
  72. 72.
    Agarwal A, et al. Role of oxidative stress in pathogenesis of varicocele and infertility. Urology. 2009;73(3):461–9.PubMedGoogle Scholar
  73. 73.
    Nallella KP, et al. Relationship of interleukin-6 with semen characteristics and oxidative stress in patients with varicocele. Urology. 2004;64(5):1010–3.PubMedGoogle Scholar
  74. 74.
    Konukoglu D, Serin O, Turhan MS. Plasma leptin and its relationship with lipid peroxidation and nitric oxide in obese female patients with or without hypertension. Arch Med Res. 2006;37(5):602–6.PubMedGoogle Scholar
  75. 75.
    Ishikawa T, et al. Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22–7.PubMedGoogle Scholar
  76. 76.
    Chen Z, et al. Glial cell line-derived neurotrophic factor promotes survival and induces differentiation through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathway respectively in PC12 cells. Neuroscience. 2001;104(2):593–8.PubMedGoogle Scholar
  77. 77.
    Akkoyunlu G, et al. Immunolocalization of glial cell-derived neurotrophic factor (GDNF) and its receptor GFR-alpha1 in varicocele-induced rat testis. Acta Histochem. 2007;109(2):130–7.PubMedGoogle Scholar
  78. 78.
    Benoff S, et al. Deletions in L-type calcium channel alpha1 subunit testicular transcripts correlate with testicular cadmium and apoptosis in infertile men with varicoceles. Fertil Steril. 2005;83(3):622–34.PubMedGoogle Scholar
  79. 79.
    Benoff SH, et al. Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele. Hum Reprod. 2004;19(3):616–27.PubMedGoogle Scholar
  80. 80.
    Shiraishi K, Naito K. Increased expression of Leydig cell haem oxygenase-1 preserves spermatogenesis in varicocele. Hum Reprod. 2005;20(9):2608–13.PubMedGoogle Scholar
  81. 81.
    Schlesinger MH, Wilets IF, Nagler HM. Treatment outcome after varicocelectomy. A critical analysis. Urol Clin North Am. 1994;21(3):517–29.PubMedGoogle Scholar
  82. 82.
    Kim ED, et al. Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure. J Urol. 1999;162(3 Pt 1):737–40.PubMedGoogle Scholar
  83. 83.
    Cayan S, et al. Can varicocelectomy significantly change the way couples use assisted reproductive technologies? J Urol. 2002;167(4):1749–52.PubMedGoogle Scholar
  84. 84.
    Smit M, et al. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol. 2010;183(1):270–4.PubMedGoogle Scholar
  85. 85.
    Aitken RJ, Irvine DS, Wu FC. Prospective analysis of sperm-oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynecol. 1991;164(2):542–51.PubMedGoogle Scholar
  86. 86.
    Barbieri ER, et al. Varicocele-associated decrease in antioxidant defenses. J Androl. 1999;20(6):713–7.PubMedGoogle Scholar
  87. 87.
    Smith R, et al. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2006;21(4):986–93.PubMedGoogle Scholar
  88. 88.
    Saleh RA, et al. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril. 2003;80(6):1431–6.PubMedGoogle Scholar
  89. 89.
    Zini A, et al. Effect of varicocelectomy on the abnormal retention of residual cytoplasm by human spermatozoa. Hum Reprod. 1999;14(7):1791–3.PubMedGoogle Scholar
  90. 90.
    Mostafa T, et al. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Int J Androl. 2001;24(5):261–5.PubMedGoogle Scholar
  91. 91.
    Mancini A, et al. Seminal antioxidant capacity in pre- and postoperative varicocele. J Androl. 2004;25(1):44–9.PubMedGoogle Scholar
  92. 92.
    Chen SS, et al. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J Urol. 2008;179(2):639–42.PubMedGoogle Scholar
  93. 93.
    Dada R, et al. Attenuation of oxidative stress & DNA damage in varicocelectomy: implications in infertility management. Indian J Med Res. 2010;132(6):728–30.PubMedGoogle Scholar
  94. 94.
    Cervellione RM, et al. Effect of varicocelectomy on the plasma oxidative stress parameters. J Pediatr Surg. 2006;41(2):403–6.PubMedGoogle Scholar
  95. 95.
    Evenson DP, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14(4):1039–49.PubMedGoogle Scholar
  96. 96.
    Zini A, et al. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril. 2001;75(4):674–7.PubMedGoogle Scholar
  97. 97.
    Spano M, et al. Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team. Fertil Steril. 2000;73(1):43–50.PubMedGoogle Scholar
  98. 98.
    Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl. 2001;22(4):604–10.PubMedGoogle Scholar
  99. 99.
    de Yebra L, et al. Detection of P2 precursors in the sperm cells of infertile patients who have reduced protamine P2 levels. Fertil Steril. 1998;69(4):755–9.PubMedGoogle Scholar
  100. 100.
    Sakkas D, et al. Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodelling during spermatogenesis. Reprod Biomed Online. 2003;7(4):428–32.PubMedGoogle Scholar
  101. 101.
    Aitken RJ, De Iuliis GN. Origins and consequences of DNA damage in male germ cells. Reprod Biomed Online. 2007;14(6):727–33.PubMedGoogle Scholar
  102. 102.
    Enciso M, et al. Infertile men with varicocele show a high relative proportion of sperm cells with intense nuclear damage level, evidenced by the sperm chromatin dispersion test. J Androl. 2006;27(1):106–11.PubMedGoogle Scholar
  103. 103.
    Simsek F, et al. Role of apoptosis in testicular tissue damage caused by varicocele. Arch Esp Urol. 1998;51(9):947–50.PubMedGoogle Scholar
  104. 104.
    El-Domyati MM, et al. The expression and distribution of deoxyribonucleic acid repair and apoptosis markers in testicular germ cells of infertile varicocele patients resembles that of old fertile men. Fertil Steril. 2010;93(3):795–801.PubMedGoogle Scholar
  105. 105.
    Hsu HS, et al. Decreased blood flow and defective energy metabolism in the varicocele-bearing testicles of rats. Eur Urol. 1994;25(1):71–5.PubMedGoogle Scholar
  106. 106.
    Li H, et al. Effect of surgically induced varicocele on testicular blood flow and Sertoli cell function. Urology. 1999;53(6):1258–62.PubMedGoogle Scholar
  107. 107.
    Fujisawa M, et al. The significance of gonadotropin-releasing hormone test for predicting fertility after varicocelectomy. Fertil Steril. 1994;61(4):779–82.PubMedGoogle Scholar
  108. 108.
    Mieusset R, Bujan L. Testicular heating and its possible contributions to male infertility: a review. Int J Androl. 1995;18(4):169–84.PubMedGoogle Scholar
  109. 109.
    Zini A, et al. Varicocele is associated with abnormal retention of cytoplasmic droplets by human spermatozoa. Fertil Steril. 2000;74(3):461–4.PubMedGoogle Scholar
  110. 110.
    Benoff S, et al. A potential role for cadmium in the etiology of varicocele-associated infertility. Fertil Steril. 1997;67(2):336–47.PubMedGoogle Scholar
  111. 111.
    Marmar JL. The pathophysiology of varicoceles in the light of current molecular and genetic information. Hum Reprod Update. 2001;7(5):461–72.PubMedGoogle Scholar
  112. 112.
    French DB, Desai NR, Agarwal A. Varicocele repair: does it still have a role in infertility treatment? Curr Opin Obstet Gynecol. 2008;20(3):269–74.PubMedGoogle Scholar
  113. 113.
    Werthman P, et al. Significant decrease in sperm deoxyribonucleic acid fragmentation after varicocelectomy. Fertil Steril. 2008;90(5):1800–4.PubMedGoogle Scholar
  114. 114.
    Zini A, et al. Beneficial effect of microsurgical varicocelectomy on human sperm DNA integrity. Hum Reprod. 2005;20(4):1018–21.PubMedGoogle Scholar
  115. 115.
    Zini A, et al. Effect of microsurgical varicocelectomy on human sperm chromatin and DNA integrity: a prospective trial. Int J Androl. 2010;34(1):14–9.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of SurgerySt. Mary’s HospitalMontréalCanada

Personalised recommendations