Current Urology Reports

, Volume 2, Issue 6, pp 432–436 | Cite as

The pathophysiology of varicocele-associated male infertility

  • Richard A. Schoor
  • Samir M. Elhanbly
  • Craig S. Niederberger
Article

Abstract

Varicocele is the most commonly identifiable, surgically correctable lesion associated with male-factor infertility. Surgical correction of a varicocele, whether unilateral or bilateral, results in improvement not only in semen parameters but also in spontaneous and assisted pregnancy rates. Varicoceles seem to induce a number of changes in the testicular microenvironment. These alterations in temperature, hemodynamics, and reactive oxidative species and antioxidant concentrations have been demon-strated to produce deleterious effects on spermatogenesis. However, despite current knowledge in the patho-physiology of varicocele-associated male infertility, the exact mechanism—or mechanisms—by which varicoceles impair fertility remains elusive. This review examines scientific evidence regarding the pathophysiology of varicocele-associated male infertility.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Alcalay J, Kedem R: The ethnic distribution of varicocele. Mil Med 1986, 151:327–328.PubMedGoogle Scholar
  2. 2.
    Jarow J, Coburn M, Sigman M: Incidence of varicoceles in men with primary and secondary infertility. Urol 1996, 47:73–76.PubMedCrossRefGoogle Scholar
  3. 3.
    Kursh E: What is the incidence of varicocele in a fertile population. Fertil Steril 1987, 48:510–511.PubMedGoogle Scholar
  4. 4.
    Meacham R, Townsend D, Rademacher D, Drose J: The incidence of varicoceles in the general population when evaluated by physical examination, gray scale sonography and color doppler sonography. J Urol 1994, 151:1535–1538.PubMedGoogle Scholar
  5. 5.
    World Health Organization: The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril 1992, 57:1289–1293. This is a seminal publication on the statistical association of varico-cele and male-factor infertility. It is a heavily cited article. The current urologic treatment approach to varicocele-associated male infertility is based in large part on this publication.Google Scholar
  6. 6.
    Greenberg S: Varicocele and male infertility. Fertil Steril 1977, 28:699.PubMedGoogle Scholar
  7. 7.
    Madgar I, Weissenberg R, Lunenfeld B, et al.: Controlled trial of high spermatic vein ligation for varicocele in infertile men. Fertil Steril 1995, 63:120–124. Provides good data on pregnancy rates after varicocelectomy.PubMedGoogle Scholar
  8. 8.
    Holland K, Brill R, Chang R, et al.: Physiological and behav-ioural thermoregulation in bigeye tuna (Thunnus obesus). Nature 1992, 358:410–412.PubMedCrossRefGoogle Scholar
  9. 9.
    Schmidt-Nielsen K: Countercurrent systems in animals. Sci Am 1981, 244:118–128.PubMedCrossRefGoogle Scholar
  10. 10.
    Stevens E, Lam H, Kendall J: Vascular anatomy of the counter-current heat exchanger of the skipjack tuna. J Exp Biol 1974, 61:145–153.PubMedGoogle Scholar
  11. 11.
    Hillman P, Scott N, van Tienhoven A: Vasomoti on i n chicken foot: dual innervation of arteriovenous anastomoses. Am J Physiol 1982, 242:R582–590.PubMedGoogle Scholar
  12. 12.
    Stoner H, Barker P, Riding G, et al.: Relationships between skin temperature and perfusion in the arm and leg. Clin Physiol 1991, 11:27–40.PubMedGoogle Scholar
  13. 13.
    Glad Sorensen H, Lambrechsten J, Einer-Jensen N: Efficiency of the countercurrent transfer of heat and 133Xenon between the pampiniform plexus and the testicular artery of the bull under in-vitro conditions. Int J Androl 1991, 14:232–240.Google Scholar
  14. 14.
    Goldstein M, Eid J: Elevation of intratesticular and scrotal skin surface temperature in men with varicocele. J Urol 1989, 142:743–745. Demonstrates in humans elevated scrotal temperatures.PubMedGoogle Scholar
  15. 15.
    Green K, Turner T, Howards S: Varicocele: reversal of the testicular blood flow and temperature effects by varicocele repair. J Urol 1984, 131:1208–1211. This is an excellent basic science paper. The authors surgically induced varicoceles and measured testicular blood flow and temperature. It is a well-controlled, well-conducted investigation.PubMedGoogle Scholar
  16. 16.
    Kay R, Alexander N, Baugham WL: Induced varicoceles in Rhesus monkeys. Fertil Steril 1979, 31:195–199.PubMedGoogle Scholar
  17. 17.
    Saypol D, Howards S, Turner T, Miller E: Influence of surgically induced varicocele on testicular blood flow, temperature, and histology in adult rats and dogs. J Clin Invest 1981, 68:39–45. Another good basic science investigation that demonstrates that varicoceles produce elevated testicular temperatures, altered blood flow, and parenchymal damage.PubMedCrossRefGoogle Scholar
  18. 18.
    Mieusset R, Grandjean H, Mansat A, Pontonnier F: Inhibiting effect of artificial cryptorchidism on spermatogenesis. Fertil Steril 1985, 43:589–594.PubMedGoogle Scholar
  19. 19.
    Wang C, McDonald V, Leung A, et al.: Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril 1997, 68:334–339. Temperature effect on spermatogenesis.PubMedCrossRefGoogle Scholar
  20. 20.
    Kandeel F, Swerdloff R: Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception. Fertil Steril 1988, 49:1–23.PubMedGoogle Scholar
  21. 21.
    Sigman M, Lipshultz L, Howards S: Evaluation of the infertile male. In Infertility in the Male. Edited by: Lipshultz L, Howards S. St. Louis: Mosby; 1997.Google Scholar
  22. 22.
    Sarge K, Cullen K: Regulation of hsp expression during rodent spermatogenesis. Cell Mol Life Sci 1997, 53:191–197. Good review of molecular mechanisms by which heat may adversely affect spermatogenesis.PubMedCrossRefGoogle Scholar
  23. 23.
    Guo C, Tang T, Mu X, et al.: Cloning of novel temperature-related expressed sequence tags in rat testis during spermato-genesis. Biochem Biophys Res Comm 1999, 258:401–406.PubMedCrossRefGoogle Scholar
  24. 24.
    Socher S, Yin Y, Dewolf W, Morgentaler A: Temperature-mediated germ cell loss in the testis is associated with alterted expression of the cell-cycle regulator p53. J Urol 1997, 157:1986–1989.PubMedCrossRefGoogle Scholar
  25. 25.
    Kadioglu T, Koksal I, Tunc M, et al.: Treatment of idiopathic and postvaricocelectomy oligospermia with oral tamoxifen citrate. BJU Int 1999, 86:646–648.CrossRefGoogle Scholar
  26. 26.
    Turner T, Caplis L, Brown K: Vascular anatomy of experimen-tally induced left varicocele in the rat. Lab Anim Sci 1996, 46:206–210.PubMedGoogle Scholar
  27. 27.
    Lang F, Greger R, Deetjen P, Knox F: Factors affecting urate reabsorption in the rat kidney. Adv Exp Med Biol 1977, 76B:100–109.PubMedGoogle Scholar
  28. 28.
    Haikun L, Dubocq F, Jlang Y, et al.: Effect of surgically induced varicocele on testicular blood flow and sertoli cell function. Urol 1999, 53:1258–1262.CrossRefGoogle Scholar
  29. 29.
    Wilson R, Griswold M: Secreted proteins from rat Sertoli cells. Exp Cell Res 1979, 123:127–135.PubMedCrossRefGoogle Scholar
  30. 30.
    Aitken R, Clarkson J: Cellular bases of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 1987, 81:459–469.PubMedCrossRefGoogle Scholar
  31. 31.
    Mitropoulos D, Delinconstantinos G, Zervas A, et al.: Nitric oxide synthase and xanthine oxidase activities in the spermatic vein of patients with varicocele: a potential role for nitric oxide and peroxynitrate in sperm dysfunction. J Urol 1996, 156:1952–1958.PubMedCrossRefGoogle Scholar
  32. 32.
    Alkan I, Simsek F, Kaklar C, et al.: Reactive oxygen species production by the spermatozoa of patients with idiopathic infertility: relationship to seminal plasma antioxidants. J Urol 1997, 157:140–143.PubMedCrossRefGoogle Scholar
  33. 33.
    Sharma R, Pasqualotto F, Nelson D, et al.: The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility. Hum Reprod 1999, 14:2801–2807. Good review of ROS and TAC and their effects on spermatogenesis in humans.PubMedCrossRefGoogle Scholar
  34. 34.
    Hendin B, Kolettis P, Sharma R, et al.: Varicocele is associated with elevated spermatozoal reactive oxygen species produc-tion and diminished seminal plasma antioxidant capacity. J Urol 1999, 161:1831–1834. Correction of varicoceles improves ROS and TAC levels.PubMedCrossRefGoogle Scholar
  35. 35.
    Mazzilli F, Rossi B, Marchesini M, et al.: Superoxide anion in human semen related to seminal parameters and clinical aspects. Fertil Steril 1994, 62:862–868.PubMedGoogle Scholar
  36. 36.
    Weese D, Peaster M, Himsl K, et al.: Stimulated reactive oxygen species generation in the spermatozoa of infertile men. J Urol 1993, 149:64–67.PubMedGoogle Scholar
  37. 37.
    Delinconstantinos G, Villiotou V, Stavrides JC: Modulation of particulate nitric oxide synthase activity and peroxynitrite synthesis in cholesterol enriched endothelial cell membranes. Biochem Pharmacol 1995, 49:1589–1600.CrossRefGoogle Scholar
  38. 38.
    Beckman J, Crow J: Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans 1993, 21:330–334.PubMedGoogle Scholar
  39. 39.
    Ozbek E, Turkoz Y, Gokdeni R, et al.: Increased nitric oxide production in the spermatic vein of patients with varicocele. Eur Urol 2000, 37:172–175.PubMedCrossRefGoogle Scholar
  40. 40.
    Lewis S, Boyle P, McKinney K, et al.: Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril 1995, 64:868–870.PubMedGoogle Scholar
  41. 41.
    Barbieri E, Hidalgo M, Venegas A, et al.: Varicocele-associated decrease in antioxidant defenses. J Androl 1999, 20:713–717.PubMedGoogle Scholar
  42. 42.
    Rolf C, Cooper T, Yeung C, Nieschlang E: Antioxidant treatment of patients with asthenospermia or moderate oligoasthenospermia with high dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod 1999, 14:1028–1033.PubMedCrossRefGoogle Scholar
  43. 43.
    Ferlin A, Moro E, Garolla A, Foresta C: Human male infertility and Y chromosome deletions: role of the AZF-candidate genes DAZ, RBM, DFFRY. Hum Reprod 1999, 14:1710–1716.PubMedCrossRefGoogle Scholar
  44. 44.
    Moro E, Marin P, Rossi A, et al.: Y chromosome microdeletions in infertile men with varicocele. Mol Cell Endocrinol 2000, 161:67–71. Association of genetic infertility in men with severe defects in spermatogenesis and varicoceles.PubMedCrossRefGoogle Scholar
  45. 45.
    Reijo R, Alagappan R, Patrizio P: Severe oligospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet 1996, 347:1290–1293.PubMedCrossRefGoogle Scholar
  46. 46.
    Reijo R, Lee T, Salo P: Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 1995, 10:383–393.PubMedCrossRefGoogle Scholar
  47. 47.
    Kim E, Leibman B, Grinblat D, Lipshultz L: Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure. J Urol 1999, 162:737–740. Varicocelectomy benefits even men with severe oligospermia and azoospermia.PubMedCrossRefGoogle Scholar
  48. 48.
    Mathews G, Mathews E, Goldstein M: Induction of spermato-genesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe asthenospermia. Fertil Steril 1998, 70:71–75.CrossRefGoogle Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • Richard A. Schoor
    • 1
  • Samir M. Elhanbly
    • 1
  • Craig S. Niederberger
    • 1
  1. 1.Department of Urology/Andrology, Division of AndrologyUniversity of Illinois at ChicagoChicagoUSA

Personalised recommendations