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The pathophysiology of varicocele-associated male infertility

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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.

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References and Recommended Reading

  1. Alcalay J, Kedem R: The ethnic distribution of varicocele. Mil Med 1986, 151:327–328.

    PubMed  CAS  Google Scholar 

  2. Jarow J, Coburn M, Sigman M: Incidence of varicoceles in men with primary and secondary infertility. Urol 1996, 47:73–76.

    Article  PubMed  CAS  Google Scholar 

  3. Kursh E: What is the incidence of varicocele in a fertile population. Fertil Steril 1987, 48:510–511.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. Greenberg S: Varicocele and male infertility. Fertil Steril 1977, 28:699.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  8. Holland K, Brill R, Chang R, et al.: Physiological and behav-ioural thermoregulation in bigeye tuna (Thunnus obesus). Nature 1992, 358:410–412.

    Article  PubMed  CAS  Google Scholar 

  9. Schmidt-Nielsen K: Countercurrent systems in animals. Sci Am 1981, 244:118–128.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  16. Kay R, Alexander N, Baugham WL: Induced varicoceles in Rhesus monkeys. Fertil Steril 1979, 31:195–199.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  18. Mieusset R, Grandjean H, Mansat A, Pontonnier F: Inhibiting effect of artificial cryptorchidism on spermatogenesis. Fertil Steril 1985, 43:589–594.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  29. Wilson R, Griswold M: Secreted proteins from rat Sertoli cells. Exp Cell Res 1979, 123:127–135.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  38. Beckman J, Crow J: Pathological implications of nitric oxide, superoxide and peroxynitrite formation. Biochem Soc Trans 1993, 21:330–334.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  41. Barbieri E, Hidalgo M, Venegas A, et al.: Varicocele-associated decrease in antioxidant defenses. J Androl 1999, 20:713–717.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  45. Reijo R, Alagappan R, Patrizio P: Severe oligospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet 1996, 347:1290–1293.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Urology/Andrology, Division of Andrology, University of Illinois at Chicago, 840 South Wood Street, M/C 955, 60612-7316, Chicago, IL, USA

    Richard A. Schoor MD, Samir M. Elhanbly & Craig S. Niederberger MD

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  1. Richard A. Schoor MD
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  2. Samir M. Elhanbly
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  3. Craig S. Niederberger MD
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Schoor, R.A., Elhanbly, S.M. & Niederberger, C.S. The pathophysiology of varicocele-associated male infertility. Curr Urol Rep 2, 432–436 (2001). https://doi.org/10.1007/s11934-001-0035-7

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