Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Varicocele and male infertility

Key Points

  • Varicoceles have detrimental effects on semen quality, sperm function, and pregnancy outcomes in some men

  • Oxidative stress seems to have a central role in the pathogenesis of varicocele-induced infertility

  • Current evidence supports beneficial effects of varicocelectomy on semen parameters, sperm function, and pregnancy outcomes in men from couples with documented infertility with clinical varicoceles and affected semen parameters

  • The optimal technique for performing varicocelectomy is a microsurgical approach, owing to reduced complication rates and increased pregnancy rates compared with other techniques

  • Current evidence supports varicocele repair in adolescents with clinical varicoceles when progressive testicular growth retardation and/or impaired semen quality is observed

  • Varicocelectomy might have beneficial effects on pregnancy outcomes following assisted reproduction>


The link between varicoceles and male infertility has been a matter of debate for more than half a century. Varicocele is considered the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention. In addition, improvements in semen quality after varicocelectomy do not always result in spontaneous pregnancy. Studies regarding possible pathophysiological mechanisms behind varicocele-induced infertility have tried to address these controversies. Oxidative stress seems to be a central mechanism; however, no single theory is able to explain the differential effect of varicoceles on infertility. As a consequence, careful patient selection for treatment based on couple fertility status, varicocele grade, and semen quality is critical for achieving a chance of a subsequent pregnancy. A substantial amount of data on the effects of varicocelectomy has been gathered, but inadequate study design and considerable heterogeneity of available studies mean that these data are rarely conclusive. Current evidence suggests a beneficial effect of varicocelectomy on semen quality and pregnancy outcomes in couples with documented infertility only if the male partner has a clinically palpable varicocele and affected semen parameters.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Anatomy of the venous drainage from the testes.
Figure 2: The central role of oxidative stress in the pathophysiology of varicocele induced male infertility.
Figure 3: Treatment algorithm for adult infertile men with varicoceles.


  1. 1

    Dubin, L. & Amelar, R. D. Etiologic factors in 1294 consecutive cases of male infertility. Fertil. Steril. 22, 469–474 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. 2

    Damsgaard, J. et al. Varicocele is associated with impaired semen quality and reproductive hormone levels: a study of 7035 healthy young men from six European countries. Eur. Urol. 70, 1019–1029 (2016).

    Article  CAS  PubMed  Google Scholar 

  3. 3

    [No authors listed.] The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization. Fertil. Steril. 57, 1289–1293 (1992).

  4. 4

    Wang, Y. J., Zhang, R. Q., Lin, Y. J., Zhang, R. G. & Zhang, W. L. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod. Biomed. Online 25, 307–314 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. 5

    Vigil, P., Wohler, C., Bustos-Obregon, E., Comhaire, F. & Morales, P. Assessment of sperm function in fertile and infertile men. Andrologia 26, 55–60 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. 6

    Abdelrahim, F. et al. Testicular morphology and function in varicocele patients: pre-operative and post-operative histopathology. Br. J. Urol. 72, 643–647 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. 7

    Dubin, L. & Hotchkiss, R. S. Testis biopsy in subfertile men with varicocele. Fertil. Steril. 20, 51–57 (1969).

    Article  CAS  PubMed  Google Scholar 

  8. 8

    Etriby, A., Girgis, S. M., Hefnawy, H. & Ibrahim, A. A. Testicular changes in subfertile males with varicocele. Fertil. Steril. 18, 666–671 (1967).

    Article  CAS  PubMed  Google Scholar 

  9. 9

    Cayan, S. et al. The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele. BJU Int. 84, 1046–1049 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. 10

    Agarwal, A., Hamada, A. & Esteves, S. C. Insight into oxidative stress in varicocele-associated male infertility: part 1. Nat. Rev. Urol. 9, 678–690 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. 11

    Tulloch, W. S. Consideration of sterility; subfertility in the male. Edinb. Med. J. 59, 29–34 (1952).

    CAS  Google Scholar 

  12. 12

    Gorelick, J. I. & Goldstein, M. Loss of fertility in men with varicocele. Fertil. Steril. 59, 613–616 (1993).

    Article  CAS  PubMed  Google Scholar 

  13. 13

    Jarow, J. P., Coburn, M. & Sigman, M. Incidence of varicoceles in men with primary and secondary infertility. Urology 47, 73–76 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. 14

    Akbay, E., Cayan, S., Doruk, E., Duce, M. N. & Bozlu, M. The prevalence of varicocele and varicocele-related testicular atrophy in Turkish children and adolescents. BJU Int. 86, 490–493 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. 15

    Saypol, D. C. Varicocele. J. Androl. 2, 61–71 (1981).

    Article  Google Scholar 

  16. 16

    de Castro, M. P. & Mastrorocco, D. A. Reproductive history and semen analysis in prevasectomy fertile men with and without varicocele. J. Androl 5, 17–20 (1984).

    Article  CAS  PubMed  Google Scholar 

  17. 17

    Hamada, A., Esteves, S. C. & Agarwal, A. Varicocele and Male Infertility: Current Concepts, Controversies and Consensus (Springer International Publishing, 2016).

    Book  Google Scholar 

  18. 18

    Naughton, C. K., Nangia, A. K. & Agarwal, A. Pathophysiology of varicoceles in male infertility. Hum. Reprod. Update 7, 473–481 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. 19

    McClure, R. D. & Hricak, H. Scrotal ultrasound in the infertile man: detection of subclinical unilateral and bilateral varicoceles. J. Urol. 135, 711–715 (1986).

    Article  CAS  PubMed  Google Scholar 

  20. 20

    Gat, Y., Bachar, G. N., Zukerman, Z., Belenky, A. & Gornish, M. Varicocele: a bilateral disease. Fertil. Steril. 81, 424–429 (2004).

    Article  PubMed  Google Scholar 

  21. 21

    Gat, Y. et al. Right varicocele and hypoxia, crucial factors in male infertility: fluid mechanics analysis of the impaired testicular drainage system. Reprod. Biomed. Online 13, 510–515 (2006).

    Article  PubMed  Google Scholar 

  22. 22

    Agarwal, A., Prabakaran, S. & Allamaneni, S. S. Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod. Biomed. Online 12, 630–633 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Krzysciak, W. & Kozka, M. Generation of reactive oxygen species by a sufficient, insufficient and varicose vein wall. Acta Biochim. Pol. 58, 89–94 (2011).

    CAS  PubMed  Google Scholar 

  24. 24

    Allamaneni, S. S., Naughton, C. K., Sharma, R. K., Thomas, A. J. Jr & Agarwal, A. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil. Steril. 82, 1684–1686 (2004).

    Article  PubMed  Google Scholar 

  25. 25

    Hurtado de Catalfo, G. E., Ranieri-Casilla, A., Marra, F. A., de Alaniz, M. J. & Marra, C. A. Oxidative stress biomarkers and hormonal profile in human patients undergoing varicocelectomy. Int. J. Androl. 30, 519–530 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. 26

    Romeo, C. & Santoro, G. Free radicals in adolescent varicocele testis. Oxid. Med. Cell. Longev. 2014, 912878 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27

    Cho, C. L., Esteves, S. C. & Agarwal, A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J. Androl. 18, 186–193 (2016).

    Article  CAS  PubMed  Google Scholar 

  28. 28

    Masson, P. & Brannigan, R. E. The varicocele. Urol. Clin. North Am. 41, 129–144 (2014).

    Article  PubMed  Google Scholar 

  29. 29

    Pastuszak, A. W. & Wang, R. Varicocele and testicular function. Asian J. Androl. 17, 659–667 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30

    Bonde, J. P. et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352, 1172–1177 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. 31

    Baazeem, A. et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur. Urol. 60, 796–808 (2011).

    Article  PubMed  Google Scholar 

  32. 32

    Agarwal, A. et al. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology 70, 532–538 (2007).

    Article  PubMed  Google Scholar 

  33. 33

    Breznik, R., Vlaisavljevic, V. & Borko, E. Treatment of varicocele and male fertility. Arch. Androl. 30, 157–160 (1993).

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Mansour Ghanaie, M. et al. Effects of varicocele repair on spontaneous first trimester miscarriage: a randomized clinical trial. Urol. J. 9, 505–513 (2012).

    PubMed  Google Scholar 

  35. 35

    Abdel-Meguid, T. A., Al-Sayyad, A., Tayib, A. & Farsi, H. M. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. Eur. Urol. 59, 455–461 (2011).

    Article  PubMed  Google Scholar 

  36. 36

    Sakamoto, Y., Ishikawa, T., Kondo, Y., Yamaguchi, K. & Fujisawa, M. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 101, 1547–1552 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. 37

    Chen, S. S., Huang, W. J., Chang, L. S. & Wei, Y. H. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J. Urol. 179, 639–642 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Smit, M. et al. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J. Urol. 189, S146–S150 (2013).

    Article  PubMed  Google Scholar 

  39. 39

    Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing: a guideline. Fertil. Steril. 99, 673–677 (2013).

  40. 40

    Nieschlag, E., Hertle, L., Fischedick, A., Abshagen, K. & Behre, H. M. Update on treatment of varicocele: counselling as effective as occlusion of the vena spermatica. Hum. Reprod. 13, 2147–2150 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. 41

    Evers, J. L., Collins, J. A. & Vandekerckhove, P. Surgery or embolisation for varicocele in subfertile men. Cochrane Database Syst. Rev. 1, CD000479 (2001).

    Google Scholar 

  42. 42

    Evers, J. L. & Collins, J. A. Surgery or embolisation for varicocele in subfertile men. Cochrane Database Syst. Rev. 3, CD000479 (2004).

    Google Scholar 

  43. 43

    Evers, J. H., Collins, J. & Clarke, J. Surgery or embolisation for varicoceles in subfertile men. Cochrane Database Syst. Rev. 3, CD000479 (2008).

    Google Scholar 

  44. 44

    Kroese, A. C., de Lange, N. M., Collins, J. & Evers, J. L. Surgery or embolization for varicoceles in subfertile men. Cochrane Database Syst. Rev. 10, CD000479 (2012).

    PubMed  Google Scholar 

  45. 45

    Marmar, J. L. et al. Reassessing the value of varicocelectomy as a treatment for male subfertility with a new meta-analysis. Fertil. Steril. 88, 639–648 (2007).

    Article  PubMed  Google Scholar 

  46. 46

    Resorlu, B., Kara, C., Sahin, E. & Unsal, A. The significance of age on success of surgery for patients with varicocele. Int. Urol. Nephrol. 42, 351–356 (2010).

    Article  PubMed  Google Scholar 

  47. 47

    Tanrikut, C. et al. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU Int. 108, 1480–1484 (2011).

    Article  CAS  PubMed  Google Scholar 

  48. 48

    Dabaja, A. A. & Goldstein, M. When is a varicocele repair indicated: the dilemma of hypogonadism and erectile dysfunction? Asian J. Androl. 18, 213–216 (2016).

    Article  PubMed  Google Scholar 

  49. 49

    Benoff, S., Marmar, J. L. & Hurley, I. R. Molecular and other predictors for infertility in patients with varicoceles. Front. Biosci. (Landmark Ed.) 14, 3641–3672 (2009).

    CAS  Google Scholar 

  50. 50

    Chehval, M. J. & Purcell, M. H. Deterioration of semen parameters over time in men with untreated varicocele: evidence of progressive testicular damage. Fertil. Steril. 57, 174–177 (1992).

    Article  CAS  PubMed  Google Scholar 

  51. 51

    Lund, L. & Larsen, S. B. A follow-up study of semen quality and fertility in men with varicocele testis and in control subjects. Br. J. Urol. 82, 682–686 (1998).

    Article  CAS  PubMed  Google Scholar 

  52. 52

    Dhabuwala, C. B., Hamid, S. & Moghissi, K. S. Clinical versus subclinical varicocele: improvement in fertility after varicocelectomy. Fertil. Steril. 57, 854–857 (1992).

    Article  CAS  PubMed  Google Scholar 

  53. 53

    Yamamoto, M., Hibi, H., Hirata, Y., Miyake, K. & Ishigaki, T. Effect of varicocelectomy on sperm parameters and pregnancy rate in patients with subclinical varicocele: a randomized prospective controlled study. J. Urol. 155, 1636–1638 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. 54

    Grasso, M. et al. Low-grade left varicocele in patients over 30 years old:the effect of spermatic vein ligation on fertility. BJU Int. 85, 305–307 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. 55

    Kim, H. J. et al. Clinical significance of subclinical varicocelectomy in male infertility: systematic review and meta-analysis. Andrologia 48, 654–661 (2016).

    Article  CAS  PubMed  Google Scholar 

  56. 56

    Jungwirth, A. et al. EAU Guidelines on Male Infertility (European Association of Urology, 2016).

    Google Scholar 

  57. 57

    Esteves, S. C., Miyaoka, R., Roque, M. & Agarwal, A. Outcome of varicocele repair in men with nonobstructive azoospermia: systematic review and meta-analysis. Asian J. Androl. 18, 246–253 (2016).

    Article  PubMed  Google Scholar 

  58. 58

    Mori, M. M., Bertolla, R. P., Fraietta, R., Ortiz, V. & Cedenho, A. P. Does varicocele grade determine extent of alteration to spermatogenesis in adolescents? Fertil. Steril. 90, 1769–1773 (2008).

    Article  PubMed  Google Scholar 

  59. 59

    Bong, G. W. & Koo, H. P. The adolescent varicocele: to treat or not to treat. Urol. Clin. North Am. 31, 509–515 (2004).

    Article  PubMed  Google Scholar 

  60. 60

    Laven, J. S. et al. Effects of varicocele treatment in adolescents: a randomized study. Fertil. Steril. 58, 756–762 (1992).

    Article  CAS  PubMed  Google Scholar 

  61. 61

    Li, F. et al. Effect of varicocelectomy on testicular volume in children and adolescents: a meta-analysis. Urology 79, 1340–1345 (2012).

    Article  PubMed  Google Scholar 

  62. 62

    Kolon, T. F. et al. Transient asynchronous testicular growth in adolescent males with a varicocele. J. Urol. 180, 1111–1114 (2008).

    Article  PubMed  Google Scholar 

  63. 63

    Chu, D. I. et al. The natural history of semen parameters in untreated asymptomatic adolescent varicocele patients: a retrospective cohort study. J. Pediatr. Urol. 13, 77.e1–77.e5 (2017).

    Article  Google Scholar 

  64. 64

    Cayan, S., Shavakhabov, S. & Kadioglu, A. Treatment of palpable varicocele in infertile men: a meta-analysis to define the best technique. J. Androl. 30, 33–40 (2009).

    Article  PubMed  Google Scholar 

  65. 65

    Ding, H. et al. Open non-microsurgical, laparoscopic or open microsurgical varicocelectomy for male infertility: a meta-analysis of randomized controlled trials. BJU Int. 110, 1536–1542 (2012).

    Article  PubMed  Google Scholar 

  66. 66

    Palomo, A. Radical cure of varicocele by a new technique; preliminary report. J. Urol. 61, 604–607 (1949).

    Article  CAS  PubMed  Google Scholar 

  67. 67

    Ivanissevich, O. Left varicocele due to reflux; experience with 4,470 operative cases in forty-two years. J. Int. Coll. Surg. 34, 742–755 (1960).

    CAS  PubMed  Google Scholar 

  68. 68

    Will, M. A. et al. The great debate: varicocele treatment and impact on fertility. Fertil. Steril. 95, 841–852 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  69. 69

    Crestani, A. et al. Antegrade scrotal sclerotherapy of internal spermatic veins for varicocele treatment: technique, complications, and results. Asian J. Androl. 18, 292–295 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  70. 70

    Sautter, T., Sulser, T., Suter, S., Gretener, H. & Hauri, D. Treatment of varicocele: a prospective randomized comparison of laparoscopy versus antegrade sclerotherapy. Eur. Urol. 41, 398–400 (2002).

    Article  CAS  PubMed  Google Scholar 

  71. 71

    Yavetz, H. et al. Efficacy of varicocele embolization versus ligation of the left internal spermatic vein for improvement of sperm quality. Int. J. Androl. 15, 338–344 (1992).

    Article  CAS  PubMed  Google Scholar 

  72. 72

    Scherr, D. & Goldstein, M. Comparison of bilateral versus unilateral varicocelectomy in men with palpable bilateral varicoceles. J. Urol. 162, 85–88 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. 73

    Elbendary, M. A. & Elbadry, A. M. Right subclinical varicocele: how to manage in infertile patients with clinical left varicocele? Fertil. Steril. 92, 2050–2053 (2009).

    Article  PubMed  Google Scholar 

  74. 74

    Zheng, Y. Q. et al. Efficacy of bilateral and left varicocelectomy in infertile men with left clinical and right subclinical varicoceles: a comparative study. Urology 73, 1236–1240 (2009).

    Article  PubMed  Google Scholar 

  75. 75

    Kirby, E. W., Wiener, L. E., Rajanahally, S., Crowell, K. & Coward, R. M. Undergoing varicocele repair before assisted reproduction improves pregnancy rate and live birth rate in azoospermic and oligospermic men with a varicocele: a systematic review and meta-analysis. Fertil. Steril. 106, 1338–1343 (2016).

    Article  PubMed  Google Scholar 

  76. 76

    Esteves, S. C., Roque, M. & Agarwal, A. Outcome of assisted reproductive technology in men with treated and untreated varicocele: systematic review and meta-analysis. Asian J. Androl. 18, 254–258 (2016).

    Article  PubMed  Google Scholar 

  77. 77

    Miersch, W. D., Schoeneich, G., Winter, P. & Buszello, H. Laparoscopic varicocelectomy: indication, technique and surgical results. Br. J. Urol. 76, 636–638 (1995).

    Article  CAS  PubMed  Google Scholar 

  78. 78

    Tan, S. M., Ng, F. C., Ravintharan, T., Lim, P. H. & Chng, H. C. Laparoscopic varicocelectomy: technique and results. Br. J. Urol. 75, 523–528 (1995).

    Article  CAS  PubMed  Google Scholar 

  79. 79

    Ross, L. S. & Ruppman, N. Varicocele vein ligation in 565 patients under local anesthesia: a long-term review of technique, results and complications in light of proposed management by laparoscopy. J. Urol. 149, 1361–1363 (1993).

    Article  CAS  PubMed  Google Scholar 

  80. 80

    Jungwirth, A. et al. Clinical outcome of microsurgical subinguinal varicocelectomy in infertile men. Andrologia 33, 71–74 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Kumar, R. & Gupta, N. P. Subinguinal microsurgical varicocelectomy: evaluation of the results. Urol. Int. 71, 368–372 (2003).

    Article  PubMed  Google Scholar 

  82. 82

    Lenk, S., Fahlenkamp, D., Gliech, V. & Lindeke, A. Comparison of different methods of treating varicocele. J. Androl. 15 (Suppl.), 34S–37S (1994).

    PubMed  Google Scholar 

Download references

Author information




C. F. S. J. researched data for the article and wrote the manuscript. M. F. and C. F. S. J. made substantial contributions to discussion of content. All authors reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Mikkel Fode.

Ethics declarations

Competing interests

J.M.D. receives grant funding from Blue Cross Blue Shield of Michigan for his role in the Michigan Value Collaborative and Michigan Urological Surgery Improvement Collaborative and owns common stock in Lipocine. D.A.O is a consultant for Coloplast and Pfizer and receives research funding from Endo. J.S. is a consultant for Astellas, Neotract, and Pfizer, and is a shareholder of Multicept. M.F. is a consultant and speaker for Astellas. C.F.S.J and P.B.Ø. declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Jensen, C., Østergren, P., Dupree, J. et al. Varicocele and male infertility. Nat Rev Urol 14, 523–533 (2017).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing