[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Journal Information::
Indexing Sources::
Editorial Board::
Executive Members::
Articles Archive::
Instruction to Authors::
Contact Us::
Site Facilities::
Search in website

Advanced Search
Receive site information
Enter your Email in the following box to receive the site news and information.
:: Volume 21, Issue 3 (10-2019) ::
J Gorgan Univ Med Sci 2019, 21(3): 1-12 Back to browse issues page
Prevalence, etiology, testicular function and clinic outcome before and after varicocelectomy: A systematic review
Maryam Mirchenari1 , Behzad Abbasi2 , Marziyeh Tavalaee * 3, Leila Azadi1 , Mohammad-Hossein Nasr- Esfahani4
1- M.Sc in Physiology, Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
2- Medicine Faculty, Isfahan University of Medical Sciences, Isfahan, Iran
3- Assistant Professor, Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran , tavalaee.m@royaninstitute.org
4- Professor, Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Isfahan Fertility and Infertility Center, Isfahan, Iran
Abstract:   (6675 Views)

Varicocele is a deficiency of the testicular veins which is recognized by elongation and tortuosity of the pampiniform or cremasteric venous plexus and can lead to impaired spermatogenesis. Varicocele intensity is associated with the reduction of male fertility potential. This review article discusses the effects of varicocele on spermatogenesis process and fertility potential, etiology of varicocele, therapeutic approaches, and the result of treatment. All the published papers from 1975 to 2018 from databases bank such as Science Direct, Google Scholar, Scopus, and PubMed with keywords; infertility, varicocele, varicocelectomy, spermatogenesis, clinical outcome were collected and within these papers, only 74 papers were included for this study. Increased of testicular temperature, backflow of toxic metabolites from the kidney or adrenal glands, hypoxia, hormonal disturbances and oxidative stress are the most prevalent pathogenic cause of varicocele that they can alter testis and sperm functions. Several studies show that varicocelectomy can improve sperm parameters, chromatin statue and fertility potential in infertile men with varicocele. Possibly, treatment of varicocele before assisted reproduction technologies could increase the chance of spontaneous pregnancy in these infertile men.

Keywords: Testis, Infertility, Varicocele, Varicocelectomy, Spermatogenesis
Full-Text [PDF 337 kb]   (9794 Downloads)    
Type of Study: Review Article | Subject: Urology
1. Lundy SD, Sabanegh ES Jr. Varicocele management for infertility and pain: A systematic review. Arab J Urol. 2017 Dec; 16(1): 157-70. doi: 10.1016/j.aju.2017.11.003
2. Levinger U, Gornish M, Gat Y, Bachar GN. Is varicocele prevalence increasing with age? Andrologia. 2007 Jun; 39(3):77-80. doi: 10.1111/j.1439-0272.2007.00766.x
3. Serefoglu EC, Saitz TR, La Nasa JA Jr, Hellstrom WJ. Adolescent varicocoele management controversies. Andrology. 2013 Jan; 1(1): 109-15. doi: 10.1111/j.2047-2927.2012.00004.x
4. World Health Organization. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril. 1992 Jun; 57(6): 1289-93.
5. Turner TT. The study of varicocele through the use of animal models. Hum Reprod Update. 2001 Jan-Feb; (1): 78-84. doi: 10.1093/humupd/7.1.78
6. Sofikitis N, Dritsas K, Miyagawa I, Koutselinis A. Anatomical characteristics of the left testicular venous system in man. Arch Androl. 1993 Mar-Apr; 30(2): 79-85.
7. Hsiung R, Nieva H, Clavert A. Scrotal hyperthermia and varicocele. Adv Exp Med Biol. 1991; 286: 241-44. doi: 10.1007/978-1-4684-5913-5_27
8. Afiyani AA, Deemeh MR, Tavalaee M, Razi M, Bahadorani M, Shokrollahi B, et al. Evaluation of heat-shock protein A2 (HSPA2) in male rats before and after varicocele induction. Mol Reprod Dev. 2014 Aug; 81(8): 766-76. doi: 10.1002/mrd.22345
9. Navaeian-Kalat E, Tavalaee M, Azadi L, Abbasi H, Deemeh MR, Arbabian M, et al. [Known pathophysiological mechanisms in the incidence of varicoceles]. J Shahrekord Univ Med Sci. 2016; 18(1): 122-40. [Article in Persian]
10. Nasr Esfahani MH, Abbasi H, Mirhosseini Z, Ghasemi N, Razavi Sh, Tavalaee M, et al. Can altered expression of HSPA2 in varicocele patients lead to abnormal spermatogenesis? International Journal of Fertility and Sterility. 2010; 4(3): 104-13.
11. Afshar K, Domes T. Varicocele. Can Urol Assoc J. 2018 Apr; 12 (4 Suppl 1): S34-S36. doi: 10.5489/cuaj.5231
12. Rajfer J, Turner TT, Rivera F, Howards SS, Sikka SC. Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats. Biol Reprod. 1987 May; 36(4): 933-37. doi: 10.1095/biolreprod36.4.933
13. Sofikitis N, Stavrou S, Skouros S, Dimitriadis F, Tsounapi P, Takenaka A. Mysteries, Facts, and Fiction in Varicocele Pathophysiology and Treatment. European Association of Urology. 2014 Nov; 13(4): 89-99. https://doi.org/10.1016/j.eursup.2014.07.002
14. Wright EJ, Young GP, Goldstein M. Reduction in testicular temperature after varicocelectomy in infertile men. Urology. 1997 Aug; 50: 257-9.
15. Gat Y, Zukerman Z, Chakraborty J, Gornish M. Varicocele, hypoxia and male infertility. Fluid Mechanics analysis of the impaired testicular venous drainage system. Hum Reprod. 2005 Sep; 20(9): 2614-19. doi: 10.1093/humrep/dei089
16. Ito H, Fuse H, Minagawa H, Kawamura K, Murakami M, Shimazaki J. Internal spermatic vein prostaglandins in varicocele patients. Fertil Steril. 1982 Feb; 37(2): 218-22.
17. Sofikitis N, Miyagawa I. Left adrenalectomy in varicocelized rats does not inhibit the development of varicocele-related physiologic alterations. Int J Fertil Menopausal Stud. 1993 Jul-Aug; 38(4): 250-55.
18. Reyes JG, Farias JG, Henríquez-Olavarrieta S, Madrid E, Parraga M, Zepeda AB, et al. The hypoxic testicle: physiology and pathophysiology. Oxid Med Cell Longev. 2012; 2012: 929285. doi: 10.1155/2012/929285
19. Kilinç F, Kayaselcuk F, Aygun C, Guvel S, Egilmez T, Ozkardes H. Experimental varicocele induces hypoxia inducible factor-1alpha, vascular endothelial growth factor expression and angiogenesis in the rat testis. J Urol. 2004 Sep; 172(3): 1188-91. doi: 10.1097/01.ju.0000135455.97627.15
20. Hsu HS, Chang LS, Chen MT, Wei YH. Decreased blood flow and defective energy metabolism in the varicocele-bearing testicles of rats. Eur Urol. 1994; 25(1): 71-75.
21. Wang H, Sun Y, Wang L, Xu C, Yang Q, Liu B, et al. Hypoxia-induced apoptosis in the bilateral testes of rats with left-sided varicocele: a new way to think about the varicocele. J Androl. 2010 May-Jun; 31(3): 299-305. doi: 10.2164/jandrol.108.007153
22. Hayden RP, Tanrikut C. Testosterone and Varicocele. Urol Clin North Am. 2016 May; 43(2): 223-32. doi: 10.1016/j.ucl.2016.01.009
23. Li F, Yue H, Yamaguchi K, Okada K, Matsushita K, Ando M, et al. Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis. Int J Urol. 2012 Feb; 19(2): 149-54. doi: 10.1111/j.1442-2042.2011.02890.x
24. Fisch H, Hyun G. Varicocele repair for low testosterone. Curr Opin Urol. 2012 Nov; 22(6): 495-98. doi: 10.1097/MOU.0b013e328358e0fb
25. Sathya Srini V, Belur Veerachari S. Does varicocelectomy improve gonadal function in men with hypogonadism and infertility? Analysis of a prospective study. Int J Endocrinol. 2011; 2011: 916380. http://dx.doi.org/10.1155/2011/916380
26. Su LM, Goldstein M, Schlegel PN. The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles. J Urol. 1995 Nov; 154(5): 1752-55.
27. Jeng SY, Wu SM, Lee JD. Cadmium accumulation and metallothionein overexpression in internal spermatic vein of patients with varicocele. Urology. 2009 Nov; 73(6): 1231-35. doi: 10.1016/j.urology.2009.01.008
28. Benoff SH, Millan C, Hurley IR, Napolitano B, Marmar JL. Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele. Hum Reprod. 2004 Mar; 19(3): 616-27. doi: 10.1093/humrep/deh139
29. Benoff S, Hurley IR, Barcia M, Mandel FS, Cooper GW, Hershlag A. A potential role for cadmium in the etiology of varicocele-associated infertility. Fertil Steril. 1997 Feb; 67(2): 336-47. doi: 10.1016/S0015-0282(97)81921-8
30. Marmar JL. The pathophysiology of varicoceles in the light of current molecular and genetic information. Hum Reprod Update. 2001 Sep-Oct; 7(5): 461-72. doi: 10.1093/humupd/7.5.461
31. Naughton CK, Nangia AK, Agarwal A. Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001 Sep-Oct; 7(5): 473-81. doi: 10.1093/humupd/7.5.473
32. Hurt GS, Howards SS, Turner TT. The effects of unilateral, experimental varicocele are not mediated through the ipsilateral testis. J Androl. 1987 Nov-Dec; 8(6): 403-408.
33. Sofikitis N, Takahashi C, Nakamura I, Hirakawa S, Miyagawa I. Surgical repair of secondary right varicocele in rats with primary left varicocele: effects on fertility, testicular temperature, spermatogenesis, and sperm maturation. Arch Androl. 1992 Jan-Feb; 28: 43-52.
34. Oztürk H, Tander B, Aydin A, Okumus Z, Cetinkursun S. The effects of chemical sympathectomy on testicular injury in varicocele. BJU Int. 2001 Feb; 87(3): 232-34.
35. Agarwal A, Sharma RK, Desai NR, Prabakaran S, Tavares A, Sabanegh E. Role of oxidative stress in pathogenesis of varicocele and infertility. Urology. 2009 Mar; 73(3): 461-69. doi: 10.1016/j.urology.2008.07.053
36. Aitken RJ, Baker MA. Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development. Int J Dev Biol. 2013; 57(2-4): 265-72. doi: 10.1387/ijdb.130146ja
37. Bahreinian M, Tavalaee M, Abbasi H, Kiani-Esfahani A, Shiravi AH, Nasr-Esfahani MH. DNA hypomethylation predisposes sperm to DNA damage in individuals with varicocele. Syst Biol Reprod Med. 2015; 61(4): 179-86. doi: 10.3109/19396368.2015.1020116
38. Nasr-Esfahani MH, Abasi H, Razavi S, Ashrafi S, Tavalaee M. Varicocelectomy: semen parameters and protamine deficiency. Int J Androl. 2009 Apr; 32(2): 115-22. doi: 10.1111/j.1365-2605.2007.00822.x
39. Nasr Esfahani MH, Tavalaee M. Origin and role of DNA damage in varicocele. Int J Fertil Steril. 2012 Oct; 6(3): 141-46.
40. Mohammadi P, Hassani-Bafrani H, Tavalaee M, Dattilo M, Nasr-Esfahani MH. One-carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats. BJU Int. 2018 Sep; 122(3): 480-89. doi: 10.1111/bju.14385
41. Azadi L, Abbasi H, Deemeh MR, Tavalaee M, Arbabian M, Pilevarian AA, et al. Zaditen (Ketotifen), as mast cell blocker, improves sperm quality, chromatin integrity and pregnancy rate after varicocelectomy. Int J Androl. 2011 Oct; 34(5 Pt 1): 446-52. doi: 10.1111/j.1365-2605.2010.01112.x
42. Barekat F, Tavalaee M, Deemeh MR, Bahreinian M, Azadi L, Abbasi H, et al. A Preliminary Study: N-acetyl-L-cysteine Improves Semen Quality following Varicocelectomy. Int J Fertil Steril. 2016 Apr-Jun; 10(1): 120-26. doi: 10.22074/ijfs.2016.4777
43. Tavalaee M, Abbasi H, Deemeh MR, Fotohi F, Sadoughi Gilani MA, Nasr Esfahani MH. Semen parameters and chromatin packaging in microsurgical varicocelectomy patients. Int J Fertil Steril. 2012 Oct-Dec; 6(3): 165-74.
44. Tavalaee M, Bahreinian M, Barekat F, Abbasi H, Nasr-Esfahani MH. Effect of varicocelectomy on sperm functional characteristics and DNA methylation. Andrologia. 2015 Oct; 47(8): 904-909. doi: 10.1111/and.12345
45. Bonyadi MR, Madaen SK, Saghafi M. Effects of Varicocelectomy on Anti-sperm Antibody in Patients with Varicocele. J Reprod Infertil. 2013 Apr; 14(2): 73-78.
46. Sofikitis N, Miyagawa I. Effects of surgical repair of experimental left varicocele on testicular temperature, spermatogenesis, sperm maturation, endocrine function, and fertility in rabbits. Arch Androl. 1992 Sep-Oct; 29(2): 163-75.
47. Harrison RM, Smith SD, Roberts JA. Testicular temperatures measured by thermistor probe and contact thermography. Fertil Steril. 1990 Jul; 54: 173-74.
48. Breznik R, Vlaisavljević V, Borko E. Treatment of varicocele and male fertility. Arch Androl. 1993 May-Jun; 30(3): 157-60.
49. Giagulli VA, Carbone MD. Varicocele correction for infertility: which patients to treat? Int J Androl. 2011 Jun; 34(3): 236-41. doi: 10.1111/j.1365-2605.2010.01081.x
50. Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, Salonia A, et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol. 2011Oct; 60(4): 796-808. doi: 10.1016/j.eururo.2011.06.018
51. Choi WS, Kim SW. Current issues in varicocele management: a review. World J Mens Health. 2013 Apr; 31(1): 12-20. doi: 10.5534/wjmh.2013.31.1.12
52. Nasr Esfahani MH, Tavalaee M. [Varicocele and infertility from cellular and molecular aspect]. Tehran: Royan Institute. 2017. [Persian]
53. Cayan S, Shavakhabov S, Kadioğlu A. Treatment of palpable varicocele in infertile men: a meta-analysis to define the best technique. J Androl. 2009 Jan-Feb; 30(1): 33-40. doi: 10.2164/jandrol.108.005967
54. Zhang H, Li H, Hou Y, Jin J, Gu X, Zhang M, et al. Microscopic retroperitoneal varicocelectomy with artery and lymphatic sparing: An alternative treatment for varicocele in infertile men. Urology. 2015 Sep; 86(3): 511-15. doi: 10.1016/j.urology.2015.06.033
55. Glassberg KI, Poon SA, Gjertson CK, DeCastro GJ, Misseri R.. Laparoscopic lymphatic sparing varicocelectomy in adolescents. J Urol. 2008 Jul; 180(1): 326-30. doi: 10.1016/j.juro.2008.03.064
56. Johnson D, Sandlow J. Treatment of varicoceles: techniques and outcomes. Fertil Steril. 2017 Sep; 108(3): 378-84. doi: 10.1016/j.fertnstert.2017.07.020
57. Smith SJ, Sewall LE. Treating varicoceles with embolization. Endovascular Today. 2009 Apr; pp: 57-60.
58. Sivanathan C, Abernethy LJ. Retrograde embolisation of varicocele in the paediatric age group: a review of 10 years' practice. Ann R Coll Surg Engl. 2003 Jan; 85(1): 50-51.
59. Gat Y, Bachar GN, Everaert K, Levinger U, Gornish M. Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele. Hum Reprod. 2005 Apr; 20(4): 1013-17. doi: 10.1093/humrep/deh706
60. Matthews GJ, Matthews ED, Goldstein M. Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia. Fertil Steril. 1998 Jul; 70(1): 71-75.
61. Kadioglu A, Tefekli A, Cayan S, Kandirali E, Erdemir F, Tellaloglu S. Microsurgical inguinal varicocele repair in azoospermic men. Urology. 2001 Feb; 57(2): 328-33.
62. Giannakis D, Baltogiannis D, Tsoukanelis K, Loutradis D, Miyagawa I, Makrydimas G, et al. Role of testicular tissue telomerase assay for the prediction of the presence of testicular spermatozoa in azoospermic men with varicoceles, pre- and post-varicocelectomy. Andrologia. 2004 Jun; 36(3): 111-22. doi: 10.1111/j.1439-0272.2004.00615.x
63. Okuyama A, Fujisue H, Matsui T, Doi Y, Koh E, Kondoh N, et al. Preoperative parameters related to the improvement of semen characteristics after surgical repair of varicocele in subfertile men. Eur Urol. 1988; 14(6): 442-46.
64. Decastro GJ, Shabsigh A, Poon SA, Laor L, Glassberg KI. Adolescent varicocelectomy--is the potential for catch-up growth related to age and/or Tanner stage? J Urol. 2009 Jan; 181(1): 322-27. doi: 10.1016/j.juro.2008.09.037
65. Nilsson S, Edvinsson A, Nilsson B. Improvement of semen and pregnancy rate after ligation and division of the internal spermatic vein: fact or fiction? Br J Urol. 1979 Dec; 51(6): 591-96.
66. Gazzera C, Rampado O, Savio L, Di Bisceglie C, Manieri C, Gandini G. Radiological treatment of male varicocele: technical, clinical, seminal and dosimetric aspects. Radiol Med. 2006 Apr; 111(3): 449-58. doi: 10.1007/s11547-006-0041-4 [Article in English, Italian]
67. Kim KH, Lee JY, Kang DH, Lee H, Seo JT, Cho KS. Impact of surgical varicocele repair on pregnancy rate in subfertile men with clinical varicocele and impaired semen quality: a meta-analysis of randomized clinical trials. Korean J Urol. 2013 Oct; 54(10): 703-709. doi: 10.4111/kju.2013.54.10.703
68. Shiraishi K, Matsuyama H, Takihara H. Pathophysiology of varicocele in male infertility in the era of assisted reproductive technology. Int J Urol. 2012 Jun; 19(6): 538-50. doi: 10.1111/j.1442-2042.2012.02982.x
69. Kohn TP, Kohn JR, Pastuszak AW. Varicocelectomy before assisted reproductive technology: are outcomes improved? Fertil Steril. 2017 Sep; 108(3): 385-91. doi: 10.1016/j.fertnstert.2017.06.033
70. Garg H, Kumar R. An update on the role of medical treatment including antioxidant therapy in varicocele. Asian J Androl. 2016 Mar-Apr; 18(2): 222-28. doi: 10.4103/1008-682X.171657
71. Festa R, Giacchi E, Raimondo S, Tiano L, Zuccarelli P, Silvestrini A, et al. Coenzyme Q10 supplementation in infertile men with low-grade varicocele: an open, uncontrolled pilot study. Andrologia. 2014 Sep; 46(7): 805-807. doi: 10.1111/and.12152
72. Mićić S, Tulić C, Dotlić R. Kallikrein therapy of infertile men with varicocele and impaired sperm motility. Andrologia. 1990 Mar-Apr; 22(2): 179-83.
73. Cavallini G, Biagiotti G, Ferraretti AP, Gianaroli L, Vitali G. Medical therapy of oligoasthenospermia associated with left varicocele. BJU Int. 2003 Apr; 91(6): 513-18.
74. Mostafa RM, Abol-Magd R, Younis SE, Dessouki OF, Azab M, Mostafa T. Assessment of seminal mast cells in infertile men with varicocele after surgical repair. Andrologia. 2017 Apr; 49(3): e12625. doi: 10.1111/and.12625
Send email to the article author

XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mirchenari M, Abbasi B, Tavalaee M, Azadi L, Nasr- Esfahani M. Prevalence, etiology, testicular function and clinic outcome before and after varicocelectomy: A systematic review. J Gorgan Univ Med Sci 2019; 21 (3) :1-12
URL: http://goums.ac.ir/journal/article-1-3439-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 21, Issue 3 (10-2019) Back to browse issues page
مجله دانشگاه علوم پزشکی گرگان Journal of Gorgan University of Medical Sciences
Persian site map - English site map - Created in 0.05 seconds with 36 queries by YEKTAWEB 4657