Abstract
Varicocele is an abnormal condition characterized by dilatation of the pampiniform plexus veins draining the testis and is present in 15 % of men. Varicoceles have an adverse effect on spermatogenesis and are the most common cause of male infertility. Approximately 35 % of infertile men and more than 70 % of men with secondary infertility were reported to have varicoceles. Although data on methods of varicocele repair are accumulating, there remains controversy regarding the indications and techniques for varicocele repair. In addition, the role of varicocele repair in this era of assisted reproductive technologies continues to be debated. In this study, we performed a comprehensive PubMed search in order to review the current status of varicocele repair for male infertility. We reviewed English-language studies published from 1992 through 2013. After reviewing the articles, we identified a recent meta-analysis of four randomized controlled trials, which found that varicocele repair for oligozoospermic men was associated with better pregnancy rates as compared with observation. Our review of prospective studies showed that all semen parameters, including sperm concentration, motility, and progressive motility, were significantly improved after varicocele repair. We also summarize the findings of recent studies reporting beneficial effects of varicocele repair, i.e., decreased oxidative stress and sperm DNA fragmentation after varicocele repair and superior cost effectiveness versus in vitro fertilization/intracytoplasmic sperm injection alone, which may be important in the era of assisted reproductive technologies. Varicocele repair is a widespread, well-established procedure that can improve semen parameters in men with infertility. The effect of such treatment on the pregnancy rate is unclear because evidence is limited due to difficulties in recruiting patients for studies. Among the repair techniques, microsurgical repair using a subinguinal approach is potentially the best practice, although this procedure requires training in microsurgery. All these topics require further research in studies with sufficient patient enrollment and follow-up.
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References
World Health Organization. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization. Fertil Steril. 1992;57:1289–93.
Asci R, Sarikaya S, Buyukalpelli R, Yilmaz AF, Yildiz S. The effects of experimental varicocele on testicular histology and fertility in monorchic adult rats. BJU Int. 1999;83:493–7.
Takihara H, Sakatoku J, Cockett AT. The pathophysiology of varicocele in male infertility. Fertil Steril. 1991;55:861–8.
Naughton CK, Nangia AK, Agarwal A. Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001;7:473–81.
Jarow JP. Effects of varicocele on male fertility. Hum Reprod Update. 2001;7:59–64.
Moore RDaQ WJ. The scrotum as a temperature regulator for the r\testes. Am J Physiol. 1923;68:70–9.
Goldstein M, Eid JF. Elevation of intratesticular and scrotal skin surface temperature in men with varicocele. J Urol. 1989;142:743–5.
Agarwal A, Sharma RK, Desai NR, Prabakaran S, Tavares A, Sabanegh E. Role of oxidative stress in pathogenesis of varicocele and infertility. Urology. 2009;73:461–9.
Altunoluk B, Efe E, Kurutas EB, Gul AB, Atalay F, Eren M. Elevation of both reactive oxygen species and antioxidant enzymes in vein tissue of infertile men with varicocele. Urol Int. 2012;88:102–6.
Allamaneni SS, Naughton CK, Sharma RK, Thomas AJ Jr, Agarwal A. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil Steril. 2004;82:1684–6.
Pasqualotto FF, Sundaram A, Sharma RK, Borges E Jr, Pasqualotto EB, Agarwal A. Semen quality and oxidative stress scores in fertile and infertile patients with varicocele. Fertil Steril. 2008;89:602–7.
Agarwal A, Hamada A, Esteves SC. Insight into oxidative stress in varicocele-associated male infertility: part 1. Nat Rev Urol. 2012;9:678–90.
Abd-Elmoaty MA, Saleh R, Sharma R, Agarwal A. Increased levels of oxidants and reduced antioxidants in semen of infertile men with varicocele. Fertil Steril. 2010;94:1531–4.
Zalata AA, Ahmed AH, Allamaneni SS, Comhaire FH, Agarwal A. Relationship between acrosin activity of human spermatozoa and oxidative stress. Asian J Androl. 2004;6:313–8.
Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril. 1997;68:519–24.
Aitken RJ, Curry BJ. Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid Redox Signal. 2011;1(14):367–81.
Mostafa T, Anis TH, El-Nashar A, Imam H, Othman IA. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Int J Androl. 2001;24:261–5.
Chen SS, Huang WJ, Chang LS, Wei YH. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J Urol. 2008;179:639–42.
Ficarra V, Crestani A, Novara G, Mirone V. Varicocele repair for infertility: what is the evidence? Curr Opin Urol. 2012;22:489–94.
Cocuzza M, Athayde KS, Agarwal A, 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;90:1103–8.
Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril. 2010;1(93):1027–36.
La Vignera S, Condorelli R, Vicari E, D’Agata R, Calogero AE. Effects of varicocelectomy on sperm DNA fragmentation, mitochondrial function, chromatin condensation, and apoptosis. J Androl. 2012;33:389–96.
Smit M, Romijn JC, Wildhagen MF, Veldhoven JL, Weber RF, Dohle GR. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol. 2013;189:S146–50.
Zini A, Blumenfeld A, Libman J, Willis J. Beneficial effect of microsurgical varicocelectomy on human sperm DNA integrity. Hum Reprod. 2005;20:1018–21.
Bertolla RP, Cedenho AP, HassunFilho PA, Lima SB, Ortiz V, Srougi M. Sperm nuclear DNA fragmentation in adolescents with varicocele. Fertil Steril. 2006;85:625–8.
Turner TT, Lopez TJ. Effects of experimental varicocele require neither adrenal contribution nor venous reflux. J Urol. 1989;142:1372–5.
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;38:250–5.
Jungwirth A, Giwercman A, Tournaye H, et al. European Association of Urology guidelines on male infertility: the 2012 update. Eur Urol. 2012;62:324–32.
Lee J, Binsaleh S, Lo K, Jarvi K. Varicoceles: the diagnostic dilemma. J Androl. 2008;29:143–6.
Dhabuwala CB, Hamid S, Moghissi KS. Clinical versus subclinical varicocele: improvement in fertility after varicocelectomy. Fertil Steril. 1992;57:854–7.
Miyaoka R, Esteves SC. A critical appraisal on the role of varicocele in male infertility. Adv Urol. 2012;2012:597495.
Gat Y, Bachar GN, Zukerman Z, Belenky A, Gorenish M. Physical examination may miss the diagnosis of bilateral varicocele: a comparative study of 4 diagnostic modalities. J Urol. 2004;172:1414–7.
Trum JW, Gubler FM, Laan R, van der Veen F. The value of palpation, varicoscreen contact thermography and colour Doppler ultrasound in the diagnosis of varicocele. Hum Reprod. 1996;11:1232–5.
Jarow JP, Ogle SR, Eskew LA. Seminal improvement following repair of ultrasound detected subclinical varicoceles. J Urol. 1996;155:1287–90.
Rifkin MD, Foy PM, Kurtz AB, Pasto ME, Goldberg BB. The role of diagnostic ultrasonography in varicocele evaluation. J Ultrasound Med. 1983;2:271–5.
Pilatz A, Altinkilic B, Kohler E, Marconi M, Weidner W. Color Doppler ultrasound imaging in varicoceles: is the venous diameter sufficient for predicting clinical and subclinical varicocele? World J Urol. 2011;29:645–50.
Van Batavia JP, Badalato G, Fast A, Glassberg KI. Adolescent varicocele-is the 20/38 harbinger a durable predictor of testicular asymmetry? J Urol. 2013;189:1897–901.
Van Batavia JP, Woldu SL, Raimondi PM, et al. Adolescent varicocele: influence of Tanner stage at presentation on the presence, development, worsening and/or improvement of testicular hypotrophy without surgical intervention. J Urol. 2010;184:1727–32.
Diamond DA. Adolescent varicocele. Curr Opin Urol. 2007;17:263–7.
Misseri R, Gershbein AB, Horowitz M, Glassberg KI. The adolescent varicocele. II: the incidence of hydrocele and delayed recurrent varicocele after varicocelectomy in a long-term follow-up. BJU Int. 2001;87:494–8.
Glassberg KI. The adolescent varicocele: current issues. Curr Urol Rep. 2007;8:100–3.
Diamond DA. Adolescent varicocele: emerging understanding. BJU Int. 2003;92(Suppl 1):48–51.
Bong GW, Koo HP. The adolescent varicocele: to treat or not to treat. Urol Clin North Am. 2004;31:509–15 (ix).
Kumanov P, Robeva RN, Tomova A. Adolescent varicocele: who is at risk? Pediatrics. 2008;121:e53–7.
Jungwirth A, Giwercman A, Tournaye H, Diemer T, Kopa Z, Dohle G, Krausz C, European Association of Urology Working Group on Male Infertility. European Association of Urology guidelines on Male Infertility: the 2012 update. Eur Urol. 2012;62(2):324–32.
Diamond DA, Zurakowski D, Bauer SB, et al. Relationship of varicocele grade and testicular hypotrophy to semen parameters in adolescents. J Urol. 2007;178:1584–8.
Baazeem A, Belzile E, Ciampi A, et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol. 2011;60:796–808.
Hopps CV, Lemer ML, Schlegel PN, Goldstein M. Intraoperative varicocele anatomy: a microscopic study of the inguinal versus subinguinal approach. J Urol. 2003;170:2366–70.
Cayan S, Shavakhabov S, Kadioglu A. Treatment of palpable varicocele in infertile men: a meta-analysis to define the best technique. J Androl. 2009;30:33–40.
Diegidio P, Jhaveri JK, Ghannam S, Pinkhasov R, Shabsigh R, Fisch H. Review of current varicocelectomy techniques and their outcomes. BJU Int. 2011;108:1157–72.
Evers JL, Collins JA, Vandekerckhove P. Surgery or embolisation for varicocele in subfertile men. Cochrane Database Syst Rev. 2001;1:CD000479.
Evers JL, Collins JA. Assessment of efficacy of varicocele repair for male subfertility: a systematic review. Lancet. 2003;31(361):1849–52.
Marmar J. Male factor infertility: innovations in varicocele surgery. Nat Rev Urol. 2009;6:470–1.
Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. Eur Urol. 2011;59:455–61.
Smit M, Romijn JC, Wildhagen MF, Veldhoven JL, Weber RF, Dohle GR. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol. 2010;183:270–4.
Zini A, Azhar R, Baazeem A, Gabriel MS. Effect of microsurgical varicocelectomy on human sperm chromatin and DNA integrity: a prospective trial. Int J Androl. 2011;34:14–9.
Ozden C, Ozdal OL, Bulut S, Guzel O, Koyuncu HH, Memis A. Effect of varicocelectomy on serum inhibin B levels in infertile patients with varicocele. Scand J Urol Nephrol. 2008;42:441–3.
Zucchi A, Mearini E, Porena M, et al. Cytosolic calcium levels in spermatozoa are modulated differently in healthy subjects and patients with varicocele. Fertil Steril. 2006;85:144–8.
Colpi GM, Carmignani L, Nerva F, et al. Surgical treatment of varicocele by a subinguinal approach combined with antegrade intraoperative sclerotherapy of venous vessels. BJU Int. 2006;97:142–5.
Li F, Yamaguchi K, Okada K, et al. Significant improvement of sperm DNA quality after microsurgical repair of varicocele. Syst Biol Reprod Med. 2012;58:274–7.
Esteves SC, Oliveira FV, Bertolla RP. Clinical outcome of intracytoplasmic sperm injection in infertile men with treated and untreated clinical varicocele. J Urol. 2010;184:1442–6.
Pasqualotto FF, Braga DP, Figueira RC, Setti AS, Iaconelli A Jr, Borges E Jr. Varicocelectomy does not impact pregnancy outcomes following intracytoplasmic sperm injection procedures. J Androl. 2012;33:239–43.
Schlegel PN, Goldstein M. Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction. Fertil Steril. 2011;96:1288–93.
Ishikawa T, Kondo Y, Yamaguchi K, Sakamoto Y, Fujisawa M. Effect of varicocelectomy on patients with unobstructive azoospermia and severe oligospermia. BJU Int. 2008;101:216–8.
Cakan M, Altug U. Induction of spermatogenesis by inguinal varicocele repair in azoospermic men. Arch Androl. 2004;50:145–50.
Esteves SC, Glina S. Recovery of spermatogenesis after microsurgical subinguinal varicocele repair in azoospermic men based on testicular histology. Int Braz J Urol. 2005;31:541–8.
Youssef T, Abd-Elaal E, Gaballah G, Elhanbly S, Eldosoky E. Varicocelectomy in men with nonobstructive azoospermia: is it beneficial? Int J Surg. 2009;7:356–60.
Cocuzza M, Pagani R, Lopes RI, et al. Use of subinguinal incision for microsurgical testicular biopsy during varicocelectomy in men with nonobstructive azoospermia. Fertil Steril. 2009;91:925–8.
Mehta A, Goldstein M. Varicocele repair for nonobstructive azoospermia. Curr Opin Urol. 2012;22:507–12.
Schlegel PN, Kaufmann J. Role of varicocelectomy in men with nonobstructive azoospermia. Fertil Steril. 2004;81:1585–8.
Inci K, Hascicek M, Kara O, Dikmen AV, Gurgan T, Ergen A. Sperm retrieval and intracytoplasmic sperm injection in men with nonobstructive azoospermia, and treated and untreated varicocele. J Urol. 2009;182:1500–5.
Schlegel PN. Is assisted reproduction the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis. Urology. 1997;49:83–90.
Penson DF, Paltiel AD, Krumholz HM, Palter S. The cost-effectiveness of treatment for varicocele related infertility. J Urol. 2002;168:2490–4.
Lee R, Li PS, Goldstein M, Schattman G, Schlegel PN. A decision analysis of treatments for nonobstructive azoospermia associated with varicocele. Fertil Steril. 2009;92:188–96.
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Masaki Kimura and Koichi Nagao declare that they have no conflict of interest.
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Kimura, M., Nagao, K. Role of varicocele repair for male infertility in the era of assisted reproductive technologies. Reprod Med Biol 13, 185–192 (2014). https://doi.org/10.1007/s12522-014-0181-5
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DOI: https://doi.org/10.1007/s12522-014-0181-5