Date Published: November 28, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Ricardo Miyaoka, Sandro C. Esteves.
Varicocele is a major cause of male infertility, as it may impair spermatogenesis through several distinct physiopathological mechanisms. With the recent advances in biomolecular techniques and the development of novel sperm functional tests, it has been possible to better understand the mechanisms involved in testicular damage provoked by varicocele and, therefore, propose optimized ways to prevent and/or reverse them. Up to now, there is still controversy involving the true benefit of varicocele repair in subfertile men as well as in certain specific situations such as concomitant contralateral subclinical varicocele or associated nonobstructive azoospermia. Also, with the continued development of assisted reproductive technology new issues and questions are emerging regarding the role of varicocelectomy in this context. This paper reviews the most recent data available on the pathogenesis, diagnosis, and management of varicocele with regard to male infertility.
Approximately 8% of men in reproductive age seek medical assistance for fertility-related problems. Among them, 1%–10% carry a condition that compromise their fertility potential and varicocele alone accounts for 35% of these cases [1, 2]. Our personal database of a referral tertiary center for male reproduction presents an incidence of 21.9% of varicocele in 2,875 analyzed subjects .
Varicocele is identified in 7% and 10%–25% of prepubertal and postpubertal males, respectively [10, 11]. The higher frequency in elderly males and in men with secondary infertility suggests that it is a progressive disease [12, 13].
Despite the several different theories that aim to explain the impact of varicocele on testicular function, none can fully clarify the variable effect of varicocele on human spermatogenesis and male fertility. Proposed mechanisms include hypoxia and stasis, testicular venous hypertension, autoimmunity, elevated testicular temperature, reflux of adrenal catecholamines, and increased oxidative stress .
The idea supporting varicocele relationship with infertility stands on three aspects:
Physical examination with the patient standing in a warm room is currently the preferred method for varicocele diagnosis and has a sensitivity and specificity of around 70% compared with other diagnostic tools [42, 43]. The term clinical varicocele refers to those detectable by either visual inspection or palpation. The most widely used classification is the Dubin grading system :
Treatment of varicocele in infertile men aims to restore or improve testicular function. Current recommendations propose treatment for couples with documented infertility whose male partner has a clinical varicocele and at least one abnormal semen parameter. Men who are not attempting to achieve conception but fit into this description and have a desire for future fertility are also candidates for varicocele repair [49–51].
The definition of a subclinical varicocele is precisely what the term means: varicose veins from the pampiniform plexus which cannot be diagnosed solely by physical examination but rather depends on adjunctive diagnostic tools including Doppler examination, color Doppler ultrasound, scrotal thermography or venography [42, 43, 45–48, 75].
Nonobstructive azoospermia (NOA) comprises a spectrum of altered testicular histopathology related with several diverse factors (genetic, gonadotoxins, trauma, infectious, etc.). Although infertile men presenting with NOA are the most difficult to treat, the recent advances in ART coupled with surgical methods of testicular sperm extraction (TESE) made it possible for approximately 20%–40% of men with NOA to father children of their own .
In 2010, the World Health Organization (WHO) established new reference values for human semen characteristics, which are markedly lower than those previously reported . Current guidelines propose that varicocele should be treated if palpable and in the presence of abnormal semen analyses [49–51].
Varicocele is a highly prevalent condition in the infertile male population. Its epidemiologic features suggest that it is a progressive pathology with genetic predisposition. Recent studies on the physiopathology of varicocele-related infertility have shown the likely influence of ultrastructural testicular changes and increased oxidative stress with implications on the seminal antioxidant capacity and sperm chromatin integrity. Controversy still remains regarding the benefit of varicocele repair to improve male fertility. Evidence exist both in favor and against it, but as of now, most specialty societies recognize that varicocele is detrimental to male reproductive health and its treatment may improve sperm function and chances of conceiving. The cornerstone of varicocele diagnosis remains the physical examination although ultrasound may be helpful in certain scenarios. Surgical treatment is the gold standard, and subinguinal microsurgical approach seems to offer the best results with fewer complications. Subclinical varicoceles should only be considered for treatment when associated with a contralateral clinical one. Fertility improvement in men with treated varicocele may have a favorable impact on assisted reproductive technology outcomes. In nonobstructed azoospermic men, varicocele repair may increase the likelihood of finding sperm in the ejaculates of men with biopsy-proven hypospermatogenesis or maturation arrest testicular histopathology or in the testis of those who remained azoospermic using sperm retrieval techniques. Lastly, the adoption of the newly released 2010 WHO reference values for semen parameters normality is likely to have a significant impact on varicocele treatment indication by excluding former candidates for varicocele repair based on the current recommendations for surgery. This should be looked at with caution so as not to miss the adequate timing to intervene and prevent testicular damage.