Pathophysiology of Varicocele

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The true effect of varicocele on testicular function and male fertility remains unknown. Although numerous studies have clearly demonstrated an association between varicocele and reduced male reproductive function (e.g., poor semen parameters, infertility), most varicocele studies involve highly selected populations (e.g., infertile men), making it difficult to ascertain the role of varicoceles in male infertility. Moreover, the lack of reliable end-points for measuring fertility represents another challenge in relating varicoceles with male infertility. Conventional sperm parameters (sperm concentration, motility, and morphology) are generally monitored in varicocele studies, but these parameters exhibit a high degree of biological variability and are of modest value in predicting male fertility potential [14]. Pregnancy is also of limited value in assessing the influence of varicocele on male fertility potential because this outcome is heavily influenced by female factors [15]. Studies of noninfertility populations provide conflicting results on the relationship between varicocele and fertility. As such, a cause and effect relationship between varicocele and male infertility has not been established.

An adverse effect of varicocele on male fertility is suggested by the testicular atrophy that is frequently associated with this condition [16-22]. In men with a left varicocele, mean left testicular volume is less than right testicular volume [18, 22]. However, the relationship between varicocele grade and the degree of testicular atrophy is less clear. Zini et al. [23] found that in men with unilateral left varicocele, the loss of left testicular volume relative to the right (i.e., right minus left) increased with increasing varicocele grade, whereas Alukal et al. [24] found no such correlation between varicocele grade and volume differential.

The impact of testicular atrophy on male fertility remains to be established, even though most studies indicate that testicular atrophy is associated with poor sperm parameters. Sigman and Jarow [20] have reported that in men with left varicocele, those with testicular atrophy have poorer semen parameters than do men without atrophy. Similarly, Diamond et al. [25] have shown that in the adolescent, a volume differential greater than 10% between the normal and varicocele testis correlates with a significantly decreased sperm concentration and total motile sperm count. Nonetheless, loss of testicular volume is not clearly associated with loss of fertility [19],

Varicocele is associated with bilateral spermatogenic abnormalities and Leydig cell dysfunction [26-29]. The testicular histology in infertile men with varicocele is variable, but most studies report reduced spermatogenesis (hypospermatogenesis) [30, 31], Recently, Santoro and Romeo [32] described abnormalities in the ultrastructure of testicular tissue of men with varicocele. They noted that histologic changes were less pronounced in adolescents than in adults, supporting the concept that an uncorrected varicocele is associated with a progressive decline in testicular function. The observed increase in germ cell apoptosis associated with varicocele is thought to occur as a result of hyperthermia and low testosterone levels in the testis [33]. Serum testosterone levels are lower in older (>30 years) compared to younger men with varicocele, a trend not seen in men without varicocele, suggesting a progressive, adverse effect of varicocele on Leydig cell function [21].

The influence of varicocele on sperm parameters has not been established conclusively. In studies of infertile men, varicoceles have been associated with abnormal sperm parameters. MacLeod [34] and other investigators [21] observed that the majority of semen samples from infertile men with varicocele have poorer sperm parameters (lower sperm counts, increased numbers of spermatozoa with abnormal forms, and decreased sperm motility) than fertile men. However, the "stress pattern" described by MacLeod (i.e., increased proportions of sperm with tapered heads and immature forms) is not a specific marker for varicocele and, therefore, is not diagnostic of this condition [35] . In studies of unselected men (i.e., noninfertile), the relationship between varicocele and sperm parameters is less clear. Johnson et al. [36] showed that in a cohort of asymptomatic military recruits, nearly 70% of men with a palpable varicocele had an abnormality on semen analysis. In contrast, Zargooshi [37] observed that most young military recruits with moderate-to-large (grade 2 and 3) varicoceles have normal semen parameters.

Although studies on the prevalence of varicocele in men with primary and secondary infertility suggest that the presence of a varicocele may cause a progressive decline in fertility, this has not been confirmed by prospective studies. Chehval and Purcell [38] conducted a prospective, uncontrolled study of untreated varicocele and observed a significant deterioration in both sperm density and motility at 9-96 months follow-up. In contrast, Lund and Larsen [39] conducted a prospective, controlled trial of untreated men with and without varicocele and found no decline in semen parameters in either group after 8 years of follow-up.

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  • petra
    What is pathophysiology of varicocele?
    2 years ago

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