Pathogenesis and treatment of varicoceles

The varicocele is an enigma in the treatment of male infertility. Despite over 30 years of evidence that repair of varicoceles results in improved fertility,¹ the retrospective nature of most of these reports has led to controversy regarding the utility of treatment. This is compounded by the fact that not all varicoceles cause infertility. Varicocele is present in approximately 15% of men, and, although it is the most commonly diagnosed cause of male infertility, nearly two thirds of men with varicoceles remain fertile. The reason for this discrepancy remains unknown, although it is postulated that the cause of infertility is related to both temperature and time.² The anatomical and physiological principles of the testicular vasculature and the evidence base regarding surgical treatment are outlined here.

The blood supply to the testis, as well as the resulting counter current heat exchange, results in cooler intratesticular temperatures compared with body temperature.³ Disruption of this system can result in hyperthermia of the testes.⁴ As the left side drains into a system with higher resistance, small venules may persist or open during embryogenesis. Testicular blood flow remains low before puberty, and therefore these veins do not become clinically apparent until adolescence when testicular blood flow increases, which explains the appearance of most varicoceles around puberty.⁵ Endocrine dysfunction may contribute to varicocele related infertility. Studies have shown altered function of the Leydig, Sertoli, and germ cells in men with notable varicoceles.⁶ Whether this is due to the increased intratesticular temperature or other factors is unknown.

Treatments vary from radiological ablation to surgical ligation of the varicocele, although most urologists reserve the radiological approach for the rare surgical failures. Numerous studies have examined various operative methods, attempting to show a difference in efficacy and outcome. Although most of these methods result in similar short term results, the open microsurgical methods tend to yield fewer long term complications, such as recurrences and hydroceles.⁷ Although laparoscopic varix ligation was once touted as a minimally invasive method compared with open surgical repair, several authors have shown similar recovery rates, equal efficacy, fewer complications, and the advantage of not having to enter the abdomen.⁷ Most experts agree that only clinically apparent varicoceles should be treated. Although subclinical varicoceles (those identified by imaging studies only) may result in improvement in some seminal variables, evidence of efficacy is lacking regarding pregnancy rates.⁸

A Cochrane review identified five randomised controlled trials that examined the outcomes in couples with male factor infertility and varicoceles and concluded that they did not show sufficient evidence regarding the treatment of varicoceles to warrant their repair.⁹,¹⁰ However, these studies were chosen for this review only because of to their status as randomised clinical trials; no evaluation of the methods was performed. On review of these trials, one examined only subclinical varicoceles, and three others exhibited methodological problems including the use of embolisation, high pregnancy rates in untreated couples (25% in a one year period), and inherent selection bias in the study (many couples opted to pursue assisted reproductive technology rather than enter the study).

The one study that did show sizeable benefit was a randomised crossover design, in which over 50% of couples who underwent repair achieved pregnancy compared with 10% in the untreated couples. When the untreated couples were then crossed over and treated, another 50% became pregnant in the following year. However, men with severe oligospermia were excluded from this trial.¹¹ Furthermore, preliminary data from an ongoing prospective randomised controlled trial have shown a fourfold increase in the spontaneous pregnancy rate in men with treated varicoceles compared with the control group.¹² Although some of the reviewed studies had flaws, these findings raise the valid point of why most men with varicoceles are fertile, as well as why some infertile men with varicoceles do not improve after repair.

Although few randomised controlled trials show the benefit of treating varicocele related infertility, many non-randomised studies support this concept.¹² A published review performed a careful analysis examining the issue of treatment outcome after varicocelectomy. Numerous studies were reviewed, most retrospective, and the following conclusions made. Most participants showed improvement in postoperative sperm density and motility. The natural pregnancy rates varied, but the overall average was 37%, a clearly higher figure than any reported for non-treatment. Although many of these studies suffer from the flaws of non-randomised trials, these results would be difficult to explain on the basis of chance alone.

Varicoceles continue to stimulate controversy among reproductive experts. Despite conflicting evidence from both randomised and non-randomised trials, clinical experience still favours the surgical treatment of clinical varicoceles in men with infertility. However, it is incumbent on fertility specialists to design and recruit participants (or patients) in randomised, properly controlled trials to reach a definitive conclusion.