Do varicoceles really affect male fertility?

How varicoceles develop 

Varicoceles are a dilation of the veins that drain the testis. These veins are found in the spermatic cord and are called the pampiniform plexus (Figure 1).

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Figure 1. How varicoceles develop. The major source of blood supply to the testis is the testicular artery. Varcicoceles occur when the veins that drain the testis, known as the pampiniform plexus, become dilated. Small venules may persist or open during embryogenesis but may not become clinically apparent until puberty, when testicular blood flow increases.

The main blood supply to the testis comes from the aorta. The internal spermatic (testicular) artery is the major source, with collateral flow from the deferential artery, as well as the cremasteric arteries. Venous drainage is variable, with the pampiniform plexus draining into the internal spermatic (testicular) veins. These veins insert into the renal vein on the left and the inferior vena cava on the right. The veins surround the artery, thus providing a mechanism for cooling the warm arterial blood via countercurrent heat exchange.3 This is one way that the intratesticular temperature is maintained several degrees below body temperature. Disruption of this system can result in hyperthermia of the testes.

Varicoceles typically develop after puberty, although many are not detected until the patient is evaluated for fertility problems. The development of varicoceles is controversial. Classically, it was thought that varicoceles developed due to failure of the valves within the internal spermatic vein(s). However, more recent studies have demonstrated intact valves in men with clinical varicoceles, as well as absent valves in men without varicoceles. Thus, it appears that the anatomy of the drainage system plays a major role in the development of varicoceles. Because the left side drains into a system with higher resistance (the renal vein), small venules may persist or open during embyrogenesis. And because testicular blood flow remains low prior to puberty, these veins do not become clinically apparent until adolescence, when testicular blood flow increases, thus explaining the appearance of most varicoceles around puberty.4 Varicoceles are thought to cause spermatogenic defects by raising the intratesticular temperature in both the affected and contralateral testes.

Endocrine dysfunction may also contribute to the effects of varicoceles on fertility. Studies have demonstrated altered function of Leydig, Sertoli, and germ cells in men with significant varicoceles.5 Whether this is due to increased intratesticular temperature or other factors is unknown at present. Other studies have demonstrated subtle hormonal abnormalities, most notably an exaggerated response to gonadotropin-releasing hormone (GnRH). The clinical utility of this information, however, is debatable. Repair of varicocele may halt any further damage to testicular hormone function and, in a large percentage of men, result in improved spermatogenesis as well as enhanced Leydig cell function.

Key points 

■Although varicoceles are common, not all require treatment. Most authors recommend treatment of varicoceles in the event of male factor infertility.

■Varicoceles are thought to cause spermatogenic defects by raising the intratesticular temperature in both the affected and contralateral testes.

■Varicoceles may cause progressive, duration-dependent injury to the seminiferous epithelium. Repair is thought to halt this duration-dependent process.

■The goals of varicocele repair are to relieve pain in symptomatic cases and to improve semen parameters, testicular function, and pregnancy rates in couples with varicocele-associated male factor infertility.

Making the diagnosis 

Varicoceles are typically diagnosed by physical examination. They are most easily detected when the patient has been standing in a warm room for several minutes. Often, they will expand when the patient bears down (Valsalva maneuver), as the blood reverses flow back toward the testicle.

Most experts agree that only varicoceles detected by physical examination are clinically significant. Therefore, confirmatory testing is usually not necessary except under certain circumstances.

Ultrasound can identify varicoceles as small as 2–3 mm in diameter. However, ultrasound will also identify “subclinical” varicoceles—those that are not clinically palpable. Because the original studies examining the effects of varicocele ligation on seminal parameters did not find a significant correlation between size of the varicocele and response, some believe that correcting subclinical varicoceles would lead to the same rate of improvement as the correction of clinical varicoceles. However, most studies report a lower response rate following repair of subclinical varicoceles, and even lower pregnancy rates.6

Doppler studies are easily performed in the office and identify the reversal of blood flow during Valsalva maneuver. Doppler may also detect a subclinical varicocele, although it is also useful in examining men with tight scrotal skin or short spermatic cords, and in exploring the right side when the patient has a palpable left varicocele.

Varicoceles are usually associated with abnormalities in all of the seminal parameters. However, they can also cause isolated defects in sperm count, motility, morphology, or function. Therefore, the results of semen analysis are not a good predictor of the presence or absence of a varicocele.

Goals of varicocele repair 

The objectives of varicocele repair are to:

Studies have shown that varicocele repair can result in a significant improvement in semen parameters in 60% to 70% of men.7 Men with large varicoceles tend to have poorer preoperative semen quality than men with small varicoceles, but repair of large varicoceles results in greater improvement than repair of small ones.

Varicoceles are identified in 35% to 40% of men with primary infertility and 81% of men with secondary infertility.8 Studies have shown that varicoceles cause progressive duration-dependent injury to the seminiferous epithelium. Repair is thought to halt this duration-dependent process. The goal: A significant percentage of couples will go on to achieve pregnancy without assisted techniques, and those who do proceed to assisted reproductive technology will have optimized the sperm quality.

Methods of varicocele repair 

Treatment modalities for varicocele vary from radiologic ablation to surgical ligation. Studies have examined a variety of methods, attempting to demonstrate a difference in efficacy and outcomes. Although most methods yield similar short-term results, open microsurgery tends to have lower long-term complications, such as recurrences and hydroceles. This is due to the ability to tie off all veins while sparing the arterial blood supply and lymphatic vessels.

It also seems that the higher the ligation (e.g., in the retroperitoneum) the higher the persistence/recurrence rate. Such complications most likely occur because small venous channels branch off or cross over from the testicular veins below the level of ligation. As a result, most experts in male infertility prefer a low inguinal/subinguinal approach. Although laparoscopic varicocele ligation was once touted as a minimally invasive method of repair, several authors have demonstrated similar recovery rates with open microsurgical methods9 along with equal efficacy, fewer complications, and the advantage of not having to enter the abdomen.

Most men prefer general anesthesia, though the procedure may be performed under local with intravenous sedation. Time to recovery varies, but most men get back to work within 3–4 days and resume full activity within 7–10 days.

The most common complications from varicocelectomy are hydrocele, varicocele recurrence, and testicular artery injury. Use of the operating microscope allows for reliable identification of spermatic cord lymphatics, internal spermatic veins and venous collaterals, and the testicular artery or arteries, so that the incidence of these complications can be reduced significantly. Thus, in a significant number of men, the microsurgical technique provides a safe and effective approach to varicocele repair that preserves testicular function, enhances semen quality, and improves partners’ pregnancy rates.

What the evidence shows 

Although there is a paucity of randomized controlled trials determining the benefit of treating varicocele-related infertility, many non-randomized studies support this notion.10 Most of those studies are retrospective and somewhat biased in their patient selection. Nevertheless, there is both direct and indirect evidence that varicocele repair improves seminal parameters in up to 60%–70% of cases, with natural pregnancy rates up to 50%. However, a Cochrane review of several randomized controlled trials did not show sufficient evidence regarding the treatment of varicoceles to warrant their repair.11 Although some of the trials in this review suffered from significant problems in methodology, the review once again raises the question of whether treating varicoceles improves fertility.

Despite the lack of large randomized trials, the majority of available evidence favors the surgical treatment of clinical varicoceles in men with infertility. Current research, both basic and clinical, seeks to further characterize this common, yet poorly understood, condition. Until more definitive results are reported, varicoceles will continue to stimulate controversy among reproductive experts.