The varicocele is the most common cause of male infertility world wide. Varicoceles have been found in 15% of the normal male population and in up to 40% of patients with male infertility. In approximately 70% of patients with secondary infertility, a varicocele is an underlying cause. Understanding of the pathophysiology, treatments, and outcomes of a varicocele and varicocele repair has evolved significantly over the past several decades. Our goal is to discuss the approach to its diagnosis and treatment that has evolved.
The varicocele is the most common cause of male infertility world wide ( Table 1 ). Varicoceles have been found in 15% of the normal male population and in up to 40% of patients with male infertility . In approximately 70% of patients with secondary infertility, a varicocele is an underlying cause . Understanding of the pathophysiology, treatments, and outcomes of a varicocele and varicocele repair has evolved significantly over the past several decades. Our goal is to discuss the approach to its diagnosis and treatment that has evolved.
| Category | Number | Percent (%) |
|---|---|---|
| Varicocele | 603 | 42.2 |
| Idiopathic | 324 | 22.7 |
| Obstruction | 205 | 14.3 |
| Normal/female factor | 119 | 7.9 |
| Cryptorchidism | 49 | 3.4 |
| Immunologic | 37 | 2.6 |
| Ejaculatory dysfunction | 18 | 1.3 |
| Testicular failure | 18 | 1.3 |
| Drug/radiation | 16 | 1.1 |
| Endocrinopathy | 16 | 1.1 |
| Others (all < 1%) | 31 | 2.1 |
| Total | 1430 | 100.0 |
History of the varicocele
Varicoceles were recognized as early as the first century ad by Celsius, who described dilation of scrotal veins and noted an association between a varicocele and testicular atrophy . Later, in the sixteenth century, Ambroise Pare (1500–1590) described this vascular abnormality as containing “melancholic blood.” In 1856, Curling was the first to describe a varicocele’s association with infertility when he reported decreased “secreting powers of the gland” in the presence of a varicocele . In the twentieth century, many other surgeons reported an association with an “arrest of sperm secretion” and subsequent improvement in fertility after varicocele repair. It was not until 1955, however, that Tulloch first reported the results of treating infertility with varicocele repair. Currently, a varicocele repair is the world’s most commonly performed male infertility procedure .
Pathophysiology of the varicocele
In 1978, Greenberg and colleagues found not only that varicoceles were associated with testicular atrophy but also that the testicular damage associated with a varicocele was progressive with age. Infertile patients with varicoceles have been found to have semen with decreased density, decreased motility, and abnormal morphology. Varicoceles also have been associated with abnormal testosterone and follicle-stimulating hormone levels .
Many theories have been suggested to explain why varicoceles lead to impaired spermatogenesis and subsequent infertility. The prevailing theory is that poor venous drainage leads to disruption of the countercurrent exchange of heat from the spermatic cord, which elevates scrotal temperatures. The elevated scrotal temperature leads to impaired spermatogenesis. Thus, a unilateral varicocele may have effects on both testicles . Increased scrotal temperatures have been shown to result in decreased testosterone synthesis by Leydig cells, injury to germinal thermolabile cell membranes, decreased protein biosynthesis, decreased amino acid transport, and altered Sertoli cell function and morphology .
Other theories that are less commonly ascribed to as to why varicoceles result in impaired spermatogenesis include oxygen deprivation, poor venous drainage that leads to impaired drainage of gonadotoxins from the testis, and increased oxidants within the semen. Allamaneni and colleagues reported a positive correlation between seminal reactive oxygen species (ROS) or “oxidant” levels and varicocele grade. They demonstrated that higher seminal ROS levels are seen in men with grade 2 and 3 varicoceles compared with men with grade 1 varicoceles. Another recent study demonstrated that levels of oxidants are significantly higher in semen of infertile men than in semen of fertile men . This study demonstrated that varicoceles significantly increase the oxidant levels within semen of infertile men and that repairing the varicoceles in these infertile men led to a significant decrease in the semen’s oxidant levels. In reality, it is likely that a varicocele causes testicular damage through multiple simultaneous mechanisms, all of which result in male infertility.
Pathophysiology of the varicocele
In 1978, Greenberg and colleagues found not only that varicoceles were associated with testicular atrophy but also that the testicular damage associated with a varicocele was progressive with age. Infertile patients with varicoceles have been found to have semen with decreased density, decreased motility, and abnormal morphology. Varicoceles also have been associated with abnormal testosterone and follicle-stimulating hormone levels .
Many theories have been suggested to explain why varicoceles lead to impaired spermatogenesis and subsequent infertility. The prevailing theory is that poor venous drainage leads to disruption of the countercurrent exchange of heat from the spermatic cord, which elevates scrotal temperatures. The elevated scrotal temperature leads to impaired spermatogenesis. Thus, a unilateral varicocele may have effects on both testicles . Increased scrotal temperatures have been shown to result in decreased testosterone synthesis by Leydig cells, injury to germinal thermolabile cell membranes, decreased protein biosynthesis, decreased amino acid transport, and altered Sertoli cell function and morphology .
Other theories that are less commonly ascribed to as to why varicoceles result in impaired spermatogenesis include oxygen deprivation, poor venous drainage that leads to impaired drainage of gonadotoxins from the testis, and increased oxidants within the semen. Allamaneni and colleagues reported a positive correlation between seminal reactive oxygen species (ROS) or “oxidant” levels and varicocele grade. They demonstrated that higher seminal ROS levels are seen in men with grade 2 and 3 varicoceles compared with men with grade 1 varicoceles. Another recent study demonstrated that levels of oxidants are significantly higher in semen of infertile men than in semen of fertile men . This study demonstrated that varicoceles significantly increase the oxidant levels within semen of infertile men and that repairing the varicoceles in these infertile men led to a significant decrease in the semen’s oxidant levels. In reality, it is likely that a varicocele causes testicular damage through multiple simultaneous mechanisms, all of which result in male infertility.
Beneficial effects of varicocele repair
Our understanding of how a varicocele repair affects overall semen and hormone parameters has evolved over the past several decades. For example, correction of varicoceles has been shown to improve not only sperm motility, density, and morphology but also specific functional sperm defects . Improvements in the sperm penetration assay , oxidant determination (ROS) , and DNA fragmentation have been achieved after a varicocele repair. A varicocele repair also has been shown to improve serum follicle-stimulating hormone and testosterone levels . Su and colleagues demonstrated that after a varicocele repair, the mean serum testosterone level significantly increased from a preoperative level of 319 ± 12 to 409 ± 23 ng/dL postoperatively. Cayan and colleagues also reported a significant decrease in mean follicle-stimulating hormone level from 15.21 mIU/mL before surgery to 10.82 mIU/mL after surgery. In 1987, Kass and Belman were the first to demonstrate a significant increase in testicular volume after varicocele repair in adolescents. Finally, pregnancy rates after varicocele repair have been shown to increase with intrauterine insemination despite the absence of significant changes in gross semen analyses . It is believed that improved functional factors not measured on routine semen analysis may explain these increased intrauterine insemination success rates.
The evolution of the varicocele repair in patients who have azoospermia
In 1955, Tulloch was one of the first surgeons to report a varicocele repair in a patient who had azoospermia. He reported that a varicocele repair resulted in restoration of spermatogenesis and subsequent pregnancy in a patient who had azoospermia. Since then, many other studies have demonstrated the return of motile sperm after varicocele repair in patients who have azoospermia. Matthews and associates found that 55% of men with azoospermia and 69% of men with zero motile sperm before surgery had motile sperm in their ejaculate after varicocele repair. Kim and colleagues demonstrated that varicocele repair can result in sperm in the ejaculate of men who have azoospermia when severe hypospermatogenesis or late maturation arrest is identified histologically. Some studies have demonstrated that the best chance of having motile sperm return in the ejaculate occurs when sperm or spermatids are present on preoperative testis biopsy . Other investigators have found that men with nonobstructed azoospermia rarely have adequate sperm in their ejaculate after varicocele repair to avoid testicular sperm extraction, however .
Diagnosis
Varicoceles are diagnosed primarily by physical examination. Patients should be examined in standing and supine positions. While standing, patients should be asked to perform the Valsalva maneuver so the physician can assess reversal of venous flow. The duplex ultrasound has significantly improved our ability to diagnose varicoceles. Since its introduction, the use of other radiographic tools, such as venography, the Doppler stethoscope, and radionucleotide scans such as technetium 99m pyrophosphate, has greatly decreased. It should be noted, however, that the diagnosis of a varicocele is made primarily by physical examination, and the duplex ultrasound should be used only to corroborate or confirm results of the physical examination. Most clinicians would agree that the diagnosis of a varicocele by ultrasound should be based on a patient having veins dilated between 2 and 3 mm and reversal of venous flow with Valsalva maneuver. There are currently no standard and clearly defined criteria for diagnosing a varicocele by ultrasound, however.
Subclinical varicoceles are not palpable on physical examination but rather are diagnosed radiographically. Most authors agree that subclinical varicoceles are varicoceles less than 3 mm in diameter . There has been much debate as to the clinical relevance of subclinical varicoceles. Studies have shown that subclinical varicoceles have no significant impact on fertility and that repairing subclinical varicoceles has no significant impact on improving fertility rates . Radiographic testing to diagnose a varicocele should be performed only when there is uncertainty on a physical examination or to identify recurrent or persistent varicoceles.
Indications for treatment
The Male Infertility Best Practice Policy Committee of the American Urological Association recommended that a varicocele repair should be offered to the male partner of a couple attempting to conceive when all four of the following conditions are present :
- 1.
The female partner has normal fertility or a potentially correctable cause of infertility
- 2.
The couple has documented infertility
- 3.
A varicocele is palpable or, if suspected, is corroborated by ultrasound
- 4.
The male partner has one or more abnormal semen parameters or sperm function test results
Adult men who have a varicocele and abnormal semen parameters and do not wish to conceive currently but might in the future could be considered for a varicocele repair. Adolescent boys with varicoceles should be considered for a varicocele repair if there is testicular pain or a reduction in the ipsilateral testicular volume. If there is no identifiable reduction in ipsilateral testicular volume, these young men can be followed with annual physical examinations or a semen analysis. These patients and their families should be fully apprised of the concerns and controversies surrounding adolescents with a varicocele.
Evolution of the surgical treatments of varicocele
The scrotal approach was one of the first operations used for varicocele repairs. In 1904, Hartman was the first to describe radical resection of the scrotum and external clamping of varicoceles . The scrotal approach is no longer performed because of the increased risk of injury to the testicular artery and its high rate of recurrence. Currently, there are three main surgical approaches to a varicocele repair: inguinal, subinguinal, and retroperitoneal ( Fig. 1 ). The retroperitoneal approach can be performed either open or laparoscopically. Each of these approaches has its own pros and cons, which are discussed briefly.
Related posts:
Hormonal Evaluation of the Infertile Male: Has It Evolved?
Assessing Sperm Function
Ejaculatory Duct Obstruction
Restructuring Reconstructive Techniques—Advances in Reconstructive Techniques
Intrauterine Insemination and Male Subfertility
Intracytoplasmic Sperm Injection (ICSI) – What are the Risks?
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