Varicocele

Article Author:
Stephen Leslie
Article Author:
Hussain Sajjad
Article Editor:
Larry Siref
Updated:
7/21/2020 4:20:44 PM
For CME on this topic:
Varicocele CME
PubMed Link:
Varicocele

Introduction

A varicocele is abnormal dilation and enlargement of the scrotal venous pampiniform plexus which drains blood from each testicle. While usually painless, varicoceles are clinically significant because they are the most commonly identified cause of abnormal semen analysis, low sperm count, decreased sperm motility, and abnormal sperm morphology.[1][2]

The testicular veins originate in the testicle and form the pampiniform plexus. Venous blood then travels up through the inguinal canal as part of the spermatic cord, forms the internal spermatic or testicular vein and terminates in the abdomen. The right internal spermatic vein terminates directly into the low-pressure inferior vena cava while on the left side, it joins with the relatively high-pressure left renal vein. This anatomy explains why the majority of clinically detectable varicoceles are on the left side.

Varicoceles occur in around 15% to 20% of all males but are found in about 40% of infertile males. It is unclear exactly how a varicocele impairs the production, structure, and function of sperm, although there are several theories. However, the association between clinically significant varicoceles and male infertility is undeniable. This association was first noted in the late 1800s by Barfield, a British surgeon, and was subsequently confirmed by others in the early 1900s.

Varicoceles are classified as small, medium, and large based on their clinical appearance and obvious size.

Etiology

The precise cause of varicoceles is not known, but it is thought to develop from a backup of venous blood flow in the internal spermatic vein that causes venous engorgement which is clinically detectable on scrotal examination.[3][4]

Varicoceles are far more common (80% to 90%) in the left testicle. If a left varicocele is identified, there is a 30% to 40% probability it is a bilateral condition.

There are three theories as to the anatomical cause:

  1. The "Nutcracker" effect which occurs when the left internal spermatic vein gets caught between the superior mesenteric artery and the aorta. This entrapment causes venous compression and spermatic vein obstruction.
  2. Failure of the anti-reflux valve where the internal spermatic vein joins the left renal vein. This failure causes reflux and retrograde flow in the testicular vein.
  3. Angulation at the juncture of the left internal spermatic vein and the left renal vein.

Rare causes of varicoceles include deep vein thrombosis, renal arteriovenous malformations, and thrombosis of the pampiniform plexus.

Tobacco smoking and mutations in the gene expressing glutathione S-transferase Mu 1 increase the risk of male infertility. These factors may also increase the risk for a varicocele.

When a varicocele contributes to an abnormal semen analysis, it typically causes a "stress pattern" on microscopic semen examination. This pattern consists of a low sperm count, poor motility and an increase in the percentage of abnormal sperm.

Epidemiology

Around 15% to 20% of all adult males will have a varicocele, and up to 40% percent of men who are evaluated for infertility will also have it.[4][5][6]

There appears to be a significant delay in the male evaluation in infertile couples for possible varicoceles.  18% of men referred to one academic center after various costly assisted reproductive procedures, were ultimately found to qualify for a simple varicocelectomy. The female partner had no identifiable fertility findings in 70% of these couples. [7]

Pathophysiology

Usually, the primary concern with a varicocele is infertility. Many men with varicoceles are fertile, but others have sperm that is compromised in function, morphology, numbers, or movement. Researchers theorize that the sperm may be damaged due to excess heat caused by increased oxidative stress on the sperm from blood pooling causing reduced oxygenation, direct hydrostatic pressure injury effects on the testis, toxin formation, hypoxia, autoimmunity, or an increase in adrenal steroids concentration being delivered to the testicle since the adrenal veins empty into the left renal vein almost directly opposite the entry of the internal spermatic vein. The most accepted theory is that increased blood flow leads to higher intratesticular temperatures which are the main cause of impaired sperm in varicoceles.[8]

While untreated varicoceles may progress, they seldom cause pain although this is possible.  Suggested mechanisms for such pain include increased testicular temperatures, higher venous pressure, oxidative stress, hormonal imbalances, reflux of toxic metabolites from the kidneys or adrenals, hypoxia or possible stretching of nerve fibers in the spermatic cords from the dilated varicocele complex. Orchialgia associated with varicoceles is typically described as aching, dull or throbbing but rarely can be acute, sharp or stabbing. [9]

It is thought that large varicoceles might eventually cause testicular failure, ultimately resulting possibly in lower hormonal production, oligospermia, and testicular atrophy. Varicoceles can also decrease sperm nuclear DNA integrity which has been linked to reduced sperm motility, viability, counts and abnormal morphology. [10]

Varicoceles can cause a reduction in testosterone production by the Leydig cells in the testes. Varicocelectomy leads to improvement in the serum testosterone level in >80% of patients, with a mean increase between 100 and 140 ng/mL. The greatest increase in testosterone was found in hypogonadal (testosterone <300 ng/mL) men.  This finding suggests that varicocelectomy might be a viable surgical option to permanently treat low testosterone levels in hypogonadal men with significant varicoceles. 

History and Physical

Varicoceles are usually asymptomatic. The patient may describe a "bag of worms" if the varicocele is large enough. Varicoceles present as soft lumps above the testicle, usually on the left side of the scrotum. Right-sided and bilateral varicoceles may also occur. Patients may sometimes complain of pain or heaviness in the scrotum. Often they are found in the course of an infertility workup.

Large varicoceles are easily identified on simple inspection alone and will show the typical "bag of worms" appearance. Medium varicoceles would describe those that are identifiable by palpation or physical examination without any bearing down by the patient. Small varicoceles are defined as those that can be identified only during a strong Valsalva (bearing down).

Evaluation

After the physical exam, the varicocele can be confirmed with high-resolution color-flow Doppler ultrasound, which will show dilation of the vessels of the pampiniform plexus, typically greater than 3 mm in diameter. Venography is not needed.

Thermal imaging is another non-invasive, painless and non-contact technique for evaluation and confirmation of a possible varicocele.[11][12][13]

Testicular strain elastrography is being studied for its potential benefit in identifying varicocele patients who would benefit from treatment.

Always consider the possibility of renal cell carcinoma as a possible cause of any isolated right-sided varicocele.  A right-sided renal vein tumor thrombus can extend into the vena cava causing venous obstruction resulting in spermatic vein obstruction and a right-sided varicocele. If this is considered possible, CT imaging is recommended.[14]

Treatment / Management

There are no effective medical treatments. If a varicocele is causing pain or discomfort, the use of analgesics and scrotal support can be used initially. When a varicocele is treated surgically, it is usually as an outpatient procedure. The most common approaches are retroperitoneal abdominal laparoscopic, infra-inguinal, sub-inguinal below the groin or intrascrotal. Regardless of approach, avoidance of the vas deferens and the testicular artery during surgery is mandatory.[15][16][17][18]

Percutaneous embolization can also be done, usually by interventional radiology. This involves passing a catheter from the femoral vein, up the vena cava, laterally into the left renal vein and then inferiorly into the spermatic vein. This approach is usually reserved for open surgical failures or recurrences. An 89% success rate with this technique has been reported. 

Microsurgical techniques allow for identification of small anastomosing vessels that might otherwise be missed. It also permits better identification of the testicular artery thereby minimizing its inadvertent injury.

Some pediatric urologists prefer a retroperitoneal, laparoscopic approach which allows for control of the spermatic vein very near its insertion into a left renal vein. However, this technique has a relatively high recurrence rate (15%).

Complications include hematoma, hydrocele, infection, scrotal tissue injury, and arterial injury to the testis that may result in loss of the testicle.

It is unclear in the literature which of the procedures improves male fertility more.

Couples with infertility as a result of nonobstructive azoospermia and a varicocele may benefit from microsurgical testicular sperm extraction and intracytoplasmic sperm injection (ICSI).

The indications to remove a varicocele include relief of pain, reducing testicular atrophy, and infertility. Candidates for repair meet the following conditions:[9]

  • Infertility in males, normal fertility in females (although female infertility factors are not a contraindication for varicocele surgery in the male)
  • Palpable varicocele
  • Abnormal semen parameters ("stress pattern")
  • Pain related to the varicocele
  • In adolescents when associated with failure of testicular development and growth

If bilateral varicoceles are found, both are repaired at the time of surgery.  If there is a clinically significant left varicocele but only a subclinical right varicocele, there is evidence that repairing both may be ultimately be beneficial in producing a pregnancy.

Following surgery, approximately 70% have improved semen parameters, and 40% to 60% have improved conception rates. This improvement in semen quality will typically become noticeable at approximately 3 to 4 months after surgery and become final at 6 months.

Meta-analyses have indicated that the expected improvement in sperm count from varicocele repair is 9.71 to 12.32 × 10 ml while motility improves 10.86% and morphology 9.69%.  Surgery for infertility is not recommended for subclinical varicoceles by the majority of experts as this will not typically affect fertility or sperm parameters. [19]

Alternate venous drainage from the testicle includes the cremasteric veins and the deferential vein.

Recently, the use of intraoperative indocyanine green angiography has been reported to help identify the testicular artery during microsurgical dissection for varicoceles. The indocyanine green dye is given intravenously during the procedure. This causes arterial vessels to demonstrate an infrared fluorescence which facilitates their identification thereby preventing inadvertent arterial injuries.indocyanine green agn[20]

Differential Diagnosis

  • Epididymitis
  • Hydrocele
  • Inguinal hernia
  • Paratesticular tumours
  • Spermatocele
  • Testicular tumour
  • Testicular torsion
  • Trauma

Pearls and Other Issues

Surgical repair is contradicted in patients with subclinical varicoceles, those with normal semen quality and in patients with isolated teratozoospermia.

If a varicocele is discovered during vasectomy or vasectomy reversal, the varicocele repair should be delayed 6 months to allow for the development of collateral vessels that will minimize the risk of delayed vascular compromise.

Varicocele repair has not been shown to be of any benefit in patients who are pursuing intracytoplasmic sperm injection treatment.

Varicocelectomy surgery improves testosterone production and might be a viable option in selected hypogonadal men as an alternative to permanent testosterone supplementation. 

Reminder: Isolated right sided varicoceles could be an indication of vena cava obstruction such as from a right renal cancer venous tumor thrombus. In such cases, appropriate imaging is recommended.

Enhancing Healthcare Team Outcomes

Most varicoceles are discovered incidentally and do not require treatment unless symptomatic.  In patients with infertility, varicoceles offer an opportunity to easily improve sperm count and function which should not be overlooked if present.

Primary care physicians, nurse practitioners, and physician assistants should be aware that the best available current evidence indicates that varicocele treatment should be offered to infertile males with a palpable varicocele and abnormal semen parameters. This also agrees with the current American Urological Association and European Association of Urology Guidelines regarding varicocele treatment.  Unfortunately, at this time, there there are no available, randomized prospective trials of sufficient size, duration and statistical validity to be considered absolutely definitive on the issue of varicocelectomy for male infertility. The best available evidence supports the conclusions, recommendations and guidelines previously described. 

However, multiple studies have shown no significant improvement in pregnancy rates nor sperm counts, morphology or motility from repairs of sub-clinical varicoceles. 

an interprofessional team approach to the evaluation and treatment of this condition will result in the best outcomes.[21][22][23] [Level v]


References

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