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Varicocele
Introduction
A varicocele is an 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][3] They can also affect testicular growth.[4]
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 empties directly into the low-pressure inferior vena cava, while on the left side, it joins with the relatively high-pressure left renal vein, which can impede left testicular venous drainage. This anatomy explains why the overwhelming majority of clinically detectable varicoceles are on the left side.[5]
Varicoceles occur in approximately 15% to 20% of all males but are found in about 40% of infertile males.[5] It is unclear exactly how a varicocele impairs the production, structure, and function of sperm, although there are several theories. The association between clinically significant varicoceles and male infertility is undeniable.[6] This association was first noted in the late 1800s by Barfield, a British surgeon, and was subsequently confirmed by others in the early 1900s.
There is clear and compelling evidence from multiple studies and meta-analyses that surgical repair of clinically significant varicoceles in infertile males with abnormal semen parameters can significantly improve sperm counts, motility, morphology, and pregnancy rates.[3][6][7][8][9][10][11][12][13][14][15][16][17]
Repairs of clinically apparent (large or medium-sized) varicoceles in adolescent males may normalize hormonal values, testis size, and sperm characteristics.[4][7][18][19][20][21][22]
Etiology
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Etiology
Varicoceles are 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.[23][24] Alternate venous drainage from the testicle includes the cremasteric and deferential veins.
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.[25]
There are 3 theories as to the anatomical cause: [5][26][27][28]
- Failure of the antireflux valve where the internal spermatic vein joins the left renal vein. This failure causes reflux and retrograde flow in the testicular vein.
- Angulation at the juncture of the left internal spermatic vein and the left renal vein.
- 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.
- There is 50% or more compression of the left renal vein between the abdominal aorta and the superior mesenteric artery. This causes increased venous pressure in the left renal vein, resulting in left spermatic vein obstruction.
- See our companion StatPearls reference article on "Nutcracker Syndrome."[27]
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.
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.[6]
Epidemiology
Approximately 15% to 20% of all adult males will have a varicocele, and up to 40% percent of men evaluated for infertility will also have a varicocele.[24][29][30]
During the workup of infertile couples, there appears to be a significant delay in the male evaluation for possible varicoceles. At 1 academic center, 18% of the infertile men referred after various costly assisted reproductive procedures were ultimately found to have varicoceles and qualified for a simple varicocelectomy. The female partner had no identifiable negative fertility findings in 70% of these infertile couples.[31]
Pathophysiology
Usually, the primary concern with a varicocele is infertility. Most men with varicoceles are fertile, but others have sperm compromised in function, morphology, numbers, and/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.[5]
Varicoceles may also reduce spermatic DNA integrity (fragmentation), increase oxidative stress, and negatively affect other aspects of spermatic function.[32]
The most accepted theory is that increased blood flow leads to higher intratesticular temperature, the main cause of impaired sperm in varicoceles.[33]
While untreated varicoceles may progress, they infrequently cause pain, although this is reported in 2% to 10% of varicocele patients.[2][34] 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.[2] Orchialgia associated with varicoceles is typically described as aching, dull, or throbbing but rarely can be acute, sharp, or stabbing.[35]
It is thought that large varicoceles may eventually cause testicular failure, ultimately resulting 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.[36]
Varicoceles can cause a reduction in testosterone production by the Leydig cells in the testes, particularly in older men.[37][38][39][40] Varicocelectomy improves the serum testosterone level in >80% of patients, with a mean increase between 100 ng/mL and 140 ng/mL. The greatest increase in testosterone was found in hypogonadal (testosterone <300 ng/mL) men. This finding and other data suggest that varicocelectomy may be a viable surgical option to permanently treat low testosterone levels in older hypogonadal men with significant varicoceles.[38][39][40][41][42]
History and Physical
Most often, varicoceles are found during a routine physical examination or an infertility workup. Varicoceles are usually asymptomatic, but 2% to 10% of patients will complain of pain.[2][34] The discomfort is usually described as an aching, dull, or throbbing pain, and only rarely is it characterized as sharp, acute, or stabbing.[2] Patients may sometimes complain of heaviness in the scrotum.
Varicoceles present as soft lumps above the testicle, usually on the left side of the scrotum. The patient may describe a "bag of worms" if the varicocele is large enough. Right-sided and bilateral varicoceles may also occur.
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 maneuver (bearing down). Subclinical varicoceles cannot be detected clinically but are only identified on ultrasound imaging.
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 3 mm in diameter or more.[43][44][45] This is most useful in equivocal or borderline cases. Routine imaging is not necessary for clinically significant varicoceles, and venography, in particular, is rarely needed or recommended but can be of some use for recurrent or treatment-resistant varicoceles.[46][47][48]
Thermal imaging is another noninvasive, painless, and non-contact technique for evaluating and confirming a possible varicocele.[49][50][51][52]
Testicular strain elastography is being studied for its potential usefulness in identifying varicocele patients who would benefit from treatment.[53][54][55][56]
Traditionally, it was always recommended to consider the possibility of renal cell carcinoma tumor extending into the vena cava as a possible cause of any isolated right-sided varicocele. A right-sided renal vein tumor thrombus can extend into the vena cava, causing a venous blockage resulting in spermatic vein obstruction and a right-sided varicocele. Computed tomography (CT) imaging is recommended if this is considered likely or possible.[57][58] A significant unilateral right-sided varicocele, sudden onset of the varicocele, or if the varicocele is not reducible are considered suspicious characteristics for retroperitoneal pathology.
Recently, this practice has been reevaluated as the incidence of such malignancies is quite low and insufficient to justify routine imaging.[58][59][60] It has been suggested that a quick right renal ultrasound performed at the time of scrotal ultrasonography would be a very cost-efficient way to identify any clinically significant retroperitoneal pathology, right renal masses, vena cava obstructions, and right renal vein thrombi without the cost, anxiety or radiation exposure of a CT scan.[60][61][62][63]
Treatment / Management
There are no effective medical treatments for varicoceles. 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 an outpatient procedure. The most common approaches are retroperitoneal abdominal laparoscopic, infrainguinal, subinguinal below the groin, or intrascrotal. Antegrade scrotal sclerotherapy may also be performed.[64][65][66] Avoiding the vas deferens and the testicular artery during surgery is mandatory regardless of approach.[67][68][69][70](A1)
Percutaneous embolization can also be performed, usually by interventional radiology.[64][71] 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.[64][65][71] An 89% success rate with this technique has been reported. While less invasive than open surgery, it can be technically challenging and is generally less cost-effective.[72] Percutaneous endovascular embolization is commonly used for recurrent varicoceles as an alternative to repeat open surgery.(B3)
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%).
Open surgical and percutaneous endovascular embolization approaches to varicocele treatment have roughly equivalent success and complication rates, as well as antegrade scrotal sclerotherapy. Still, pregnancy rates appear to be higher with surgical therapy.[72][73][74][75](A1)
Microsurgical techniques allow for the identification of small anastomosing vessels that might otherwise be missed. It also permits better identification of the testicular artery, thereby minimizing its inadvertent injury.[76][77][78] The procedure can be facilitated and even safer by applying a topical vasodilator and utilizing a mini-Doppler 20 MHz microvascular ultrasound probe.(A1)
Overall, the microsurgical subinguinal varicocelectomy is considered the preferred corrective procedure for the condition as it has a lower rate of recurrences, fewer complications, a quicker return to work, and demonstrates a greater improvement in sperm counts and motility as well as a higher pregnancy rate than alternative procedures.[12][79][80][81](A1)
The indications to remove a varicocele include relief of pain, reducing the risk of testicular atrophy, and treating or preventing infertility. Candidates for repair should meet the following conditions: [7][35]
- Abnormal semen parameters ("stress pattern") in infertile men
- Male infertility with normal fertility in females (although female infertility factors are not a contraindication for varicocele surgery in the male)
- Pain or discomfort related to the varicocele
- Palpable or clinically apparent varicocele
- When a clinically significant, high-grade varicocele is associated with failure of testicular development and growth in adolescent males (>20% difference in testis size)
The European Association of Urology guidelines on male infertility are similar but suggest that in addition to a clinically significant varicocele, there should also be evidence of oligozoospermia or otherwise unexplained fertility of 2 years or longer to justify surgery. They do not recommend surgery in men with normal semen parameters or subclinical varicoceles.[8]
Very large varicoceles may also be repaired; however, in the absence of pain, testicular atrophy, or abnormal semen analysis, this indication remains controversial.
If bilateral varicoceles are found, both should be repaired at the time of surgery.[82] If there is a clinically significant left varicocele but only a subclinical right varicocele, there is evidence that repairing both may ultimately be beneficial in producing a pregnancy.[83][84] Following surgery, approximately 70% of patients have improved semen parameters, and 40% to 60% of couples have improved conception rates. This improvement in semen quality will typically become noticeable at approximately 3 to 4 months after surgery and becomes final at 6 months.(A1)
Meta-analyses have indicated that the expected improvement in sperm count from a varicocele repair is 9.71 to 12.32 million/mL, while motility improves by 10.86% and morphology by 9.69%.[6][15](A1)
Infertile men with clinically significant varicoceles who have initial semen values of >8 million sperm/mL and >18% for progressive sperm motility have the best and most substantial improvement in their semen parameters after varicocelectomy surgery.[85] If the patient is a smoker or obese, outcomes from varicocele repair procedures will be negatively affected.[86]
Surgery for infertility is not recommended for subclinical varicoceles by most experts or guidelines, as this will not typically affect fertility or improve semen parameters.[87][88](B2)
Recently, the use of intraoperative indocyanine green angiography has been reported to help identify the testicular artery during microsurgical dissection for varicoceles.[89] The indocyanine green dye is given intravenously during the procedure. This causes arterial vessels to demonstrate an infrared fluorescence, facilitating their identification and preventing inadvertent arterial injuries.[89][90][91][92][93][94][95](B3)
There is limited data on the treatment of recurrent or persistent varicoceles after a surgical procedure. A repeat procedure offers very good rates of varicocele resolution, improved semen parameters, and pain control.[96][97] A repeat surgery utilizing the same surgical approach is typically performed in most cases. It appears reasonable, although the quality of the published data and studies is low.[96] No comparison of the use of an alternate approach with a repeat procedure of the same modality has yet been performed.(A1)
Couples with infertility due to nonobstructive azoospermia and a varicocele may benefit from microsurgical testicular sperm extraction and intracytoplasmic sperm injection (ICSI).
A follow-up semen analysis is typically performed about 4 months after the varicocelectomy procedure. Spermatogenesis generally takes about 74 days, so any noticeable effect on sperm quality will take 3 to 4 months to become clinically apparent.[98]
A large global survey of urologists and male infertility specialists showed that many clinicians do not appear to follow established guidelines regarding surgical indications for varicocele repair and the management of subclinical varicoceles. The survey also indicated significant gaps in the published clinical practice guidelines, as many clinical situations were not included or addressed.[99](B2)
Differential Diagnosis
A broad differential diagnosis for varicocele includes the following:
- Epididymal tumors
- Epididymitis
- Hydrocele
- Inguinal hernia
- Paratesticular tumors
- Scrotal lipomas and liposarcomas
- Spermatocele
- Testicular torsion
- Testicular tumors
- Trauma
Prognosis
The prognosis of a varicocele is quite good. If the varicocele is causing pain, this can be relieved with surgical repair. Improvement in semen parameters is generally noted in infertile men with abnormal semen parameters and clinically significant varicoceles. Varicocelectomy procedures for large varicoceles in adolescents with a small testis can allow testicular catch-up growth and help prevent future infertility.[4][21] Asymptomatic varicoceles in fertile men with normal testosterone levels do not need treatment and appear to cause no adverse effects.
Complications
Untreated clinically significant varicoceles may cause pain or discomfort and negatively affect fertility. In adolescents, they can affect the growth and size of the testes.[100]
Complications of surgery include scrotal hematomas, hydroceles, infection, scrotal tissue damage, wound infections, and arterial injury to the testis that may result in atrophy of the testis or even loss of the testicle.
Hydroceles may develop in up to 5% of varicocelectomy patients postoperatively.
Scrotal wound infections will generally become apparent within 3 to 5 days after surgery.
Testicular atrophy is rare even if the testicular artery is inadvertently ligated (5%), as there is adequate collateral arterial circulation from the cremasteric and vasal arteries. Inadvertent injuries to the testicular artery can be minimized by using optical magnification (loops) or performing microsurgery.
A recurrent varicocele may develop in up to 10% of treated patients.
Scrotal pain may develop after varicocele surgery. This is thought to be due to hydrocele formation, neuralgia, ureteral lesions, Nutcracker syndrome, varicocele recurrence, or referred pain from elsewhere.[101]
Deterrence and Patient Education
Patients diagnosed with clinically significant varicoceles should be informed of the possible harmful effects. If the varicocele is subclinical, there may not be an indication to repair it surgically. Surgery is not required if a varicocele is found incidentally in an otherwise asymptomatic, fertile male. A varicocelectomy procedure in an adolescent can help preserve future fertility and allow for increased growth of the testis.[4][21] All healthcare team members should reinforce the correct information about varicoceles to the patient and his family.
Pearls and Other Issues
Surgical repair is contradicted in asymptomatic patients with subclinical varicoceles, those with normal semen quality, and patients with isolated teratozoospermia.
If a varicocele is discovered during a vasectomy or vasectomy reversal, the varicocele repair should be delayed by 6 months to allow for the development of collateral vessels that will minimize the risk of delayed vascular compromise.
Varicocele repair is not 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 or long-term testosterone supplementation.[86]
Although rare, isolated significant right-sided varicoceles could be an indication of vena cava obstruction, such as from a right renal cancer venous tumor thrombus extending to the vena cava, especially if clinically large, unilateral, of sudden onset, or cannot be reduced.[58][59][60] In such cases, appropriate imaging is recommended, such as ultrasound. Most reported cases of such tumors will have other significant signs or symptoms of vena cava or retroperitoneal pathology.[61][62]
In borderline cases, it may be possible in the future to perform sperm DNA fragmentation and oxidative stress testing to help identify which infertile patients would benefit from varicocele repair procedures.[102]
Enhancing Healthcare Team Outcomes
An interprofessional team approach to evaluating and treating varicoceles will result in the best outcomes.[103][104][105] Healthcare professionals involved in caring for patients with varicoceles should possess the clinical skills to accurately diagnose and manage the condition. This includes the ability to perform physical examinations, interpret imaging studies, and conduct minimally invasive surgical procedures.
Each healthcare team member has specific responsibilities in caring for patients with varicoceles. Physicians provide medical expertise and surgical interventions, while advanced care practitioners, nurses, and pharmacists contribute to patient education, medication management, and postoperative care.
A well-defined strategy involves developing clinical pathways and treatment guidelines for varicoceles, ensuring that evidence-based practices are followed. Health professionals should collaborate on treatment plans considering individual patient needs and preferences.
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.[6][106] 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 or clinically significant 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 are no available large 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 from large meta-analyses and other data supports the previously described conclusions, recommendations, and guidelines, which strongly support the value of corrective surgery for clinically significant varicoceles in male infertility patients with abnormal semen parameters.[6][7][8][9][12][13][14][15][16][106][107] However, multiple studies have shown no significant improvement in pregnancy rates nor sperm counts, morphology, or motility from repairs of subclinical varicoceles.[36][106]
Healthcare professionals must exchange information, share insights, and collaborate on patient care plans, treatment outcomes, and potential complications. Interprofessional communication and care coordination will enhance patient-centered care, improve outcomes, prioritize patient safety, and optimize team performance. This holistic approach ultimately leads to improved healthcare quality in patients affected with varicoceles.
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