The value of ultrasonography in the diagnosis of varicocele

Abstract

A varicocele is described as pathologically enlarged, tortuous veins of the pampiniform plexus, leading to an increased testicular temperature and adrenal metabolite reflux into the testes. Varicocele can impair spermatogenesis and is considered to be the most common cause of male infertility. Patients may palpate a thickening in the scrotum or complain of dull scrotal or inguinal pain, which increases when standing or during erection. In the case of a sudden onset of varicocele in elderly men, it is necessary to exclude renal tumor and extend diagnostic ultrasound with the assessment of the abdominal cavity. The diagnosis of varicocele is based on medical history and physical examination, which involves palpation and observation of the scrotum at rest and during the Valsalva maneuver. Ultrasound is the imaging method of choice. The width and the number of vessels in the pampiniform plexus as well as the evaluation and measurement of regurgitation during the Valsalva maneuver are typical parameters analyzed during ultrasound assessment. However, diagnostic ultrasound is still a controversial method due to numerous and often divergent classification systems for varicocele assessment as well as its poor correlation with clinical manifestations. As a result of introduction of clear ultrasound criteria as well as the development of elastography and nuclear magnetic resonance, diagnostic imaging can play an important role in assessing the risk of damage to the testicular parenchyma, qualifying patients for surgical treatment and predicting the effects of therapy.

Introduction

A varicocele, defined as a pathological enlargement of the pampiniform plexus with veins often running in a winding course, is considered the most common cause of male infertility⁽¹⁾. The incidence of varicocele in males with primary (35%) and secondary (80%) infertility is significantly higher compared to the general male population (15%)⁽²⁾. Epidemiological data also indicate an increasing incidence of varicocele with age: varicocele is rarely reported in children under 10 years of age; it affects 7–14% of boys during puberty; and shows an about 10%-increase in the incidence per each decade of life^(3–5). The etiology of varicocele is multifactorial. Differences in the course of testicular veins are considered to underlie the higher incidence of left-sided varicocele (>80% of cases). The left testicular vein runs vertically and enters the left renal vein at a right angle, which predisposes to turbulent blood flow and reverse pressure, while the right testicular vein opens directly into the inferior vena cava at a sharp angle^{(6, 7)}. The lack or incompetence of testicular vein valves are another factor predisposing to reverse pressure. Sofikitis et al. showed the absence of valves in the left testicular vein at the pelvic and lumbar level in 33% and 37% of patients, respectively⁽⁸⁾. Testicular venous developmental variants are significantly more commonly observed in boys with varicocele compared to adult men^{(9, 10)}. Compression of the left renal or testicular vein, either as a result of the so-called nutcracker mechanism or due to renal or retroperi-toneal tumors, is a relatively rare cause of varicocele^{(6, 11)}. A sudden onset of varicocele in a man over the age of 30 years requires the exclusion of renal tumors, particularly in elderly patients. In such cases it is necessary to extend diagnostic ultrasonography with abdominal examination.

Researchers suggested several pathophysiological mechanisms underlying the adverse effects of varicocele. It seems that an increase in the scrotal temperature is the most likely cause of endocrine and spermatogenic testicular dysfunction^{(12, 13)}. Spermatogenesis disorders can also result from renal and adrenal metabolite reflux into the left testicular vein^{(14, 15)}. It has also been shown that Leydig cell dysfunction with a secondary reduction of intratesticular testosterone levels as well as an impairment of both Sertoli cell secretory function and sperm maturation process affect both testes, regardless of whether the varicocele is uni- or bilateral^{(16, 17)}. Varicocele reduces semen quality. In such cases, treatment using varicocelectomy or obliteration of varicose veins is attempted. Indications for this type of treatment include infertility and pain during physical activity or sexual intercourse, which is typical of varicocele ⁽¹⁸⁾. Varicocele without concomitant pain or semen pathology is not an indication for surgical treatment. Agarwal et al. confirmed in their meta-analysis in 2007 improved semen parameters (number, motility and quality) after procedures in infertile men with varicocele⁽¹⁹⁾.

Clinical assessment

The diagnosis of varicocele is based on medical history and physical examination. Most patients with varicocele are asymptomatic. Other patients may palpate a scrotal thickening above the testis or complain of dull pain in the scrotum or groin, increasing during a long-lasting standing position or erection. Physical examination involves palpation and observation of the scrotum at rest and during the Valsalva maneuver. Classification proposed by Dubin and Amelar is still the most widely used system for the assessment of the severity of varicocele⁽²⁰⁾. It is recommended for qualifying patients for surgical treatment (Tab. 1).

Tab. 1.

Classification of varicocele according to Dubin and Amelar

Grade I	Dilatation of the pampiniform plexus palpable only during the Valsalva maneuver, and not at rest
Grade II	Invisible varicocele palpable at rest
Grade III	Visible and palpable varicocele at rest

A number of other classification systems can be found in the literature, such as those proposed by Isakov (1977), Łopatkin (1978) or Coolsaet (1980). However, they are not used in common clinical practice. Only the WHO classification, which expanded the division proposed by Dubin and Amelar with the definition of subclinical varicocele, which are diagnosed only based on imaging techniques, has gained general acceptance (Tab. 2) ⁽¹⁸⁾.

Tab. 2.

Classification of varicocele according to the WHO

Subclinical	Non-palpable dilation of the pampiniform plexus, even during the Valsalva maneuver, but visible on ultrasound
Grade I	Palpable dilation of the pampiniform plexus only during the Valsalva maneuver
Grade II	Invisible but clearly palpable dilation of the pampiniform plexus without the Valsalva maneuver
Grade III	Visible and palpable varicocele at rest

Physical examination is often ambiguous due to its subjective nature and dependence on the experience of the examiner. It is of limited value in very obese patients, patients with high-located testes, those with a history of surgery in the scrotal or groin region, those with a coexistent hydro-cele as well as in patients with postoperative recurrence of varicocele. Ultrasound assessment may be very helpful or even necessary in these cases.

However, the use of ultrasonography is not generally recommended. It is recommended only by the European Association of Urology in patients with visible or palpable dilated veins in the pampiniform plexus⁽²¹⁾. The infertility diagnostics recommended by the American Association of Urology does not involve standard ultrasound assessment in patients with varicocele⁽²²⁾. According to the American Society for Reproductive Medicine, ultrasonography should not be used as a basic examination in all patients with varicocele, but its place in the diagnostic algorithm should be defined as complementary⁽²³⁾. These differences result from the controversy regarding the role of subclinical varicocele in the development of infertility as well as the lack of clearly confirmed beneficial effects of surgical treatment in this patient population^{(24, 25)}.

Ultrasonographic assessment

Currently, ultrasound is the most commonly performed imaging technique in patients with varicocele. Non-invasiveness, patient’s safety and wide availability are the main advantages of this method⁽²⁶⁾. A linear transducer with a frequency of 7–14 MHz and with real-time Doppler function is the minimum hardware requirement to evaluate varicocele, as in accordance with the American Institute of Ultrasound in Medicine⁽²⁷⁾. It is important to avoid excessive compression of the scrotum by the ultrasound transducer as this reduces the vessel diameter and increases flow rate in Doppler analysis. The apparatus should be able to document the obtained images in analogue or digital form. The examination should be performed in a warm room, using preheated ultrasound gel and ensuring intimacy for the patient.

Ultrasound examination of varicocele is performed in a patient in a supine position. It is preceded by a manual examination of the scrotum, necessary for a proper interpretation of the ultrasound image. The measurement of the diameter of the veins in the pampiniform plexus (Fig. 1) and the assessment of potential reflux are performed in a supine position. This is followed by the Valsalva maneuver, during which the diameters of the veins in the pampiniform plexus are measured and regurgitation is evaluated. It is very important to instruct the patient on the Valsalva maneuver technique as well as to standardize the test so that it is conducted in the same manner and the patient’s movements are as limited as possible. This allows to obtain diagnostic images with no motion artifacts. Additionally, the examination should be performed in a standing position and include vascular diameter measurements with the assessment of changes in flow direction between rest and the Valsalva maneuver. The inguinal channel, the upper part of the scrotum as well as the supra- and peritesticular regions should be checked for the presence of varicocele. The US assessment of regurgitation may be performed using color or spectral Doppler. The reverse flow during the Valsalva maneuver is associated with Doppler color changes (Fig. 2). The assessment of reflux based on the spectral flow curve focuses on identifying a change in the flow direction as well as on the measurement of flow duration and maximum velocity (Fig. 3). Ultrasonography also allows for testicular volume measurement, which is of significant importance for the pre- and postoperative assessment as well as conservative treatment^{(28, 29)}. The volume is expressed in milliliters, and the measurement is performed using an ellipsoid volume formula, i.e. 0.52 × length ×width × height.

Fig. 1.

Varicocele in B-mode presentation (1= 0.34 cm)

Fig. 2.

A. Varicocele. B. Regurgitation during the Valsalva maneuver in color Doppler

Fig. 3.

An assessment of reflux based on the spectral flow curve

Despite the popularity of ultrasound imaging, there is no universal and recognized system to classify varicocele severity. There are several methods for their assessment, which are mainly based on venous width measurement, evaluation of blood flow direction at rest and during the Valsalva maneuver as well as reflux duration and the rate of regurgitation. Although the first systems for the assessment of the size of varicocele were already based on the measurement of the diameter of the veins in the pampiniform plexus, there still are some discrepancies between the methods for their evaluation. The main reason for this is the lack of clear boundary values for the diameter of the veins in the pampiniform plexus (Tab. 3)^(30–36).

Tab. 3.

Boundary values for the veins in the pampiniform plexus, above which the diagnosis of varicocele is recommended by different authors

Vascular diameter [mm]	Authors	Source
2	Rifkin et al.	(30)
2	Gonda et al.	(31)
3	Hoekstra et al.	(32)
3	McClure et al.	(33)
3.6	Eskew et al.	(34)
5	Metin et al.	(35)
5.7	Orda et al.	(36)

Apart from vascular dilation, the presence of regurgitation is another important parameter for the assessment of varicocele. Varicocele is graded based on reflux assessment by a number of classification systems. One of the first classification systems was proposed by Sarteschi⁽³⁷⁾. Grade 1–3 reflux does not cause scrotal deformation or testicular hypotrophy, which distinguishes it from grade 4 reflux, which is accompanied by scrotal deformation and, often, testicular growth arrest as well as grade 5 reflux, which is always accompanied by testicular hypotrophy (Tab. 4).

Tab. 4.

Classification according to Sarteschi⁽³⁷⁾

Grade I	Reflux at the level of groin only during the Valsalva maneuver, without scrotal deformation or testicular hypotrophy
Grade II	Reflux at the level of the proximal segment of the pampiniform plexus only during the Valsalva maneuver, without scrotal deformation or testicular hypotrophy
Grade III	Reflux in the distal vessels at the level of lower scrotum only during the Valsalva maneuver, without scrotal deformation or testicular hypotrophy
Grade IV	A spontaneous reverse flow, increasing during the Valsalva maneuver, with scrotal deformation and possible testicular hypotrophy
Grade V	Resting reflux in the dilated pampiniform plexus, possibly increasing during the Valsalva maneuver, always accompanied by testicular hypotrophy

This extensive classification is not widely used for the assessment of varicocele, which is also the case of the classification system proposed by Chiou. This system takes into account the maximum venous diameter (scores 0 to 3), the presence of venous plexuses (scores 0 to 3) and a change in flow direction during the Valsalva maneuver (scores 0 to 3). A score of at least 4 is required for the diagnosis of varicocele⁽³⁸⁾. There are several other modifications of the above classification systems, which are also based on reflux assessment, e.g. classification proposed by Ios and Lazzarini⁽³⁹⁾. The criticism of the above described classification systems is primarily related to their poor correlation with the clinical status of patients qualified for varicocele surgical treatment. Furthermore, they are of low predictive value for impaired spermatogenesis, which is the primary indication for surgical treatment⁽⁴⁰⁾. Recently proposed classification systems based on the assessment of regurgitation velocity or duration in varicocele during the Valsalva maneuver put great emphasis on the correlation between the identified manifestations and the clinical status as well as the course of disease^{(28, 29)}. Kozakowski et al. proposed an assessment scheme for varicocele in adolescents⁽²⁸⁾. It evaluates the maximum regurgitation velocity during the Valsalva maneuver and the difference in venous diameters at rest and during the Valsalva maneuver. Regurgitation velocity during the Valsalva maneuver of more than 38 cm/s, and >20% difference in the diameters of the veins in the pampiniform plexus between rest and the Valsalva maneuver, indicate a significantly increased risk of testicular growth arrest in young patients. According to a number of authors, surgical treatment in this group of patients should be initiated as early as possible to avoid testicular hypotrophy. Patients with regurgitation velocity during the Valsalva maneuver of less than 38 cm/s and <20% difference in the diameters of the veins in the pampiniform plexus between rest and the Valsalva maneuver did not show significant testicular growth arrest or testicular atrophy during the follow-up period. Conservative treatment and an active follow-up are the method of choice in this patient population. The role of ultrasonography in the qualification for surgical treatment is significantly greater in adolescents than in adults as testicular volume differences, which are difficult to evaluate during physical examination, are an important parameter in this group of patients. Surgical treatment is usually implemented in patients with testicular diameter difference of >20%; an annual follow-up of semen volume and parameters is recommended in other patients^{(41, 42)}. Goren et al. assessed the relationship between the duration of regurgitation and the effects of treatment⁽²⁹⁾. After varicocelectomy, improved semen parameters were observed statistically more commonly in patients with preoperative regurgitation lasting more than 4.5 seconds. The authors suggest that a fast and simple measurement of regurgitation duration during the Valsalva maneuver may in the future become an important ultrasonographic criterion in determining the indications for surgical treatment. Patil et al. also based their assessment of varicocele on reflux duration⁽⁴³⁾. The authors investigated the duration of regurgitation in the veins of the pampiniform plexus during the Valsalva maneuver in patients in the supine position. The obtained measurements allowed to determine time intervals for the duration of regurgitation, which positively correlated with the clinical severity of varicocele, as in accordance with Dubin and Amelar (Tab. 5).

Tab. 5.

Classification of varicocele based on the measurement of the duration of regurgitation in accordance with Patil

Dubin and Amelar	Patil	The duration of regurgitation during the Valsalva maneuver
	Grade 0	<1000 ms
Grade I	Grade I	1000–2500 ms
Grade II	Grade II	2500–4000 ms
Grade III	Grade III	>4000 ms

It seems that elastography may prove useful for assessing the effects of varicocele on the testes in the future. Dede et al. conducted a prospective study to assess the possibility to detect changes in testicular structure using acoustic radiation force impulse elastography (ARFI)⁽⁴⁴⁾. The study included 30 patients with left-sided varicocele and 30 varicocele-free men with normal laboratory findings. Comparison of both these groups demonstrated lower testicular stiffness values in patients with varicocele despite the absence of perceptible changes in testicular cohesion on palpation. Furthermore, the authors found an inverse correlation between elastography findings and the clinical severity of varicocele as well as the level of follicle-stimulating hormone.

Other imaging techniques

The wide availability of ultrasonography has significantly limited the importance of other imaging techniques assessing varicocele, thermography and nuclear medicine in particular. Thermography allows for a detection of varicocele by identifying regional hyperthermia at the level of the pampiniform venous plexus or the testis^{(45, 46)}. It is believed that a temperature in the pampiniform venous plexus of >34°C and the temperature in the testis of >32°C indicates varicocele, similarly as a temperature difference of >0.5°C between the left and the right side of the scrotum⁽⁴⁷⁾. The examination is limited by its low specificity as both, scrotal inflammation and neoplasms can cause local temperature elevation^{(46, 47)}. Scintigraphy allows for a detection of varicocele as well as for an assessment of hemodynamics of arterial and venous scrotal vascularization^(48–50). However, multiple factors prevent the routine use of scintigraphy in varicocele diagnosis. These include, for example, the need for intravenous radioisotope administration, and thus its more invasive nature compared to ultrasonography, heterogeneous methodology of the published studies, not entirely clear link between abnormalities reveled by scintigraphy and treatment outcomes as well as significantly lower availability.

Venography, introduced by Ahlberg in 1966, represents a historical gold standard in the diagnosis of varicocele⁽⁵¹⁾. Currently, it is no longer applied for purely diagnostic purposes, but used for intraoperative assessment (ascending venography) or as an introduction to intravascular treatment (ascending or descending venography) to evaluate the anatomy of collateral circulation and developmental variations^{(9, 10)}.

So far, there has been only one publication on the possibilities of computed tomography in the dynamic diagnosis of the veins in the pampiniform plexus⁽⁵²⁾. The authors evaluated the cross sectional area of spermatic cords using two cross-sections, one at rest and one during the Valsalva maneuver. Both, the cross-sectional area at rest and its percentage increase during the Valsalva maneuver was statistically higher on the side of varicocele compared to the healthy site (80–100 mm² vs. 100–200 mm² and 4080% vs. 100–200%, respectively)⁽⁵²⁾. However, this subject was not continued in later publications, probably due to exposure to ionizing radiation during the examination. CT is a recognized method for the assessment of retroperitoneal anatomy and pathology. Research using CT angiography confirmed the role of variations in the retroperitoneal venous system, such as retroaortic left renal vein, in the etiopathogenesis of varicocele^{(53, 54)}. Although a routine use of CT for the assessment of the retroperitoneal space in patients with varicocele is not indicated, it is justified in the case of clinical suspicion that the varicocele is a manifestation of retroperitoneal space tumor, e.g. in the case of sudden onset of unilateral or isolated right-sided varicocele in an elderly patient^{(55, 56)} (Fig. 4).

Fig. 4.

A. Computed tomography: a 70-year-old patient with varicocele, with larger varicocele on the right (arrows). B. A large right renal cell carcinoma (RCC) with lymph node metastases. C. A tumor plug entering the inferior vena cava and filling nearly its entire cross-section

Magnetic resonance angiography represents an attractive alternative for CT scans in the assessment of the retroperitoneal space and allows for varicocele visualization. The absence of ionizing radiation and the possibility to perform the test in patients with contraindications to iodinated contrast agents are advantages of this method⁽⁵⁷⁾. Karakas et al. assessed in their pioneering work the possibility to detect testicular damage in patients with left-sided varicocele using diffusion-weighted MRI (DW-MRI). They demonstrated lower apparent diffusion coefficient (ADC) in the testes of patients with varicocele compared to healthy volunteers⁽⁵⁸⁾. The lesions were bilateral, and the ADC values were inversely proportional to the degree of venous dilation. The authors suggest that ADC reduction may reflect testicular fibrosis. However this subject needs further investigation as no correlation with histopathological findings was evaluated and no post-treatment ADC changes were assessed.

Summary

Ultrasound is currently the most widely used imaging technique for the assessment of varicocele. Its role in the diagnostic algorithm is still controversial, which is reflected by the differences in clinical recommendations published by recognized urologic societies. This is due to an insufficient correlation between ultrasonographic classification systems and clinical assessment of varicocele severity as well as limited prognostic value for treatment outcomes. Therefore, the future attempts of researchers and ultra-sonography societies should aim to overcome these problems. Attempts to determine the manifestations of testicular damage that precede morphological changes, which could increase the importance of imaging techniques in treatment planning, are particularly promising.

Conflict of interest

Authors do not report any financial or personal connections with other persons or organizations, which might negatively affect the contents of this publication and/or claim authorship rights to this publication.