Although a multitude of radiologic and physical exam techniques exist for describing varicoceles, the lack of quantitative gold standards for classifying varicoceles has made it difficult to perform comparative studies and outcome analyses. Most clinicians agree, however, that a diligent physical examination is the cornerstone for diagnosis.
The examination is initially performed in a warm room with the patient standing, to accentuate venous dilatation. The scrotum should first be carefully observed for a bluish distenrion of the dilated cord veins. If the varicocele is not visually apparent, the cord structures should then be bilaterally palpated, with Valsalva maneuver (which tends to distend venous cord structures) as well as without Valsalva. A palpable varicocele has been described as feeling like a “bag of worms,” although in less obvious cases, there may be simple asymmetry or thickening of the cord. The examination should continue with the patient supine, primarily to differentiate a cord lipoma (thickened, fatty cords found while standing that do not disappear when supine) from a varicocele. Palpation and measurement of the testicle using an orchidometer (for consistency and size, respectively) may also give the clinician insight into intragonadal pathology. Classically, if disproportionate testicular lengths or volumes are found, the index of suspicion for a varicocele should increase.
Varicoceles have been arbitrarily assigned a clinical grading classification (Table Classification of Varicocele). Although this system allows practitioners to clinically follow their own patients more easily, it is subjective in nature and has developed without validation. In a physical examination study, Hargreave compared the physical findings by two experienced clinicians and found disagreement in 26% of the patients. Yet, the authors of this paper feel that the optimal diagnosis of varicocele can still be made by a skilled clinician with an acceptable degree of error despite inherent flaws in both physical examination techniques and the current grading system. In an effort to ameliorate the present inconsistencies in the classification and diagnosis of varicoceles, however, various radiologic modalities including ultrasound, venography, thermography, scintigraphy, and magnetic resonance imaging (MRI) continue to be studied.
Table Classification of Varicocele
|Grade||Physical examination findings|
|I||Detectable by palpation with difficulty|
|More prominent with Valsalva|
|II||Detectable easily by palpation|
|More prominent with Valsalva|
|Not visible through scrotal skin|
|III||Palpable without Valsalva|
|Visible through scrotal skin|
Color Doppler ultrasound (CDUS) is a simple, inexpensive, noninvasive, objective method that may be used to investigate the scrotum not only for the presence of varicocele but also for other pathologic processes and the documentation of testicular size. Sensitivities are reportedly as high as 97%, with specificities around 94%. Generally, varicoceles are considered present by gray scale evaluation if two or more veins are identified, with at least one vein having a diameter of 3 mm. Dilated veins that are 5 mm or larger in diameter have been proven to be almost always clinically palpable.
In 1991, Petros et al. hypothesized that retrograde flow within the pampiniform plexus detected on color Doppler sonography was diagnostic of varicocele regardless of the dimensions of the veins involved. Two small subsequent papers, however, disputed these controversial findings: in 1993, Aydos et al. demonstrated that 59% to 83% of their infertile male patient population had reflux detected by CDUS without clinical evidence of varicocele, and Eskew et al. subsequently published that CDUS reflux was relatively insensitive for the detection of venographically confirmed varicoceles in a population of 33 men with possible male-factor infertility. In addition to identifying retrograde flow with questionable meaningfulness, ulrrasonography sensitivity has also progressed to detecting scrotal varicocities that are too subtle to identify on physical examination, known as “subclinical varicoceles.” Studies continue to be published concerning the development of criteria to differentiate pathological from physiologically normal components of testicular vasculature. Because of these reasons, scrotal ultrasound is not routinely used in the varicocele evaluation. Further, ultrasound is extremely operator dependent, and improper interpretations of flow or subclinical findings of unknown significance may lead to unwarranted surgical procedures.
Historically, radiologic placement of contrast through a catheter tip into the spermatic vein orifice (venography) is considered the best diagnostic test for varicocele. Result reproducibility is high, assessment of anatomy and presence of reflux is feasible, and simultaneous, immediate treatment with embolizarion (detachable coils or balloons) or sclerosing therapy is certainly an option. The procedure is invasive, however, and has associated complication rates (see section “Treatment”). Most authors agree that variations in operator technique and the lack of standardization for contrast injection pressures make the assessment of results and outcomes difficult. When used exclusively for diagnostic purposes, venography is recommended only in the subset of patients with recurrent varicoceles post varicocelectomy to aid in the detection of aberrant venous drainage.
Thermography, Scintigraphy, and MRI
Originally described in 1979 using scrotal skin contact strips, thermography assessment of varicoceles is an infrequent form of varicocele evaluation. Although newer liquid crystal contact strips have been developed, multiple studies have found these strips to be unreliable during the physical exam (sensitivity 97% and specificity 9%). More promising is the development of a fairly sensitive, focal-plane-array thermal imaging camera designed to look for asymmetrical patterns of scrotal temperatures. Small, promising correlation studies between thermography and venography have recently been published and may have some promise for future varicocele diagnosis. Published studies on 99mTc-based compound scintigraphy time-activity curves as well as the use of gadolinium-enhanced magnetic resonance angiography to evaluate varicoceles have not been demonstrated to be clinically reliable and are limited by the need for sophisticated equipment and cost.
Consequence of Varicocele
Once the diagnosis of varicocele is made, a discussion of its relevance to infertility may be warranted, particularly in the case of male patients presenting with infertility problems.
Although studied extensively, there is no consensus on the relationship between varicocele and changes in semen count, morility, or morphology. MacLeod introduced the following varicocele-associated impairments in semen parameters in 1965: a decrease in morility (observed in 85% of study patients), oligospermia (defined as a sperm concentration of less than 20xl06 and observed in 65% of study patients), as well as the concept of “stress pattern.” MacLeod’s classic description of stress pattern included the following characteristics: greater than 15% of sperm having a tapered shape (tapered forms), immature cells of the germinal line (typically, early spermarids), and increased amorphous cells. MacLeod did acknowledge that similar morphologic changes were present in infertile patients without varicocele, including those suffering from viral illness, acute allergic reactions, and other environmental insults with antispermatogenic agents. Multiple other papers have subsequently affirmed that “stress pattern” is not specific for varicocele and can be found in infertile patients without varicocele. Fertile men with varicoceles do not, in general, exhibit the stress pattern of tapered spermatozoa.
Moro discovered that 20% of men with varicocele and severe oligospermia (defined as a sperm concentration less than 5 million / mL) have microdeletions of the Y chromosome. Three recent studies in men with large varicoceles (Grade III) and varicocele-associated testicular atrophy have demonstrated lower sperm counts and motility than men with smaller varicoceles or without atrophy, respectively. Overall, there is no reliable, predictable relationship between semen parameter changes and varicoceles. While abnormal semen parameters do not confirm nor exclude a varicocele, they do, however, provide insight into abnormal testicular function and may be followed serially when treating men with varicoceles and infertility.
Pathologic and Endocrine Changes
Alterations in testicular tissue and the hypothalamicpiruitary axis in men with varicoceles have repeatedly been proven. Apoptoric germ cells are increased to 10% in men with varicocele compared with 0.1% in normal fertile controls. Histologic changes present in both testicles in the presence of unilateral varicocele include tubular thickening, interstitial fibrosis, decreased spermatogenesis in seminiferous tubules, degenerative changes in Leydig and Sertoli cells, and maturation arrest. Lastly, multiple adult and adolescent studies have demonstrated that the presence of a unilateral varicocele causes a progressive decline in testicular function over time, as well as impaired ipsilateral testicular growth.
Elevations in serum follicle-stimulating hormone (follicle-stimulating hormone) and abnormal gonadotropin releasing hormone (gonadotropin-releasing hormone) stimulation tests are occasionally present in subferrile men with varicocele, but no causality has been established in most cases. Serum luteinizing hormone and testosterone levels in men with varicoceles are quite variable and not reliably predictive. Some have speculated that variable serum testosterone findings in men with varicocele may relate to compensatory Leydig cell hyperplasia, suggesting that the majority of men with varicoceles are fertile because they start with “high spermatogenic potential” and thus “remain within the fertile range despite the adverse effect of the varicocele”.
Overall, it is clear that varicoceles are detrimental to testicular spermatogenesis. They are associated with testicular decline over time and may or may not show systemic endocrine effects. Most importantly, physicians should remember that the presence of a varicocele alone does not necessarily translate into infertility. Other causes of infertility such as the female factor and microdeletion of the Y chromosome should be explored if clinically applicable.