Cornell University

NEW YORK
CORNELL		Cornell University
Weill Medical College
Cornell Institute for Reproductive Medicine

Center for Male Reproductive Medicine and Microsurgery

"State-of-the-Art Compassionate Care for the Infertile Couple"

Varicocele

Introduction
Etiology
Pathophysiology
Diagnosis
Surgical Treatment
  1. Indications
  2. Microsurgical technique
Complications of varicocele Repair
Results
Cost-effectiveness
Summary
Reference and Suggested Reading


Introduction

Varicoceles are abnormally dilated testicular veins (pampiniform plexus) of in the scrotum, which is normally secondary to internal spermatic vein reflux. Varicocele is found in approximately 15% of the general population, 35% of men with primary infertility and in 75-81% of men with secondary infertility. It is more common on the left side. In adolescents, the incidence of varicocele is approximately 15%; the abnormality is extremely rare in prepubertal boys

Although most men with varicoceles are able to father children, there is abundant evidence that varicoceles are detrimental to male fertility. A study by the World Health Organization (WHO) on over 9,000 men showed that varicoceles are commonly accompanied by decreased testicular volume, impaired sperm quality, and a decline in Leydig cell function.2 Another report by Johnson and colleagues showed that 70% of healthy, asymptomatic military recruits with palpable varicoceles had an abnormality on semen analysis.3 Furthermore, studies in animals4,5 and humans6-8 suggest that varicoceles cause progressive testicular damage over time. It appears that surgical repair of varicoceles not only halts this declines in testicular function but often reverses it. Whether the improvements in semen parameters, seen in 80% of men after varicocele ligation, translate into improved pregnancy and delivery rates has been a matter of ongoing controversy. Recent studies employing non-operated control groups clearly indicate that varicocelectomy does improve pregnancy rates.48


Etiology

Presumably due to anatomic differences, varicoceles are much more common on the left side. The incidence of bilaterality is anywhere from 15 to 50% but isolated right varicoceles are fairly rare. The left internal spermatic vein empties into the left renal vein. It is 8 to 10cm longer than the right internal spermatic vein, which drains into the inferior vena cava. This is believed to result in increased hydrostatic pressure that is transmitted down the vein to the scrotal pampiniform plexus, causing dilation and tortuosity of these vessels.9 Elevated pressure in the left internal spermatic vein may also result from compression of the left renal vein between the aorta and the superior mesenteric artery, a phenomenon known as the “nutcracker effect.” Radiologic studies have documented relative distention of the proximal left renal vein suggesting partial distal obstruction.10

Varicoceles may also arise secondary to reflux of venous blood into the pampiniform plexus as a result of absent or incompetent valves within the internal spermatic vein. A report by Braedel et al. on over 650 consecutive men with varicoceles revealed that 73% had absent internal spermatic venous valves on venography.11

Varicoceles generally become clinically manifest at the time of puberty. Although there is no data to suggest a genetic basis for these lesions and hereditary patterns have not been identified, these issues have been poorly studied. Retroperitoneal masses such as sarcomas, lymphomas, and renal tumors have been known to cause varicoceles by obstructing venous outflow from the testicles but varicoceles are not known to be a component of any clinically recognized syndrome.


Pathophysiology

Despite a large number of animal and human studies, the exact mechanism whereby varicoceles cause impaired testicular function remains poorly understood. Theories include abnormally high scrotal temperature, hypoxia due to venous stasis, dilution of intratesticular substrates (e.g. testosterone), imbalances of the hypotalamic-pituitary-gonadal axis, and reflux of renal and adrenal metabolites down the spermatic vein. Data exist to both support and refute each of these possibilities. In addition, nitric oxide,12 reactive oxygen species,13 and regulators of apoptosis14 have all recently been implicated in the pathophysiology of varicoceles. It appears that cigarette smoking in the presence of varicocele has a greater adverse effect than either factor alone.15

The most vigorously studied pathophysiologic theory is that of increased testicular temperature. It has long been observed that even minor fluctuation in temperature can affect spermatogenesis and sperm function.16,17 It has been suggested that varicoceles impair testicular thermoregulation by disrupting the countercurrent heat exchange mechanism in the pampiniform venous plexus. Reversal of testicular blood flow abnormalities and a drop in testicular temperature have been seen in the rat after varicocele repair.18 Recently, Wright and colleagues showed in humans that scrotal skin surface temperatures were elevated in men with varicoceles compared to control patients. Following varicocele ligation, scrotal temperatures returned to a level nearly identical to those of controls.19 Previous studies have demonstrated that scrotal skin surface temperatures reliably reflect intratesticular temperatures.20 The pathophysiology of varicocele is probably multi-factorial.


Diagnosis

Varicoceles are defined as dilations of veins of the pampiniform plexus, which are believed to be caused by incompetent valves of the internal spermatic veins.

The diagnosis of a clinical significant varicocele is generally made on physical examination of the scrotum and its contents. The patient is examined in the supine and standing position in a warm room that promotes relaxation of the scrotal dartos muscle and facilitates accurate evaluation for varicocele. The scrotum should be inspected carefully for any easily visible dilated veins (Figure 1a, 1b). The spermatic cord should be palpated between thumb and forefingers for palpable vein. Both sides of spermatic cords should be palpated while the patient performs a Valsalva maneuver.

The severity of the varicoceles is graded I through III using the system outlined in following table 1. Grade I varicoceles can be thought of as small, Grade II, medium and Grade III, large. Varicoceles should significantly diminish in size when the patient assumes the supine position. If the varicocele remains prominent with the patient supine, this finding suggests a mechanical obstruction to testicular venous outflow such as a retroperitoneal mass (sarcoma, lymphoma or a renal tumor with venous thrombus). An abdominal ultrasound or CT scan should be obtained to evaluate the retroperitoneum in these patients.

Table1: Clinical Varicocele Classification
ClassificationDefinition
Clinical ( palpable):
    Grade III ( Large)
    Grade II (Medium)
    Grade I ( Small)
Subclinical ( not palpable)

  • Easily visible ( Figure1A)
  • Palpable at rest (without Valsalva maneuver), invisible.
  • Palpable with Valsalva maneuver only

  • Vein larger than 3 mm on ultrasound; Doppler reflux on Valsalva maneuver


Scrotal ultrasonography with color flow Doppler imaging may prove useful in equivocal cases or in patients with a body habitus that makes accurate physical examination of the scrotum impossible. Using ultrasonography, the diameter of the internal spermatic vein can be measured and retrograde flow through the vein during Valsalva documented. Veins that are greater the 3.5mm can generally be detected on physical exam. Those that are 2.7mm or less are usually not palpable and have been termed “subclinical” varicoceles.21 The need for diagnosing and treating subclinical varicoceles is controversial.22 Recent studies have indicated that repair of subclinical varicoceles is of questionable value.23 However, other reports have indicated that repair of small palpable or subclinical right varicoceles may be beneficial if present in conjunction with a larger left sided varix.24-26

Venography is generally considered the most accurate method of varicocele diagnosis when performed by an experienced interventional radiologist.27 Due to its invasiveness, venography is usually only performed in the research setting to document recurrences or for a comparison to other, less invasive diagnostic techniques.

A multi-center WHO study on the influence of varicocele on fertility parameters demonstrated that the mean Testosterone (T) concentration of men older than 30 years of age with varicoceles was significantly lower than that of younger patients with varicoceles, whereas this trend was not seen in men without varicoceles.2,32 When exogenous hCG is administered to men with varicoceles, a blunted T response is observed compared to controls without varicoceles.28 Repairing varicoceles appears to improve serum Testosterone (T) levels. This observation was made over twenty years ago by Comhaire and Vermeulen29 and was confirmed recently in a larger series by Su, et al.30 Taken together, these findings indicate that varicoceles result in abnormal Leydig cell function in some men, but these patients may also be the ones to most benefit from surgical repair.

The abnormalities of semen parameters in infertile men with varicocele were first objectively described by Macleod in 1965 57. In that study, Macleod observed that the vast majority of semen samples, obtained from 200 infertile men with varicocele, were found to have an increased number of abnormal forms, decreased motility and lower mean sperm counts. This 'stress pattern', which is also characterized by an increased number of tapered forms and immature cells, was also reported in other studies. However, other investigators have shown that the characteristic stress pattern is not a sensitive marker for varicocele, and believe that it is not diagnostic of this pathology. A large number of studies have evaluated the effects of varicocelectomy on semen parameters. Most of these studies have demonstrated an improvement in sperm density with or without a concomitant increase in sperm motility and morphology after varicocelectomy, suggesting a cause and effect relationship between varicocele and abnormal semen parameters. However, because the bulk of the reported outcome data on varicocelectomy comes from uncontrolled or poorly designed controlled studies, the value of those results is limited. The impact of the grade of varicocele on the magnitude of improvement in semen quality after varicocelectomy is equivocal. Steckel et al., reported that men with larger varicoceles present with lower sperm densities, and show greater relative improvement in semen quality than men with smaller varicoceles who present with higher mean sperm densities59. On the other hand, Braedel et al., demonstrated less of an improvement in sperm density in men with grade 3 varicocele, than men with smaller varicoceles.60

Although the relationship between varicocele size and seminal improvement following varicocele repair was controversial for many years, the overall rates of seminal improvement following varicocele repair have been approximately 65%. Moreover, some recent studies indicated that the degree of improvement of semen parameters following varicocele repair is directly proportional to the size of the varicocele repaired surgically.


Surgical Treatment

1. Indications: The majority of men with varicoceles remain fertile and asymptomatic. Therefore, treatment of all varicoceles is clearly unnecessary. The authors advocate surgical correction of clinically detectable varicoceles associated with abnormal semen parameters in an infertile couple following appropriate evaluation of the female partner. This includes men with azoospermia and very severe oligospermia.

Palpable varicoceles should be corrected in adolescent boys when accompanied by ipsilateral testicular atrophy or if the varicocele is very large. It has been suggested that adolescents with varicocele and an abnormal gonadotropin response to LHRH may also benefit from repair.32 Finally, varicoceles associated with debilitating testicular pain may be considered for repair.

A variety of surgical approaches have been advocated for varicocele repair (varicocelectomy), including open surgical, laparoscopic, and percutaneous techniques. Ideally, the perfect procedure would be one that ligates both the veins contributing to the varix at the time of repair and those that could cause a recurrence in the future. However, some veins clearly must be preserved so as to allow drainage of blood from the testis and prevent vascular engorgement. Therefore, the ideal procedure should be one that leaves the testicular arteries, lymphatics, and vas deferens intact. A minimally invasive procedure which reduces morbidity, pain and recovery time is also desirable.

2. Microsurgical Technique: We believe that the technique most closely approaching this “ideal” is the mini-incision, inguinal, or subinguinal microsurgical varicocelectomy with delivery of the testicle.33 Although it is a technically demanding approach, the real advantages of the microsurgical approach to varicocele repairs are reliable identification and preservation of the testicular artery or arteries, cremasteric artery or arteries, and lymphatic channels and reliable identification of all internal spermatic veins and gubernacular veins. Delivery of the testis assures direct visual access to all possible routes of venous return, including external spermatic, cremasteric, and gubernacular veins. Postoperatively, venous return is via the vasal veins, which drain into the internal pudental system and usually have competent valves.

The introduction of microsurgical technique to varicocelectomy has resulted in a substantial reduction in the incidence of postoperative hydrocele formation and testicular atrophy or azoospermia, respectively. This is because the lymphatics can be more easily identified and preserved. Furthermore, the use of magnification enhances the ability to identify and preserves the 0.5 - 1.5-mm testicular artery, thus avoiding the complications of atrophy or azoospermia.

Microsurgical Approaches: After standard preparation and draping of the patient, the position of the external inguinal ring is marked as " X" on the skin. The incision extends about 2 cm from the mark following natural skin line (Figure 2). The size of the incision depends somewhat on the obesity of the patient and the size of the testicle being delivered.

The spermatic cord is exposed by hooking an index finger under the external inguinal ring while sliding a small Richardson retractor in the incision along the dorsum of the index finger and pulling in the opposite direction .The cord is encircled with a Babcock clamp (Figure 3). With gentle traction the cord is exposed, encircled with a Babcock clamp, and delivered. The ilioinguinal and genital branches of the genitofemoral nerve are excluded and preserved. The Babcock clamp is replaced with a Penrose drain and the testis is delivered.

The gubernaculum is carefully inspected and any veins encountered are either electrocoagulated or clipped and divided depending on their size. All perforating external spermatic veins and gubemacular veins are also divided (Figure 4). The gubernacular veins have been demonstrated radiographically to account for 10% of varicocele recurrences10.



Delivery of the testicle enables the surgeon to identify and ligate these vessels, which are responsible for some varicocele recurrences (Figure 5).



Once all external spermatic perforators and gubernacular veins have been divided, the testicle is returned to the scrotum and the spermatic cord remains elevated over a large Penrose drain for stabilization in preparation for microscopic examination (Figure 6)


The operating microscope is then brought into the operating field and the cord is examined under 8 to 15-power magnification. The internal and external spermatic fascias are opened longitudinally and the cord is examined. The magnification is increased to 15 power and 1 % papverine is dripped over the cord. The testicular artery is identified by its pulsation and is dissected free from all surrounding tissue, tiny veins, and lymphatics using a fine-tipped, non-locking micro-needle holder and Pierse tissue forceps. The pulsation of suspected by seeing a pulsating column of blood appears just over the needle holder. The artery is identified and then encircled with a zero silk suture to preserve it (Figure 7). Any additional artery encountered are also identified and preserved in this manner. All remaining internal spermatic veins with the exception of the vasal veins are clipped with hemoclips or ligated and divided. Care is taken to preserve a majority of lymphatics as these can contribute to hydrocele formation postoperatively when divided.

At the completion of varicocelectomy, the cord should contain only the testicular artery or arteries, vas deferens and associated vessels, cremasteric muscle (with its veins ligated and artery preserved), and spermatic cord lymphatics.

This meticulous approach to varicocelectomy requires extensive training and the use of a high-quality operating microscope. Even loupe magnification is inadequate for the reliable identification of the tiny vascular channels and lymphatics of the spermatic cord. An experienced surgeon can perform this procedure in less than 30 minutes per side, and the procedure is always performed on an ambulatory basis.

Using the microsurgical technique at Cornell, we have reviewed our results of over 1,500 men who underwent microsurgical varicocelectomy, the couples' pregnancy rate was 43 % after one year and 69% after 2 years compared to 16% in couples with men who declined surgery and had hormone treatment or used insemination. There have been only 14 recurrences (1%), no hydrocele, no testicular atrophy, and a 1% incidence of inadvertent unilateral (one side only) testicular artery ligation14.

Some authors have suggested that the technique employed should be governed by the clinical situation. In a recent report, Abdulmaaboud et al. advocated percutaneous embolization for isolated left-sided varicoceles and laparoscopy for bilateral varicoceles.35 Failure rate for Balloon occlusion is 25% and laparoscopic approach requires general anesthesia and is also with great potential morbidity.


Complications of Varicocele Repair

Hydrocele formation is the most common complication reported after non-microsurgical varicocelectomy, with an average incidence of about 7%36 Hydroceles form secondary to ligation of the testicular lymphatics. At least half of all post-varicocelectomy hydroceles grow to a size that produces sufficient discomfort to warrant surgical hydrocelectomy. The effect of hydrocele function on spermatogenesis and fertility is unknown. Theoretically, large hydroceles may impair testicular function by insulating the testis and preventing normal thermoregulation. Use of the operating microscope has essentially eliminated the development of hydroceles following varicocelectomy.37, 38

Testicular artery ligation is also a common complication of non-microsurgical varicocelectomy although its true incidence is unknown.39 Injury or ligation of the testicular artery may cause testicular atrophy, impaired spermatogenesis, or both. Animal studies indicate that testicular atrophy occurs anywhere from 20% to 100% of the time following testicular artery ligation.40,41 In humans, Penn, et al. reported a 14% incidence of frank testicular atrophy, when the testicular artery was purposefully ligated during renal transplantation.42 Optical magnification and/or the use of a fine tipped Doppler probe facilitate identification and preservation of the testicular artery.

The incidence of varicocele recurrence following surgical repair varies from 1% to 45%. The incidence of recurrence depends upon the type of procedure performed and the use of magnification. Venographic studies have shown that recurrent varicoceles are caused by periarterial, parallel inguinal, midretroperitoneal, gubernacular and transcrotal collateral veins.36 The only approach equipped to deal with these vessels is the inguinal or subinguinal microscopic technique with delivery of the testis. A comparison of the various approaches to varicocelectomy is summarized in table 2.

Table 2: Techniques of Varicocelectomy

TechniqueArtery PreservedHydrocele (%)Recurrence (%)Potential for Serious Morbidity
Microscopic inguinalYes01no
RetroperitonealNo715-25no
Conventional inguinalNo3-305-15no
LaparoscopicYes125-15yes
BalloonYes07-25yes


Our recurrence rate at Cornell is less than 1%. Unintentional testicular artery ligation occurs in less than 1% of cases and hydroceles have been essentially eliminated. We have seen clinically significant improvements in semen parameters for over 80% of patients and natural pregnancy rates of 43% and 69% at one and two years respectively, controlling for female factors.


Results

Increasing evidence suggests that varicocele ligation improves semen quality and pregnancy rates. Unfortunately, the bulk of this data comes from retrospective, poorly controlled studies. Only two randomized, prospective, controlled studies have been performed. Nieschlag and colleagues reported on 125 couples with varicoceles who underwent either angiographic embolization, surgical ligation, or counseling.43 They found that semen parameters improved significantly in the treatment groups but pregnancy rates were no different than those couples receiving only counseling. Most of the varicoceles in this study were small (Grade I) and a microsurgical, artery sparing technique was not applied. A second study by Madgar, et al. was especially convincing because it employed a cross over design.44 Forty-five couples were randomized to receive either immediate varicocelectomy or delayed varicocelectomy following one year of observation. Despite the fact that a retroperitoneal, high ligation technique was used, pregnancy rates were 6 times higher in the men undergoing immediate varicocelectomy compared to those in the observation group (60% vs. 10% respectively) over the first year. Furthermore, pregnancy rates rose 4-fold in the observation group during the first year after surgical correction.

Overall, varicocelectomy results in significantly improved semen parameters in 60% to 80% of men and pregnancy rates of 20% to 60%. 45 One should keep in mind, however, that most of the studies used to generate these figures employed what the authors believe to be suboptimal varicocelectomy techniques. Using the microscopic subinguinal approach, we have observed a 69% pregnancy rate at two years postoperatively when female infertility factors were excluded.46

As mentioned previously, varicocelectomy can even be effective in men with azoospermia or severe oligospermia. Matthews and Goldstein recently reported that 55% of azoospermic men and 69% of men with zero motile sperm before surgery had motile sperm observed in their ejaculate after varicocele repair.47 Thirty-one percent of these otherwise sterile men contributed to pregnancies leading to live births including 19% who did so without the help of assisted reproduction. Steckel and co-workers found that men with large varicoceles have poorer semen quality than men with small varicoceles.59 Fortunately, the men with larger (Grade III) varicoceles also showed a greater degree of improvement following varicocelectomy.

When discussing varicocelectomy as a treatment for male infertility, it is again important to remember that varicoceles cause a progressive decline in testicular function (both spermatogenesis and steroidogenesis) with time.2 Thus, for couples desiring more than one child, the ability of varicocelectomy to prevent further deterioration may be even more important than the procedure's early beneficial effects on semen quality.

Varicocelectomy is indicated in adolescents when accompanied by ipsilateral testicular atrophy. Studies on adult men with varicoceles have shown that the degree of testicular atrophy is proportional to the clinical grade of the varicocele.48 Varicocele patients with testicular atrophy have worse semen parameters than those without atrophy.49 Several studies have shown quite convincingly that correction of adolescent varicocele results in rapid catch-up growth of the affected testis.50,53 In addition, a recent study by Lenzi and colleagues showed that adults who had varicoceles corrected during adolescence had significantly better semen parameters than adults with varicoceles detected during adolescence who did not have them repaired.54

Many men with varicoceles often experience intermittent, mild discomfort in the testis and scrotum on the affected side. The pain is usually described as a dull, throbbing ache. On rare occasions, the pain caused by a varicocele can become debilitating. After exhausting more conservative measures and ruling out other etiologies, varicocele ligation may be the only treatment alternative remaining. Peterson and colleagues recently reported on 35 patients who underwent varicocelectomy purely for the relief of pain.55 Eighty-six percent of the men experienced complete resolution of the pain postoperatively. Unfortunately, 11% had either persistent or worsening symptoms.


Cost -effectiveness

In the last decade, assisted reproductive techniques such as intracytoplasmic sperm injection (ICSI) have revolutionized the treatment of male infertility. The rising success rates and widespread availability of ICSI has led some gynecologists and reproductive endocrinologists to “bypass” both the evaluation and treatment of the male while proceeding straight to assisted reproduction. This is unfortunate because many cases of male infertility are caused by correctable conditions such as varicocele.

The managed care era has ushered in a heightened awareness of cost effectiveness and outcomes research. Schlegel recently performed a comparison of ICSI and varicocelectomy for the treatment of varicocele-associated infertility using a “cost per delivery” analysis.56 Total hospital delivery costs, complication costs, and costs attributable to multiple gestations were taken into account along with the published pregnancy and delivery rates for the two procedures. The overall cost per delivery for varicocelectomy averaged $26,300 compared to a striking $89,000 per delivery for ICSI in 1994 U.S. dollars. The European experience is similar. Comhaire, et al. has estimated that varicocelectomy is seven times more cost effective than ICSI.57 Although ICSI can clearly facilitate pregnancies in couples with varicocele-associated infertility, it is a very expensive alternative.


Summary

Varicoceles are common. They may be detected in 15% of the male population, 35% of men with primary infertility and up to 80% of men with secondary infertility. Studies have shown that varicocele causes progressive duration-dependent injury to the seminiferous epithelium and testicular function over time. The most likely pathophysiologic mechanism is an elevation of testicular temperature due to impaired scrotal thermoregulation. Varicocele repair will halt this duration-dependent process.

The most common complications from varicocelectomy are hydrocele, varicocele recurrence, and testicular artery injury. Use of the operating microscope allows for reliable identification of spermatic cord lymphatics, internal spermatic veins and venous collateral, and the testicular artery or arteries so that the incidence of these complications can be reduced significantly. Delivery of the testis through a small subinguinal incision provides direct visual access to all possible avenues of testicular drainage. Although some controversy continues to surround varicocelectomy as a treatment of male factor infertility, a great deal of data does exist to support this form of therapy. Ultimately, a final answer will require a large, prospective, randomized and controlled study using a microsurgical, artery and lymphatic sparing technique.


Reference and Suggested Reading

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2. World Health Organization: The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril 57:1289, 1992. 3. Johnson DE, Pohl DR, Rivera-Correa H: Varicocele: an innocuous condition? South Med J 63:34, 1970.

4. Nagler HM, Li XZ, Lizza EF, et al: Varicocele: temporal considerations. J Urol 134:411, 1985.

5. Harrison RM, Lewis RW, Roberts JA: Pathophysiology of varicocele in nonhuman primates: long-term seminal and testicular changes. Fertil Steril 46:500, 1986.

6. Russell JK: Varicocele, age, and fertility. Lancet 2:222, 1957.

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8. Witt MA, Lipshultz LI: Varicocele: a progressive or static lesion? Urology 42:541, 1993.

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13. Sharma RK, Agarwal A: Role of reactive oxygen species in male infertility. Urology 48: 835, 1996.

14. Baccetti B, Collodel G, Piomboni P: Apoptosis in human ejaculated cells (notulae seminologicae 9). J Submicrosc Cytol Pathol 28:587, 1996.

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17. Dutt RH, Hamm PT: Effect of exposure to high environmental temperatures and shearing on semen production in rams in winter. J Anim Sci 16:328, 1957.

18. Hurt GS, Howards SS, and Turner TT: Repair of experimental varicoceles in the rat: long-term effects on testicular blood flow and temperature and cauda epididymal sperm concentration and motility. J Androl 7:271, 1986.

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20. Kurz KR, Goldstein M: Scrotal temperature reflects intratesticular temperature and is lowered by shaving. J Urol 135:290, 1986.

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24. Kondoh N, Meguro N, Matsumiya K, et al: Significance of subclinical varicocele detected by scrotal sonography in male infertility: a preliminary report. J Urol 150:1158, 1993.

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37. Goldstein M, Gilbert BR, Dicker AP, et al: Microsurgical inguinal varicocelectomy with delivery of the testis: an artery and lymphatic sparing technique. J Urol 148:1808, 1992.

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47. Matthews GJ, Matthews ED, Goldstein M: Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectimy in men with azoospermia and severe oligoasthenospermia. Fertil Steril 70:71, 1998.

48. Zini A, Buckspan, M, Berardinucci D, et al: Loss of left testicular volume in men with clinical left varicocele: correlation with grade of varicocele. Arch androl 41:37, 1998.

49. Sigman M, Jarow JP: Ipsilateral testicular hypotrophy is associated with decreased sperm counts in infertile men with varicoceles. J Urol 158:605, 1997.

50. Lemack GE, Uzzo GR, Schlegel PN, et al: Microsurgical repair of the adolescent varicocele. J Urol 160:179, 1998.

51. Paduch DA, Niedzielski J: Repair versus observation in adolescent varicocele: a prospective study. J Urol 158:1128, 1997.

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