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 and Microsurgical Varicocelectomy
Microsurgical inguinal and sub-inguinal varicocelectomies
Complications of varicocele Repair
Reference and Suggested Reading
Varicoceles are abnormally dilated testicular veins (pampiniform plexus) in the scrotum.. Varicocele is found in approximately 15% of the general population, 35% of men with primary infertility and in 75-80% 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 pre-pubertal boys. Varicocele repair is by far the most commonly performed operation for the treatment of male infertility.
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 (the cells that manufacture the male hormone testosterone) function. Another report by Johnson and colleagues showed that 70% of healthy, asymptomatic military recruits with palpable varicoceles had abnormal semen analyses.
Furthermore, studies in animals and human 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 70 - 80% of men after varicocelectomy, translate into improved pregnancy and delivery rates had previously been a matter of controversy. Recent controlled studies clearly indicate that varicocelectomy improves pregnancy rates. The potentially important role of urologists in preventing future infertility and/or androgen (testosterone) deficiency underscores the importance of utilizing a varicocelectomy technique that minimizes the risk of complications and recurrence.
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 rare. The left internal spermatic (testicular) vein empties into the left renal (kidney) 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. 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.” Varicoceles arise due to reflux of venous blood into the testicular 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. Varicoceles generally become clinically manifest at the time of puberty.
Despite a large number of animal and human studies, the exact mechanism whereby varicoceles cause impaired testicular function remains uncertain. 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,reactive oxygen species,and regulators of apoptosis 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.
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. 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. Previous studies have demonstrated that scrotal skin surface temperatures reliably reflect intratesticular temperatures. The pathophysiology of varicocele is probably multi-factorial.
Varicoceles are defined as dilations of the veins of the testicular pampiniform plexus, which are believed to be caused by absent or incompetent valves in the internal spermatic veins. The diagnosis of a clinically significant varicocele is generally made on physical examination of the scrotum and its contents. The patient is examined in the supine and standing position with the scrotum warmed first with a heating pad. This 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. The spermatic cord should be palpated between thumb and forefinger for palpable tortuous veins. Both spermatic cords should be palpated while the patient performs a Valsalva maneuver in the upright position.
Varicoceles are graded I through III using the system outlined in Table 1. Grade I varicoceles are small, Grade II moderate and Grade III, large. Varicoceles should collapse in the supine position. If the varicocele remains prominent with the patient supine, this finding suggests a mechanical obstruction to testicular venous outflow from 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 men.
Scrotal ultrasonography with color flow Doppler imaging with the patient upright and supine 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 maneuver documented. Veins that are greater than 3.5 mm can generally be detected on physical exam. Those that are 2.5 mm or larger but are not palpable and have been termed “subclinical” varicoceles. The need for diagnosing and treating subclinical varicoceles in controversial. Reports have indicated that repair of small palpable or subclinical right varicoceles may be beneficial if present in conjunction with a larger left sided varicocele. A recent meta-analysis by Marmar et al. clearly shows a significant increase in pregnancy rates after microsurgical varicocelectomy.
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. When exogenous hCG is administered to men with varicoceles, a blunted T response is observed compared to controls without varicoceles. Repairing varicoceles appears to improve serum testosterone (T) levels. This observation was made over twenty years ago by Comhaire and Vermeulen and was confirmed recently in a larger series by Su, et al.Taken together, these findings indicate that varicoceles result in abnormal Leydig cell function in some men, and 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 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. The impact of the grade of varicocele on the magnitude of improvement in semen quality after varicocelectomy is not surprising. Steckel et al., reported that men with larger varicoceles present with lower sperm densities, and show greater relative improvement in semen quality after microsurgical repair than men with smaller varicoceles.
A: The indications for repairing varicoceles in adolescents include the following:
Palpable (especially Grade III) left varicocele associated with decreased testicular size (with the volume of the left testis being at least 20% less than that of the right) Palpable (especially Grade III) varicocele with abnormal semen analysis results or
Large (Grade III) symptomatic (painful) varicocele or
Bilaterally palpable varicocele with testicular atrophy
Although preventive treatment of adolescent varicocele for the prevention of future infertility and androgen deficiency is controversial, the author feels that it is much easier to prevent future infertility and androgen deficiency than to treat it once it has occurred. In view of the high success rate and low morbidity of microsurgical repair, repair of Grade III varicoceles is the conservative therapy since it conserves testicular function.
B: Based on the Best Practice Policies for Male Infertility of the American Urological Association (AUA) and Society and Society for Reproductive Medicine and Urology (SMRU), varicocele treatment should be offered to the male partner of a couple attempting to conceive when all of the following are present:
A varicocele is palpable (can be felt);
The male partner has one or more abnormal semen parameters or sperm function test results;
The couple has documented infertility;
The female partner has normal fertility or potentially correctable infertility.
In addition, testicular pain associated with varicocele (in the absence of other pathology), psychological concern regarding future fertility, and cosmetic reasons are all relative indications. Varicocele repair is not indicated in men with normal semen analysis, sperm function assays or only a subclinical (non-palpable) varicocele.
2. Microsurgical inguinal and sub-inguinal varicocelectomies: The preferred approaches
Subinguinal microsurgical varicocelectomy is currently the most popular approach. It has the advantage of allowing the spermatic cord structures to be pulled up and out of the wound so that the testicular artery, lymphatics and small periarterial veins may be more easily identified. In addition, an inguinal or subinguinal approach allows access to the external spermatic and even gubernacular (scrotal) veins , which may bypass the spermatic cord and result in recurrence if not ligated. Lastly, an inguinal or subinguinal approach allows access to the testis for biopsy or examination of the epididymis for obstruction or repair of hydrocele.
Anesthesia: If the testis is delivered, as described below, regional or light general anesthesia is preferred. If only the cord is delivered, local anesthesia with a 50-50% combination of 0.25% bupivacaine and 1% lidocaine is satisfactory with adjunctive intravenous heavy sedation. After infiltration of the skin and subcutaneous tissues, the cord is infiltrated prior to delivery. Blind cord block carries with it a small risk of inadvertent testicular artery injury. A 30-gauge needle should therefore be employed for cord block to minimize the risk of injury and hematoma.
Inguinal and Subinguinal 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 . 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. 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. The gubernacular veins have been demonstrated radiographically to account for 10% of varicocele recurrences.
Delivery of the testicle enables the surgeon to identify and ligate these vessels, which are responsible for some varicocele recurrences.
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.
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 ov er the needle holder.
Before beginning the dissection, the cord is inspected under 15 to 20 power magnification for the presence of pulsations, indicating the location of the underlying testicular artery.
The VTI 20 MHz Microvascular Doppler probe is useful in helping to identify the artery, which is often hidden within a network of veins.
The artery is identified and then encircled with a vessel loop to preserve it. 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. The procedure is always performed on an ambulatory basis. Some authors have advocated radiographic percutaneous embolization for isolated left-sided varicoceles and laparoscopy for bilateral varicoceles. Failure rate for radiographic embolizaztion is 15-25% but the late failure rate is much higher. The procedure is not durable. The laparoscopic approach requires general anesthesia, makes presentation of the testicular arteries and lymphatics much more difficult and is associated 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% 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.
Testicular artery ligation is also a common complication of non-microsurgical varicocelectomy although its true incidence is unknown. 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. In humans, Penn, et al. reported a 14% incidence of frank testicular atrophy, when the testicular artery was purposefully ligated during renal transplantation. 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. Venographicstudies have shown that recurrent varicoceles are caused by periarterial, parallel inguinal, midretroperitoneal, gubernacular and transcrotal collateral veins.The only approach equipped to deal with these vessels is the inguinal or subinguinal microscopic technique with delivery of the testis. Using the microsurgical technique at Cornell, we have reviewed our results of over 3000 men who underwent microsurgical varicocelectomy, the couples' pregnancy rate was 43 % after one year and 69% after 2 years compared to 17% in couples with men who declined surgery and had hormone treatment or used insemination. There have been only 25 recurrences (0.9%), 5 hydroceles (0.2%) , no testicular atrophy, and a 1% incidence of inadvertent unilateral (one side only) testicular artery ligation.
Varicocelectomy results in significant improvement in semen analysis in 60 to 80% of men and natural pregnancy rates of 43% and 69% at one and two years respectively, controlling for female factors. Reported pregnancy rates after varicocelectomy vary from 20 to 60%. A randomized controlled trial of surgery versus no surgery in infertile men with varicoceles revealed a pregnancy rate of 44% at one year in the surgery group versus 10% in the control group. In our series of 1,500 microsurgical operations, 43% of couples were pregnant at one year 59 and 69% at two years when couples with female factors were excluded. Microsurgical varicocelectomy results in return of sperm to the ejaculate in up to 50% of azoospermic men with palpable varicoceles.
The results of varicocelectomy are also related to the size of the varicocele. Repair of large varicoceles results in a significantly greater improvement in semen quality than repair of small varicoceles. In addition, large varicoceles are associated with greater pre-operative impairment of semen quality than small varicoceles, and consequently overall pregnancy rates are similar regardless of varicocele size. Some evidence suggests that the younger the patient is at the time of varicocele repair, the greater the improvement after repair and the more likely the testis is to recover from varicocele induced injury.66 Varicocele recurrence, testicular artery ligation or post-varicocelectomy hydrocele formation are often associated with poor post-operative results. In infertile men with low serum testosterone levels, microsurgical varicocelectomy alone results in substantial improvement in serum testosterone levels.
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. 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. Lee and Schlegel reported the overall cost per delivery for varicocelectomy averaged $38,300 compared to a striking $89,000 per delivery for ICSI in 2006. The European experience is similar. Comhaire, et al. has estimated that varicocelectomy is seven times more cost effective than ICSI. Although ICSI can clearly facilitate pregnancies in couples with varicocele-associated infertility, it is a very expensive alternative.
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 testicular function over time. The most likely pathophysiologic mechanism is an elevation of testicular temperature due to impaired scrotal thermoregulation. Varicocele repair will halt and often reverse this duration-dependent process.
The most common complications from non-microsurgical varicocelectomy are hydrocele formation, varicocele recurrence, and testicular artery injury.
Use of the operating microscope allows for reliable identification of spermatic cord lymphatics, internal spermatic veins and venous collaterals, and the testicular artery or arteries so that the incidence of these complications can be virtually eliminated. 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.
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