Review Article. Evaluation and Management of the Adolescent Varicocele. Thomas F. Kolon

Transcription

1 Review Article Evaluation and Management of the Adolescent Varicocele Thomas F. Kolon From the Department of Urology (Surgery), Children s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania Abbreviations and Acronyms AMH ¼ anti-m ullerian hormone FSH ¼ follicle-stimulating hormone GnRH ¼ gonadotropin-releasing hormone LH ¼ luteinizing hormone LTV ¼ left testicular volume RTV ¼ right testicular volume TMC ¼ total motile count TTV ¼ total testicular volume TV ¼ testicular volume TVdiff ¼ testicular volume differential Accepted for publication June 9, Purpose: Varicocele is one of the most common genital conditions referred to pediatric urologists. Most adolescents with varicocele are asymptomatic and their fertility future (and surgery benefit) is largely unknown. This review assesses varicocele evaluation, management and indications for repair, as well as types and success of varicocelectomy. Materials and Methods: A systematic literature review was performed on EmbaseÔ, PubMedÒ and Google ScholarÔ for adolescent varicocele. Original research articles and relevant reviews were examined, and a synopsis of these data was generated for a comprehensive review of clinical adolescent varicocele management. Results: The prevalence of adolescent varicocele is similar to the adult population. While ultrasound is the most sensitive method for determining testicular volumes, orchidometer measurement may be adequate to gauge significant discordance. Significant hypotrophy of the affected testis with poor total testicular volume may indicate a testis at risk and warrant surgical repair. Similar findings have been noted with an associated high peak retrograde venous flow. Testicular hypotrophy often resolves following surgery but may also improve spontaneously if followed through adolescence. Continued scrotal pain despite adequate support or serial abnormal semen analysis in Tanner stage V boys is an indication for varicocelectomy. Artery and lymphatic sparing techniques (microscopic subinguinal or laparoscopic) are associated with the lowest risk of recurrence and complications. Conclusions: Overtreatment and under treatment are medically and financially costly. Abnormal serial semen analysis with or without testicular hypotrophy is an indication for varicocele repair. If observation remains the treatment, followup with an adult urologist should be encouraged until paternity is achieved. Key Words: adolescent, infertility, semen analysis, testis, varicocele VARICOCELE is among the most common genital issues referred to pediatric urologists. While the condition is relatively uncommon in boys before age 10 years, its prevalence increases to 8% to 16% through puberty. In the 15 to 19-year-old age group the prevalence of varicocele is about 15%, similar to that seen in the adult population. 1 While varicocele repair in symptomatic men may improve fertility potential, it has been estimated that 85% of men with varicocele will not encounter male factor infertility. 2 In contrast, most adolescents who present with varicocele are asymptomatic and their fertility future is unknown. Thus, evaluation and treatment of the adolescent varicocele remain unclear and 1194 j /15/ /0 THE JOURNAL OF UROLOGY Ó 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. Vol. 194, , November 2015 Printed in U.S.A.

2 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE 1195 controversial despite significant research during the last several decades. This review will cover varicocele evaluation, management and indications for repair, as well as types and success of varicocelectomy. EVALUATION Evaluation of the patient with varicocele should be geared toward identification of possible risk factors associated with long-term subfertility. To this end, the primary points of assessment have been varicocele grade, testicular volume (differential or total), ultrasound venous investigation, endocrine evaluation and semen analysis. Varicocele grade (I, palpable when standing with Valsalva; II, palpable when standing; III, visible when standing) association with poor left testicular growth has been variable. In adolescents a direct correlation between varicocele grade and semen parameters has not been observed. Some have correlated a higher grade with poor ipsilateral growth, while Kass et al showed that the right testis may similarly be at growth risk with large grade III varicoceles. 3 However, others have observed no relationship. 4e8 Thus, varicocele grade alone is not an indicator for surgical repair. Testicular size has been used by many authors to gauge developing spermatogenic potential in adolescent males with varicocele. The association of varicocele with left testicular hypotrophy was demonstrated several decades ago in adults and subsequently in adolescents. 9 Several studies have revealed that left testicular hypotrophy may improve after varicocele repair and so may represent a testis at risk. 10e12 Significant LTV vs RTV differential has been identified as 10% to 20%, or a 2 to 3 ml difference in size. Possible testicular hypotrophy has generally been evaluated as either an atrophy index compared to the right, ie (RTV LTV)/(RTV), or as a testicular volume differential similar to renal function evaluation, ie TVDiff ¼ (RTV LTV)/(TTV). Both formulas are interchangeable, and differential TVs can easily be converted from one formula to another with near perfect accuracy. 13 Paltiel et al measured testicular volume in anesthesized dogs using Prader and Rochester orchidometers, and then in vivo by ultrasound. 14 The ultrasound measurements were calculated using 2 formulas, ie volume ¼ length width height 0.52 (volume of an ellipsoid) and volume ¼ length width height 0.71 (Lambert formula). These measures were compared to the volumes definitively obtained by water displacement. Paltiel et al found that ultrasound was more accurate than orchidometry and the Lambert formula was superior to the formula of an ellipsoid for determining testicular volume. 14 Diamond et al examined this matter in humans and concluded that orchidometer measurement is too insensitive to assess volume differentials to determine growth impairment compared to ultrasound. 15 However, testis ultrasound measurement may also be somewhat imprecise regarding the placement of cursors for determining length, width and depth. This inherent variability seen in clinical practice is why many have maintained that the decision for surgery should not be based on a single measure at a single point in time, but that several measures through time will settle true significant asymmetry. Recently Goede et al obtained reference data for testicular volume measured by ultrasound in asymptomatic boys 0.5 to 18 years old. 16 For Tanner stage V boys individual testis volumes ranged from 20 to 40 cm 3. They found an accurate correlation between volume measurements by ultrasound and by the Prader orchidometer (R 2 ¼ 0.956), and concluded that orchidometry can be used as a valid parameter for monitoring testicular growth. The exact method of testicular volume measurement is left to the discretion of the urologist. The key point is that a consistent method needs to be used to obtain a reliable measure of testicular growth in an individual adolescent through time. MANAGEMENT Management of the adolescent with varicocele remains controversial. Coutinho et al recently queried members of the American Academy of Pediatrics Section on Urology regarding varicocele management. 17 They found that if significant testicular size discrepancy is identified, 32% of practitioners immediately intervene surgically, while 59% repeat measurements in 6 to 12 months. When there is no volume differential identified, 37% of practitioners discharge their patients with no followup, 23% refer to an infertility specialist and 31% evaluate with semen analysis. Interestingly 57% of practitioners had never sent patients for semen analysis. Pastuszak et al similarly surveyed members of the Society for Pediatric Urology. 18 Most respondents operate for decreased ipsilateral testis size, while some operate for varicocele grade alone. Only 39% operate because of altered semen parameters, and 89% were unaware of the later fertility status of the patients they operated on. Unfortunately with a low response rate in both surveys (28% to 54%) a definitive practice pattern consensus could not be reached. While some have argued for surgical correction if the affected testicular volume is 10% to 20% less than that of its contralateral normal mate, others have noted that nearly 80% of these volume

3 1196 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE discrepancies resolve in time without surgery. 7 Although early repair may prevent infertility, unrestricted repair of all adolescent varicoceles would involve unnecessary surgery for the majority of patients. 2 Delaying treatment until infertility is shown in adulthood prevents unnecessary surgery but may compromise outcomes, as approximately 30% of adults undergoing varicocele repair demonstrated no improvement in semen parameters. 19 Similarly testicular hypotrophy does not usually improve in adulthood, and varicocele damage may be progressive through time in adults. 20,21 Thus, early repair during adolescence is attractive but only if the correct predictors are found. Several investigators have studied testicular volume changes. Poon et al reported that 67% of boys with greater than 15% TVdiff had persistent or worse asymmetry after a median followup of 21 months. 22 Van Batavia et al reported that catchup growth is rare when a peak retrograde venous flow greater than 38 cm per second is associated with a 20% or greater TVdiff (ie the 20/38 harbinger). 23 They followed 53 boys who met either the 20/38 (44 patients) or 15/38 (9) cutoffs for an average of 15 months, and only 3 boys exhibited catch-up growth to a differential of less than 15%. To minimize subjectivity with this Doppler ultrasound test, it is important that the peak retrograde flow be obtained with the patient supine and achieving a satisfactory Valsalva maneuver. Other groups have observed significant testicular catch-up growth without surgery. Kolon et al followed 161 boys nonsurgically with scrotal ultrasound for a median of 39 months. 7 Of the patients 54% initially had a 15% or greater TVdiff. After 2 years 85% had testicular volume differentials in the normal range (less than 15%). Testis volume differentials as large as 66% resolved without intervention, and 71% of patients were spared potential surgery based on size criteria. Preston et al found normalization of left hypotrophy in boys 8 to 16 years old after a nonsurgical median followup of 2.1 years. 24 The catch-up growth remained significant even after adjustment for age, length of observation and need for surgery. Despite this initial nonsurgical management, they caution that those individuals who exhibit a testicular size discrepancy that is steadily increasing should be considered for surgical intervention. Moursy et al compared surgical and nonsurgical management of unilateral varicoceles in adolescents. 25 Catch-up testicular growth was observed in 70% of surgical patients and 50% of nonsurgical patients, and semen analysis normalized in all surgical patients and all but 1 patient in the nonsurgical group. Testicular volume was not different between the 2 groups. Further research has examined the association of testicular volume changes and semen analysis. Diamond et al evaluated the relationship between unilateral left varicocele grade or TVdiff and semen parameters in adolescents. 5 They found that TVdiff greater than 10% correlated with decreased TMC. While as a group comparison (less than 10% vs 10% to 20% vs greater than 20%) there is more likelihood of an abnormal TMC when there is a larger TVdiff, there are also patients with normal range TMC in all of the groups. Thus, they do not recommend prophylactic surgery for all boys with more than a 10% differential. Rather, TVdiff greater than 10% may serve as a marker for someone who is at risk for subfertility and needs further followup. They also noted that sperm morphology only improved when there was also improvement in sperm concentration. Sperm morphology is an as yet undefined factor in the evaluation of adolescent varicocele. Paduch and Niedzielski reported on 17 to 19-yearold boys with grades II and III varicoceles, and noted poorer semen quality in those with greater backflow velocity and greater asymmetry. 10 Semen analysis in adolescence is graded against the World Health Organization standards set for adult males. Christman et al correlated serial ultrasound TVdiff and TTV in patients followed for several years with eventual semen analysis. 26 TTV performed superiorly to TVDiff for predicting TMC but none of the TV parameters analyzed had a simultaneously high sensitivity and specificity. TTV and TVdiff had a small to moderate predictive ability for a normal TMC. The authors concluded that following TV through time affords a limited clinical ability to differentiate patients based on the outcome of TMC. It has also been noted that the relationship between TVdiff and low total motile sperm levels is not significant. However, when low TTV is associated with marked asymmetry, total motile sperm counts are at their lowest. Thus, before the ability to obtain a semen analysis, marked TVdiff with a low TTV may identify an adolescent at risk. Bogaert et al evaluated the ability to achieve paternity in adults who had been diagnosed with varicocele in adolescence and either underwent antegrade sclerotherapy or received no further treatment. 27 They concluded that there is no beneficial effect to screening for varicocele, since treating the varicocele at diagnosis does not appear to improve later paternity. While some interval data (Tanner stage, testicular volume through time, semen analysis) were missing that might have helped us treat adolescents/young adults, the findings of Bogaert et al 27 reinforce the historical data confirming that 80% to 85% of adults with varicocele do not have paternity issues prompting an infertility

4 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE 1197 evaluation. Two-thirds of Tanner stage V boys with an uncorrected varicocele achieve a normal TMC regardless of varicocele grade or testicular volumes. When these boys are sequentially followed with serial semen analyses, 46% with an initial poor semen analysis will improve to good status (normal TMC) without surgery. 28 Early studies of the rodent varicocele model and the histology of the adolescent testis suggest some element of Leydig cell dysfunction leading to an intratesticular androgen environment that is inadequate for full Sertoli cell function and spermatogenesis. 29,30 Hadziselimovic et al examined bilateral testis biopsies at varicocele repair and noted abnormal adult dark spermatogonia maturation. 31 Ten-year followup revealed normal LH, FSH and testosterone levels in all patients, and the investigators were unable to correlate histological findings with abnormal semen parameters. In addition to the possible effect on germ cells, endocrine imbalances have been noted in individuals with varicocele. Damage to germinal epithelium results in compensatory stimulation of the pituitary gland and a resultant increase in FSH and LH production. Kass et al reported that some patients with varicocele have an exaggerated increase in LH and FSH secretion after exogenous GnRH administration, implying a varicocele effect on the hypothalamic-pituitary-gonadal axis. 32 Recent data have also shown a correlation between the GnRH stimulation test, testicular hypotrophy and pathological semen analysis. 33 However, GnRH stimulation has not yet been demonstrated to be helpful in identifying adolescents at risk for future infertility. Since the GnRH test is fairly expensive, requires multiple blood draws and lacks a definite association between abnormal results, testicular growth arrest and infertility, it has not been universally adopted. Romeo et al examined various androgen related hormones associated with untreated varicoceles. 34 In a small series of boys with testis volume differential measured at a single point in time they found that inhibin B was decreased and positively correlated with testicular volume. However, all other hormones (GnRH stimulated LH, FSH, testosterone) were normal, and there was no correlation with semen parameters. Trigo et al similarly compared untreated prepubertal and pubertal boys and adolescent controls, and found that inhibin B levels were higher in prepubertal patients with varicocele than in controls, with no further increment in inhibin B in the pubertal patients. 35 Higher levels of AMH were found in Tanner stage I, III, IV and V patients with varicocele compared to normal boys by Tanner stage. The direct correlation found in normal boys between inhibin B levels and LH, testosterone and testicular volume was not observed in patients with varicocele. They concluded that the altered serum profile of gonadal hormones observed in patients with untreated varicocele may indicate an early abnormal regulation of the seminiferous epithelium function. At this time there is not an absolute consensus on hormonal evaluation of the adolescent varicocele. Thus, we currently offer measurement of the hormones LH, FSH, testosterone, inhibin B and AMH, which has been observed to be helpful in adults. INDICATIONS FOR REPAIR The American Urological Association Male Infertility Best Practice Policy Committee and the American Society for Reproductive Medicine Practice Committee state that treatment of adult varicocele should be considered when 1) varicocele is palpable on physical examination, 2) the couple has known infertility, 3) the female partner has normal fertility or a potentially treatable cause of infertility and 4) the male partner has abnormal semen parameters or abnormal results on sperm function tests. 36 However, these indications are rarely available in the adolescent/young adult population. Varicocele treatment for infertility is not indicated in patients with either normal semen quality or a subclinical varicocele. Varicocele repair in adolescents should be considered when there is objective evidence of reduced ipsilateral testicular size. In the absence of objective evidence the committees recommend that adolescents/young adults be followed with yearly ultrasound or semen analysis to detect the earliest signs of accelerated testicular injury. The European Association of Urology recently released similar guidelines, which state that 1) varicocele treatment is recommended for adolescents with progressive failure of testicular development documented by serial clinical examination, 2) there is no evidence indicating benefit of varicocele treatment in infertile men who have normal semen analysis or a subclinical varicocele, and 3) varicocele repair should be considered in cases of clinical varicocele, oligospermia, infertility duration greater than 2 years and otherwise unexplained infertility in the couple. 37 Given the aforementioned recent research of varicocele effect on testicular volume, androgen levels and semen analysis, the current adolescent recommendations for surgery will likely be adjusted. TREATMENT OPTIONS Surgical options for varicocelectomy include the open inguinal (Ivanissevich), high retroperitoneal (Palomo ligation of testicular veins and artery) and

5 1198 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE subinguinal microsurgical approaches, as well as laparoscopic repair (Palomo type mass ligation or artery sparing). Antegrade or retrograde embolization or sclerotherapy is a nonsurgical option. Practice patterns among urologists vary widely in the adult and adolescent populations. 17,18 The key surgical question is whether adolescent varicocele repair has any effect on reversal of testicular hypotrophy or improvement in semen parameters. While the ultimate patient goal is paternity, semen analysis is critical to appropriate treatment of these patients. Several studies have revealed catch-up growth in the varicocele treatment groups. One study randomized 15 to 19-yearold males with grade II to III varicoceles to surgery or observation, and showed a reversal of testicular growth arrest and catch-up growth within 12 months of surgery. 10 Lenzi et al reported better semen parameters in adults who underwent varicocele repair in adolescence compared to those who did not undergo repair. 38 Cayan et al demonstrated that varicocelectomy improved low sperm concentration in 15 to 19-year-old males with hypotrophy, even in those who did not achieve catch-up growth. 39 Randomized controlled studies have also revealed improvement in semen parameters only after varicocele repair. 11,12 Ku et al compared preoperative and postoperative semen analyses between adolescents and fertile and infertile adults with varicocele after microsurgical varicocelectomy. 40 There was no significant difference in sperm count, motility or morphology among the 3 groups. While the adolescent group had better overall end points, they also had better baseline semen parameters than the adults, and the authors could not show a clear advantage to early repair. Kolon et al studied 14 consecutive adolescents with preoperative and postoperative semen analyses. 28 In that series mean preoperative TMC was 3.6 million (range 0 to 16.9 million) and mean postoperative TMC was 24.2 million (0.23 to 84.4 million). Of 14 patients 11 (78.6%) demonstrated significant improvement (p ¼ 0.01) in TMC, with 7 patients moving into the normal adult range. While they did not have a control group, comparison to historical adult improvement in semen parameters reveals a slight advantage for adolescent repair. The effect of lymphatic sparing on catch-up growth was examined by Poon et al in 136 boys (mean age 15 years) with greater than 10% TVdiff. 22 Of the patients 107 were treated with laparoscopic lymphatic sparing and 29 with nonlymphatic sparing varicocelectomy. Catch-up growth was achieved in 62.8% of patients but there was no significant difference between the 2 approaches regarding catch-up growth (51.7% vs 66.3%, p ¼ 0.19). Complications of repair include hydrocele formation, persistence or recurrence of varicocele, and testicular atrophy. In adults and adolescents subinguinal microscopic varicocelectomy is associated with the lowest postoperative complication rate. Postoperative improvements in semen analysis of microsurgical repair are comparable to open inguinal and laparoscopic varicocelectomy, with lower rates of hydrocele formation or varicocele recurrence. 41 Hydrocele formation, reported in about 7% of cases, is the most common complication after nonmicrosurgical varicocelectomy. Hydrocele formation is thought to be due to ligation of the testicular lymphatics. Approximately half of all postoperative hydroceles are of a size that may warrant surgical hydrocelectomy, although the effect of hydrocele pressure on spermatogenesis and fertility is unknown. Use of the operating microscope has essentially eliminated development of hydroceles following varicocelectomy due to the ability to easily visualize and spare inguinal lymphatics. The incidence of varicocele recurrence following surgical repair varies from 1% to 45%. The rate of recurrence depends on the type of procedure performed and the use of magnification. Venography has shown that recurrent varicoceles are caused by collateral periarterial, parallel inguinal, mid retroperitoneal, gubernacular and transscrotal veins. Thus, some have recommended that dissection below the inguinal cord with delivery of the testis affords the best chance for ligation of all perforating external spermatic veins and gubernacular veins, and is associated with a 10% varicocele recurrence rate. Testicular artery injury or ligation may cause testicular atrophy and/or impaired spermatogenesis. Microscopic or laparoscopic magnification and use of a Doppler probe facilitate identification and preservation of the testicular artery. When the testicular artery is ligated, as in a classic open or laparoscopic Palomo repair, the patient should be cautioned that future vasectomy might result in testicular atrophy. Therefore, a deferential artery sparing vasectomy should be recommended if desired. Although most advocate surgical correction, percutaneous varicocele embolization is a well tolerated technique with a high benefit-to-cost ratio. In men with grade III left varicocele, abnormal sperm parameters and documented infertility embolization is associated with a significant improvement in sperm concentration, motility and morphology but not in serum testosterone, FSH or inhibin B levels. These results are in contradistinction to findings at several centers demonstrating improvement in hormonal levels with surgical repair. 42 Chuang et al followed 39 patients for 3 years after primary or salvage

6 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE 1199 Initial Presentation Take History Physical Exam (standing) to establish grade Orchidometer to establish baseline volumes Grade Varicocele (standing) I. Palpable with valsalva II. Palpable at rest III. Grossly visible Follow-up every 2 yrs (if good volumes) with orchidometer volume until at least age 15 AND Tanner V Follow-up annually (if poor volumes) with orchidometer volume until at least age 15 AND Tanner V Consider Surgery if persistent low TTV (<age 15) Follow-up in one year Discuss SA again Measure testes with orchidometer If no SA obtained/family refuses or if not Tanner V TMC >20 million Age 15/Tanner V Obtain orchidometer volume, semen analysis, labs (LH, FSH, testosterone, inhibin B, AMH) TMC <20 million If SA refused at age 16, recommend f/u at 18 for SA Discuss repeat SA and orchidometer at age 18 TMC >20 million Repeat SA in 3-6 mos (repeat labs if clinically indicated) TMC <20 million Discuss repeat SA and orchidometer at age 18 Surgical Repair of Varicocele Repeat SA and orchidometer 3-6 mos after surgery (repeat labs if abnormal preop) Repeat SA and orchidometer at age 18 Evaluation and management algorithm for adolescent varicocele. f/u, followup. SA, semen analysis. selective gonadal vein embolization. 43 The postembolization complication rate was 7.5% and 1 patient in the primary treatment group reported recurrence. However, concerns remain that recurrence rates after percutaneous embolization may be higher than the reported data due to possible later recanalization through the coils. Embolization also adds the radiological risk of fluoroscopy, which is not encountered with other surgical repairs. For information on pregnancy rates based on type of repair conclusions must be deduced from the adult population. Cayan et al analyzed 36 studies to define which technique affords the highest pregnancy rate after varicocele repair. 39 They concluded that microsurgical varicocelectomy is associated with higher spontaneous pregnancy rates and less postoperative recurrence compared to other varicocelectomy techniques and radiological embolization in infertile men. Diegidio et al reviewed pooled data from more than 5,000 patients in 33 studies. 41 Overall pregnancy rate was 38% and was highest for the microsurgical subinguinal (45%) or microsurgical inguinal technique (42%), compared to the Palomo procedure (34%), radiological embolization (32%), conventional inguinal repair (31%) and the laparoscopic technique (28%). In a meta-analysis (2 randomized controlled trials and 3 observational studies) Marmar et al evaluated pregnancy rates after varicocelectomy among men with grade I to III varicoceles and at least 1 abnormal semen parameter. 44 They concluded that varicocele repair has beneficial effects on fertility status (OR 2.87). Kim et al performed a similar meta-analysis and found a significant fixed effects pooled OR of

7 1200 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE Several investigators have evaluated the response of hormones to varicocele repair. Fisch et al examined the response in boys to GnRH stimulation before and after unilateral varicocele repair and associated testicular atrophy. 46 The FSH response to GnRH stimulation increased following surgery but they noted that the GnRH stimulation test could not be used to determine which adolescent would benefit from surgical repair. Others have documented a postoperative increase in testosterone in Tanner stage I to III cases but no differences in basal LH and FSH or stimulated FSH. A decrease of maximal LH response to GnRH stimulation was noted postoperatively in Tanner stages IV and V. 47 Testosterone response has primarily been evaluated in the adult population. Su et al noted a modest increase in testosterone from 319 ng/dl preoperatively to 409 ng/dl (p <0.05) in infertile men, although this finding did not necessarily cause a direct improvement in semen quality. 48 A metaanalysis revealed that mean serum testosterone levels increased by 97.5 ng/dl after surgical correction of the adult varicocele. 49 Hsiao et al showed that microscopic varicocelectomy results in significant increases in testosterone regardless of varicocele grade, 50 although the accompanying editorial comment cautions that currently varicocele repair should not be advocated for hypogonadism alone. Further studies of greater number are needed to fully evaluate the adolescent hormonal profile preoperatively and postoperatively with semen analysis correlation. MANAGEMENT ALGORITHM Overtreatment and under treatment are medically and financially costly. Expensive ultrasound, office visits and surgery must be avoided in those who do not need this management, while early intervention is warranted in some to preempt the need for later assisted reproductive techniques (although no financial assessment of evaluation/treatment options has been done in adolescents). Based on current evidence, abnormal semen parameters are the most reasonable measurements that are potentially predictive of future fertility (see figure). All boys with varicoceles should undergo assessment of testicular size (preferably with an orchidometer for cost savings) yearly, or every other year if the total testicular volume is normal, until the patient reaches Tanner V maturity. The patient can then be offered semen analysis and perhaps androgen hormone levels, testing pituitary, Sertoli cell and Leydig cell function (LH, FSH, testosterone, anti-m ullerian hormone, inhibin B). A semen analysis discussion with the patient and family should consider any individual ethical and religious concerns. If the total testicular volume is low, semen parameters are low, androgen laboratory results are abnormal or the patient is symptomatic (uncommon), varicocele correction should be discussed. As in adults, abnormal serial semen analyses with or without testicular hypotrophy is an indication for varicocele repair. If observation remains the treatment, followup with an adult urologist should be encouraged until paternity is achieved. It seems that all patients with varicocele should be followed into adulthood if we wish to determine the best parameters in adolescence that predict adult fertility. Only then will we really know whether we are making a difference in the overall testicular health of these patients. REFERENCES 1. Akbay E, Çayan S, Doruk E et al: The prevalence of varicocele and varicocele-related testicular atrophy in Turkish children and adolescents. BJU Int 2000; 86: Skoog SJ, Roberts KP, Goldstein M et al: The adolescent varicocele: what s new with an old problem in young patients? Pediatrics 1997; 100: Kass EJ, Stork BR and Steinert BW: Varicocele in adolescence induces left and right testicular volume loss. BJU Int 2001; 87: Alukal JP, Zurakowski D, Atala A et al: Testicular hypotrophy does not correlate with grade of adolescent varicocele. J Urol 2005; 174: Diamond DA, Zurakowski D, Bauer SB et al: Relationship of varicocele grade and testicular hypotrophy to semen parameters in adolescents. J Urol 2007; 178: Steeno O, Knops J, Declerck L et al: Prevention of fertility disorders by detection and treatment of varicocele at school and college age. Andrologia 1976; 8: Kolon TF, Clement MR, Cartwright L et al: Transient asynchronous testicular growth in adolescent males with a varicocele. J Urol 2008; 180: Kass EJ and Belman AB: Reversal of testicular growth failure by varicocele ligation. J Urol 1987; 137: Lipshultz LI and Corriere JN Jr: Progressive testicular atrophy in the varicocele patient. J Urol 1977; 117: Paduch DA and Niedzielski J: Semen analysis in young men with varicocele: preliminary study. J Urol 1996; 156: Yamamoto M, Hibi H, Katsuno S et al: Effects of varicocelectomy on testis volume and semen parameters in adolescents: a randomized prospective study. Nagoya J Med Sci 1995; 58: Thomas JC and Elder JS: Testicular growth arrest and adolescent varicocele: does varicocele size make a difference? J Urol 2002; 168: Christman MS, Zderic SA and Kolon TF: Comparison of testicular volume differential calculations in adolescents with varicoceles. J Pediatr Urol 2014; 10: Paltiel HJ, Diamond DA, Di Canzio J et al: Testicular volume: comparison of orchidometer

8 EVALUATION AND MANAGEMENT OF ADOLESCENT VARICOCELE 1201 and US measurements in dogs. Radiology 2002; 222: Diamond DA, Paltiel HJ, DiCanzio J et al: Comparative assessment of pediatric testicular volume: orchidometer versus ultrasound. J Urol 2000; 164: Goede J, Hack WW, Sijstermans K et al: Normative values for testicular volume measured by ultrasonography in a normal population from infancy to adolescence. Horm Res Paediatr 2011; 76: Coutinho K, McLeod D, Stensland K et al: Variations in the management of asymptomatic adolescent grade 2 or 3 left varicoceles: a survey of practitioners. J Pediatr Urol 2014; 10: Pastuszak AW, Kumar V, Shah A et al: Diagnostic and management approaches to pediatric and adolescent varicocele: a survey of pediatric urologists. Urology 2014; 84: Gorelick JI and Goldstein M: Loss of fertility in men with varicocele. Fertil Steril 1993; 59: Gershbein AB, Horowitz M and Glassberg KI: The adolescent varicocele I: left testicular hypertrophy following varicocelectomy. J Urol 1999; 162: Witt MA and Lipshultz LI: Varicocele: a progressive or static lesion? Urology 1993; 42: Poon SA, Kozakowski KA, Decastro GJ et al: Adolescent varicocelectomy: postoperative catch-up growth is not secondary to lymphatic ligation. J Pediatr Urol 2009; 5: Van Batavia JP, Badalato G, Fast A et al: Adolescent varicoceledis the 20/38 harbinger a durable predictor of testicular asymmetry? J Urol 2013; 189: Preston MA, Carnat T, Flood T et al: Conservative management of adolescent varicoceles: a retrospective review. Urology 2008; 72: Moursy EE, ElDahshoury MZ, Hussein MM et al: Dilemma of adolescent varicocele: long-term outcome in patients managed surgically and in patients managed expectantly. J Pediatr Urol 2013; 9: Christman MS, Zderic SA, Canning DA et al: Active surveillance of the adolescent with varicocele: predicting semen outcomes from ultrasound. J Urol 2014; 191: Bogaert G, Orye C and De Win G: Pubertal screening and treatment for varicocele do not improve chance of paternity as adult. J Urol 2013; 189: Kolon TF, Zderic SA, Shukla AR et al: Personal communication. 29. Turner TT, Evans WS and Lopez TJ: Gonodotroph and Leydig cell responsiveness in the male rat. Effects of experimental left varicocele. J Androl 1990; 11: Hienz HA, Voggenthaler J and Weissbach L: Histological findings in testes with varicocele during childhood and their therapeutic consequences. Eur J Pediatr 1980; 133: Hadziselimovic F, Herzog B and Jenny P: The chance for fertility in adolescent boys after corrective surgery for varicocele. J Urol 1995; 154: Kass EJ, Freitas JE, Salisz JA et al: Pituitary gonadal dysfunction in adolescents with varicocele. Urology 1993; 42: Guarino N, Tadini B and Bianchi M: The adolescent varicocele: the crucial role of hormonal tests in selecting patients with testicular dysfunction. J Pediatr Surg 2003; 38: Romeo C, Arrigo T, Impellizzeri P et al: Altered serum inhibin B levels in adolescents with varicocele. J Pediatr Surg 2007; 42: Trigo RV, Bergada I, Rey R et al: Altered serum profile of inhibin B, Pro-alphaC and anti-m ullerian hormone in prepubertal and pubertal boys with varicocele. Clin Endocrinol (Oxf) 2004; 60: Male Infertility Best Practice Policy Committee of the American Urological Association and Practice Committee of the American Society for Reproductive Medicine: Report on varicocele and infertility. Fertil Steril, suppl., 2004; 82: S Jungwirth A, Giwercman A, Tournaye H et al: European Association of Urology Guidelines on Male Infertility: the 2012 update. Eur Urol 2012; 62: Lenzi A, Gandini L, Bagolan P et al: Sperm parameters after early left varicocele treatment. Fertil Steril 1998; 69: Cayan S, Shavakhabov S and Kadioglu A: Treatment of palpable varicocele in infertile men: a meta-analysis to define the best technique. J Androl 2009; 30: Ku JH, Kim SW, Park K et al: Benefits of microsurgical repair of adolescent varicocele: comparison of semen parameters in fertile and infertile adults with varicocele. Urology 2005; 65: Diegidio P, Jhaveri JK, Ghannam S et al: Review of current varicocelectomy techniques and their outcomes. BJU Int 2011; 108: Prasivoravong J, Marcelli F, Lema^ıtre L et al: Beneficial effects of varicocele embolization on semen parameters. Basic Clin Androl 2014; 24: Chuang K, Waingankar N, George AK et al: Long-term outcomes of adolescent varicoceles treated with selective gonadal vein embolization: 23 years experience. J Urol, suppl., 2014; 191: e255, abstract MP Marmar JL, Agarwal A, Prabakaran S et al: Reassessing the value of varicocelectomy as a treatment for male subfertility with a new meta-analysis. Fertil Steril 2007; 88: Kim KH, Lee JY, Kang DH et al: Impact of surgical varicocele repair on pregnancy rate in subfertile men with clinical varicocele and impaired semen quality: a meta-analysis of randomized clinical trials. Korean J Urol 2013; 54: Fisch H, Hyun G and Hensle TW: Testicular growth and gonadotrophin response associated with varicocele repair in adolescent males. BJU Int 2003; 91: Podesta ML, Gottlieb S, Medel R Jr et al: Hormonal parameters and testicular volume in children and adolescents with unilateral varicocele: preoperative and postoperative findings. J Urol 1994; 152: Su LM, Goldstein M and Schlegel PN: The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles. J Urol 1995; 154: Li F, Yue H, Yamaguchi K et al: Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis. Int J Urol 2012; 19: Hsiao W, Rosoff JS, Pale JR et al: Varicocelectomy is associated with increases in serum testosterone independent of clinical grade. Urology 2013; 81: 1213.