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AUA2024 Plenary Recap: Adolescent Varicocele and Current Clinical Management
By: Robert E. Brannigan, MD, Northwestern University, Chicago, Illinois; Michael P. Kurtz, MD, MPH, Boston Children’s Hospital, Massachusetts; Jason Van Batavia, MD, MSTR, Children’s Hospital of Philadelphia, Pennsylvania; David A. Diamond, MD, University of Rochester Medical Center, New York | Posted on: 03 Jul 2024
Optimal management of the adolescent varicocele remains controversial. With 15% incidence of varicocele in adolescents and adult men, the problem assumes considerable significance. Fertility preservation is the overriding concern with 20% of adult varicocele patients experiencing infertility. Varicocele correction can restore fertility in half of these men, with the other half remaining infertile. This begs the question, could earlier intervention have restored fertility to the other half? In an effort to select those boys who may benefit from surgical intervention, various clinical markers have been studied, including grade of varicocele, testis volumes, hormone levels, and semen analysis.1 These approaches are reviewed, as is the recommended surgical technique for varicocele correction.
Testis volume is often used to draw conclusions regarding fertility in adolescent varicocele. Although it is logical (the testis is largely composed of tubules2), this involves a series of inferential leaps. The primary volumetric measures are total testis volume (TTV), the sum of the volumes of the testes, and testis volume differential (TVD), a measure of the degree to which the left testis is smaller than the right. Because fertility is still in development for adolescents, total motile sperm count (TMSC) is only a surrogate for fertility. TTV3 (and to some extent TVD4) are associated with TMSC, ultrasound measures have inherent variability,5 and orchidometry tends to overestimate testis volume and is saddled with substantial variance.6 While TTV is most strongly associated with TMSC, it is a measure at the end of development. At that point, obtaining a semen analysis is a preferable option. On the other hand, while TVD can be measured at any point in development, it may be transient—particularly within a year from the initial diagnosis in a Tanner 1–2 patient. Therefore, TVD should only be used if findings are persistent as the boy proceeds through puberty. Some studies have found that boys with a TVD > 20% may achieve symmetry.7 With these factors in mind, caution is warranted, and TMSC offers the firmest footing on which to base surgical decisions.
While the relationship between adolescent varicoceles and hormones have been investigated extensively over the past decades, the association and causality, if any, between the two is still controversial. Baseline luteinizing hormone, follicle stimulating hormone (FSH), and testosterone levels have not been consistently shown to be different between adolescent males with varicoceles and age-/Tanner-matched controls.8,9 Furthermore, there is little evidence that repair of adolescent varicoceles favorably alters hormonal profiles, particularly testosterone levels.8,10,11 Importantly, hormone levels and profiles change naturally during puberty, which may add to the confusion. Recently, investigators have focused on FSH and inhibin B in adolescent males at later stages of puberty. Zampieri and colleagues found that FSH was higher in 13–16-year-old, Tanner 5 males with unilateral grade 3 left varicoceles and those with testicular hypotrophy.12 Interestingly, FSH was the only hormone with significant level improvement after varicocelectomy.12 A smaller study of Tanner 4 and 5 adolescent males found that only inhibin B was significantly different between untreated varicocele patients compared to control males.9 Inhibin B positively correlated with total testicular volume, leading the authors to suggest that inhibin B may be a proxy for early Sertoli cell function and spermatogenesis.9 Similar to these studies, investigators from the Children’s Hospital of Philadelphia recently found that FSH and inhibin B, as well as TTV, correlated with abnormal total motile sperm count in Tanner 5 males with unilateral left varicoceles, and thus may be a reasonable surrogate for late-Tanner-stage adolescent males who defer semen analysis.13
Numerous surgical options are available for varicocele correction, including the high retroperitoneal (Palomo), inguinal, microsurgical subinguinal, laparoscopic, and robotic approaches. Among these techniques, the microsurgical subinguinal approach has the lowest recurrence rate (1.05%) and the lowest hydrocele formation rate (0.44%). Regarding reproductive outcomes, a landmark randomized, controlled study by Abdel-Meguid et al demonstrated significantly higher rates of natural conception with microsurgical varicocelectomy versus observation for men with palpable varicoceles (32.9% vs 13.9% [odds ratio 3.04 (1.33-6.950)]).14 Even if varicocele correction does not result in natural conception, the subsequent improvement in semen parameters can result in a “downstaging” of the level of assisted reproductive techniques that the female partner must undergo. Samplaski et al reported that among men starting with baseline sperm concentrations of < 5 million sperm per mL, 21.6% would have enough improvement to make them good candidates for intrauterine insemination, and another 31.7% would have enough improvement to make them reasonable candidates for attempts at conception by natural means.15
In conclusion, indications for correction of the adolescent varicocele continue to evolve. Most compelling is the finding of a distinctly abnormal TMSC in the Tanner 5 patient. Improved markers for fertility potential in the prepubertal patient are required. If surgical correction is indicated, a microsurgical, subinguinal approach is favored.
- Diamond DA, Gargollo PC, Caldamone AA. Current management principles for adolescent varicocele. Fertil Steril. 2011;96(6):1294-1298. doi:10.1016/j.fertnstert.2011.10.034
- Johnson L, Petty CS, Neaves WB. Age-related variation in seminiferous tubules in men. A stereologic evaluation. J Androl. 1986;7:316. doi:10.1002/j.1939-4640.1986.tb00939.x
- Christman MS, Zderic SA, Canning DA, Kolon TF. Active surveillance of the adolescent with varicocele: predicting semen outcomes from ultrasound. J Urol. 2014;191(5):1401-1406. doi:10.1016/j.juro.2013.11.020
- Kurtz MP, Zurakowski D, Rosoklija I, et al. Semen parameters in adolescents with varicocele: association with testis volume differential and total testis volume. J Urol. 2015;193(5S):1843-1847. doi:10.1016/j.juro.2014.10.111
- Welliver C, Cardona-Grau D, Elebyjian L, et al. Surprising interobserver and intra-observer variability in pediatric testicular ultrasound volumes. J Pediatr Urol. 2019;15(4):386.e1-386.e6. doi:10.1016/j.jpurol.2019.04.016
- Kurtz MP, Migliozzi M, Rosoklija I, et al. Accuracy of orchidometry in boys with varicocele. J Pediatr Urol. 2015;11(4):185.e1-185.e1855. doi:10.1016/j.jpurol.2015.02.011
- Kolon TF, Clement MR, Cartwright L, et al. Transient asynchronous testicular growth in adolescent males with a varicocele. J Urol. 2008;180(3):1111-1115. doi:10.1016/j.juro.2008.05.061
- Fideleff HL, Boquete HR, Suárez MG, et al. Controversies in the evolution of paediatric-adolescent varicocele: clinical, biochemical and histological studies. Eur J Endocrinol. 2000;143(6):775-781. doi:10.1530/eje.0.1430775
- Romeo C, Arrigo T, Impellizzeri P, et al. Altered serum inhibin b levels in adolescents with varicocele. J Pediatr Surg. 2007;42(2):390-394. doi:10.1016/j.jpedsurg.2006.10.013
- Podesta ML, Gottlieb S, Medel R, Jr, Ropelato G, Bergada C, Quesada EM. Hormonal parameters and testicular volume in children and adolescents with unilateral varicocele: preoperative and postoperative findings. J Urol. 1994;152(2 Part 2):794-797. doi:10.1016/s0022-5347(17)32712-x
- Cayan S, Acar D, Ulger S, Akbay E. Adolescent varicocele repair: long-term results and comparison of surgical techniques according to optical magnification use in 100 cases at a single university hospital. J Urol. 2005;174(5):2003-2007. doi:10.1097/01.ju.0000176488.44895.7b
- Zampieri N. Hormonal evaluation in adolescents with varicocele. J Pediatr Urol. 2021;17(1):49.e1-49-e5. doi:10.1016/j.jpurol.2020.11.024
- Van Batavia JP, Lawton E, Frazier JR, et al. Total motile sperm count in adolescent boys with varicocele is associated with hormone levels and total testicular volume. J Urol. 2021;205(3):888-894. doi:10.1097/JU.0000000000001405
- Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. Eur Urol. 2011;59(3):455-461. doi:10.1016/j.eururo.2010.12.008
- Samplaski MK, Lo KC, Grober ED, Zini A, Jarvi KA. Varicocelectomy to “upgrade” semen quality to allow couples to use less invasive forms of assisted reproductive technology. Fertil Steril. 2017;108(4):609-612. doi:10.1016/j.fertnstert.2017.07.017
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