Current approaches to the undescended testicle

By Fernando A. Ferrer, MD, and Patrick H. McKenna, MD

Cryptorchidism is more common that you might think, especially in premature infants. Accurate diagnosis and early correction, made easier by laparoscopy, relieve stress on the family and may reduce the risks of long-term complications such as infertility.

Cryptorchidism, the arrested descent of a testicle from its intrabdominal location in utero, is estimated to occur in 3.4% of all male term infants and up to 30% of premature male infants.¹ The relative frequency of this disorder and the psychosocial implications of a genital abnormality for both parents and child make it essential that pediatricians be familiar with the etiology, diagnosis, and treatment of cryptorchidism. Equally important is a knowledge of its long-term consequences, particularly with regard to fertility and the risk of malignancy. Conveying accurate information dispels myths about children with an undescended testis, reassures the family, and reaffirms the need for treatment.

What causes cryptorchidism?

We know that descent of the testis from an intrabdominal position to a location in the scrotum is necessary for normal spermatogenesis in humans. The probable explanation for this is that to produce normal sperm the temperature of the testis must be lower than the intra-abdominal temperature. Even elevations in testicular temperature as small as 1° or 2° C appear to be important.²

Sometime after the seventh month of gestation the testes, which lie in the abdomen until that time, travel from a location near the inguinal ring through the abdominal wall and into the scrotum.³ Several theories have been proposed to explain the mechanism of descent.^4­9 An endocrinologic effect on the gubernaculum testis, a fetal ligament that connects the testis and the scrotal sac, is the most likely explanation. This theory is supported by studies showing androgen receptors on the gubernaculum and the genitofemoral nerve that innervates it. Thus a disruption of the normal hormonal influence on the gubernaculum or its innervation is believed to be the most likely cause of testicular maldescent.¹⁰

Undescended, ectopic, or retractile?

To classify an undescended testis it is important to understand the difference between two conditions commonly confused with cryptorchidism: the ectopic testis and the retractile testicle. A cryptorchid testis is a testicle whose descent has been arrested somewhere along the normal pathway between its original abdominal location and a scrotal position. The most common locations for an undescended testis in order of frequency are prescrotal (below the external inguinal ring but not in the scrotum), inguinal or canalicular (between the internal and external inguinal rings), and abdominal (impalpable), as shown in Figure 1.

An ectopic testis refers to a testicle that has been diverted from the normal pathway of descent and come to lie in a location outside that which the normal testis travels on its way to the scrotum. Current thinking is that this occurs because the gubernaculum. which normally guides the testis into a scrotal position, has an abnormal insertion point and the testis follows it to an ectopic location.¹¹ Five sites of testicular ectopia, also shown in Figure 1, are generally recognized. The superficial inguinal location is by far the most common. The other sites include the suprapubic or penile position, femoral, perineal, and, least common, the contralateral position. The key point to remember about ectopic testes is that they will never descend to the appropriate position as the child ages.

The retractile testis is very often confused with an undescended testis. One study showed that up to 20% of 600 boys 12 years of age or younger had evidence of a retractile testis. In testicular retraction stimulation of the cremasteric muscle causes the testis to ascend, leaving an empty hemiscrotum and the appearance of an undescended testis. The testis usually rises to the level of the upper scrotum but may reach the superficial inguinal pouch just at the external inguinal ring. The retractile response of the testis to various stimuli is likely a protective reflex. The key points to look for when evaluating a suspected retractile testis are a history indicating that at one time the testis was documented to be in the scrotum on exam, or a testis that can be brought completely into the scrotum on examination.

How common is cryptorchidism?

The incidence of cryptorchidism at birth is directly related to the gestational age of the infant. This is because descent of the testes is a late event in development, occurring during the last trimester of pregnancy. Consequently, premature infants have the highest rate of cryptorchidism--30%. Full-term infants have an incidence of about 3.4% at birth (Table 1). About 10% of patients with an undescended testis have bilateral cryptorchidism, and 3% to 5% are found to be without a testicle.¹

As children age, the cryptorchid testis may descend spontaneously as plasma androgen levels rise so that the incidence of undescended testicle at 1 year of age is the same as in adults (about 0.8% as determined and validated largely by studies of military populations). If spontaneous descent is to occur, it will most likely happen in the first three months of life. The chance of spontaneous descent is directly related to the severity of the cryptorchidism.

How do you make the diagnosis?

Diagnosing an undescended testis begins with the physical examination. The patient should be examined in a comfortable setting while lying supine with his legs elevated (the frog leg position). The evaluation should include a full genital examination with observation for penile abnormalities, such as hypospadias. First examine the scrotum to determine whether its size and development are normal. The scrotum of a patient with an undescended testis is often underdeveloped. If the scrotum is empty, palpate the sites where an ectopic testis might be located and examine the normal pathway of development to locate the gonad.

If a testis is palpable, attempt to bring it into the scrotal cavity. It often helps to try to "milk" the testis downward by pressing down just above the inguinal canal and gliding a lubricated hand from this point toward the scrotum. If the testis can be brought down all the way into the scrotum, it is retractile. Document this finding and perform annual examinations during routine physical exams to confirm it. If an ectopic testis is found, document the location for future treatment. Testes that are not ectopic or retractile are classified as undescended.

Patients with bilateral undescended testes may suffer from anorchia (absence of both testicles) or an intersex disorder such as hermaphroditism and should undergo chromosomal and hormonal evaluation. We measure serum gonadotropins and androgens--follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone--in patients with suspected anorchia. Marked elevation of the gonadotropins along with lack of testosterone in young boys implies an absence of testicular tissue.

When gonadotropin levels are not elevated, we perform a diagnostic human chorionic gonadotropin (hCG) test in conjunction with a urologic surgical consultation. This test consists of a short course of intramuscular hCG (newborns 1,500 units, 2-year-olds 41,000 units, 5-year-olds 121,500 units) given daily for four days with measurement of FSH, LH, and testosterone before the fourth day's dose. Patients with cryptorchidism respond to hCG stimulation with increasing testosterone levels; anorchic patients do not.^12,13 In some cases hCG treatment will make a previously nonpalpable testis palpable.¹⁴ Hormonal treatment also may improve the vascular supply of the testes facilitating future surgical correction.

Imaging studies are rarely indicated in evaluating cryptorchidism because of their overall poor accuracy (44%) regardless of the modality used.¹⁵ If an imaging study is indicated--in the case of an older patient with an unclear surgical history, for example--MRI is most likely to be helpful in localizing an intra-abdominal testis.

Laparoscopy is now the preferred method of diagnosing an impalpable testis.¹⁶ The technique is safe, conclusively documents the fate of the impalpable gonad, and can assist in planning surgical correction.¹⁷ Specifically, it documents the absence of a testis, an atrophied nonviable gonad, or a viable intra-abdominal gonad. In the case of a viable intra-abdominal gonad, laparoscopy also can also be used to correct the condition.¹⁸

Although cryptorchidism is associated with various inherited disorders, chromosomal evaluation of cryptorchid boys who are otherwise normal has failed to reveal any significant findings. For this reason, we do not perform chromosomal studies in cases of simple cryptorchidism.

Why, when, and how do you treat?

There are three reasons for treating children with undescended testes:

• The abnormal appearance of the undescended testis may cause psychosocial stress for the child and parents.

• Increased long-term risk of malignancy in undescended testes makes it essential that they be moved to an anatomic location where the child can readily perform self-examination to detect abnormalities early.

• Placing the undescended testicle in the scrotum early may benefit its potential for future fertility.

The timing of correction is determined primarily by two factors. First, histologic evidence of damage to the undescended testicle is apparent between 1 and 2 years of age, so it is generally recommended that attempts to position the testis correctly be made before this time to preserve fertility. Second, available data suggest that if the testis has not descended spontaneously by 1 year of age, the likelihood of spontaneous descent is small, so waiting beyond that point to perform correction has no benefit. In our practice we generally recommend correction at 1 year, although some now recommend earlier treatment. Given the trend toward surgery at a younger age, patients are best managed by pediatric urologists at a children's center providing specialized pediatric anesthesiology and postop care.

For patients with unilateral cryptorchidism evaluation for treatment begins with a careful physical examination (Figure 2). The key is to differentiate the undescended testis from the retractile or ectopic testis. If the testis is palpable, we generally recommend ongoing observation followed by correction at 1 year of age. Another option for these patients is administration of hCG or gonadotropin-releasing (GnRH) to induce descent on the theory that elevating testosterone levels will cause spontaneous descent of the testes.¹⁰ Unfortunately, reports of success with this therapy have been mixed, and it requires parents to give the IM injections (in the buttocks), which are uncomfortable.¹⁹ Nevertheless, some patients may respond to exogenous hormonal therapy.

If the testis is not palpable, laparoscopy at 6 months to 1 year of age has become the standard treatment. It is performed as an outpatient procedure by a pediatric urologic surgeon. The overall complication rate is very low. Laparoscopy has revolutionized management of the undescended gonad, not only for diagnosing absent testes but also removing nonviable intra-abdominal testes and providing initial therapy for children with high but salvageable testes. Since patients with true ectopic testes are unlikely to experience spontaneous descent, they should undergo repair anytime after 6 months of age. Patients with retractile testes should be examined periodically to ensure that the testicle can be brought into the scrotum as they grow.

Patients with bilateral cryptorchidism should undergo careful evaluation for intersex disorders and have a chromosomal evaluation as well (Figure 3). Those with at least one palpable testis should undergo repair at 6 months to 1 year of age. We also perform laparoscopy to localize the contralateral nonpalpable testis and treat it at this time. The rationale for intervening early in these patients is to preserve as much fertility potential as possible.

Patients with bilateral impalpable testes should undergo hormonal evaluation initially. If the FSH and LH are elevated, a presumptive diagnosis of anorchia is made. If the FSH and LH are normal, indicating possible presence of testes, an hCG stimulation test is performed to prove that functioning tissue is present. In either case, laparoscopy is recommended to remove nonfunctional tissue or localize and repair the undescended gonads. In rare cases when standard orchidopexy procedures cannot relocate the testis into the scrotum, testicular autotransplantation may be considered. This technique involves removing the testis from the abdomen and performing a microvascular anastomosis using an inguinal vessel so that the testis can be placed in the scrotum.²⁰

What are the risks?

Complications and long-term risks associated with cryptorchidism include cancer, impaired fertility, testicular torsion, and hernia. There are no risks associated with a retractile testis.

Cancer. An increased lifetime risk of testicular cancer in patients with cryptorchidism has been well documented. It is estimated that the undescended testis is 35 to 48 times more likely to develop cancer than a normal testis.^{21, 22} About 10% of all testicular tumors occur in patients with an undescended testis.²³ It is interesting to note that around one in five such tumors occurs in the contralateral normal testis, suggesting that some factor affecting both testes is present. In patients with bilateral undescended testes the risk of malignancy in one testis if the other develops cancer is 15%, even higher if both testes are intra-abdominal.²⁴ Germ cell tumors (seminomas and nonseminomas) are the most common pathologic findings in these patients.

Because histologic changes occur early in undescended testes, the increased risk of malignancy supports early surgical correction. It is important to inform families that while early surgical correction is not known to decrease the risk of cancer, it does permit examination and early detection of malignancy in an organ that is at high risk. Patients (or parents of younger children) should examine the testes monthly with annual or biannual follow-up exams by the physician. Periodic biopsy of the testes has no role in management.

Impaired fertility. The cryptorchid testis clearly is at risk of diminished fertility resulting from histologic changes that can be seen as early as 1 to 2 years of age--specifically, degeneration of the seminiferous tubules and a decrease in both the quality and quantity of sperm. We counsel parents that patients with unilateral cryptorchidism will probably have some decrease in fertility.²⁵ Patients with bilateral cryptorchidism will have significantly diminished fertility.²⁶ We also tell families, however, that advanced reproductive techniques should make available a growing number of options for these patients in the future.

The degree of fertility impairment is directly related to the amount of time the testis resides outside the scrotum and to its location. Thus, while early correction may not prevent histologic damage to the testis, placement of the testis into the scrotum at about 1 year of age does help to preserve fertility potential.²⁷ The endocrine function of the Leydig cells of the undescended testis appears to be less affected and testosterone levels are generally normal in patients who undergo early correction.

Testicular torsion. Structural abnormalities of the undescended testis and its mesentery increase the risk of torsion. This risk is greatest during puberty and the early teen years when the testis is growing rapidly. We counsel patients to seek immediate evaluation of acute onset testicular pain or discomfort.

Hernia. Hernia sacs are found in up to 90% of patients with an undescended testis and are corrected at the same time the testis is brought down into the scrotum.¹ The association between hernias and cryptorchid testes exists because the processus vaginalis, which usually travels with the testes into the scrotum and then closes, remains patent, allowing intra- abdominal contents to enter the processus and cause a hernia.

Where do we stand now?

Tremendous advances have been made in understanding the consequences of a testis that remains in an undescended location, but the exact mechanism controlling descent has yet to be completely explained. The first critical step in managing the patient with cryptorchidism is differentiating a retractile or ectopic testis from a truly undescended testis. It is clear that most testes that remain undescended at 1 year of age will not descend spontaneously. The histologic consequences of leaving the testis outside the scrotum past 1 year of age thus outweigh the low risk of early surgical intervention.

Advances in surgical techniques over the last ten years, such as the routine use of magnification and laparoscopy, have simplified the approach to the nonpalpable testis, making it a same-day surgery procedure in most cases. It is important to understand that relocating the testis to the scrotum does not diminish the risk of malignancy and that long-term periodic follow-up by the pediatrician and routine self-examination by the patient are therefore mandatory.

DR. FERRER is in the Department of Pediatric Urology, Connecticut Children's Medical Center, Hartford, and the University of Connecticut Health Center, Farmington and is a Pediatric Urology Fellow at the Brady Urologic Institute, Johns Hopkins Hospital, Baltimore.

DR. McKENNA is in the Department of Pediatric Urology Connecticut Children's Medical Center and the University of Connecticut Health Center.

REFERENCES

1. Scorer CG, Farrington GH: Congenital Deformities of the Testis and Epididymis. New York, Appleton-Century-Crofts, 1971

2. Mieusset R, Fouda PJ, Vaysse P, et al: Increase in testicular temperature in cases of cryptorchidism in boys. Fertil Steril 1993;59:1319

3. Backhouse KM: Embryology of the normal and cryptorchid testis, in Fonkalsrud EW, Mengel W (eds): The Undescended Testis. Chicago, Year Book Publishers, 1981, p 5

4. Sonneland CG: Undescended testicle. Surg Gynecol Obstet 1925;40:535

5. Hunter PA: The etiology of congenital inguinal hernia and abnormally placed testes. Br J Surg 1927;14:125

6. Attah AA, Hutson JM: The role of intra-abdominal pressure in cryptorchidism. J Urol 1993;150:994

7. Hadziselimovac F: Pathogenesis of cryptorchidism. Clin Androl 1981;7:147

8. Beasley SW, Hutson JM: Effect of division of the genitofemoral nerve on testicular descent in the rat. Aust N Z J Surg 1988;57:49

9. Rajfer J, Walsh PC: Hormonal regulation of testicular descent: Experimental and clinical observations. J Urol 1977;118:985

10. Rajfer J: Congenital anomalies of the testis and scrotum, in Walsh PC, Retik AB, Vaughan, ED, et al (eds): Campbell's Urology. Philadelphia, WB Saunders Co, 1998, p 2172

11. Lockwood, CG: Development and transition of the testis, normal and abnormal. J Anat Physiol 1988;22:505

12. Grant DB, Laurence BM, Atherden SM, et al: hCG Stimulation test in children with abnormal sexual development. Arch Dis Child 1976;51:596

13. Kogan S: Cryptorchidism, in Kelalis PP, King LR, Belman AB (eds): Clinical Pediatric Urology. Philadelphia, WB Saunders Co, 1992, pp 1050­1083

14. Polascik TJ, Chan-Tack KM, Jeffs RD, et al: Reappraisal of the role of human chorionic gonadotropin in the diagnosis and treatment of the nonpalpable testis: A 10-year experience. J Urol 1996;156:804

15. Hrebinko RL, Bellinger MF: The limited role of imaging techniques in managing children with undescended testes. J Urol 1993;150:458

16. Silber SJ, Cohen R: Laparoscopy for cryptorchidism. J Urol 1980;124:928

17. Cisek LJ, Peters CA, Atala A, et al: Current findings in diagnostic laparoscopic evaluation of the nonpalpable testis. J Urol 1998;160:1145

18. Law GS, Perez LM, Joseph DB: Two-stage Fowler- Stephens orchiopexy with laparoscopic clipping of the spermatic vessels. J Urol 1997;158:1205

19. Job JC, Carnlorbe P, Garagorri JM, et al: Hormonal therapy of cryptorchidism with hCG. Urol Clin North Am 1982;9:405

20. Wacksman J, Billmore DA, Lewis AG, et al: Laparoscopically assisted testicular autotransplantation for the management of the intra-abdominal undescended testis. J Urol 1996;156:772

21. Martin DC, Menck HR: The undescended testis: Management after puberty. J Urol 1975;114:77

22. Martin DC: Germinal cell tumors of the testis after orchiopexy. J Urol 1979;121:422

23. Abratt RP, Reddi VB, Sarembock LA: Testicular cancer and cryptorchidism. Br J Urol 1992;70:656

24. Gilbert JB, Hamilton JB: Incidence and nature of tumors in ectopic testis. Surg Gynecol Obstet 1970;71:731

25. Lee PA, O'Leary LA, Songer NJ, et al: Paternity after unilateral cryptorchidism: A controlled study. Pediatrics 1996;98:676

26. Wollach Y, Shaher E, Schacter AS, et al: Fertility and sexual development after bilateral orchiopexy for cryptorchidism. Isr J Med Sci 1980;16:707

27. American Academy of Pediatrics, Section of Urology: The Committee Action Report from the Section of Urology of The American Academy of Pediatrics. Pediatrics 1996;97:590

ACCREDITATION

This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Jefferson Medical College and Medical Economics, Inc.

Jefferson Medical College of Thomas Jefferson University, as a member of the Consortium for Academic Continuing Medical Education, is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians. All faculty/authors participating in continuing medical education activities sponsored by Jefferson Medical College are expected to disclose to the activity audience any real or apparent conflict(s) of interest related to the content of their article(s). Full disclosure of these relationships, if any, appears with the author affiliations on page 1 of the article.

CONTINUING MEDICAL EDUCATION CREDIT

This CME activity is designed for practicing pediatricians and other health-care professionals as a review of the latest information in the field. Its goal is to increase participants' ability to prevent, diagnose, and treat important pediatric problems.

Jefferson Medical College designates this continuing medical educational activity for a maximum of one hour of Category 1 credit towards the Physician's Recognition Award (PRA) of the American Medical Association. Each physician should claim only those hours of credit that he/she actually spent in the educational activity.

This credit is available for the period of January 15, 2000, to January 15, 2001. Forms received after January 15, 2001, cannot be processed.

Although forms will be processed when received, certificates for CME credits will be issued every four months, in March, July, and November. Interim requests for certificates can be made by contacting the Jefferson Office of Continuing Medical Education at 215-955-6992.

HOW TO APPLY FOR CME CREDIT

1. Each CME article is prefaced by learning objectives for participants to use to determine if the article relates to their individual learning needs.

2. Read the article carefully, paying particular attention to the tables and other illustrative materials.

3. Complete the CME Registration and Evaluation Form below. Type or print your full name and address in the space provided, and provide an evaluation of the activity as requested. In order for the form to be processed, all information must be complete and legible.

4. Send the completed form, with $20 payment if required (see Payment, next page), to:
Office of Continuing Medical Education/JMC
Jefferson Alumni Hall
1020 Locust Street, Suite M32
Philadelphia, PA 19107-6799

5. Be sure to mail the Registration and Evaluation Form on or before January 15, 2001. After that date, this article will no longer be designated for credit and forms cannot be processed.

FACULTY DISCLOSURES

Jefferson Medical College, in accordance with accreditation requirements, asks the authors of CME articles to disclose any affiliations or financial interests they may have in any organization that may have an interest in any part of their article. The following information was received from the authors of "Current approaches to the undescended testicle:"

Fernando A. Ferrer, MD, has no information to disclose.

Patrick H. McKenna, MD, has no information to disclose.

Fernando Ferrer, Patrick McKenna. Current approaches to the undescended testicle. Contemporary Pediatrics 2000;1:106.