Updated: Sep 18, 2009
Cryptorchidism is the most common abnormality of male sexual development. In this condition, the testis is not located in the scrotum. The testis can be ectopic, incompletely descended, retractile, and absent or atrophic. The term cryptorchidism is translated from a Greek term that means hidden or obscure testis. Sir John Hunter, the British anatomist, reported this condition in 1786. In 1877, Annandale performed the first successful orchidopexy. In 1899, Bevan published the principles of testicular mobilization, separation of the processus vaginalis, and repositioning of the testis into the scrotum. Testicular maldescent has been the subject of many clinical studies, but its embryology, effects on fertility, and ultimate clinical impact still remain a topic of discussion and research.
Embryology of testis development
The embryology of testis development is critical to understanding the most common theories that explain cryptorchidism.
Shortly after 6 weeks' gestation, the testis-determining SRY gene on chromosome Y directly affects the differentiation of the indifferent gonad into a testis. Germ cells are located in the germinal ridge close to the kidney in the retroperitoneum. Around 6-7 weeks' gestation, Sertoli cells develop and secrete Müllerian inhibitory substance (MIS), which leads to the regression of the female genital organs. Around 9 weeks' gestation, Leydig cells start producing testosterone, which promotes development of the wolffian duct into portions of the male genital tract. Concurrently, the testis organizes as a distinct organ with its distinct seminiferous tubules surrounded by vessels and encapsulated by the tunica albuginea. Owing to the differential growth of the fetus, the testicles move into the pelvis, close to the internal ring.
The testis remains in a retroperitoneal position until 28 weeks' gestation, at which time inguinal descent of the testicle begins. Most testes have completed their descent into the scrotum by 40 weeks' gestation.
Theories of cryptorchidism pathophysiology
Several theories have been offered to explain the pathophysiology of cryptorchidism, including gubernacular abnormalities, reduced intra-abdominal pressures, intrinsic testicular and/or epididymal abnormalities, and endocrine abnormalities, as well as anatomic anomalies (eg, fibrous bands within the inguinal canal or abnormal arrangement of the cremasteric muscle fibers).
The gubernaculum testis is a structure that attaches the lower portion of the tunica vaginalis to base of the scrotum. The gubernaculum is thought to aid in testicular descent by widening the inguinal canal and guiding the testis down to the scrotum. Therefore, anomalies in this attachment may contribute to cryptorchidism.
Cryptorchidism is common in patients with prune belly syndrome and those with gastroschisis; both are associated with decreased intra-abdominal pressures. However, the theory based on reduced pressures does not explain most cases of cryptorchidism.
Another theory of testicular maldescent is based on intrinsic testicular and/or epididymal abnormalities. Several studies have shown that, histologically, the germinal epithelium of the maldescended testis may be abnormal. Infertility is associated with cryptorchidism, and the risk of infertility increases with the degree of maldescent. Moreover, approximately 23%-86% of maldescended testes have been associated with some form of epididymal abnormality. Studies have shown an increase in the degree of epididymal abnormalities in intra-abdominal testis compared with mild cases of cryptorchidism.1
Abnormalities in the hypothalamic-pituitary-gonadal axis have been postulated as a possible explanation for anomalies of testicular descent and abnormal germ-cell development. However, both animal and human endocrine studies have not been able to shed clear light on the pathophysiology of testicular maldescent. The causative hormonal abnormality may be found at different levels. The fact that the condition most often affects one side indicates that endocrine anomalies may be partially responsible but does not completely explain why the testis does not descend normally.
Current and future research
The molecular mechanisms by which the newly determined testicle descends from its position in the posterior abdomen into the scrotum is a complex process that likely involves multiple genetic, hormonal, environmental, and stochastic factors. Although a comprehensive explanation has not yet been elucidated, several exciting observations suggest that specific genetic loci play important roles in normal testicular descent and the occurrence of cryptorchidism.
Models for the study of cryptorchidism include experiments in knockout mice. Homozygous mutants for the loss of Hoxa-10 and Hoxa-11 exhibit cryptorchidism. Both genes are members of the family of homeobox (Hox) genes, which are highly conserved throughout evolution and which play a critical role in anteroposterior positioning in the developing embryo. Early orchiopexy rescues Hoxa-11 mutants from an infertile state. Hoxa-10 polymorphisms have been found in human cryptorchid populations, although the functional significance of these genetic changes has not yet been established.
In the literature, much attention has been focused on insulinlike factor 3 (Insl-3 or relaxinlike factor) and its receptor, leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8), or G-protein–coupled receptor affecting testes descent (GREAT).2 Homozygous knockouts of either Insl-3 or LGR8 lead to the phenotype of bilateral intra-abdominal testes. As in the murine Hoxa-11 model, early orchiopexy of Insl-3–genetically deficient mice allows for the development of fertility.
Although some have suggested that mutations in the Insl-3 gene might not play a substantial role in human cryptorchidism, a missense mutation in Insl-3 has been found in a patient with cryptorchidism; this mutation causes a nonconservative amino acid substitution. A proof-of-principle study has not yet been conducted to determine if this Insl-3 mutation leads to cryptorchidism.
LGR8 polymorphisms have been identified in both cryptorchid and healthy human populations. One of the receptor mutations found in a cryptorchid patient precluded a response to ligand stimulation in vitro.
In the search for a genetic cause of cryptorchidism, other areas of focus include Y-chromosome microdeletions, increased aromatase activity, and abnormalities in the Wilms tumor gene (WT1).
A palpable undescended testis is found in 3%-5% of newborns, and bilateral undescended testis is found in 15% of newborns with cryptorchidism. Most undescended palpable testes later spontaneously descend within the first 4 months of life; only 0.7%-1% of 1-year-old infants have a persistent undescended testis. Studies have shown that spontaneous descent does not occur after age 9 months. The incidence does not change between age 1 year and adulthood. However, some testes that were descended in early childhood may ascend later in life.
Nonpalpable testes account for approximately 20% of all undescended testes. Approximately 40% of the nonpalpable testes are intra-abdominal, 40% are inguinal, and 20% are atrophic or absent.
Cryptorchidism is found in 30% of babies born prematurely. Other predisposing factors include low birth weight, small size for gestational age, twin pregnancy, and maternal estrogen exposure. Cryptorchidism is found in 7% of siblings and in about 2% of fathers of babies with this condition.
Cryptorchidism has not been associated with any factors for mortality. However, testicular maldescent has been associated with a slight increase in the risk of testicular cancer, infertility, trauma, and testicular torsion. If not treated, testicular maldescent may also affect the psychological well-being of young men in whom negative self-esteem issues may arise.
Cryptorchidism has no reported racial predilection.
Cryptorchidism affects only males.
See Frequency above.
Determining if the testis was palpable in the scrotum at any time is important. The patient's prenatal history should include his gestational age at birth, any need for assisted reproduction, maternal hormonal treatment, and the mother's number of gestations. Any previous history of inguinal surgery should be noted, as should a family history of cryptorchidism and other associated conditions.
Cryptorchidism is associated with inguinal hernia and/or patent processus vaginalis, hypospadias, cerebral palsy, mental retardation, Down syndrome, Wilms tumor, prune belly syndrome, and Prader-Willi syndrome.
Physical examination is most important tool in the diagnostic evaluation of cryptorchidism. The patient must be examined in a warm, relaxed environment. Closely observing the scrotum before manipulation is important. The frog-leg or catcher position may be used to aid palpation of the testis.
Determining if the testis is palpable is essential. If the testis is palpable, ascertain retractibility of the testicle. The retractile testis should stay in the dependent portion of the scrotum after manipulation.
The best technique to evaluate for an undescended testis is to start palpating at level of the inguinal canal and perform a milking motion down toward the scrotum. Look for hemiscrotal asymmetry and for contralateral testicular hypertrophy; both are partial indicators of an absent testis.
Examination of potential ectopic sites such as penile, femoral, and perineal areas is important if the testicle cannot be felt in the inguinal area. Patients with hypospadias and cryptorchidism have a higher incidence of disorders of sexual differentiation (DSD) or intersex conditions, and a workup should be considered. If any doubt remains after the initial examination, reevaluation of the patient is mandatory prior to recommending surgical management.
Retractile testis
Anorchia
Intra-abdominal testis
Vanishing testis syndrome or nubbin testicle resulting from perinatal torsion
The histologic findings of an undescended testis range from normal histology to acquired germ-cell hypoplasia with Leydig cell hyperplasia. The severity of the histologic findings is correlated with an intra-abdominal testis and/or delayed orchiopexy.
Carcinoma in situ is present in up to 8% of infertile patients undergoing testicular biopsy with a history of orchiopexy. In children with undescended testis, the overall incidence of carcinoma in situ is approximately 0.4%. The clinical significance of these 2 findings is unclear.
No staging system is reported. The physical finding of a palpable testis versus a nonpalpable testis is the most reliable and easy way to group cryptorchidism cases.
General issues
Engle proposed hormonal manipulation as a treatment for cryptorchidism in the 1930s. The main goals of hormonal or surgical treatment are to allow for a normal anatomic position of the testicle, the preservation of fertility and hormonal production, and the diagnosis of potential testicular malignancies. Other putative benefits include correction of associated hernias and prevention of testicular torsion.
The risk of trauma and possible psychological effects of having a missing testis must be taken into account. Orchiopexy should be considered after 4 months of life, as the rate of descent diminishes considerably after this point.
For postpubertal adolescents and men younger than 32 years who underwent unilateral orchiopexy, orchiectomy should be considered. For postpubertal men older than 32 years, close observation and routine physical examination should be considered. Any man with bilateral undescended testes should undergo bilateral testicular biopsy and orchiopexy.
Hormonal therapy
Hormonal therapy should be considered in patients in whom the diagnosis of retractile testis is not certain. In patients who are not candidates for surgical interventions, hormonal therapy might be appropriate. Hormonal therapy has been used in Europe for many years as a primary therapy for cryptorchidism. hCG or LH-releasing hormones (LHRH) are mainly used. In Europe, hCG and LHRH have been used in combination, with initial success rates of 14%-65%. However, some long-term studies have shown lower success rates.
Similarly to LH, hCG acts on Leydig cells to stimulate the production of gonadal steroid hormones. However, its effects on testicular descent are not fully understood. In most patients with retractile testis, their condition responds to hCG. Studies have shown short-term success rates as high as 70%. Controlled studies have shown results less impressive than this, with rates around 14%. Multiple dosage schedules have been proposed. The authors' current protocol is 1000 IU/wk for children who weigh less than 10 kg, 1500 IU/wk for children who weigh 10-20 kg, and 2500 IU/wk for children who weigh more than 20 kg. The duration of therapy is 4 weeks.
LHRH acts indirectly in the pituitary by stimulating the release of gonadotropins LH and FSH. LHRH may be more efficient in increasing testosterone than hCG. LHRH is currently available only in Europe for use in cryptorchidism. Success rates are similar to those of hCG and are in the range of 10%-15%.
Adverse effects from both hormonal therapies include increase in scrotal rugae, pigmentation, growth of pubic hair, increased penile size, and erections. Adverse effects of LHRH are fewer than those of hCG.
Several surgical approaches to the undescended testis have been described. The approach chosen is determined by the position of the testis and the surgeon's expertise.
The palpable testis can be approached from a scrotal, subinguinal, inguinal, or suprainguinal approach. The nonpalpable testis can be approached using an inguinal, suprainguinal, or laparoscopic approach.
Routine testicular biopsy during orchiopexy is not recommended and should be considered only in cases involving prune belly syndrome, ambiguous genitalia, abnormal karyotypes, or postpubertal adolescents or men. Some authors have recommended that, if the biopsy reveals carcinoma in situ, repeat exploration and unilateral orchiectomy should be performed. In bilateral cases, radiation therapy may be useful.
Surgical pearls regarding the palpable testis
Surgical pearls for the nonpalpable testis
Maneuvers to increase length of an undescended testis
Success rates
Patients with bilateral anorchia or an intersex condition may benefit from a consultation with a pediatric endocrinologist.
No changes in diet are required after treatment.
After surgery, patients should be advised to limit their activities for a week and refrain from straddling.
This treatment should be considered when the diagnosis of retractile testis is uncertain. This is also used for cases of nonpalpable testis in which Fowler-Stephens orchiopexy is considered or in patients who are poor candidates for surgical intervention. Hormonal therapy has been used in Europe for many years as a primary therapy for cryptorchidism.
Acts on Leydig cells similar to pituitary LH by stimulating production of gonadal steroid hormones, including testosterone. Effect on testicular descent not fully understood. Success rates 14-70%.
Not established
500-1000 U 3 times/wk; adjust by protocol
Various protocols exist, eg:
<10 kg: 1000 IU IM qwk for 4 wk
10-20 kg: 1500 IU IM qwk for 4 wk
>20 kg: 2500 IU IM qwk for 4 wk
None reported
Documented hypersensitivity; prostatic carcinoma, precocious puberty
X - Contraindicated; benefit does not outweigh risk
Caution in asthma, seizure disorders, cardiac or renal disease, and migraine; may cause increase in scrotal rugae, pigmentation, pubic hair growth, increase penile size and erection; other adverse effects include headache, irritability, restlessness, depression, or gynecomastia
Most surgeries used to treat cryptorchidism are performed on an ambulatory basis.
Pain control medications should be prescribed as needed.
Early orchiopexy performed before age 2 years may prevent possible damage to the testis and may improve spermatogenetic viability.
Barthold JS, Redman JF. Association of epididymal anomalies with patent processus vaginalis in hernia, hydrocele and cryptorchidism. J Urol. Dec 1996;156(6):2054-6. [Medline].
Nguyen MT, Showalter PR, Timmons CF, Nef S, Parada LF, Baker LA. Effects of orchiopexy on congenitally cryptorchid insulin-3 knockout mice. J Urol. Oct 2002;168(4 Pt 2):1779-83; discussion 1783. [Medline].
Banieghbal B, Davies M. Laparoscopic evaluation of testicular mobility as a guide to management of intra-abdominal testes. World J Urol. May 2003;20(6):343-5. [Medline].
Bassel YS, Scherz HC, Kirsch AJ. Scrotal incision orchiopexy for undescended testes with or without a patent processus vaginalis. J Urol. Apr 2007;177(4):1516-8. [Medline].
Breyer BN, DiSandro M, Baskin LS, Hsieh MH. Obesity does not decrease the accuracy of testicular examination in anesthetized boys with cryptorchidism. J Urol. Feb 2009;181(2):830-4. [Medline].
Ferlin A, Simonato M, Bartoloni L, et al. The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism. J Clin Endocrinol Metab. Sep 2003;88(9):4273-9. [Medline].
Giannopoulos MF, Vlachakis IG, Charissis GC. 13 Years' experience with the combined hormonal therapy of cryptorchidism. Horm Res. 2001;55(1):33-7. [Medline].
Hack WW, van der Voort-Doedens LM, Sijstermans K, Meijer RW, Pierik FH. Reduction in the number of orchidopexies for cryptorchidism after recognition of acquired undescended testis and implementation of expectative policy. Acta Paediatr. Jun 2007;96(6):915-8. [Medline].
Hutson JM, Hasthorpe S, Heyns CF. Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev. Apr 1997;18(2):259-80. [Medline].
Kaleva M, Arsalo A, Louhimo I, et al. Treatment with human chorionic gonadotrophin for cryptorchidism: clinical and histological effects. Int J Androl. Oct 1996;19(5):293-8. [Medline].
Koff SA, Sethi PS. Treatment of high undescended testes by low spermatic vessel ligation: an alternative to the Fowler-Stephens technique. J Urol. Aug 1996;156(2 Pt 2):799-803; discussion 803. [Medline].
Law GS, Perez LM, Joseph DB. Two-stage Fowler-Stephens orchiopexy with laparoscopic clipping of the spermatic vessels. J Urol. Sep 1997;158(3 Pt 2):1205-7. [Medline].
Lee MM, Donahoe PK, Silverman BL, et al. Measurements of serum müllerian inhibiting substance in the evaluation of children with nonpalpable gonads. N Engl J Med. May 22 1997;336(21):1480-6. [Medline].
Lee PA, Coughlin MT. Fertility after bilateral cryptorchidism. Evaluation by paternity, hormone, and semen data. Horm Res. 2001;55(1):28-32. [Medline].
Lee PA, Coughlin MT. The single testis: paternity after presentation as unilateral cryptorchidism. J Urol. Oct 2002;168(4 Pt 2):1680-2; discussion 1682-3. [Medline].
Lee PA, O'Leary LA, Songer NJ, et al. Paternity after bilateral cryptorchidism. A controlled study. Arch Pediatr Adolesc Med. Mar 1997;151(3):260-3. [Medline].
Lenzi A, Gandini L, Lombardo F, et al. Unilateral cryptorchidism corrected in prepubertal age: evaluation of sperm parameters, hormones, and antisperm antibodies in adult age. Fertil Steril. May 1997;67(5):943-8. [Medline].
Lewis AG, Pecha BR, Smith EP, et al. Early orchiopexy restores fertility in the Hoxa 11 gene knockout mouse. J Urol. Jul 2003;170(1):302-5. [Medline].
Lim HN, Hughes IA, Hawkins JR. Clinical and molecular evidence for the role of androgens and WT1 in testis descent. Mol Cell Endocrinol. Dec 20 2001;185(1-2):43-50. [Medline].
Lindgren BW, Darby EC, Faiella L, et al. Laparoscopic orchiopexy: procedure of choice for the nonpalpable testis?. J Urol. Jun 1998;159(6):2132-5. [Medline].
Matthews LA, Abdul-Karim FW, Elder JS. Effect of preoperative human chorionic gonadotropin on intra-abdominal rat testes undergoing standard and Fowler-Stephens orchiopexy. J Urol. Jun 1997;157(6):2315-7. [Medline].
Merry C, Sweeney B, Puri P. The vanishing testis: anatomical and histological findings. Eur Urol. 1997;31(1):65-7. [Medline].
Miller KD, Coughlin MT, Lee PA. Fertility after unilateral cryptorchidism. Paternity, time to conception, pretreatment testicular location and size, hormone and sperm parameters. Horm Res. 2001;55(5):249-53. [Medline].
Mirilas P, Mamoulakis C, De Almeida M. Puberty does not induce serum antisperm surface antibodies in patients with previously operated cryptorchidism. J Urol. Dec 2003;170(6 Pt 1):2432-5. [Medline].
Nane I, Ziylan O, Esen T, Kocak T, Ander H, Tellaloglu S. Primary gonadotropin releasing hormone and adjunctive human chorionic gonadotropin treatment in cryptorchidism: a clinical trial. Urology. Jan 1997;49(1):108-11. [Medline].
Palmer LS, Gill B, Kogan SJ. Endocrine analysis of childhood monorchism. J Urol. Aug 1997;158(2):594-6. [Medline].
Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. May 3 2007;356(18):1835-41. [Medline].
Pohl HG, Joyce GF, Wise M, Cilento BG Jr. Cryptorchidism and hypospadias. J Urol. May 2007;177(5):1646-51. [Medline].
Radmayr C, Oswald J, Schwentner C, Neururer R, Peschel R, Bartsch G. Long-term outcome of laparoscopically managed nonpalpable testes. J Urol. Dec 2003;170(6 Pt 1):2409-11. [Medline].
Thorsson AV, Christiansen P, Ritzen M. Efficacy and safety of hormonal treatment of cryptorchidism: current state of the art. Acta Paediatr. May 2007;96(5):628-30. [Medline].
Toppari J. Physiology and disorders of testicular descent. Endocr Dev. 2003;5:104-9. [Medline].
Wood HM, Elder JS. Cryptorchidism and testicular cancer: separating fact from fiction. J Urol. Feb 2009;181(2):452-61. [Medline].
cryptorchidism, undescended testis, undescended testes, undescended testicles, ectopic testis, ectopic testes, ectopic testicles, retractile testis, retracted testis, retracted testes, retracted testicles, absent testis, absent testes, absent testicles, atrophic testis, atrophic testes, atrophic testicles, hidden testis, hidden testes, hidden testicles, obscure testis, obscure testes, obscure testicles, Fowler Stephens orchidopexy, Fowler-Stephens orchidopexy, testicular maldescent, SRY gene, Hoxa-10 gene, Hoxa-11 gene, intra-abdominal testis, intraabdominal testis, inguinal testis
Marcos Perez-Brayfield, MD, Consulting Staff, HIMA-San Pablo, San Juan, Puerto Rico
Marcos Perez-Brayfield, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, and American Urological Association
Disclosure: Nothing to disclose.
Andrew J Kirsch, MD, FAAP, FACS, Clinical Professor of Urology, Emory University School of Medicine, Children's Healthcare of Atlanta; President, Georgia Urology, PA
Andrew J Kirsch, MD, FAAP, FACS is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, and Society for Fetal Urology
Disclosure: QMED Grant/research funds Investigation, Consulting; COOK Urological Royalty Consulting
Adam G Baseman, MD, Pediatric Urologist, North Texas Pediatric Urology Associates, Urology Clinics of North Texas
Disclosure: Nothing to disclose.
Bartley G Cilento, Jr, MD, Instructor, Department of Surgery, Division of Urology, Children's Hospital of Boston and Harvard Medical School
Bartley G Cilento, Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, and Massachusetts Medical Society
Disclosure: Nothing to disclose.
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner
Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond
Harry P Koo, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, and American Urological Association
Disclosure: Nothing to disclose.
Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.
Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston
Marc Cendron, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, European Society for Paediatric Urology, Johns Hopkins Medical and Surgical Association, New Hampshire Medical Society, Society for Fetal Urology, and Society for Pediatric Urology
Disclosure: Nothing to disclose.
© 1994-
by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)