AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

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. Hunter first described 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.

Pathophysiology

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. 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 the 9 weeks' gestation, Leydig cells start producing testosterone, which promotes development of the wolffian duct into portions of the male genital tract. Because of the differential growth of the fetus, the testicles move into the pelvis, close to the internal ring.

The testis remains in an 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 the 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 pole of the testis 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 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 maldescended. 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 a 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 knockout experiments in 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 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).

Frequency

United States

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 testis 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.

Mortality/Morbidity

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.

Race

No race predilection is reported.

Sex

This condition affects only males.

Age

See Frequency above.

CLINICAL

Section 3 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

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

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.

DIFFERENTIALS

Section 4 of 10  

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Other Problems to be Considered

Retractile testis
Anorchia
Intra-abdominal testis
Vanishing testis syndrome or nubbin testicle resulting from perinatal torsion

WORKUP

Section 5 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• Routine laboratory workup is not indicated with unilateral cryptorchidism.
• Patients with bilateral nonpalpable testis and those with unilateral or bilateral undescended testis associated with hypospadias should undergo evaluation to rule out an intersex condition.
• • The evaluation should include chromosomal analysis and measurement of 17-hydroxylase progesterone, testosterone, LH, and follicular-stimulating hormone (FSH).
  • For bilateral nonpalpable testis, abdominal-pelvic ultrasonography is advisable, mainly to determine if any Müllerian structures, such as a uterus, are present.
• Anorchia can be confirmed with hormonal stimulation (with hCG) with baseline and poststimulation measurement of LH, FSH, and testosterone hormone levels.
• • Many hCG stimulation protocols are described. The authors favor a single injection of hCG 2940 IU per body surface area, with hormonal levels assessed at 72 hours.
  • Anorchia is found in patients with elevated baseline LH and FSH levels and low testosterone levels without an increase in testosterone after stimulation.
• Another marker of testicular function is MIS. MIS levels of more than 5 ng/mL suggest the presence of testicular tissue and are an indication for exploration. However, this study is rarely used and may not have any application in older children.

Imaging Studies

• Imaging studies have little or no role in the diagnosis of cryptorchidism.
• Ultrasonography, CT scanning, MRI, and angiography have been used to detect undescended testes. However, these studies have unacceptable false-positive and false-negative rates. CT scanning exposes to high levels of radiation, and MRI requires sedation or anesthesia; both are costly.
• Diagnostic laparoscopy is the most effective and efficient modality to identify an intra-abdominal testis.

Procedures

• Diagnostic laparoscopy is the most reliable technique for localizing the nonpalpable testis.
• Laparoscopy is performed in conjunction with definite therapy (laparoscopic orchiopexy or open orchiopexy).
• Laparoscopic findings can be helpful in determining the need for inguinal exploration, for deciding between 1-stage and 2-stage repair, and for assessing viability of the gonad.
• Findings from laparoscopy can also help clarify the anatomy in complex DSD (intersex) cases.

Histologic Findings

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.

Staging

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 patients.

TREATMENT

Section 6 of 10  

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Medical Care

General issues

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 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 candidate 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%. Some long-term studies have shown rates of success lower than this.

Similar 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 success 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 in only 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.

Surgical Care

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

• Look for the testis after incising the Scarpa fascia to avoid injuring a testis found outside of the external inguinal ring (ectopic testis in the superficial inguinal pouch) 
• Divide all attachments, including the gubernaculum, the cremasteric fibers, and the lateral spermatic fascia.
• Identify the patent processus vaginalis in the anteromedial surface of the cord, and perform a high ligation; be careful not to trap the vas or vessels.
• Place the testis in a subdartos pouch.

Surgical pearls for the nonpalpable testis

• Preference should be to carry out diagnostic laparoscopy versus inguinal exploration.
• Blind-ending vas and vessels confirm the diagnosis of a vanishing testis and do not warrant further therapy. Consideration should be given to exploring the contralateral scrotum and placing some anchoring stitches to prevent possible testis torsion on the other side.
• Vessels entering the internal inguinal ring require further inguinal or scrotal exploration to identify the undescended testis or testicular nubbin.
• In patients with findings of a vanishing testis or a testicular nubbin, fixation of the contralateral testis fixation should be considered but is controversial.
• A small intra-abdominal testis or an abnormal testis requires orchiectomy.

Maneuvers to increase length of an undescended testis

• The Prentiss maneuver involves rerouting the cord under the epigastric vessels or the division of epigastric vessels.
• The internal inguinal ring can be opened to perform more complete retroperitoneal mobilization.
• The Fowler-Stephens principle involves dividing the testicular vessels to allow the blood supply to the vas deferens to keep the undescended testis viable. The testicular vessels should be divided away from the testis.
• Testicular autotransplantation can be performed by transecting the testicular vessels and by performing a microvascular anastomosis to the inferior epigastric vessels

Success rates

• Orchiopexy for palpable testis (scrotal, inguinal and suprainguinal) - 80-90%
• Orchiopexy for nonpalpable testis
• • Inguinal approach - 60-88%
  • Suprainguinal approach - Up to 95%
  • 1-stage Fowler-Stephens procedure - 67-96%
  • 2-stage Fowler-Stephens procedure - 77-95%
  • Microvascular transplantation - 83-96%
  • Laparoscopic orchiopexy - 80-95%
  • Laparoscopic Fowler-Stephens procedure - Up to 96%

Consultations

Patients with bilateral anorchia or an intersex condition may benefit from a consultation with a pediatric endocrinologist.

Diet

No changes in diet are required after treatment.

Activity

After surgery, patients should be advised to limit their activities for a week and refrain from straddling.

MEDICATION

Section 7 of 10  

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Drug Category: Hormonal therapy

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.

FOLLOW-UP

Section 8 of 10  

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• Follow-up
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Further Inpatient Care

Most surgeries are performed on an ambulatory basis.

Further Outpatient Care

• The surgical procedure is done on an outpatient basis.
• • Minimal pain medication is needed in the first 24-48 hours.
  • The surgical incision site should be kept dry for 48 hours.
  • If surgical buttons were used, consider removing then 7-10 days after the operation.
  • Children should avoid playing on straddle toys and participating in physical education for 1-2 weeks after surgery.
• Office visits should be scheduled postoperatively and at 1 year to evaluate the location, size, and viability of the testis.
• Discussions of fertility issues and the need for self-examination to detect of cancer should be revisited.

In/Out Patient Meds

Pain control medications should be prescribed as needed.

Deterrence/Prevention

Early orchiopexy performed before age 2 years may prevent possible damage to the testis and may improve spermatogenetic viability.

Complications

• Complications related to the surgical correction of the maldescended testis include the following:
• • Testicular atrophy (5%)
  • Injury to vas deferens (1-2%)
  • Reascent of the testicle or abnormal anatomic position (<10%)
  • Epididymoorchitis
  • Hydrocele

Prognosis

• Testicular cancer
• • In patients with cryptorchidism, the risk of testicular cancer is 3-5%, a 4-7–fold increased risk compared with the 0.3-0.7% risk in the healthy population.
  • The most common tumor in an undescended testis is a seminoma, whereas the most common tumor after successful orchiopexy is nonseminomatous germ-cell tumor. Approximately 20% of these tumors occur in a contralateral descended testis.
  • Carcinoma in situ occurs in approximately 0.4% of patients undergoing orchiopexy.
  • Orchiopexy is not protective against subsequent testis cancer and does place the testis in a favorable position for routine self-examination.
  • The patient and family must be educated about the risk of future testicular cancer.
  • Self-examination in the early recognition of testicular cancer.
• Infertility
• • Approximately 6% of infertile men have a history of orchiopexy or untreated cryptorchidism.
  • The rate of infertility is greater in patients with bilateral cryptorchidism than in those with unilateral cryptorchidism or in the general male population.
  • The paternity rate for patients with bilateral cryptorchidism is around 60% versus 90% in patients with unilateral cryptorchidism. The rate in those with unilateral cryptorchidism is slightly less that the 94% in the general population.
  • The location of the undescended testis may play a role in fertility potential. Worsening testicular biopsy findings are correlated with high locations (eg, intra-abdominal testis).
  • Normal spermatograms are found in 20% of patients with bilateral undescended testis compared with 75% of patients with unilateral cryptorchidism.
  • The decision to perform orchiopexy in patients younger than 24 months might be made because testicular biopsy shows that the rate of germ-cell aplasia substantially increases after age 2 years. Long-term studies are needed to determine the true effect of early orchiopexy on fertility.

Patient Education

• One evaluation of the referral practices of local pediatricians showed that physicians tended to refer patients for treatment at a mean age of around 4 years. This finding shows the importance of educating primary physicians about the timing of surgery (before age 1 y) and the benefits of early surgical intervention.
• The patient and his family should be informed about the risks of infertility and malignancy. Self-examination should be discussed as very important for the early diagnosis and successful treatment of testicular cancer.

MULTIMEDIA

Section 9 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Hypoplastic right hemiscrotum in a patient with an undescended right testis.
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Media file 2:  Ectopic testis.
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Media file 3:  Diagnostic laparoscopy of a crossed ectopic testis.
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Media type:  Photo

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
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• Follow-up
• Multimedia
• References

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Article Last Updated: Nov 1, 2007