Pediatric Cryptorchidism Surgery 

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).

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 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.

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

Cryptorchidism has no reported racial predilection.

Sex

Cryptorchidism affects only males.

Age

See Frequency above.