Cryptorchidism

Updated: Mar 27, 2017
  • Author: Joel M Sumfest, MD; Chief Editor: Edward David Kim, MD, FACS  more...
  • Print
Overview

Practice Essentials

Cryptorchidism is the most common genital problem encountered in pediatrics. Cryptorchidism literally means hidden or obscure testis and generally refers to an undescended or maldescended testis.

Despite more than a century of research, many aspects of cryptorchidism are not well defined and remain controversial. Untreated cryptorchidism clearly has deleterious effects on the testis over time. Understanding the abnormalities of morphogenesis and the molecular and hormonal milieu associated with cryptorchidism is critical to contemporary diagnosis and treatment of this extremely common entity.

Guidelines published by the American Urological Association in 2014 include the following [1] :

  • Referral for cryptorchidism should occur by 6 months of age
  • Imaging for cryptorchidism is not recommended prior to referral
  • Orchiopexy is the most successful therapy to relocate the testis into the scrotum
  • Hormonal therapy is not recommended
  • Successful scrotal repositioning of the testis may reduce but does not prevent the potential long-term issues of infertility and testis cancer
  • Appropriate counseling and follow-up of the patient are essential
Next:

History of the Procedure

Cryptorchidism has been recognized for centuries. It was first described in the medical literature in 1786 by Hunter. The first surgical orchiopexy was attempted in 1820 by Rosenmerkal. However, it was not until 1877 that Annandale performed the first successful orchiopexy. [2]

Previous
Next:

Problem

Normal testicular development begins at conception. The testis-determining factor is now identified as the SRY gene (sex-determining region on Y chromosome). The presence of this gene and an intact downstream pathway generally result in testicular formation.

At 3-5 weeks' gestation, the gonadal ridge or indifferent gonad develops, and, at 6 weeks' gestation, primordial germ cell migration occurs. Soon after, Sertoli cells develop and secrete müllerian-inhibiting substance (MIS), the level of which remains high throughout gestation and causes regression of müllerian ducts. At 9 weeks' gestation, Leydig cells develop and secrete testosterone.

Prenatal ultrasonography shows no testicular descent before 28 weeks' gestation, other than transabdominal movement to the internal inguinal ring. Transinguinal migration, thought to be under hormonal control, occurs at 28-40 weeks' gestation, usually resulting in a scrotal testis by the end of a full term of gestation.

Previous
Next:

Epidemiology

Frequency

Overall, 3% of full-term male newborns have cryptorchidism, decreasing to 1% in male infants aged 6 months to 1 year. The prevalence of cryptorchidism is 30% in premature male neonates. Factors that predispose to cryptorchidism include prematurity, low birth weight, small size for gestational age, twinning, and maternal exposure to estrogen during the first trimester. Seven percent of siblings of boys with undescended testes have cryptorchidism. Spontaneous descent after the first year of life is uncommon.

In the United States, the prevalence of cryptorchidism ranges from 3.7% at birth to 1.1% from age 1 year to adulthood. Internationally, prevalence ranges from 4.3-4.9% at birth to 1-1.5% at age 3 months to 0.8-2.5% at age 9 months. Cryptorchidism is identified in 1.5-4% of fathers and 6.2% of brothers of patients with cryptorchidism. Heritability in first-degree male relatives is estimated to be 0.67.

Previous
Next:

Etiology

The etiology of cryptorchidism is multifactorial. Extensive research and clinical observations have elucidated some of the factors involved, but the exact mechanism of cryptorchidism has proved elusive.

Birth weight is the principal determining factor for undescended testes at birth to age 1 year, independent of the length of gestation.

One study found that almost 23% of index patients with undescended testes had a positive family history of cryptorchidism, as opposed to 7.5% in control families. [3] The familial cluster is 3.6 fold overall, 6.9 if a brother is affected and 4.6 if the father. Mutations in the homeobox gene HOXA10, which plays a pivotal role in regulation of testicular descent, may be involved in select cases. [4]

Transabdominal descent of the testis involves differential growth of vertebrae and pelvis until 23 weeks’ gestation. Afterward, further descent is facilitated by the development of the gubernaculum, processus vaginalis, spermatic vessels, and scrotum. [2] A normal hypothalamic-pituitary-gonadal axis is a prerequisite for testicular descent. [5] Furthermore, testosterone and its conversion to dihydrotestosterone (DHT) are also necessary for continued migration, especially during the inguinoscrotal phase. [6, 7, 8]

Exposure to endocrine-disrupting chemicals may contribute to cryptorchidism, and may account for the increasing incidence rate of cryptorchidism seen in some regions. Synthetic chemicals identified as endocrine disruptors include phthalates, pesticides, brominated flame retardants, diethylstilbestrol, and dioxins. [9] Different studies have found conflicting data regarding the involvement of müllerian-inhibiting substance, prenatal estrogen exposure, and descendin (a specific gubernacular growth factor) in the pathophysiology of cryptorchidism. [10, 11, 12]

Although its exact mechanism of action is unclear, the gubernaculum has significant importance in undescended testes. In patients with cryptorchidism, the gubernaculum is not firmly attached to the scrotum, and the testis is not pulled into the scrotum. [13] Both hormonal and mechanical factors appear to mediate the aid of the gubernaculum and descent of the testis. [14] The genitofemoral nerve may also aid in descent and gubernacular differentiation, which may be mediated by calcitonin gene-related peptide. [15, 16]

Intra-abdominal pressure also appears to play a role in testicular descent. Conditions associated with decreased pressure include prune belly syndrome, cloacal exstrophy, omphalocele, and gastroschisis, among other various syndromes. Each is associated with an increased risk of undescended testes. [17, 18] The effect of decreased intra-abdominal pressure is most significant during transinguinal migration to the scrotum, probably in conjunction with androgens and a patent processus vaginalis. [19, 20]

Epididymal abnormalities often accompany undescended testes, but the causal relationship has not been established. In 1992, Elder concluded that most epididymal abnormalities probably do not contribute to maldescent. [21]

Previous
Next:

Presentation

In cryptorchidism, the most useful determination is whether the testes are palpable upon physical examination. Although this is seemingly self-explanatory, accurately determining the exact location of the testis is occasionally difficult. Body habitus, testicular position, and compliance of the child all are factors during the physical examination. Nonpalpable testes may be intra-abdominal or absent. Palpable testes may be undescended, ectopic, or retractile.

Approximately 80% of undescended testes are palpable and 20% are nonpalpable. [22] Most intra-abdominal testes are found within a few centimeters of the internal ring. Absent or vanishing testes are thought to be due to an intrauterine or perinatal vascular event, most likely during late gestation since most of these testicular nubbins are found below the internal inguinal ring. Only 20-40% of nonpalpable testes are absent upon surgical exploration.

Ectopic testes exit the external inguinal ring and are then misdirected along the normal course of the testis. Retractile testes may be palpated anywhere along the natural course of the testis, although most are inguinal. Although not truly undescended, these testes may be suprascrotal secondary to an active cremasteric reflex. This reflex is usually weak in infants and most active in boys aged 5 years. These testes can be manipulated into the scrotum, where they remain without tension. This condition is considered a variant of normal; however, the risk of ascent may approach 50%. [23, 24] Ascent probably represents an undescended testis that was almost in normal position. The distinction can be difficult, even to an experienced pediatric urologist. Therefore, children with retractile testes should be monitored regularly, at least until puberty.

Several authors have examined the anatomic position of cryptorchid testes. Cendron and Duckett documented the position upon physical examination and compared this with position at the time of surgery. [25] On physical examination, testicular positions were as follows:

  • Nonpalpable - 32.8%
  • Above the tubercle - 11.8%
  • At the tubercle - 34.7%
  • Upper scrotum - 15.3%
  • Suspected ectopia - 5.4%

At surgery, testicular findings were as follows:

  • Intra-abdominal - 9%
  • Peeping testis - 20%
  • Tubercle - 42%
  • Upper scrotum - 8%
  • Superficial inguinal pouch (SIP)/ectopic - 12%
  • Absent or atrophic - 9%

Associated anomalies and conditions may include the following:

  • Patent processus vaginalis
  • Abnormal epididymis
  • Mental retardation
  • Abdominal wall defects (eg, gastroschisis, omphalocele, prune belly syndrome)

In general, ductal abnormalities, hernias (patent processus vaginalis), and testicular maldevelopment are more common in patients with abdominal testes. Overall, 32-79% of undescended testes are associated with some type of epididymal abnormality. However, abnormalities that inhibit sperm transport (eg, complete caput separation, atresia, agenesis) have been reported in only 8% of patients with cryptorchidism. In addition, when the processus vaginalis is patent, the epididymis is more likely to be abnormal.

History

The medical history should cover the following questions:

  • Has the testis ever been palpable in the scrotum?
  • Was the patient born prematurely?
  • Has the patient undergone prior inguinal surgery?
  • Is or was the patient's mother on a vegetarian diet? Was the patient fed soy formula during infancy?
  • What was the patient's birth weight?

The prenatal history should cover the following questions:

  • Did the patient's parents used an assisted reproductive technique?
  • Did his mother receive hormonal treatment?
  • Were there multiple gestations?

The family history should cover the following topics:

Physical examination

Considerations and questions in the physical examination include the following:

  • The patient should be warm and relaxed for the examination.
  • Observation should precede the examination.
  • The patient should be placed in the frog-leg position for examination;  this is especially useful in obese children with fatty infiltration of the scrotum and when retractility is a concern.
  • Milk down, palpating from iliac crest to scrotum (soap or lubrication on fingertips may help).
  • What are the features of the scrotum and its contents (eg, hypoplasticity, bifidity, rugae, transposition, pigmentation)?
  • Is the contralateral testicle hypertrophic?
  • Is the undescended testis located in an unusual position, such as in an ectopic site (ie, superficial inguinal pouch or transverse scrotal, femoral, prepenile, perineal, or contralateral hemiscrotum)?
  • Note the presence of any hypospadias or chordee. Does the patient have a normal stretched penile length?
  • If the findings are equivocal, perform serial examinations.
Previous
Next:

Indications

Indications for hormonal or surgical correction of cryptorchidism include the following:

To increase the likelihood of fertility

  • Impairment of germ cell maturation is a well-recognized consequence of cryptorchidism.
  • Early reposition of the testis into the scrotum has been a mainstay of treatment to reduce the risk of infertility; however, recent studies have cast some doubt on this. [26, 27, 28]
  • Abnormal germ cell maturation correlates with abnormal spermiogram findings in adulthood.
  • Biopsy findings in children with unilateral undescended testis demonstrated reduced total germ cell counts due to failure of the two critical prepubertal steps involved in maturation and proliferation of germ cells: (1) transformation of the fetal stem cell pool (gonocytes) into adult stem cell pool (type Ad spermatogonia) at age 2-3 months and (2) transformation of type Ad spermatogonia into primary spermatocytes at age 4-5 years. [29]
  • Hadziselimovic and Herzog (2001) found a negative association between age and germ cell count by age 6 months in children undergoing orchiopexy. [30]
  • Lee (1995) postulated that paternity itself is a better index than sperm count. Compared with controls, paternity was significantly compromised in men with bilateral, but not unilateral, undescended testes. [31] This finding was supported by two subsequent studies in which up to 90% men with unilateral undescended testis had fathered children, as opposed to only 33-65% with bilateral undescended testes. [32, 33]

Facilitation of testicular self-examination for testicular cancer

  • Males with undescended testis are 40 times as likely to develop testicular cancer as males without undescended testis. [34] Ten percent of testicular cancer cases involve patients with undescended testis. [35, 36]
  • Prepubertal orchiopexy reduces this risk. [37, 38]
  • The ability for patients to perform testicular self-examination with the testes in the scrotum is a clear benefit of surgery.
  • The location of the undescended testis affects the relative risk of testicular cancer. Up to 50% of malignant testicular tumors associated with cryptorchidism involve intra-abdominal testes. [39, 40]
  • Seminoma is the most common malignant tumor type associated with cryptorchidism. [41]
  • Correction of associated hernia: A patent processus vaginalis is found in more than 90% of patients with undescended testis. [24, 21]

Additional indications

  • Prevention of testicular torsion
  • Prevention of injury against pubic bone
  • Psychological effects of an empty scrotum

Treatment recommendations for postpubertal men

Men younger than 32 years with a unilateral undescended testis and normal contralateral testis should undergo orchiectomy. Men older than 32 years with a unilateral undescended testis should receive close observation and physical examination. If examination is difficult, orchiopexy or orchiectomy should be considered; this recommendation is based on the relative risk of testicular cancer along with the risks associated with anesthesia. [42, 43]

Previous
Next:

Relevant Anatomy

The undescended testis, when palpable, is usually found in the superficial inguinal pouch or in the inguinal canal under the external oblique aponeurosis. Care must be taken during dissection to avoid the ilioinguinal nerve near the spermatic cord.

After dissection of the cremasteric fibers off the cord, the patent processus vaginalis, or hernia sac, may be located on the anteromedial surface of the cord. The intra-abdominal view of the anatomy is best seen in the image below. The vas deferens can be seen exiting the internal inguinal ring and crossing the median umbilical ligament. The testicular vessels (ie, spermatic artery) can be seen entering the internal ring from its origin off the aorta near the renal hilum.

Laparoscopic view of normal vas deferens and testi Laparoscopic view of normal vas deferens and testicular vessels entering a closed internal inguinal ring.
Previous