Cryptorchidism

Article Author:
Stephen Leslie
Article Editor:
Carlos Villanueva
Updated:
10/23/2018 9:26:48 AM
PubMed Link:
Cryptorchidism

Introduction

Cryptorchidism is the absence of at least one testicle from the scrotum. It is the most common birth defect involving the male genitalia. About 3% of full-term and 30% of premature male infants are born with one or both testicles undescended. Approximately 80% of cryptorchid testes descend by the third month of life. This makes the true incidence around 1%.

Cryptorchidism may occur on one or both sides, but more commonly affects the right testicle.

The testicle may be anywhere along the "path of descent," such as:

  • Located high in the retroperitoneal abdomen to the inguinal ring
  • In the inguinal canal
  • Ectopic from the path of descent
  • Hypoplastic
  • Dysgenetic
  • Missing or Absent
  • Unilateral (two-thirds)

The undescended testicle can usually be palpated in the inguinal canal. In a minority of patients, the missing testicle may be located in the abdomen or be nonexistent.

Undescended testicles are associated with decreased fertility (bilateral cases), increased testicular germ cell tumors (overall risk under 1%), testicular torsion, inguinal hernias, and psychological problems.

Without surgical correction, an undescended testicle may descend during the first three months of life. To reduce risks, undescended testes may be brought into the scrotum with an orchiopexy.

Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up testicular dysgenesis syndrome (TDS).  This syndrome is thought to be due to harmful environmental factors that disrupt embryonal programming and gonadal development during fetal life.

Etiology

A normal hypothalamic-pituitary-gonadal axis is a prerequisite for normal testicular descent.

Birth weight appears to be the main risk factor for undescended testes, followed by family history.

Absence of an appendix testis has been linked to abdominal testes and cryptorchid testes especially if located proximal to the external ring.  The exact role of the appendix testis in testicular descent is unclear.

In full-term infants, the cause of cryptorchidism often cannot be determined, making this a common but sporadic, idiopathic birth defect. It is thought that genetics, combined with maternal and environmental factors, may disrupt hormones and physical changes that influence testicular development and descent. 

Possible underlying risk factors include:

  • Premature infants born before the descent of the testicles
  • Small for gestational age infants
  • Smaller placental weight
  • Chemicals endocrine disruptors may interfere with normal fetal hormone balance
  • Maternal obesity
  • Maternal diabetes
  • Maternal exposure to DES
  • Pesticides
  • Alcohol consumption during pregnancy (5 or more drinks per week, 3x increase)
  • Cigarette smoking
  • Family history
  • Cosmetics use
  • Exposure to phthalate (DEHP)
  • Ibuprofen
  • Preeclampsia (The more severe the preeclampsia, the greater the risk of cryptorchidism)
  • Congenital malformation syndromes - Down syndrome, Prader–Willi syndrome, and Noonan syndrome
  • Persistent Mullerian Duct Syndrome
  • In vitro fertilization

Epidemiology

Three percent of full-term, newborn infants have cryptorchidism. This decreases to 1% in infants aged six months to 1 year.

  • The prevalence of cryptorchidism is 30% in premature male neonates.
  • Seven percent of siblings of boys with undescended testes have cryptorchidism.
  • In the United States, cryptorchidism ranges from about 3% at birth to 1% from 1 year to adulthood.
  • Internationally, prevalence ranges from 4% to 5% at birth to about 1% to 1.5% at age three months and 1% to 2.5% at nine months.
  • Cryptorchidism occurs in approximately 1.5% to 4% of fathers and 6% of brothers of individuals with cryptorchidism.
  • Heritability in first-degree male relatives is estimated to be approximately 0.5% to 1%.
  • There may also be an association between cryptorchidism and autism.

Pathophysiology

One contributing mechanism for the reduced function of cryptorchid testes is temperature. It is also likely that transient hormone deficiencies may lead to a lack of testicular descent and impair the development of spermatogenic tissue.

History and Physical

Signs and symptoms of undescended testicles include the following:

Infertility

Men with undescended testes may have reduced fertility, even after orchiopexy.

  • The infertility rate for unilateral cases is not believed to be that different from the general population.
  • The fertility reduction after orchiopexy for bilateral cryptorchidism is about 38%. This is the basis for the universal recommendation for early surgery which shows degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in patients with untreated undescended testes.

Psychological Consequences

Boys with undescended testicles do not tend to be effeminate, gender-disordered, or pre-homosexual. A disturbed self-image may occur when the family dynamics are destructive toward male self-esteem. When cryptorchism is surgically corrected, a healthy masculinity generally occurs. 

Cancer

Overall, the risk of testicular cancer if orchiopexy is done before puberty is around 2 to 3 times that of the general population. It is 5 to 6 times higher when orchiopexy is done after puberty. The risk of cancer does not seem to be different when orchiopexy is done early in infancy compared to in late childhood. 

  • The most common type of testicular cancer in untreated undescended testes is seminoma. 
  • The peak age range for this tumor is 15 to 45 years.
  • In contrast, after orchiopexy, seminomas represent only 30% of testicular tumors in previously undescended testes.
  • It is treatable if caught early, so boys who had an orchiopexy as infants should be taught testicular self-examination.

Evaluation

A common diagnostic challenge is distinguishing a retractile testicle from a testicle that is not spontaneously descending into the scrotum. Retractile testes are more common than undescended testes and do not require surgical correction. In normal males, as the cremaster muscle contracts, the testicles retract into the upper scrotum and inguinal canal. This reflex is more active in infants. 

A retractile testicle high in the scrotum is difficult to distinguish from one positioned in the lower inguinal canal. Maneuvers used to assist identification include the cross-legged position, soaping the clinician's fingers, and examining the patient in a warm bath. 

The American Urological Association (AUA) Guidelines define a retractile testis as "...one that is initially extrascrotal on examination or moves easily out of scrotal position, (often associated with a vigorous cremasteric reflex), but that can be manually replaced in stable, dependent scrotal position and remain there without tension at least temporarily."

Also from the AUA Guidelines: “In the hands of an experienced provider, more than 70% of cryptorchid testes are palpable by physical examination and need no imaging. In the remaining 30% of cases with a nonpalpable testis, the challenge is to confirm absence or presence of the testis and to identify the location of the viable nonpalpable testis". 

Ultrasound is non-contributory in routine use, with sensitivity and specificity to localize nonpalpable testes at 45% and 78%, respectively. The cost and ionizing radiation exposure associated with CT scanning preclude its use. MRI with or without angiography has been more widely used with greater sensitivity and specificity but is discouraged by its cost, low availability, and the need for anesthesia. At this time, there is no radiological test that can conclude with 100% accuracy that a testis is absent "...regardless of preoperative radiological findings, these studies rarely assist in the decision making and may at times yield misleading information (such as absence when actually present or vice versa).”

A karyotype can confirm or exclude dysgenetic primary hypogonadism. Hormone levels such as gonadotropins and Anti-Mullerian Hormone (AMH) may confirm hormonally functional testicles worth salvation, as can stimulation with human chorionic gonadotropin to elicit a rise in the testosterone level. In some cases, further testing is crucial and has a high likelihood of detecting intersex conditions.

Treatment / Management

Medical Treatment

The AUA Guidelines state: "Providers should not use hormonal therapy to induce testicular descent as evidence shows low response rates and lack of evidence for long-term efficacy."

The American Pediatric Association Guidelines do recommend the use of hormones for cases of undescended testis associated with Prader-Willi Syndrome. A therapeutic trial of human chorionic gonadotropin (hCG) is indicated for treatment of undescended testes before surgery, because avoidance of general anesthesia is desirable for infants with low muscle tone and potential for underlying respiratory compromise.

  • The most commonly used hormone is human chorionic gonadotropin (HCG). A series of HCG injections is given, and the status of the undescended testicle is reassessed. The success rate is reported as 5% to 50%. 
  • Hormone treatment also will confirm Leydig cell responsiveness and induce additional growth of a small penis due to a rise in testosterone levels. 

The cost of hormone treatment is less than surgery, and the chance of complications are minimal. However, a recent meta-analysis of seven randomized clinical trials concluded that hormonal therapy was no more effective than placebo.

Surgery

Surgery is recommended for congenital undescended testes between the ages of 6 and 18 months (AUA Guidelines). For premature babies, corrected age is used to determine surgery timing. Fertility is improved if the orchidopexy is performed early.  Patients with bilateral undescended testes who receive orchidopexies as adults are almost always infertile and azoospermic  but there are now a few anecdotal reports of pregnancies achieved through assisted reproduction in this group.

For acquired (testis documented normal before diagnosis) and entrapped (after hernia repair) undescended testes, surgery is recommended soon after diagnosis. 

For retractile testes, a yearly physical examination is recommended because of the 2% to 50% reported risk of a retractile testis becoming an acquired undescended testis. 

Technique of Orchiopexy

For palpable undescended testes, an inguinal or scrotal orchiopexy is recommended. 

  1. An incision is made in the high scrotum, median scrotal raphe, high edge of the scrotum, or groin. Many different type of retractors can be used depending of the size of the incision. Inguinal incisions can be as small as 1 cm. Scrotal incisions can be larger as they tend to heal concealed specially when in the median raphe. 
  2. The testis can be approached first or the cord first; for scrotal cases, the testis is found first. For an inguinal approach, the testis can be approached first or the external oblique fascia opened proximal to the external ring and the cord approached first. 
  3. When approaching the testis first, all the cremasteric muscles are divided as well as everything not going into the external ring.
  4. The more difficult part of the case is separating the hernia sac from the vas and testicular vessels. This can be approached anteriorly or posteriorly. The posterior approach is much easier to teach and learn.
  5. How the testis is positioned and secured in the scrotum varies. Most would agree that a sub-dartos pouch is desirable. Some surgeons do not suture the testis in place, others use absorbable sutures, others non-absorbable, and others just close the passage into the groin. 

For nonpalpable testes under anesthesia, exploratory laparoscopy is recommended. If a testis is found during exploratory laparoscopy, the options are: 

  1. Laparoscopic orchiopexy preserving the vessels: the testis is dissected off a triangular pedicle containing the gonadal vessels and the vas.
  2. Laparoscopic one stage Fowler Stevens (FS) orchiopexy: gonadal vessels are divided and the testis is dissected off a pedicle of the vas and brought down in one stage.
  3. Laparoscopic two stage Fowler Stevens: vessels are divided with clips but dissection of the testis is postponed for 6 months. 

If no testis is found during exploratory laparoscopy, one has to determine the presence of either blind ending vessels or a testicular nubbin to completely rule out a missing testis. The vas can be dissociated from the testis and thus is not always a good guide to find the gonad.

If the internal ring is closed but vessels are going into it, a scrotal exploration usually will find a testicular nubbin. Look for a small structure with a brown spot.

If vessels are going into an open inguinal ring, one can usually push the testis into the abdomen but if not, an inguinal or scrotal exploration would be warranted. 

Orchiopexy is associated with two major complications: atrophy and testicular ascent. For palpable testes, these occur less than 5% of the time. For laparoscopic orchiopexies, the rate is also around 5%. For Fowler-Stephens orchiopexies (dividing the vessels) in one or two stages, the testicular atrophy rate is around 20% to 30% (worse for one stage procedures).

Pearls and Other Issues

There may be a slight decrease in penis size in cryptorchid patients. 

It has been suggested that adjuvant LHRH treatment be offered to cryptorchid patients with a high risk for infertility due to their insufficient gonadotropin stimulation at the time of surgery. Sperm cryopreservation is another prophylactic option in case of resultant infertility in spite of the adjuvant LHRH.

Enhancing Healthcare Team Outcomes

An undescended testicle is the most prevalent male congenital defect affecting the male genitalia. Most (about 80%) will descend by the third month of life.  It is more frequently found in premature infants.  Risks for infertility and cancer are increased compared to the general population but still relatively small. Optimal timing of surgical orchidopexy (<18 months of age) is not always followed. Close collaboration and communication between pediatricians and urology will result in better outcomes and avoid unnecessary procedures while increasing the incidence of timely surgery when indicated.