Cryptorchidism

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Continuing Education Activity

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. Undescended testes may be brought into the scrotum with an orchiopexy to reduce risks. 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. This activity reviews the workup of cryptorchidism and describes the role of health professionals working together to manage this condition.

Objectives:

  • Review the risk factors for cryptorchidism.
  • Describe the presentation of cryptorchidism.
  • Summarize the management strategies for cryptorchidism.
  • Outline the workup of cryptorchidism and describe the role of health professionals working together to manage this condition.

Introduction

Cryptorchidism is the absence of at least one testicle from the scrotum. It is the most common congenital defect involving male genitalia. About 3% of full-term and 30% of premature male infants are born with one or both testicles undescended. The testes normally descend by month 7 of gestation. Approximately 80% of cryptorchid testes descend by the third month of life after birth. This makes the true incidence around 1%.[1] If the testis has not descended by six months of age, it is unlikely to do so spontaneously, and surgical correction should be considered.[2]

Cryptorchidism may occur on one or both sides but more commonly affects the right testicle. Bilateral cryptorchidism is present in about 10% of all undescended testicle patients.

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

  • High in the retroperitoneal abdomen close to the inguinal ring
  • In the inguinal canal
  • Ectopic from the path of descent
  • Hypoplastic
  • Dysgenetic
  • Missing or Absent
  • Unilateral (two-thirds)[3]

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. About 20% to 30% of undescended testes are non-palpable. 

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

From 10% to 30% of patients with a unilateral undescended testis will develop infertility. This increases to 35% to 65% or more for bilateral disease. If bilateral cryptorchid testes are left untreated, the infertility rate increases to over 90%.

Without surgical correction, an undescended testicle will likely descend during the first three months of life. If it remains undescended, to reduce risks and minimize infertility, the testis should be brought into the scrotum with an orchiopexy starting at age six months.

Cryptorchidism is associated with male infertility due to poor semen quality in adults. It impairs Sertoli cell function and possibly Leydig cell function as well.[4] 

Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up testicular dysgenesis syndrome. 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.

The absence of an appendix testis has been linked to abdominal 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 congenital 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[1][2]

Epidemiology

Three percent of full-term newborn infants have cryptorchidism. This decreases to 1% in infants aged six months to one year.[1][2]

  • 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 one 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.[3]

History and Physical

The obvious finding in a patient with a cryptorchid testis is the lack of a palpable scrotal testicle. This is usually accompanied by an inguinal hernia and a decreased degree of scrotal rugae or ridges. A careful examination should be made of the entire inguinal and pelvic area as well as the contralateral testicle. Normal rugae and a testicle sometimes noted in the scrotum is a retractile testicle that does not require further treatment.

Signs and symptoms of undescended testicles include the following:

Infertility

There are multiple reasons for reduced fertility in men with cryptorchidism. One would be hyperthermia as the intrascrotal temperature is several degrees cooler than ectopic positions which would result in impaired spermatogenesis. Various anatomical abnormalities are associated with undescended testis such as testis-epididymal disjunction. There may be an inadvertent injury to the vas, epididymis, or testis during orchiopexy. There is a higher incidence of anti-sperm antibodies in infertile patients with a history of cryptorchidism.[5][6] Whatever chemical exposure or other etiology led to the abnormal descent of the testis is likely to have affected both testicles and not just the cryptorchid testis even though a specific causative defect or disorder may not be determinable. 

Men with undescended testes tend to have reduced fertility, even after orchiopexy.[7]

  • About 10% to 30% of unilateral cryptorchid testicle patients will develop infertility.
  • Azoospermia is found in 13% of unilateral undescended testicle patients.[5]
  • Azoospermia increases to about 90% in bilateral cryptorchid patients who are left untreated.[5]
  • The reduction in fertility after orchiopexy for bilateral cryptorchidism is at least about 38%.
  • This is the basis for the universal recommendation for early surgery due to 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 are not more likely to be gender-disordered, effeminate, or pre-homosexual. When the family dynamics are destructive to male self-esteem, disturbed self-image may occur. When cryptorchism is surgically corrected, healthy masculinity generally occurs. 

Cancer

Overall, the risk of testicular cancer if orchiopexy is done before puberty is about three 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 later in childhood.[7]

  • 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.
  • Testicular cancer is quite treatable if caught early, so boys who had an orchiopexy as infants should be taught testicular self-examination to assist with early cancer detection.
  • Self-examination is particularly important for all males with a history of undescended testes starting right after puberty.

Evaluation

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 the absence or presence of the testis and to identify the location of the viable nonpalpable testis."[8] 

Ultrasound is non-contributory in routine use, with sensitivity and specificity to localize nonpalpable testes reported at 45% and 78%, respectively.[9] The data also shows that in boys with a nonpalpable testicle and a negative ultrasound, 49% will ultimately be shown to have an intraabdominal testis.[9]

The cost and ionizing radiation exposure associated with CT scanning preclude its use. MRI with or without angiography has been more widely used with somewhat greater sensitivity and specificity but is discouraged due to its cost, low availability, and the need for anesthesia.[10] At this time, there is no radiological test that can conclude, with 100% accuracy and reliability, 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)."[11]

A karyotype can confirm or exclude dysgenetic primary hypogonadism. Hormone levels such as gonadotropins and Mullerian inhibitory substance 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 is highly likely to detect intersex conditions.[7]

Bilateral Cryptorchidism

Bilateral cryptorchidism with palpable testes can undergo surgery. There is some controversy regarding the timing of surgery. Some experts suggest two separate procedures to allow for the complete healing of one testicle before fixing the contralateral side. While this ensures that at least one testicle survives, it requires subjecting a young child to two separate procedures and anesthesia. For these reasons, many specialists prefer to repair both sides in a single surgery based on the overall low complication rate of about 1%.[12] Infertility may be present in 35% to 75% of men who originally presented with bilateral cryptorchidism as children.

Patients with bilateral impalpable testes, which may occur in 20% to 30% of all cryptorchid boys, require additional workup for a possible disorder of sexual development.[13] No circumcision should be done until the evaluation is completed. Some genetic females with severe congenital adrenal hyperplasia can be initially misidentified as males with bilateral cryptorchidism. The initial step should be to evaluate the patient for possible congenital adrenal hyperplasia. This includes measuring electrolytes (for hyponatremia and hyperkalemia), karyotype analysis, and hormonal profiling (androstenedione, 17-hydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone).[8]

If congenital adrenal hyperplasia has been ruled out, the next step is to determine if there is testicular tissue present. The presence of Mullerian inhibiting substance, produced by the testicular Sertoli cells, would indicate that there is testicular tissue somewhere, possibly intraabdominal. FSH can be used to stimulate inhibin B and Mullerian inhibiting substance, while hCG will stimulate Leydig cells to manufacture testosterone.[14] 

Patients with a male karyotype (46 XY), bilateral nonpalpable testes, elevated serum FSH along with no detectable serum Mullerian inhibiting substance and inhibin B can be reasonably diagnosed as having no testicular tissue (anorchia).[14] HCG stimulation testing has been done in the past, but the positive predictive value of an undetectable Mullerian inhibiting substance at 92% is far better.[15] If testicular tissue is deemed present, an exploratory laparoscopy can be done to determine the testicular location and optimal surgical approach.

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."[8]

The American Pediatric Association Guidelines recommend using hormones for cases of undescended testis associated with Prader-Willi Syndrome. They argue that a therapeutic trial of human chorionic gonadotropin (HCG) is indicated for the treatment of undescended testes before surgery because avoidance of general anesthesia is desirable for infants with low muscle tone and at high risk for underlying respiratory compromise.

  • The most commonly used hormone is human chorionic gonadotropin (HCG). A series of HCG injections are 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 is minimal. However, a recent meta-analysis of seven randomized clinical trials concluded that hormonal therapy was no more effective than a placebo.[16]

Surgery

Surgery is recommended for congenital undescended testes between the ages of 6 and 18 months (AUA Guidelines).[8] Many experts recommend surgery early, at around six months, to optimize testicular growth and fertility. For premature babies, corrected age is used to determine optimal surgical timing. The longer the cryptorchid testis remains untreated, the greater the germ cell loss and the decrease of fertility which is why early orchidopexy is the usual, standard remedy.[4] 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.[17]

For acquired (testis documented normal before diagnosis) and entrapped (after hernia repair) undescended testes, surgery is recommended shortly 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.[17]

  1. An incision is made in the high scrotum, median scrotal raphe, high edge of the scrotum, or groin. Many different types of retractors can be used depending on the incision size. Inguinal incisions can be as small as 1 cm. Scrotal incisions can be larger as they tend to heal concealed, especially 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 is 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, while others use either absorbable or non-absorbable sutures. Some will 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:[17]

  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: the 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 orchiopexy: the vessels are divided with clips, but dissection of the testis is postponed for six months to allow for optimal development of collaterals.
  4. Laparoscopic two-stage traction-orchidopexy (Shehata technique): the intrabdominal testis is fixed to a point one inch (2 cm) medial and superior to the contralateral anterior superior iliac spine, which provides traction. The testis is left there for three months, after which a laparoscopy-assisted ipsilateral subdartos orchidopexy is performed. This technique is an alternative to the two-stage Fowler Stevens orchidopexy. Its main advantage is that it allows an intraabdominal testis to be relocated into the scrotum without the need to sacrifice the main testicular vessels. It should be considered whenever a single-stage laparoscopic orchidopexy cannot be performed due to inadequate length. It provides a very high success rate with the preservation of testicular vasculature without atrophy. Overall success with this technique is from 84% to 100%.[18][19]

If no testis is found during exploratory laparoscopy, one must 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 finding the gonad.[17]

If the internal ring is closed, but vessels are going into it, a scrotal exploration usually will find a testicular nubbin. It will appear as 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 is warranted.

Differential Diagnosis

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 extra-scrotal on examination or moves easily out of the scrotal position, (often associated with a vigorous cremasteric reflex), but that can be manually replaced in a stable, dependent scrotal position and remain there without tension at least temporarily."[8]

Prognosis

When properly diagnosed and treated, the prognosis is excellent. Testicular cancer risk and infertility remain somewhat increased compared to the general population.[20] However, a recent Danish study of over 6,000 men suggested testicular hypofunction, smaller testis volume (by 3.5 cc), 28% reduction in sperm concentration, and reduced Leydig cell function in men with a history of cryptorchidism compared to normal men.[21]

Complications

Orchiopexy is associated with two major testicular complications: atrophy and testicular ascent.[2] For palpable testes, these occur about 1% of the time. For laparoscopic orchiopexies, the rate is 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 the one-stage procedure).[22] Loss of the testis due to the over-skeletonization of the spermatic cord is one of the most severe complications of orchiopexy.

Deterrence and Patient Education

It is imperative that physicians carefully check and recheck neonates for the presence or absence of properly placed testicles. While there is a chance for spontaneous descent for up to 6 months, both clinicians and parents should carefully check the scrotum routinely. Patients and families of patients should be informed of the nature and natural history of untreated cryptorchidism and the recommendation for early surgery, including its benefits and the risks associated with undue delay.[8]

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 despite the adjuvant LHRH.

Non-union, a rare anomaly involving the epididymis and testicle, can sometimes be mistaken for a testicular nubbin (atrophic testis) when it is actually the vas and epididymis. The actual testicle in this condition is located proximally and can be identified via laparoscopy.[23]

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 male infertility and cancer are increased compared to the general population but are still relatively small. The optimal timing of surgical orchidopexy (<18 months of age) is not always followed, and ultrasound is still being done too often unnecessarily. Close collaboration and communication between physicians, nurse practitioners, physician assistants, pediatricians, and urologic surgeons will result in better outcomes and avoid unnecessary procedures while increasing the incidence of timely surgery when indicated.


Article Details

Article Author

Stephen W. Leslie

Article Author

Hussain Sajjad

Article Editor:

Carlos A. Villanueva

Updated:

6/11/2022 2:44:26 PM

PubMed Link:

Cryptorchidism

References

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