Continuing Education Activity

Cryptorchidism is the most prevalent congenital defect involving male genitalia and is characterized by the absence of at least one testicle from the scrotum. This condition poses significant challenges in both its diagnosis and management. Cryptorchidism can manifest on either one or both testicles, with a higher frequency of involvement observed in the right testicle. Approximately 3% of full-term and 30% of premature male infants are born with one or both testicles undescended, necessitating a nuanced understanding of this disorder among healthcare professionals. Undescended testes can result in potential long-term complications, such as fertility issues, testicular cancer, testicular torsion, inguinal hernias, and psychological issues, if left untreated.

Testicular descent usually occurs by the seventh month of gestation. However, around 80% of cryptorchid testes descend within the first 3 months after birth, thereby reducing the true incidence to approximately 1%. Clinicians can determine the location of undescended testicles, which are predominantly situated in the inguinal canal but are also potentially found in the abdomen or, in some cases, are entirely absent, using palpation techniques. Spontaneous descent is unlikely if the testis has not descended by 6 months, and surgical correction should be considered. Undescended testes can be repositioned into the scrotum through orchiopexy to minimize risks. This activity reviews the workup of cryptorchidism and describes the role of health professionals working together to manage this condition. This activity discusses the diagnosis and management of cryptorchidism or undescended testes and elucidates the collaborative efforts of interprofessional healthcare providers in managing this condition.

Objectives:

• Identify the signs and symptoms of cryptorchidism during routine examinations, ensuring early detection and intervention.

• Implement evidence-based interventions, such as orchiopexy, promptly following diagnosis and adhering to established guidelines to optimize patient outcomes.

• Assess the psychological impact of cryptorchidism on patients and their families, providing necessary support and counseling to address concerns and ensure holistic care.

• Coordinate care seamlessly, ensuring smooth transitions between primary care, specialist consultations, and surgical interventions, promoting a continuum of care and improving patient experience.

Introduction

Cryptorchidism is the most prevalent congenital defect involving male genitalia and is characterized by the absence of at least one testicle from the scrotum. Approximately 3% of full-term and 30% of premature male infants are born with one or both testicles undescended. Testicular descent usually occurs by the seventh month of gestation. However, around 80% of cryptorchid testes descend within the first 3 months after birth, thereby reducing the true incidence to approximately 1%.[1] Cryptorchidism can manifest on either one or both testicles, with a higher frequency of involvement observed in the right testicle. Bilateral cryptorchidism is observed in approximately 10% of all patients with undescended testicles.

Clinicians can determine the location of undescended testicles, which are predominantly situated in the inguinal canal but are also potentially found in the abdomen or, in some cases, are entirely absent, using palpation techniques. Approximately 20% to 30% of undescended testes are nonpalpable. Spontaneous descent is unlikely if the testis has not descended by 6 months, and surgical correction should be considered.[2] Without surgical intervention, an undescended testicle will likely descend during the initial 3 months of life. However, if undescended testes persist, it is advisable to perform an orchiopexy between the ages of 6 and 18 months to reposition the testes into the scrotum, thereby reducing risks and minimizing the potential for infertility.

The testicle can be situated at any point along the descent pathway, exhibiting characteristics such as dysgenetic, ectopic (deviating from the usual descent path), positioned high in the abdomen near the inguinal ring, hypoplastic, located in the inguinal canal, missing or absent, and often presenting unilaterally (in two-thirds of cases).[3] 

Undescended testes can result in potential long-term complications, including decreased fertility (particularly true in cases where both testicles are affected), an increased risk of testicular germ cell tumors (with an overall risk of <1%), testicular torsion, inguinal hernias, and psychological issues, if left untreated. Approximately 10% to 30% of individuals with unilateral undescended testis may experience infertility, with the risk escalating from 35% to 65% or higher for those with bilateral disease. If bilateral cryptorchid testes are left untreated, the infertility rate can exceed 90%.

Cryptorchidism is associated with male infertility in adulthood, primarily due to poor semen quality, which can be linked to compromised Sertoli cell function and its impact on Leydig cell function.[4] Cryptorchidism, hypospadias, testicular cancer, and poor semen quality collectively constitute testicular dysgenesis syndrome. This syndrome is believed to result from 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, as it coordinates hormonal signals necessary for the developmental process. The absence of an appendix testis has been associated with abdominal and cryptorchid testes, particularly when located proximal to the external ring. However, the exact role of the appendix testis in testicular descent remains unclear.

In full-term infants, the cause of cryptorchidism is often indeterminate, rendering it a common yet sporadic, idiopathic congenital defect. Experts believe that a combination of genetics, maternal factors, and environmental influences may disrupt the hormonal and physical processes that influence testicular development and descent. 

Birth weight appears to be the primary risk factor for undescended testes, followed by family history. Furthermore, other potential contributing risk factors include:[1][2]

• Alcohol consumption during pregnancy (5 or more drinks per week, which can increase the risk up to 3 times)
• Chemical endocrine disruptors interfering with normal fetal hormone balance
• Cigarette smoking
• Congenital malformation syndromes such as Down, Prader–Willi, and Noonan
• Cosmetics use
• Exposure to phthalate (di(2-ethylhexyl) phthalate or DEHP)
• Family history of cryptorchidism
• Ibuprofen use
• In vitro fertilization
• Maternal diabetes
• Maternal exposure to diethylstilbestrol (DES)
• Maternal obesity
• Persistent Müllerian duct syndrome
• Pesticide exposure
• Preeclampsia (especially in its more severe forms, poses an increased risk of cryptorchidism)
• Premature infants born before the descent of the testicles
• Small for gestational-age infants
• Smaller placental weight

Epidemiology

Cryptorchidism is observed in 3% of full-term newborn infants, and this prevalence decreases to 1% in infants aged 6 months to 1 year.[1][2] In the United States, cryptorchidism ranges from approximately 3% at birth to 1% from 1 year to adulthood. Globally, the prevalence varies, starting at around 4% to 5% at birth, decreasing to about 1% to 1.5% at age 3 months, and further decreasing to 1% to 2.5% at 9 months. The prevalence of cryptorchidism is 30% in premature male neonates. This elevated prevalence highlights the significance of closely monitoring their testicular development and considering timely interventions when necessary.

Cryptorchidism affects approximately 1.5% to 4% of fathers and 6% of brothers of individuals with cryptorchidism. The heritability in first-degree male relatives is estimated to be around 0.5% to 1%. Additionally, 7% of siblings of boys with undescended testes also experience cryptorchidism, highlighting its potential genetic predisposition within families. Ongoing research aims to understand the nature and significance of the potential association between cryptorchidism and autism.

Pathophysiology

Compared to the scrotum, the altered microenvironment within the abdominal cavity or inguinal canal can disrupt the optimal conditions required for normal testicular function. The scrotum provides a cooler temperature, which is crucial for the proper functioning of the testes and the production of sperm. The elevated temperature in the abdominal or inguinal region can negatively impact sperm development, ultimately affecting fertility.

Cryptorchidism can disrupt communication between the testes and the rest of the endocrine system, leading to transient hormone deficiencies. These hormonal imbalances may contribute to the failure of testicular descent and impede the development of the spermatogenic tissue, further compromising fertility.[3]

History and Physical

The most evident sign in a patient with a cryptorchid testis is the absence of a palpable scrotal testicle. The presence of an inguinal hernia and a decreased degree of scrotal rugae or ridges often accompanies this. A thorough examination of the entire inguinal and pelvic area is essential, including an evaluation of the contralateral testicle. In cases where normal rugae and a testicle are observed in the scrotum, it might indicate a retractile testicle, which usually does not require further treatment.

Common signs and symptoms associated with undescended testicles are listed below.

Infertility

Several factors contribute to reduced fertility in males with cryptorchidism. One key factor is hyperthermia, which can impair spermatogenesis, as the intrascrotal temperature is several degrees cooler than ectopic positions. Various anatomical abnormalities, such as testis-epididymal dissociation, are commonly associated with undescended testes. In some cases, inadvertent injury to the vas deferens, epididymis, or testis may occur during orchiopexy procedures. A higher incidence of anti-sperm antibodies exists in infertile patients with a history of cryptorchidism.[5][6] 

Factors influencing abnormal testicular descent, whether due to chemical exposure or other etiological factors, are likely to have affected both testicles, not just the cryptorchid testis. However, identifying a specific causative defect or disorder may not be determinable. Males with undescended testes often face reduced fertility, which may persist even following orchiopexy.[7] Specifically, approximately 10% to 30% of patients with a unilateral cryptorchid testicle will develop infertility, and azoospermia is found in 13% of individuals with unilateral undescended testicles.[5] In contrast, azoospermia rates can increase to around 90% in patients with untreated bilateral cryptorchidism.[5] 

Even after orchiopexy for bilateral cryptorchidism, fertility remains significantly reduced, amounting to at least 38%. This emphasizes the universal recommendation for early surgical intervention, as untreated undescended testes can undergo degeneration of spermatogenic tissue and reduced spermatogonia after the second year of life, further compromising fertility prospects.

Psychological Consequences

Boys with undescended testicles are not inherently more likely to exhibit gender-related disorders, effeminate traits, or prehomosexual characteristics. However, when the family dynamics are destructive to male self-esteem, it can lead to disturbances in self-image. The surgical correction of cryptorchidism generally promotes the development of healthy masculinity. 

Cancer

The risk of testicular cancer is about 3 times higher than that of the general population when orchiopexy is performed before puberty. However, this risk increases to 5 to 6 times higher when orchiopexy is conducted after puberty. The timing of orchiopexy, whether in early infancy or later in childhood, does not appear to significantly alter the risk of developing testicular cancer.[7]

Seminoma is the most common type of testicular cancer found in untreated undescended testes, with the peak age range for this tumor occurring between the ages of 15 and 45. However, following orchiopexy, seminomas represent only 30% of testicular tumors in previously undescended testes. Early detection is crucial for the effective treatment of testicular cancer. Educating boys who underwent orchiopexy as infants about testicular self-examination is essential to facilitate timely cancer detection.

Evaluation

According to American Urological Association (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 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] 

Routine ultrasound usage is generally unhelpful, as it exhibits limited sensitivity and specificity in localizing nonpalpable testes, with reported values of 45% sensitivity and 78% specificity.[9] In addition, data indicate that among boys with a nonpalpable testicle and a negative ultrasound, 49% are ultimately found to have an intra-abdominal testis.[9]

The utilization of computed tomography is limited due to cost and concerns about ionizing radiation exposure. Magnetic resonance imaging has been widely used with or without angiography and demonstrates greater sensitivity and specificity. However, its use is discouraged due to the associated high cost, low availability, and the requirement for anesthesia.[10] Currently, no radiological test can definitively and with absolute reliability confirm the absence of a testis. Multiple studies have indicated that, regardless of the findings seen on radiological tests, these studies rarely provide conclusive assistance in decision-making and may sometimes offer misleading information, such as indicating absence when the testis is actually present, or vice versa.[11]

A karyotype analysis can confirm or exclude dysgenetic primary hypogonadism. Hormone levels, such as gonadotropins and Müllerian inhibitory substance, may confirm hormonally functional testicles worthy of salvation, making them suitable for preservation. Additionally, human chorionic gonadotropin (hCG) stimulation can increase testosterone levels. In some cases, additional testing is crucial and highly likely to detect intersex conditions.[7]

Bilateral Cryptorchidism

Bilateral cryptorchidism with palpable testes can be addressed through surgery, although there is some debate regarding the optimal timing for this intervention. Some experts advocate for 2 separate procedures, allowing complete healing of one testicle before addressing the contralateral side. Although this approach ensures the survival of at least one testicle, it requires subjecting a young child to 2 separate procedures and anesthesia. Consequently, many specialists prefer to repair both sides in a single surgery, primarily due to the overall low complication rate of about 1%.[12] Infertility may be observed in 35% to 75% of men who initially presented with bilateral cryptorchidism during childhood.

Patients with bilateral impalpable testes, a condition that can affect approximately 20% to 30% of all boys with cryptorchidism, necessitate further evaluation to investigate the potential presence of a disorder of sexual development.[13] Notably, it is crucial to withhold any circumcision procedures until the evaluation is complete.

In some instances, individuals born with female genetics and severe congenital adrenal hyperplasia may be initially misidentified as males with bilateral cryptorchidism. The initial action should involve assessing the patient for possible congenital adrenal hyperplasia. This includes measuring electrolytes for hyponatremia and hyperkalemia, conducting karyotype analysis, and performing hormonal profiling, including androstenedione, 17-hydroxyprogesterone, luteinizing, follicle-stimulating (FSH), and testosterone hormones.[8]

After ruling out congenital adrenal hyperplasia, the next step is to ascertain the presence of testicular tissue. The presence of Müllerian inhibiting substance, produced by the testicular Sertoli cells, would indicate the presence of testicular tissue somewhere, possibly intra-abdominal. FSH can stimulate the production of inhibin B and Müllerian inhibiting substance, whereas hCG can stimulate Leydig cells to manufacture testosterone.[14] 

Patients possessing a male karyotype (46, XY chromosomes), bilateral nonpalpable testes, elevated serum FSH levels, and no detectable serum Müllerian inhibiting substance and inhibin B can be reasonably diagnosed as having no testicular tissue (anorchia).[14] Although hCG stimulation testing has been conducted in the past, an undetectable Müllerian inhibiting substance offers a notably superior positive predictive value at 92%.[15] In instances where testicular tissue is presumed to be present, an exploratory laparoscopy can be performed to determine the location of the testicular tissue and the optimal surgical approach.

Treatment / Management

Medical Treatment

According to the AUA guidelines, healthcare professionals should refrain from hormonal therapy to induce testicular descent, as evidence indicates low response rates and a lack of long-term efficacy.[8] This recommendation aligns with the European Society for Pediatric Urology, the European Association of Urology (EAU), the Canadian Urological Association, the British Association of Pediatric Surgeons, and the British Association of Pediatric Urology Surgeons.[7][16][17][18]

The American Pediatric Association guidelines recommend the use of hormones in cases of undescended testis associated with Prader-Willi syndrome. The rationale is based on the belief that a therapeutic trial of hCG is indicated as a treatment for undescended testes before considering surgery. This approach is motivated by the preference to avoid general anesthesia in infants with low muscle tone and at high risk for underlying respiratory compromise.

The most commonly used hormone for hormone therapy is hCG. A series of hCG injections is administered, followed by a reevaluation of the status of the undescended testicle. The reported success rate for this treatment approach ranges from 5% to 50%. In addition, hormone treatment serves the dual purpose of confirming Leydig cell responsiveness and stimulating further growth of a small penis due to the elevation in testosterone levels. 

Hormone therapy is generally more cost-effective than surgery, and the risk of complications is minimal. However, a recent meta-analysis of 7 randomized clinical trials concluded that hormonal treatment was no more effective than a placebo.[16]

Surgery

Surgery is recommended for congenital undescended testes within the age range of 6 to 18 months, as per the AUA guidelines.[8] Many experts advocate for early surgical intervention, typically around 6 months, to optimize testicular growth and preserve fertility. Furthermore, performing the procedure at a younger age is preferable because the distance the testes must be moved increases as the child ages.

Unfortunately, many young boys do not undergo orchidopexy within the recommended guidelines. A study reported that 70% of males with cryptorchid testes underwent surgery at least 6 months later than advised.[19] The causes of this delay were multifaceted, including secondary cryptorchidism, reduced well-child visits, familial challenges, and a reliance on family care providers for surgical referrals rather than pediatricians. This suggests the possibility of inadequate examinations or a lack of familiarity with the guidelines among some practitioners.[20][21] Moreover, race and insurance status were identified as significant contributing factors.[21][22] For every 6-month delay in performing the orchidopexy, patients may experience a 1% decrease in fertility, a 5% increase in the need for assisted reproductive techniques, and a 6% increased risk of developing testicular malignancy later in life.[20] 

In the case of premature babies, corrected age is used to determine optimal surgical timing. The longer the cryptorchid testis remains untreated, the more significant the loss of germ cell loss and the subsequent decrease in fertility. Therefore, early orchidopexy is typically the standard intervention.[4] Patients with bilateral undescended testes who undergo orchidopexies as adults are almost invariably infertile and exhibit azoospermia. However, there have been a few anecdotal reports of pregnancies achieved through assisted reproduction in this group.[23]

Surgery is recommended shortly after diagnosis for acquired undescended testes (those documented as normal before diagnosis) and entrapped undescended testes (those occurring after hernia repair). Conversely, in the case of retractile testes, a yearly physical examination is recommended due to the reported risk of 2% to 50% of a retractile testis potentially transitioning into an acquired undescended testis. 

Techniques of Orchiopexy

For palpable undescended testes, performing an inguinal or scrotal orchiopexy is recommended.[23] The procedure typically involves the following factors:

• An incision is made in the high scrotum, median scrotal raphe, high edge of the scrotum, or groin, depending on the case. Many different types of retractors can be used depending on the incision size. Inguinal incisions can be as small as 1 cm, whereas scrotal incisions can be larger as they tend to heal concealed, especially when placed along the median raphe. 

• The surgeon can choose to approach either the testis or the cord first. In scrotal cases, the testis is typically located first. In an inguinal approach, the testis can be approached first, or the external oblique fascia is opened proximal to the external ring, and the cord can be accessed first. 

• The surgeon initially divides all the cremasteric muscles before approaching the testis, as not everything goes into the external ring.

• A more challenging aspect of the procedure is separating the hernia sac from the vas deferens and testicular vessels. This can be approached anteriorly or posteriorly, with the posterior approach typically easier to teach and learn.

• How the testis is positioned and secured in the scrotum can vary among surgeons. Most surgeons prefer to create a sub-dartos pouch. Some surgeons do not suture the testis in place, while others use absorbable or nonabsorbable sutures. Alternatively, some may choose to simply close the passage into the groin. 

For nonpalpable testes under anesthesia, exploratory laparoscopy is the recommended approach. During exploratory laparoscopy, if a testis is discovered, the surgeons perform any of the following available options for their patients.[23][24][25][26][27]

Laparoscopic orchiopexy with preservation of the vessels: This procedure involves dissecting the testis from a triangular pedicle containing the gonadal vessels and the vas deferens.

Laparoscopic 1-stage Fowler-Stephens (FS) orchiopexy: In this process, the gonadal vessels are divided, and the testis is dissected off a pedicle of the vas deferens, bringing it down in one stage.

Laparoscopic 2-stage FS orchiopexy: This technique uses clips to divide the gonadal vessels. However, dissection of the testis is deferred for 6 months, allowing for optimal development of collaterals before proceeding with the testicular relocation.

Laparoscopic 2-stage traction-orchidopexy (Shehata technique): In this procedure, the intra-abdominal testis is fixed to a point 1 inch (2 cm) medially and superiorly to the contralateral anterior superior iliac spine to provide traction. The testis remains in its undescended position for 3 months. Afterward, a laparoscopy-assisted ipsilateral subdartos orchidopexy is performed. This technique serves as an alternative to the 2-stage FS orchidopexy. 

The primary advantage of the Shehata technique is that it can relocate an intra-abdominal testis into the scrotum without sacrificing the main testicular vessels. This technique requires only a 3-month delay, whereas the FS method needs 6 months. The Shehata technique should be considered in cases where a single-stage laparoscopic orchidopexy cannot be performed due to inadequate length. This procedure has a very high success rate of preserving testicular vasculature and minimizing the risk of atrophy. Studies have reported an overall success rate ranging from 84% to 100% with this approach.[24][25]

A testicular ischemia test has been suggested to assess the feasibility of an FS orchidopexy. During laparoscopic surgery, the spermatic cord vessels are temporarily tied off with a silk ligature that can easily be loosened. After a 10-minute interval, the testis is re-examined and compared to its appearance before the cord ligation. If no signs of ischemic changes are observed in the testis, it indicates an adequate collateral blood supply, suggesting the safety of proceeding with an FS surgical approach.[28]

Systematic comparison and meta-analysis of the 2 laparoscopic 2-staged surgical procedures concluded that the Shehata internal fixation technique exhibited superior overall success and a lower atrophy rate when compared to the FS approach. No significant difference was noted in the retraction rate or operative time.[29] 

The selection of a surgical approach depends on the surgeon's specific training, experience, skill level, and personal preference. The Shehata technique is theoretically preferred as it does not sacrifice the testicular artery and has a lower rate of gonadal atrophy. This method is particularly recommended for patients who fail the testicular ischemia test.

If no testis is located during exploratory laparoscopy, it becomes crucial to ascertain the presence of either blind-ending vessels or a testicular nubbin to rule out a missing testis definitively. The vas deferens can be dissociated from the testis, making it unreliable as a sole guide in locating the gonad.[23]

If the internal ring is closed but vessels are observed entering it, a scrotal exploration typically reveals a testicular nubbin. This nubbin will appear as a small structure with a brown spot. If veentertering an open inguinal ring, pushing the testis into the abdomen is usually possible. However, an inguinal or scrotal exploration is warranted if this cannot be accomplished.

Differential Diagnosis

A typical diagnostic challenge involves differentiating a retractile testicle from a testicle that does not spontaneously descend into the scrotum. Retractile testes are more prevalent than undescended testes and do not necessitate surgical correction. The cremaster muscle contracts in normal males, causing the testicles to retract into the upper scrotum and inguinal canal. This reflex is more active in infants. 

Distinguishing a retractile testicle positioned high in the scrotum from one in the lower inguinal canal can be challenging. Various maneuvers are used to aid in identification, such as having the patient in a cross-legged position, using soaped fingers during examination, and assessing the patient while in a warm bath.

According to the AUA guidelines, a retractile testis is described as initially located outside the scrotum or easily movable out of it, typically associated with the cremasteric reflex. However, at least temporarily, it can be manually returned to a stable, dependent scrotal position without tension.[8]

Prognosis

With proper diagnosis and treatment, the prognosis for cryptorchidism is excellent. However, there is a slight increase in the risks of testicular cancer and infertility compared to the general population.[30] A Danish study involving over 6,000 men indicated that individuals with a history of cryptorchidism exhibited testicular hypofunction, with a 3.5 mL reduction in testis volume, a 28% reduction in sperm concentration, and diminished Leydig cell function compared to men without cryptorchidism.[31]

Complications

Orchiopexy is associated with 2 major testicular complications—atrophy and testicular ascent.[2] These complications occur in approximately 1% of the time for palpable testes. The rate increases to around 5% for laparoscopic orchiopexies. In FS orchiopexies, whether performed in 1 or 2 stages, the rate of testicular atrophy is around 20% to 30%, with the one-stage procedure resulting in worse outcomes.[32] Over-skeletonization of the spermatic cord leading to the loss of the testis represents a severe complication of orchiopexy.

Deterrence and Patient Education

Physicians should carefully assess neonates for the proper placement of their testicles, which is imperative, as there is a chance for spontaneous descent within the first 6 months of life. In addition, it is important for both clinicians and parents to regularly examine the scrotum of their pediatric patients and boys, respectively, for any abnormalities or signs of discomfort. Patients and their families should be informed by their healthcare providers about the nature and natural progression of untreated cryptorchidism, emphasizing the recommendation for early surgery. This patient education should emphasize the importance of timely intervention and the risks associated with undue surgical delay.[8]

Pearls and Other Issues

Adjuvant luteinizing hormone-releasing hormone (LHRH) treatment is offered for patients with cryptorchidism with a high risk for infertility due to insufficient gonadotropin stimulation during 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 deferens and epididymis. The actual testicle in this condition is located proximally and can be identified through laparoscopy.[33]

Undescended testes are invariably associated with pediatric hernias and must be differentiated from retractile testes, which do not require treatment. A calm examination of the patient in a warm room can assist with this differentiation. 

Enhancing Healthcare Team Outcomes

Awareness of the optimal timing for surgical orchidopexy at or before 18 months of age is crucial for all pediatric and family healthcare professionals, given the risks for further male infertility and cancer. Unfortunately, this guideline is not consistently followed, resulting in unnecessary and excessive use of ultrasound in many cases.

Effective collaboration and communication among healthcare professionals, including physicians, nurse practitioners, physician assistants, pediatricians, and urological surgeons, are essential. Such coordination leads to better outcomes, reduces unnecessary procedures, and increases timely surgeries when required.