Cryptorchidism

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

• References

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]

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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.

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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.

• References

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, 5]}

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.^[6] Furthermore, testosterone and its conversion to dihydrotestosterone (DHT) are also necessary for continued migration, especially during the inguinoscrotal phase.^{[7, 8, 9]}

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.^[10] 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.^{[11, 12, 13]}

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.^[14] Both hormonal and mechanical factors appear to mediate the aid of the gubernaculum and descent of the testis.^[15] The genitofemoral nerve may also aid in descent and gubernacular differentiation, which may be mediated by calcitonin gene-related peptide.^{[16, 17]}

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.^{[18, 19]} 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.^{[20, 21]}

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.^[22]

A Japanese study found that nationwide, the discharge rate of cryptorchidism increased by 14.3% after the Fukushima nuclear accident. Rates of other risk factors for cryptorchidism (ie, low-weight babies, preterm births) remained almost constant during the study period, and age distribution of cryptorchidism surgery also did not change.^[23]

• References

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.^[24] 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%.^{[25, 26]} 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.^[27] 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
• Cerebral palsy
• Mental retardation
• Wilms tumor
• Abdominal wall defects (eg, gastroschisis, omphalocele, prune belly syndrome)
• Hypospadias

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:

• Cryptorchidism
• Hypospadias
• Intersexuality
• Precocious puberty
• Infertility
• Consanguinity

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.

• References

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.^{[28, 29, 30]}
• 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.^[31]
• Hadziselimovic and Herzog (2001) found a negative association between age and germ cell count by age 6 months in children undergoing orchiopexy.^[32]
• 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.^[33] 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.^{[34, 35]}

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.^[36] Ten percent of testicular cancer cases involve patients with undescended testis.^{[37, 38]}
• Prepubertal orchiopexy reduces this risk.^{[39, 40]}
• 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.^{[41, 42]}
• Seminoma is the most common malignant tumor type associated with cryptorchidism.^[43]
• Correction of associated hernia: A patent processus vaginalis is found in more than 90% of patients with undescended testis.^{[26, 22]}

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.^{[44, 45]}

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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.

View Image

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

• References

Laboratory Studies

For unilateral undescended testis without hypospadias, no laboratory studies are needed. Bilateral nonpalpable testes associated with either hypospadias or ambiguous genitalia may represent a life-threatening situation. Consultation with a pediatric endocrinologist and/or geneticist is recommended.

For unilateral or bilateral undescended testes with hypospadias or bilateral nonpalpable testes, tests include the following:

• Testing to rule out intersexuality (mandatory)
• 17-hydroxylase progesterone
• Testosterone
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Further laboratory studies, depending on initial results

To determine anorchia in cases of bilateral nonpalpable gonads, perform the following:

• LH testing
• FSH testing
• Testosterone level testing before and after stimulation with human chorionic gonadotropin (hCG)

Elevated basal gonadotropin levels and a negative testosterone response to hCG stimulation suggests congenital bilateral anorchism. Numerous protocols exist for hCG stimulation tests, but the most practical is a single injection of hCG (100 IU/kg or 2940 IU/body surface area) followed by a testosterone evaluation 72-96 hours postinjection.

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Imaging Studies

Radiologic studies to localize the testis are currently of very little value. The overall accuracy of radiologic testing for undescended testis is only 44%.^[46]

Computed tomography (CT) scanning and ultrasonography yield high false-negative rates in the evaluation of a nonpalpable testis and are not recommended.^[47] Magnetic resonance angiography (MRA) has been reported to have a nearly 100% sensitivity but requires sedation or anesthesia and is expensive and may not be cost-effective. To date, examination by a pediatric urologist has proven to be more valuable than ultrasonography, CT scanning, or MRA.

Abdominal and pelvic ultrasonography combined with genitography should be used when intersexuality is suspected. Ultrasonography of the upper urinary tract has been investigated because of the embryologic association of the ureteric bud and the Wolffian duct, but the yield of significant urinary pathology is no greater than the incidence of anomalies found in the general population.^[48]

For discussion and images, see Cryptorchidism Imaging.

• References

Approach Considerations

Cryptorchidism should be treated when the patient is approximately 6 months old. This age recommendation has been pushed up over recent decades and is based on (1) the rarity of spontaneous descent after age 6 months and (2) the possible improvements in fertility that early intervention may confer. The choice of initial treatment is a reflection of the preference of both physician and the patient or the patient’s caretaker(s).

Patient selection is paramount to achieve satisfactory results. Higher success rates are reported in older children and in patients with testes in a lower pretreatment position.^{[49, 50, 51]}  Regular re-examination of successful descent is necessary, as re-ascent can occur in up to 25% of treated children.

• References

Medical Therapy

Primary hormonal therapy with hCG (see choriogonadotropin alfa) or gonadotropin-releasing hormone (GnRH or luteinizing hormone–releasing hormone [LHRH]) has been used for many years, especially in Europe. In the United States, only hCG is currently available.

Human chorionic gonadotropin

The action of hCG is virtually identical to that of pituitary LH, although hCG also appears to have a small degree of follicle-stimulating hormone (FSH) activity. It stimulates production of gonadal steroid hormones by stimulating the Leydig cells to produce androgens. The exact mechanism of action of the increased androgens in testicular descent is not known but may involve effects on the testicular cord or cremaster muscle. hCG is administered via intramuscular injection.

Multiple series on the efficacy of hCG have been published; however, because of differences in patient age, treatment schedules, and possible inclusion of retractile testes, very divergent results have been reported. A  meta-analysis of hCG treatment of cryptorchidism concluded that hCG treatment is no more effective than placebo.^[52]   American Urological Association guidelines recommend against the use of hormonal therapy to induce testicular descent, due to low response rates and lack of evidence for long-term efficacy.^[1]

Many dosage schedules have been reported, ranging from 3-15 doses. However, hCG appears to be as effective in 3 or 4 doses as with 9 or 10 doses. One of the most common schedules is 250 IU/dose in young infants, 500 IU/dose in children 6 years or younger, and 1000 IU/dose in individuals older than 6 years given twice a week for 5 weeks (as per the International Health Foundation).^[53]

Success rates for descent into the scrotum are 25-55% in uncontrolled studies but only 6-21% in randomized blinded studies. Distally located testes in older boys are more likely to descend in response to hormonal treatment than abdominal testes. Repeated courses have offered little advantage.

Adverse effects of hCG treatment include increased scrotal rugae, pigmentation, pubic hair, and penile growth, which regress after treatment cessation. A total dose of more than 15,000 IU may induce epiphyseal plate fusion and retard future somatic growth.

Gonadotropin-releasing hormone

Agonistic analogs of GnRH such as nafarelin or buserelin stimulate the release of the pituitary gonadotropins, LH and FSH, temporarily increasing gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland, and twice-daily administration decreases secretion of gonadal steroids by 4 weeks. GnRH is available as a nasal spray but is approved for the treatment of cryptorchidism only in Europe.

The interpretation of results is tainted by multiple treatment strategies. Success rates in uncontrolled studies range from 13-78%, while better-controlled investigations resulted in rates of 6-38%. Rajfer et al conducted a randomized double-blind study comparing hCG at 3300 IU per week for 4 weeks with GnRH spray at 200 mcg 6 times per day for 4 weeks. Descent into the scrotum occurred in 6% of the hCG group and in 19% of the GnRH group.^[49]

Several authors have recommended combined GnRH and hCG hormonal treatment.

Lala et al administered LHRH at 1.2 mg/d for 4 weeks. Those who did not respond also received hCG at 500 IU 3 times per week for 3 weeks. After combined treatment, 38% of testes descended.^[54]

Bica and Hadziselimovic treated patients with a low dose of buserelin (20 mcg) as a daily spray for 28 days, followed by hCG in those in whom treatment failed. Approximately 26% of the testes descended with the spray alone, and hCG increased the descent rate to 37%.^[55] Hadziselimovic advocated initial treatment with GnRH spray at 400 mcg tid into each nostril for 4 weeks, followed by salvage treatment in those in whom treatment failed, with hCG at 1500 IU/week for 3 weeks. The success rate of 56% with GnRH was increased to 65% with the addition of hCG.^[56]

The recognized adverse effects of increased androgens, including increased penile or testicular size, scrotal erythema, or erections, seem to be less with GnRH than with hCG.

Initial treatment with GnRH may deserve some consideration because it is administered as a spray rather than an injection. Even in 20% of patients, it may aid descent in more distal testes, make intra-abdominal testes palpable, or help differentiate retractile from true undescended testes.

In summary, hormonal treatment yields an overall efficacy rate of less than 20% for undescended testes. The decision to use hormonal treatment depends on the pretreatment location of the testis.

Treatment with GnRH has also been used as an adjunct to orchiopexy, to increase fertility. A meta-analysis and systematic review by Chua et al found evidence suggesting that a subset of boys with cryptorchidism may benefit in that respect. However, the characteristics of cryptorchidism patients who would will clearly benefit from GnRH treatment have not been identified.^[57]  European guidelines note that there is no consensus on hormonal treatment for testicular descent but suggest offering endocrine treatment for bilateral undescended testes, to possibly improve further fertility potential.^[58]

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Surgical Therapy

Successful surgical placement of the testis in the scrotum is based on the principles originally described by Bevan in 1899. These include adequate mobilization of the testis and spermatic vessels, ligation of the associated hernia sac, and adequate fixation of the testis in a dependent portion of the scrotum. Many different techniques have been described and are highlighted in the following Intraoperative Details section.^[59] Orchiectomy is usually performed laparoscopically.

In a 1995 meta-analysis of orchiopexy by Docimo, location-based success rates were as follows^[60] :

• Testes located beyond the external ring: 92%
• Peeping testes: 82%
• Canalicular testes: 87%
• Abdominal testes: 74%

The success rates by surgical approach were as follows^[60] :

• Inguinal orchiopexy: 89%
• Microvascular orchiopexy: 84%
• Transabdominal orchiopexy: 81%
• Staged Fowler-Stephens orchiopexy: 77%
• Standard Fowler-Stephens orchiopexy: 67%

According to a study of 51 formerly cryptorchid subjects who had undergone surgery in the first 2 years of life, sperm count and motility were normal in more than 95% at 18-26 years of age, with even better fertility prognosis if orchiopexy was performed during the first year of life (96.3% for both normal sperm count and sperm motility).^[61]  A systematic review and meta-analysis found that atrophy and complication rates do not appear different between orchiopexy performed before or after 1 year of age, but fertility potential may be better with early orchidopexy.^[62]

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Preoperative Details

Laboratory studies are generally unnecessary in patients with unilateral cryptorchidism. Orchiopexy is performed routinely as a same-day surgical procedure in the absence of significant associated morbidities. Definitive surgical therapy should be performed between ages 6 and 12 months.

• References

Intraoperative Details

The child is placed supine in the frog-leg position. Reexamination is performed under anesthesia. A previously nonpalpable testis may become palpable, circumventing abdominal exploration.

Palpable testis

An incision is made over the inguinal canal along the Langer lines. For gonadal identification, care is taken when the Scarpa fascia is incised because the testis may be located in the superficial inguinal pouch rather than in the inguinal canal. Identification of the shelving edge of the inguinal ligament is helpful for orientation, especially in chubby infants.

The distal gubernacular attachments are divided. The cremasteric muscle fibers are then mobilized. (The author has found bipolar cautery to be helpful in this regard.) If the undescended testis is in a low position, incision of the external oblique fascia may be unnecessary. Separate the cord structures from the peritoneum above the internal inguinal ring during ligation of the hernia sac. Divide the lateral spermatic fascia to allow medial movement of the testis. Isolate and perform high ligation of the patent processus vaginalis on the anteromedial surface of the cord. Relocate the testis into the scrotum in a subdartos pouch.

The preferred method of testis fixation is controversial. Options are as follows:

• A subcutaneous pouch with suture fixation versus a sutureless subdartos pouch
• Absorbable versus permanent suture
• Tunica vaginalis fixation versus tunica albuginea fixation

Considerations regarding those options include the following:

• Bellinger et al (1989)^[63] and Dixon (1993)^[64] have shown that sutures through the tunica albuginea cause testicular parenchymal damage in rats
• Chromic sutures produce more fibrosis than permanent sutures
• A sutureless subdartos pouch offers the least fibrosis
• Jarow determined that subtunical sutures may damage the testicular blood supply, more in the lower pole than in the upper. If sutures are used, they should be fine and nonabsorbable (eg, 5-0 Prolene) and placed with minimal depth in the tough tunica albuginea.^[65]

Further maneuvers may be used to achieve adequate length of an inguinal testis. For the Prentiss maneuver, divide (or pass the testis under) the inferior epigastric artery and vein and open the transversalis fascial layer. Open the internal inguinal ring by dividing the internal oblique muscles and more of the lateral spermatic fascia. The inguinal incision may also be lengthened to enable this dissection.

Continue dissection in the retroperitoneal space. The Fowler-Stephens orchiopexy with division of the internal spermatic artery allows the testis to survive on the blood supply of the vas deferens and the cremasteric attachments. This may be used only if extensive dissection of the vas and cord has not already occurred.

The region of transection of the spermatic artery is controversial. Fowler and Stephens originally reviewed the vascular anatomy to the testis and determined that the spermatic artery is an end artery. Thus, the parenchyma of the testis supplied by this artery would become ischemic if it were transected close to the testis. The recommended ligation is as far from the testis as possible to maximize collateral blood flow.

Testicular autotransplantation by microvascular anastomosis of the testis to the ipsilateral inferior epigastric artery and vein may be used.

In rare cases, a 2-stage orchiopexy without division of the spermatic vessels is performed when the Prentiss maneuver and cord dissection have failed to gain adequate length. The testis is anchored in its most dependent position (high scrotum or pubic tubercle) with or without the cord covered by a silastic sheath. The second stage is performed 6-12 months later.

Nonpalpable testis

An extended inguinal incision; an abdominal incision; or, more commonly, diagnostic laparoscopy is used to explore for a nonpalpable testis. At the time of exploration, one the following 3 main features is likely to be encountered:

1. Blind-ending spermatic vessels above the internal inguinal ring (44%)
2. Intra-abdominal testis (36%)
3. Cord structures (vessels and vas deferens) that enter the internal ring (20%)

Blind-ending vessels suggest vanishing testis syndrome, likely due to an early prenatal vascular event. A blind-ending vas deferens or absent spermatic vessels warrant further exploration of the retroperitoneum up to the level of the renal hilum in order to document the presence or absence of testicular vasculature.

Whether the spermatic cord or vessels entering the ring warrants inguinal exploration for identification of a testis or a testicular nubbin is a topic of debate. Storm et al (2007) have shown residual tubules in up to 18% of these testicular remnants.^[66] In addition, removal of the remnants is possible with laparoscopic dissection, sparing the need for an inguinal incision. If a testicular nubbin is found within the scrotum, some surgeons recommend contralateral scrotal testis fixation because a previously unrecognized torsion may have occurred.

Options for the treatment of an intra-abdominal testis vary depending on the patient's age, testis size, contralateral testis, and the surgeon's skills. The author prefers the laparoscopic approach to the intra-abdominal testis.

For the laparoscopic approach, place the patient in the supine Trendelenburg position and secure him to the operating table to allow tilting. Insert a bladder catheter and orogastric tube.

The authors use an open Hasson (mini-laparoscopic ["mini-lap"]) technique. Insufflate the abdomen with carbon dioxide at a low rate (1 L/min) until distension occurs. Initial pressures should be less than 7 mm Hg. Create a 5-mm umbilical camera port (newer 2- to 3-mm needlescopes are now available). In infants who are to undergo orchiopexy or orchiectomy, one or two 2-mm working ports need to be placed, usually lateral to the ipsilateral inferior epigastric vessels and at the midline below the umbilicus. Again, in patients with vanishing testis syndrome, the remnant is mobilized and removed via the ocular port. Laparoscopy is sufficient for the diagnosis of blind-ending spermatic vessels (see video below).

View Video

Laparoscopic management of the vanishing testis.

Jordan et al (1992) first described the technique of laparoscopic orchiopexy, and all modern techniques are similar.^[67] It is necessary to decide early if a staged laparoscopic Fowler-Stephens orchiopexy is necessary. If the testis is farther than 4 cm from the internal ring, this should be considered. However, note that more than 90% of intra-abdominal testes can be brought down successfully without such extreme maneuvers. If the staged procedure is used, the first and second operations are separated by 6-9 months to allow collateralization of the deferential artery.

The peritoneum is incised around the internal ring and continued superiorly lateral to the vessels and medial to the vas deferens. A triangle of peritoneum is left between the vas and vessels distally. The vessels are carefully mobilized, and optical magnification with the laparoscopic approach is quite helpful in this regard. The testis is brought down after a subdartos pouch is created by passing a 12-mm radially dilating trocar into the peritoneum just lateral to the lateral umbilical ligament. Afterward, additional dissection of the vessels is necessary in some cases. Ensure that the cord is torsion-free as the testis is brought down. Standard scrotal fixation is performed. The 2-mm ports do not require closure, but the 5-mm umbilical port is closed to avoid omental herniation.

For standard abdominal orchiopexy, choose between an extended inguinal versus an abdominal (vertical midline or Pfannenstiel) incision. This procedure yields an 81% success rate, defined as scrotal testis without atrophy. Orchiopexy to correct a so-called peeping testis at the internal inguinal ring yields a success rate of 82%. If the testis is in the abdominal cavity, the success rate is 74%. The surgeon may proceed to other techniques for orchiopexy (ie, 2-stage, artery ligation) depending on testis mobility.

The 2-stage orchiopexy can be used after extensive cord mobilization; however, spermatic cord injury is a risk during the second procedure. The success rate is 73%.

The single-stage Fowler-Stephens procedure must be planned ahead to avoid devascularization of the secondary blood supply from the vas deferens and the cremaster muscles. It can be performed using open or laparoscopic technique. The success rate is 67%. The 2-stage Fowler-Stephens procedure theoretically allows improved collateral blood supply, but a second stage is required. It may also be performed with an open or laparoscopic technique. The success rate is 77%. A literature review reveals no statistically significant difference between success rates of 1-stage versus 2-stage Fowler-Stephens orchidopexies.

Shehata et al describe an alternative to the two-stage Fowler-Stephens technique for patients with a high intra-abdominal testis, two-stage laparoscopic traction orchiopexy, which permits elongation of the testicular vessels without division. In the first stage, the testis is fixed to a point 1 inch above and medial to the contralateral anterior superior iliac spine for 12 weeks. Subdartos orchiopexy is done at the second stage. In their study of boys 6 months to 9 years of age, scrotal testes were achieved in 105 (84%) of 125 cases.^[68]

For laparoscopy-assisted orchiopexy (LAO), mobilize the testicular vessels laparoscopically up to the renal level to avoid tension for a classic open inguinal orchiopexy. Increased magnification aids in dissection. Make abdominal port incisions and an open inguinal incision.

A comparison study of primary LAO with laparoscopic two-stage Fowler-Stephens orchiopexy (FSO) in 94 patients with 110 nonpalpable testes reported overall success rates of 88% for LAO versus 63% for FSO. For high intra-abdominal testes, atrophy rates were 3% for LAO versus 20% for FSO (odds ratio 0.14, P = 0.049).^[69]

Microvascular orchiopexy allows adequate scrotal position with preservation of the spermatic artery blood flow. However, it requires special expertise. The success rate is 84%.

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Postoperative Details

Pain medication is used as needed. Keep the surgical area dry for 1-2 days. Absorbable sutures are used during closure; therefore, removal is not necessary. The patient should avoid using straddle toys or participating in physical education for 2-3 weeks.

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Follow-up

Treatment of cryptorchidism should not end with the first postoperative visit. The primary care provider or surgeon should evaluate the child at 2-3 weeks and 6-12 months following surgery to determine testis location, size, and viability. When the child reaches puberty, the physician should readdress the potential issues of fertility and testicular cancer and give instructions concerning the boy's monthly testicular self-examination.

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Complications

Complications of orchiopexy are as follows:

• Inadequate testis position occurs in up to 10% of patients and is due to incomplete retroperitoneal dissection. It is usually corrected with a second procedure.
• Testicular atrophy due to devascularization during dissection of the cord occurs in approximately 5% of patients. Orchiectomy may be indicated to treat cancer, with subsequent prosthesis placement if requested.
• Accidental division of the vas deferens occurs in 1-2% of patients. Immediate or postpubertal microvascular repair may be used.
• Epididymoorchitis is uncommon and may be treated with antibiotics.
• Scrotal swelling may occur and is usually secondary to edema. If progressive, it may be due to bleeding and should be explored. A later presentation of swelling may be secondary to a hydrocele, which, if large, requires transscrotal repair.

Complications of laparoscopy include the following:

• Preperitoneal emphysema may develop secondary to poor needle or trocar placement and insufflation.
• Hypercarbia may occur with pneumoperitoneum. This can be counteracted by increasing minute ventilation and keeping insufflation pressures at less than 12 mm Hg.
• The puncture of a viscus with the Veress needle is not harmful unless insufflated or dilated by a trocar.
• The puncture of a major abdominal vessel is a life-threatening complication. The needle or sheath should be left in place for tamponade, and an emergency open laparotomy is performed. (Almost all the above potentially life-threatening vascular and enteric complications can be avoided by using an open technique for access.)
• Injury to the inferior epigastric vessels may also occur with trocar placement. Hemostasis can be achieved via direct cautery or via suture/clip ligation from the external surface or laparoscopically.
• Bladder puncture may occur because the bladder is intra-abdominal in younger children. Care must be taken when placing lower abdominal and scrotal trocars. Repair can be achieved laparoscopically or through a small suprapubic incision. A ureteral injury requires stenting.

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Future and Controversies

Testis cancer

In children or young adults who present late with cryptorchidism, some authors recommend initial management with orchiopexy while others advise proceeding directly to orchiectomy. Chung and Lee suggest an individualized approach to postpubertal cryptorchidism: offer orchiectomy, but if that is declined, perform orchiopexy followed by careful surveillance for malignant changes. In cases where convincing evidence exists of testicular descent at birth, with secondary ascent of the testis, they note that postpubertal orchiopexy may reduce the risk of infertility without increasing the risk of malignancy.^[70]  

Giwercman et al recommend biopsy of all cryptorchid testes in adults. If carcinoma in situ (CIS) is present, they recommend contralateral biopsy and unilateral orchiectomy. If the remaining contralateral testis also harbors CIS, they recommend radiation therapy.^[71]  

Lenz et al demonstrated an abnormal echo pattern in 3% of postpubertal testes that had undergone orchiopexy. This abnormal ultrasonographic finding may be associated with CIS, and they suggest offering scrotal ultrasonography to postpubertal patients.^[72]

Infertility

Based on retrospective human data and orchiopexy studies in rats, Bellinger et al believe that the practice of transparenchymal sutures to fixate the testis or the use of scrotal wall bolsters put the testis at significant risk for direct trauma. Suture violation of the blood-testis barrier may also play a role in future antisperm antibody development. Further investigation is necessary to fully define this concept of testicular injury.^[63]

Studies have shown that patients with a fertility index of less than 0.2 based on testis biopsy at orchiopexy are at a severe risk for later infertility, and these counts correlate with sperm density in adulthood. Hadziselimovic et al (1997) suggested that such patients may benefit from adjuvant hormonal therapy with resultant increased numbers of germ cells later in life.^[73] LHRH agonists may improve testicular germ cell and postpubertal sperm counts. Huff et al (2001) showed that 75% of boys with significantly reduced germ cell counts who were treated with nafarelin after orchiopexy and bilateral testicular biopsy showed a significant improvement in total germ cell counts on rebiopsy after 5 months.^[31] Neoadjuvant GnRH in prepubescent boys may also positively affect future fertility, with the highest fertility indices reported with therapy before age 2 years.^[74]

Future

Schneck et al reported a trend of significantly lower inhibin B levels in boys with cryptorchidism compared with age-matched controls. Inhibin B is produced by the Sertoli cells and is an important regulator of FSH secretion. Kawada et al demonstrated that adult patients who previously had cryptorchidism and markedly low inhibin levels and elevated FSH levels had severely compromised sperm production.^[75]

Kolon et al demonstrated mutations in the developmental homeobox gene, HOXA10, in boys with cryptorchidism and polymorphisms in patients with cryptorchidism and in the general population.^[5] Analysis of paralogous and orthologous genes of HOXA10 will help elucidate the role of regulatory genes in normal and abnormal testicular descent. Several authors have examined the role of various gene alterations in humans; however, despite findings in animal models, no human isolated cryptorchidism gene has yet been identified. This further supports the notion that the etiology of cryptorchidism is multifactorial.

Further evaluation is needed to identify the role, if any, of isolated cryptorchidism in the spectrum of intersexuality. Histologic, molecular, radiologic, and hormonal studies may reveal similar or dissimilar etiologies for the common isolated undescended testis compared with the relatively uncommon ambiguous genitalia of intersexuality.

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Guidelines Summary

American Urological Association (AUA) guidelines on cryptorchidism contain the following recommendations on diagnosis by primary care providers:

• Obtain gestational history at initial evaluation of boys with suspected cryptorchidism. (Standard; Evidence Strength: Grade B)
•  Palpate testes for quality and position at each recommended well-child visit. (Standard; Evidence Strength: Grade B)
• Refer infants with a history of cryptorchidism (detected at birth) who do not have spontaneous testicular descent by 6 months (corrected for gestational age) to an appropriate surgical specialist for timely evaluation. (Standard; Evidence Strength: Grade B)
• Refer boys with possible newly diagnosed (acquired) cryptorchidism after 6 months (corrected for gestational age) to an appropriate surgical specialist. (Standard; Evidence Strength: Grade B)
• Immediately consult an appropriate specialist for all phenotypic male newborns with bilateral, nonpalpable testes for evaluation of a possible disorder of sex development (DSD). (Standard; Evidence Strength: Grade A)
• Do not perform ultrasound (US) or other imaging modalities in the evaluation of boys with cryptorchidism prior to referral, as these studies rarely assist in decision making. (Standard; Evidence Strength: Grade B)
• Assess the possibility of a disorder of sex development (DSD) in cases of increasing severity of hypospadias with cryptorchidism. (Recommendation; Evidence Strength: Grade C)
•  In boys with bilateral, nonpalpable testes who do not have congenital adrenal hyperplasia (CAH), measure Müllerian Inhibiting Substance (MIS or Anti-Müllerian Hormone [AMH]) level), and consider additional hormone testing, to evaluate for anorchia. (Option; Evidence Strength: Grade C)
• In boys with retractile testes, assess the position of the testes at least annually to monitor for secondary ascent. (Standard; Evidence Strength: Grade B)

The AUA guidelines recommend against the use of hormonal therapy to induce testicular descent, due to low response rates and lack of evidence for long-term efficacy. (Standard; Evidence Strength: Grade B). AUA recommendations for treatment by surgical specialists are as follows:

• If spontaneous testicular descent has not occurred by 6 months (corrected for gestational age), perform surgery within the next year. (Standard; Evidence Strength: Grade B)
•  In prepubertal boys with palpable, cryptorchid testes, perform scrotal or inguinal orchidopexy. (Standard; Evidence Strength: Grade B)
• In prepubertal boys with nonpalpable testes, perform examination under anesthesia to reassess for palpability of testes. If nonpalpable, surgical exploration—and, if indicated, abdominal orchidopexy—should be performed. (Standard; Evidence Strength: Grade B)
• At the time of exploration for a nonpalpable testis in boys, identify the status of the testicular vessels to help determine the next course of action. (Clinical Principle)
• In boys with a normal contralateral testis, consider performing orchiectomy (removal of the undescended testis) if a boy has a normal contralateral testis and either very short testicular vessels and vas deferens, dysmorphic or very hypoplastic testis, or postpubertal age. (Clinical Principle)

The AUA advises that providers should counsel boys with a history of cryptorchidism and/or monorchidism, and their parents, regarding potential long-term risks and provide education on infertility and cancer risk. (Clinical Principle)

European guidelines

Guidelines on cryptorchidism from the European Association of Urology and the European Society for Paediatric Urology include the following recommendations^[58] :

• Do not offer medical or surgical treatment to boys with retractile testes but follow up closely until puberty (Level of Evidence [LE] 2a, Grade A)
• Offer surgical orchidolysis and orchidopexy before the age of 12 months, and by 18 months at the latest (LE 2b, Grade B)
• Evaluate male neonates with bilateral non-palpable testes for possible DSDs (LE 1b, Grade A)
• In boys with non-palpable testes and no evidence of DSDs, offer laparoscopic intervention because of its excellent sensitivity and specificity in identifying an intra-abdominal testis, as well as the possibility for subsequent treatment in the same session (LE 1a, Grade A)
• Do not routinely offer hormonal therapy, either in an adjuvant or neo-adjuvant setting, for testicular descent; patients have to be evaluated on an individual basis (LE 2a, Grade C)
• In cases of bilateral undescended testes, offer endocrine treatment to possibly improve further fertility potential (E 4, Grade C)
• For an undescended testis in a post-pubertal boy or older who has a normal contralateral testis, discuss removal with the patient/parents because of the theoretical risk of a later malignancy (LE 3, Grade B)

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