Editing Undescended Testicle

'''See [[AUA: Cryptorchidism (2018)|2018 AUA Guidelines on Cryptorchidism/Undescended Testicle]]'''

'''Includes 2017 CUA UDT Guidelines'''

See [https://www.youtube.com/watch?v=-VSyortn7YQ Video Lecture (Dr. Doug Storm)]

== Embryology of Testicular Development ==

=== Differentiation of the Testis ===
* '''<span style="color:#ff0000">Gonads are first identified at 32 days (≈4.5 weeks)''' in humans.
** '''<span style="color:#ff0000">At this sexually indifferent stage, the gonads and the internal and external genitalia are identical in males and females.'''
** '''<span style="color:#ff0000">Gonadal determination involves separate genetic pathways for development of testis and ovary.'''
*** '''<span style="color:#ff0000">SRY (sex-determining region on the Y chromosome) is a master switch in males that regulates downstream testis-determining genes.'''
* '''<span style="color:#ff0000">By 6 weeks’ gestation, primordial germ cells</span>''' migrate from the yolk sac and '''<span style="color:#ff0000">differentiate into gonocytes</span>'''
* '''<span style="color:#ff0000">In males, expression of SRY begins at 41 to 44 days (≈6 weeks) followed by the histologic appearance of Sertoli cells'''
** '''<span style="color:#ff0000">SRY expression in the indifferent gonad triggers testicular development.'''
** SRY is important for Sertoli cell specification, but downstream testis-determining genes are required for Sertoli cell differentiation and proliferation
* '''<span style="color:#ff0000">Fetal Sertoli cells produce anti-müllerian hormone (AMH) (also called müllerian inhibiting substance [MIS]) soon after they differentiate'''
** Fetal and early postnatal Sertoli cells lack androgen-receptor expression.
*** Precense of androgen-receptor on Sertoli cells would allow inappropriate androgen-induced inhibition of AMH production and precocious stimulation of spermatogenesis.
** '''<span style="color:#ff0000">The process of müllerian regression occurs at 9 to 10 weeks'''
*** The early development of the external genitalia in the two sexes is relatively similar before the 9th week of gestation.
** '''AMH levels remain high during childhood and are downregulated at puberty.'''

=== Testicular Hormone Production ===
* Critical for masculinization of the reproductive tract and testicular descent
* '''In the fetus, Leydig cell development is divided into 3 phases:'''
*# '''Proliferation and differentiation phase at 7-14 weeks’ gestation'''
*# '''Maturation phase until 18 weeks’ gestation'''
*# '''Involution phase that continues until term'''
* '''<span style="color:#ff0000">Synthesis of testosterone by fetal Leydig cells starts as early as 6 to 7 weeks’ gestation and appears to be initially independent of gonadotropin stimulation.'''
** '''Placental human chorionic gonadotropin (hCG) stimulates a peak in androgen production by fetal Leydig cells at 14-16 weeks, and the testis then becomes responsive to fetal luteinizing hormone (LH)'''
* '''<span style="color:#ff0000">At 9-13 weeks of gestation, dihydrotestosterone (DHT) simulates androgen receptors in the'''
*# '''<span style="color:#ff0000">Genital tubercle to differentiate into penis'''
*# '''<span style="color:#ff0000">Urethral folds to differentiate into the ventral aspect of penis'''
*# '''<span style="color:#ff0000">Labioscrotal swellings to differentiate into scrotum'''
*#* '''Also known as genital swellings or labioscrotal folds'''§
*#* The labioscrotal swellings are first visible at 7 weeks and fuse by 10-12 weeks
* '''<span style="color:#ff0000">By the end of the first trimester (12 weeks), the external genitalia are completely masculinized'''
* '''Locally produced estrogen may play a role in testis development'''

== Normal testicular descent ==

* '''Factors contributing to descent (5):'''
*# '''Testis'''
*# '''Genitofemoral nerve'''
*# '''Hormones'''
*# '''Gubernaculum'''
*# '''Processus vaginalis'''
** '''Genitofemoral nerve'''
*** Origin: L1, L2
*** Motor: genital branch innervates cremesteric muscle
*** Sensory: genital branch provides sensation from anterior scrotum; femoral branch provides sensation from upper anterior thigh
** '''Hormones'''
*** '''Descent is regulated by 2 Leydig cell hormones:'''
***# '''Insulin-like 3 (INSL3)''' via its receptor relaxin/insulin-like family peptide receptor 2 (RXFP2)
***# '''Androgens (testosterone)''' via the androgen receptor (AR)
**** Downstream pathways are poorly defined
**** '''These hormones peak at 14-17 weeks and stimulate development of the gubernaculum and testicular descent in the second and third trimesters'''
**** '''Altered expression or function of key molecules that participate in testicular and/or gubernacular development could potentially contribute to an increased risk of cryptorchidism'''
** '''Gubernaculum'''
*** '''Caudal gonadal ligament that faciltates gonadal descent in both sexes'''
**** No cranial gonadal ligament exists in humans as noted in other species
*** '''Develops in both sexes beginning at 7 weeks’ gestation'''
*** '''Swelling of the gubernaculum, which starts in the second trimester, provides space for passage of the testis'''
* '''<span style="color:#ff0000">The testis passes into the inguinal canal at 20 to 28 weeks’ gestation'''
** '''<span style="color:#ff0000">Majority of testes are scrotal by 27 weeks'''
** '''Time spent in the inguinal canal seems to be limited for the majority of human fetal testes'''

== Definitions ==

* '''Normal scrotal position: positioning of the midpoint of the testis at or below the midscrotum'''
* '''Undescended testis (UDT) or cryptorchidism: inability to palpate the testicle in the expected normal anatomical position''' (i.e., within its respective hemi-scrotum)
* '''<span style="color:#ff0000">May be palpable or non-palpable'''
** '''<span style="color:#ff0000">The majority (80%) of UDT palpable and are unilateral (60-70%)'''
*** '''<span style="color:#ff0000">Involvement of the right side is more common overall  '''
**** '''Attributed to the later descent of the right testicle'''
** '''<span style="color:#ff0000">Non-palpable testis can be either undescended or absent'''
*** '''<span style="color:#ff0000">Absent testicle can be either vanishing (most common) or agenesis'''
**** '''<span style="color:#ff0000">Vanishing: testicle was present initially in development but becoming lost as a result of vascular accident or spermatic cord torsion,''' unilaterally (monorchia) or, very rarely, bilaterally (anorchia), '''occurring after completion of genital masculinization''' but before fixation of the testis in the scrotum
***** '''The processus vaginalis is closed in most cases of vanishing testis.'''
**** '''<span style="color:#ff0000">Agenesis: testis that was never present and therefore is associated with ipsilateral müllerian duct persistence'''
* '''<span style="color:#ff0000">Recurrent cryptorchidism: cryptorchid testes that were undescended at birth, descended spontaneously, and are subsequently defined as extra-scrotal'''
* '''<span style="color:#ff0000">Secondary cryptorchidism and testicular retraction: testes that are supra-scrotal after inguinal hernia repair and as a complication of orchidopexy, respectively.'''
** '''Testicular malposition after hernia repair could be caused by either post-operative scarring or primary maldescent'''
* '''<span style="color:#ff0000">Retractile testes: scrotal testes that retract easily out of the scrotum along the normal path of descent due to a brisk cremasteric reflex but can be manually replaced in a stable scrotal position and remain there at least temporarily until there is recurrent stimulation.'''

== Epidemiology ==

* '''<span style="color:#ff0000">One of the most common congenital anomalies'''
** '''<span style="color:#ff0000">Occurs in 1-4% of full-term and 1-45% of preterm newborn boys'''
** '''Following spontaneous decent, often seen in the first 3‒6 months of life, prevalence stabilizes at 0.7–1.0% by age 1'''
* '''Majority of cases are isolated''' '''(ratio of non-syndromic:syndromic UDT > 6:1)'''

== Pathogenesis ==

* '''<span style="color:#ff0000">Classified congenital vs. acquired'''
** '''<span style="color:#ff0000">Distinction based on findings documented during the neonatal exam.'''
*** In congenital cases, the testicle is not palpable in the scrotum at birth
*** In acquired cryptorchidism (or “ascending” testicle) is in a normal location at birth (or on subsequent well-child exams), but not later in life.

=== Congenital ===
* '''<span style="color:#ff0000">Perinatal risk factors (4):'''
*# '''<span style="color:#ff0000">Prematurity'''
*# '''<span style="color:#ff0000">Low birth weight or small size for gestational age'''
*# '''<span style="color:#ff0000">Breech presentation'''
*# '''<span style="color:#ff0000">Maternal diabetes'''
* '''<span style="color:#ff0000">Genetic susceptibility'''
** '''<span style="color:#ff0000">Family history</span>'''; susceptibility is likely polygenic and multifactorial
** Although multiple genetic variants likely contribute to the risk of non-syndromic cryptorchidism, most remain unknown at this time.
* '''<span style="color:#ff0000">Environmental risk factors (4):'''
*# '''<span style="color:#ff0000">Maternal smoking'''
*# '''<span style="color:#ff0000">Maternal use of acetaminophen'''
*# '''<span style="color:#ff0000">Abnormalities in pituitary and/or gonadal hormone secretion during infancy''' in the absence of generalized, persistent endocrine dysfunction
*# '''<span style="color:#ff0000">Environmental chemicals:</span>''' potential associations in selected populations but not strongly supported as a cause of increased susceptibility to cryptorchidism
* '''<span style="color:#ff0000">Syndromic Cryptorchidism'''
** '''Undescended testes are frequently present in diseases associated with reduced androgen production and/or action, such as androgen biosynthetic defects, androgen insensitivity, Leydig cell agenesis, and gonadotropin deficiency disorders'''
** '''Conditions associated with cryptorchidism'''
**# '''<span style="color:#ff0000">Persistent müllerian duct syndrome'''
**#* '''See [[Disorders of Sexual Differentiation]] Chapter Notes'''
**# '''<span style="color:#ff0000">Klinefelter syndrome'''
**#* '''See [[Disorders of Sexual Differentiation]] Chapter Notes'''
**# '''<span style="color:#ff0000">Down syndrome (trisomy 21)'''
**# '''<span style="color:#ff0000">Prune-belly syndrome'''
**# '''<span style="color:#ff0000">Prader-Willi syndrome'''
**# '''<span style="color:#ff0000">Noonan’s syndrome'''
**# '''<span style="color:#ff0000">Myelomeningocele'''
**# '''<span style="color:#ff0000">Posterior urethral valve'''
**# '''<span style="color:#ff0000">Cerebral palsy'''
**# '''<span style="color:#ff0000">Arthrogryposis'''
**# '''<span style="color:#ff0000">Spigelian hernia, omphalocele, gastroschisis, imperforate anus, umbilical hernia'''

=== Acquired ===
* Most likely represents a milder presentation of congenital cryptorchidism that escapes detection in infancy
* '''Diagnosed at an average age of 8 to 11 years'''
* '''More commonly in a lower position, associated with a closed processus vaginalis and normal epididymis, than in cases diagnosed as congenital.'''
* '''May be more likely in boys with retractile testes''' (scrotal testes that retract easily out of the scrotum but can be manually replaced in a stable scrotal position and remain there at least temporarily until there is recurrent stimulation), although testis retractility is common in normal populations

== Associated Pathology ==

* '''Testicular Maldevelopment'''
** Histological abnormalities that may be present in UDT include:
**# Delayed disappearance of gonocytes
**# Reduced numbers of adult dark (Ad) spermatogonia
**# Reduced number of germ cells per testicular tubule
**# Carcinoma in situ (CIS)
**# Microlithiasis
** '''The number of spermatogonia''' per tubule is reduced after infancy and '''fails to increase normally with age in the UDT and to a lesser degree in contralateral scrotal testes.'''
*** Ad spermatogonia counts may help define fertility potential
** '''<span style="color:#ff0000">Impaired transformation of gonocytes to spermatogonia</span>''' is often present after early infancy in cryptorchid testes.
*** Similar degree of pathology in true ectopic, superficial inguinal pouch, and ascending testes
** The undescended testis is smaller at birth and '''<span style="color:#ff0000">grows less well</span>''' than the scrotal testis, even if spontaneous descent occurs.
*** In an RCT, post-operative testicular growth was superior in boys undergoing orchidopexy at age 9 months vs. age 3 years.
** Some have '''reduced LH and/or testosterone levels during the postnatal surge'''
* '''Anomalies of the Epididymis in Non-Syndromic Cryptorchidism'''
** '''A normal epididymis is the most common finding in boys undergoing orchidopexy for acquired cryptorchidism'''
*** An abnormal ipsilateral epididymis was reported to 11-31% of acquired undescended testes at surgery
** '''Abnormal epididymal anatomic findings include (decreasing order of frequency):'''
**# '''Partial or complete non-fusion between the caput and/or cauda epididymis and the testis'''
**# '''Epididymal elongation and/or looping'''
**# '''Atresia'''
* '''Anomalies of the Processus Vaginalis and Gubernaculum in Non-Syndromic Cryptorchidism'''
** '''Failure of closure of the processus vaginalis and abnormal attachment of the gubernacular remnant are common in association with UDT.'''
** '''Anomalies of the tunica and processus vaginalis in cryptorchidism predispose to development of <span style="color:#ff0000">testicular torsion or clinical hernia</span>''', respectively, in rare cases.
*** Torsion of an UDT can occur at any age and may be confused with an incarcerated inguinal hernia.
* '''Other Testicular Anomalies Associated with UDT:'''
** '''Intra-testicular varicocele'''
** '''Polyorchidism'''
** '''Splenogonadal fusion'''
*** Characterized by continuous or discontinuous fibrous union between splenic tissue and the gonad
** '''Transverse testicular ectopia'''

== Rationale for treatment ==

* '''Surgical correction is offered early after diagnosis'''
* '''<span style="color:#ff0000">Long-term complicated of untreated UDT</span>'''
*# '''<span style="color:#ff0000">Hypogonadism</span>'''
*# '''<span style="color:#ff0000">Reduced fertility</span>'''
*#* Sperm counts are reduced in > 25% of formerly unilateral and the majority of formerly bilateral cryptorchid men
*#* '''Paternity rates are largely unchanged for men with unilateral cryptorchidism compared to the general population''' (≈90%), '''but are significantly lower (33‒65%) for those with bilateral UDT'''
*#* '''Both location and time of UDT correlate with Leydig and germ cell loss.'''
*#** '''Intra-abdominal/non-palpable testes depict severe germ cell loss, as do testes that remain undescended by age 2'''
*# '''<span style="color:#ff0000">Risk of testicular cancer</span>'''
*#* '''Relative risk (RR) of UDT: 2.75‒8x; risk is slightly increased also in the normally descended testis.'''
*#* '''Performing orchiopexy prior to puberty appears to decrease the RR of subsequent testicular cancer to 2.23, but it still remains above that of the normal non-cryptorchid male'''
*#* '''Pathology'''
*#** '''Persistent (untreated) UDT: seminoma more likely (74%)'''
*#** '''Scrotal (treated) testis: non-seminoma more likely (63%)'''
*#* '''The risk of benign testicular tumours (e.g. mature teratoma) is not increased with cryptorchidism'''
* '''<span style="color:#ff0000">Goals of treatment</span>'''
*# '''<span style="color:#ff0000">Maximize chances of adequate hormone production and future fertility potential</span>''' by preventing acquired/progressive damage
*# '''<span style="color:#ff0000">Prevent testicular torsion</span>'''
*# '''<span style="color:#ff0000">Locate testicle(s) in a position amenable to self-exam</span>''' (or caretaker/healthcare provider regular assessment in patients unable to reliably conduct self-examination) which aids in early diagnosis of testicular cancer
*# '''<span style="color:#ff0000">Treat associated conditions, such a patent processus vaginalis/inguinal hernia</span>'''
*# Avoid missing viable gonadal tissue in an abnormal location (most important intra-abdominal), as it could lead to delayed diagnosis of '''testicular neoplasm'''
*# Relocate all viable gonad(s) in scrotum to maximize '''psychological benefits of normal anatomy'''
*# '''<span style="color:#ff0000">Prevent direct testicular trauma</span>''' against the pelvic bones during intercourse or sports
*# '''Avoid unnecessary imaging studies'''
*# '''Minimize parental anxiety'''

== Diagnosis and Evaluation ==

=== History and Physical Exam ===

==== History ====
* '''<span style="color:#ff0000">History of prior testicular position''' 
**'''Genital exam by an experienced healthcare provider with good documentation of testicular position should be conducted in all newborn males.'''
***History provided by the patient's family is least useful to the provider in determining the diagnosis of retractile vs. UDT.

==== Physical Exam ====
* '''<span style="color:#ff0000">Physical exam should focus on the''' 
**'''<span style="color:#ff0000">Inguinal canal'''
**'''<span style="color:#ff0000">Scrotum'''
**'''<span style="color:#ff0000">Ectopic sites (see below)'''
*'''<span style="color:#ff0000">Position: examine child in the supine and, if possible, upright cross-legged and standing positions'''
** '''Abduction of the thighs contributes to inhibition of the cremasteric reflex''', which is elevation of the testis that is elicited by scratching the inner thigh.
* '''<span style="color:#ff0000">Helpful maneuvers to facilitate exam:'''
*#'''<span style="color:#ff0000">Quiet room'''
*#'''<span style="color:#ff0000">Patient distraction'''
*#'''<span style="color:#ff0000">Warm room and hands'''
*#'''<span style="color:#ff0000">Use of lubrication/liquid soap on the examiner’s hands'''
*'''<span style="color:#ff0000">Distinguish between a normally located gonad, retractile testicle, palpable undescended/ectopic testicle, and non-palpable testicle.'''
** '''<span style="color:#ff0000">Assess testicular palpability</span>''', position, mobility, size, and possible associated findings such as hernia, hydrocele, penile size, scrotal asymmetry, and urethral meatus position.
***'''<span style="color:#ff0000">Palpable'''
**** '''<span style="color:#ff0000">Testicle may be:'''
***** '''<span style="color:#ff0000">Anywhere along the line of normal descent between the abdomen and scrotum ("true" undescended)'''
***** '''<span style="color:#ff0000">Ectopic, such as (7):'''
*****# '''<span style="color:#ff0000">Anterior to the rectus abdominus muscle (also called the superficial inguinal pouch)'''
*****#* '''<span style="color:#ff0000">Most common site of ectopic testicle'''
*****# '''<span style="color:#ff0000">Perirenal'''
*****# '''<span style="color:#ff0000">Prepubic'''
*****# '''<span style="color:#ff0000">Femoral'''
*****# '''<span style="color:#ff0000">Peripenile'''
*****# '''<span style="color:#ff0000">Perineal'''
*****# '''<span style="color:#ff0000">Contralateral scrotal position'''
**** '''Careful examination of these areas is needed to correctly classify a testis as palpable or non-palpable,''' a critical step that influences further diagnosis and treatment
**** '''Perirenal or other abdominal testes may be associated with multicystic dysplastic or absent ipsilateral kidneys and/or nonunion of the testis and epididymis'''
**** '''Determine the lowest position the testis may attain'''
***'''<span style="color:#ff0000">Non-palpable'''
****'''<span style="color:#ff0000">Possible clinical findings at surgery include (3):'''
****# '''<span style="color:#ff0000">Abdominal or transinguinal “peeping” location (25-50%)'''
****# '''<span style="color:#ff0000">Complete atrophy (vanishing testis, 15-40%)'''
****# '''<span style="color:#ff0000">Extra-abdominal location but nonpalpable testis because of body habitus, testicular size, and/or limited cooperation of the patient (10-30%)'''
*'''<span style="color:#ff0000">Evaluate contralateral testicle'''
**'''In patients with unilateral cryptorchidism, evaluation of the contralateral gonad is important in order to detect potential problems with the normally located testicle (such as atrophy, varicocele, abnormal volume, or consistency for age).'''
** '''Testicular hypertrophy, most often suspected when the axial length of the testicle is > 1.8‒2 cm),is associated with a higher likelihood of an absent or atrophic non-palpable gonad.'''
*'''<span style="color:#ff0000">Assess for associated abnormalities'''
**'''<span style="color:#ff0000">Inguinal hernia'''
**'''<span style="color:#ff0000">Hypospadias'''
**'''<span style="color:#ff0000">Ipsilateral scrotal hypoplasia'''
* '''<span style="color:#ff0000">CAUTION: A virilized newborn with bilateral non-palpable gonads should be considered to be 46XX with congenital adrenal hyperplasia (CAH) until proven otherwise.'''

=== Labs ===
* '''<span style="color:#ff0000">Karyotype'''
** '''<span style="color:#ff0000">Routine karyotype or genetic workup of patients with UDT is not recommended'''
*** '''The incidence of karyotype or other genetic abnormalities in boys with cryptorchidism is low'''
** '''<span style="color:#ff0000">Indications for karyotype in UDT (2):'''
**# '''<span style="color:#ff0000">Bilateral non-palpable UDT and a normal phallus with an orthotopic urethral meatus'''
**#* '''A phenotypically male newborn with bilateral non-palpable testicles should be considered to be a genetic female with congential adrenal hyperplasia (21-hydroxylase deficiency) until proven otherwise'''
**#** '''If XX karyotype found, obtain 17-hydroxy-progesterone levels (elevated in congential adrenal hyperplasia )'''
**#** '''If XY karyotype found, the diagnosis of bilateral vanishing testicles/testicular regression syndrome (anorchia) should be considered.'''
**#*** '''In such patients, the combination of high gonadotropins, low testosterone levels (even after hCG stimulation), and very low or undetectable levels of anti-Mullerian hormone and inhibin B may preclude any surgical intervention.'''
**#**** '''In most cases, laparoscopic or surgical abdominal exploration is performed [regardless of hormonal levels], although hormone testing can also be useful and may be sufficient for the diagnosis of anorchia.'''
**#**** '''hCG stimulation is no longer the test of choice for anorchia because it is not well standardized and has the potential for side effects and inaccuracy'''
**# '''<span style="color:#ff0000">At least one UDT (particularly if non-palpable) and proximal hypospadias'''
**#* '''≈1/3 of these patients have a DSD'''
**#* '''DSD has not been observed in patients with UDT and distal hypospadias'''
**#* '''Hypospadias is associated with cryptorchidism in 12-24% of cases'''
**#* WT1 mutations have been identified in 7.5% of males with proximal hypospadias and at least one UDT who were tested. '''Targeted WT1 genetic testing in patients with proximal hypospadias and at least one UDT should be considered'''
** '''Routine circumcision should be delayed until evaluation confirms a genetically normal male.'''
* '''If small penile size: testosterone, LH, and FSH levels can facilitate early identification of hormone deficiency or anorchia in the first few months of life and allow early treatment'''
** '''Micropenis''' '''was reported in 46% of boys with anorchia''' '''caused by bilateral vanishing testes'''
** Small penile size associated with cryptorchidism is also observed in '''hypogonadotropic hypogonadism'''
** Contralateral testicular hypertrophy and a palpable scrotal nubbin may present in boys with unilateral vanishing testis and increase serum FSH and micropenis may be seen in boys with bilateral vanishing testes.

=== Imaging ===
* '''Not indicated for diagnosis of the non-palpable testis'''
** '''Has limited accuracy''' (sensitivity and specificity of US in localizing the nonpalpable testis are 45% and 78%, respectively) to confidently rule out the presence of intra-abdominal viable gonadal tissue, '''is not cost-effective, may delay referral and surgical treatment, and does not obviate the need for definitive surgical intervention.'''
**'''Ultrasound evaluation is not a substitute for a well-performed exam''' '''and it does not add diagnostic accuracy to an evaluation by a less experienced healthcare provider or a limited exam due to an uncooperative child.'''
** Imaging studies that require sedation or anesthesia (such as MRI), regardless of the diagnostic performance of the test, do not have any therapeutic value. Thus, under most circumstances, surgical exploration is not avoided and a second anesthetic will be required for treatment.
** The use of imaging modalities that employ ionizing radiation (such as CT scans) should be avoided
** '''Imaging tests may have potential merit solely in directing the best initial approach (e.g. scrotal vs. inguinal vs. laparoscopic exploration).'''

=== Other ===

==== Diagnostic Laparoscopy ====
* '''Diagnostic laparoscopy, followed by laparoscopic orchidopexy if an abdominal testis is present, has become the preferred approach to the non-palpable testis for many clinicians.'''
** '''Laparoscopy is preceded by an examination under anesthesia, which may be a useful adjunct that helps to define the appropriate course of action.'''
*** '''The gold standard for diagnosis ofUDT remains careful examination of a child in several positions and confirmation of incomplete descent of the testis to a dependent scrotal position after induction of anesthesia.'''
**** '''Preoperative testicular position correlates poorly with intraoperative findings'''
** '''Laparoscopy is the procedure of choice to confirm or exclude the presence of a viable or remnant abdominal testis, UNLESS a prominent scrotal nubbin is palpable with other clinical signs of monarchism, such as contralateral testicular hypertrophy (testicular length ≥1.8 cm)''' 
* Important laparoscopic observations include the size and position of the spermatic vessels and vas; testicular size, quality, and position if visible; and patency of the internal inguinal ring.
* '''A hernia is frequently but not always associated with a viable abdominal or distal testis.'''

== Management ==

=== Options ===
*'''Observation''' 
**'''Indications (1)'''
***'''First 6 post-natal months (corrected for gestational age) to allow spontaneous testicular descent'''
**** No strong evidence in support of observation as the recommended approach for cases of acquired cryptorchidism.
* '''Medical Therapy'''
** '''Hormone therapy is not recommended'''
***Lack of rigorous data supporting its efficacy
* '''Surgery (orchiopexy/orchidopexy)'''
**'''If spontaneous testicular descent does not occur, surgical treatment after 6 months of (corrected gestational) age is indicated.'''
*** In boys with a history of prematurity, spontaneous descent may be delayed, and therefore observation is continued for 6 months beyond the expected date of delivery or, especially if testicular position is marginal, until a year of age.
*** '''After spontaneous testicular descent, continued observation is needed because of the risk for recurrent cryptorchidism or testicular re-ascent'''
**'''Timing of Surgery'''
***'''Orchidopexy is recommended between 6-18 months of age'''
**** '''Testicular descent is unlikely to occur in full-term babies after 6 months of age'''
**** '''Consider surgical morbidity, comorbidities, life expectancy, and fertility expectations in special situations'''
***** '''UDT is associated with a multitude of syndromes, some of which can lead to limited life expectancy and/or severe developmental delay (e.g., Down’s, Prader-Willi, and Noonan’s syndromes)'''
***** Given the reports of testicular cancer (sometimes at an early age) in these patients, '''we recommend orchidopexy when they are clinically fit for anesthesia for the purpose of surveillance'''

=== Orchiopexy/Orchidopexy ===

==== Surgical Approach to the Palpable Testis ====
* '''<span style="color:#ff0000">Options (2):</span>'''
*#'''<span style="color:#ff0000">Inguinal</span>''' (with repair of an associated hernia if present)
*#*Traditional approach
*#'''<span style="color:#ff0000">Pre-scrotal/scrotal orchidopexy</span>'''
* '''High (proximal) ligation of the processus vaginalis is an essential surgical step to allow placement of the testis in a sub-dartos pouch within the hemi-scrotum, without tension'''
* '''<span style="color:#ff0000">Inguinal'''
** '''<span style="color:#ff0000">Maneuvers to provide spermatic cord length include (4):'''
**# '''<span style="color:#ff0000">Divide lateral fascial bands along the cord and at the internal inguinal ring'''
**# '''<span style="color:#ff0000">Blunt dissection of the cranial retroperitoneal spermatic vessels'''
**# '''<span style="color:#ff0000">Medial transposition of the testis beneath the epigastric vessels (Prentiss maneuver)'''
**# '''<span style="color:#ff0000">Cranial extension of the incision'''
*** '''Very rarely, the testis cannot be brought to dependent scrotal position after these maneuvers and a''' '''Fowler-Stephens (FS) orchidopexy''' '''may be considered''' as an alternative to orchiectomy, which is preferentially reserved for visibly abnormal or atrophic testes, postpubertal patients, or cases associated with insufficient vasal length.
**'''Complications'''
*** '''Uncommon'''
*** '''Serious complications include testicular retraction and atrophy'''
** '''A minimum of 6 months’ follow-up is recommended to determine postoperative testis position and size.'''
*** Long-term follow-up should be considered for counseling of the patient regarding fertility issues, risk of testicular malignancy, and self-examination.
** Torsion of a scrotal testis after orchidopexy has been reported but is very rare, and the risk may be minimized by routine extravaginal testicular fixation in a subdartos pouch.
** If complete intrascrotal testicular atrophy occurs postoperatively, further intervention is not needed, but the option of testicular prosthesis placement should be offered to the patient and family.
*** Implantation of a testicular prosthesis should occur at least 6 months after any scrotal procedure or after puberty and is best performed through an inguinal approach.
*** Fixation of the prosthesis to the dartos and closure of the scrotal fascia above the implant using purse-string nonabsorbable suture are required.
*** Complications including displacement, pain, or infection occur in < 5% of cases.
* '''Scrotal'''
** Used selectively in many series; '''efficacy and complication rates are similar to those of standard inguinal orchidopexy'''

==== Surgical Approach to the Non-palpable Abdominal Testis ====
* '''If the testicle is not palpable preoperatively, as may occur in up to 20% of UDT cases, examination under anesthesia (EUA) can sometimes allow identification of the testicle. Otherwise, diagnostic laparoscopy is the procedure of choice in most centres.'''
** '''In certain non-palpable testicle cases, confident palpation of an ipsilateral scrotal nubbin and identification of contralateral compensatory testicular hypertrophy may preclude diagnostic laparoscopy by means of initially performing a scrotal incision, which allows for testicular nubbin removal and confirmation of the vanishing testicle diagnosis'''. Inguinal exploration and/or laparoscopy can then be reserved for cases in which the initial scrotal approach is non-diagnostic.
*** '''It is critical to highlight the importance of confidently identifying atrophic testicular tissue with associated vas deferens and gonadal vessels if a scrotal or inguinal approach is chosen, as any doubt should trigger further exploration.''' Presence of a looping vas or incorrectly identifying non-gonadal tissue as a nubbin may lead to misdiagnosis, potentially leaving viable testicular tissue in the abdomen'''. In uncertain cases or when tissue analysis is not consistent with atrophic testicular tissue, laparoscopic exploration should be strongly considered'''
* '''<span style="color:#ff0000">Diagnostic laparoscopy'''
** '''<span style="color:#ff0000">Potential findings:'''
**# '''<span style="color:#ff0000">Blind-ending vas and vessels confirms a vanishing intra-abdominal testicle (IAT), and no further exploration is necessary''' (10‒30% of cases).
**#* '''An atretic spermatic cord coursing through a closed inguinal ring is suggestive of a distal vanishing testis, but this finding may be subjective and, conversely, normal appearing vessels may be associated with both viable and vanishing testes'''
**# '''<span style="color:#ff0000">Testicular vessels and vas entering the inguinal canal through the internal inguinal ring.'''
**#* '''Inguinal exploration may find a healthy palpable UDT amenable to standard orchidopexy, or a testicular nubbin either in the inguinal region or, most commonly, in the scrotum.''' Remnant cord structures are usually removed to confirm the diagnosis and because viable residual testicular elements are present in up to 14% of the cases. It should be noted that to date, no cases of intratubular germ cell neoplasia have been reported within these specimens.
**# '''<span style="color:#ff0000">Peeping (just inside internal ring) or intra-abdominal testis (50%), which will require either an open or a laparoscopic orchidopexy in one or two stages.'''
*** '''If neither vas nor spermatic artery is found at the time of laparoscopy, dissection of the perivesical area and retroperitoneum up to the level of the kidney is required for exclusion of the presence of a testis, because true agenesis is extremely rare'''
**** '''If both testes are non-palpable and not distal to the internal inguinal ring in a genetic male, > 95% are abdominal'''
** '''Therefore, if laparoscopy does not unequivocally localize the testis or blind-ending spermatic artery, additional surgical exploration is needed for definitive diagnosis. This may be performed laparoscopically after the placement of additional working ports.'''
* '''Primary orchidopexy without transection of the spermatic vessels is preferable whenever possible'''
** Pooled success rates for primary, one-stage Fowler-Stephens and two-stage Fowler-Stephens procedures are ≈95%, 80%, and 85%, respectively.
* '''The feasibility of primary vs. Fowler-Stephens orchidopexy depends on the length of the vas and vessels, presence or absence of looping ductal structures, and age of the patient.'''
** Observed testicular position alone may correlate poorly with the ultimate length of the cord after mobilization.
* '''Fowler-Stephens orchidopexy'''
** Originally described as a single-stage open inguinal approach for the intra-abdominal testis in which the testicular artery and veins were too short to allow adequate testicular mobilization into the scrotum through standard orchidopexy
** '''The major steps are (4):'''
**# '''Mobilization of any structures extending distal to the internal ring'''
**# '''Transection of the peritoneum lateral to the vessels and distal to the vas'''
**# '''Proximal mobilization of the vessels while maintaining collateral blood supply between the vas and spermatic vessels.  '''
**#* '''The peritoneum should be left intact over the vasal vessels, and the gubernacular vessels should be left intact if possible'''
**# '''Once mobilized, the testis is brought through a new hiatus medial to the epigastrics and lateral to the medial umbilical ligament or through the existing internal inguinal ring.'''
**#* Recall that medial umbilical ligament containst the obliterated umbilical artery
** '''Principles:'''
*** '''Open approach'''
**** '''Ligating and dividing the testicular vessels'''
**** '''Preserving the''' '''distal gubernacular attachments and the collateral vessels on the floor of the inguinal canal, maintaining the cremasteric blood supply'''
*** '''Laparoscopic approach'''
**** '''Ligating and dividing the testicular vessels and cremasteric collaterals'''
**** '''Preserving the gubernaculum''', mimicking one of the surgical steps of the open FS technique, may help decrease the likelihood of testicular atrophy
**** '''Testicle is advanced medial to the inferior epigastric vessels or obliterated umbilical artery'''
**** '''An inguinal hernia or patent processus vaginalis does not require formal repair at the time of laparoscopic orchidopexy.'''
*** '''In general, the preferred approach is avoidance of spermatic vessel transection whenever possible; the available data suggest this is possible in the majority of cases of abdominal orchidopexy.'''
*** '''When the testis is > 2 cm above the internal ring with no vascular redundancy, it is unlikely that the testis will be able to reach the scrotum without dividing the spermatic vessels. In this situation, staged Fowler-Stephens procedure with division of the gonadal vessels at the first stage has a significantly higher success rate than single-stage Fowler-Stephens procedure'''
** '''Open vs. laparoscopic orchidopexy for NPT'''
*** '''The Fowler-Stephens procedure is now typically performed laparoscopically''' with spermatic vessel clipping followed by laparoscopic or open testicular mobilization in the same setting (one-stage, or in a staged approach 6 months later (two-stage).
*** Laparoscopic orchidopexy outcomes are comparable to those of open surgery
*** '''Laparoscopic approach is associated''' with shorter operative time, shorter return to normal activities, '''and reduced risk of atrophy at one year (10% laparoscopic vs. 19% open)'''

* '''Complications'''
** '''Complications of laparoscopic orchidopexy are rare and potentially include bladder or vascular injury, hypercapnia, delayed small bowel obstruction, testicular ascent''', where the testicle gets pulled to the entrance of the scrotum, '''and vas deferens injury'''.
** '''The most serious complication of inguinal orchidopexy is testicular atrophy, which occurs when the testicular vessels are damaged'''
** Other orchidopexy related complications might include those associated with any surgical procedure, such as wound infection, dehiscence, and hematoma.
* '''Prophylactic contralateral orchidopexy'''
** '''Contralateral fixation of a solitary testis in cases of monarchism is advocated by some but not universally supported.'''
** In the absence of literature strongly supporting or discouraging prophylactic orchidopexy, '''the decision should be made based on informed discussion of options with the patient parents or legal guardian'''
*** The need for excision [of a testicular remnant] and contralateral scrotal orchidopexy in vanishing testis cases remains controversial. The risk of malignancy is [of the remnant] unknown.
*** Preventive orchidopexy of the normally descended contralateral testicle in the setting of blind-ending spermatic vessels found upon exploration of a non-palpable testis has been advocated by some authors, based on the reported risk of bell-clapper deformity and abnormal testicular fixation found in the remaining solitary testis.
*** The risk of torsion is admittedly low, conceptually not different from the general population.
* '''Testicular biopsy is not indicated at the time of orchidopexy'''

== Follow-up ==

* '''Redo orchidopexy is recommended for cases where inadequate position is detected postoperatively'''
* Although UDT are unquestionably associated with a higher risk for development of testicular cancer, the incidence rates of this type of cancer are small and hence '''no screening policy is justified'''.
* '''There is no need for formal long-term urological follow-up of patients with UDT.'''
* '''Periodic self-exam after puberty is recommended''' with prompt referral to an urologist if an abnormality is noted.

== Age at which orchiectomy is advisable over orchidopexy ==

* '''Orchiectomy is an option for pubertal and post-pubertal boys, and remains the treatment of choice for the majority of post-pubertal males presenting with unilateral cryptorchidism especially if the testis is:'''
*# '''Abdominal or difficult to mobilize'''
*# '''Small in size (hypotrophic/atrophic).'''
** Most of these testes demonstrate
*** Poor spermatogenesis (Sertoli only syndrome).
*** Risk of torsion
*** Significant malignant potential
* '''Observation of a hypotrophic/atrophic UDT is appropriate if patient age > 50'''
** At age 50 for ASA class I and II cases, risk of operative mortality exceeds the risk of mortality from germ cell cancer§

== Acquired cryptorchidism ==

* Acquired UDT are diagnosed at an average age of 8‒11 years.
* The percentage of retractile testicles that ascends and requires orchidopexy is difficult to estimate, ranging from 3‒30% in prepubertal children. It is difficult to set a specific age for correction of these cases because it may vary from child to child.

== Questions ==

# When are the gonads first identified?
# When is Mullerian regression usually complete by?
# When do fetal testosterone levels peak?
# When are the testicles usually in the scrotal location?
# What structures do the genital tubercle, urethral folds, and labioscrotal swellings differentiate into in the male and female?
# List risk factors for undescended testicle.

== Answers ==

# When are the gonads first identified?
#* 35 days
# When is Mullerian regression usually complete by?
#* 9-10 weeks
# When do fetal testosterone levels peak?
#* 14-16 weeks
# When are the testicles usually in the scrotal location?
#* 27 weeks
# What structures do the genital tubercle, urethral folds, and labioscrotal swellings differentiate into in the male and female?
# List risk factors for undescended testicle.

== References ==

* Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 4, chap 146
* Braga, Luis H., Armando J. Lorenzo, and Rodrigo LP Romao. "Canadian Urological Association-Pediatric Urologists of Canada (CUA-PUC) guideline for the diagnosis, management, and followup of cryptorchidism." ''Canadian Urological Association Journal'' 11.7 (2017): E251.