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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
mllerian-inhibiting substance (MIS), the level of which remains high throughout gestation and
causes regression of mllerian 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.
Epidemiology
Frequency
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
proven to be elusive.
Birth weight is the principal determining factor for undescended testes at birth to age one year,
independent of the length of gestation.
A recent 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 sibling is affected and 4.6 if father.
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.[4] A normal hypothalamicpituitary-gonadal axis is a prerequisite for testicular descent.[5] Furthermore, testosterone and its
conversion to dihydrotestosterone (DHT) are also necessary for continued migration, especially
during the inguinoscrotal phase.[6, 7, 8]
Different studies have found conflicting data regarding the involvement of mllerian-inhibiting
substance, prenatal estrogen exposure, and descendin (a specific gubernacular growth factor) in
the pathophysiology of cryptorchidism.[9, 10, 11]
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.[12] Both hormonal and mechanical
factors appear to mediate the aid of the gubernaculum and descent of the testis.[13] The
genitofemoral nerve may also aid in descent and gubernacular differentiation, which may be
mediated by calcitonin gene-related peptide.[14, 15]
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.[16, 17] 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.[18, 19]
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.[20]
Presentation
In cryptorchidism, the most useful determination is whether the testes are palpable upon physical
examination. Although this is seemingly self-explanatory, it is occasionally difficult to accurately
determine the exact location of the testis. Body habitus, testicular position, and compliance of the
child all are factors during the physical examination. Approximately 80% of undescended testes
are palpable and 20% are nonpalpable.[21] Nonpalpable testes may be intra-abdominal or absent.
Palpable testes may be undescended, ectopic, or retractile.
Approximately 20-30% of patients with cryptorchidism have nonpalpable testes. Most intraabdominal 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%.[22, 23] 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.[24] The results were as follows:
Physical examination
o Nonpalpable - 32.8%
o Above the tubercle - 11.8%
o At the tubercle - 34.7%
Surgery
o Intra-abdominal - 9%
o Peeping testis - 20%
o Tubercle - 42%
o Upper scrotum - 8%
o Superficial inguinal pouch (SIP)/ectopic - 12%
o Absent or atrophic - 9%
Abnormal epididymis
Cerebral palsy
Mental retardation
Wilms tumor
Hypospadias
Is or was the patient's mother on a vegetarian diet? Was the patient fed soy formula
during infancy?
Determine the prenatal history, including whether the patient's parents used an assisted
reproductive technique, whether his mother received hormonal treatment, and whether
there were multiple gestations.
Physical 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 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?
Indications
Correction of associated hernia: A patent processus vaginalis is found in more than 90%
of patients with undescended testis. [23, 20]
Younger than 32 years with a unilateral undescended testis and normal contralateral testis
- Orchiectomy
Older than 32 years with a unilateral undescended testis - Close observation and physical
examination (orchiopexy vs orchiectomy if difficult to examine)
This recommendation is based on the relative risk of testicular cancer along with the risks
associated with anesthesia. [41, 42]
Relevant Anatomy
The 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 inthe image below. The vas deferens
can be seen exiting the internal inguinal ring and crossing the median umbilical ligament (see
image below). The testicular vessels (ie, spermatic artery) can be seen entering the internal ring
from its origin off the aorta near the renal hilum.
Laboratory Studies
See the list below:
For unilateral undescended testis without hypospadias, no laboratory studies are needed.
Imaging Studies
See the list below:
Radiologic studies to localize the testis are currently of very little value. The overall
accuracy of radiologic testing for undescended testis is only 44%.[43] CT scanning and
ultrasonography yield high false-negative rates in the evaluation of a nonpalpable testis
and are not recommended. 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.
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.[44]
Abdominal and pelvic ultrasonography combined with genitography should be used when
intersexuality is suspected.
Medical Therapy
Cryptorchidism should be treated when the patient is aged approximately 6 months. 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 patients 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.[45, 46, 47] Regular reexamination of successful descent is necessary, as re-ascent can occur in up to 25% of treated
children.
Primary hormonal therapy with hCG (see choriogonadotropin alfa) or gonadotropin-releasing
hormone (GnRH or LH-releasing hormone [LHRH]) has been used for many years, especially in
Europe. In the United States, only hCG is currently available.
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
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.[52]
A 1995 meta-analysis of orchiopexy by Docimo revealed a location-based success rate of 92%
for tested located beyond the external ring, 82% for peeping and 87% for canalicular testes, and
74% for abdominal testes. Based on the surgical approach, the success rates were as follows:
89% for inguinal orchiopexy, 84% for microvascular orchiopexy, 81% for transabdominal
orchiopexy, 77% for staged Fowler-Stephens orchiopexy, and 67% for standard Fowler-Stephens
orchiopexy.[53]
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).[54]
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.
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 include (1) a subcutaneous
pouch with suture fixation versus a sutureless subdartos pouch, (2) absorbable versus permanent
suture, and (3) tunica vaginalis fixation versus tunica albuginea fixation. Bellinger et al (1989)[55]
and Dixon (1993)[56] 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 sutures) and placed with minimal depth
in the tough tunica albuginea.[57]
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, 3 main
features are likely to be encountered: (1) blind-ending spermatic vessels above the internal
inguinal ring (44%), (2) intra-abdominal testis (36%), and (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.[58] 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).
Laparoscopic management of the vanishing testis.
Jordan et al (1992) first described the technique of laparoscopic orchiopexy, and all modern
techniques are similar.[59] 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 FowlerStephens 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 1stage versus 2-stage Fowler-Stephens orchidopexies.
For laparoscopy-assisted orchiopexy, 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 success rate of
100% is reported from one small study population.
Microvascular orchiopexy allows adequate scrotal position with preservation of the spermatic
artery blood flow. However, it requires special expertise. The success rate is 84%.
Orchiectomy, either open or laparoscopic, is usually performed laparoscopically.
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.
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.
Complications
Complications of orchiopexy are as follows:
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.
Preperitoneal emphysema may develop secondary to poor needle or trocar placement and
insufflation.
The puncture of a viscus with the Veress needle is not harmful unless insufflated or
dilated by a trocar.
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.
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.[55]
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.[62] 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.[28] Neoadjuvant GnRH in prepubescent boys may also
positively affect future fertility, with the highest fertility indices reported with therapy before age
2 years.[63]
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.[64]
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.[65] 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.
Author
Joel M Sumfest, MD Director of Pediatric Urology, Janet Weis Children's Hospital, Geisinger
Medical Center; Vice Chairman, Department of Urology, Geisinger Medical Center
http://emedicine.medscape.com/article/438378-overview