Cryptorchidism (undescended testis/UDT) affects 1% of boys at one year of age, and is one of the most common congenital anomalies of the male genitalia. The mechanism of normal testicular descent was first described in 1786 when Hunter dissected a human fetus. He found that the intra-abdominal testis was connected to the inguino-abdominal wall by a ligament, which he called the gubernaculum testis because it appeared to steer the testis into the scrotum (1).
Although the etiology of cryptorchidism remains poorly understood, management has changed with recognition that hormonal treatment is ineffective and early surgery prior to 2 years of age leads to better testicular outcomes. Diagnostic laparoscopy is now a standard approach to impalpable testes, and can be combined with one or two-stage orchidopexy with up to 90% success rates.
The management of UDT in Africa is challenged by older presentations, lack of laparoscopic equipment and skills, few specialized pediatric centres, and difficult follow-up. Given its high incidence and the few African reports, it is likely that most African men with UDT are not treated. The impact of unilateral UDT on fertility is negligible, but the morbidity from associated incarcerated hernias, torsion, trauma and malignancy in men with untreated UDT may be significant.
This review is intended for all surgeons taking care of children, and it is expected that general surgeons in Africa should be trained to do orchidopexies. Some of the questions that remain controversial include:
These questions will be addressed in this review article.
Cryptorchidism means “hidden testis” and is synonymous with UDT, although most UDT are palpable. An undescended testis can be located anywhere between the abdominal cavity and the entrance of the scrotum, usually along its normal path of descent. Although rare, the testis may sometimes be located ectopically in the perineum, femoral triangle or penile shaft (Figure 1b). UDT is therefore the result of a developmental defect where the testis fails to descend completely into the dependent portion of the scrotum by the normal age of 6 months.
Fig 1a. Right undescended testis with scrotal hemihypoplasia
Figure 1b: Ectopic testis in penile shaft (courtesy Dr. Ameh)
Undifferentiated gonads are bipotential for either gender within the first 3 to 5 weeks of gestation. Differentiation of the testis is initiated by the SRY gene located in the short arm of the Y chromosome by week 7 of gestation. The SRY gene induces Sertoli cells to produce Müllerian Inhibiting Substance (MIS), which causes involution of Müllerian duct cells. During the 8th week of gestation, testicular androgens produced by fetal testicular Leydig cells and MIS produced by fetal testicular Sertoli cells are responsible for the development of normal male internal genitalia by weeks 10 to 13 of gestation.
The transabdominal descent of the testes takes place between 10 and 23 weeks of gestation under hormonal direction. The descending testicles move from the urogenital ridge to the inguinal region simultaneously with shortening of the gubernaculum, testicular differentiation, and eversion of the cremasteric muscle. The Leydig cell produced insulin-like hormone (Insl3) termed descendin mediates this transabdominal migration. (3) Its receptor, relaxin family peptide 2 (RXFP2 gene), is expressed on the gubernaculum.
The inguinoscrotal descent occurs between 24 and 34 weeks of gestation. This process is androgen dependent, and relies on testosterone and androgen receptors to move the testis from the inguinal canal to the scrotum. Androgens act on the genitofemoral nerve inducing the release of calcitonin gene-related peptide (CGRP), which promotes rhythmic contractions of the gubernaculum, leading to its extension and protrusion into the scrotal sac. (1) As the gubernaculum testis protrudes towards the scrotum it pulls the testis down into the same direction. In addition, the processus vaginalis - an evagination of the parietal peritoneum - elongates through the internal inguinal ring between the internal and external oblique muscles, creating a path for the descending testis to reach the scrotum. Once this process is complete, the inguinal canal is dilated by the gubernacular bulb and the testis pushed through the canal by increase in the intra-abdominal pressure. Premature boys are more likely to have UDT at birth, but most will descend to the scrotum by 6 months corrected gestational age. If the testis is not in the scrotum by 8 months of age, then it will not descend spontaneously.
A disruption in any phase of testicular descent triggered by hereditary, hormonal, anatomical (4), environmental, or social factors can result in cryptorchidism. (5)
One of the main risk factors for cryptorchidism is low birth weight, which suggests retarded intrauterine growth. Maternal risk factors associated with higher risk of UDT are: low birth parity, intrauterine insemination, complicated pregnancy such as pre-eclampsia, peripartum asphyxia, exposure to diethylstilbestrol (an anti-androgen) and nicotine during pregnancy.
Genetic alternations are 17 times more likely in boys with unilateral or bilateral UDT, including mutations in the Insl3 or RXFP2 genes. (6)(7) Cryptorchidism can present as part of chromosomal conditions, for example Klinefelter syndrome. A familial inheritance pattern has also been demonstrated for isolated cryptorchidism (2)(7). If a father or brother has UDT, the newborn male will have a 4-6 times relative risk of UDT.
Androgen receptor (AR) gene mutations can result in androgen resistance, and prevent the inguino-scrotal descent of the testes. If any form of androgen resistance or exposure to estrogens is present during the inguinoscrotal descent, bilateral testicular migration may be hindered resulting in disorders of sex development (DSD).
The following questions should be asked before evaluating a newborn with an UDT:
Was the baby premature? Was there maternal use or exposure to hormones during pregnancy? One should also ask about a family history of undescended testes, other congenital anomalies, precocious puberty, or consanguinity. Boys should be referred to a pediatric surgeon for evaluation if the testis has not descended by 6 months of age.
The most common challenge is to differentiate a retractile from a true undescended testis. The parent should be asked if they have ever seen the testis in the scrotum, for example when bathing the child. Retractile testes are often bilateral and are caused by an overactive cremasteric reflex, which pulls the testis out of the scrotum towards the inguinal canal especially when the child is cold. This is a normal condition, although a minority of retractile testes may later become fixed above the scrotum – the so-called ‘ascending testis’. There is controversy as to the incidence, significance, natural history and management of the ascending testis. (8) If in doubt, annual follow-up should be scheduled and orchidopexy considered if the testis has not descended before puberty.
The physical examination is still the most important step in making the diagnosis of UDT and distinguishing it from a retractile testis. The child should be examined supine, with his legs slightly separated. Hypoplasia of the ipsilateral side of the scrotum suggests a true UDT (Fig 1a). With warm hands, the surgeon should examine the size, location, and texture of the contralateral descended testis (if present). The UDT is then sought by gently advancing the fingers along the inguinal canal, sweeping the groin from lateral to medial. The inguinal testis may be felt to pop up under the fingers. If the testis is palpable, one should attempt to bring it down to the scrotum and hold it in the scrotum for about one minute to cause fatigue of the cremasteric muscle. If the testis remains in the scrotum after release, even momentarily, it is not undescended but retractile. However, if it instantly pops back, it is considered as true UDT. In overweight children, in whom palpation may be more challenging, sitting cross-legged may facilitate finding the testis. (7)
The most important distinction is between palpable vs. nonpalpable testis. Other terms used to describe the position of the palpable testis are ‘peeping’ (sliding in and out of the internal inguinal ring), canalicular, extra-canalicular (superficial inguinal pouch), suprapubic (high scrotal/gliding), (9) or ectopic. Non-palpable testes may be intra-abdominal, absent, or atrophic. Intra-abdominal testes are usually located just inside the internal ring, but may be anywhere between the lower pole of the kidney and the internal ring.
5.3. Laboratory investigations
In cases of unilateral cryptorchidism, lab work is unnecessary. Bilateral non-palpable testes warrant laboratory investigation to confirm the presence of testicular tissue and to rule out intersex disorders. Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels should be measured. (7)(2) After 3 months of age, a human chorionic gonadotropin hormone (HCG) stimulation test can be performed to evaluate testicular response by measuring testosterone levels. If LH and FSH are elevated but testosterone levels are below normal range, a diagnosis of anorchia can be confirmed.
No imaging is necessary if the testis is palpable. Ultrasound can misdiagnose retractile testes as undescended by triggering the cremaster reflex. Ultrasonography is reported to have a sensitivity of 76% in the diagnosis of non-palpable testis, but it does not alter the surgical approach so most surgeons consider it unnecessary. (10) Ultrasound may, however, be useful in obese patients. (7)
There are 6 reasons supporting early intervention for UDT, which is now recommended at 1-2 years of age (1). These are reduced fertility, risk of testicular malignancy, associated inguinal hernia, risk for testicular torsion or trauma, as well as psychological distress.
Any correlation of infertility with UDT must be tempered by the fact that 15-20% of all couples have difficulty conceiving, and there is often more than one factor. Paternity rates are unchanged for men with only one testis, but are lower (33-65%) for those with bilateral UDT. (2) The histology of the UDT is normal at birth and becomes progressively abnormal after 1 year of age, with 40% of UDT losing their germ cells by 2 years of age. (1) A randomized study found larger testicular volumes after orchidopexy was done at 9 months versus 3 years, suggesting that the testis, at least partly, loses its capacity for recovery if left out of the scrotum beyond 1 year of age. (11) Based on this histological evidence and the suggestion that early surgery may prevent or reverse it, most pediatric surgeons perform orchidopexy around 1 year of age. The European Association of Urology now recommends orchidopexy be performed at the latest by 12-18 months of age. (12)
6.2. Risk of testicular cancer
Testicular cancer is rare, with an incidence of 4.2/100,000 in Canada (13), and lifetime risk of 1 in 270 males. (http://seer.cancer.gov/statfacts/html/testis.html , accessed Feb 28/10) There has long been an association noted between UDT and testicular malignancy, with 11% of testicular cancers developing in men with a history of UDT. (14) Recent studies have found the Relative Risk (RR) of developing testicular cancer in a boy with UDT is 2.75-8, (15) corresponding to a lifetime risk of 1-3% (35). The risk is slightly increased also in the normally descended testis. (16) Performing orchidopexy prior to puberty decreases the RR of subsequent testicular cancer. (17)(18) It is recommended that unilateral inguinal and intraabdominal testes, identified after puberty, should be removed. (12) (15)
6.3. Risk of inguinal hernia, torsion, trauma, and psychological distress
About 90% of UDT are associated with a persistent processus vaginalis. An incarcerated hernia may risk ischemia and atrophy to an UDT, so hernias should be repaired when diagnosed and orchidopexy performed at the same time. (1)
Testicular torsion is more common in UDT because the inguino-scrotal attachments are looser. A testis in the inguinal canal may be subjected to blunt traumatic injury by compression against the pubic bone. Psychological distress is more likely in the parents than the pre-pubertal child, so parents should be reassured about the excellent outcomes for fertility and low risk of cancer in boys with unilateral UDT. A teenager with one testicle can be offered a testicular prosthesis.
Boys with unilateral UDT have been treated with human chorionic gonadotropin (HCG), gonadoropin-releasing hormone (GnRH) or LH-releasing hormone (LHRH) with resulting testicular descent in only 20%, less when the testicle is higher. (1)(12) Androgens are not used because they can trigger precocious puberty. Side-effects of HCG may include increased scrotal rugae and pigmentation of skin, increased pubic hair growth and penile growth, with high doses (more than 15000 IU) inducing epiphyseal plate fusion and retard future somatic growth.
Hormonal therapy may be considered in bilateral cryptorchidism, to distinguish retractile/ascending testis from undescended testes, or to improve collateral testicular blood supply during redo orchidopexy. (1) There is some evidence that intranasal GnRH may increase the fertility index of the testis if given preoperatively. (12)(2)
A meta-analysis of randomized controlled trials found success rates of 0-55% with HCG and 9-78% with GnRH. There was some advantage of HCG over GnRH, and for LHRH over placebo. However the conclusion was that hormonal treatment “cannot be recommended for everyone,” and that better RCTs are needed. (19) Orchidopexy remains the gold standard primary treatment for unilateral UDT. (2) “Considering the poor efficacy, possible side effects of the treatment and delay of definitive treatment (with the attendant sequelae of late treatment), the general use of HCG and GnRH in cryptorchidism cannot be recommended.” (Canadian Pediatric Surgical Wait Times Project: Clinical Practice Guidelines for Cryptorchidism – in press).
8.1. Surgery for the Palpable Testis
Palpable testes should be approached via inguinal exploration. The technical details of the operation are well described in standard current pediatric surgical and urological texts. (1)(2) The key steps of the operation are:
A scrotal orchidopexy approach has been described, (20) but is only really appropriate for high scrotal or ascending testes, and is not widely used.
Fig 2. Undescended testis with macroscopic epididymal anomaly.
Fig 3. Intra-operative position of undescended testis located at the superficial inguinal pouch (extra-canalicular).
Fig 4 . Elongation of the spermatic vessels with testicular descent after dissection of the hernia sac.
Fig 5. Tegaderm dressing covering the surgical wound.
8.2. Surgical Approach to the non-palpable testis - the role of diagnostic laparoscopy
If the testis is non-palpable preoperatively, as is the case in 20% of UDT, physical examination under anesthesia can sometimes allow identification of the testis. Otherwise, diagnostic laparoscopy is the procedure of choice. (21)(22) If laparoscopy is unavailable, an inguinal and, if necessary, an abdominal exploration, will be necessary to find or rule out an intra-abdominal testis. The surgical findings will either be:
a) Blind-ending vessels, indicating a ‘vanishing testis’, and no further need for exploration (10-50%).
b) Spermatic cord structures entering the inguinal canal through the internal inguinal ring. Inguinal exploration may find an atrophic testis, which should be removed; or a healthy testis amenable to orchidopexy.
c) Intra-abdominal or peeping testis (50%) which will require either an open or laparoscopic approach.
Fig. 6: Right intra-abdominal testis visualized at laparoscopy
8.3. Inguinal approach to the high inguinal, peeping or intra-abdominal testis
Bringing a high testicle down to the scrotum while preserving its blood supply can be a formidable surgical challenge. Helpful maneuvers can include division of the lateral fibrinous attachments of the cord at the internal ring, mobilization of the retroperitoneal spermatic vessels (which are the limiting factor) by blunt dissection up to the lower pole of the kidney, and bringing the cord medial to the inferior epigastric vessels (which does not usually add much length). The testis can be fixed in the scrotum even if it causes upward traction of the scrotal skin. If the testis still does not reach the scrotum, one option is to suture it to the pubic tubercle and return in 6-12 months for a second stage operation. However the testicular blood supply is at increased risk of injury during a second inguinal operation.
8.4. Fowler-Stephens procedure
The Fowler-Stephens orchidopexy was originally described as a single-stage open inguinal approach for the high intra-abdominal testis in which the testicular artery and veins are too short to allow the testis to reach the scrotum with a standard orchidopexy. (23) The Fowler-Stephens technique involves clipping and transection of the testicular vessels with preservation of the collateral arterial flow through the vas deferential artery and cremasteric vessels. The main risk of this technique is the failure of the deferential artery to supply adequate blood flow, leading to testicular atrophy. The presence of a long looping vas (LLV) increases that risk, especially when done laparoscopically. (24) Performing the Fowler-Stephens in two stages (first ligating the testicular vessels then performing orchidopexy 6-12 months later) theoretically allows the collateral blood supply to develop. Preservation of the gubernaculum also may decrease the likelihood of testicular atrophy.
The main surgical steps of open Fowler-Stephens orchidopexy are briefly described as follows: After opening the external oblique fascia through an inguinal incision, the hernia sac is dissected at the level of the internal inguinal ring without dividing the cremasteric fibers. The distal gubernacular attachments and the collateral vessels on floor of the inguinal canal are left undisturbed. The medial peritoneal strip between the vas and testis is carefully preserved. Further mobilization especially with a LLV is preferably done under direct control of a small tunica albuginea incision on the testis to ensure good blood supply before dividing any potential collateral present between the two vasal limbs (Fowler-Stephens test). After ligating and dividing the testicular vessels, the normal path of testicular descent through the inguinal canal is maintained in bringing the testis down to the scrotum after adequate mobilization. This ensures preserved cremasteric blood supply.
A laparoscopic approach is now widely used for the one or two-stage Fowler-Stephens orchidopexy. (25)
Fig 7 & 8: High inguinal testis mobilized through an inguinal incision, preserving the gubernaculum with some cremasteric blood supply. The spermatic vessels were divided and the viable testis brought down into the scrotum (Fowler-Stephens orchidopexy)
8.5. Other surgical findings at orchidopexy
Most undescended testes have concomitant epididymal abnormalities. An appendix testis or appendix epididymis can be removed. Ectopic adrenal tissue rests are golden yellow and have little significance. Rarely the vas deferens may be congenitally absent (associated with renal agenesis). Another rare finding is the presence of Müllerian duct remnants (fallopian tubes) associated with undescended testes and deficiency of Müllerian Inhibiting Substance.
9. Complications and outcomes of orchidopexy
Immediate surgical complications of damage to the vas deferens, wound infection, and hematoma should be rare. Boys should be assessed at one month after surgery and at 6-12 months to examine for evidence of testicular atrophy or testicular ascent. Testicular atrophy occurs in less than 5% of boys after unilateral orchidopexy. The risk of atrophy is higher in infants presenting with an associated incarcerated hernia, and with intra-abdominal testes. There is some evidence that early orchidopexy improves the likelihood of the testis producing sperm, (11) but there is no evidence that men with unilateral cryptorchidism have decreased fertility even without surgery. The cancer risk may be diminished by early surgery, but again the evidence is weak. (17)
Results of surgery for intra-abdominal testes are better with a one-stage orchidopexy preserving the testicular vessels, than with the Fowler-Stephens technique. (26) However we have seen excellent results as measured by preserved testicular size in boys with intra-abdominal testes having a one-stage Fowler-Stephens orchidopexy and preserving the gubernaculum with its blood supply. (27)
10. Suggested treatment algorithm
11. Reported experience with orchidopexy in Africa
Two Nigerian population based studies each examined over 1000 prepubertal schoolboys for cryptorchidism. (28)(29) The combined prevalence of UDT was 1.8%, similar to that generally reported. Both studies concluded there was a need to screen male children to identify UDT earlier. Several other African publications report their experiences with orchidopexy for UDT. In Tanzania, 40 children had surgery over 7 years at the Pediatric Surgery Unit in Dar-es-Salaam. (30) 17.5% presented with inguinal hernia, and 2.5% presented with testicular torsion. The majority had orchidopexy after age 5 and smaller or atrophic testes were noted in 30%. 15% of the testes were intra-abdominal, with all managed by orchidopexy and only one orchidectomy.
The Ahmadu Bello University Teaching Hospital in Zaria, Nigeria reported 36 children having surgery over 10 years, at a median age of 6 years (range 14 months to 12 years). (31)
Ultrasonography was done in 3 cases but was not helpful in identifying nonpalpable testes. Testes were macroscopically atrophic in 24%, and intra-abdominal in 12%. Orchidopexy was completed in 86% of undescended testes and 10% of these needed a second operation because of testicular retraction. Four (10%) of children had orchidectomy.
Ghana’s Komfo Anokye Teaching Hospital reviewed elective pediatric inguino-scrotal surgical cases over a 4 period including 56 orchiopexies. (32) A third had surgery prior to one year of age, and all had an inguinal approach. Two children had a laparotomy to confirm vanishing testes when nothing was found in the inguinal canal. Single-stage orchidopexy was successful in 86%; others were managed in two stages.
Several conclusions can be drawn from these reports. The incidence of UDT is similar in Africa to the rest of the world, but most children are not identified. This may be because of a lack of education of parents and community health workers, or lack of access to pediatric surgical care. School screening programs may be one way to identify children earlier when orchidopexy is technically easier and likely to achieve better results. Assuming the incidence of testicular cancer is similar to western countries then it can be estimated that there is an annual excess of 6 cases of testicular cancer per million people (2% x .03%) due to untreated UDT. Testicular cancer is most common in men during their early productive years (age 20-30). One pathologic case series from Ibadan, Nigeria found only 3/74 cases of testicular cancer in their registry occurred in undescended testes, all seminomas. (33)
Where laparoscopic equipment and skills are being developed in tertiary hospitals, diagnostic laparoscopy is a simple procedure that could be introduced for boys with nonpalpable testes to decrease the morbidity of negative inguinal exploration. Laparoscopic orchiectomy is a low-morbidity procedure recommended for men over the age of 15 presenting with UDT in a rural hospital in India. (34)
All boys should be examined routinely to ensure the testes are in the scrotum. If the testis is not in the scrotum by 6 months of age it will not descend on its own. The questions raised at the beginning of this article can be answered with some confidence, based on this review of the current evidence.
1. What is the natural history of the retractile testicle and does it ever need surgery? Retractile testes can be distinguished on physical exam and do not require surgery. Parents can be reassured that the testis will almost always stay in the scrotum as the child gets older. Occasionally the retractile testis will subsequently “ascend” and not stay in the scrotum, needing orchidopexy at an older age.
2. What is the risk of infertility and testicular cancer in a child with UDT?
Men with one testis have no measurable difference in their capacity to father children. However the undescended testis begins losing its spermatogenesis capacity after the age of one, so orchidopexy is recommended between 9-18 months of age. The risk of cancer is increased with undescended and especially intra-abdominal testes, but is still low overall at 12-33 per 100,000.
3. Is diagnostic ultrasound necessary in boys with nonpalpable testes?
Ultrasound may identify a nonpalpable testis, but will usually not alter the management algorithm, so is not routinely necessary.
4. Which boys with UDT would benefit from hormonal treatment?
The standard treatment for unilateral UDT is surgery. Hormonal therapy may be considered in bilateral cryptorchidism, to distinguish retractile/ascending testis from undescended testes, or to improve collateral testicular blood supply during redo orchidopexy.
5. What surgical techniques are available for intra-abdominal testes?
The Fowler-Stephens orchidopexy technique is useful for high intra-abdominal testes and can be done in one or two stages. Many centres use a laparoscopic approach.
6. When should orchiectomy be performed instead of orchidopexy?
Orchiectomy is recommended for inguinal or abdominal UDT in post-pubertal boys. (34)
Luis H Braga MD MSc, Julia Pemberton MSc, Brian Cameron MD, FRCS(C)
McMaster Children’s Hospital, Hamilton, Canada
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