You are in: eMedicine Specialties > Urology > Common Problems of the Testicle CryptorchidismArticle Last Updated: Mar 8, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Thomas F Kolon, MD, Department of Urology, Division of Pediatric Urology, Assistant Professor of Urology, The Children's Hospital of Philadelphia Thomas F Kolon is a member of the following medical societies: Society for Pediatric Urology Editors: Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Martin I Resnick, MD †, Former Lester Persky Professor and Chair, Department of Urology, Former Professor, Department of Oncology, Case Western Reserve University School of Medicine; Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy; William J Cromie, MD, MBA, President and Chief Executive Officer, Health Care, Capital District Physicians' Health Plan Author and Editor Disclosure Synonyms and related keywords: cryptorchidism, undescended testis, hidden testis, obscure testis, male genitalia, testicles, testis, testicular development, maldescended testis, orchidopexy, hypogonadotropic hypogonadism, epididymal abnormality, abnormal epididymis, intersex, pseudohermaphroditism, hypospadias INTRODUCTIONSection 2 of 12
  Cryptorchidism is the most common genital problem encountered in pediatrics. Cryptorchidism literally means hidden or obscure testis and generally refers to an undescended or maldescended testis. Despite more than 100 years of research, many aspects of cryptorchidism are not well defined and remain controversial. Untreated cryptorchidism clearly has deleterious effects on the testis over time. Understanding the abnormalities of morphogenesis and the molecular and hormonal milieu associated with cryptorchidism is critical to contemporary diagnosis and treatment of this extremely common entity. History of the ProcedureThis condition was first described in 1786 by Hunter and has been recognized for centuries. The first surgical orchidopexy was attempted in 1820 by Rosenmerkal, but the first successful surgery with patient survival was not until 1877 by Annandale. ProblemNormal 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, primordial germ cell migration occurs. Soon after, Sertoli cells develop and secrete müllerian-inhibiting substance (MIS), the level of which remains high throughout gestation and causes regression of müllerian ducts. At 9 weeks, Leydig cells develop and secrete testosterone. Prenatal ultrasonography shows no testicular descent before 28 weeks, other than transabdominal movement to the internal inguinal ring. Transinguinal migration, thought to be under hormonal control, occurs from weeks 28-40, usually resulting in a scrotal testis by the end of a full term of gestation. FrequencyOverall, cryptorchidism is seen in 3% of full-term newborn boys, decreasing to 1% in boys aged 6 months to 1 year. The prevalence rate is 30% in premature boys. Predisposing factors include prematurity, low birth weight, small size for gestational age, twinning, and maternal exposure to estrogen during the first trimester. A 7% incidence rate is seen in siblings of boys with undescended testes. Spontaneous descent after the first year of life is uncommon. In the United States, prevalence ranges from 3.7% at birth to 1.1% from age 1 year to adulthood. Internationally, prevalence ranges from 4.3-4.9% at birth to 1-1.5% at 3 months to 0.8-2.5% at 9 months. Cryptorchidism is identified in 1.5-4% of fathers and 6.2% of brothers of patients with cryptorchidism. Heritability in first-degree male relatives is estimated to be 0.67. EtiologyThe multifactorial mechanism of occurrence involves (1) differential body growth relative to spermatic cord/gubernaculum; (2) increased abdominal pressure; (3) hormonal factors, including testosterone, MIS, and extrinsic estrogen; (4) development/maturation of the epididymis; and (5) gubernacular attachment. PathophysiologyStudies support the notion that cryptorchidism is a disease state with a spectrum of associated findings rather than an isolated malformation. Three main areas of development have been researched, (1) the hypothalamus-pituitary-gonadal axis, (2) the epididymis, and (3) the gubernaculum and genitofemoral nerve. Cryptorchidism may be a variant of hypogonadotropic hypogonadism. The normal initial postnatal gonadotropin surge at 60-90 days is absent or blunted in some boys with cryptorchidism. Without this surge, Leydig cells do not proliferate, testosterone does not increase, and germ cells do not mature. Thus, infertility may result. The initial intra-abdominal aspect of testicular descent occurs normally in mice with complete androgen resistance (testicular feminization) in which the androgen receptor (AR) has been knocked out. Deletions and mutations may cause structural changes in the AR, altering its function. Of male pseudohermaphroditism, which usually includes hypospadias and cryptorchidism, 50-70% of cases are due to AR disorders. Although AR gene mutations have been identified in patients with isolated hypospadias, these mutations have not yet been identified in isolated cryptorchidism. Thus, isolated cryptorchidism may have a different etiology than the cryptorchidism associated with intersex conditions. The epididymis may play a key role in testicular descent because some mammals have been noted to have a descended epididymis and an undescended testis. However, no mammal has had a descended testis with an undescended epididymis. Approximately 23-86% of cryptorchid testes have epididymal abnormalities. In general, the greater the degree of cryptorchidism, the greater the epididymal abnormality. Androgens are known to act on the genitofemoral nerve, which is sexually dimorphic, and release genitofemoral nerve/calcitonin gene–related peptide (CGRP) upon stimulation. CGRP causes intracellular release of cyclic adenosine monophosphate, which produces rhythmic contractions of the mouse gubernaculum. Although AR gene mutations are not linked to isolated cryptorchidism, abnormalities in CAG or GGC repeat lengths in the gene may be associated. Knockouts of HOXA10, HOXA11, ESR1, INSL3, and the LGR8/GREAT receptor genes have resulted in cryptorchidism in rodent models, and these gene alterations are currently being investigated in patients with cryptorchidism. ClinicalThe most useful classification is whether testes are palpable upon physical examination. If nonpalpable, testes may be intra-abdominal or absent. If palpable, testes may be undescended, ectopic, or retractile. Nonpalpable testes occur in approximately 20-30% of those who have cryptorchidism. The absent testis is thought to occur from an intrauterine or perinatal vascular event. This likely is a late gestational event because 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 then are 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 due to an active cremasteric reflex. This reflex usually is weak during infancy and most active in boys aged 5 years. These testes can be manipulated into the scrotum, where they remain without tension. Several authors have examined the anatomic position of cryptorchid testis. Cendron and Duckett documented the position upon physical examination and compared this with position at the time of surgery. The results are as follows:
Kleintach et al compiled results on 14,548 testes from several studies, and the results were abdominal, 10%; inguinal, 68%; prescrotal, 24%; ectopic/SIP, 11.5%; bilateral, 30%; and unilateral right (vs left) testis, 70%. Associated anomalies/conditions may include the following:
Generally, ductal abnormalities, hernias (patent processus vaginalis), and testicular maldevelopment are more common in abdominal testes. Overall, 32-79% of undescended testes are reported to be associated with some type of epididymal abnormality. However, abnormalities that inhibit sperm transport (eg, complete caput separation, atresia, agenesis) have been reported in only 8% of patients. Also, when the processus vaginalis is patent, the epididymis is more likely to be abnormal. Elements of the medical history should include the following:
Elements of the physical examination should include the following:
INDICATIONSSection 3 of 12
Indications for hormonal or surgical correction of cryptorchidism include the following:
RELEVANT ANATOMYSection 4 of 12
The testis, when palpable, usually is found in the superficial inguinal pouch or in the inguinal canal under the external oblique aponeurosis. Care must be taken during dissection to avoid the ilioinguinal nerve near the spermatic cord. After dissection of the cremasteric fibers off the cord, the patent processus vaginalis, or hernia sac, may be located on the anteromedial surface of the cord. The intra-abdominal view of the anatomy is best seen in Image 1. The vas deferens can be seen exiting the internal inguinal ring and crossing the median umbilical ligament. The testicular vessels (ie, spermatic artery) can be seen entering the internal ring from its origin off the aorta near the renal hilum. CONTRAINDICATIONSSection 5 of 12
Nothing contraindicates intervention for undescended testis in prepubertal boys. Current recommendations for postpubertal men are as follows:
WORKUPSection 6 of 12
Lab Studies
Imaging Studies
TREATMENTSection 7 of 12
Medical therapyThe appropriate time for treatment is when the individual is aged approximately 6 months. This age limit has decreased over the recent decades and is based on (1) the rarity of spontaneous descent after age 6 months and (2) the possible salvage of improved fertility by earlier intervention. The choice of initial treatment is a reflection of both physician and patient preference Primary hormonal therapy with hCG or gonadotropin-releasing hormone (GnRH or LH-releasing hormone [LHRH]) has been used for many years, especially in Europe. Human chorionic gonadotropin The action of hCG is virtually identical to that of pituitary LH, although hCG also appears to have a small degree of FSH activity. It stimulates production of gonadal steroid hormones by stimulating the Leydig cells to produce androgens. The exact mechanism of action of the increased androgens in testicular descent is not known but may involve effects on the testicular cord or cremaster muscle. This medication is administered by intramuscular injection. Multiple series have been published; however, due to differences in patient age, treatment schedules, and possible inclusion of retractile testes, very divergent results have been reported. Many dosage schedules are reported, ranging from 3-15 doses. However, hCG appears to be as effective in 3 or 4 doses compared to 9 or 10 doses. One of the most common schedules is 250 IU/dose in young infants, 500 IU/dose for children 6 years or younger, and 1000 IU/dose for individuals older than 6 years given twice a week for 5 weeks (as per the International Health Foundation). Success rates for descent into the scrotum are 25-55% in uncontrolled studies but only 6-21% in randomized blinded studies. Distally located testes in older boys are more likely to descend in response to hormonal treatment than abdominal testes. Repeated courses have offered little advantage. Adverse effects of hCG treatment include increased scrotal rugae, pigmentation, pubic hair, and penile growth, which regress after treatment cessation. A total dose of more than 15,000 IU may induce epiphyseal plate fusion and retard future somatic growth. Gonadotropin-releasing hormone Agonistic analogs of GnRH such as nafarelin or buserelin stimulate the release of the pituitary gonadotropins, LH and FSH, resulting in a temporary increase of gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland, and twice-daily administration leads to decreased secretion of gonadal steroids by 4 weeks. This hormone is available as a nasal spray but is approved for the treatment of cryptorchidism only in Europe. Interpretation of results, again, is tainted by multiple treatment strategies. Success rates in uncontrolled studies range from 13-78%, while better-controlled investigations resulted in rates of 6-38%. Rajfer et al conducted a randomized double-blind study comparing hCG at 3300 IU per week for 4 weeks with GnRH spray at 200 mcg 6 times a day for 4 weeks. Descent into the scrotum occurred in 6% of the hCG group and in 19% of the GnRH group. Several authors have recommended combined GnRH and hCG hormonal treatment. Lala et al administered LHRH at 1.2 mg/d for 4 weeks. Those who did not respond also received hCG at 500 IU 3 times a week for 3 weeks. After combined treatment, 38% of testes descended. Bica and Hadziselimovic treated patients with a low dose of buserelin (20 mcg) as a daily spray for 28 days, followed by hCG for those in whom treatment failed. Approximately 26% of the testes descended with the spray alone, and hCG increased the descent rate to 37%. Hadziselimovic advocated initial treatment with GnRH spray at 400 mcg tid into each nostril for 4 weeks, followed by salvage treatment for those in whom treatment failed, with hCG at 1500 IU/week for 3 weeks. The success rate of 56% with GnRH was increased to 65% with the addition of hCG. The recognized adverse effects of increased androgens, including increased penile or testicular size, scrotal erythema, or erections, seem to be less with GnRH than with hCG. Initial treatment with GnRH may deserve some consideration because it is administered as a spray rather than an injection. Even in 20% of patients, it may aid descent in more distal testes, make intra-abdominal testes palpable, or help differentiate retractile from true undescended testes. Surgical therapySuccessful placement of the testis in the scrotum by surgery 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. Preoperative detailsLab studies generally are not needed for a patient with unilateral cryptorchidism. Orchidopexy is performed routinely as a same-day surgical procedure. Intraoperative detailsThe 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 incising the Scarpa fascia because the testis may be located in the superficial inguinal pouch and not in the inguinal canal. For mobilization of the testis, the distal gubernacular attachments are divided. Then, the cremasteric muscle fibers are transected. 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 subcutaneous or subdartos pouch. Controversy exists as to the method of testis fixation. The surgeon's choices 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 have shown that sutures through the tunica albuginea cause testicular parenchymal damage in rats. Chromic sutures produce more fibrosis than permanent sutures. The least fibrosis occurs with a sutureless subdartos pouch. Jarow determined that subtunical sutures might damage the testicular blood supply, more in the lower pole rather than in the upper pole. 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 also may be lengthened to enable this dissection. Continue dissection in the retroperitoneal space. The Fowler-Stephens orchidopexy 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. Rarely, a 2-stage orchidopexy may be used without division of the spermatic vessels 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 used 6-12 months later. Nonpalpable testis Exploration for a nonpalpable testis may occur through an extended inguinal incision, an abdominal incision, or, more commonly, via diagnostic laparoscopy. At the time of exploration, 3 main findings 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) that enter the internal ring (20%). Blind-ending vessels suggest the diagnosis of vanishing testis syndrome, likely due to an early prenatal vascular event. A blind-ending vas deferens or spermatic vessels that are not seen 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. Cord vessels entering the ring warrant an inguinal exploration for identification of a testis or a testicular nubbin. 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, and contralateral testis and on the skills of the surgeon. For laparoscopy, put the patient in the supine Trendelenburg position. Insert a bladder catheter and, possibly, a nasogastric tube if gastric distension is present. Choose between Veress needle insufflation and an open Hasson (mini-lap) technique. Institute carbon dioxide insufflation at a low rate (1 L/min) until abdominal distension occurs. Initial pressures should be less than 7 mm Hg. The total amount of carbon dioxide required is approximately 2-3 L. Create a 5-mm umbilical camera port (newer 2- to 3-mm needlescopes now are available). In infants who need orchidopexy or orchiectomy, one or two 5-mm working ports are needed at the McBurney point at the umbilical level. For standard abdominal orchidopexy, choose between an extended inguinal versus an abdominal (vertical midline or Pfannenstiel) incision. This procedure has an 81% success rate (scrotal testis without atrophy). The success rate for orchidopexy of a so-called peeping testis at the internal inguinal ring is 82%. If in the abdominal cavity, the success rate is 74%. The surgeon may proceed to other techniques for orchidopexy (ie, 2-stage, artery ligation) depending on testis mobility. The 2-stage orchidopexy can be used after extensive cord mobilization; however, a risk of spermatic cord injury exists during the second procedure. The success rate is 73%. The 1-stage Fowler-Stephens procedure must be planned ahead to avoid devascularization of the secondary blood supply from the vas deferens and the cremaster muscles. It can be performed using open or laparoscopic technique. The success rate is 67%. The 2-stage Fowler-Stephens procedure theoretically allows improved collateral blood supply, but a second stage is required. It also may be performed with an open or laparoscopic technique. The success rate is 77%. A literature review reveals no statistically significant difference between success rates of 1-stage versus 2-stage Fowler-Stephens orchidopexies. For laparoscopy-assisted orchidopexy, mobilize the testicular vessels laparoscopically up to the renal level to avoid tension for a classic open inguinal orchidopexy. 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 orchidopexy 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, usually is performed laparoscopically. Postoperative detailsPain medication is used as needed. Keep the surgical area dry for 3 days. Absorbable sutures are used during closure; therefore, removal is not necessary. If an external button or bolster is used externally on the scrotum, it usually is removed in the office after 1 week. The patient should avoid using straddle toys or participating in physical education for 2-3 weeks. Follow-upTreatment should not end with the first postoperative visit. Evaluate the child at age 1 month and 6-12 months postoperatively for 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. The author recommends checking a semen analysis when the boy reaches age 18 years. COMPLICATIONSSection 8 of 12
Complications of orchidopexy are as follows:
Complications of laparoscopy include the following:
OUTCOME AND PROGNOSISSection 9 of 12
Success rates of medical or surgical orchidopexy are addressed in Treatment. Risk of malignancy Cryptorchidism places the affected patient at increased risk for testicular tumor development. Cromie estimated the risk of malignancy developing in those with cryptorchidism to be 48.91 cases in 100,000 persons, representing a 22-fold increase over the rate of 2.2 cases in 100,000 adults with normally descended testes. More recently, Giwercman et al demonstrated that 6 of 506 (1.1%) men who previously had cryptorchidism developed testis cancer. Orchidopexy is not protective against subsequent testis cancer. Testicular tumors after previously successful orchidopexy most frequently are nonseminomatous germ cell tumors, while abdominal testes may develop seminomas. The increased incidence of nonseminomatous tumors after orchidopexy has been postulated to be due to ischemic atrophy and secondary hypergonadotrophism. Approximately 15-20% of tumors occur in a contralateral descended testis. Carcinoma-in-situ (CIS) is present in 1.7-3% of previously cryptorchid testes and is theorized to originate from fetal gonocytes. Furthermore, the risk of testis cancer formation from gonads with CIS may be near 50% in 5 years. Risk of infertility Men who previously had bilateral cryptorchidism have greatly reduced fertility compared to those who had unilateral cryptorchidism and those of the general male population. Lee et al showed a paternity rate of 62% (38% infertile) in those with bilateral cryptorchidism compared to a matched control group (rate of 94%, ie, 6% infertile), indicating a 6-times increased risk. In contrast, men with unilateral cryptorchidism had a paternity rate of 89.5%. Although this represents a 2-fold increase in infertility, this rate is similar to the level of infertility found in other studies of the general population. Examination of subfertility, or time to pregnancy, shows that with bilateral cryptorchidism, men have greatly increased waiting times to pregnancy (33.9 mo vs 11.1 mo for those with unilateral cryptorchidism and controls). Lee, Coughlin, and Bellinger also examined the association of pretreatment testis location with fertility rates and various hormone levels (inhibin B, LH, FSH, testosterone) in adulthood. They concluded, "preoperative testis location in men with previous unilateral cryptorchidism is not a major determinant of fertility according to paternity, sperm count, or hormone levels." Although semen quality may be impaired in men with a unilateral cryptorchid history, the correlation between semen analysis results that indicate impairment, decreased fertility index (number of spermatogonia per 50 tubules), and paternity has been poor. Thus, paternity may be a more useful indicator of fertility in these patients. FUTURE AND CONTROVERSIESSection 10 of 12
ControversiesTestis cancer Giwercman et al recommend biopsy of all cryptorchid testes in adults. If CIS is present, they recommend contralateral biopsy and unilateral orchiectomy. If the remaining contralateral testis also harbors CIS, they recommend radiation therapy. Lenz et al demonstrated an abnormal echo pattern associated with 3% of postpubertal testes that had undergone orchidopexy. This abnormal ultrasound finding may be associated with CIS, and they suggest offering a scrotal ultrasound to postpubertal patients. Infertility Based on retrospective human data and orchidopexy studies in rats, Bellinger et al believe that the practice of transparenchymal sutures to fixate the testis or using scrotal wall bolsters put the testis at significant risk for direct trauma. Suture violation of the blood-testis barrier also may play a role in future antisperm antibody development. Further investigation is necessary to fully define this concept of testicular injury. Studies have shown that patients with a fertility index of less than 0.2 by testis biopsy at orchidopexy are at a severe risk for later infertility, and these counts correlate with sperm density in adulthood. Hadziselimovic et al have suggested that these boys with cryptorchidism may benefit from adjuvant hormonal therapy with increased numbers of germ cells. LHRH agonists may improve testicular germ cell and postpubertal sperm counts. FutureSchneck et al reported a trend of significantly lower inhibin B levels compared to controls in the same age group of boys. 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. 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. 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. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
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