Cryptorchidism Treatment & Management

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

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

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

Human chorionic gonadotropin

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

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

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

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

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

Gonadotropin-releasing hormone

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

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

Several authors have recommended combined GnRH and hCG hormonal treatment.

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

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

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

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

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

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

 

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

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

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

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

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

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

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.

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

Palpable testis

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

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

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

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

Considerations regarding those options include the following:

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

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

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

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

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

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

Nonpalpable testis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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 of orchiopexy are as follows:

• Inadequate testis position occurs in up to 10% of patients and is due to incomplete retroperitoneal dissection. It is usually corrected with a second procedure.

• Testicular atrophy due to devascularization during dissection of the cord occurs in approximately 5% of patients. Orchiectomy may be indicated to treat cancer, with subsequent prosthesis placement if requested.

• Accidental division of the vas deferens occurs in 1-2% of patients. Immediate or postpubertal microvascular repair may be used.

• Epididymoorchitis is uncommon and may be treated with antibiotics.

• Scrotal swelling may occur and is usually secondary to edema. If progressive, it may be due to bleeding and should be explored. A later presentation of swelling may be secondary to a hydrocele, which, if large, requires transscrotal repair.

Complications of laparoscopy include the following:

• Preperitoneal emphysema may develop secondary to poor needle or trocar placement and insufflation.

• Hypercarbia may occur with pneumoperitoneum. This can be counteracted by increasing minute ventilation and keeping insufflation pressures at less than 12 mm Hg.

• The puncture of a viscus with the Veress needle is not harmful unless insufflated or dilated by a trocar.

• The puncture of a major abdominal vessel is a life-threatening complication. The needle or sheath should be left in place for tamponade, and an emergency open laparotomy is performed. (Almost all the above potentially life-threatening vascular and enteric complications can be avoided by using an open technique for access.)

• Injury to the inferior epigastric vessels may also occur with trocar placement. Hemostasis can be achieved via direct cautery or via suture/clip ligation from the external surface or laparoscopically.

• Bladder puncture may occur because the bladder is intra-abdominal in younger children. Care must be taken when placing lower abdominal and scrotal trocars. Repair can be achieved laparoscopically or through a small suprapubic incision. A ureteral injury requires stenting.

Testis cancer

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

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

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

Infertility

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

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

Future

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

Kolon et al demonstrated mutations in the developmental homeobox gene, HOXA10, in boys with cryptorchidism and polymorphisms in patients with cryptorchidism and in the general population. ^[6] 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.