1. Testicular Descent and Ascent: A Matter of Timing
Yegappan Lakshmanan, MD, FAAP
Pediatric Urology
Children’s Hospital of Michigan

2. Disclosures
None

3. Why do testes descend?
2 to 3 degree F difference in temperature needed for spermatogenesis
Only in primates do testes descend at or near birth (hibernating animals descend only during breeding season, whales cooled by water, birds by air during flight)

5. Testicular Descent: Why the fuss?
A fused scrotum with 2 descended testes is better than any genetic or hormonal test for “manhood”
Porphyry Chair - “La Sedia Gestatoria”
Middle Ages: (Paschal II) and 1513 (Leo X)

6. “duo testes bene pendulum” (‘he has 2 testes and they hang well’)

7. Terminology Cryptorchidism vs Undescended Testis Retractile testis
In and out of scrotum but returns to a dependent scrotal position
Ascended testis (acquired)
Documented scrotal position after birth but subsequently not in scrotum

8. Objectives Testicular Descent Current perspectives in treating UDT
Timing of orchidopexy
Bianchi or scrotal approach
Nubbins
Testicular Ascent
Extravaginal torsion

9. Testicular Descent: Trans-abdominal phase
Gubernaculum – swelling reaction
Cranial suspensory ligament regression
Insl3 from Leydig cells + MIS /DHT
Few mutations of Insl3 / Lgr8 described in patients
Klonisch et al, Dev Bio, 270:1-18, 2004; Hutson et al, J Ped Surg, 40: , 2005

10. Testicular Descent: Inguinoscrotal Phase
Androgen dependent
Deficiency of this phase with retention of CSL in:
LuRKO (LH receptor knockout)
Natural hpg mouse
Natural tfm mouse
Androgens do not suppress CSL in male bats
Klonisch et al, Dev Bio, 270:1-18, 2004; Hutson et al, J Ped Surg, 40: , 2005

11. Epidemiology Most frequent anomaly of the male GU system
No predilection for race or geographic location
Mostly sporadic but may be associated with genetic disorders

12. Undescended Testis: Incidence
Newborn:3 to 5% (Full-term, >2500 gm)
At 1 year:0.8 to 1% (after 6 months)
Adults:0.8%

13. Incidence By 1 year of age: 0.8-1.5% (constant into adulthood)
75% of full term and 95% of premature testes will descend (usually in 1st 3 months)
10% bilateral
80% of UDT palpable
20% impalpable (cryptorchid)
Half intra-abdominal
Other half – vanishing or atrophic
14% of boys have family history of same

14. Classification Abdominal Canalicular
Ectopic- perineum, femoral canal, superficial inguinal pouch, suprapubic, contralateral scrotum
(due to gubernacular attachments)

15. Investigations
Imaging does not influence management (overall accuracy of 44%)
Physical exam is 84% accurate when done by a pediatric urologist
Hormonal workup
Bilateral impalpable testes: HCG stimulation (if normal gonadotrophin levels)
False negatives possible
FSH / MIS / Inhibin B

16. Histology
The longer the testis is cryptorchid, the more likely it is to be histologically abnormal - changes appear by 1 ½ yrs of age
The higher the testis the more pronounced the abnormality
Hypolasia of Leydig cells, smaller seminiferous tubules, fewer spermatogonia, peritubular fibrosis
Unclear whether changes in testis are due to intrinsic defect or secondary to cryptorchid state (changes often seen in contralateral testis)

17. Undescended Testis: Histology & Germ Cell maturation
Primary dysgenesis in 20 – 100%
By 2 years, 30 – 40% are aspermatogenic (as early as 15 months)
Ong et al, Pediatr Surg Int, 21: , 2005

18. Undescended Testis: Effects on Fertility - Paternity

19. Undescended Testis: Fertility – hormone levels
Inhibin B and FSH:
Biomarkers of seminiferous tubule integrity
Correlate well with sperm density
In a cohort of post-op patients, age at orchidopexy was found to correlate
Inversely with Inhibin B levels
Positively with FSH and serum Testosterone levels
Indirect evidence favoring early orchidopexy
Lee et al, J Urol, 160: , 1998 and 167: , 2002

20. Current recommendations
For truly undescended testes:
Surgical correction anytime after 6 months, preferably before age 1
Testes that descend are likely to do so by the age of 6 months (Wenzler et al, J Urol, 2004)
Biopsy at orchidopexy has demonstrated more spermatogonia per tubule and larger diameter of seminiferous tubules <1 year of age

21. Risk of Neoplasia Testicular Ca incidence 1 in 100,000
10% have a H/O UDT
Incidence of Test Ca in UDT is 1 in 2550 (Farrer et al, 1985) for a RR of 40x
Intra-abdominal testes have 6 times greater risk than inguinal testes (half the tumors)
RR 3.6 in contralateral descended normal testis in men with unilateral cryptorchidism

22. Nubbins?
Remnant gonadal tissue at inguinal exploration should be excised because 13% have viable residual testicular elements
Theoretical risk:
Approx 10% contain residual tubules
5.6% contain germ cells
(De Luna et al, 2003)

23. Biopsy? Carcinoma in situ incidence – 1.7%
More common in abdominal testis
But no definite correlation with later development of malignancy
Justifiable in high risk groups:
Danish
Older boys presenting with cryptorchidism
Transplant considerations

24. Surgical Intervention
EUA to locate testis
Palpable – Inguinal orchidopexy
Impalpable – Laparoscopy

25. Laparoscopy For locating non-palpable testes (>95% accuracy)
Findings:
Blind ending vessels above internal ring
Cord structures entering internal ring
Intra-abdominal testis

30. Surgical Intervention
Nubbin – excise
Contralateral orchidopexy?
Role of Scrotal Orchidopexy
Bianchi approach

31. Bianchi procedure Single high scrotal incision – 1980’s
Several large reported series since
Rajimwale et al, Ped Surg Int 2004 (Denver)
Samuel and Izzidien, Ped Surg Int 2008 (Cardiff)
Bassel et al, J Urol, 2007 (Atlanta)
Applicable in UDT situated in the superficial inguinal pouch or lower
Processus vaginalis approachable
Single incision

33. Extravaginal Torsion
“Bilateral neonatal torsion” – LaQuaglia et al, J Urol, 1987
4 cases between ; 2 asynchronous, 1 salvaged
“Perinatal extravaginal torsion of the testis in the first month of life is a salvageable event” – Sorensen et al, Urology, 2003
10 boys < 30 days old, with unilateral torsion – 4 saved

34. Extravaginal Torsion
“Management of perinatal torsion: today, tomorrow or never?” – Yerkes et al, J Urol, 2005
18 pts in 3 institutions over 3 years; 4 had contralateral unsuspected torsion resulting in atrophy (22%) – 2 others in early stages were salvaged
“Perinatal testicular torsion: preoperative radiological findings and the argument for urgent surgical exploration.” – Ahmed et al, J Pediatric Surg 2008 (San Diego – 2 pts)
“Neonatal bilateral testicular torsion: a plea for emergency exploration” – Baglaj and Carachi, J Urol, 2007 (Scotland – 3 cases and lit review)

35. Extravaginal Torsion Management: Timing: If diagnosis certain: If not:
Scrotal exploration / orchiectomy / contralateral orchidopexy
If not:
Inguinal exploration
Timing:
If seen immediately: at next available opportunity
If seen later: decide after due counseling

37. Testicular Ascent
Prevalence of undescended testes stable after age 1 ~ 1%
Reported orchidopexy rates are as high as 2 to 3% of all boys up to age 14 to 17 years
Barthold et al, J Urol, 170: , 2003
Initially thought to be due to treatment of retractile testes

38. Testicular Ascent Possible Etiologies: Persistent processus vaginalis
Ligamentous PV causing tethering
Cremaster spasticity i.e Cerebral Palsy
High scrotal testes (“gliding”)
Mobile superficial inguinal pouch testes
Failure of testicular vessels to elongate
Scarring after groin surgery
Error in diagnosis – missed during infancy

39. Testicular Ascent: To Pex or Not to Pex?
Dutch ‘national testis registry’ – 1986
Orchidopexy in ascended testis only for failure to descend at puberty (with testicular volume appropriate for age)
In 2003, of 63 boys with 74 ascended testes: Hack et al, Br J Surg, 90:728-31, 2003
15 boys (20 testes) – operated at parental request
4 boys (4 testes) – lost to followup
42 of remaining 50 descended at puberty
Recommended conservative management

40. Testicular Ascent: To Pex or Not to Pex?
Confirm diagnosis by serial examination of “retractile testes”
5 to 7% incidence of secondary ascent
Conservative management if testicular volume appropriate for age, until puberty
Operate if progressively higher location, or smaller volume
Histological changes and germ cell counts similar to UDT
? Role of HCG

41. Conclusions Testicular location after birth variable
Spontaneous descent & ascent occur
All boys need routine examination throughout childhood
Closer surveillance of ‘retractile testes’
If undescended, orchidopexy between age 6 to 12 months
Ascended testes may also need orchidopexy