Clinical Aspect and Outcome of UDT

Clinical IssuesDefinitions & epidemiologyNormal testicular development and descentCauses of cryptorchidismConsequencesAzospermiaIncreased risk for neoplasiaTreatmentMedical/hormonalSurgical

EpidemiologyMost common male developmental abnormalitiesFrequency 3.4 % in term boysBy 1 yr, incidence 0.8% (spontaneous descent in 75% term dan 90% preterm)Most spontaneous descent happen first 3 months (testosterone post natal surge)Spontaneous descent rare > 6 months old

Incidence of UDT in RSCM Batubara, et al 1994-1995Untreated bilateral UDT 89% develop azospermiaLifetime risk of neoplasia 2-3%4 fold higher than average risk

Epidemiology

DefinitionCryptorchidism = Undescended testis (Greek, kryptos=hidden, orchis=testicle) Definition: testis which has been arrested anywhere along its normal pathway of descent. No racial or geographic predispositioncan be associated with congenital, chromosomal, or intersex disorders.

Clinical presentationPalpableNonpalpableUnilateralBilateralhCG testWith / without other genital abnormality61% of referred cases proven cryptorchidism (Giannopoulos et al, 2001)

DefinitionsEctopic: aberrant course

Retractile (39%): can be manipulated into scrotum where it remains without tension (most common misdiagnosis)

Gliding (12-18%): can be manipulated into upper scrotum but immediately retracts when released

Ectopic testisAberrant coursebase of the penis, superficial inguinal pouch, (most common) medial aspect of the upper thigh, contralateral scrotal sacperinealHormonal therapy useless

Retractile testesHormone production and fertility are normal no increased risk for malignancy. A hyperactive cremasteric muscle reflex, which lessens with time, is the suspected cause of the retraction. Most retractile testes remain in the scrotum permanently by the onset of puberty.

Retractile testesNormal fertility and no increased risk for malignancy. hyperactive cremasteric muscle reflexSpontaneous descent no interventionMost permanent in scrotum at onset of pubertyGiannopoulos et al (2001)Follow up every 6 months6% ascend needs hormonal therapy

Physical ExaminationThe patient should be comfortable supine with his legs elevated (the frog leg position). full genital examination penile abnormalities, such as hypospadias. scrotum (size and development)

Physical ExaminationTestes examinationIf palpable manipulate into scrotal "milking" (pressing down just above the inguinal canal and gliding a lubricated hand toward the scrotum)Cremasteric reflex: Stroking the inner thigh elevation of > 0.5 cm of the ipsilateral testicle

Physical ExaminationIf testis can be brought all the way into scrotum, it is retractile check annually If ectopic record the location for future treatment. UDT: testes not ectopic or retractile

Physical ExaminationIf the testis is not palpable in the supine positioncross-legged (tailor) or squatting position relaxation of the cremasteric reflex Warm compresses of the inguinal region

Clinical IssuesDefinitions & epidemiologyNormal testicular development and descentCauses of cryptorchidismConsequencesAzospermiaIncreased risk for neoplasiaTreatmentMedical/hormonalSurgical

Spontaneous testicular descent (Wenzler et al, 2004)10-year experience (1990-2000) of treating infants with cryptorchidism N= 1,235 patients with cryptorchidism; 278 presented before age 12 months.

CONCLUSIONS: spontaneous testicular descent is uncommon in infants with cryptorchidism is rare beyond age 6 months (spontaneous descent in 75% term dan 90% preterm)Most spontaneous descent happen first 3 months (testosterone post natal surge)Spontaneous descent rare > 6 months oldSpontaneous testicular descent (Wenzler et al, 2004)

IssuesDefinitions & epidemiologyNormal testicular development and descentCauses of cryptorchidismConsequencesAzospermiaIncreased risk for neoplasiaTreatmentMedical/hormonalSurgical

Causes (Giannopoulos, 2001)

Gonadotropins profiles Insufficient T response to hCG in 36.5% (Forest,1979)Blunting of LH and FSH surge at 3 months (Gendrel,1980)Leydig cell hypoplasia (Hadziselimovic, 1986)May indicate deficiency of HP-gonadal axis as a cause of defective meiosis

IssuesDefinitions & epidemiologyNormal testicular development and descentCauses of cryptorchidismConsequencesAzospermiaIncreased risk for neoplasiaTreatmentMedical/hormonalSurgical

Azoospermia (Hadziselimovic, 2001)(Hadziselimovic, 2001)

Unilateral UDTBilateral UDTUntreated13.6%88.6%Medically treated13.3%32.0%Surgically treated13.3%46.4%N=1255;incidence in normal population 0.4-0.5%

(Hadziselimovic, 2001)

Number Ad spermatogonia per tubular cross-section from 0-9 years old(Hadziselimovic, 2001)

# germ cells/tubular cross-section

Normal in 1st 6 mo, greatly decreasedBetween 6-24 mo

Hadziselimovic 2001Sperm/ejaculate (1x106)

If Ad spermatogonia present at orchidopexy,Tended to have normal sperm count as adults

AdspermatogoniaNo Ad spermatogonia

IssuesDefinitions & epidemiologyNormal testicular development and descentCauses of cryptorchidismConsequencesAzospermia- Increased risk for neoplasiaTreatmentMedical/hormonalSurgical

Neoplasm and UDTUDT is 35-48x more likely to have malignancy Abdominal 4x >inguinal testis 1/5 occurs in contralateral testis10% of testis CA are in UDTGerm cell tumors (seminomas and nonseminomas) are the most common

IssuesDefinitions & epidemiologyNormal testicular development and descentCauses of cryptorchidismConsequencesAzospermiaIncreased risk for neoplasiaTreatmentsMedical/hormonalSurgical

When to treat?Hamza 2001As spontaneous testicular descent closely related to postnatal LH and T surges,In term boys, 4 moIn premies, 6 moPotential concerns premature epiphyseal plate fusion Induce secondary sexual characteristics

TreatmentsHormonalhCGGnRHhMGCombined (hCG & GnRH)Surgical

Hormonal TherapyhCG supplementation Leydig's cells testosterone production promotes testicular descent.

Dosage: The International Health Foundation250 IU for young infants, 500 IU for children up to 6 years of age,1000 IU for patients older than 6 years. The injections are given biweekly for 5 weeks.

Potential concerns about premature epiphyseal plate fusion.

hCG vs GnRH: multicenter trialChristiansen 1992

330 boys (?ages) Randomized to hCG 100 IU/kg IM twice weekly x 3 wkGnRH 200 ug intranasal TID x 28 dPlacebo intranasal TID x 28 dSuccess if both testes located at bottom of scrotum after treatment

Rates of descent of the UDT following treatment. Christiansen 1992.Bilateral: p=0.0016Unilateral: p=0.013

Meta-analysis of hormonal treatment for cryptorchidism (Pyorala 1995)Reports from 1958-1990, in EnglishPrimary treatment with GnRH or hCGExcluded articles not documenting final testicular positionDurations of treatment GnRH 1 day 4 wkhCG 1 wk 12 mo

Review & meta-analysis33 studies including 3282 boys, 4524 undescended testesRCTs (n=11) included 872 boys, 1174 undescended testesMeta-analysis only on RCTs that compared GnRH vs placebo (n=9 trials)Risk ratio for descent after GnRH 3.21 (1.83-5.64) (p

Mean success rate (%) for treatment in combined RCTs (Pyorala 1995) # Trials 9 2 11 Testes 472 148 554

Mean success rate (%) for treatment in RCTs excluding retractile testes (Pyorala 1995) # Trials 4 2 5 Testes 308 148 335

Mean success rates (%) by original location (Pyorala 1995) # trials 17 21 14 4# testes 907 1430 295 67

Mean success rates (%) of hormonal treatment (GnRH or hCG) according to age (Pyorala, 1995) # trials 2 2 3 4# testes 48 49 167 267 p=NS

Response of UDT to LH-RH followed by HCG related to clinical positionsGiannopoulos 2001

Long term outcomes5/11 randomized GnRH trials24% (13-35%) ascended/relapsedConclusions:GnRH more effective than placebohCG seems effective, but not as much data

Comparison of hormonal treatment (Esposito et al,2003)Success rateOverall success in 27.7% (38.2% in UDT bilateral; 23.8% in UDT unilateral; p=0.007)

When to operate?Age 6 12 monthsFailure of hormonal therapyLocationCoincide with herniaEctopicBy 18 months of age in infants with an undescended testis, light microscopy reveals a diminished number of germ cells, diminished seminiferous tubular size, peritubular hyalinization, and fibrosis orchidopexy is generally recommended when the child is 12 to 18 months of age.

Conclusion UDT = non retractile or non ectopic testisSpontaneous descent rare > 6 months old check testis position at 6 months old regularlyUDT: Hormonal intervention at 6 monthsSurgical at 1 year regular examsRetractile: follow up every 6 months 6% ascent