Evaluation and Treatment of

Cryptorchidism
Prepared for:
Agency for Healthcare Research and Quality
www.ahrq.gov
Outline of Material
Introduction to cryptorchidism and the available
strategies for evaluating and treating this condition
Systematic review methods
Clinical questions addressed by the comparative
effectiveness review
Results of studies and evidence-based conclusions about
the effectiveness and safety of various modalities for
evaluating and treating cryptorchidism
Gaps in knowledge and future research needs
What to discuss with patients and their caregivers

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Background: Definition and Clinical Presentation
of Cryptorchidism
Cryptorchidism is a congenital condition in which one or both
testicles are not appropriately positioned in the scrotum at
birth.
Cryptorchidism may be unilateral or bilateral, and the
undescended testicles may be palpable or nonpalpable.
The undescended testicles may be present in the abdomen or
the groin area or misplaced in the scrotum.
The undescended testicles may be functional or atrophied.
Some individuals have no testicles at all (anorchia).

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Background: Etiology, Prevalence, and
Consequences of Cryptorchidism
The etiology of cryptorchidism is not well understood.

Cryptorchidism affects an estimated 3 percent of full-term

male neonates and up to 30 percent of premature infants.
About 70 percent of cryptorchid testicles spontaneously
descend within the first year of life.
However, the number of boys whose condition persists after this
period remains constant at approximately 1 percent.

Long-term consequences of cryptorchidism may include

testicular malignancy and infertility/subfertility.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Background:
Treatment Planning for Cryptorchidism
The appropriate evaluation and treatment strategy for
cryptorchidism may be influenced by many factors including:
Whether or not the testicle is palpable
Whether the condition is present unilaterally or bilaterally
The age at presentation
Comorbid conditions

The majority of undescended testicles (UDTs) can be

located on physical examination.
For locating nonpalpable UDTs, exploratory laparoscopic
surgery is routinely used in clinical practice.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Background:
Treatment Strategies for Cryptorchidism
Treatment for cryptorchidism is usually initiated between
the ages of 6 months and 1 year.
There are three key surgical options commonly used to
treat cryptorchidism.
Surgical options depend on the location and appearance
of the undescended testicle and include:
Primary orchiopexy
Single-stage Fowler-Stephens orchiopexy
Two-stage Fowler-Stephens orchiopexy

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Objectives of This Comparative Effectiveness
Review
In addition to surgery, clinical treatment planning (imaging
versus no imaging; hormonal stimulation testing or none) and
intervention approaches including hormonal therapy have been
investigated in the literature.

The authors of this systematic review examined the available

evidence on the use of imaging and hormonal testing for
evaluation and the on use of various treatment options for
managing cryptorchidism.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development
Topics are nominated through a public process, which includes
submissions from health care professionals, professional organizations,
the private sector, policymakers, members of the public, and others.
A systematic review of all relevant clinical studies is conducted by
independent researchers, funded by AHRQ, to synthesize the evidence in
a report summarizing what is known and not known about the select
clinical issue. The research questions and the results of the report are
subject to expert input, peer review, and public comment.
The results of these reviews are summarized into Clinician Research
Summaries and Consumer Research Summaries for use in decisionmaking
and in discussions with patients. The Research Summaries and the full
report, with references for included and excluded studies, are available
at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Clinical Questions Addressed by This
Comparative Effectiveness Review (1 of 4)

Key Question 1a. For determining a course of treatment, is imaging

equivalent to laparoscopy in determining the presence and location
of a nonpalpable undescended testicle?

Key Question 1b. In male children with bilateral nonpalpable

undescended testicles, does the use of hormonal stimulation testing
reduce the need for surgery as part of a treatment plan?

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Clinical Questions Addressed by This
Comparative Effectiveness Review (2 of 4)

Key Question 2. What is the effectiveness of initial hormonal therapy

(human chorionic gonadotropin or luteinizing hormone-releasing
hormone) for the treatment of cryptorchidism for outcomes,
including but not limited to:
Further surgical intervention?
The effect on infertility/subfertility?
The development of testicular malignancy?
The size, location, and function of the testicles

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Clinical Questions Addressed by This
Comparative Effectiveness Review (3 of 4)

Key Question 3. What is the effectiveness of surgical therapies (one-

stage vs. two-stage Fowler-Stephens orchiopexy; laparoscopic vs.
open approach) for the treatment of cryptorchidism for outcomes
including but not limited to:
Further surgical intervention?
The effect on infertility/subfertility?
The development of testicular malignancy?
The size, location, and function of the testicles?

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Clinical Questions Addressed by This
Comparative Effectiveness Review (4 of 4)

Key Question 4. How do the age at presentation, physical

presentation of cryptorchidism (unilateral vs. bilateral; palpable vs.
nonpalpable; anatomic location), and occurrence of associated
abnormalities (e.g., hernia) modify diagnosis, treatment, and
outcomes?
Key Question 5. What are the nature and frequency of harms
associated with workup or treatment for cryptorchidism?

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Rating the Strength of Evidence From the
Comparative Effectiveness Review
The strength of evidence was classified into four broad
categories:

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Evaluation of Cryptorchidism: Imaging Modalities
Used To Identify Nonpalpable Undescended Testicles*
The overall sensitivity and specificity of the various imaging
modalities are reported in Table 1 in the next slide.
The evidence is based on mostly poor-quality studies and only one
good-quality study.
The studies were too limited to provide evidence for changing current
practice for evaluating nonpalpable testes.

* The strength of evidence was not assessed for these findings.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
 Table 1. Overall Accuracies of Imaging Modalities
in Identifying Nonpalpable Undescended Testicles
Number and Quality
of Studies Performance Characteristic Measures

Positive Negative Overall

Imaging Predictive Predictive Accuracy
Technique Good Fair Poor Sensitivity* Specificity Value** Value Rate
US 1 2 6 1580 67100 67100 080 2176
MRI 0 3 7 3391 56100 83100 075 4292
CT 0 0 1 57 100 100 14 60
MRA 0 1 1 100 NA100 100 NA100 100
MRV 0 0 1 100 100 100 100 100
MRI & MRAr/V 0 0 1 57 NA 100 0 57
CT = computed tomography; MRA = magnetic resonance angiography; MRAr/V = magnetic resonance arteriography/venography;
MRI = magnetic resonance imaging; MRV = magnetic resonance venography; NA = not available; US = ultrasonography
*Sensitivity: The proportion of testicles correctly identified as present by imaging among those identified as present by surgery.

Specificity: The proportion of testicles correctly identified as absent or vanishing by imaging among those considered absent by surgery.
**Positive predictive value: Among those testicles identified as present by imaging, what is the probability that it will be confirmed by surgery?

Negative
Penson predictive
DF, Krishnaswami value:
S, Jules Among
A, et al. those with
AHRQ Comparative a negative
Effectiveness imaging
Review No. 88. result, what is the probability that the surgery also did not find them?
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.

Overall accuracy rate: The proportion of testicles correctly identified by imaging as present or absent among all testicles subjected to both
imaging and surgery.

MRA and MRV are invasive techniques that require anesthesia or sedation.
Evidence for the Benefits of Surgical Interventions
in Treating Cryptorchidism (1 of 2)
The overall success rate* for achieving testicular descent with primary
orchiopexy** was 96.4 percent (range 89.1100%).
Strength of Evidence: High
The overall success rate for achieving testicular descent with one-stage
Fowler-Stephens orchiopexy* was 78.7 percent (range 3394.3%).
Strength of Evidence: Moderate
The overall success rate for achieving testicular descent with two-stage
Fowler-Stephens orchiopexy* was 86 percent (range 6798%).
Strength of Evidence: Moderate
However, each of the three types of surgery is used for a different clinical
presentation, so the success rates cannot be compared with one another.
* Success rate was defined as the proportion of testicles achieving testicular descent or testicular
positioning.
** These findings were based on retrospective studies. Each intervention was compared with an implicit
control based on the known natural history of the disease.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Evidence for the Benefits of Surgical Interventions
in Treating Cryptorchidism (2 of 2)
Laparoscopy and open repair surgery appeared to be
equally effective in achieving testicular descent.
Strength of Evidence: Low

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Evidence for the Benefits of Hormonal Therapies
in Treating Cryptorchidism (1 of 2)
The studies on hormonal therapies had several limitations:
The studies were small (the number of patients ranged from 33 to 324) and
mainly of poor quality.
The studies included patients with retractile testicles.
The initial location of the testis was lower in most of the patients included
in the studies.
The doses of human chorionic gonadotropin used in the studies were highly
variable.
Luteinizing hormone-releasing hormone is not available for the treatment of
cryptorchidism in the United States and has been discussed here for purposes
of comparison.
The followup period in the included studies was short, so there were
insufficient data on long-term reascension/treatment failure.
These studies excluded patients with an inguinal hernia, which can
accompany an undescended testicle and would require surgical treatment.
Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Evidence for the Benefits of Hormonal Therapies
in Treating Cryptorchidism (2 of 2)
Human chorionic gonadotropin (hCG) achieves slightly higher rates of
testicular descent when compared with placebo (successful bilateral and
unilateral descent rates* of 23% and 15%, respectively, with hCG vs. 0%
with placebo in both cases).
Strength of Evidence: Low
Luteinizing hormone-releasing hormone (LHRH)** achieves slightly higher
rates of testicular descent when compared with placebo (successful
descent rates of 962% with LHRH vs. 018% with placebo).
Strength of Evidence: Moderate
hCG is as effective as LHRH in achieving testicular descent (successful
descent rates of 018.8% with LHRH vs. 5.923% with hCG).
Strength of Evidence: Low
* The success rate was defined as the proportion of testicles achieving testicular descent or testicular positioning.
** LHRH is not available in the United States for treating cryptorchidism and has been included for comparative data.
Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Evidence for the Adverse Effects of Surgical and Hormonal
Interventions in Treating Cryptorchidism (1 of 2)
The overall testicular atrophy rate for primary orchiopexy was 1.83 percent
(range 04%).
Strength of Evidence: Moderate
The overall testicular atrophy rates for one-stage and two-stage Fowler-
Stephens orchiopexy were 28.1 percent (range 2267%) and 8.2 percent (range
012%), respectively.
Strength of Evidence: Low
Laparoscopy and open surgical repair were associated with similar rates of
testicular atrophy.
Strength of Evidence: Low
Other adverse events associated with surgery were rare and included Veress
needle puncture (injury to the sigmoid colon during laparoscopy),
laparoscopic port-site hernia, and incarcerated hernia.*

*This finding was not rated.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Evidence for the Adverse Effects of Surgical and Hormonal
Interventions in Treating Cryptorchidism (2 of 2)
Reported harms of hormonal treatments were mild and included
virilizing effects (e.g., pubic hair, increase in penis size and in
erections) and behavioral changes (e.g., aggression). All harms were
transient.
Strength of Evidence: Moderate

The followup period in all the included studies was short, so there
were insufficient data on long-term fertility and cancer outcomes.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Conclusions (1 of 2)
With regard to treatment planning, current evidence does not
suggest that any specific imaging technique is able to evaluate
nonpalpable, undescended testicles with sufficient accuracy to
eliminate the need for laparoscopic evaluation.

For the treatment of cryptorchidism, surgical options are effective.

Rates of achieving successful testicular positioning are 96.4 percent with primary
orchiopexy and 78.7 percent and 86 percent with one-stage and two-stage Fowler-
Stephens orchiopexy, respectively.
Rates of testicular atrophy vary with these surgical procedures, and adverse
effects are rare.
However, each of the three types of surgery is used for a different clinical
presentation, so the success rates cannot be compared with one another.
Low levels of evidence suggest that open and laparoscopic repair appear to be
equally effective in achieving testicular positioning.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Conclusions (2 of 2)
With regard to hormonal treatment options for
undescended testicles, only human chorionic
gonadotropin is available in the United States.
Studies on hormonal treatment are small and mostly of
poor quality, with evidence related to benefits and harms
too limited to inform changes in practice.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Gaps in Knowledge (1 of 2)
The studies included in this review are of poor quality
and are too limited to determine:
The relative effectiveness of computed tomography, magnetic
resonance venography, and magnetic resonance angiography in
locating testicles
The comparative effectiveness of single-stage or two-stage
Fowler-Stephens orchiopexy for treating cryptorchidism
In the studies that assessed treatment modalities,
analyses are not stratified based on the pretreatment
location of the testicles, which might affect treatment
outcomes.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
Gaps in Knowledge (2 of 2)
Data on the long-term effects, including harms, of
hormonal therapy for undescended testicles are missing
in the literature.
The appropriate age for treatment remains unknown,
and data on the effect of age on outcomes are limited.
Studies of important long-term outcomes of treatment,
including infertility and testicular cancer, have not been
identified in the current literature.

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.
What To Discuss With the Parents and/or
Caregivers of Your Patients
What cryptorchidism is and the consequences of the
condition
The clinical characteristics of the patients case,
including the location and viability of the undescended
testicle(s)
How cryptorchidism is evaluated and the options for
guiding its treatment, and the associated benefits and/or
harms of those options
The limited value of imaging for locating nonpalpable
undescended testicles in these patients

Penson DF, Krishnaswami S, Jules A, et al. AHRQ Comparative Effectiveness Review No. 88.
Available at www.effectivehealthcare.ahrq.gov/undescended-testicle.cfm.