REVIEW ARTICLE

Effectiveness of Hormonal and Surgical Therapies for

Cryptorchidism: A Systematic Review
AUTHORS: David Penson, MD, MPH,a Shanthi
Krishnaswami, MBBS, MPH,b Astride Jules, MD, MPH,c abstract
and Melissa L. McPheeters, PhD, MPHb,d
BACKGROUND AND OBJECTIVE: Controversy remains concerning the
aDepartment of Urology, Center for Surgical Quality and
optimal treatment approach for cryptorchidism. The objective of this
Outcomes, bVanderbilt Evidence-based Practice Center, Institute
for Medicine and Public Health, cDepartment of Preventive study was to assess effectiveness of hormone therapy or surgery for
Medicine, and dObstetrics and Gynecology, Vanderbilt Medical cryptorchidism.
Center, Nashville, Tennessee
METHODS: We searched Medline and other databases from 1980 to
KEY WORDS
cryptorchidism, undescended testicle, systematic review
February 2012. Two reviewers independently assessed studies against
predetermined criteria. Two reviewers independently extracted data
ABBREVIATIONS
FS—Fowler-Stephens procedure and assigned overall quality and strength of evidence ratings using
hCG—human chorionic gonadotropin predetermined criteria.
LHRH—luteinizing hormone releasing hormone
RCT—randomized controlled trial RESULTS: Fourteen studies addressed effectiveness of hormonal treat-
SOE—strength of evidence ments, and 26 studies addressed surgical intervention outcomes. Hor-
All authors helped to conceptualize the study, extract and monal treatment is associated with testicular descent in some
analyze data, draft the manuscript, revise it critically for children, but rates generally do not exceed those seen with placebo
important intellectual content, and gave final approval of the
by .10%. Surgical treatment is associated with success rates of
manuscript submitted.
testicular descent ranging from 33% to 100%, depending on surgery.
www.pediatrics.org/cgi/doi/10.1542/peds.2013-0072
Weighted success averages were 78.7% for 1-stage Fowler-Stephens
doi:10.1542/peds.2013-0072
(FS), 86% for 2-stage FS, and 96.4% for primary orchiopexy. Descent
Accepted for publication Feb 11, 2013
rates were similar among studies comparing laparoscopic and open
Address correspondence to David Penson, MD, MPH, Center for surgeries. Reported harms of hormonal treatments were mild and
Surgical Quality and Outcomes Research, Urologic Surgery and
Medicine, 2525 West End Ave, Ste 1200, Nashville, TN 37203-1738. transient. Adverse effects specifically associated with surgical repair
E-mail: [email protected] were rare.
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). CONCLUSIONS: The body of the reviewed literature comprises primar-
Copyright © 2013 by the American Academy of Pediatrics ily fair- and poor-quality studies, limiting our ability to draw definitive
FINANCIAL DISCLOSURE: The authors have indicated they have conclusions. Hormonal treatment is marginally effective relative to
no financial relationships relevant to this article to disclose. placebo but is successful in some children and with minimal
FUNDING: Supported by the Agency for Healthcare Research and harms, suggesting that it may be an appropriate trial of care for
Quality (contract number: HHSA 290 2007 10065 I).
some patients. Surgical options are effective, with high rates of
COMPANION PAPER: A companion to this article can be found on testicular descent (moderate strength of evidence for FS
page e1908, and online at www.pediatrics.org/cgi/doi/10.1542/
peds.2013-0073. procedures, high for primary orchiopexy). Comparable outcomes
occur with laparoscopic and open approaches. Pediatrics 2013;131:
e1897–e1907

PEDIATRICS Volume 131, Number 6, June 2013 e1897

Cryptorchidism is a congenital condi- orchiectomy may be performed. For for treating cryptorchidism on out-
tion in which 1 or both testicles are not nonpalpable testicles located just comes including testicular descent,
appropriately positioned in the scrotum inside the internal inguinal ring or in function of testicles, further surgical
at birth and cannot be moved into the the abdomen, surgical management is intervention, infertility/subfertility, and
proper position manually. It affects an more complicated and is dependent on development of testicular malignancy.
estimated 3% of full-term male neo- location in the abdomen and the length We present these findings here; the full
nates and up to 30% of premature of the gonadal vessels. If the testicle is report and review protocol are avail-
infants, making it the most common of normal size and appearance and if able from the Agency for Healthcare
male genital anomaly identified at the vessels are of adequate length, Research and Quality Effective Health
birth.1,2 Although about 70% of crypt- primary orchiopexy is usually per- Care Web site (http://effectivehealthcare.
orchid testicles spontaneously de- formed.3,4 If the vessels are so short as ahrq.gov).
scend within the first year of life (most to prohibit tension-free placement of
occurring in the first 3 months), the the testicle in the scrotum, a Fowler- METHODS
number of boys whose condition per- Stephens (FS) orchiopexy is performed.
Search Strategy
sists remains constant at ∼1%.1,2 This procedure entails ligating the tes-
Longer-term consequences of cryptor- ticular vessels. The testicular blood We searched Medline via the PubMed
chidism can include testicular malig- supply then depends on collateral cir- interface, the Cumulative Index to Nurs-
nancy and infertility/subfertility. Once culation from the deferential artery and ing and Allied Health Literature, and
cryptorchidism is diagnosed, treat- the cremasteric system.3 Embase from 1980 to February 2012
ment choices may include watchful This procedure can be performed as by using controlled vocabulary terms
waiting, hormonal treatment, or sur- a single-stage operation, in which the and key terms related to cryptorchi-
gery. vessels are ligated and the testicle is dism. We also hand-searched the ref-
In clinical practice, the choice of initial then placed into the proper position in erence lists of all included studies and
therapy is often selected on the basis of the scrotum, or as a 2-stage procedure. of recent reviews related to cryptor-
age at presentation and the location of In a 2-stage procedure, the vessels are chidism treatment to identify additional
the cryptorchid testicle.3,4 Watchful ligated in the first operation, the testicle references.
waiting may be used in boys ,1 year of is allowed to develop presumably better
age with lower-lying testis in whom collateral circulation in its abdominal Study Selection
spontaneous descent is still a realistic position and is then moved to the proper Study inclusion and exclusion criteria
possibility. Hormonal and surgical position in the scrotum during a second were developed in conjunction with
options are primarily selected on the procedure, usually 3 to 6 months later. an expert panel of clinicians and re-
basis of location and appearance of the Both primary orchiopexy and the FS searchers involved in treating cryptor-
undescended testicle. Hormonal treat- procedure can be performed using chidism. Studies were limited to those
ment with luteinizing hormone re- laparoscopic or open surgical tech- whose participants were prepubescent
leasing hormone (LHRH) analogs and/ nique. boys with cryptorchidism. Studies that
or human chorionic gonadotropin The immediate goal of most inter- evaluated hormonal or surgical treat-
(hCG) could theoretically increase cir- ventions for cryptorchidism is to re- ments had to include at least 1 com-
culating androgens that may, in turn, position the undescended gonad in parison group and provide data on the
promote testicular descent. a “normal” position in the scrotum. position of the testicles after treat-
Surgical options include various forms Intermediate outcomes include psy- ment. Two investigators independently
of orchiopexy or orchiectomy. Primary chological benefits in terms of body reviewed each study against the inclu-
orchiopexy (surgical mobilization of the image, and long-term goals include sion criteria (Table 1) with disagree-
testicle with placement and fixation in preservation of fertility and prevention ments resolved through adjudication by
the scrotum) is usually performed for of testicular malignancy a senior investigator.
palpable cryptorchid testicles that are As part of a larger systematic review of
of relatively normal size and appear- evaluation methods and treatments for Data Extraction
ance that are located in the inguinal cryptorchidism funded by the Agency Investigators extracted data using
canal.3 In cases in which the testicle is for Healthcare Research and Quality,5 a standardized form. Data were verified
found to be atrophic with little or no we assessed the effectiveness of hor- by a second investigator. We collected
viable germ cell tissue remaining, mone therapy and surgical approaches data on study design, study population

e1898 PENSON et al
 REVIEW ARTICLE

TABLE 1 Study Inclusion Criteria: Population, Intervention, Comparator, Outcomes, Timing, Setting confidence in the estimate of effect and
Category Criteria may change the estimate; “low,” in-
Study population Prepubescent males presenting with cryptorchidism or suspected cryptorchidism dicating low confidence that the evi-
Interventions Hormones, including hCG or gonadotropin-releasing hormone, surgical therapy, dence reflects the true effect and
and specific surgical techniques (ie, 1-stage versus 2-stage orchiopexy,
laparoscopic versus open approach)
further research is likely to change our
Comparators Nontreatment, later treatment, hormones, and different surgical techniques confidence in the estimate of effect and
Outcomes • Immediate (within 6 wk of therapy) and short-term (6 wk to 2 y is likely to change the estimate; or
of therapy) outcomes:
○ Testicular size and appearance
“insufficient,” indicating that evidence
○ Testicular position is either unavailable or does not permit
○ Pain
estimation of an effect.
○ Parent/patient satisfaction
○ Need for further surgical intervention
○ Emotional/psychosocial response Data Synthesis
○ Adverse effects, including but not limited to pain, infection, hematoma,
and edema
Data on the hormonal treatments were
• Long-term (.2 y after therapy) outcomes: analyzed qualitatively with the devel-
○ Testicular size and appearance opment of evidence tables. For the
○ Testicular position
○ Endocrine function
surgical interventions, data on pro-
○ Body image portions achieving testicular descent
○ Parent/patient satisfaction were pooled and the weighted pro-
○ Infertility/subfertility
○ Torsion
portions (sum of all successful
○ Testicular malignancy and cancer testicles/total number of testicles in
○ Hernia studies) were calculated for each
○ Emotional/psychosocial response
Timing Time frame for reporting of outcomes was not restricted.
treatment type. Similarly, weighted
Setting All settings were considered, including hospitals and university or academic testicular atrophy rates were derived
medical centers. for each of the surgical techniques.
hCG, human chorionic gonadotropin.

RESULTS
characteristics, baseline and follow-up Conversion details are provided in the
Figure 1 outlines the flow of studies
data on testicular position and other full report. identified for the review. We identified
outcomes as available, and harms. The strength of evidence (SOE) reflects 3448 unique abstracts. Of these, 14
an assessment of the overall body of studies met our inclusion/exclusion
Study Quality Assessment literature, and specifically reflects our criteria and addressed the effective-
Two investigators independently as- confidence that the observed effect is ness of hormonal treatments, and 26
sessed each study using the Cochrane close to the actual effect and unlikely to addressed outcomes of surgical inter-
Risk of Bias tool6 for randomized con- change with further research. We ventions. Information on modifiers of
trolled trials (RCTs) and the Newcastle- assessed SOE for the primary outcomes hormonal and surgical treatments was
Ottawa Quality Assessment Scale7 for of treatment based on 4 major domains, available in 23 studies, and 11 studies
cohort studies. Results were adjudi- including risk of bias (low, medium, or included data on harms.
cated when necessary. The domains high), consistency of findings (in-
used to assess quality for RCTs in- consistency not present or present or Effectiveness of Hormones for
cluded sequence generation, allocation unknown), directness (whether the Achieving Testicular Descent
concealment, blinding, completeness outcome measured was the direct Fourteen studies in 19 publications
of outcome data, and selective report- health outcome of interest), and pre- assessed the effectiveness of hormonal
ing bias. For the cohort studies, the cision (precise or imprecise).8 The therapy as a treatment of cryptorchi-
criteria included selection of study overall SOE was graded “high,” in- dism. Individual studies often included
groups, comparability of study groups, dicating high confidence that evidence multiple arms. Six studies compared
and ascertainment of exposure or reflects true effect; “moderate,” in- LHRH with placebo, 1 compared hCG with
outcome of interest. The scores for dicating moderate confidence that evi- placebo, 4 compared LHRH with hCG, and
each study were converted into a rat- dence reflects the true effect and 6 compared various doses or regimens
ing of “good,” “fair,” or “poor” quality. further research may change our of the same agent. Of the 14 studies,

PEDIATRICS Volume 131, Number 6, June 2013 e1899

 bilateral and unilateral patients, but
the SOE was considered low (Table 3).
Four studies provided data on LHRH
compared with hCG, with no clear in-
dication of either being better than the
other. The studies that compared doses
and dosing schedules within hormone
type were of poor quality and too het-
erogeneous to permit drawing useful
conclusions.
We assessed the SOE for our primary
outcome of testicular descent. There is
moderate SOE for increased testicular
descent with LHRH compared with
placebo, low SOE for increased testic-
ular descent with hCG compared with
placebo, and low SOE for equivalence
between LHRH and hCG.
No studies provided cancer or fertility
outcomes for the comparisons listed,
so the SOE is insufficient for these
outcomes.

Effectiveness of Surgical
Procedures
We identified 26 studies, including 5
RCTs and 1 prospective and 20 retro-
spective cohort studies, that evaluated
surgical treatments.27–53 Four studies
FIGURE 1 were judged good quality,27,45,49,52 1 fair
Disposition of studies identified. *Articles may be excluded for multiple reasons.
quality,32 and the remainder poor
quality.28–31,33–40,42–44,46–48,50,51,53
11 were RCTs,9–22 2 were prospective a benefit to LHRH therapy, 4 did not Eleven studies reported outcomes
cohort studies,23,24 and 1 was a retro- assess statistical significance at all, after either 1-stage FS orchiopexy,
spective cohort study.25,26 Three studies whereas 1 failed to document statisti- 2-stage FS orchiopexy, or primary
were of good quality,17,23,25,26 2 were of cal significance likely because of in- orchiopexy.36–40,42–45,47,48 Nine of these
fair quality,14,15 and 9 were of poor adequate sample size. No harms of studies, all retrospective cohorts,
quality.9–13,16,18–22,24 hormonal treatment were reported. provided success rates by surgical
procedure, although the choice of
Six studies9–16 specifically compared One of the studies comparing LHRH to
successful testicular descent rates af- placebo also included a third hCG arm.14 surgical method is made clinically and
ter administration of LHRH versus pla- As noted previously, results comparing not with the intent of comparative ef-
cebo (2 fair quality14,15 and 4 poor LHRH to placebo were equivocal, with fectiveness. Only 1 study controlled for
quality9–13,16). Five of 6 studies con- LHRH being more effective in achiev- starting testicle location.28
cluded that LHRH was more effective ing testicular descent than placebo in Surgical treatment of cryptorchidism
than placebo in inducing testicular patients with bilateral cryptorchidism, was associated with success rates of
descent with variable reported effect but no better than placebo in patients testiculardescent that ranged from 33%
sizes across studies, whereas 1 study with unilateral cryptorchidism. In this to 100% (Tables 4, 5, and 6), depending
was equivocal (see Table 2).12–16 In the study, hCG was better than placebo at on type of surgery. Each surgical ap-
5 studies that appeared to show achieving testicular descent in both proach was assessed independently for

e1900 PENSON et al
 REVIEW ARTICLE

TABLE 2 Short-Term Testicular Descent in Randomized, Placebo-Controlled Studies of LHRH

Study n Length of LHRH Dose LHRH Frequency LHRH Duration LHRH Descent, % Placebo Descent, %
Follow-up Quality
Statistical Significance
Olsen et al 199215 400 mg 3 times daily 4 wk 9.7 1.6
n = 123
4 wk
Fair
P = .12 (95% CI: 0.1%–16.6%)
Christiansen et al 198814 200 mg 3 times daily 4 wk 9 (bilateral cryptorchidism) 0 (bilateral cryptorchidism)
n = 220 0 (unilateral cryptorchidism) 0 (unilateral cryptorchidism)
4 wk
Fair
NS
De Muinck Keizer-Schrama and 200 mg 3 times daily 4 wk 9.0 8.0
Hazebroek et al 1986–19879–11
n = 237
8 wk
Poor
NR
Hagberg and Westphal, 198212 100 mg 3 times daily 28 d 62.0 3.0
n = 50
4 wk
Poor
NR
Karpe et al 198313 100 mg 6 times daily 28 d 20.0 12.0
n = 50
6 mo
Poor
NR
Wit et al 198616 400 mg 3 times daily 28 d 37 18
n = 49
8 wk
Poor
NR
CI, confidence interval; LHRH, luteinizing-hormone-releasing hormone; NR, not reported; NS, not significant.

ability to achieve testicular descent Only 1 study assessing testicular de- The weighted success rate for all 3
because, as described in the report, scent was rated as good quality.45 This approaches exceeds 75%. The overall
each approach is used under different study had a testicular descent rate of success rate for 1-stage FS is 78.7%
clinical circumstances, and thus it is 63% for 1-stage FS, 67.6% for 2-stage (Table 4). The overall success rate for 2-
inappropriate to compare them with FS, and 89.1% for primary orchiopexy, stage FS is 86% (Table 5). The overall
one another. No studies compared slightly lower in all types of surgery success rate of primary orchiopexy is
hormonal therapy alone to surgery. than the pooled estimate. 96.4% (Table 6).
Atrophy rates were reported in 5
TABLE 3 Strength of Evidence of Hormonal Treatments for Cryptorchidism studies and pooled results were 1.83%
No. of Studies; Total Risk of Bias Consistency Directness Precision Strength of Evidence and for primary orchiopexy (range 0%–4%,
Subjects; Testes Treated Magnitude of Effect 5 studies),37,39,40,43,48 28.1% for 1-stage
Testicular descent FS (range 22%–67%, 3 studies),40,43,48
LHRH versus placebo RCTs/Moderate Consistent Direct Imprecise Moderate LHRH: 9%–62%
and 8.2% for 2-stage FS (range 0%–
6; 752; 935 Placebo: 0%–18%
hCG versus placebo RCT/Moderate Unknown Direct Unknown Low Bilateral: 23% vs 0% 12%, 5 studies).37,39,40,43,48
1; 243; 280 Unilateral: 15% vs 0%
We assessed the SOE as our confidence
LHRH versus hCG RCT/Low Inconsistent Direct Imprecise Low RCT:
3; 431; 465 LHRH: 0%–18.8% in the weighted average of successful
hCG: 5.9%–23.0% testicular descent associated with each
LHRH versus hCG Cohort/High Consistent Direct Imprecise Cohort:
1; 324; 198 LHRH: 29.4%
surgical approach separately (Table 7).
hCG: 34.5% Although retrospective studies typi-
hCG human chorionic gonadotropin; LHRH Luteinizing-hormone-releasing hormone; RCT randomized controlled trial. cally had high risk of bias because of

PEDIATRICS Volume 131, Number 6, June 2013 e1901

TABLE 4 Success Rates After 1-Stage FS authors note that all patients had
Author and Country Quality Total Total Testicles % Success “satisfactory results in relation to size
Participants (n Testicles Treated) and location of testicle,” details re-
Stec et al 200945 United States Good 136 156 63 (27) garding these outcomes are lacking.32
Baker et al 200148 United States Poor 226 263 74.1 (27)
Chang et al 200144 United States Poor 80 92 84 (19)
Another poor-quality cohort study that
Chang et al 200847 United States Poor 48 48 94.3 (35) included both palpable and non-
Comploj et al 201136 Austria Poor 41 50 79 (33) palpable testicles, failed to control for
Denes et al 200843 Brazil Poor 46 54 33 (3)
the location of the testicle in the anal-
Kim et al 201038 South Koreaa Poor 67 86 82 (11)
Pooled % Total: 644 Total: 749 78.7 ysis, and grouped both primary and FS
All studies were retrospective cohorts. orchiopexies into two heterogeneous
a Controlled for location.
groups based on whether an open or
laparoscopic approach was used, mak-
lack of a control group, in grading the We also assessed SOE for the outcome ing it difficult to draw meaningful
overall SOE, we used an implicit com- of testicular atrophy, and on the same conclusions in terms of postoperative
parator group given the known natural methodological basis as was used for testicular position or viability.51
history of disease. Given the low rate testicular descent, found the SOE to be Finally, 1 poor-quality RCT compared
of spontaneous testicular descent, low for a 28.10% atrophy rate with 1- outcomes after various types of lapa-
despite the high risk of bias of ret- stage FS, low for an 8.20% atrophy rate roscopic or open orchiopexies for
rospective studies, SOE might be con- with 2-stage FS, and moderate for nonpalpable testicles.28 This study is
sidered high because of the high a 1.83% atrophy rate for primary one of the few reports in the literature
magnitude of effect when compared orchiopexy. that controlled for location of the tes-
with an implicit control. ticle within the abdomen, allowing for
For the outcome of testicular descent, Effectiveness of Surgical Approach comparisons between procedures and
SOE was moderate for 1- and 2-stage (Open Versus Laparoscopic) minimizing the possibility of con-
orchiopexy and high for primary orchi- Five studies compared an open versus founding by indication. If a testicle was
opexy. All studies were retrospective laparoscopic approach for the same noted via laparoscopic evaluation to
cohort studies, and thus had high risk of procedure (1 good,27 1 fair,32 and 3 poor be high in the abdomen, the patient
bias, but we deemed these to be an quality28,50,51). Two studies noted suc- underwent a laparoscopic 1-stage FS
appropriate study design for the ques- cess rates for laparoscopic surgeries procedure (laparoscopic clipping of
tion of ability of orchiopexy to achieve similar to those of open surgeries.27,50 the testicular vessels). Patients were
testicular descent and considered the One fair-quality cohort study reported then randomized to receive either
relative challenges of this design to be that participants undergoing a laparo- open or laparoscopic 2-stage FS
outweighed by the magnitude of effect. scopic approach “had less pain when orchiopexy.
Primary orchiopexy had higher SOE than compared to the open technique in 80% Perioperative outcomes between par-
1-stage and 2-stage procedures based of cases” using a visual analog scale, ticipants undergoing laparoscopic or
on the higher number of testicles (out- but how this comparison was made open second procedures were com-
comes) reported in the literature. is unclear. Similarly, although the pared, with patients undergoing lapa-
roscopic 2-stage FS orchiopexy noted to
TABLE 5 Success Rates After 2-Stage FS
have statistically significantly shorter
operative times (P = .000), time to
Author and Country Quality Total Participants Total Testicles % Success (n Testicles)
oral feeding (P = .004), hospital stays
Stec et al 200945 United States Good 136 156 67.6 (37)
Baker et al 200148 United States Poor 226 263 87.9 (58) (P = .008), and return to normal activ-
Chang et al 200144 United States Poor 80 92 86 (7) ities (P = .000). Although all testicles in
Chang et al 200847 United States Poor 48 48 80 (10) both groups were noted to have satis-
Comploj et al 201136 Austria Poor 41 50 82 (17)
Denes et al 200843 Brazil Poor 46 54 88 (25)
factory scrotal position after surgery, 2
Dhanani et al 200442 United States Poor 74 83 98 (49) (10%) of the 20 testicles in the laparo-
Kim et al 201038 South Koreaa Poor 67 86 67 (3) scopic arm and 3 (19%) of the 16 tes-
Moursy et al 201137 Egypt Poor 66 76 88.8 (36)
Pooled % Total: 784 Total: 908 86.0
ticles in the open arm had atrophied
All studies were retrospective cohorts.
after 1 year of follow-up. Patients in this
a Controlled for location. study who had viable testicles located

e1902 PENSON et al
 REVIEW ARTICLE

TABLE 6 Success Rates After Primary Orchiopexy hormonal therapy to surgery, finding no
Author and Country Quality Total Participants Total Testicles % Success advantage to the combination of hor-
(n Testicles Treated) mones and surgery compared with
Stec et al 200945 United States Good 136 156 89.1 (92) surgery alone. No studies compared
Baker et al 200148 United States Poor 226 263 97.2 (178)
paternity rates between surgery and
Chang et al 200144 United States Poor 80 92 100 (66)
Denes et al 200843 Brazil Poor 46 54 96 (26) hormonal therapy in isolation. To this
Dhanani et al 200442 United States Poor 74 83 100 (28) end, no data are available to assess
Kim et al 201038 South Koreaa Poor 67 86 98 (49) whether 1 approach is superior for
Moursy et al 201137 Egypt Poor 66 76 100 (28)
Pooled % Total: 695 Total: 810 96.4 fertility outcomes, although it is ac-
All studies were retrospective cohorts. cepted that untreated cryptorchidism is
a Controlled for location.
associated negatively with later fertility.

Harms of Treatments
in the lower portion of the abdomen cohort studies of fair and poor 32 51
Eleven studies of hormonal and surgi-
(close to the inguinal ring) were ran- quality, although the individual studies cal interventions included harms; 2
domized to undergo either laparoscopic report that success rates are similar studies were of good quality,17,52 2 were
or open primary orchiopexy. Like the with both approaches. Similarly, SOE of fair quality,14,15 and 7 were of poor
high abdominal group, patients ran- was low for the effect of the approach quality.12,13,16,18,24,37,48 Eight12–18,24 of 14
domized to laparoscopic orchiopexy on atrophy (Table 7). hormonal studies reported harms.
had statistically superior perioperative There are few studies comparing the The most common outcomes were vir-
outcomes. Of the 21 testicles random- effectiveness of interventions on future ilizing effects (eg, hair, increase in pe-
ized to laparoscopic orchiopexy and the fertility associated with treatment of nis size, and erections), and behavioral
18 randomized to open orchiopexy, all cryptorchidism. Furthermore, in those changes (eg, aggression). Of the 8 hor-
were satisfactorily placed in the scro- studies (where the participants are monal studies reporting harms, 2 did
tum and no cases of atrophic testicles adults who had cryptorchidism in not segregate data by study arm, and
were noted after 1 year of follow-up. childhood), the primary outcome is thus harms could have presented in
We assessed the SOE for equivalence of usually semen analysis parameters, either a treatment or placebo arm.17,24
laparoscopic and open approaches for which is at best a proxy for fertility. One One study reported that 74% of 116
achieving testicular descent to be low study examined ability to father chil- boys receiving hCG had virilizing
with only 1 RCT28 of poor quality and 2 dren and focused on the addition of effects, compared with 5.1% of boys

TABLE 7 Strength of Evidence of Surgical Treatments for Cryptorchidism

No. of Studies; Total Subjects; Risk of Bias Consistency Directness Precision Strength of Evidence and
Treated Testicles Magnitude of Effecta
Testicular descent
1-stage FS 7; 644; 155 Retrospective cohorts/ High Consistent Direct Imprecise Moderate
78.7% (range: 33%–94.3%)
2-stage FS 9; 784; 242 Retrospective cohorts/ High Consistent Direct Imprecise Moderate
86.0% (range: 67%–98%)
Primary orchiopexy 7; 695; 467 Retrospective cohorts/ High Consistent Direct Precise High
96.4% (range: 89.1%–100%)
Open versus laparoscopic RCT High Unknown Direct Unknown Low RCT: No difference in postoperative
repair 1; 75; 75 testicular position
Open versus laparoscopic Cohorts/High Consistent Direct Imprecise Cohorts: No difference in postoperative
repair 2; 96; 110 testicular position
Atrophy
1-stage FS 3; 320; 32 Retrospective cohorts/ High Consistent Direct Imprecise Low
28.1% (range: 22%–67%)
2-stage FS 5; 470; 158 Retrospective cohorts/ High Consistent Direct Precise Low
8.2% (range: 0%–12%)
Primary orchiopexy 5; 470; 273 Retrospective cohorts/ High Consistent Direct Precise Moderate
1.83% (range: 0%–4%)
Open versus laparoscopic RCT High Unknown Direct Unknown Low Laparoscopy: 10%
repairb 1; 75; 75 Open: 19%
a Pooled proportion (range).
b Atrophy rates for second-stage orchiopexy; no atrophy reported with primary orchiopexy.

PEDIATRICS Volume 131, Number 6, June 2013 e1903

receiving only LHRH, but 1 of the hCG slightly higher rates of testicular de- being said, SOE was high only for the
arms also included LHRH and another scent for LHRH and hCG compared with effect of primary orchiopexy on testic-
included human menopausal gonado- placebo and seem to suggest that lower ular descent, for which the most data
tropin.18 All side effects had receded by initial location of the testicle may be are available.
the 6-month follow-up. No other study associated with a greater likelihood of There is increased use of laparoscopic
reported side effects to be as common success (although none of the studies techniques throughout pediatric sur-
as virilization. Reported harms of was sufficiently powered for this as- gery, primarily because of techno-
hormonal treatments were mild and sessment). In addition, some harms of logical advances coupled with the
transient and had receded by 6 treatment were also noted. Specifically, commonly accepted belief that it is less
months. some studies reported more frequent invasive and, therefore, better tolerated
Three studies reported harms associ- temporary virilizing side effects, in- by patients. The literature comparing
ated with laparoscopic surgery.37,48,52 cluding increased penile length, erec- open to laparoscopic surgery in crypt-
Rare cases of intestinal injury due to tions, and testicular enlargement, orchidism appears to indicate that
Veress needle puncture (1 case),48 although all side effects were transi- success rates are at least comparable
postoperative laparoscopic port site tory. between the 2 approaches, although it
reducible (3 cases),52 and incarcerated With regard to the surgical treatment of is worth noting that the SOE was low.
(2 cases) hernia37 were noted with cryptorchidism, all approaches were There appeared to be some evidence
laparoscopy. They are not specific to associated with success rates of 75% or that patients undergoing laparoscopy
cryptorchidism repair and can occur higher. When surgically treating boys reported shorter convalescence and
with any type of laparoscopy. Overall, with cryptorchidism, providers must less postoperative pain; however, cer-
adverse effects specifically associated select both a specific procedure (pri- tain studies reported rare harms that
with surgical repair for cryptorchidism mary orchiopexy, 1- or 2-stage FS were unique to laparoscopic surgery,
were rare. orchiopexy, or orchiectomy) and ap- such as hernia at the port site or Veress
proach (open versus laparoscopic). In needle injury.
DISCUSSION the case of specific procedures, al- Despite the low SOE associated with the
The goal of any intervention for crypt- though the fairly substantive observa- literature on laparoscopy in cryptor-
orchidism is to move the undescended tional literature reviewed here reports chidism, it is clear that this approach
testicle to a normal position in the outcomes after various types of orchi- plays an important role in the diagnosis
scrotum, in as safe and least invasive opexies, the fact that the choice of and treatment of cryptorchidism. In
way possible. Although there are procedure is based primarily on the 2013, diagnostic laparoscopy is almost
a number of therapeutic options avail- initial location of the testicle makes always the approach of choice when
able to parents and providers, our study comparing the results of studies diffi- attempting to localize a nonpalpable
found that the current literature on cult. Specifically, primary orchiopexy is cryptorchid testicle thought to be po-
comparative effectiveness may not more likely to be used in cryptorchid tentially located in the abdomen. As
provide definitive answers for those testes found to be in lower positions, evidence, all but 1 of the studies in our
seeking to provide guidance in clinical closer to the scrotum, increasing the review published in the past 5 years that
decision-making. Specifically, only 7 likelihood of success. Conversely, FS included assessment of the abdomen
studies identified in our analysis were orchiopexies (whether 1 or 2 stage) fora nonpalpable testicle28,32,36–38,43,47,51
of good quality17,23,25–27,45,49,52 and this tend to be reserved for higher-located used laparoscopy for this part of the
is reflected in the SOE, which was testicles, which, by their nature, are procedure, even if they used an open
generally low to moderate for any in- more difficult to treat and more likely to technique to repair the cryptorchi-
tervention and outcome. This, in turn, retract back to an abnormal position dism.
underscores the need for further re- after surgery. To this end, the obser- Clearly, the existing evidence leaves
search. vation that primary orchiopexy is as- many questions regarding the optimal
In the case of hormonal treatment, sociated with higher success rates approach to the treatment of cryptor-
most studies were of poor quality, when compared with the FS approach is chidism unanswered. In the case of
precluding definitive conclusions as more likely due to underlying baseline hormonal therapy, most studies have
to a specific expected effect rate for differences in patients undergoing this focused primarily on LHRH and its
any hormone or combination thereof. procedure than true differences in the agonists because it is easily adminis-
Acknowledging this, studies report effectiveness of the technique. That tered intranasally. A wide range of

e1904 PENSON et al
 REVIEW ARTICLE

success rates is seen across studies, and unilateral or bilateral disease. This children and with minimal side effects,
possibly owing to heterogeneity in the is particularly important for initial suggesting that it may be an appro-
study populations or potentially owing testicular location, which may be both priate trial of care for some patients. If
to variability in drug absorption a modifier of effectiveness and a factor successful, these patients should con-
through the intranasal route. Some used to choose the surgical procedure. tinue to be monitored for late re-ascent,
literature suggests that differences Finally, these studies must include as most of the studies on this issue did
may be because of initial location of the follow-up for at least 6 to 12 months to not include long-term follow-up. Sur-
testicle, but this is an area warranting observe for delayed atrophy of the gical options appear effective, with
more study, including conducting ad- testicle. rates of normal postoperative scrotal
ditional studies in which patients are The literature available to assess treat- position .75%. Our ability to draw
carefully selected to assess efficacy by ment of cryptorchidism also is charac- definitive conclusions regarding the
testicle location, or analyses carefully terized by a lack of standardization of comparative effectiveness of the sur-
controlled for this effect. Given that any outcomes. Studies routinely use the gical approaches is limited by con-
side effects from hormonal therapy are founding by indication in the individual
term “success rates” but fail to define
temporary and not life-threatening, it studies, which also affects the quality
a successful outcome. In some cases,
would be of some value to be able to of the literature. The strength of the
the authors report success rates as
accurately inform parents of what the evidence for the effects of either 1-
proper placement of the testicle in the
possibility of success is with this stage or 2-stage FS procedures on
scrotum in the early postoperative pe-
treatment, as even a small likelihood of testicular descent is moderate (low for
riod and then report $6-month atro-
success coupled with the avoidance of atrophy) and high for primary orchi-
phy rates separately. Given that the
surgery may be appealing. opexy (moderate for atrophy). Compa-
goal of the procedure is usually to
Because most reviewed studies of place the testicle in the scrotum and to rable outcomes have been seen with
surgery were observational, the po- maximize long-term endocrine func- laparoscopic and open approaches to
tential for confounding and effect tion and fertility, the definition of suc- surgical repair (low SOE for testicular
measure modification in this literature cess should always reflect both of descent and atrophy in studies com-
to obscure true effects is significant. paring these approaches).
these important end points (testicular
Studies intended to address compara-
location and size), and we encourage
tive effectiveness of treatment in this ACKNOWLEDGMENTS
researchers to report both.
condition, including 1-stage versus 2- We thank Tanya Surawicz and Nila Sathe
stage FS orchiopexy for nonpalpable for their assistance with this article. We
abdominal testicles should either use CONCLUSIONS also thank our Technical Expert Panel
a randomized design or carefully con- Hormonal treatment is marginally and Agency for Healthcare Research
trol for covariates, such as testicular effective relative to placebo, with mod- and Quality Task Order Officer for their
location, size and appearance, ectopia, erate SOE, but is successful in some input on the full review.

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