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Interventions for undescended testes in children

  1. Aniruddh V Deshpande1,*,
  2. Peter Michail2,
  3. Grahame H Smith3

Editorial Group: Cochrane Renal Group

Published Online: 13 FEB 2014

DOI: 10.1002/14651858.CD010978


How to Cite

Deshpande AV, Michail P, Smith GH. Interventions for undescended testes in children (Protocol). Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD010978. DOI: 10.1002/14651858.CD010978.

Author Information

  1. 1

    University of Newcastle, School of Medicine and Public Health, Newcastle, New South Wales, Australia

  2. 2

    School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia

  3. 3

    The Children's Hospital at Westmead, Department of Urology, Westmead, NSW, Australia

*Aniruddh V Deshpande, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. deshpande.aniruddh@gmail.com. deshpande.aniruddh@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 13 FEB 2014

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
 

Description of the condition

Undescended testes is a common problem in boys and is defined as failure of testis to reach a scrotal position (Acerini 2009).The prevalence of undescended testes at birth has been reported to be 9% to 30% in preterm males and 4% to 5% of full-term males (Acerini 2009; Hutson 2007). The undescended testes can be found in any location along the line of descent of testis (e.g. lower pole of the kidney to the superficial inguinal pouch). Depending on the severity of the maldescent, undescended testes are commonly discussed as "palpable" or "impalpable". Palpable undescended testes are located in the superficial inguinal pouch or in the inguinal canal. Impalpable undescended testes may be in the inguinal canal or in the abdomen proximal to the deep inguinal ring. It has been estimated that only about 20% of undescended testes are at the deep inguinal ring or proximal to that. If left untreated, testis in an undescended location is prone to possible complications like histological changes leading to subfertility, increased risk of malignancy, trauma and torsion (Hutson 2007). Prompt recognition and treatment of undescended testes has been recommended in order to optimise long term testicular function since progressive damage to germ cells has been convincingly proven beyond the age of two years (Ong 2005).

 

Description of the intervention

Treatment of undescended testes is aimed at relocating the affected testis in its anatomically appropriate scrotal position in a timely manner to prevent the sequelae and complications including subfertility and testicular cancer (Hutson 2007; Pettersson 2007). The current standard treatment for undescended testes is surgical (orchiopexy). In recent literature, an increase in both the incidence of undescended testes and surgical correction for the same has been reported (Acerini 2009; Mandat 1992). The increase in the incidence is likely to be due an increased awareness and hence an increase in detection during the first year of life (Acerini 2009). Surgical correction of undescended testes is thus one of the commonest interventions to be performed in children. Various surgical techniques are currently practiced (Aycan 2006; Cortesi 1976; Esposito 2003; Jallouli 2009; Park 2010). The comparative efficacy of these techniques has not been evaluated using meta-analytic techniques. In addition, hormonal therapy is also used for stimulating testicular descent (Jallouli 2009; Zivkovic 2006; Zucchini 1996).

 

Surgical treatment (orchiopexy)

Surgical correction of undescended testes was first performed in 1877 by Annandale (Fischer 2005). The surgical technique was further refined through the contributions of Schuller, Bevan and Lattimer (Park 2010). The basic principles underpinning orchiopexy include separation of the processus vaginalis from the cord structures, achieving adequate cord length and anchoring the testis in a subdartos pouch within the scrotum. A success rate of 90% has been reported for this technique for all undescended testes except the high abdominal ones (Park 2010). Fowler and Stephens described a technique of dividing the testicular vessels in order to enable testes with short vessels to be brought down to the scrotum (Fowler 1959). This technique relies on the development of collateral circulation through the cremasteric artery and the artery to the vas deferens. The success of this procedure was reported to be about 70%, failure was due to an ischaemic loss of the testis. This procedure is now done as a two-stage procedure with some improvement in the testicular survival (Elyas 2010). In the 1970s, laparoscopy was first used to locate the impalpable testis (Cortesi 1976). The use of laparoscopy has had a significant impact on the management of the high intra-abdominal testis (Gatti 2007) and lead to a resurgence in the popularity of the Fowler-Stephens orchiopexy both as a single-stage and a two-stage procedure.

 

Hormonal therapy

Human chorionic gonadotropin (HCG), human menopausal gonadotropin, and gonadotropin releasing hormone (GnRH) analogue have been reported to effect the descent of testis in a child with undescended testis (Aycan 2006; Dixon 2007; Esposito 2003; Giannopoulos 2001). If hormonal therapy is used, it is typically commenced in the neonatal period (Dixon 2007) but has also been reported to induce descent at a later age (Esposito 2003).The reported success rates are as high as 60% (Aycan 2006; Giannopoulos 2001) when a combination of HCG and luteinising hormone releasing hormone (LH) have been used whereas success rates between 25% to 35% have been reported by others (Esposito 2003). A 20% response was noted in bilateral undescended testes (Dixon 2007). Beneficial effects of hormonal therapy on the contralateral testis have also been reported (Zivkovic 2006). On the other hand, a high incidence of side effects has also been reported (Cortes 2000; Thorsson 2007).

There has been an ongoing debate over the optimal age of intervention for undescended testes (Hutson 2007; Ong 2005; Thorup 2009). Some authors believe that early surgical correction (between three and six months) prevents histological changes which could reduce fertility or increase malignancy risk (Hutson 2007), while others believe that correction up to two years of age prevents long-term complications (Thorup 2009). Traditionally, surgical interventions have been delayed beyond six months due to a higher incidence of complications of orchiopexy in early infancy

 

How the intervention might work

The aim of interventions in children with undescended testes is to achieve a viable testis in a scrotal position at an optimal age. Germ cell development is an active process that continues till about four years after birth (Ong 2005). It is known that testes in an undescended location are prone to progressive histological damage resulting in a possible decrease in the germ cells (Ong 2005). Maturation of neonatal gonocytes into spermatogonia is an active process that extends to up to four years of age (Ong 2005). Timely relocation of the testis in a scrotal position can halt further damage to the germ cells (Tasian 2009; Thorup 2009). A 2% risk/month of severe germ cell loss and 1% risk/month of Leydig cell depletion for each month a testis remains undescended, and a 50% greater risk of germ cell depletion in nonpalpable testes has been reported, thus emphasising the need for early relocation of an undescended testis (Tasian 2009). At the same time, early relocation of undescended testes appeared to have no effect on the risk of malignancy or sperm extraction (Pike 1986; Wiser 2009).

Surgery is currently recommended before the age of two years (Hutson 2007; Thorup 2009) and this is believed to decrease the chance of impact on germ cell maturation. Hormonal therapy is commenced in the newborn period to induce testicular descent (Dixon 2007). Hormonal therapy has also been used after surgical correction since it may have beneficial effects on germ cell maturation in the operated as well as the contralateral testis (Zivkovic 2006).

 

Why it is important to do this review

In reported literature, hormonal therapy and surgical correction have been used with varying successes (Ong 2005; Park 2010). Hormonal therapy has also been used as an adjunct to surgical correction (Jallouli 2009; Zivkovic 2006). The precise role of either modality (surgical and hormonal) of therapy needs to be clarified on the backdrop of the possible benefits and harms.

Overall, robust comparisons between hormonal therapy and surgical correction, between various surgical approaches and between different recommended ages of correction will provide useful information for clinicians and policy makers to tailor the clinical practice and also design future research studies.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

This review aims to look at the benefits and harms of interventions for undescended testes in children performed in order to facilitate placement of the testis or testes in a scrotal position without subsequent atrophy.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
 

Criteria for considering studies for this review

 

Types of studies

All randomised controlled trials (RCTs), and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) that are comparing an intervention for undescended testes with another intervention or no treatment or comparing early versus late intervention. We will include studies looking at both surgical and medical treatment. We will also compare types of surgical interventions with each other.

 

Types of participants

We will include studies of children undergoing surgery or hormonal therapy for children up to 16 years with undescended testes.

 

Types of interventions

  1. Orchiopexy versus no treatment
  2. Hormonal therapy versus no treatment
  3. Orchiopexy versus hormonal therapy
  4. Open orchiopexy versus laparoscopic orchiopexy
  5. Single-stage orchiopexy versus two-stage orchiopexy
  6. All types of testicular fixation
  7. Adjuvant hormonal therapy versus no treatment (in combination with orchiopexy).

Expected procedures include inguinal orchiopexy, scrotal 'Bianchi' orchiopexy, single-stage Fowler-Stephen's orchiopexy (open or laparoscopic), two-stage Fowler-Stephen orchiopexy (open or laparoscopic) and laparoscopic orchiopexy. Hormonal therapy for undescended testes will include primary treatment with HCG or GnRH analogues. Studies may also include hormonal therapy used as an adjuvant to surgical interventions.

We will exclude studies if they include the following (only).

  • Re-do surgery for failed orchiopexy
  • Orchiopexy or testicular fixation for retractile testes
  • Orchiopexy or testicular fixation for ascending testes (acquired undescended testes). The diagnosis of ascending testes (i.e. testes in an undescended location after being noted to have been completely descended) is being made with increasing frequency in recent years (Tasian 2010). The precise aetiology remains unclear. We have chosen to exclude the ascending testes from this review due to the underlying differences in the age of diagnoses, pathogenetic mechanisms and outcomes of treatment.
  • Orchiopexy beyond childhood
  • Trapped testes resulting from prior inguinal surgery

 

Types of outcome measures

 

Primary outcomes

  1. Presence of testis in a scrotal position without atrophy
  2. Testicular growth (measured in comparison to the unaffected contralateral side). The size of the affected testis is often smaller than the normally descended peer. Testicular volume is an approximate indicator of underlying spermatogenesis and hence catch up growth following intervention can be compared as a surrogate outcome of improvement in spermatogenesis in the affected testis.
  3. Histology
    1. Histological fertility index. The histological fertility index is defined as the number of Ad spermatogonia per tubule. Ad (dark) spermatogonia seen on testicular biopsy obtained at the time of surgery are an indicator of defective germ cell maturation
  4. Sperm counts or paternity rates. This will only be relevant if the study includes a long follow-up into late adolescence or adulthood.

 

Secondary outcomes

  1. Complications of intervention: wound infection, testicular atrophy, other surgical complications, side effects of hormones
  2. Effects on contralateral testis
  3. Need to redo intervention. This will not include multiple doses of hormones if the regime has been explicitly pre stated in the protocol
  4. Compare outcomes of intervention on palpable versus impalpable testes, only if data is available
  5. Satisfaction scores (parents or children)
  6. Other fertility indices: Inhibin B, FSH and LH

 

Search methods for identification of studies

 

Electronic searches

We will search the following databases from inception using search terms developed through contact with the Cochrane Renal Group's Trials Search Co-ordinator.

  1. Cochrane Register of Controlled Trials (CENTRAL) via TheCochraneLibrary.com
  2. MEDLINE (OvidSP)
  3. EMBASE (OvidSP)
  4. BIOSIS Previews
  5. International Clinical Trials Register (ICTRP) Search Portal
  6. ClinicalTrials.gov.

We will use search filters for retrieving RCTs in MEDLINE and EMBASE as listed in Chapter 6 of the Cochrane Handbook of Systematic Reviews of Interventions (Lefebvre 2011).

See Appendix 1 for search terms used in strategies for this review.

 

Searching other resources

  1. Reference lists of paediatric surgery and paediatric urology textbooks, clinical practice guidelines, review articles and relevant studies.
  2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

 

Data collection and analysis

 

Selection of studies

The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts will be screened independently by two authors, who will discard studies that are not applicable; however, studies and reviews that might include relevant data or information on studies will be retained initially. Two authors will independently assess retrieved abstracts and, if necessary, the full text of these studies to determine which studies satisfy the inclusion criteria. A third author will be consulted to resolve any disagreement that arises between the two authors.

 

Data extraction and management

Data extraction will be carried out independently by two authors using standard data extraction forms. Studies reported in non-English language journals will be translated before assessment. Where more than one publication of one study exists, reports will be grouped together and the publication with the most complete data will be used in the analyses. Where relevant outcomes are only published in earlier versions, these data will be used. Any discrepancy between published versions will be highlighted.

 

Assessment of risk of bias in included studies

The following items will be independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?
  • Was allocation adequately concealed (selection bias)?
  • Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?
    • Participants and personnel
    • Outcome assessors
  • Were incomplete outcome data adequately addressed (attrition bias)?
  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
  • Was the study apparently free of other problems that could put it at a risk of bias?

 

Measures of treatment effect

For dichotomous outcomes (successful versus unsuccessful surgery, need for re-do surgery) results will be expressed as risk ratio (RR) with 95% confidence intervals (CI). We anticipate the misclassification of the categorical pretreatment characteristics as well as the outcomes to be a 'non-differential type' and hence likely to shift the point estimate towards the null. Where continuous scales of measurement are used to assess the effects of treatment (testicular size, histological fertility index), the mean difference (MD) will be used, or the standardised mean difference (SMD) if different scales have been used.

 

Unit of analysis issues

We will only include RCTs with a parallel group design in our review.

The unit of analysis in our review is an undescended testis.

Cluster randomisation (where individuals are randomised in groups) and cross-over studies are unlikely to be used to investigate the role of any single therapy for undescended testes and it is anticipated that the majority of studies will be parallel group RCTs.

 

Dealing with missing data

Any further information required from the original author will be requested by written correspondence (e.g. emailing or writing to corresponding author) and any relevant information obtained in this manner will be included in the review. Evaluation of important numerical data such as screened, randomised patients as well as intention-to-treat (ITT), as-treated and per-protocol (PP) population will be carefully performed. Attrition rates, for example drop-outs, losses to follow-up and withdrawals will be investigated. Issues of missing data and imputation methods (e.g. last-observation-carried-forward (LOCF)) will be critically appraised (Higgins 2011).

 

Assessment of heterogeneity

Heterogeneity will be analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² test (Higgins 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.

 

Assessment of reporting biases

If possible, funnel plots will be used to assess for the potential existence of small study bias (Higgins 2011).

 

Data synthesis

Data will be pooled using the random-effects model but the fixed-effect model will also be used to ensure robustness of the model chosen and susceptibility to outliers.

 

Subgroup analysis and investigation of heterogeneity

Subgroup analysis will be used to explore possible sources of heterogeneity. Heterogeneity among participants could be related to the pretreatment location of the undescended testis or the age of the child at the time of the intervention. For example, the outcomes of intra-abdominal testes may be different (less efficacy) as compared to the testes located outside the superficial inguinal ring. Heterogeneity in treatments could be related to the type of surgical procedure used or the dose of the hormone used to effect descent. Adverse effects will be tabulated and assessed with descriptive techniques, as they are likely to be different for the various interventions used. Where possible, the risk difference with 95% CI will be calculated for each adverse effect, either compared to no treatment or to another agent.

 

Sensitivity analysis

We will perform sensitivity analyses in order to explore the influence of the following factors on effect size.

  • Repeating the analysis excluding unpublished studies
  • Repeating the analysis taking account of risk of bias, as specified above
  • Repeating the analysis excluding any very long or large studies to establish how much they dominate the results
  • Repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), country.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

We would like to thank the referees for their feedback and advice during the preparation of this protocol.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
 

Appendix 1. Electronic search strategies


DatabaseSearch terms

CENTRAL
  1. Cryptorchidism:ti,ab,kw
  2. cryptorchism:ti,ab,kw
  3. (undescended next (test*s or testicle*)):ti,ab,kw
  4. (ectopic next (test*s or testicle*)):ti,ab,kw
  5. (maldescended next (test*s or testicle*)):ti,ab,kw
  6. (impalpable next (test*s or testicle*)):ti,ab,kw
  7. "testicular maldescent":ti,ab,kw
  8. "maldescensus testis":ti,ab,kw
  9. (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8)

MEDLINE
  1. Cryptorchidism/
  2. cryptorchidism.tw.
  3. cryptorchism.tw.
  4. (undescended adj (test#s or testicle*)).tw.
  5. (ectopic adj (test#s or testicle*)).tw.
  6. (maldescended adj (test#s or testicle*)).tw.
  7. (impalpable adj (test#s or testicle*)).tw.
  8. testicular maldescent.tw.
  9. maldescensus testis.tw.
  10. or/1-9

EMBASE
  1. Cryptorchism/
  2. Ectopic Testis/
  3. cryptorchidism.tw.
  4. cryptorchism.tw.
  5. (undescended adj (test#s or testicle*)).tw.
  6. (ectopic adj (test#s or testicle*)).tw.
  7. (maldescended adj (test#s or testicle*)).tw.
  8. (impalpable adj (test#s or testicle*)).tw.
  9. testicular maldescent.tw.
  10. maldescensus testis.tw.
  11. or/1-10



 

Appendix 2. Risk of bias assessment tool


Potential source of biasAssessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).

High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.

Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).

High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors.
Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data.
Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.

High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.

Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting
Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).

High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table
Low risk of bias: The study appears to be free of other sources of bias.

High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.

Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

  1. Draft the protocol: AD, GS, PM
  2. Study selection: AD, GS, PM
  3. Extract data from studies: AD, GS, PM
  4. Enter data into RevMan: AD, GS, PM
  5. Carry out the analysis: AD
  6. Interpret the analysis: AD, GS, PM
  7. Draft the final review: AD, GS, PM
  8. Disagreement resolution: AD, GS, PM
  9. Update the review: AD

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest

None known.

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Acknowledgements
  7. Appendices
  8. Contributions of authors
  9. Declarations of interest
  10. Additional references
Acerini 2009
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Aycan 2006
  • Aycan Z, Ustunsalih-Inan Y, Cetinkaya E, Vidinlisan S, Ornek A. Evaluation of low-dose hCG treatment for cryptorchidism. Turkish Journal of Pediatrics 2006;48(3):228-31. [MEDLINE: 17172066]
Cortes 2000
Cortesi 1976
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Dixon 2007
Elyas 2010
Esposito 2003
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Fischer 2005
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Gatti 2007
Giannopoulos 2001
Higgins 2003
Higgins 2011
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Hutson 2007
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Jallouli 2009
  • Jallouli M, Rebai T, Abid N, Bendhaou M, Kassis M, Mhiri R. Neoadjuvant gonadotropin-releasing hormone therapy before surgery and effect on fertility index in unilateral undescended testes: a prospective randomized trial. Urology 2009;73(6):1251-4. [MEDLINE: 19371931]
Lefebvre 2011
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Ong 2005
Park 2010
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Pettersson 2007
Pike 1986
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Tasian 2009
  • Tasian GE, Hittelman AB, Kim GE, DiSandro MJ, Baskin LS. Age at orchiopexy and testis palpability predict germ and Leydig cell loss: clinical predictors of adverse histological features of cryptorchidism. Journal of Urology 2009;182(2):704-9. [MEDLINE: 19539332]
Tasian 2010
Thorsson 2007
Thorup 2009
  • Thorup J, Cortes D. Surgical treatment and follow up on undescended testis. Pediatric Endocrinology Reviews 2009;7(1):38-43. [PUBMED: 19696715]
Wiser 2009
  • Wiser A, Raviv G, Weissenberg R, Elizur SE, Levron J, Machtinger R, et al. Does age at orchidopexy impact on the results of testicular sperm extraction?. Reproductive Biomedicine Online 2009;19(6):778-83. [MEDLINE: 20031016]
Zivkovic 2006
  • Zivkovic D, Bica DG, Hadziselimovic F. Effects of hormonal treatment on the contralateral descended testis in unilateral cryptorchidism. Journal of Pediatric Urology 2006;2(5):468-72. [EMBASE: 2006540340]
Zucchini 1996
  • Zucchini S, Cacciari E. Medical therapy of cryptorchidism. Pediatria Medica e Chirurgica 1996;18(5 Suppl):35-6. [MEDLINE: 9045221]