The undescended testis: Clinical management and scientific advances

doi:10.1053/j.sempedsurg.2016.05.007

Seminars in Pediatric Surgery

Volume 25, Issue 4, August 2016, Pages 241-248

https://doi.org/10.1053/j.sempedsurg.2016.05.007 Get rights and content

Abstract

Undescended testes (UDT), where one or both testes fail to migrate to the base of the scrotum, can be congenital (2–5% of newborn males) or acquired (1–2% of males). The testis may be found in any position along its usual line of descent. Cryptorchidism affects the developing testicular germ cells and increases the risk of infertility and malignancy. Clinical management aims to preserve spermatogenesis and prevent the increased risk of seminoma. Examination to document the testicular position will guide the need for imaging, medical management and the surgical approach to orchidopexy.

Introduction

An undescended or cryptorchid testis, by definition, does not lie at the base of the scrotum, and it occupies an alternative position either in the groin or within the abdominal cavity. Congenital undescended testis (UDT) affects 2–5% of newborn males, when one or both testes are not located in the scrotum at birth.¹ This figure decreases to 1–2% by 3 months of age, as about half will descend spontaneously shortly after birth.² However, by about 12 weeks post term, an UDT is very unlikely to spontaneously descend further, and medical management is required.³ At present, the recommended age for orchidopexy is between 6 and 12 months, and there is reasonable consensus for this in North America,4, 5 Europe6, 7 and the UK.⁸

Foetal testicular hormones are vital for testicular descent, and the primary cause for most cases of UDT is thought to be insufficient pituitary or placental stimulation causing inadequate production of insulin-like hormone 3 (INSL3) and androgens in the developing testis. Androgens are thought to act via the two genitofemoral nerves, with minor deficiencies affecting one side more than the other, leading to unilateral pathology.⁹ Risk factors for congenital UDT include intrauterine growth retardation, prematurity, excessive oestrogen exposure and smoking during pregnancy.¹⁰

Acquired or ascending UDT is another form of UDT, which presents later in childhood and has an incidence of 1–2%.¹¹ In these cases, the testis has been clearly documented to be within the scrotum in infancy but does not remain there over time. We have attributed the cause of the ascending testis to failure of the spermatic cord to elongate as the child grows, causing the testis to ‘ascend’ out of its previously occupied scrotal position,¹² as the distance from the inguinal canal to the scrotum doubles in childhood because the pelvis enlarges. A persistent fibrous remnant of the processus vaginalis has been shown at surgery,¹² which is thought to prevent normal elongation of the spermatic cord between birth and later childhood. Boys with delayed (or postnatal) testicular descent are at higher risk of acquired UDT,¹³ and should be kept under annual review for surveillance of testicular ascent.

Section snippets

Normal testicular descent

While the complete mechanism of testicular descent remains elusive, it is generally accepted to occur in two distinct stages. The first, or trans-abdominal stage, occurs between 8 and 15 weeks of gestation and involves swelling and strengthening of the distal gubernaculum (genito-inguinal ligament) under the control of insulin-like hormone 3 (Insl3). This ‘swelling reaction’ holds the gubernaculum at a fixed length, so that it does not elongate with foetal growth as happens in a female. At the

Effects of cryptorchidism

The scrotal environment is 4°C cooler than core body temperature, and the postpartum human testis is adapted to function at this cooler temperature. Failure of testicular descent subjects the postnatal testis in infants to higher temperatures and leads to progressive abnormalities in the biochemistry and physiology of the testis secondary to heat stress.

It is interesting to note that in the standard laboratory models of UDT, the rat and mouse, testicular descent is not complete until puberty.

The germ cells (normal and abnormal)

It is critical for the pluripotent gonocyte to undergo transformation at 3–6 months of age to become a unipotent spermatogonial stem cell, the type-A spermatogonium, during mini-puberty. Gonocyte transformation involves morphological changes including cell migration (from the centre of the tubule to the periphery), proliferation and differentiation, while the remaining gonocytes undergo apoptosis.23, 24, 25, 26, 27, 28 As human testes descend into the scrotum before birth, the gonocyte

Clinical management of UDT

Management of UDT aims to preserve testicular function (spermatogenesis) and prevent the increased risk of seminoma. Management of UDT varies in palpable versus impalpable testes, with diagnostic investigations dependent on this classification. Newborns with cryptorchidism and an associated bifid scrotum and/or hypospadias require immediate investigation, as the clinical findings may represent a form of disorder of sex development (DSD).²⁹ Similarly, those with bilateral impalpable testes also

Classification of UDT

Examination is best done with a relaxed child (shortly after removing the nappy is ideal), and observation of the scrotum is vital. An empty, under-developed hemi-scrotum is suggestive of congenital cryptorchidism, while a developed hemi-scrotum is more likely in ascending testis. The lowest, tension-free testicular position is the most popular method of description of UDT.¹³ Testes are classified as normal, high scrotal, supra-scrotal, nonpalpable or other.

In congenital UDT, the testis has

Diagnostic imaging

The mode of diagnostic imaging is guided by the clinical presentation, as the yield varies according to testicular location, specifically whether it is palpable or not. Options include ultrasound scanning (USS), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and magnetic resonance venography (MRV). Computed tomography (CT) is rarely utilised due to the alternative (radiation-free) modalities that are widely available. Any patient with abnormal anatomy certainly warrants

Hormone therapy

Hadziselimovic and Hoecht²² and Hadziselimovic and Herzog⁴⁸ have advocated for several decades that hormone treatment may be required in cryptorchidism. This is because a group of boys with cryptorchidism and high risk of infertility could be identified in infancy if testicular biopsies showed low germ cell number and lack of adult dark spermatogonia (the putative stem cells) in the germinative epithelium.21, 47 According to this hypothesis, insufficient gonadotrophin stimulation of germ cell

Surgical management of UDT

The principle behind surgery for UDT remains to mobilise the testis on an adequate blood supply before relocating it within the scrotum. Mobilisation requires separation of the PV and/or hernial sac and other investing structures. Traditionally any associated hernial sac was divided and ligated to prevent postoperative development of inguinal hernia. Orchidopexy without PV ligation has been instituted for more than a decade with the perceived benefit of decreased risk of damage to cord

Complications of surgery

Surgical success following orchidopexy is defined as a testis in the scrotal position with no evidence of testicular atrophy. Complications include infection, haematoma and wound breakdown, testicular atrophy or obstruction/trauma to the vas. Stitch abscess with silk has also been reported, but is less common now with the widespread use of absorbable sutures. Orchidopexy complication rates vary between 1.2% and 6%,⁸³ with outcome dependent on the pre-operative position before surgical

Late presentation of UDT

Management of young adults who present late with cryptorchidism is contentious. Maldescent of the testis is clearly associated with malignant change, with a relative risk of between 2.75 and 8.⁸⁴ Therefore, should post-pubertal UDT in patients fit for anaesthesia be managed with orchidopexy or should they proceed straight to orchidectomy? Analysis of histopathology of orchidectomy specimens in post-pubertal patients demonstrated normal spermatogenesis in only 1 of 52 samples (aged 15–66 years),

Conclusion

Congenital and acquired UDT account for a large burden of disease in children. Surgical correction remains a necessity despite medical treatments, with the surgical approach dictated according to the position of the UDT.

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Paediatric urology covers all aspects of urological care in children. Many conditions are specific to children and, although there is some crossover with adult urology, diagnosis and management can be significantly different. Paediatric urology is increasingly undertaken in tertiary centres and many adult urologists will only deal with basic paediatric urology in their practice. A broad knowledge of the topic, however, and the implications on development and adult presentations is essential. This article will covers all the relevant topics for a broad understanding of paediatric urology, antenatal hydronephrosis including pelvi-ureteric junction obstruction, vesico-ureteric reflux and megaureter, posterior urethral valves, urinary tract infection, incontinence, undescended testis, hypospadias, hydrocoele, phimosis, the acute scrotum, disorders of sexual development and bladder extrophy and epispadias.
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Many studies conducted in different species investigated the effect of heat on testes [60]. Undescended testes are exposed to body temperature that is higher than at the scrotal area [61]. This thermal stress inhibits the differentiation of spermatogonia resulting in an arrest of spermatogenesis, reduced seminiferous tubule size, germ cell depletion, and fibrosis [62], but also enhances the production of reactive oxygen species and specific heat shock proteins involved in SCT proliferation [48,49].
Cryptorchidism is a common disorder in the canine population with some aspects still unclear. Although the bilateral condition is known to lead to fertility problems and predisposition to testicular cancer, the neoplastic risk for scrotal testis in unilateral cryptorchid dog is controversial. Therefore, the therapeutic approach to the canine unilateral cryptorchid is arbitrary so far.
This study aimed to investigate precancerous testicular lesions, such as immaturity and atrophy, and compare them in scrotal and undescended testes using an in-depth diagnostic analysis based on immunophenotypic patterns. With this purpose, 26 adult male dogs of different ages and breeds, affected by unilateral or bilateral cryptorchidism were enrolled. After surgical removal, testes were examined immunohistochemically to assess their positivity for specific markers of the canine foetal/neonatal period, that is vimentin (VIM), cytokeratin (CK), desmin (DES), inhibin-α (INH), and anti-Müllerian hormone (AMH) in Sertoli cells, and placental alkaline phosphatase (PLAP) in germ cells. Except for the ubiquitous VIM, all the markers were more expressed in neoplastic gonads compared to healthy ones (P < 0.05). Similarly, testes detected with Sertoli cell-only tubules as well as with Sertoli cells hyperplasia showed higher expression than gonads without such alterations for CK, DES, AMH and PLAP, and for CK and DES, respectively (P < 0.05). The same trend was observed in undescended respect to scrotal testes even though their positivity was significant only for DES, INH and AMH (P < 0.05). Immunohistochemical positivity found in scrotal testes of unilateral cryptorchid dogs, even in absence of detectable anatomical abnormalities, was suggestive of precancerous lesions.
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Therefore the incidence of undescended testis (UDT) is more common in prematurity (1–45%). At term, the incidence is approximately 3% and reduces to 1% by 6 months.16 Neonatal and GP examinations should prompt specialist referral.
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Although the surgical treatment was proved to be the recommended line of management for congenital undescended testis, hormonal therapy with human chorionic gonadotrophin hormone has been started long years ago and is still used in some areas with variable degrees of success. The factors responsible for treatment failure are not well explored. In this study, we aimed to highlight the anatomical abnormalities in the congenital undescended testis that might contribute to treatment failure.
During the period from January 2014 to December 2015, 75 boys with congenital undescended testes received treatment with human chorionic gonadotrophin, in pediatric surgery department, Faculty of medicine, Ain Shams University. Their age ranged between 6 months and 4 years (mean 1.6 years, median 2 years). In 70 boys, the testes were palpable and in the remaining 5 boys, the testes were impalpable. Fifty boys had unilateral and 25 had bilateral undescended testes. Seven of the palpable testes were high scrotal in position and the remaining 83 were palpated in the inguinal canal. The patients were followed up for 6 months to determine the position of the testis after the treatment and surgical intervention was done for those who did not respond to the hormonal treatment either partially or completely.
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The undescended testis: Clinical management and scientific advances

Abstract

Introduction

Section snippets

Normal testicular descent

Effects of cryptorchidism

The germ cells (normal and abnormal)

Clinical management of UDT

Classification of UDT

Diagnostic imaging

Hormone therapy

Surgical management of UDT

Complications of surgery

Late presentation of UDT

Conclusion

Age at orchidopexy in the UK: has new evidence changed practice?

J Pediatr Urol

Prevalence and natural history of cryptorchidism

Pediatrics

Evaluation and management of the infant with cryptorchidism

Curr Opin Pediatr

Evaluation and treatment of cryptorchidism: AUA guideline

J Urol

AUA guideline on the diagnosis and treatment of cryptorchidism

J Urol

Paediatrics: new cryptorchidism guidelines reach a consensus

Nat Rev Urol

Cryptorchidism: a clinical perspective

Pediatr Endocrinol Rev

The undescended testis: working towards a unified care pathway for 2014

Arch Dis Child

The regulation of testicular descent and the effects of cryptorchidism

Endocr Rev

Maternal cigarette smoking during pregnancy and reproductive health in children: a review of epidemiological studies

Asian J Androl

Long-term testicular volume after orchiopexy at diagnosis of acquired undescended testis

J Urol

Incomplete disappearance of the processus vaginalis as a cause of ascending testis

J Urol

Cryptorchidism: an apparent substantial increase since 1960

Br Med J (Clin Res Ed)

The antiandrogen flutamide perturbs inguinoscrotal testicular descent in the rat and suggests a link with mammary development

J Pediatr Surg

Hidden in plain sight: the mammary line in males may be the missing link regulating inguinoscrotal testicular descent

J Pediatr Surg

Development of the gubernaculum during testicular descent in the rat

Anat Rec (Hoboken)

The development of the gubernaculum and inguinal closure in the marsupial Macropus eugenii

J Anat

Neurotrophin signaling in a genitofemoral nerve target organ during testicular descent in mice

J Pediatr Surg

A review of surgical treatment of undescended testes with emphasis on anatomical position

J Urol

Anatomical, morphological and volumetric analysis: a review of 759 cases of testicular maldescent

J Urol

Examination for intratubular germ cell neoplasia at operation for undescended testis in boys

J Urol

Testicular histology related to fertility outcome and postpubertal hormone status in cryptorchidism

Klin Padiatr

Quantitative study of the cell population of the seminiferous tubules in immature rats

Am J Anat

The histochemistry and ultrastructure of the genocyte

J Anat

Is matrix metalloproteinase required in postnatal testicular tubules for germ cell maturation?

J Pediatr Surg

Postnatal germ cell development during mini-puberty in the mouse does not require androgen receptor: implications for managing cryptorchidism

J Urol

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Reproduction

Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?

Front Endocrinol (Lausanne)

Disorders of Sex Development: An integrated approach to management

Cryptorchidism as a caudal developmental field defect. A new description of cryptorchidism associated with malformations and dysplasias of the kidneys, the ureters and the spine from T10 to S5

APMIS

Serum inhibin B values in boys with unilateral vanished testis or unilateral cryptorchidism

J Urol

Current management of the undescended testicle

Semin Pediatr Surg

The anatomy of gubernaculum testis and processus vaginalis in cryptorchidism

Scand J Urol Nephrol