A testicle is cryptorchid when it has stopped its descent and remains hidden in the abdominal cavity, or is located in the inguinal canal, or occupies a high position in the scrotum and during the physical examination cannot be mobilized to the scrotal fundus. The best diagnostic method is physical examination. In some cases, MRI is useful. The value of the ultrasonography is controversial.
Testicular descent is a process that is completed in the last months of pregnancy; however, 4–5% of newborns have incompletely descended testicles. This percentage is very high in premature children and reaches 100% in children of less than 900 gr. Most of these testes descend in the first three months of extrauterine life. At the age of 1 year, only 0.96–1.18% remain cryptorchid. After the first year, the spontaneous descent is exceptional. It is generally accepted that true cryptorchidism is present in 25% of patients with empty scrotum. High canalicular and scrotal sites are more frequent than abdominal ones. From the epidemiological point of view, the incidence of cryptorchid testis is greater in maternal obesity, high maternal stature, history of subfertility, increased maternal age, alcohol consumption, toxemia of pregnancy, late pregnancy bleeding, exposure to endocrine-disrupting chemicals during fetal development, intrauterine growth restriction, birth by cesarean section, low birth weight at birth, prematurity twinning, hypospadias and other congenital malformations, and those born between September and November and between May and June. Fourteen percent of patients have a family history of cryptorchidism.
There are still cases that are not diagnosed in childhood and are discovered at puberty or even in adulthood. We must also bear in mind the possibility of a testicular rise during childhood (acquired cryptorchidism).
The right testicle is affected with a slightly higher frequency than the left one. In 18% of cases, cryptorchidism is bilateral.
Surgical treatment is the first choice followed or not by medical treatment. Orchiopexy is recommended within the first year of life and excision of the cryptorchid testis in adult patients (Bergbrant et al. 2018). The effectiveness of hormonal treatment is controversial (Wei et al. 2018). In the most optimistic series, treatments with hCG or with GnRH produce 15–20% of descents, but a fifth of this amount rises again later. If we take into account only the number of descents achieved, we would say that the response is modest, but what the hormonal treatment intend is not only the descent, but the most important target is to correct the cause as much as possible, and provide the testicle with an optimal number of Ad type spermatogonia, which are the stem cells. An early hormonal treatment would make it possible for the gonocytes still present in the first months of postnatal life to be transformed into Ad-type spermatogonia. The presence of Ad-type spermatogonia is a good indicator for future spermatogenesis. The strategy to know the functional efficiency of a surgically descended testis would involve the performance of a testicular biopsy that informs us about the state of germ cells at the starting point of the hormonal treatment.
The main problems faced by a patient to whom the testes have descended are infertility, testicular tumor, torsion and iatrogenic atrophy. The history of undescended testes, corrected or not, is present in 2.5–9% of infertile patients. Infertility related to cryptorchidism depends on several factors: (a) anatomical factors such as unilaterality or bilateralism of the undescended testicle, location and size of the testicle, congenital abnormalities of the excretory ducts, (b) histological factors: tubular fertility index, number of germ cells per cross section, distribution of germ cells either diffusely or only in some lobules, DNA content in germ cells, Ad spermatogonia number, and (c) possible iatrogenic injuries during orchiopexy that can affect the testis, epididymis, or vas deferens (Nistal et al. 2017).
Testicular tumors are more frequent in both the undescended and the contralateral testis. It is estimated that the risk is 6.33 times higher than in the general population for the testicle that has been descended and from 1.74 to 2.90 for the contralateral testicle. The further away from the scrotum the testis is, the greater the risk. The most frequent tumor is seminoma. The incidence of tumors in patients with acquired cryptorchidism is not higher than in the general population.
Testicular torsion is estimated to be 10 times higher in the undescended testis than in those in the scrotum. The following are considered possible causes: absence of gubernaculum, a closed internal inguinal ring, and laxity in the fixation of structures of the spermatic cord.
The cryptorchid testicles are small, and are often associated with local abnormalities such as patent vaginal process both ipsilateral (62–90%) and contralateral (34%) and inguinal hernia (65–75%) although often not apparent (Favorito et al. 2017). Urological abnormalities are reported in 10.5% of cases, the most frequent being hypospadias followed by duplication of the urinary tract, nonobstructive urethral dilation, kidney malrotation, and posterior urethral valves.
Of special interest are the epididymal anomalies, whose frequency varies from 36% to 79% of patients according to severity. The malformations range from absence of connection with the testicle at the level of the head or tail, partial or total hypoplasia of the epididymis or marked elongation associated or not to defects of the vas deferens (De Miguel et al. 2001).
The information obtained from testicular biopsies performed at different ages of childhood and puberty, as well as the study of specimens of orchiectomy of patients of different ages, allow us to know the lesions of the undescended testes and the possible prognosis in terms of fertility and tumor development (Nistal et al. 2007).
Injuries of the testicles in childhood. One of the first signs that is observed is the slow growth and the reduced volume of the testicle, facts that are already detectable at six months of age. Many testes show histological lesions in the first year of life suggesting that they are primary and probably congenital. Many patients do not have mini-puberty (elevation of pituitary gonadotrophins that reach a peak normally between the third and sixth month of life). The absence of this fact is so important that it determines an incomplete maturation of gonocytes and fetal spermatogonia moving from inside of the tubule to the basement membrane, an absence of transformation of the gonocytes into Ad spermatogonia, persistence of gonocytes inside the tubule beyond of the first year of life (Hadziselimovic et al. 2005), and failure in the appearance of first-order spermatocytes at the end of the third year and during the fourth year.
Lesions of the undescended testes during puberty. The testes show marked delay in the maturation and development of both tubular and interstitial components. The failure of growth in length and tortuosity is manifested by an apparent hyperplasia of Sertoli cells by cross tubular section. As puberty progresses, there is marked irregularity in the tubular development from one lobule to the other. It is easy to observe tubules that have started spermatogenesis alongside others with prepubertal pattern. The maturation of Sertoli cells is frequently incomplete (absence of triangular nuclei with folds in the kariotheca and prominent nucleoli, absence of androgen receptors, and absence of tubular fluid) and has a lobular pattern.
The rete testis in more than half of the cases shows lesions of simple hypoplasia, microcystic hypoplasia, or adenomatous hyperplasia. In its proximities, there may be fatty cell metaplasia (Nistal et al. 2003).
In 5% of the testes, from the first year on, in the central part of the seminiferous tubules, gonocytes (positive for C-kit and PLAP) can be detected, which is interpreted as a delay in maturation. In some cases, the cells are also positive for OCT3/4, which suggests that they are carriers of a GCNIS. From the age of four, there are groups of seminiferous tubules close together, which suggest that they belong to the same lobule, in which Sertoli cells lack androgenic receptors. In adulthood, tubules commonly have irregular deposits of type IV collagen in the basal lamina, suggesting an abnormal function of Sertoli cells. Sertoli cells can also express a broad-spectrum of cytokeratins and desmin in the subnuclear cytoplasm. Peritubular myoid cells show disorganized actin filaments.
The causes of testicular maldescent are multiple, and very little is known about molecular bases. Two types of congenital and acquired cryptorchidism are distinguished. Congenital cryptorchidism can be due to several factors: (a) dysfunction involving testosterone, anti-Müllerian hormone, epidermal growth factor, and estrogen; (b) mechanical causes such as insufficient intra-abdominal pressure, short spermatic cord, anatomical anomalies of the gubernaculum, underdeveloped vaginal process, and maldevelopment of the epididymis; (c) neuromuscular causes that include abnormalities in the calcitonin gene-related peptide (CGRP) and the cremaster nucleus; (d) genetic causes, mutations in insulin-like factor 3 or in its receptor. The most frequent cause is related to an increase in estrogen and decrease in testosterone during fetal life.
The “acquired cryptorchidism” is present in 1.5% of prepubertal boys. There are two types of so-called postoperative trapped testis and spontaneous ascent. The first is an iatrogenic complication that appears in 1.25% of the patients operated on for inguinal hernia or hydrocele. The spontaneous ascent is considered a late manifestation of congenital cryptorchidism and among its causes are considered: failure in the postnatal elongation of the spermatic cord, defect in the postnatal release of CGRP by the genitofemoral nerve, failure in the reabsorption of the vaginalis process, inadequate growth of the spermatic vessels, permanent spasm of the cremaster muscle, abnormal insertion of the gubernaculum, and deficit or decreased androgen activity.
When finding an empty scrotum, the first problem that arises is whether or not there is a testicle and in case there is a testis, where is it located. The following diagnoses must be considered: anorchia, testicular ectopia, and retractile testicles. Anorquia, in 5% of patients with nonpalpable testes, this testis does not exist. Ectopic testes, the testes are located outside the descent pathway: interstitial ectopia (superficial inguinal), femoral (crural), perineal, transverse (crossed testicular ectopia), pubopenile, pelvic and abdominal wall. Retractile testes represent 1/3 to 1/4 of the testicles that can be mobilized to the bottom of the scrotum but ascend to their abnormal situation upon completion of the examination.
References and Further Reading
- Nistal, M., Paniagua, R., Riestra, M. L., Reyes-Múgica, M., & Cajaiba, M. M. (2007). Bilateral prepubertal testicular biopsies predict significance of cryptorchidism-associated mixed testicular atrophy, and allow assessment of fertility. The American Journal of Surgical Pathology, 31, 1269–1276.CrossRefGoogle Scholar
- Wei, Y., Wang, Y., Tang, X., Liu, B., Shen, L., Long, C., Lin, T., He, D., Wu, S., & Wei, G. (2018). Efficacy and safety of human chorionic gonadotropin for treatment of cryptorchidism: A meta-analysis of randomised controlled trials. Journal of Paediatrics and Child Health, 54, 900–906.CrossRefGoogle Scholar