Consequences of bilateral cryptorchidism in adults.

Bilateral cryptorchidism treatment results are often shadowed by the majority of unilateral cases. We report the long-term follow-up results of boys treated for bilateral cryptorchidism during childhood. Patients treated in two main paediatric surgery centres were selected from medical registries and invited for a clinical examination including scrotal ultrasound, salivary testosterone measurement and a semen sample. Thirty-six men (38.3%) replied to the written invitation, and 21 agreed to be examined. The mean age at orchidopexy was 74 months (range 24-138). Sperm count was 0.42 × 106 (SD ± 0.64 × 106 ) ml-1 . The correlation between total testicular volume and total sperm count was statistically significant (r = 0.481; P = 0.032). These results show that surgical treatment of bilateral cryptorchidism after the age of 2 years does not prevent infertility. Sperm count and endocrine evaluation advocated after the treatment of bilateral cryptorchidism in all adult patients.

Complete testis-epididymis nonfusion anomaly: a typical association with cryptorchid testis.

INTRODUCTION: Fusion anomalies of the testis and epididymis are associated with cryptorchidism. We present an analysis of the fusion anomalies of the epididymis in cryptorchid boys. PATIENTS AND METHODS: We performed a retrospective review of patients presenting with undescended testes between 1986 and 1993. Patients were stratified among four groups based on the degree of testis-epididymis nonfusion. RESULTS: A total of 880 testes were eligible for review, of which 93% (815/880) had normal fusion, 3.6% (32/880) had epididymal head nonfusion, 2% (19/880) had epididymal tail nonfusion, and 1.6% (14/880) had complete nonfusion. Increasing degree of nonfusion was associated with higher perioperative testes position. Head and tail nonfusion were observed together with a contralateral descended testis, but less frequently than in bilateral undescended testes (p = 3.89 × E-10). Complete nonfusion was not observed in the contralateral descended testes in unilateral cryptorchid boys. CONCLUSIONS: Different degrees of fusion anomalies of the epididymis are associated with unilateral and bilateral undescended testis, indicating that nonfusion anomalies interact with epididymal-testicular descent because of impaired epididymal function.

Differences in testicular development between 5alpha-reductase 2 deficiency and isolated bilateral cryptorchidism.

PURPOSE: We demonstrated that infertility develops in most patients with steroid 5alpha-reductase 2 deficiency. MATERIALS AND METHODS: We compared the testicular histopathology of boys with steroid 5alpha-reductase 2 deficiency to that of boys with isolated bilateral cryptorchidism. RESULTS: Testes with steroid 5alpha-reductase 2 deficiency lacked spermatocytes but had Ad spermatogonia and a normal germ cell count. In contrast, bilateral cryptorchid testes had severe germ cell depletion and the majority lacked Ad spermatogonia. CONCLUSIONS: In patients with steroid 5alpha-reductase 2 deficiency the impaired second step of germ cell maturation results in defective transformation of spermatogonia into spermatocytes. The position of the undescended testis appears to have no major pathological impact on the development of germ cells in patients with steroid 5alpha-reductase 2 deficiency.

Hypoplasia of the corpus callosum and growth hormone deficiency in the XXXXY syndrome.

A 3-year-old Libyan boy with the XXXXY syndrome is described. MRI examination of the brain showed hypoplasia of the corpus callosum. He had growth retardation and endocrine studies demonstrated growth hormone (GH) deficiency. Dermatoglyphic pattern was different from previous reports. At histological examination of the undescended testes, Leydig cells were seen although they are usually not found in this variant of the Klinefelter syndrome.

Does hydrocele affect later fertility?

The purpose of this study was to investigate the prognosis for fertility in children with hydrocele. Our results show that hydrocele seems to be more of a symptom than an actual pathological entity. It occurs both with an open and a closed processus vaginalis. Bilateral hydrocele seems to be a rare occurrence, mostly affecting infants or children under 1 year of age. Hydrocele on its own seems to have no direct effect on later fertility. In the presence of certain associated pathological findings, however, the testes are significantly altered. Children with hydrocele and pathological findings are significantly older than hydrocele patients with no associated pathology. As a practical recommendation, hydrocele does not require immediate surgery. In the presence of hydrocele and certain associated pathology, however, surgery makes good sense.

The role of the epididymis in descensus testis and the topographical relationship between the testis and epididymis from the sixth month of pregnancy until immediately after birth.

The position of the testis, the relationship between the epididymis and the testis, as well as the development and regression of the gubernaculum were investigated in 18 testicles of children from the 26th week of pregnancy until a few weeks after birth. The most important role in descensus testiculorum is ascribed to the differentiation of the epididymis and the ductus deferens. It is androgen dependent. The testis descends in the processus vaginalis, being attached to its dorsal wall.

The meaning of the Leydig cell in relation to the etiology of cryptorchidism: An experimental electron-microscopic study.

In our electron-microscopic studies of testicular biopsies, both normal and cryptorchid, we found a simple atrophy of the Leydig cell in the cryptorchid testis. Based on experiments by Raynaud1,2 and Jean3 on pregnant mice, we tried to find the reason for changes in the Leydig cell relating to the etiology of cryptorchidism. We found on electron microscopic study of testes in the offspring of pregnant mice treated with estrogen the same atrophy of the Leydig cell as we see in human cryptorchidism. These changes are not evident when estrogen and HCG are given together. We can conclude from this experiment that lack of gonadotropin stimulation leads to the atrophy of Leydig cells. This atrophy then produces a lack of androgen which could be responsible for cryptorchidism.

Surgical correction of cryptorchism at 2 years: electron microscopic and morphometric investigations.

Electron microscopic and morphometric investigations on undescended testicles show a decreased volume density of the spermatogonia up to the age of 5 (approximately 60%, p smaller than 0.005), corresponding to investigations by light microscopy. There are no ultrastructural differences in the seminiferous tubules between normal and undescended testicles up to the age of 1 yr. There are ultrastructural changes of Leydig cells within the first year of life. Based on these investigations, we conclude that the optimal time for surgical intervention in case of undescended testes is in the second year.

Omphalocele, cryptorchidism, and brain malformations.

Nineteen male infants died with a large omphalocele and 52% had associated cryptorchidism. However, two different groups with both omphalocele and cryptorchidism were recognized: (1) Eleven patients with omphalocele without brain malformation and an incidence of undescended testes not significantly different from the normal population; (2) Eight patients with omphalocele and brain malformation all having cryptorchidism. A comparison of the groups indicated that intact intraabdominal pressure during intrauterine life is not a main driving force of testicular descent, whereas normal testicular descent may occur only when the brain is normally developed. Whenever a child with omphalocele and cryptorchidism is examined, careful evaluation of the central nervous system is indicated. This triad of malformations may have prognostic and therapeutic implications.

The effect of needle biopsy procedure on prepubertal rat testis.

Testicular needle biopsies were performed in 20 prepubertal rats. Ten rats were used as a control group. Spermatohistogenesis was observed in the tubuli (mean number: 17) of each biopsy. The biopsy procedure caused tubular damage which extended to 0.2-4% of the entire testicular volume. Twenty percent of the rats had severe unilateral testicular atrophy at the site of the procedure. A significant compensatory tubular hypertrophy occurred in the contralateral testis that was observed 50 days after the procedure. Eighty percent of the rats produced the normal number of offspring, independent of the occurrence of unilateral testicular atrophy. The histology of the contralateral testis was normal in all animals; thus, no adverse effect from the biopsied testis occurred.

A novel syndrome involving primary skeletal growth and retardation in siblings.

An identical pattern of malformations was found in two brothers both having microcephaly and severe developmental delay. Additionally, they had hypotelorism, epicanthic folds, and convergent strabismus. There was shortening of either the radius or the tibia and shortening of the first metacarpals. Persistently dorsally flexed fingers and toes were noted, all of which are unusually long. Both boys had a high-pitched voice and were unable to communicate verbally at the age of 4.5 years. They both developed short stature. One brother has anal atresia; the other had a pulmonary artery atresia, VSD, ASD, and an over-riding aorta. This apparently new syndrome is possibly an autosomal, or a X-linked recessive trait.

[Cryptorchidism: pathogenesis and histology]. / Cryptorchidie: pathogénie et histologie.

An impairment of the hypothalamopituitarygonadal axis was found to be the main cause of undescended testicles in 80 per cent of patients. Basing himself on personal observation, the author develops the theory that the mechanism of testicular descent is the stimulation by GnRH of the pituitary gland to release gonadotrophins, which in turn stimulate the interstitial cells to secrete testosterone. High local testosterone concentration fosters the development of the differentiating portion of the mesonephric duct into the epididymis. The epididymis induces descent by pushing rather than pulling the testis into the scrotal position. Any interference with this mechanism during the embryonal life leads to cryptorchid testes, which, in the vast majority of cases are localized at the external inguinal ring. The earlier the scrotal position is reached, the greater the chances of subsequent fertility.

[Andrological problems in adolescence]. / Andrologische Probleme in der Adoleszenz.

The physician is consulted because of pains in the testicles or enlarged or empty scrotum, and he is primarily challenged to eliminate a possible testicular tumor. He is also questioned about the possibility of a later impairment of fertility. If severe testicular pains prevail, it usually signifies an acute testicular twist, the appearance of which every physician should be familiar with because immediate action is important--possibly an attempt of manual retorsion should be made, and most often the immediate referral to a specialist is imperative--in order to maintain the functioning of the endangered testicle. The testicular twist causes sudden testicular pains, frequently while sleeping or during sportive activities. The pain spreads into the groin region and can even lead to symptoms of shock. Frequent consequences are the disturbance of spermatogenesis. Less frequent infectious causes for testicular pains may manifest themselves as epididymitis or concomitant orchitis (parotitis epidemica). The assessment of the success of a consequent anti-infectious treatment should consider the genital symptomatology as well. Varicocele occurs almost only in the left side of the scrotum. The spermatogenesis of the left testicle is consequently often disturbed. In infertile men the varicocele is about three times more frequent than in fertile ones. If varicocele is found in adolescents, in which case it is important to compare both sides of the scrotum, the indication for a preventive surgical treatment is always impending. This question, however, is seen controversially (physiological state of transition or disease with remaining defects). We see an indication for surgical treatment also in varicocele of the adolescent boy, and not only in proven infertility of the adult male.

Decreased expression of genes associated with memory and x-linked mental retardation in boys with non-syndromic cryptorchidism and high infertility risk.

An elevated odds ratio for low IQ has been found for cryptorchid boys. Furthermore, poor school performance has been observed in cryptorchid boys with impaired mini-puberty. Gene expression analysis, qPCR and immunohistology were performed on testicular biopsies from 7 boys who underwent orchiopexy and had testicular histology typical of a high risk of infertility (HIR). The results were compared with 12 biopsies from cryptorchid boys with a low risk for developing infertility. The following genes associated with mental retardation were identically expressed: GDI1, OPHN1, PAK3, ARHGEF6, IL1RAPL, ACSL4, MECP2, RPS6KA3, ARX, and ATRX. However, boys in the HIR group had low or no expression of EGR4, FMR2 (AFF2) and VCX3A. In conclusion, impaired expression of genes known to encode proteins involved in signaling pathways that regulate cytoskeletal organization, synaptic vesicle transport and the establishment of connections between neuronal cells may contribute to reduced intellectual and cognitive functioning in infertile cryptorchid males.

Testicular gene expression in cryptorchid boys at risk of azoospermia.

Despite timely and successful surgery, 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy. During mini-puberty increased gonadotropin and testosterone secretion stimulate transformation of gonocytes into Ad spermatogonia. In the azoospermia risk group this transformation is to a great extent impaired. This study aimed to analyze data on whole genome expression signatures of undescended testes at risk of developing azoospermia. Twenty-three testicular biopsies from 22 boys were analyzed (19 testes from 18 boys with cryptorchidism and 4 contralateral descended testes from patients with testicular agenesis). Expression profiling identified 483 genes not or under-expressed in the azoospermia risk group compared with the control and low risk for azoospermia (LAZR) groups. Annotated loci were associated with spermatogenesis. Other significant genes were cellular defense response genes and hormone-controlled loci involved in spermatogenesis. Some genes transcribed in normal adult meiotic and post-meiotic germ cells are activated in healthy juvenile Ad spermatogonia. Thus, molecular events initiating the testicular expression program at the onset of puberty and maintaining it during adulthood occur very early in prepubertal testes. This molecular event is to a great extent impaired in the high risk for azoospermia (HAZR) group lacking Ad spermatogonia (stem cells for spermatozoa) indicating impaired mini-puberty.