Dina Cortes

Nordic consensus on treatment of undescended testes

Aim: To reach consensus among specialists from the Nordic countries on the present state‐of‐the‐art in treatment of undescended testicles.

Cryptorchidism: Aspects of Fertility and Neoplasms

Purpose: An attempt to make a rational strategy for treatment of cryptorchidism. Materials and Methods: 1,335 cryptorchid boys with biopsy at surgery (1,638 specimens). We studied: frequency of no germ cells in biopsies from 698 patients <12 years at surgery; fertility potential of 140 patients who were now adults, and apperance of testicular neoplasia in all biopsies. Results: Lack of germ cells appeared from 18 months. The frequency increased with increasing age. It appeared in 30% (61/202) bilateral, and 18% (88/496) unilateral cases. In men who had undergone bilateral or unilateral orchiopexy, respectively, there was normal sperm count in 19% (14/75) and 83% (54/65), and infertility was suspected in 56% (42/75) and 8% (5/65) (FE, p < 0.00005, p < 0.00005), respectively. The lowest, the mean, and the highest age-matched spermatogonia count per tubule at orchiopexy was associated with sperm count (Spearman test, p < 0.0001, p < 0.005, p < 0.05). Isolated, this was demonstrated for the 75 formerly bilateral (Spearman, p < 0.0001, p < 0.0001, p < 0.0001), but not the 65 formerly unilateral cases (Spearman, p = 1.0). No germ cells at orchiopexy was associated with suspected infertility. Risk was 78–100% in bilateral (dependent on one or both testes affected), and 33% in unilateral cryptorchidism. There was one invasive germ cell tumor, six cases of carcinoma in situ testis, and one Sertoli cell tumor. Three neoplasms were diagnosed in intra-abdominal testes, four in boys with abnormal external genitalia, and two in boys with known abnormal karyotype. Risk of neoplasia was 5% (7/150) in patients with intra-abdominal testis, abnormal external genitalia or diagnosed abnormal karyotype, versus 0% (0/1,185) in patients without these characteristics (FE, p < 0.00005). Conclusion: We recommend surgery for cryptorchidism before 15–18 months of age because: (a) lack of germ cells is very rare before, and (b) lack of germ cells is associated with subsequent risk of infertility. At primary surgery for cryptorchidism, we recommend examination for testicular neoplasia in cases of intra-abdominal testis, abnormal external genitalia or known abnormal karyotype.

Cryptorchidism: classification, prevalence and long-term consequences

Undescended testis is a common finding in boys, and the majority of cases have no discernible aetiology. There are unexplained geographical differences and temporal trends in its prevalence. Cryptorchidism, especially bilateral, is associated with impaired spermatogenesis and endocrine function and increases the risk of testicular cancer. There is an urgent need to identify factors that adversely affect testicular development and optimize treatment.

What is new in cryptorchidism and hypospadias—a critical review on the testicular dysgenesis hypothesis ☆

It has been hypothesized that poor semen quality, testis cancer, undescended testis, and hypospadias are symptoms of one underlying entity--the testicular dysgenesis syndrome--leading to increasing male fertility impairment. Though testicular cancer has increased in many Western countries during the past 40 years, hypospadias rates have not changed with certainty over the same period. Also, recent studies demonstrate that sperm output may have declined in certain areas of Europe but is probably not declining across the globe as indicated by American studies. However, at the same time, there is increasing recognition of male infertility related to obesity and smoking. There is no certain evidence that the rates of undescended testes have been increasing with time during the last 50 years. In more than 95% of the cases, hypospadias is not associated with cryptorchidism, suggesting major differences in pathogenesis. Placental abnormality may occasionally cause both cryptorchidism and hypospadias, as it is also the case in many other congenital malformations. The findings of early orchidopexy lowering the risk of both infertility and testicular cancer suggest that the abnormal location exposes the cryptorchid testis to infertility and malignant transformation, rather than there being a primary abnormality. Statistically, 5% of testicular cancers only are caused by cryptorchidism. These data point to the complexity of pathogenic and epidemiologic features of each component and the difficulties in ascribing them to a single unifying process, such as testicular dysgenesis syndrome, particularly when so little is known of the actual mechanisms of disease.

The Treatment of Obese Pregnant Women (TOP) study: a randomized controlled trial of the effect of physical activity intervention assessed by pedometer with or without dietary intervention in obese pregnant women

OBJECTIVE The objective of the study was to assess physical activity intervention assessed by a pedometer with or without dietary intervention on gestational weight gain (GWG) in obese pregnant women by comparing with a control group. STUDY DESIGN This study was a randomized controlled trial of 425 obese pregnant women comparing 3 groups: (1) PA plus D, physical activity and dietary intervention (n = 142); (2) PA, physical activity intervention (n = 142); and (3) C, a control group receiving standard care (n = 141). All participants routinely in gestational weeks 11-14 had an initial dietary counseling session and were advised to limit GWG to less than 5 kg. Physical activity intervention included encouragement to increase physical activity, aiming at a daily step count of 11,000, monitored by pedometer assessment on 7 consecutive days every 4 weeks. Dietary intervention included follow-up on a hypocaloric Mediterranean-style diet. Instruction was given by a dietician every 2 weeks. The primary outcome measure was GWG, and the secondary outcome measures were complications of pregnancy and delivery and neonatal outcome. RESULTS The study was completed by 389 patients (92%). Median values of GWG (ranges) were lower in each of the intervention groups (PA plus D, 8.6 [-9.6 to 34.1] kg, and group PA, 9.4 [-3.4 to 28.2] kg) compared with the control group (10.9 [-4.4 to 28.7] kg [PA+D vs C]; P = .01; PA vs C; P = .042). No significant difference was found between the 2 intervention groups. In a multivariate analysis, physical activity intervention decreased GWG by a mean of 1.38 kg (P = .040). The Institute of Medicines recommendations for GWG were more frequently followed in the intervention groups. CONCLUSION Physical activity intervention assessed by pedometer with or without dietary follow-up reduced GWG compared with controls in obese pregnant women.

HORMONAL TREATMENT MAY HARM THE GERM CELLS IN 1 TO 3-YEAR-OLD BOYS WITH CRYPTORCHIDISM

PURPOSE Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing hormone and testosterone values are normally low. MATERIALS AND METHODS We measured the number of spermatogonia per tubule at orchiopexy in 72 consecutive boys with cryptorchidism who underwent simultaneous testicular biopsy. In 19 patients gonadotropin releasing hormone was unsuccessful, while 8 received HCG and 45 underwent orchiopexy without hormonal therapy. Groups were otherwise equal. RESULTS Patients who underwent surgery only had a higher number of spermatogonia per tubule than those in whom hormonal treatment was unsuccessful (p<0.05). Spermatogonia per tubule values were normal only after surgery alone (p = 0.06). Gonadotropin releasing hormone and HCG influenced germ cells equally. CONCLUSIONS In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells.

Development and descent of the testis in relation to cryptorchidism

The testis descends in two phases. Animal studies suggest, that the transabdominal descent of the testis depends on the insulin‐like hormone 3 (INSL3). Androgens are important in the inguinoscrotal testicular descent in animals and humans. In general, the cause of cryptorchidism is unknown and the aetiology is possibly multifactorial. Histological changes in cryptorchid testes demonstrate disturbed development.

Quantitative histology of germ cells in the undescended testes of human fetuses, neonates and infants

PURPOSE We investigated the number of germ cells per tubular cross section and testicular weight in cryptorchid fetuses, neonates and infants, and characterized additional abnormalities. MATERIALS AND METHODS Our series comprised 35 fetuses and 58 boys with cryptorchidism, and 22 normal fetuses and 25 normal boys. Age ranged from 28 weeks of gestation to 3 years. RESULTS Cryptorchid fetuses had reduced germ cells per tubular cross section values and lower testicular weights. Values were reduced in cryptorchid boys without a symptomatic inguinal hernia. If a hernia was present, values were normal in the first year of life but decreased at age 1 to 3 years. Malformations or dysplasia of the kidneys, ureter or T10 to S5 vertebrae were present in 34% of the cryptorchid fetuses and 18% of the cryptorchid boys without a symptomatic inguinal hernia. CONCLUSIONS Our study suggests a reduced number of germ cells in undescended testes from week 28 of gestation and germ cell hypoplasia as a consequence of continued postnatal undescended testicular position. Cryptorchidism may result from abnormal development of the caudal developmental field.

FERTILITY POTENTIAL AFTER UNILATERAL ORCHIOPEXY: SIMULTANEOUS TESTICULAR BIOPSY AND ORCHIOPEXY IN A COHORT OF 87 PATIENTS

PURPOSE We investigated the prognostic value of the number of spermatogonia per tubular cross section in a testicular biopsy specimen obtained at orchiopexy for unilateral cryptorchidism. MATERIALS AND METHODS A total of 87 consecutive 10 to 12-year-old cryptorchid boys underwent testicular biopsy simultaneously with unilateral orchiopexy. In adulthood 56 of the 87 patients agreed to measurement of serum follicle-stimulating hormone, luteinizing hormone, testosterone and testicular volume, and 54 provided specimens for semen analysis. RESULTS The number of spermatogonia per tubular cross section correlated to the volume of the operated testis and total testicular volume in adulthood. Serum follicle-stimulating hormone negatively correlated to these volumes, sperm concentration and total sperm count. Contralateral testicular volume correlated to sperm concentration, total sperm count, and percent of living and mobile sperm. When biopsy revealed Sertoli cells only or 1 spermatogonium per 100 tubular cross sections, the age matched number of spermatogonia per tubular cross section was 1% or less. Of these patients 33% later presented with 5 million spermatozoa per ml. or less, no normal motility and generally lower sperm concentrations that those with more than 1 spermatogonium per 100 tubular cross sections (greater than 1%) in the biopsy specimen. When the value was greater than 1%, later sperm quality was not significantly reduced in comparison to that of the general population. CONCLUSIONS The age matched number of spermatogonia per tubular cross section is significant in regard to fertility potential, and a value of 1% or less (approximately Sertoli cells only) may predict low fertility potential. To our knowledge Sertoli cells only have not been observed before 15 months of life, which makes it logical to treat cryptorchidism before this age even in unilateral cases.

Infertility despite surgery for cryptorchidism in childhood can be classified by patients with normal or elevated follicle‐stimulating hormone and identified at orchidopexy

To analyse infertility despite orchidopexy in childhood.