Scrotal ultrasound findings in previously congenital and acquired unilateral undescended testes and their contralateral normally descended testis.

The aim of this study was to report on different anomalies found by physical examination and scrotal ultrasound in men with previously unilateral congenital undescended testes (UDT; N = 50), acquired UDT (N = 49), their contralateral normally descended testis (CNDT) and control testes (N = 53). Acquired UDT significantly more often had a testicular volume being <15 mL than congenital UDT (88% vs. 68%). In the congenital group, significant differences were found between UDT and CNDT for soft consistency (UDT 36% vs. CNDT 14%), epididymal diameter (UDT 7.6 mm vs. CNDT 8.9 mm), testicular volume (UDT 9.8 mL vs. CNDT 13.8 mL), and inhomogeneous parenchyma (UDT 38% vs. CNDT 14%). In the acquired group, significant differences were found between UDT and CNDT for epididymal diameter (UDT 7.5 mm vs. CNDT 8 mm), testicular volume (UDT 9.3 mL vs. CNDT 14.1 mL), testicular volume <15 mL (UDT 88% vs. CNDT 59%), and inhomogeneous parenchyma (UDT 27% vs. CNDT 6%). The following parameters of congenital UDT, acquired UDT, congenital CNDT, and/or acquired CNDT significantly differed compared with controls: soft testicular consistency (congenital UDT 36%, acquired UDT 20%, congenital CNDT 14%, acquired CNDT 12% vs. controls 0%), epididymal diameter (congenital UDT 7.6 mm, acquired UDT 7.5 mm, acquired CNDT 8 mm vs. controls 9.2 mm), testicular volume (congenital UDT 9.8 mL, acquired UDT 9.3 mL, congenital CNDT 13.8 mL, acquired CNDT 14.1 mL vs. control testes 15.8 mL), testicular volume <15 mL (congenital UDT 68%, acquired UDT 88%, congenital CNDT 66% vs. controls 43%), inhomogeneous parenchyma (congenital UDT 38%, acquired UDT 27%, congenital CNDT 14% vs. controls 0%), and testicular microlithiasis (congenital CNDT 24% vs. control testes 8%). Few differences between congenital and acquired unilateral UDT and congenital and acquired CNDT support the hypothesis of a spectrum of maldescended testes containing congenital and acquired UDT instead of them being two different entities. The CNDT also has anomalies albeit less severe than the UDT, indicating that in unilateral UDT both testes are affected.

Fatherhood in tall men treated with high-dose sex steroids during adolescence.

BACKGROUND/OBJECTIVE: Sex steroid treatment to reduce final height of tall boys has been available since the 1950s. In women, it has been shown to interfere with fertility. In men, no such data are available. We therefore evaluated fertility and gonadal function in tall men who did or did not receive high-dose androgen treatment in adolescence. METHODS: We conducted a retrospective cohort study of 116 tall men, of whom 60 had been treated. Reproductive and gonadal function was assessed by standardized interview, semen analysis, endocrine parameters, ultrasound imaging, and fatherhood. Mean age at treatment commencement was 14.2 yr, and mean follow-up was 21.2 yr. RESULTS: Sixty-six men (36 treated and 30 untreated) had attempted to achieve fatherhood. The probability of conceiving their first pregnancy within 1 yr was similar in treated and untreated men (26 vs. 24; Breslow P=0.8). Eleven treated and 13 untreated men presented with a left-sided varicocele (P=0.5). Testicular volume, sperm quality, and serum LH, FSH, and inhibin B levels were comparable between treated and untreated men. However, treated men had significantly reduced serum T levels, adjusted for known confounders [mean (sd) 13.3 (1.8) vs. 15.2 (1.9) nmol/liter; P=0.005). In addition, testicular volume and serum inhibin B and FSH levels in treated men were significantly correlated with age at treatment commencement. CONCLUSION: At a mean follow-up of 21 yr after high-dose androgen treatment, we conclude that fatherhood and semen quality in tall treated men are not affected. Serum testosterone levels, however, are reduced in androgen-treated men. Future research is required to determine whether declining testosterone levels may become clinically relevant for these men as they age.

Sperm DNA integrity in cancer patients before and after cytotoxic treatment.

BACKGROUND: We assessed sperm DNA fragmentation index (DFI) in cancer patients before and after treatment to evaluate if sperm DNA integrity is compromised by cancer itself or its treatment. METHODS: In a prospective study, DFI was assessed in 127 patients diagnosed with testicular germ cell tumours (TGCT), Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL) and various malignancies. The severity of cancer and tumour markers at diagnosis was recorded. Follow-up DFI after treatment was available in 52 patients who were mostly less severely affected. RESULTS: In patients diagnosed with TGCT, HL and various malignancies, pretreatment DFI levels were not significantly different from that of proven fertile controls, but in patients with NHL an increased DFI was found. An overall significant decrease in post-treatment DFI (13.2% range 5.0-70.5) compared with pretreatment values (17.1% range 5.1-66.6) was found (P = 0.040). In TGCT patients, post-treatment DFI was significantly higher in patients who were treated with radiotherapy (16.9% range 11.5-39.9) compared with that in patients treated with chemotherapy (CT) alone (10.9% range 5.5-39.9) (P = 0.037). In HL patients, the type of treatment or number of CT cycles was not associated with DFI. Overall, post-treatment DFI in cancer patients was not significantly different from that of proven fertile controls. CONCLUSIONS: In this study, the presence of cancer does not seem to negatively affect the sperm DNA integrity in TGCT and HL patients; only NHL patients showed increased DFI at the time of diagnosis compared with healthy controls. Our results confirm previous reports that DFI decreases significantly following various anti-cancer treatments. In contrast, radiotherapy in TGCT patients is associated with an increase in DFI compared with CT treatment alone.

Testicular microlithiasis and carcinoma in situ overview and proposed clinical guideline.

Testicular microlithiasis (TM) has been associated with testicular germ cell tumours (TGCTs) in adolescents and adults and with its precursor carcinoma in situ (CIS). A clear definition of TM and the need for further diagnostics and follow-up is lacking. We reviewed the literature of TM and its association with TGCT/CIS and current follow-up advises and propose a management approach based on associated risk factors for TGCT. In the literature, a wide variance of TM incidence is reported in different patient populations. A consensus concerning the malignant potential of TM has not been reached. In addition, a clear definition on TM is lacking. Although a correlation between TM and TGCT or CIS is found, precise management and follow-up schedules are absent. We suggest that all hyperechogenic foci smaller than 3 mm without shadowing should be named TM irrespective of their number. In addition, we suggest a management scheme for physicians encountering TM in daily practice. Our algorithm suggests taking a testicular biopsy in a selected patient population with at least one additional risk factor for TGCT. A long-term active follow-up schedule, including ultrasonography and physical examinations, is not indicated in the remaining patients with TM.

Evaluation of testicular biopsies for carcinoma in situ: immunohistochemistry is mandatory.

Carcinoma in situ (CIS) is the common precursor of all type II testicular germ cell tumors (TGCTs), i.e. seminomas and non-seminomas, which can be diagnosed using a surgical biopsy. The objective of this study was to investigate the additional value of immunohistochemistry for the diagnosis of CIS in assessing testicular biopsies taken in the context of infertility. A series of 21 infertile patients were retrieved from the Dutch pathological database (PALGA), being diagnosed with an invasive TGCT, while a matched previously obtained testicular biopsy was diagnosed as non-malignant. From 20 patients, both the invasive tumors as well as the biopsies were revised using morphology and immunohistochemistry for OCT3/4, placental-like alkaline phosphatase and c-KIT, all known established markers for CIS. The presence of CIS or invasive malignancies was scored. There are no interventions. Morphological criteria alone allowed an experienced pathologist in TGCTs to diagnose CIS in five and an invasive tumor in two cases (total n = 7, 35%). Application of immunohistochemistry resulted in the identification of an additional four cases of CIS (total n = 11, 55%, additional value of 20%). The initial correct diagnosis of CIS could have prevented a second gonadectomy in four patients (20%). This study, for the first time, really shows that time of progression from CIS to seminoma is longer than to non-seminoma. Our study demonstrates that immunohistochemistry should be performed for the diagnosis of CIS of the testis on single biopsies obtained because of infertility, resulting in an extra diagnostic yield of at least 20%. Application of this protocol will allow early diagnosis, and therefore prevent any adverse anti-cancer treatment sequelae including gonadectomy, and requiring life long androgen supplementation in some patients.

Use rate and assisted reproduction technologies outcome of cryopreserved semen from 629 cancer patients.

OBJECTIVE: To assess the use rate and assisted reproductive technologies (ART) outcome of the cryopreserved semen of cancer patients with an average follow-up of 7 years (range, 2-23 years). DESIGN: Retrospective data analysis. SETTING: University-affiliated andrology and reproduction center. PATIENT(S): Six hundred twenty-nine male cancer patients who were referred for semen cryopreservation between 1983 and 2004. INTERVENTION(S): Review of patient characteristics and ART outcome. MAIN OUTCOME MEASURE(S): Use rate and live births using cryopreserved semen. RESULT(S): A total of 749 semen samples from 557 men were preserved. Ninety-one patients died during follow-up, and another 29 requested disposal. Forty-two patients requested the use of their banked semen. ART data were available for 37 patients. A total of 101 ART cycles (32 IVF, 53 intracytoplasmic sperm injection [ICSIs], nine cryo-ET, and seven intrauterine inseminations [IUIs]) were performed, resulting in, respectively, 8, 16, 2, and 1 pregnancies. Pregnancies rates for IVF and ICSI were significantly higher than those for IUI. CONCLUSION(S): So far, 7.5% of the cancer survivors have used their banked semen, which led to live births in 49% of the couples. Semen cryopreservation is a reliable method to preserve fertility potential and gives couples a reasonable chance of achieving parenthood.