Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX).

INTRODUCTION: Current scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS). METHODS: In a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods. RESULTS: In total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. DISCUSSION: Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.

Potential benefits of the use of sympathomimetics for asthmatic disease, on semen quality in men of subfertile couples.

RESEARCH QUESTION: Is there an association between the use of sympathomimetics for asthmatic disease and semen quality in humans? DESIGN: Between 2007 and 2012 a prospective cohort study was conducted among couples visiting the preconception counselling clinic at a tertiary hospital in the Netherlands. The study included 882 men of subfertile couples and information on medication use was obtained from self-administered questionnaires. Moreover, data on semen parameters were retrieved from medical records. RESULTS: The study population of men revealed a mean (± SD) age of 34 ± 4 years with a mean body mass index (BMI) of 26.1 ± 2.3 kg/m2, and sympathomimetic use was reported by 3.6%. The use of sympathomimetics was positively associated with a 10% higher sperm motility (beta 10.265; 95% confidence interval [CI] 3.258-17.272) after adjustment for smoking, alcohol use, age, geographic background, BMI, folic acid supplement use, the four astronomical seasons and asthma/bronchitis. Subgroup analysis between men with total motile sperm count (TMSC) < or ≥10 million showed that this association remained (P ≤ 0.001) after adjustment for these confounders. After adjustment for confounders the sperm concentration was also positively associated with the use of sympathomimetics, but only in men with TMSC ≥10 million (beta 0.300; 95% CI 0.032-0.568). CONCLUSIONS: These preliminary data show the potential benefits of the use of sympathomimetics to improve sperm motility in men of subfertile couples, which needs further investigation.

Fertility preservation in men with cancer.

During the past decade, advances in cancer treatment have increased survival rates of both boys and men. However, cancer treatment itself can compromise fertility, especially exposure to alkylating agents and whole body irradiation, which cause substantial germ cell loss. Children and adolescents with testicular cancer, leukaemia, and Ewing sarcomas are at the highest risk of developing permanent sterility from cancer treatment. Consequently, various strategies to preserve fertility are necessary. Sperm cryopreservation is an effective but underused method to safeguard spermatozoa. In the past few years, large advances have been made in prepubertal germ cell storage aimed at subsequent transplantation of testicular tissue and associated stem cells. Although still experimental, these approaches offer hope to many men in whom germ cell loss is associated with sterility. The derivation of male gametes from stem cells also holds much promise; however, data are only available in animals, and the use of this method in human beings is probably many years away.

Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate.

PURPOSE: We prospectively evaluated changes in sperm chromatin structure in infertile patients before and after surgical repair of varicocele, and the impact on the pregnancy rate. MATERIALS AND METHODS: Included in the study were 49 men with at least a 1-year history of infertility, a palpable varicocele and oligospermia. World Health Organization semen analysis and sperm DNA damage expressed as the DNA fragmentation index using the sperm chromatin structure assay were assessed preoperatively and postoperatively. Pregnancy (spontaneous and after assisted reproductive technique) was recorded 2 years after surgery. RESULTS: Mean sperm count, sperm concentration and sperm progressive motility improved significantly after varicocelectomy from 18.3 × 10(6) to 44.4 × 10(6), 4.8 × 10(6)/ml to 14.3 × 10(6)/ml and 16.7% to 26.6%, respectively (p <0.001). The DNA fragmentation index decreased significantly after surgery from 35.2% to 30.2% (p = 0.019). When the definition of greater than 50% improvement in sperm concentration after varicocelectomy was applied, 31 of 49 patients (63%) responded to varicocelectomy. After varicocelectomy 37% of the couples conceived spontaneously and 24% achieved pregnancy with assisted reproductive technique. The mean postoperative DNA fragmentation index was significantly higher in couples who did not conceive spontaneously or with assisted reproductive technique (p = 0.033). CONCLUSIONS: After varicocelectomy sperm parameters significantly improved and sperm DNA fragmentation was significantly decreased. Low DNA fragmentation index values are associated with a higher pregnancy rate (spontaneous and with assisted reproductive technique). We suggest that varicocelectomy should be considered in infertile men with palpable varicocele, abnormal semen analysis and no major female factors.

Functional transformation of the chromatoid body in mouse spermatids requires testis-specific serine/threonine kinases.

The cytoplasmic chromatoid body (CB) organizes mRNA metabolism and small regulatory RNA pathways, in relation to haploid gene expression, in mammalian round spermatids. However, little is known about functions and fate of the CB at later steps of spermatogenesis, when elongating spermatids undergo chromatin compaction and transcriptional silencing. In mouse elongating spermatids, we detected accumulation of the testis-specific serine/threonine kinases TSSK1 and TSSK2, and the substrate TSKS, in a ring-shaped structure around the base of the flagellum and in a cytoplasmic satellite, both corresponding to structures described to originate from the CB. At later steps of spermatid differentiation, the ring is found at the caudal end of the newly formed mitochondrial sheath. Targeted deletion of the tandemly arranged genes Tssk1 and Tssk2 in mouse resulted in male infertility, with loss of the CB-derived ring structure, and with elongating spermatids possessing a collapsed mitochondrial sheath. These results reveal TSSK1- and TSSK2-dependent functions of a transformed CB in post-meiotic cytodifferentiation of spermatids.

Different surgical findings in congenital and acquired undescended testes.

OBJECTIVE: To compare surgical findings in congenital and acquired undescended testes (UDT). PATIENTS AND METHODS: A review of 139 boys with 158 congenital UDT and 69 boys with 84 acquired UDT was performed. The most caudal testicular position preoperatively, testis position at surgery, patency of the processus vaginalis and epididymal anomalies were prospectively recorded. RESULTS: In the congenital group, orchiopexy had been performed at median age (range) 4.9 (1.5-14.6) years, while the median age (range) in the acquired group was 11.9 (3.8-23.3) years. Preoperatively, only congenital UDT were found not palpable or emergent inguinal, while only acquired UDT could be manipulated in an unstable scrotal position. In comparison with congenital UDT, acquired UDT were significantly more often located at the scrotal entrance, 27/158 vs 32/84 respectively (P < 0.001). At surgery anorchia, vanished testis or testes lying intra-abdominally were only registered in the congenital UDT group. Also 37/158 congenital UDT were located in the superficial inguinal pouch vs 52/84 of the acquired UDT (P = 0.04). In congenital UDT the processus vaginalis was wide open in 74/158, while in acquired UDT the processus vaginalis was closed in 46/84 (P < 0.001) and small open in 26/84 (P = 0.04). Epididymal anomalies were more often seen in the congenital UDT group (37%) than in the acquired group (11%). CONCLUSION: The most caudal position of congenital UDT after manipulation before surgery was at the scrotal entrance. These testes were frequently associated with epididymal anomalies and wide open processus vaginalis. This was in contrast to acquired UDT, which can often be pushed down well below the scrotal entrance and are more likely to be situated in the superficial inguinal pouch, with a normal epididymis and closed processus vaginalis.

Vasovasostomy and predictors of vasal patency: a systematic review.

About 3-6% of vasectomized men requested vasectomy reversal, for various reasons. Vasal patency (VP) is an important surrogate outcome of vasectomy reversal. This article reviews the impact of surgical skills, surgical approaches, intraoperative vasal fluid characteristics and the length of obstructive interval on VP. Based on the best available evidence, the rate of patency is related to the operative frequency of the surgeons, with better results obtained by surgeons who perform the operations at least 10 times annually. Microsurgical vasovasostomy is the preferred technique for durable good results. One-layer vasovasostomy and two-layer vasovasostomy seem to be equal with regard to VP. The rate of patency following vasovasostomy in the convoluted vas and vasovasostomy in the straight vas is comparable. The patency rate is high in men with clear intraoperative vasal fluid in at least one vas. VP is still high among patients with a long obstructive interval. In conclusion, surgical skills and intraoperative vasal fluid characteristics are the most important predictors of VP. Postoperative semen quality and the age of the female partner determine the chance of spontaneous conception in these couples.

Associations of maternal urinary bisphenol and phthalate concentrations with offspring reproductive development.

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture exposure was associated with earlier pubic hair development in both sexes. In conclusion, higher maternal gestational urinary bisphenol and phthalate concentrations were associated with alterations in offspring reproductive development, mainly in boys.

Diagnosis of testicular carcinoma in situ '(intratubular and microinvasive)' seminoma and embryonal carcinoma using direct enzymatic alkaline phosphatase reactivity on frozen histological sections.

AIMS: Testis-sparing surgery might benefit quality of life, but can only be applied with histological examination for the presence of invasive germ cell tumour components, and the precursor carcinoma in situ (CIS). Currently, diagnosis is based on paraffin-embedded tissue, therefore a delay in further surgery is mainly unavoidable. The aim was to develop an intraoperative assessment technique using alkaline phosphatase as a marker. METHODS AND RESULTS: A total of 4093 snap-frozen samples and matched paraffin-embedded tissue of 1500 patients were included. Besides standard haematoxylin and eosin (H&E) staining, the direct enzymatic alkaline phosphatase reactivity (dAP) test (duration 15 min) was applied on frozen sections, while H&E and immunohistochemistry for detection of OCT3/4, α-fetoprotein, human chorionic gonadotrophin (hCG) and cytokeratin was performed on the paraffin-embedded slides. Endothelial cells served as control for the dAP test. Positive staining was found in all CIS (n=965), seminoma (n=1035) and embryonal carcinoma (n=584), either intratubular, microinvasive or invasive. Differentiated non-seminomas (n=1238) showed variable staining. No staining was identified in spermatocytic seminomas (n=5), testicular lymphomas (n=42), testicular rhabdomyosarcomas (n=7), Leydig cell tumours (n=31), Sertoli-cell-only nodules (n=4), (epi) dermoid cyst (n=16), normal testicular parenchyma (n=116), testicular torsion (n=32) and inflammation of the epididymis (n=19). The dAP test results matched H&E-stained parallel sections, as well paraffin-embedded tissue analysis, including immunohistochemistry. CONCLUSIONS: The dAP test is an informative, reproducible and easy tool to diagnose CIS, (intratubular and microinvasive) seminoma and embryonal carcinoma on frozen tissue sections, being of great value in the context of sparing surgery.

MRI evaluation of urethral diverticula and differential diagnosis in symptomatic women.

OBJECTIVE: The purpose of this study was to evaluate the role of MRI in the diagnosis and differential diagnosis of urethral diverticula in symptomatic women. MATERIALS AND METHODS: Women referred for MRI at a single institution because of suspicion of urethral diverticula were included. All MRI examinations were independently evaluated by two radiologists and compared with patients' follow-up data. Sensitivity and specificity of MRI for urethral diverticula were calculated using surgery and clinical confirmation as the reference standards. Image quality of the urethra and periurethral region performed with the endoluminal coil was compared with the pelvic phased-array coil. RESULTS: From a study group of 60 patients (mean age, 44 years), 20 patients (33%) had urethral diverticula and 28 (47%) had an alternative diagnosis, of which 13 (46%) were visualized with MRI. In the remaining 12 patients (20%) no abnormalities were found. For urethral diverticula, MRI had both sensitivity and specificity of 100%. Twenty patients had a total of 27 diverticula; these were mostly locally round (n = 12) with sharp margins (n = 25) and high (n = 19) homogeneous (n = 16) signal intensity on T2-weighted sequences. The ostium of urethral diverticula was identified in 23 diverticula (85%) by both readers. Agreement was 93% with κ = 0.72. Endoluminal coil placement in the vagina showed the best image quality of the urethra and periurethral region. CONCLUSION: Dedicated MRI is an excellent imaging modality for urethral diverticula; furthermore, MRI will show the alternative diagnosis in almost one half of the remaining patients.

Increased sperm DNA fragmentation in patients with vasectomy reversal has no prognostic value for pregnancy rate.

PURPOSE: We evaluated sperm DNA fragmentation in patients with vasectomy reversal and its prognostic value to determine spontaneous and assisted reproductive technique pregnancy rates. MATERIALS AND METHODS: We prospectively assessed DNA fragmentation with the sperm chromatin structure assay in postoperative semen samples of 70 patients with vasectomy reversal. At a median +/- SD followup of 4.3 +/- 0.5 years pregnancy rates were recorded. RESULTS: DNA fragmentation in patients with vasectomy reversal was significantly increased vs that in proven fertile controls (30.2% +/- 20.1% vs 15.3% +/- 5.4%, p <0.001). Significant negative correlations were found between DNA fragmentation index and total sperm count, progressive motility, total number of progressive sperm, normal morphology and sperm vitality (-0.325

Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate.

PURPOSE: We prospectively evaluated changes in sperm chromatin structure in infertile patients before and after surgical repair of varicocele, and the impact on the pregnancy rate. MATERIALS AND METHODS: Included in the study were 49 men with at least a 1-year history of infertility, a palpable varicocele and oligospermia. World Health Organization semen analysis and sperm DNA damage expressed as the DNA fragmentation index using the sperm chromatin structure assay were assessed preoperatively and postoperatively. Pregnancy (spontaneous and after assisted reproductive technique) was recorded 2 years after surgery. RESULTS: Mean sperm count, sperm concentration and sperm progressive motility improved significantly after varicocelectomy from 18.3 x 10(6) to 44.4 x 10(6), 4.8 x 10(6)/ml to 14.3 x 10(6)/ml and 16.7% to 26.6%, respectively (p <0.001). The DNA fragmentation index decreased significantly after surgery from 35.2% to 30.2% (p = 0.019). When the definition of greater than 50% improvement in sperm concentration after varicocelectomy was applied, 31 of 49 patients (63%) responded to varicocelectomy. After varicocelectomy 37% of the couples conceived spontaneously and 24% achieved pregnancy with assisted reproductive technique. The mean postoperative DNA fragmentation index was significantly higher in couples who did not conceive spontaneously or with assisted reproductive technique (p = 0.033). CONCLUSIONS: After varicocelectomy sperm parameters significantly improved and sperm DNA fragmentation was significantly decreased. Low DNA fragmentation index values are associated with a higher pregnancy rate (spontaneous and with assisted reproductive technique). We suggest that varicocelectomy should be considered in infertile men with palpable varicocele, abnormal semen analysis and no major female factors.

Gonadal dysfunction in male cancer patients before cytotoxic treatment.

Male patients diagnosed with cancer are often referred for semen cryopreservation before gonadotoxic treatment but often have low semen quality. The aim of this study was to evaluate which type of cancer affects gonadal function and proposes a risk factor for low pre-treatment semen quality. Between January 1983 and August 2006, 764 male cancer patients were referred for semen cryopreservation prior to chemotherapy and radiotherapy. We compared semen characteristics and reproductive hormones between different groups of cancer patients. In addition, we evaluated the role of tumour markers in patients with testicular germ-cell tumours (TGCT) on fertility. Abnormal semen parameters were found in 489 men (64%) before cancer treatment. Patients with TGCT and extragonadal germ-cell tumours had significantly lower sperm concentrations and inhibin B levels than all other patient groups. No semen could be banked in 93 patients (12.2%). Eight hundred and thirty-nine of 927 (90%) produced semen samples were adequate for cryopreservation. Inhibin B in all groups showed to be the best predictor of semen quality. Although pre-treatment raised tumour markers were associated with a decrease in inhibin B and increased follicle stimulating hormone, both predictive for low semen quality; no direct linear association could be found between raised beta-HCG, alfa-fetoprotein and semen quality. Only 1/3 of cancer patients had normal semen parameters prior to cancer treatment. Patients with TGCT and extragonadal GCT have the highest risk for impaired semen quality and gonadal dysfunction at the time of semen cryopreservation.

Erectile dysfunction in the community: trends over time in incidence, prevalence, GP consultation and medication use--the Krimpen study: trends in ED.

INTRODUCTION: In the general population, erectile dysfunction (ED) is surrounded by a "taboo." Epidemiologists studying this problem have to be aware of the phenomenon of the "tip-of-the-iceberg." AIMS: Our aim is to describe the iceberg phenomenon for ED and their help-seeking behavior in the general population during a period when public interest in ED heightened and waned after the introduction of the drug sildenafil. METHODS: The data were obtained as part of a large longitudinal community-based study, i.e., the Krimpen study. With four rounds of data collection with an approximate 2.1 years interval, the local pharmacists provided data on medication use, whereas abstracts from the medical record and history were provided by the local general practitioners (GPs). The data from the questionnaires were entered into the Krimpen study database but were not communicated to the GPs. MAIN OUTCOME MEASURES: ED: according to the ICS-questionnaire, GP consultation: search of electronic medical dossier for ED or reports from any specialist, use of ED medication as delivered by the pharmacy. RESULTS: The age-standardized prevalence of ED is stable, i.e., around 40%. During the period 1995 to 2000, the incidence increased from 5% to 6.5%, then it stabilizes around 5% per year. The first-time use of ED medication increases exponentially between 1995 and 2000, then it stabilizes at about 3.5% per year. The number of GP consultations by men with ED increases up to 1999, after which it stabilizes at about 1.8% per year. CONCLUSION: We suggest that the availability and awareness of a new pharmacological option induced a change of behavior among GPs and their patients.

Male infertility in cancer patients: Review of the literature.

The number of men surviving cancer at a young age has increased dramatically in the past 20 years as a result of early detection and improved cancer treatment protocols; more than 75% of young cancer patients nowadays are long-term survivors. Quality of life has become an important issue in childhood and adult cancer patients. The commonest cancers in patients of reproductive age are leukaemia, Hodgkin's lymphomas and testicular germ cell tumors. Fertility is often impaired after chemotherapy and radiation therapy. Cryopreservation of semen before cancer treatment starts is currently the only method to preserve future male fertility. In some malignancies, especially in germ cell tumors, sperm quality is already abnormal at the time of diagnosis. In approximately 12% of men, no viable spermatozoa are present for cryopreservation before the start of chemotherapy. Cytotoxic therapy influences spermatogenesis at least temporarily and in some cases permanently. The amount of damage inflicted by chemotherapy on spermatogenesis depends on the combination of drugs used and on the cumulative dose given for cancer treatment. Alkylating agents, such as cyclophosphamide and procarbazine, are most detrimental to germ cells. Radiation therapy, especially whole-body irradiation, is also associated with the risk of permanent sterility. Besides the cancer treatment, tumor type and pretreatment fertility are of prognostic value for future fertility in male cancer survivors. After cancer treatment, many men need artificial reproductive techniques to achieve fatherhood; usually in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is indicated for successful treatment. About 15% of men will use their cryopreserved semen because of persistent azoospermia after cancer treatment. Treatment results with cryopreserved semen are generally good and comparable to general IVF and ICSI results. So far, no studies have reported an increased rate of congenital abnormalities or malignancies in children born from fathers who had cancer treatment is the past, but close follow up is warranted, especially in children born after IVF/ICSI.

Risk factors for deterioration of erectile function: the Krimpen study.

This report from the Krimpen study explored the relationship between the determinants for worsening of erectile function in the open population. In Krimpen aan den IJssel (a municipality near Rotterdam), all men aged 50-75 years, without cancer of the prostate or the bladder and without a history of radical prostatectomy or neurogenic bladder disease, were invited to participate in June 1995. The response rate was 50%. The follow-up was until June 2004. At baseline a visit to a health centre for the measurement of urinalysis, height, weight and blood pressure was part of the ongoing study. During baseline and at the first follow-up, second follow-up and third follow-up, a self-administered booklet consisting of a compilation of validated questionnaires including the International Continence Society male sex questionnaire was completed. At the urology outpatient clinic, a urological workup was measured. All participants were asked to keep a frequency-volume chart for 3 days. A multivariate Cox-proportional hazard model was constructed to find the determinants of worsening of erectile function, correcting for age. Total follow-up time was 4948 person years consisting of 975 men. During follow-up, 441 events of worsening of erectile function occurred. Multivariate Cox-proportional hazard ratio analyses showed that body mass index (BMI), irritative lower urinary tract symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and sexual inactivity were determinants with significant hazard ratios. In addition to age, determinants for a deterioration of erectile function based on multivariate longitudinal analyses are BMI, diabetes mellitus, COPD, sexual inactivity and irritative IPSS. The mechanism of various determinants is discussed.

Erectile dysfunction and mental health in a general population of older men.

INTRODUCTION: Erectile dysfunction (ED) is more prevalent with increasing age. Previous studies showed that ED was negatively associated with mental health (MH) in specific patient groups. AIM: To examine the association, and potential mediating factors, between ED and MH in healthy elderly men. MAIN OUTCOME MEASURES: ED was defined as (almost) always having problems in achieving or maintaining an erection if desired, or not being sexually active because of erectile problems. MH was assessed with 36-item Short-Form Health Survey scale MH5 with five items on, e.g., being happy or depressed (range 0-100). Potential mediators between ED and MH were satisfaction with and importance attached to sex life. METHODS: The study population consisted of a consecutive sample of 3,810 participants from the European Randomized Study of Screening for Prostate Cancer, aged 57-78 years, who had screened negatively for prostate cancer. Associations between ED, potential mediating factors, and MH were tested by analysis of variance and analysis of covariance. RESULTS: Covariance analysis, adjusted for age, comorbidity, and use of erectile aids, showed that men with ED had significantly lower MH scores (80.8 +/- 1.2) than men without ED (83.7 +/- 1.2; P < 0.001). ED was also associated with the potential mediator "satisfaction with sex life" but not with "importance attached to sex life." Men with ED were significantly more often dissatisfied with their sex lives (P < 0.001). Adjustment for satisfaction with sex life, but not for importance attached to sex life, reduced the strength of the association (beta value) between ED and poor MH from 2.88 to -0.84. CONCLUSIONS: ED was associated with poorer MH. Satisfaction with sex life, but not importance attached to sex life, may play a mediating role in this association. These results suggest that if men with ED can be helped to be satisfied with their sex lives despite ED, MH can be preserved.

Effect of childhood cancer treatment on fertility markers in adult male long-term survivors.

BACKGROUND: Although it is accepted that pediatric cancer treatment harbors a risk of gonadal damage, large cohort studies using up-to-date fertility markers are lacking. PROCEDURE: The aim of our study was to evaluate the gonadal toxicity of childhood cancer treatment using fertility markers. We included 248 adult male long-term survivors of childhood cancer. Median age at diagnosis: 5 years, median age at follow-up: 24 years, median follow-up time 18 years. We evaluated patient characteristics, treatment modalities, testicular size, and endocrinological parameters including Inhibin B, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. RESULTS: The median value of Inhibin B in the cancer survivor group was 126 ng/L versus 177 ng/L in the control group (P < 0.001). In the survivors, 67% had Inhibin B levels below the normal reference value of 150 ng/L compared with 26% in the control group (P < 0.05). Inhibin B was the most sensitive discriminator between survivors and controls. Significantly decreased Inhibin B levels and increased FSH levels were found in men treated for Hodgkin and non-Hodgkin lymphoma, acute-myeloid leukemia, neuroblastoma, and sarcoma as compared to other malignancies. Cumulative dosages of procarbazine and cyclophosphamide were the only independent chemotherapy-related predictors for decrease of Inhibin B levels and increase of FSH. Age at time of treatment did not influence post-treatment Inhibin B or FSH levels. CONCLUSIONS: Severe gonadal impairment is a risk in a considerable subgroup of childhood cancer survivors based on current fertility markers like Inhibin B. Males receiving gonadotoxic treatment before puberty are not protected from post treatment gonadal dysfunction.

[Acquired undescended testes: treatment and consequences for future fertility]. / Verworven niet-scrotale testis.

1-3% of boys develop an acquired undescended testes (UDT), meaning that the testes cannot be returned into the scrotum after previously having been located in a stable scrotal position. Fertility issues for patients with acquired UDT are comparable to those for patients with congenital UDT. Hypothetically speaking, patients with acquired UDT are at lower risk of testicular cancer than patients with congenital UDT. The appearance of an asymmetrical scrotum, which is associated with UDT, may negatively influence quality of life. Over 50% of the acquired UDTs will spontaneously descend at the start of puberty, thereby justifying conservative management of the condition. Orchidopexy directly after diagnosis does not have any advantages over awaiting spontaneous descent until puberty when fertility in later life of patients with unilateral acquired UDT is concerned; however, it may be beneficial in bilateral acquired UDT.

Meiotic arrest occurs most frequently at metaphase and is often incomplete in azoospermic men.

OBJECTIVE: To establish which meiotic checkpoints are activated in males with severe spermatogenic impairment to improve phenotypic characterization of meiotic defects. DESIGN: Retrospective observational study. SETTING: University medical center research laboratory and andrology clinic. PATIENT(S): Forty-eight patients with confirmed spermatogenic impairment (Johnsen scores 3-6) and 15 controls (Johnsen score 10). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantitative assessment of immunofluorescent analyses of specific markers to determine meiotic entry, chromosome pairing, progression of DNA double-strand break repair, crossover formation, formation of meiotic metaphases, metaphase arrest, and spermatid formation, resulting in a novel classification of human meiotic arrest types. RESULT(S): Complete metaphase arrest was observed most frequently (27%), and the patients with the highest frequency of apoptotic metaphases also displayed a reduction in crossover number. Incomplete metaphase arrest was observed in 17% of the patients. Only four patients (8%) displayed a failure to complete meiotic chromosome pairing leading to pachytene arrest. Two new types of meiotic arrest were defined: premetaphase and postmetaphase arrest (15% and 13%, respectively). CONCLUSION(S): Meiotic arrest in men occurs most frequently at meiotic metaphase. This arrest can be incomplete, resulting in low numbers of spermatids, and often occurs in association with reduced crossover frequency. The phenotyping approach described here provides mechanistic insights to help identify candidate infertility genes and to assess genotype-phenotype correlations in individual cases.