Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Male patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life.

Gonadal function in boys with newly diagnosed cancer before the start of treatment.

STUDY QUESTION: Are Inhibin B and testosterone levels reduced in boys with newly diagnosed cancer prior to therapy? SUMMARY ANSWER: Pretreatment serum levels of Inhibin B and testosterone are significantly reduced in boys with newly diagnosed cancer, compared to reference values. WHAT IS ALREADY KNOWN: Disease-related gonadal impairment has been demonstrated in girls and young women diagnosed with cancer, prior to therapy. STUDY DESIGN, SIZE, DURATION: We conducted a descriptive study in boys newly diagnosed with cancer between January 2006 and February 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum Inhibin B and testosterone levels were determined in 224 boys, up to the age of 18 years, with newly diagnosed cancer prior to therapy. Hormone levels were compared with age-matched reference values. The cohort consisted of patients with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma (HL), non-Hodgkin lym-phoma (NHL), nephroblastoma, neuroblastoma and sarcoma. MAIN RESULTS AND THE ROLE OF CHANCE: This study demonstrates reduced serum levels of Inhibin B in boys with newly diagnosed cancer, compared to reference values (standard deviation score (SDS) -0.9, P < 0.001). Median Inhibin B level in patients was 103.5 ng/l (range 20-422). Of all patients, 78.6% showed Inhibin B levels below the 50th percentile, and 58.5% had Inhibin B levels below the 25th percentile. Serum testosterone levels were significantly lower than the reference range population (SDS -1.2, P < 0.001). Median testosterone level in pubertal patients was 7.3 nmol/l (range 0.1-23.6). No correlation with clinical signs of general illness and hormone levels were observed. LIMITATIONS, REASONS FOR CAUTION: In this study, reproductive hormone levels were compared with age-matched reference values. Future studies may compare reproductive hormone levels with case controls. WIDER IMPLICATIONS OF THE FINDINGS: Future longitudinal studies are necessary to determine whether pretreatment impaired gonadal function at the time of cancer diagnosis is an important determinant of ultimate recovery of spermatogenesis after treatment and later on in adulthood. STUDY FUNDING/COMPETING INTERESTS: W.v.D. was supported by the Pediatric Oncology Center Society for Research (KOCR), Rotterdam, The Netherlands. A.-L.L.F.v.d.K. was supported by EU FP7 PanCare LIFE study. The authors have no conflicts of interest.

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer.

PURPOSE: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18-39 years) cancer. METHODS: This study included n = 1457 male and n = 2112 female long-term survivors (Mage = 43-45 years; 5-22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry. RESULTS: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2-3.6]), not having children (OR = 5.0; 95%CI [3.2-7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to "others"), and more intense treatments (OR = 1.5; 95%CI [1.1-2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. CONCLUSIONS: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors' well-being. IMPLICATIONS FOR CANCER SURVIVORS: The extent to which cryopreservation positively affects survivors' well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.

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.

Evaluating the implementation of a multidisciplinary lifestyle intervention for people with severe mental illness in sheltered housing: effectiveness-implementation hybrid randomised controlled trial.

BACKGROUND: Lifestyle interventions can improve health-related outcomes for people with severe mental illness (SMI), but few studies evaluate this potential in everyday settings. After a successful approach in routine inpatient mental healthcare (MULTI), we sought to replicate this multidisciplinary lifestyle-enhancing support in people with SMI living in sheltered housing (MULTI_sh). AIMS: To evaluate the effectiveness and implementation of MULTI_sh (trial registration: NCT03157557). METHOD: In an effectiveness-implementation hybrid cluster-randomised controlled trial, six municipalities with sheltered housing facilities in The Netherlands were randomly assigned to MULTI_sh (n = 3) or treatment as usual (TAU, n = 3). After 12 months, we evaluated effects on metabolic health, sedentary behaviour/physical activity (ActiGraph GT3X+), quality of life (EuroQol 5D, WHOQoL-Bref) and psychopathology (Brief Psychiatric Rating Scale Expanded Version) using multiple regression, adjusting for baseline values and municipalities (intention to treat and per protocol). In addition, implementation fidelity and barriers/facilitators were evaluated (Measurement Instrument for Determinants of Innovation). RESULTS: Of 177 eligible patients, 74 (42%) could be included in the analyses. Health outcomes did not substantially improve with MULTI_sh (n = 45) compared with TAU (n = 29). MULTI_sh was not implemented as intended. Most patients and all healthcare professionals believed that patients' lifestyle should be part of treatment, but implementation was primarily (in)directly hindered by organisational factors (e.g. staff shortages, complexity of participation, lack of time and difficulty getting patients involved). CONCLUSIONS: MULTI_sh was not implemented as intended and no clinical health improvements were found. Organisations are decisive in the success or failure of the implementation of lifestyle interventions for people with SMI. More intensive implementation strategies on this level are warranted in sheltered housing.

Current practices regarding corporotomy localization during penoscrotal inflatable penile implant surgery: a multicenter cohort study.

Literature concerning corporotomy location in multicomponent inflatable penile prosthetic surgery via a penoscrotal approach is scarce if not nonexistent. Aim of our study was to report practices in low-, moderate-, and high-volume penile implant centers regarding corporotomy location and evaluate its potential impact on intraoperative and short-term postoperative complications. Data from 18 (13 European and 5 American) implant centers were collected retrospectively between September 1st, 2018 and August 31st, 2019. Variables included: intraoperative proximal and distal corpus cavernosum length measurement, total corporal length measurement, total penile implant cylinder length, and length of rear tip extenders. Eight hundred and nine virgin penile implant cases were included in the analysis. Mean age of participants was 61.5 ± 9.6 years old. In total, 299 AMS 700™ (Boston Scientific, USA) and 510 Coloplast Titan® (Minneapolis, MN USA) devices were implanted. The mean proximal/distal corporal measurement ratio during corporotomy was 0.93 ± 0.29 while no statistical difference was found among low-, moderate-, and high-volume penile implant centers. A statistically significant correlation between lower proximal/distal measurement ratio and higher age (p = 0.0013), lower BMI (p < 0.0001), lower use of rear tip extenders (RTE) (p = 0.04), lower RTE length (p < 0.0001), and absence of diabetes (p = 0.0004) was reported. In a 3-month follow up period, 49 complications and 37 revision procedures were reported. This is the first study reporting the current practices regarding corporotomy location during IPP placement in a multicenter cohort, particularly when including such a high number of patients. Nevertheless, the retrospective design and the short follow up period limits the study outcomes. Corporotomy location during penoscrotal IPP implantation does not correlate with intraoperative or short-term postoperative complication rates. Future studies with longer follow up are needed in order to evaluate the association of corporotomy location with long-term complications.

Management of Testicular Microlithiasis.

Until molecular diagnostics become available, individualized risk assessment for men with testicular microlithiasis, counseling on the current evidence base regarding the benefit of testicular biopsy or testicular self-examination, and a patient-centered approach provide the framework for the best quality of care for the individual patient.

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.

Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: a systematic review and meta-analysis.

BACKGROUND: Factor affecting sperm retrieval rate (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in patients with non-obstructive azoospermia (NOA) have not been systematically evaluated. In addition, although micro-TESE (mTESE) has been advocated as the gold standard for sperm retrieval in men with NOA, its superiority over conventional TESE (cTESE) remains conflicting. OBJECTIVE AND RATIONALE: The objective was to perform a meta-analysis of the currently available studies comparing the techniques of sperm retrieval and to identify clinical and biochemical factors predicting SRR in men with NOA. In addition, PRs and live birth rates (LBRs), as derived from subjects with NOA post-ICSI, were also analysed as secondary outcomes. SEARCH METHODS: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR derived from cTESE or mTESE in patients with NOA and their specific determinants were included. Data derived from genetic causes of NOA or testicular sperm aspiration were excluded. OUTCOMES: Out of 1236 studies, 117 studies met the inclusion criteria for this study, enrolling 21 404 patients with a mean age (± SD) of 35.0 ± 2.7 years. cTESE and mTESE were used in 56 and 43 studies, respectively. In addition, 10 studies used a mixed approach and 8 studies compared cTESE with mTESE approach. Overall, a SRR per TESE procedure of 47[45;49]% (mean percentage [95% CI]) was found. No differences were observed when mTESE was compared to cTESE (46[43;49]% for cTESE versus 46[42;49]% for mTESE). Meta-regression analysis demonstrated that SRR per cycle was independent of age and hormonal parameters at enrolment. However, the SRR increased as a function of testis volume. In particular, by applying ROC curve analysis, a mean testis volume higher than 12.5 ml predicted SRR >60% with an accuracy of 86.2% ± 0.01. In addition, SRR decreased as a function of the number of Klinefelter's syndrome cases included (S = -0.02[-0.04;-0.01]; P < 0.01. I = 0.12[-0.05;0.29]; P = 0.16). Information on fertility outcomes after ICSI was available in 42 studies. Overall, a total of 1096 biochemical pregnancies were reported (cumulative PR = 29[25;32]% per ICSI cycle). A similar rate was observed when LBR was analysed (569 live births with a cumulative LBR = 24[20;28]% per ICSI cycle). No influence of male and female age, mean testis volume or hormonal parameters on both PR and LBR per ICSI cycle was observed. Finally, a higher PR per ICSI cycle was observed when the use of fresh sperm was compared to cryopreserved sperm (PR = 35[30;40]%, versus 20[13;29]% respectively): however, this result was not confirmed when cumulative LBR per ICSI cycle was analysed (LBR = 30[20;41]% for fresh versus 20[12;31]% for cryopreserved sperm). WIDER IMPLICATIONS: This analysis shows that cTESE/mTESE in subjects with NOA results in SRRs of up to 50%, with no differences when cTESE was compared to mTESE. Retrieved sperms resulted in a LBR of up to 28% ICSI cycle. Although no difference between techniques was found, to conclusively clarify if one technique is superior to the other, there is a need for a sufficiently powered and well-designed randomized controlled trial to compare mTESE to cTESE in men with NOA.

Seminal plasma cobalamin significantly correlates with sperm concentration in men undergoing IVF or ICSI procedures.

Mild hyperhomocysteinemia is caused by B vitamin deficiencies. We hypothesize that these biochemical derangements detrimentally affect spermatogenesis. Therefore, the aim of this study was to investigate the folate, cobalamin, pyridoxine, and homocysteine concentrations in blood and seminal plasma and the associations between these biomarkers and semen parameters in men participating in an in vitro fertilization or intracytoplasmic sperm injection program. From 73 men (median age [range]: 37 years [28-53]), blood and semen samples were obtained for the determination of serum and red blood cell (RBC) folate, serum total cobalamin, whole-blood pyridoxal-5'-phosphate, plasma total homocysteine (tHcy), and serum total testosterone. Semen analysis included sperm concentration, motility, and morphology according to World Health Organization criteria. The B vitamins and tHcy concentrations were significantly correlated in blood but not in seminal plasma. The serum and RBC folate concentrations were significantly correlated also with the total folate concentration in seminal plasma (r = .44; P < .001 and r = .39; P < .001, respectively). Likewise, the total cobalamin concentration in serum and seminal plasma was significantly correlated (r = .55; P = .001). Of interest is that the total cobalamin concentration in seminal plasma was significantly correlated with the sperm concentration (r = .42; P < .001). This is in contrast to the absence of significant associations between the other vitamins and tHcy in blood and seminal plasma and any of the semen parameters. These findings suggest that folate and cobalamin are transferred from the blood to the male reproductive organs and emphasize the role of cobalamin in spermatogenesis in human.

Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia.

AIM: To evaluate whether inhibin-B can predict the outcome of a microsurgical epidymal sperm aspiration (MESA) procedure in patients with suspected primary obstructive azoospermia (OA) and if inhibin-B can replace testicular biopsy in the diagnostic work-up of these patients. METHODS: Inhibin-B levels and testicular biopsy scores were related to the outcome of MESA in 43 patients with suspected primary OA. MESA was considered to be successful when epididymal sperm could be identified during the procedure. RESULTS: Spermatozoa were present in the epididymal aspirate in 28 out of the 43 patients (65%). Inhibin-B values were not significantly different in patients with successful or unsuccessful MESA. The modified Johnsen score, however, was significantly lower in patients with unsuccessful MESA (P = 0.003). A rete testis obstruction or epididymal malfunctioning was found in 15% of patients with suspected primary OA, reflected by unsuccessful MESA despite normal inhibin-B levels and normal testicular histology. CONCLUSION: Inhibin-B cannot replace testicular biopsy as a diagnostic tool in the work-up of patients with suspected primary OA. Testicular biopsy is useful in identifying patients with spermatogenic arrest, who might have normal inhibin-B values.

Electroejaculation as a method of fertility preservation in boys diagnosed with cancer: a single-center experience and review of the literature.

OBJECTIVE: To evaluate the feasibility of electroejaculation to perform semen cryopreservation in pubertal boys before gonadotoxic therapy and to review the literature on this topic. DESIGN: Retrospective cohort study and review of the literature. SETTING: Academic children's hospital. PATIENT(S): Boys diagnosed with cancer to whom sperm cryopreservation was offered before the start of gonadotoxic therapy. INTERVENTION(S): We studied the outcome of electroejaculation, including patient characteristics, hormone levels, and pretreatment semen parameters. MAIN OUTCOME MEASURE(S): Semen cryopreservation. RESULT(S): Pretreatment semen samples were obtained by masturbation in 106/114 boys with cancer, of which 78/106 were adequate for preservation. Electroejaculation was offered to 11 boys, of which three of 11 samples appeared adequate for preservation. Reviewing all reported electroejaculation cases in children with cancer in the literature, 13/29 (45%) cases were successful. Testosterone levels were higher in patients with successful sperm yield obtained by electroejaculation (median, 8.3 nmol/L [5.2-42.4] in successful harvests, vs. median 1.7 nmol/L [0.01-17.9] in unsuccessful harvests). CONCLUSION(S): Semen cryopreservation should be offered to all pubertal boys diagnosed with cancer. If masturbation fails, electroejaculation can be considered as a useful option for semen cryopreservation and leads to adequate material for cryopreservation in about half of the cases.

Sperm chromatin structure is associated with the quality of spermatogenesis in infertile patients.

OBJECTIVE: To establish the diagnostic value of sperm chromatin structure assessment for the evaluation of male factor infertility, in addition to conventional andrological workup. DESIGN: Cross-sectional controlled study. SETTING: A tertiary referral andrology clinic. PATIENT(S): Two hundred seventy-nine male partners of infertile couples. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The DNA fragmentation index (DFI) determined by the sperm chromatin structure assay (SCSA), semen parameters, serum levels of reproductive hormones, and World Health Organization (WHO) classification of male factor subfertility. RESULT(S): In all patient categories, except those including patients with hypogonadotrophic hypogonadism, sperm antibodies, or normospermia, DFI was significantly higher compared with in proven fertile controls. After classification of the quality of spermatogenesis based on mean testicular volume (<10 ml vs. >15 ml), follicle stimulating hormone (FSH; > 10 U/L vs. <5 U/L), and inhibin-B (<100 nmol/L vs. >150 nmol/L), the DFI was significantly higher in patients with poor spermatogenesis (35.9%) than in patients with normal spermatogenesis (25.9%). In a multiple regression analysis, the teratozoospermia index, sperm vitality, and FSH were significant determinants of the DFI level. Male age was associated with DFI, but leukocytospermia, body mass index, and smoking were not confounders of DFI. CONCLUSION(S): Impaired spermatogenesis, irrespective of the WHO classification of male factor subfertility, is generally associated with an increase of sperm DNA damage.

Low folate in seminal plasma is associated with increased sperm DNA damage.

OBJECTIVE: To determine associations between vitamin B status, homocysteine (tHcy), semen parameters, and sperm DNA damage. DESIGN: Observational study. SETTING: A tertiary referral fertility clinic. PATIENT(S): Two hundred fifty-one men of couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, with subgroups of fertile (n = 70) and subfertile men (n = 63) defined according to semen concentration and proven fertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The DNA fragmentation index (DFI) as marker of sperm DNA damage determined using the sperm chromatin structure assay (SCSA), and semen parameters assessed according to World Health Organization criteria; tHcy, folate, cobalamin, and pyridoxine concentrations determined in seminal plasma and blood. RESULT(S): In the total group of fertile and subfertile men, all biomarkers in blood were statistically significantly correlated with those in seminal plasma. No correlation was found between the biomarkers in blood and the semen parameters. In seminal plasma, both tHcy and cobalamin positively correlated with sperm count. Folate, cobalamin, and pyridoxine were inversely correlated with ejaculate volume. In fertile men, seminal plasma folate showed an inverse correlation with the DNA fragmentation index. CONCLUSION(S): Low concentrations of folate in seminal plasma may be detrimental for sperm DNA stability.

Determinants of ejaculatory dysfunction in a community-based longitudinal study.

OBJECTIVE To analyse the incidence of ejaculatory dysfunction (EJD) and its associated bother, and to determine which factors predispose to incident EJD. SUBJECTS AND METHODS Men aged 50-78 years, registered in the general practices in Krimpen a/d Ijssel, the Netherlands, were recruited. Men were excluded if they had a history of prostatectomy, carcinoma of the bladder or prostate and neurogenic bladder disease. A baseline study and three follow-up assessments (I-III), all with questionnaires, i.e. the Benign Prostatic Hyperplasia impact index, International Prostate Symptom Score, International Continence Society (ICS)male sex questionnaire, and additional measurements, e.g. prostate volume, prostate specific antigen, were made at a mean of 2.2-year intervals. We assessed the objective variables of EJD as the ability to ejaculate, ejaculatory volume, painful ejaculation, and their associated bother (information extracted from the ICSmale sex questionnaire). RESULTS At baseline 671 of 1661 (40.4%) men already had EJD; the cumulative incidence of EJD was 16.5%, 24.7% and 33.1% after follow-up I, II and III, respectively. The mean percentage of men who were bothered with reduced ejaculatory volume or painful ejaculation was 18.3% and 40.6%, respectively. Multivariate analysis showed age, Sickness Impact Profile 'social' (questions on social impairment) and erectile dysfunction to be predisposing factors of EJD (P < 0.05 and R(2) = 0.048). When EJD was defined as a significantly reduced ejaculatory volume or anejaculation only, age and previous transurethral resection of the prostate (TURP) were determinants of EJD (P < 0.05 and R(2) = 0.083). Of the men who had TURP after the follow-up, 51.6% already had EJD at baseline. CONCLUSIONS The cumulative incidence of EJD after 6.5 years of follow-up was significant (33.1%) and EJD was bothersome, especially in men with painful ejaculation. Determinants of EJD were age, social impairment and erectile dysfunction. Predisposing factors of significant reduction of ejaculatory volume and anejaculation were age and TURP, although 51.6% of men already had EJD before TURP. Age appears to be the most significant predisposing factor of EJD.

Inhibin B is superior to FSH as a serum marker for spermatogenesis in men treated for Hodgkin's lymphoma with chemotherapy during childhood.

BACKGROUND: The aim of this study was to evaluate the long-term gonadal sequelae after treatment for childhood Hodgkin's lymphoma with combination chemotherapy, using up to date fertility parameters and andrological evaluation, including for the first time inhibin B. METHODS: There were 56 male patients treated from 1974-1998 for childhood Hodgkin's lymphoma with combination chemotherapy ABVD or EBVD (adriamycin/epirubicin, bleomycin, vinblastine, dacarbazine) with or without MOPP (mechlorethamine, vincristin, prednisone, procarbazine) with the intention to avoid radiotherapy. These men were studied 15.5 years (range 5.6-30.2 years) after cessation of therapy. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, testosterone, sex hormone-binding globulin (SHBG), sperm concentration and sperm DNA integrity were determined. RESULTS: In men treated with MOPP, median FSH and LH were significantly increased (P < 0.001) and inhibin B (17.5 versus 143 ng/l; P < 0.001) and sperm concentration (1.05 versus 49.5 x 10(6)/ml; P < 0.05) were significantly decreased compared with patients treated without MOPP. The number of MOPP courses was significantly correlated with FSH and inhibin B levels. Only inhibin B showed an independent correlation with sperm concentration (r = 0.86; P < 0.001). CONCLUSIONS: The use of MOPP chemotherapy causes permanent gonadal damage in the far majority of male survivors of childhood Hodgkin's lymphoma and inhibin B is the most valuable serum marker for gonadal function.

Surveillance with microsatellite analysis of urine in bladder cancer patients treated by radiotherapy.

OBJECTIVES: The interpretation of cystoscopy and cytology may be troublesome in bladder cancer patients previously treated by radiotherapy. We evaluated polymerase chain reaction (PCR)-based molecular cytology by microsatellite analysis (MA) and routine urine cytology (RUC) and expert urine cytology (EUC) as modes of surveillance for patients previously treated by radiotherapy with curative intent. METHODS: Eighty-one voided urine samples were obtained from 49 patients prior to cystoscopy and subjected to MA, RUC and EUC. RESULTS: During the follow-up period, six patients developed a recurrence. Sensitivity of MA, RUC and EUC was 83%, 50% and 33%, respectively. The specificity of MA, RUC and EUC was 93%, 85% and 97%, respectively. Cystoscopy was positive in 15 cases. Therefore, the positive predictive value of cystoscopy remained limited to 40%. CONCLUSIONS: Next to recent studies demonstrating a high accuracy for MA in non-irradiated patients, our results indicate that molecular cytology by MA may also be a useful tool to improve the surveillance of bladder cancer patients previously treated by radiotherapy.