Y chromosome microdeletions in infertile male candidates for microfertilization

Uvod. Mikrodelecije Y hromozoma su, posle Klinefelterovog (Klinefelter) sindroma, najčešći genetski uzrok neplodnosti muškaraca. Cilj rada. Cilj istraživanja je bio da se utvrdi učestalost mikrodelecija Y hromozoma kod muškaraca s idiopatskom neplodnošću koji su kandidati za mikrofertilizaciju (Intracytoplasmic Sperm Injection - ICSI), kao i da se ispita korelacija genotipa i fenotipa kod bolesnika sa delecijama Y hromozoma. Metod rada. U studiju je prvobitno uključeno 160 odabranih muškaraca s malim brojem spermatozoida (manje od 5×106 spermatozoida po mililitru ejakulata), međutim, 40 muškaraca je isključeno iz daljeg ispitivanja (kod 10 ispitanika su utvrđeni citogenetski poremećaji, a kod 30 je dijagnostikovan jedan od poznatih uzroka neplodnosti). Kontrolnu grupu ispitanika činilo je 150 muškaraca koji su ostvarili očinstvo bar jednom u poslednje dve godine. Genomska DNK je izolovana iz periferne krvi 120 odabranih ispitanika, a postojanje ili izostanak delecija Y hromozoma analizirano je u dve multipleks reakcije lančanog umnožavanja (Polimerase Chain Reaction - PCR) korišćenjem odgovarajućih prajmera. Rezultati. Izostanak amplifikacije korišćenjem bar jednog para prajmera dokazan je kod 12 ispitanika (10%), dok u kontrolnoj grupi ispitanika nije dokazana nijedna delecija Y hromozoma. Od ukupno 12 otkrivenih delecija, kod devet ispitanika delecija je lokalizovana u regionu AZFc (75%), kod jednog ispitanika je otkrivena u regionu AZFa (8%), dok su kod dva ispitanika delecije zabeležene u regionu AZFbc (17%). Zaključak. Ispitivanje mikrodelecija Y hromozoma treba razmotriti kao važan elemenat genetskog savetovanja infertilnih parova u Srbiji. Odluka o primeni tehnika asistirane reprodukcije treba da bude zasnovana na rezultatima kliničkog pregleda, spermograma, kariotipa, endokrinih ispitivanja, kao i na rezultatima analize mikrodelecija Y hromozoma.Introduction Y chromosome microdeletions are the second most frequent genetic cause of male infertility after Klinefelter's syndrome. Objective The aim of the study was to determine the frequency of Y chromosome microdeletions in a group of infertile men with an idiophatic cause of infertility, candidates for microfertilization (Intra-cytoplasmic Sperm Injection - ICSI) in Serbia and to correlate genotype-phenotype in patients with Y chromosome microdeletions. METHOD One hundred and sixty patients with low sperm count (less than 5x106 spermatozoa/ml) were enrolled in the study. Forty patients were excluded from the study: ten because they were diagnosed with cytogenetic abnormality and thirty patients were diagnosed with other known causes of infertility. The control group consisted of 150 men who fathered at least one child in the last two years. Genomic DNA was extracted from peripheral blood samples and two multiplex polymerase chain reactions (PCR) analyses were performed using specific primers to confirm the presence or absence of Y chromosome microdeletions. Results Microdeletions were detected in 12 of 120 (10%) cases, while no deletions were detected in the control group. Of total number of 12 deletions, nine were detected in AZFc region (75%), one in AZFa (8%), and two in AZFbc (17%). Conclusion Testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counselling of infertile couples in Serbia. Decisions regarding the assisted reproduction should be made based on the detailed clinical, endocrinological and cytogenetic examinations, spermogram, presence or absence and type of AZF microdeletions and CFTR gene mutations

Disease relapses after radical radiotherapy of prostate cancer: Analysis of prognostic factors

INTRODUCTION Although there is no consensus on which is the best option in prostate cancer treatment, these patients could be successfully treated with radiotherapy. Regarding some prognostic factors, it is possible today to classify prostate cancer patients into several risk groups for clinical and biochemical relapse, and therefore to choose the right treatment modality. OBJECTIVE The objective in our study was to analyze the impact of tumor stage and grade, previous transurethral resection of the prostate (TUR), initial prostate specific antigen (PSA) level and age on disease relapse after radical radiotherapy of the prostate cancer. METHOD Between January 1991 and December 2005, a clinical, retrospective study was performed at the Radiotherapy Department of the Institute for Oncology and Radiology of Serbia, which included 283 patients with prostate cancer treated only with radical radiotherapy. During regular follow-up we analyzed response to treatment and disease relapse. RESULTS After radical radiotherapy disease relapse more often occurred (with statistical significance) in patients with locally advanced tumor (stage C 35% vs. A 13% vs. B 19%), low tumor grade (grade III 38% vs. grade II 23% vs. grade I 17%), initial PSA level over 10 ng/ml (29%) and over 20 ng/ml (37%) compared to 11% in the patients with initial PSA level below10 ng/ml, and patients of lower age (less than 55 years 50% vs. 16% in patients over 70 years). CONCLUSION Tumor stage C, low tumor grade (grade II-III), initial PSA level over 10 ng/ml (over 20 ng/ml) and younger age are poor prognostic factors for disease relapse. In this case, radiotherapy as monotherapy is not an adequate approach, and it needs to be combined with other therapeutic modalities

Acute and late toxicity in radical radiotherapy of prostate cancer

Introduction. Although radical radiotherapy has proved to be a successful method in prostate cancer treatment, the conventional (box) technique can result in significant adverse events. Objective. The objective of our study was to estimate the frequency, type and severity of acute and late toxicity in radical radiotherapy of prostate cancer. Methods. In a clinical retrospective study, we included 283 patients with histologically confirmed prostate cancer. All our patients received radical, conventional radiotherapy using the four-field technique. The study was performed at the Radiotherapy Department of the Institute for Oncology and Radiology of Serbia between January 1991 and December 2005. During regular follow-up, we analyzed the frequency, type and severity of acute and late toxicity. Results. Two thirds (71%) of our patients had acute toxicity of at least one organ within the radiation field. Most frequent complication was radiation dermatitis (10.5%), and enteritis (9%), cystitis (6%) and proctitis (2.5%). Acute adverse events were mostly low grade (I and II, 28-61%). Late complications were registered in 20.5% of patients. Skin fibrosis was most frequent (12%). Chronic proctitis was detected in 4% and urethral stricture in 4.5% of our patients. All late complications were low grade. Conclusion. Treatment tolerance of radical radiotherapy is relatively good. Although most patients develop acute toxicity, it is commonly low grade and requires the interruption of radiotherapy treatment in 20% of patients only. Late toxicity is rarer than acute and, in most cases, it does not affect the quality of life

Genetic variation in circadian rhythm genes CLOCK and ARNTL as risk factor for male infertility.

BACKGROUND: The circadian system has a major role in maintaining homeostasis and proper body functions including reproductive capacity. The aim of this study was to examine whether there is an association between genetic variability in the primary clock genes CLOCK and ARNTL and male infertility in humans. METHODOLOGY/PRINCIPAL FINDINGS: We performed a case-control study, where we searched for an association between polymorphisms of CLOCK and ARNTL genes and male infertility in 961 Slovenian and Serbian Caucasian men. The study group consisted of 517 patients with idiopathic infertility and a control group of 444 fertile men. A statistically significant difference was found in genotype distribution between the two groups in the CLOCK gene: rs11932595 (p = 6·10(-5), q = 4·10(-4), OR equaled 1.9 with 95% CI 1.4-2.7), rs6811520 (p = 2·10(-3), q = 8·10(-3), OR = 1.7 with 95% CI 1.2-2.2) and rs6850524 (p = 0.01, q = 0.02, OR = 1.4 with 95% CI 1.1-1.9). Further analyses of haplotypes were consistent with genotyping results. CONCLUSIONS/SIGNIFICANCE: We provide evidence that genetic variability in the CLOCK gene might be associated with male infertility warranting further confirmation and mechanistic investigations

Y chromosome microdeletions in infertile male candidates for microfertilization

Introduction Y chromosome microdeletions are the second most frequent genetic cause of male infertility after Klinefelter's syndrome. Objective The aim of the study was to determine the frequency of Y chromosome microdeletions in a group of infertile men with an idiophatic cause of infertility, candidates for microfertilization (Intra-cytoplasmic Sperm Injection - ICSI) in Serbia and to correlate genotype-phenotype in patients with Y chromosome microdeletions. METHOD One hundred and sixty patients with low sperm count (less than 5x106 spermatozoa/ml) were enrolled in the study. Forty patients were excluded from the study: ten because they were diagnosed with cytogenetic abnormality and thirty patients were diagnosed with other known causes of infertility. The control group consisted of 150 men who fathered at least one child in the last two years. Genomic DNA was extracted from peripheral blood samples and two multiplex polymerase chain reactions (PCR) analyses were performed using specific primers to confirm the presence or absence of Y chromosome microdeletions. Results Microdeletions were detected in 12 of 120 (10%) cases, while no deletions were detected in the control group. Of total number of 12 deletions, nine were detected in AZFc region (75%), one in AZFa (8%), and two in AZFbc (17%). Conclusion Testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counselling of infertile couples in Serbia. Decisions regarding the assisted reproduction should be made based on the detailed clinical, endocrinological and cytogenetic examinations, spermogram, presence or absence and type of AZF microdeletions and CFTR gene mutations.

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

PEJCIC TP, TULIC CD, LALIC NV, GLISIC BD, IGNJATOVIC SD, MARKOVIC BB, HADZI-DJOKK JB. Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression? Can J Urol 2013;20(2):6707-6713. Introduction: Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. Materials and methods: From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV lt 31 mL and TPV >= 31 mL. Additional three groups were formed upon MTOPS study criteria: non-progressive BPH group (TPV lt 31 mL, PSA lt 1.6 ng/mL, age lt 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV >= 31 ml, PSA >= 1.6 ng/mL, age >= 62 yrs). Results: Average uPSA values in the groups TPV lt 31 mL and TPV 31 mL were 119.3 +/- 124.5 and 255.5 +/- 204.9 ng/mL, respectively and they were significantly different (p lt 0.0001). Average uPSA values in the non-progressive BPH group, intermediate group and progressive BPH group were 86.8 +/- 82.4 ng/mL, 166.6 +/- 164.9 ng/mL and 274.9 +/- 208.3 ng/mL, respectively and they were significantly different (p lt 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p lt 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. Conclusion: The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level >= 150 ng/mL can be used as additional predictive parameter of BPH progression

Clinical, sperm and hormonal characteristics of the 517 infertile men.

<p>Values are given as means ± SD.</p

Frequencies and distribution of probable haplotypes in the patient and control groups as predicted by haplo.stats.

<p>Frequencies and distribution of probable haplotypes in the patient and control groups as predicted by haplo.stats.</p

Genotype and allelic distribution of the CLOCK and ARNTL polymorphisms of the 517 infertile men and 444 fertile controls.

*<p>ARNTL SNP rs12363415 showed a departure from the Hardy-Weinberg equilibrium and was excluded.</p