Constitutional mosaic trisomy 21 and azoospermia: a case report.
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Constitutional full trisomy 21 is a common disorder in which abnormal spermatogenesis has been previously described. However, constitutional mosaic trisomy 21 in an otherwise normal but infertile male has not been explored. We report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic patient. We also propose that the patient's azoospermia may be related to the constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular failure. (+info)
Mutations in the chromosome pairing gene FKBP6 are not a common cause of non-obstructive azoospermia.
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Although it is generally thought that spermatogenic failure has a genetic background, to date only a limited percentage of men with non-obstructive azoospermia (NOA) are diagnosed with a genetic defect. The only common and well-established genetic causes of NOA in humans are numerical and structural chromosomal abnormalities and Y-chromosome deletions. In addition, some infrequent mutations have been identified in the ubiquitin-specific protease 9, Y-linked (USP9Y) and the synaptonemal complex protein 3 (SYCP3) gene that cause azoospermia. FK506-binding protein 6 (Fkbp6) is a newly discovered component of the synaptonemal complex (SC), which is essential for proper chromosome pairing and meiotic division. A null mutation of the Fkbp6 gene causes azoospermia in mice as well as in rats. We tested the hypothesis whether mutations in this gene can also cause azoospermia in humans. We performed a mutation screen in 51 men with NOA through direct sequencing methods. No homozygous mutations were identified. Two heterozygous mutations (T173T and R183C) were identified, which are likely to disrupt FKBP6 protein function. However, both mutations were also found in a group of 218 normospermic controls indicating that one FKBP6 allele appears to be sufficient for normal spermatogenesis. In conclusion, our results suggest that genetic defects in FKBP6 can be excluded as a common cause of azoospermia in humans. (+info)
Decrease of both stem cell factor and clusterin mRNA levels in testicular biopsies of azoospermic patients with constitutive or idiopathic but not acquired spermatogenic failure.
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BACKGROUND: Sertoli cells nurse germ cells during spermatogenesis, and alterations of Sertoli cell functions have been suggested in cases of spermatogenic failures. METHODS: In this work, we measured stem cell factor (SCF) and clusterin mRNA levels, by quantitative RT-PCR, in RNA extracted from testicular biopsies of 49 azoospermic patients classified according to testicular histology as having normal spermatogenesis or spermatogenic failure. RESULTS: When related to the percentage of Sertoli cells counted on a histological section of a neighbouring tissue sample, SCF and clusterin mRNA levels were significantly lower in the 'spermatogenic failure' group compared with the control group (P = 0.0297 and P = 0.0043, respectively). These levels were also significantly lower in the cases of 'constitutive' (cryptorchidism and Yq microdeletion) and 'idiopathic' spermatogenic failures when compared with the control group; conversely, they were not significantly decreased in the group with 'acquired spermatogenic failure' (orchitis, testicular traumatism, chemoradiotherapy and varicocele). CONCLUSIONS: These data further demonstrate an alteration of Sertoli cell functions in some human spermatogenic failures and suggest that a lack of Sertoli cell maturation may be involved in cases of constitutive or idiopathic spermatogenic failures. (+info)
Association of spermatogenic failure with decreased CDC25A expression in infertile men.
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BACKGROUND: DAZ gene family is crucial for human spermatogenesis that requires the precise co-ordination of cell cycle events. CDC25A is recognized as the downstream substrate of DAZ gene family and is thought to function on the M-phase regulation of cell cycles. We investigated the expression profiles of CDC25A in the testes of infertile men and evaluated the relationship between CDC25A levels and testicular phenotype, clinical hormonal parameters and sperm retrieval results. METHODS: The protein and mRNA transcript levels of CDC25A in the testes of 40 azoospermic men were determined by immunohistochemistry and quantitative real-time-PCR. CDC25A in human spermatozoa was investigated by western blotting and immunofluorescence staining. RESULTS: The CDC25A protein was expressed mainly in spermatocyte, spermatid and spermatozoa. CDC25A transcript levels were significantly decreased (P = 0.0009) in patients with spermatogenic failure, especially in men with meiotic arrest and Sertoli cell-only syndrome. Significantly higher CDC25A transcript levels were detected in patients with successful sperm retrieval than in patients with failed sperm retrieval (P = 0.005). CONCLUSIONS: Decreased CDC25A is associated with spermatogenic failure and failed sperm retrieval in infertile men. Further studies are necessary to explore the functional roles of CDC25A in human spermatozoa. (+info)
Beta-endorphin in serum and seminal plasma in infertile men.
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AIM: To access beta-endorphin levels in serum as well as seminal plasma in different infertile male groups. METHODS: Beta-endorphin was estimated in the serum and seminal plasma by enzyme-linked immunosorbent assay (ELISA) method in 80 infertile men equally divided into four groups: non-obstructive azoospermia (NOA), obstructive azoospermia (OA), congenital bilateral absent vas deferens (CBVAD) and asthenozoospermia. The results were compared to those of 20 normozoospermic proven fertile men. RESULTS: There was a decrease in the mean levels of beta-endorphin in the seminal plasma of all successive infertile groups (mean +/- SD: NOA 51.30 +/- 27.37, OA 51.88 +/- 9.47, CBAVD 20.36 +/- 13.39, asthenozoospermia 49.26 +/- 12.49 pg/mL, respectively) compared to the normozoospermic fertile control (87.23 +/- 29.55 pg/mL). This relation was not present in mean serum level of beta-endorphin between four infertile groups (51.09 +/- 14.71, 49.76 +/- 12.4, 33.96 +/- 7.2, 69.1 +/- 16.57 pg/mL, respectively) and the fertile control group (49.26 +/- 31.32 pg/mL). The CBVAD group showed the lowest seminal plasma mean level of beta-endorphin. Testicular contribution of seminal beta-endorphin was estimated to be approximately 40%. Seminal beta-endorphin showed significant correlation with the sperm concentration (r = 0.699, P = 0.0188) and nonsignificant correlation with its serum level (r = 0.375, P = 0.185) or with the sperm motility percentage (r = 0.470, P = 0.899). CONCLUSION: The estimation of beta-endorphin alone is not conclusive to evaluate male reproduction as there are many other opiates acting at the hypothalamic pituitary gonadal axis. (+info)
Does PGD for aneuploidy screening change the selection of embryos derived from testicular sperm extraction in obstructive and non-obstructive azoospermic men?
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BACKGROUND: An increased incidence of aneuploid embryos has been recently described from azoospermic men. The aim of this study was to assess if embryo selection on day 5, based on morphological criteria, would be different from the selection based on PGD for aneuploidy screening (AS) in couples undergoing ICSI for male azoospermia. METHODS: Sixty-two cycles of testicular sperm extraction (TESE)-ICSI with PGD-AS were included in the analysis. Two embryologists, blinded to the PGD-AS results, retrospectively reviewed the available embryology data from day 5 embryos and selected one, two or three embryos to be transferred. These results were compared with the selected embryos based on PGD-AS. RESULTS: A total of 39 cycles from non-obstructive azoospermia (NOA) and 23 cycles from obstructive azoospermia (OA) were retrospectively analysed. If single embryo transfer (SET) had been performed, in 64.8% of the NOA cycles and 54.5% of the OA cycles, no difference in embryo choice would have occurred compared to PGD-AS and in 10.8 and 36.6% of the cycles, respectively, an aneuploid embryo would have been chosen. If double ET (DET) had been performed, in 72.9% of the NOA cycles and 86.5% of the OA cycles, no difference in embryo choice would have occurred compared to PGD-AS and in 2.7 and 4.5% of the cycles, respectively, an aneuploid embryo would have been chosen. If triple ET (TET) had been performed, the outcome would have been the same as for DET. DISCUSSION: Our results suggest that under the terms of an SET policy, the performance of PGD-AS in azoospermia would result in a higher chance of success, as the possibility of selecting a euploid embryo is enhanced. (+info)
Role of transrectal ultrasonography in the evaluation of azoospermic men with low-volume ejaculate.
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OBJECTIVE: The purpose of this prospective study was to evaluate the incidence of distal ejaculatory system defects with transrectal ultrasonography (TRUS) among patients evaluated for azoospermia. METHODS: Forty-two patients with low-volume ejaculate and azoospermia were evaluated by physical examination, serum follicle-stimulating hormone and luteinizing hormone level determination, karyotyping, selective screening for cystic fibrosis mutations, and TRUS. RESULTS: On physical examination, in 29 patients (69%), either 1 (12 patients) or both (17 patients) of the vasa deferentia could not be palpated. In the group of 17 patients with bilateral involvement of the vasa deferentia, the ultrasonographic imaging universally showed bilateral absence or hypoplasia of the seminal vesicles with bilateral agenesis of the vasa deferentia and nonvisualization of both ejaculatory ducts. In the patients with a unilateral abnormality on physical examination, the ultrasonographic imaging showed absence of the ipsilateral seminal vesicle in 7 patients and the hypoplastic seminal vesicle in 5. In the group of 13 patients with normal physical examination findings, a variety of obstructive causes were diagnosed by TRUS examination. CONCLUSIONS: According to this study, TRUS appears to be a sensitive method for evaluating the anatomy of the distal ejaculatory system. Its safety and low costs make it a good alternative to the other invasive and expensive methods. (+info)
Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia.
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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. (+info)