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- Varicocele repair in non-obstructive azoospermic men: diagnostic value of testicular biopsy - A meta-analysis. [JOURNAL ARTICLE]
- Scand J Urol 2014 Jul 8.:1-5.
Abstract Azoospermia is observed in 10-15% of infertile men and 60% of these cases are classified as having non-obstructive azoospermia (NOA). NOA results from testicular failure, and one of the causes of this is the presence of varicocele. Varicocele is found in 5-10% of men with NOA and its repair is associated with the appearance of spermatozoa in the ejaculate in 21-55% of cases. This review discusses the diagnostic value of testicular biopsy on the outcome of varicocele repair in terms of appearance of spermatozoa in the ejaculate in men with NOA and normal genetic testing. Ninety men met the inclusion criteria and were thus included in the review. The histopathological assessment of testicular biopsies revealed hypospermatogenesis in 30 out of 90 (33%), maturation arrest in 26 out of 90 (29%) and Sertoli cell only in 34 out of 90 (38%). Following varicocele repair, spermatozoa were detected in the ejaculate in 18 of 30 (60%) of men with hypospermatogenesis; 12 of 26 (46%) of those with maturation arrest; and one of 34 (3%) of those with Sertoli cell only. Regarding men with maturation arrest, varicocele repair was successful only in those men who were classified as having arrest at the spermatid stage. In conclusion, based on the best available evidence, diagnostic testicular biopsy seems to be of great value before varicocele repair in men with NOA and normal genetic testing. The best results of varicocele repair are observed in those men with hypospermatogenesis revealed by testicular biopsy or maturation arrest at the spermatid stage.
- Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival. [JOURNAL ARTICLE]
- Appl Immunohistochem Mol Morphol 2014 Jul 2.
Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.
- Expression and Role of Leptin under Hypoxic Conditions in Human Testis:Organotypic in-Vitro Culture Experiment and Clinical Study on Patients with Varicocele. [JOURNAL ARTICLE]
- J Urol 2014 Jun 26.
To investigate the expression and the exact role of leptin under hypoxic conditions in human testis.Five testes, obtained from the patients undergoing orchiectomy for prostate cancer, were used to construct an in-vitro hypoxic culture system for human testicular tissue. Immunohistochemistry was performed to analyze leptin-protein expression. The leptin, leptin-R and HIF-1α mRNAs were examined using qRT-PCR. Serum and seminal plasma leptin, gonadal hormones and semen parameters were evaluated in 10 healthy donors and 42 infertile patients with varicocele before and after surgery.The viability of in-vitro cultured testicular tissue could be well maintained within 48h based on the results of morphological analysis, cell number and cell-specific mRNAs. The result of immunohistochemistry demonstrated that leptin was mainly expressed in seminiferous tubules. Interestingly, the OD value of leptin, leptin-mRNA and Hif-1α-mRNA were all significantly elevated under hypoxia. A positive correlation was observed between leptin-mRNA and Hif-1α-mRNA (Rs=0.843, P<0.01). In clinical study, the concentration of seminal plasma leptin before varicocelectomy was markedly higher in patients (3.01±1.23ng/L, P<0.01), especially for the grade 3 group (3.95±1.37ng/L, P<0.01, the highest), which would be significantly decreased in the post-6m-operation group (2.35±0.78, P<0.05). Furthermore, negative correlations were observed between seminal plasma leptin and sperm concentration (Rs=﹣0.187, P<0.05), as well as progressive motility (Rs=﹣0.234, P<0.05).The expression of leptin could be induced under hypoxia in human testis probably through the HIF-1α related response pathway. Seminal plasma leptin was closely correlated with varicocele-related spermatogenesis dysfunction and might effectively reflect the testicular hypoxic environment.
- Mutation analysis of TNP1 gene in infertile men with varicocele. [Journal Article]
- Iran J Reprod Med 2014 Apr; 12(4):257-62.
Background:Varicocele is associated with the failure of ipsilateral testicular growth and development, and the symptoms of pain and reduced fertility. The highly condensed structure of the sperm nuclear chromatin is provided by proper expression of Transition Nuclear Protein (TNP) genes, so any dysregulational expression of these genes results in abnormal spermatogenesis and infertility.
Objective:The aim of present study was to assess the association between TNP1 mutations and varicocele in Iranian infertile men. Materials and
Methods:Analysis of association between TNP1 gene mutation and varicocele phenotype was performed using PCR and Single-Stranded Conformational Polymorphism technique and DNA sequencing in 82 varicocele infertile men and 80 control subjects.
Results:Sequence analysis was identified one variant in this gene that found in 15 infertile men and was absent in control group. This variant was a single nucleotide polymorphism that were identified in the intron region of this gene at position g.IVS1+75T>C.
Conclusion:The effect of this nucleotide substitution in intronic region of the TNP1 gene and their role on expression remains to be determined.
- Multiple determinations of sperm DNA fragmentation show that varicocelectomy is not indicated for infertile patients with subclinical varicocele. [Journal Article]
- Biomed Res Int 2014.:181396.
Varicocele is one of the most common causes of low semen quality, which is reflected in high percentages of sperm cells with fragmented DNA. While varicocelectomy is usually performed to ameliorate a patient's fertility, its impact on sperm DNA integrity in the case of subclinical varicocele is poorly documented. In this study, multiple DNA fragmentation analyses (TUNEL, SCD, and SCSA) were performed on semen samples from sixty infertile patients with varicocele (15 clinical varicoceles, 19 clinical varicoceles after surgical treatment, 16 subclinical varicoceles, and 10 subclinical varicoceles after surgical treatment). TUNEL, SCD, and SCSA assays all showed substantial sperm DNA fragmentation levels that were comparable between subclinical and clinical varicocele patients. Importantly, varicocelectomy did improve sperm quality in patients with clinical varicocele; however, this was not the case in patients with subclinical varicocele. In summary, although infertile patients with clinical and subclinical varicocele have similar sperm DNA quality, varicocelectomy should only be advised for patients with clinical varicocele.
- [Varicocele in second adulthood and elderly men]. [English Abstract, Journal Article]
- Urologiia 2014 Mar-Apr; (2):48-51.
The prevalence ofvaricocele in second adulthood and elderly men was evaluated. It was found that varicocele in this age group occurs in 15.8 % of cases , whereas in men up to 35 years - in 18.3 % of cases. 88.5 % of men older than 35 years had children. Varicocele is often asymptomatic. The course of varicocele includes compensation and decompensation stages. Proportion of adulthood and elderly patients with decompensated stage ofvaricocele in the structure ofurological disease was 0.34 %. Pain is the main manifestation of varicocele at the stage of decompensation in second adulthood and elderly men. For surgical correction of varicocele in such patients, Sayfan technique seems appropriate, which uses transinguinal mini assess (2.5-3 cm incision) allowing to identify and eliminate most of the possible causes of pain: infantile hernia, benign tumors of adipose tissue, fibrotic changes in the tissues along the ilioinguinal nerve. This minimally invasive technique can be used in outpatient surgery. 18 patients underwent surgery using this technique. There were no early postoperative and long-term complications. At 1 to 3 years after surgery, 13 patients were re-examined, and relapses were not revealed.
- Varicocele: Early Surgery versus Observation. [JOURNAL ARTICLE]
- J Urol 2014 Jun 16.
- Hypogonadotropic hypogonadism: new identification of testicular blood flow and varicocele after treatment with gonadotropins. [JOURNAL ARTICLE]
- Fertil Steril 2014 Jun 13.
To investigate testicular changes in patients with hypogonadotropic hypogonadism (HH) after treatment with gonadotropins.Patients with HH were investigated and followed before and after treatment.T Urology and andrology clinic of a teaching hospital.Consecutive male patients with diagnosed HH.All patients were treated with gonadotropins during the study period and later.The hormonal status and scrotal color Doppler ultrasound (CDUS) of patients was recorded before and after treatment.Twenty-six patients with HH (ages 18-43 years) were followed for 8-29 months. After treatment, serum T and secondary sex characters improved in all and spermatogenesis developed in 61.5% of patients. Before treatment, testicular (intraparenchymal blood flow) was undetectable in all and barely detectable in three patients. This improved significantly to 4.53 ± 5.44 and 4.27 ± 4.97 cm/second, respectively, after treatment. Subcapsular arterial flow and testicular size also improved significantly. Similarly, after treatment, transverse epididymal diameter (TED) increased significantly. At baseline, no patient had detectable varicocele on CDUS. After treatment, varicocele was demonstrable in 23% of patients. This finding was further evaluated retrospectively from our 76 HH patient files. None of them had varicocele before treatment, but after treatment 19.73% were found to have varicocele.Patients with HH responded to gonadotropins by improvement in testicular blood flow and increase in TED. In some patients, varicocele was found to develop after treatment.
- Diagnostic and Management Approaches to Pediatric and Adolescent Varicocele: A Survey of Pediatric Urologists. [JOURNAL ARTICLE]
- Urology 2014 Jun 11.
To assess current diagnosis and management of adolescent varicoceles by pediatric urologists.Online questionnaires assessing diagnosis and management approaches to pediatric and adolescent varicocele were distributed electronically to a national listing of pediatric urologists.Of 242 pediatric urologists surveyed, 131 (54%) responded to the survey. Only 3% of respondents operate on varicoceles at diagnosis, whereas 14% observe, and 83% base treatment on further indications. Varicocelectomy is most commonly performed for decreased ipsilateral testicular size (96%), testicular pain (79%), and altered semen analysis parameters (39%), with the mean age for varicocelectomy being 12.5 ± 3.1 years. Most physicians use ultrasonography (US) or Doppler US to aid in the diagnosis of varicoceles, and half of physicians would not repair incidental findings of varicocele on US. In an otherwise asymptomatic patient with a varicocele, 28% of physicians would consider varicocelectomy depending on varicocele grade. The most common surgical approaches to varicocelectomy were laparascopic (38%), subinguinal microsurgical (28%), inguinal (14%), and retroperitoneal (13%), and most physicians used loupes for these procedures. The most common complication experienced after adolescent varicocelectomy was hydrocele followed by hematoma, testicular atrophy, chronic pain, paresthesia, and varicocele recurrence or persistence. Only 58% of physicians had follow-up data on their varicocele patients, and 89% did not know whether patients developed infertility. Of patients who developed infertility, 39% had undergone varicocele repair.Significant variation in diagnostic approaches, decision to treat, and operative approaches exists among pediatric urologists, and combined with a dearth of objective data, limits development of management guidelines.
- IL-17A concentration of seminal plasma and follicular fluid in infertile men and women with various clinical diagnoses. [JOURNAL ARTICLE]
- Immunol Invest 2014 Jun 13.:1-10.
Seminal plasma and follicular fluid (FF) cytokine analysis are valuable tools for diagnoses and validation of therapeutic approaches for improving the chance of conception. Despite the initial discovery over a decade ago, the IL-17 family has not received much attention in the case of infertility. In this study, we analyzed the level of IL-17A in seminal plasma, follicular fluid and blood serum of infertile patients with different clinical diagnoses by Enzyme Linked Immunosorbent Assay (ELISA). The results showed that the level of IL-17A was higher in seminal plasma and blood serum of varicocele patients than the control group. The level of this cytokine was higher in follicular fluid of endometriosis, polycystic ovary syndrome (PCOS) and tubal factor patients than the control group. A similar elevation in IL-17A level was observed in blood serum of these patients. Furthermore, there was a correlation between the numbers of meiosis I (MI) oocytes and the level of blood serum and follicular fluid IL-17A in PCOS patients. Our data suggest a putative role of IL-17A in mediating these conditions and may have possible applications in the development of more effective diagnostic tools and therapeutic treatments for human reproductive disorders.