Search

Background: Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility., Objective: To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men., Design, Setting, and Participants: We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls., Outcome Measurements and Statistical Analysis: We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling., Results and Limitations: We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct β-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis., Conclusions: This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease., Patient Summary: We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Oxidative stress is pre-empted by an adequate level of antioxidants, which scavenge oxidants when they are produced in excess by different sources, including leukocytes and immature spermatozoa. Enzymatic antioxidants, such as superoxide dismutase, catalase and glutathione peroxidase, and several non-enzymatic antioxidants (proteins, vitamins and minerals), working as oxidant scavengers and cofactors of enzymatic antioxidants have been identified in seminal plasma. The total antioxidant capacity (TAC) is a diagnostic test that can be utilised in the male infertility workup. TAC measures the amount of total antioxidants in seminal plasma. Therefore, it provides an assessment of the reductive potential in seminal plasma. Several studies have investigated the diagnostic application of TAC in various andrology conditions. There is substantial evidence in the literature to show that infertile patients have lower seminal TAC in comparison with fertile men. Moreover, there is a positive correlation between TAC and seminal parameters, such as sperm concentration, motility and morphology. Evaluation of TAC together with reactive oxygen species (ROS) and sperm DNA fragmentation index (DFI) may be beneficial in the diagnosis of male infertility., (© 2020 Blackwell Verlag GmbH.)

Objective: To test the ability of the smartphone-based YO Home Sperm Test to accurately and precisely measure motile sperm concentration (MSC) versus the SQA-Vision, an automated laboratory semen analyzer., Design: MSC compared for the YO device on Galaxy and iPhone smartphones versus the SQA-Vision in a double-blind manner., Setting: Academic medical center., Patient(s): Donor semen samples from 24 men in 144 aliquots., Intervention(s): None., Main Outcome Measure(s): Accuracy, precision, and agreement assessed between the YO device and the SQA-Vision for MSC results., Result(s): The YO device demonstrated good correlation and good to moderate agreement with the SQA-Vision for MSC results up to a range of 94 × 10 6 /mL with Pearson and concordance correlation coefficient above 0.92. The YO also showed a very high level of accuracy (97.8%) with positive and negative percent agreement above 94%. The difference in coefficient of variation between the YO and the SQA-Vision was low (between 9.4% and 11.2%) and not statistically significant. The precision among the YO phone devices was lower (16.0%) than the manufacturer's claim of ≤20%., Conclusion(s): The smartphone-based device has a high level of accuracy and precision when compared with the SQA-Vision. It can detect samples with abnormally "low" MSC (below 6 × 10 6 /mL cutoff), which supports its use as an effective home sperm test for screening "low" and "moderate/normal" MSC cases. In addition, the device effectively identifies varying levels of normal MSC in a precise manner over a wide range of normal MSC. Thus, the YO Score can improve patient satisfaction and empowerment., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The objectives of this study were to: (i) describe a protocol measuring the oxidation-reduction potential (ORP) by MiOXSYS System as an alternative method of seminal oxidative stress (OS) testing; (ii) establish a reference value for static ORP (sORP) to distinguish between controls and male factor infertility patients; (iii) evaluate intra-observer and inter-observer reliability; and (iv) examine association of sORP with sperm parameters predictive of male factor infertility. Elevated levels of sORP were seen in infertile patients (6.22 ± 1.10 mV/10 6 sperm/ml) compared with controls (1.59 ± 0.29 mV/10 6 sperm/ml) (P = 0.004). A sORP cut-off value 1.36 mV/10 6 sperm/ml identified normal semen and abnormal semen quality with a sensitivity 69.6%, specificity 83.1%, positive predictive value 85.3% and negative predictive value 65.9%. The test demonstrated strong intra-observer (CV 8.39%) and inter-observer reliability (correlations >0.97). Higher sORP levels were associated with poor sperm parameters across the fertility status of subjects. Negative correlations were noted with sperm parameters (concentration, total sperm count, motility and morphology) indicating these male infertility parameters are related to OS. In conclusion, the introduction of ORP as a novel clinical test for assessment of OS will help clinicians to better diagnose and manage male factor infertility patients., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins (DEP) extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors. Subjects consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry system, proteomic analysis was done on pooled samples from 3 patients with bilateral varicocele and 5 fertile men. From these samples, 73 DEP were identified of which 58 proteins were differentially expressed, with 7 proteins unique to the bilateral varicocele group and 8 proteins to the fertile control group. Majority of the DEPs were observed to be associated with metabolic processes, stress responses, oxidoreductase activity, enzyme regulation, and immune system processes. Seven DEP were involved in sperm function such as capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were validated by Western blot analysis and may serve as potential biomarkers for bilateral varicocele. In this study, we have demonstrated for the first time the presence of DEP and identified proteins with distinct reproductive functions which are altered in infertile men with bilateral varicocele. Functional proteomic profiling provides insight into the mechanistic implications of bilateral varicocele-associated male infertility.

Objective: To compare the sperm protein profile between infertile men with unilateral varicocele and infertile men with bilateral varicocele., Methods: This prospective study investigated 50 infertile patients with clinical varicocele (33 unilateral and 17 bilateral) seeking fertility workup between March 2012 and April 2014. Routine sperm parameters, reactive oxygen species, total antioxidant capacity, and sperm deoxyribonucleic acid fragmentation were assessed in their semen. Sperm protein profile was characterized only in pooled samples of 5 unilateral and 3 bilateral varicocele samples, respectively, using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Linear Trap Quadrupole-Orbitrap Elite hybrid mass spectrophotometer system. Differences in protein expression were analyzed using gel analysis software, followed by protein identification using mass spectroscopy analysis. Differentially expressed proteins and their abundance were quantified by comparing spectral counts, followed by bioinformatics analysis., Results: Unique expression of 64 proteins in the bilateral group and 31 proteins in the unilateral group was obtained. Core functions of the top protein interaction networks were post-translational modification (∼122 proteins associated with acetylation), protein folding, free-radical scavenging, cell death, and survival. The top molecular and cellular functions were protein degradation, free radical scavenging, and post-translational modifications, whereas the top pathways were protein ubiquitination and mitochondrial dysfunction. Major biological pathways for the 253 differentially expressed proteins were metabolism, apoptosis, and signal transduction., Conclusion: Functional proteomic profiling helps identify the differential processes or pathways that are affected based on the nature of varicocele (bilateral or unilateral) and provide insights into the mechanistic implications of varicocele-associated male infertility., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To standardize the TUNEL assay by establishing inter- and intraobserver variability, interassay variability, cutoff values, sensitivity and specificity of the assay, and studying the distribution of the DNA damage in a population of infertile men referred to a clinical andrology laboratory., Methods: Seminal ejaculates from 25 healthy male volunteers (controls) and 194 infertile men (with male factor infertility) referred to an andrology laboratory were examined for DNA damage by TUNEL assay using flow cytometric analysis., Results: Both the inter- and intraobserver variability and interassay variability was small (<10%). DNA damage in the controls was 11.9 ± 6.8% vs. 29.5 ± 18.7% in patients (P <.001). The cut-off value of 19.25% maximized the observed sensitivity (64.9%) and specificity (100%) of the assay. The distribution of DNA damage in the patients was as follows: 14.9% (29 of 194) with DNA damage between 0% and 10%; 22.7% (44 of 194) between 10% and 20%; 8.8% (17 of 194) between 20% and 30%; and 17.5% (34 of 194) between 30% and 40%. Finally, 27.3% (53 of 194) had TUNEL values >40%., Conclusions: We report a detailed standardization of the TUNEL assay for clinical use, as well as reference ranges for DNA damage in normal healthy donors and infertile men. A cut-off of 19.25% with observed 100% specificity established in our program can differentiate infertile men with DNA damage from healthy men. This test can be offered to infertile patients who are idiopathic, have severe oxidative stress-related abnormal semen quality, and contribute to the infertility problem of the couple who are considering assisted reproductive techniques., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To examine sperm motility, total antioxidant level (TAC), DNA fragmentation, and medical history in infertile men with high seminal high reactive oxygen species (ROS)., Design: Prospective study., Setting(s): Tertiary care hospital., Patient(s): Infertile men (n=101)., Intervention(s): Group I (n=57) included men with seminal ROS (<250 relative light units/sec/×10(6) sperm) while group II (n=44) included men with seminal ROS levels (≥250 relative light units/sec/×10(6) sperm)., Main Outcome Measure(s): Seminal ROS, TAC, sperm DNA fragmentation, ROS/TAC score were measured., Result(s): Group II had a high incidence of sperm DNA fragmentation than group I. The odds ratio of 1.25 for elevated ROS levels corresponded to >10% greater DNA fragmentation in our patients (95% confidence interval 1.01-1.53). Group II showed poor motility, a higher incidence of leukocytospermia, and higher ROS-TAC scores compared with group I. ROS was negatively correlated with sperm curvilinear velocity (r=-.24), linearity (r=-.24), and sperm motility (r=-.31). Sperm motility was correlated with %TUNEL(+ve) sperm (r=-.39)., Conclusion(s): An increase in seminal ROS levels by 25% was associated with a 10% increase in sperm DNA fragmentation. Sperm motility was affected by seminal ROS and sperm DNA fragmentation., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility. [ABSTRACT FROM AUTHOR]

Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions. The treatment approaches outlined are determined by the cause. Alkalinizing urinary pH with oral medications or by adding sperm wash media into the bladder prior to ejaculation may preserve the viability of the sperm. This article provides a step-by-step guide to diagnose RE and the optimal techniques to retrieve sperm. [ABSTRACT FROM AUTHOR]