Geographical differences in semen characteristics of 13 892 infertile men

Objective: To assess the relationship between geographical differences and all semen parameters, across 13,892 infertile men of 84 diverse nationalities, recruited at a specialised tertiary hospital that represents the main healthcare provider in Qatar. Male infertility is an important and global public health problem. Despite this, there is a significant scarcity of epidemiological male infertility and semen analysis research in the Middle East and North Africa (MENA) region, as well as geographical comparisons with other parts of the world. Patients and methods: Retrospective study of semen findings of 13 892 infertile men assessed at the Male Infertility Unit at Hamad Medical Corporation, in Qatar between January 2012 and August 2015. Based on country of origin, patients were categorised into those from the MENA region (n = 8799) and non-MENA patients (n = 5093). The two groups were compared across demographic features and semen characteristics: age, sperm volume, sperm total motility, sperm progressive motility (PMot), abnormal sperm forms (ABF), and sperm DNA fragmentation (SDF). Results: The whole sample's mean (SD) age was 35.7 (0.7) years, sperm concentration was 32.3 (0.25) × 106 sperm/mL, total motility was 45.4 (0.2)%, sperm PMot was 25.1 (0.2)%, and ABF was 79.9 (0.2)%. Overall, 841 patients had azoospermia (6.05%), 3231 had oligospermia (23.3%), 4239 had asthenospermia (30.5%) and 6772 had teratospermia (48.7%). SDF (1050 patients) was abnormal in 333 patients (31.7%). MENA patients were significantly younger than their non-MENA counterparts and had a greater semen volume. Non-MENA patients had significantly higher sperm counts, total motility and PMot, and lower ABF. SDF showed no statistical difference between the two groups. MENA patients had significantly higher prevalence of oligospermia, asthenospermia, and teratospermia; and lower prevalence of normal sperm concentration, normal motility, and normal morphology. Throughout the 4 years of the study, MENA patients constantly had significantly lower sperm counts; generally lower sperm total motility percentage and generally lower quality sperm morphology. We compared patients by age (≤40 and >40 years): in the patients aged ≤40 years, the same results as for the overall study were reproduced; in the >40-years group, the same results were reproduced with the exception of morphology, which was not significantly different between the MENA and non-MENA patients. Conclusion: Semen quality is generally lower in male infertility patients from the MENA region compared to non-MENA regions. © 2018 Arab Association of UrologyScopu

Oxidation–reduction potential and sperm DNA fragmentation, and their associations with sperm morphological anomalies amongst fertile and infertile men

Objective: To assess seminal oxidation–reduction potential (ORP) and sperm DNA fragmentation (SDF) in male infertility and their relationships with sperm morphology in fertile and infertile men. Patients and methods: Prospective case-control study comparing the findings of infertile men (n = 1168) to those of men with confirmed fertility (n = 100) regarding demographics and semen characteristics (conventional and advanced semen tests). Spearman rank correlation assessed the correlation between ORP, SDF, and different morphological indices. Means of ORP and SDF were assessed in variable levels of normal sperm morphology amongst all participants. Results: Infertile patients had a significantly lower mean sperm count (32.7 vs 58.7 × 10 6 sperm/mL), total motility (50.1% vs 60.4%), and normal morphology (5.7% vs 9.9%). Conversely, infertile patients had significantly higher mean head defects (54% vs 48%), and higher ORP and SDF values than fertile controls. ORP and SDF showed significant positive correlations and significant negative correlations with sperm head defects and normal morphology in infertile patients, respectively. ORP and SDF were significantly inversely associated with the level of normal sperm morphology. Using receiver operating characteristic curve analysis, ORP and SDF threshold values of 1.73 mV/10 6 sperm/mL and 25.5%, respectively, were associated with 76% and 56% sensitivity and 72% and 72.2% specificity, respectively, in differentiating <4% from ≥4% normal morphology. Conclusion: A direct inverse relationship exists between seminal ORP and SDF with various levels of normal sperm morphology. Using ORP and SDF measures in conjunction with standard semen morphology analysis could validate the result of the fertility status of patients. © 2017 Arab Association of UrologyScopu

End-user evaluation of software-generated intervention planning environment for transrectal magnetic resonance-guided prostate biopsies

Background: This study presents user evaluation studies to assess the effect of information rendered by an interventional planning software on the operator's ability to plan transrectal magnetic resonance (MR)-guided prostate biopsies using actuated robotic manipulators. Methods: An intervention planning software was developed based on the clinical workflow followed for MR-guided transrectal prostate biopsies. The software was designed to interface with a generic virtual manipulator and simulate an intervention environment using 2D and 3D scenes. User studies were conducted with urologists using the developed software to plan virtual biopsies. Results: User studies demonstrated that urologists with prior experience in using 3D software completed the planning less time. 3D scenes were required to control all degrees-of-freedom of the manipulator, while 2D scenes were sufficient for planar motion of the manipulator. Conclusions: The study provides insights on using 2D versus 3D environment from a urologist's perspective for different operational modes of MR-guided prostate biopsy systems

Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer

Prostate cancer (PC) castration resistance has been linked to the differentiation of PC luminal cells into hormone-refractory neuroendocrine (NE) cells. However, the molecular mechanisms controlling the emergence of lethal NE prostate cancer (NEPC) remain unclear. The present study aimed to investigate the mechanisms underlying the transition from prostate adenocarcinoma to NEPC. The microRNA miR-708 was involved in NE differentiation and was downregulated in NEPC cells and tumor specimens. miR-708 targeted Sestrin-3 to inhibit Forkhead Box O1 (FOXO1) phosphorylation, resulting in apoptosis of prostate adenocarcinoma cells and AKT-inactivated NEPC cells, the latter of which was consistent with the progression of tumor xenografts in mice under miR-708 treatment. In silico analysis of PC and NEPC tumor specimens suggested that the polycomb repressive complex subunit Enhancer of zeste homolog 2 (EZH2) was particularly overexpressed in NEPC. Notably, EZH2 bound to the miR-708 promoter and induced its silencing in NEPC. Inhibition of EZH2 prevented NE differentiation of PC cells. EZH2 expression was regulated by both Cyclin Dependent Kinase 1 (CDK1) and Wnt signaling. Silencing transcription factor 4 (TCF4), as a key protein in Wnt signaling, prevented NEPC formation. These results provide a molecular basis for the roles of miR-708 and EZH2 in NE differentiation in PC and highlight a new paradigm in NEPC formation and survival.Other Information Published in: Cell Death Discovery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41420-019-0218-y</p

Evaluation of Interventional Planning Software Features for MR-guided Transrectal Prostate Biopsies

This work presents an interventional planning software to be used in conjunction with a robotic manipulator to perform transrectal MR guided prostate biopsies. The interventional software was designed taking in consideration a generic manipulator used under the two modes of operation: side-firing and end-firing of the biopsy needle. Studies were conducted with urologists using the software to plan virtual biopsies. The results show features of software relevant for operating efficiently under the two modes of operation

Preliminary evaluation of robotic transrectal biopsy system on an interventional planning software

Prostate biopsy is considered as a definitive way for diagnosing prostate malignancies. Urologists are currently moving towards MR-guided prostate biopsies over conventional transrectal ultrasound-guided biopsies for prostate cancer detection. Recently, robotic systems have started to emerge as an assistance tool for urologists to perform MR-guided prostate biopsies. However, these robotic assistance systems are designed for a specific clinical environment and cannot be adapted to modifications or changes applied to the clinical setting and/or workflow. This work presents the preliminary design of a cable-driven manipulator developed to be used in both MR scanners and MR-ultrasound fusion systems. The proposed manipulator design and functionality are evaluated on a simulated virtual environment. The simulation is created on an in-house developed interventional planning software to evaluate the ergonomics and usability. The results show that urologists can benefit from the proposed design of the manipulator and planning software to accurately perform biopsies of targeted areas in the prostate