A comprehensive review of genetics and genetic testing in azoospermia

Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients

Is muscle activation diverse in females with isolated patellofemoral osteoarthritis contrasted with age-matched healthy controls during stair descent task?

Background: Patellofemoral osteoarthritis (PF OA) is exceptionally predominant and limiting. However, little is known about the risk factors that contribute to its onset and progression.Purpose: The aim of this study was to decide if women with PF OA descend stairs using different muscular activation strategies compared to similarly aged healthy controls.Methods: Thirty-one women with isolated PF OA and 11 similarly aged healthy women took part in this study. The activation onset and duration of PF OA in vastus medialis oblique (VMO), vastus lateralis (VL), gluteus medius (GM), transversus abdominis (TrA), and multifidus muscles were evaluated during the stair descent task using surface electromyography (EMG).Results: There was a non-significant difference between women with PF OA and healthy controls regarding all tested variables, except for the GM activation onset that was significantly delayed in women with PF OA, with the p-value of 0.011.Conclusion: The causes of PF OA differ and might not always be due to a lack of quadriceps strength or VMO activation deficiency, and prospective longitudinal studies are required to confirm this assumption

The effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality in rat ovary

Several researchers have reported the relationship between infertility in male and varicocele for so many years but the implication of varicocele in female patients is remains elusive. Here, we aim to examine the effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality of rat ovary after the experimental creation of varicocele in female rats. Materials and Methods: In this study, thirty adult female albino rats were divided into three equal groups: Group 1 as the control group has 10 rats, Group 2 as the sham group has 10 rats and they underwent a sham operation and finally Group 3 has the varicocele group has 10 rats. Antioxidant assays for superoxide dismutase, glutathione peroxidase and catalase were performed using specific assay kits and gene expression for Bax, Bmp-15, Hsp-27 and Gdf-9 was done via real time PCR. Results: The adverse effects of the experimentally induced varicocele were reported and recorded on the left ovary compared to the right sided ovary (no varicocele induction) in the varicocele group. Real time PCR data shows that the expression of Gdf-9, Hsp-27 and Bmp-15 genes were all significantly reduced at p≤ 0.05. Conclusion: The results of this study show that reduced gene expression of Bmp-15, Gdf-9 and Hsp-27, increased gene expression of bax and an imbalance between pro-oxidant/ antioxidant ratio are few of the several mechanisms by which varicocele may lead to infertility in female

Amniotic Bladder Therapy in Patients with Interstitial Cystitis/Bladder Pain Syndrome

Introduction and Objectives: Our study hypothesis postulates that if patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) bladders exhibit increased inflammation, fibrosis, and urothelial dysfunction, then treatment modalities that modulate inflammation and fibrosis, while promoting a regeneration may have a therapeutic effect in such patients. Amniotic membrane (AM) has been shown to foster a regenerative wound-healing environment. This study investigates the safety and efficacy of bladder injections of AM in patients with treatment resistant IC/BPS. Methods: Fifteen consecutive treatment resistant IC/BPS patients (mean age 50.7 ± 14.4 years) with a median disease duration of 7 years (5-12 years) were included in the study. Under general anesthesia patients received intra-detrusor injections of reconstituted 100mg micronized AM and were followed for 24 weeks. Clinical evaluation and patient-reported outcome were assessed through several different scoring modalities. Results: After amniotic bladder therapy (ABT), the lower urinary tract symptoms improved gradually up to 12 weeks in all patients. At 16 weeks, 3 patients experienced a resurgence of symptoms and requested another injection which resulted in improvement after 2, 4, and 8 weeks respectively. For the twelve patients who only received one injection, the symptoms were still significantly lower at 20 and 24 weeks compared to baseline. No safety concerns were noticed during the study. Conclusions: Our findings suggest that ABT shows promise as a treatment for refractory IC/BPS patients. However, further study is needed to establish treatment protocol, better understand the mechanism of action and determine the durability of therapeutic response of ABT in IC/BPS

Two-dimensional differential in-gel electrophoresis-based proteomics of male gametes in relation to oxidative stress

Objective: To identify the relative abundance of proteins in pooled reactive oxygen species (ROS)-positive (ROSþ) and ROS-negative (ROSÀ) semen samples with the use of two-dimensional differential in-gel electrophoresis (2D-DIGE). Design: Spermatozoa suspensions from ROSþ and ROSÀ groups by 2D-DIGE analysis. Setting: Tertiary hospital. Patient(s): 20 donors and 32 infertile men. Intervention(s): Seminal ejaculates evaluated for semen and proteomic analysis. Main Outcome Measure(s): Semen samples from 20 donors and 32 infertile men were pooled, divided into ROSþ and ROSÀ groups based on the cutoff value of <20 relative light units/s/10 6 sperm and frozen. From each pooled group, spermatozoa were labeled with Cy3/Cy5 fluorescent dye. Duplicate 2D-DIGE gels were run. Image analysis was performed with the use of Decider software. Protein spots exhibiting R1.5-fold difference in intensity were excised from the preparatory gel and identified by liquid chromatographymass spectrometry. Data were analyzed with the use of Sequest and Blast programs. Result(s): A total of 1,343 protein spots in gel 1 (ROSÀ) and 1,265 spots in gel 2 (ROSþ) were detected. The majority of protein spots had similar expression, with 31 spots were differentially expressed. Six spots were significantly decreased and 25 increased in the ROSÀ sample compared with the ROSþ sample. Conclusion(s): Significantly different expression of protective proteins against oxidative stress was found in ROSÀcompared with ROSþ samples. These differences may explain the role of oxidation species in the pathology of male infertility. (Fertil Steril Ò 2013;99:1216-26. Ó2013 by American Society for Reproductive Medicine.

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Unexplained Male infertility: diagnosis and Management

Unexplained male infertility is a diagnosis reserved for men in whom routine semen analyses results are within normal values and physical as well as endocrine abnormalities were ruled out. In addition to erectile problems and coital factors, immunologic causes and sperm dysfunction may contribute to such condition. New etiologies of unexplained male infertility include low level leukocytospermia and mitochondrial DNA polymerase gene polymorphism. Contemporary andrology may reveal cellular and sub-cellular sperm dysfunctions which may explain subfertility in such cases, thus aiding the clinician to direct the further work-up, diagnosis and counseling of the infertile male. The objective of this article is to highlight the concept of unexplained male infertility and focuses on the diagnosis and treatment of this condition in the era of modern andrology and assisted reproductive techniques. Extensive literature review was performed using the search engines: Pubmed, Science-direct, Ovid and Scopus