Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer

Purpose. TRPM7 is known to play a key role in tumor progression by regulating cellular proliferation, migration, and invasion in various cancer cell lines. However, there are no comprehensive clinical studies about the effect of TRPM7 expression on gastric cancer (GC) prognosis. In this study, it was aimed at investigating the effect of TRPM7 expression on prognosis in GC patients. Additionally, for the first time, it was investigated whether the density of Factor XIIIa-expressing tumor-associated macrophages (TAMs) in GC has an effect on the biological behaviour of the tumor. Methods. TRPM7 expression and Factor XIIIa-expressing TAM density were immunohistochemically evaluated in paraffin-embedded tumor tissues of 204 GC patients undergoing surgery at a single institution. Results. Tumor size was clearly higher in cases with high TRPM7 expression than those with low expression (p<0.001, Mann-Whitney U). TRPM7 overexpression was closely related to high depth of tumor invasion (p<0.001, ANOVA), increased lymph node metastasis (p<0.001, ANOVA), and high distant metastasis rate (p<0.001, Mann-Whitney U). These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of GC. In addition, while high CD8+ TIL density affects the prognosis positively, it was determined that high Factor XIIIa+ TAM density negatively affects the prognosis of patients with GC. Furthermore, multivariate analyses revealed TRPM7 overexpression was independently related with short overall (HR 9.64, 95% CI 5.74–16.19, p<0.001) and disease-free survival (HR 5.67, 95% CI 3.61-8.92, p<0.001) in GC patients. Conclusions. Our data suggest that high TRPM7 expression is closely related to progressive tumor behaviour in GC and independently negatively affects survival in patients. In addition, it was determined that a high density of Factor XIIIa+ TAMs negatively affects the prognosis of patients with GC

A New Determinant of Poor Outcome After Spontaneous Subarachnoid Hemorrhage: Blood pH and the Disruption of Glossopharyngeal Nerve-Carotid Body Network: First Experimental Study

AYDIN, Nazan/0000-0003-3232-7713; Kanat, Ayhan/0000-0002-8189-2877WOS: 000407713100045PubMed: 28456740OBJECTIVE: the chemoreceptor network, consisting of the glossopharyngeal nerve and carotid body (GPN-CB), is essential for the regulation of blood pH. Its ischemic insults after subarachnoid hemorrhage (SAH), which may contribute to acidosis, have not been investigated. METHODS: Twenty-three hybrid rabbits were used. They were divided into 3 groups: 5 as a control group, 5 as a sham group, and the remaining 13 as the study group. Injections included 1 cm3 serum saline and 1 cm3 autolog arterial blood into the cisterna magna in the sham and study group, respectively. Blood pH values of all animals were recorded. After 2 weeks, animals were euthanized. the number of normal and degenerated neurons of the carotid bodies (CBs) was counted by stereologic methods and analyzed statistically. RESULTS: Two of 13 rabbits died within the second week. the mean blood pH values were measured as 7.35 +/- 0.07 in the control group (n = 5), 7.33 +/- 0.06 in the sham group (n = 5), 7.29 +/- 0.05 in rabbits with slight acidosis (n = 6), and 7.23 +/- 0.02 in rabbits with prominent acidosis (n = 7). in the control group, the average normal neuronal density of the CBs was 6432 +/- 790/mm(3) and the degenerated neuron density was 11 +/- 3/mm(3), whereas the degenerated neuronal density in CBs was 35 +/- 8/mm(3) in the sham group and 1034 +/- 112/mm(3) in the slight acidosisedeveloped group (n = 6; P < 0.05). Conversely, degenerated neuron density of CBs was 2134 +/- 251/mm(3) in the prominent acidosise developed animals (n = 7; P < 0.005). Interestingly, in the rabbits who died, the degenerated neuron density of the CB was 3160 +/- 840/mm(3). CONCLUSION: An inverse relationship between neurodegeneration in the CB and pH values secondary to the disruption of the GPN-CB network after SAH was found, which may contribute to developing acidosis

A rare case of bilateral complex odontomas: Clinical, radiological and histopathological findings

Odontoma is the most common odontogenic tumor that is radiographically and histologically characterized by the production of mature enamel, dentin, cementum and pulp tissue. It grows slowly and has nonaggressive behavior. This case report presents clinical, radiological and pathological findings of bilateral complex odontoma that is rarely in literature in a 30-year-old female patient

Effects of ischemic phrenic nerve root ganglion injury on respiratory disturbances in subarachnoid hemorrhage: an experimental study

Conclusions: Phrenic nerve root ischemia may be an important factor in respiration rhythms deteriorations in SAH which has not been mentioned in the literature

The sooth beneath the taste roseas in the urethra and first description of neuro-morpho-chemical mechanism of penile erectile posture in males: an experimental study

AYDIN, Nazan/0000-0003-3232-7713; Kanat, Ayhan/0000-0002-8189-2877WOS: 000431555800010PubMed: 29199538Aim: the morphologic mechanism of orgasmic sensation has not yet been understood. Taste roseas may be stimulated by fructose via pudendal nerves, which has not been studied yet.Methods: in this study, 27 male adult rabbits were used, which were divided into three groups: 5 as control; 5 as SHAM and 17 used as study group. We injected 0.2 cc of distilled water to SHAM and 0.2 cc of fructose solution to the study group of their urethral orifices, and examined the occurrence of penile erection. the relationship between erection and pudendal nerve ganglia and penile tissues was statistically compared.Results: in animals with high neuron density of pudendal ganglia, more erection phenomenon was observed than those animals with low neuron density. Interestingly, neuron density of pudendal ganglia was 9.243 542 /mm(3) in hypoactive and was 5.980 +/- 463 /mm(3) in non-active animals (p < 0.05).Conclusions: the seminal fructose may stimulate taste roseas of the urethra and glans penis via pudendal nerves. the present study describes a new neuro-morpho-chemical mechanism of orgasmic sensation with its neurosurgical aspect

Comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study

WOS: 000330182500001PubMed: 24342001Background: Different medical therapies are employed in acute lung injury (ALI) but there is still a debate about the efficacy of these drugs. Among these therapies steroids are clinically applied and bosentan is experimentally studied. The aim of this study was to evaluate the efficacy of these two drugs to treat inflammation in ALI by histopathological comparison. Methods: The five experimental groups (n = 5 per group) were: saline control (Group I); lipopolysaccharide (LPS) + saline (Group II); LPS + dexamethasone (Group III); LPS + 50 mg/kg bosentan (Group IV); and LPS + 100 mg/kg bosentan (Group V). Bosentan was administered orally one hour before and 12 hours after LPS treatment. Dexamethasone was administered intraperitoneally in three doses of 1 mg/kg; one dose was co-administered with LPS and the other two doses were given respectively 30 minutes before and after LPS treatment. Vasodilation-congestion, hemorrhage, polymorphonuclear leukocyte (PMN) infiltration, mononuclear leukocyte (MNL) infiltration, alveolar wall thickening, alveolar destruction/emphysematous appearance, and focal organization were the parameters used as criteria for evaluating inflammation and efficacy of treatment. Results: Compared to the LPS-only group (Group II), dexamethasone treatment (Group III) resulted in significant improvements in vasodilation-congestion, hemorrhage, PMN and MNL infiltration, alveolar wall thickening and emphysematous areas. Treatment with 50 mg/kg dose of bosentan (Group IV) also resulted in significant improvements in hemorrhage, PMN and MNL infiltration, alveolar wall thickening and alveolar destruction. Reducing lung injury and reparative effects of 100 mg/kg bosentan were significant in all parameters. Conclusions: Bosentan is as effective as dexamethasone for treating lung injury in ALI. Bosentan at 100 mg/kg can be recommended as a first treatment choice based on its significant reducing lung injury and reparative effects