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

Nonalkolik yağlı karaciğer hastalığında fibrozisin noninvaziv yöntemlerle araştırılması

ÖZET Nonalkolik yağlı karaciğer hastalığı(NAFLD) olan bireylerde önemli orandaki fibrozisin tanısında noninvaziv yöntemlerin doğruluğu klinik pratikte halen sınırlıdır. Bu çalışmanın amacı yağlı karaciğerli hastalarda karaciğer fibrozisinin saptanmasında 3 farklı noninvasiv metodun [FibroMeter™ NAFLD skor, NAFLD Fibrosis skor (NFSA), ve Transient Elastrografi (TE)] tanısal performanslarını karşılaştırmaktır. Çalışmaya biyopsi ile kanıtlanmış 88 NAFLD hastası dâhil edilmiştir. Karaciğer biyopsilerinde fibrozis dereceleri Kleiner sistemi kullanılarak değerlendirilmiştir. FibroMeter™ NAFLD skor tescilli bir algoritim (regresyon skoru) kullanılarak hesaplanmıştır. NFSA ise; yaş, hiperglisemi, vücut kitle indeksi, trombosit, albümin ve serum aminotransferaz seviyeleri kullanılarak hesaplanmıştır. TE, Fibroscan aleti kullanılarak yapılmıştır. FibroMeter™ NAFLD skor, NFSA ve TE için önemli oranda fibrozis (≥F2) için hesaplanan duyarlılık/özgüllük oranları sırasıyla; %38,6 /%86,4, %52,3/%88,6 ve %75,0/%93,2 olarak bulunmuştur. TE'nin ROC eğrisi(receiver operating characteristic) altında kalan alanı(AUROC), FibroMeter™ NAFLD skor ve NFSA'ya göre belirgin olarak daha yüksek bulunmuştur. Önemli oranda ve ileri evre fibrozisi saptamada FibroMeter™ NAFLD skor ve NFSA arasında anlamlı bir fark saptanmazken, FibroMeter™ NAFLD skor sirozlu hastaları saptamada NFSA'ya göre daha başarılı bulunmuştur. Özetle; TE, NAFLD hastalarında karaciğer fibrozisini göstermede diğer noninvasiv yöntemler içinde en başarılı olanıdır. Önemli oranda fibrozisi ve ileri evre fibrozisi göstermede FibroMeter™ NAFLD skor ve NFSA arasında anlamlı fark saptanmamıştır. Anahtar sözcükler: Non-alkolik yağlı karaciğer hastalığı, fibrozis, tanı, biomarkır, steatohepatit ABSTRACT The accuracy of noninvasive methods for the diagnosis of significant fibrosis in subjects with nonalcoholic fatty liver disease(NAFLD) in clinical practice is still limited. The aim of this study is to compare the diagnostic performances of three different noninvasive methods (FibroMeter™ NAFLD score, NAFLD Fibrosis score (NFSA), and Transient Elastrography [TE]) for the detection of liver fibrosis in NAFLD patients. A total of 88 patients with biopsy-proven NAFLD were included. The Kleiner system was used for grading fibrosis in liver biopsies. The FibroMeter™ NAFLD score was determined using a proprietary algorithm (regression score). The NFSA score was calculated based on age, hyperglycemia, body mass index, platelets, albumin, and serum aminotransferase levels. TE was performed using the Fibroscan device. The sensitivities/specificities for the FibroMeter™ NAFLD score, NFSA, and TE for the diagnosis of significant fibrosis (≥F2 fibrosis) were 38.6%/86.4%, 52.3%/88.6%, and 75.0%/93.2%, respectively. The areas under the receiver operating characteristic curves of TE were significantly higher than those of both the FibroMeter™ NAFLD score and NFSA. No significant differences were found between the FibroMeter™ NAFLD score and NFSA for the detection of significant and advanced fibrosis, although the diagnostic performance of the FibroMeter™ NAFLD score was higher than that of the NFSA score for cirrhosis. In summary, TE showed the best diagnostic performance for the non-invasive assessment of liver fibrosis in NAFLD patients. The diagnostic performances of the FibroMeter™ NAFLD score and NFSA did not differ significantly for the detection of both significant and severe fibrosis. Keywords: Non-alcoholic fatty liver disease, fibrosis, diagnosis, biomarker, steatohepatiti

Nonalkolik yağlı karaciğer hastalığında fibrozisin noninvaziv yöntemlerle araştırılması

Nonalkolik yağlı karaciğer hastalığı(NAFLD) olan bireylerde önemli orandaki fibrozisin tanısında noninvaziv yöntemlerin doğruluğu klinik pratikte halen sınırlıdır. Bu çalışmanın amacı yağlı karaciğerli hastalarda karaciğer fibrozisinin saptanmasında 3 farklı noninvasiv metodun [FibroMeter™ NAFLD skor, NAFLD Fibrosis skor (NFSA), ve Transient Elastrografi (TE)] tanısal performanslarını karşılaştırmaktır. Çalışmaya biyopsi ile kanıtlanmış 88 NAFLD hastası dâhil edilmiştir. Karaciğer biyopsilerinde fibrozis dereceleri Kleiner sistemi kullanılarak değerlendirilmiştir. FibroMeter™ NAFLD skor tescilli bir algoritim (regresyon skoru) kullanılarak hesaplanmıştır. NFSA ise; yaş, hiperglisemi, vücut kitle indeksi, trombosit, albümin ve serum aminotransferaz seviyeleri kullanılarak hesaplanmıştır. TE, Fibroscan aleti kullanılarak yapılmıştır. FibroMeter™ NAFLD skor, NFSA ve TE için önemli oranda fibrozis (≥F2) için hesaplanan duyarlılık/özgüllük oranları sırasıyla; %38,6 /%86,4, %52,3/%88,6 ve %75,0/%93,2 olarak bulunmuştur. TE'nin ROC eğrisi(receiver operating characteristic) altında kalan alanı(AUROC), FibroMeter™ NAFLD skor ve NFSA'ya göre belirgin olarak daha yüksek bulunmuştur. Önemli oranda ve ileri evre fibrozisi saptamada FibroMeter™ NAFLD skor ve NFSA arasında anlamlı bir fark saptanmazken, FibroMeter™ NAFLD skor sirozlu hastaları saptamada NFSA'ya göre daha başarılı bulunmuştur. le; TE, NAFLD hastalarında karaciğer fibrozisini göstermede diğer noninvasiv yöntemler içinde en başarılı olanıdır. Önemli oranda fibrozisi ve ileri evre fibrozisi göstermede FibroMeter™ NAFLD skor ve NFSA arasında anlamlı fark saptanmamıştır. Anahtar sözcükler: Non-alkolik yağlı karaciğer hastalığı, fibrozis, tanı, biomarkır, steatohepatit ABSTRACT The accuracy of noninvasive methods for the diagnosis of significant fibrosis in subjects with nonalcoholic fatty liver disease(NAFLD) in clinical practice is still limited. The aim of this study is to compare the diagnostic performances of three different noninvasive methods (FibroMeter™ NAFLD score, NAFLD Fibrosis score (NFSA), and Transient Elastrography [TE]) for the detection of liver fibrosis in NAFLD patients. A total of 88 patients with biopsy-proven NAFLD were included. The Kleiner system was used for grading fibrosis in liver biopsies. The FibroMeter™ NAFLD score was determined using a proprietary algorithm (regression score). The NFSA score was calculated based on age, hyperglycemia, body mass index, platelets, albumin, and serum aminotransferase levels. TE was performed using the Fibroscan device. The sensitivities/specificities for the FibroMeter™ NAFLD score, NFSA, and TE for the diagnosis of significant fibrosis (≥F2 fibrosis) were 38.6%/86.4%, 52.3%/88.6%, and 75.0%/93.2%, respectively. The areas under the receiver operating characteristic curves of TE were significantly higher than those of both the FibroMeter™ NAFLD score and NFSA. No significant differences were found between the FibroMeter™ NAFLD score and NFSA for the detection of significant and advanced fibrosis, although the diagnostic performance of the FibroMeter™ NAFLD score was higher than that of the NFSA score for cirrhosis. In summary, TE showed the best diagnostic performance for the non-invasive assessment of liver fibrosis in NAFLD patients. The diagnostic performances of the FibroMeter™ NAFLD score and NFSA did not differ significantly for the detection of both significant and severe fibrosis. Keywords: Non-alcoholic fatty liver disease, fibrosis, diagnosis, biomarker, steatohepatiti

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease