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

Evidence for a role of Anopheles stephensi in the spread of drug- and diagnosis-resistant malaria in Africa

Anopheles stephensi, an Asian malaria vector, continues to expand across Africa. The vector is now firmly established in urban settings in the Horn of Africa. Its presence in areas where malaria resurged suggested a possible role in causing malaria outbreaks. Here, using a prospective case-control design, we investigated the role of An. stephensi in transmission following a malaria outbreak in Dire Dawa, Ethiopia in April-July 2022. Screening contacts of patients with malaria and febrile controls revealed spatial clustering of Plasmodium falciparum infections around patients with malaria in strong association with the presence of An. stephensi in the household vicinity. Plasmodium sporozoites were detected in these mosquitoes. This outbreak involved clonal propagation of parasites with molecular signatures of artemisinin and diagnostic resistance. To our knowledge, this study provides the strongest evidence so far for a role of An. stephensi in driving an urban malaria outbreak in Africa, highlighting the major public health threat posed by this fast-spreading mosquito

Does varicocele repair improve conventional semen parameters? A meta-analytic study of before-after data

Purpose The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p<0.001; I2=83.62%, Egger’s p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474–1.706; p<0.001; I2=97.86%, Egger’s p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526–2.121; p<0.001; I2=97.88%, Egger’s p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318–1.968; p<0.001; I2=98.65%, Egger’s p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%–2.153%; p<0.001; I2=98.97%, Egger’s p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%–1.759%; p<0.001; l2=97.98%, Egger’s p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%–1.211%; p<0.001; I2=97.87%, Egger’s p=0.1864. Conclusions The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele. Keywords Controlled before-after studies; Infertility, male; Meta-analysis; Varicocel

Surgical Management of Ejaculatory Duct Obstruction

Objective: The aim of this work is to evaluate the efficiency of transurethral resection (unroofing) of the obstructed ejaculatory ducts (TURED) as a treatment alternative for cases of obstructive ductal azoo-/ oligozoospermia. Patients and Methods: Thirty-two patients, aged 26 to 45 (mean age 34 years) with varying degrees of ejaculatory duct obstruction (EDO) were selected from a large pool of infertile patients with low semen volume presenting to the outpatient clinic of the Andrology Department of Kasr el Aini Hospital, Cairo, Egypt. The patients (24 with complete and 8 with partial EDO) were then transferred to the Urology Department of the same hospital for surgical treatment performed by one surgeon. The treated patients were sent back to the Andrology Department for follow-up lasting 6 to 30 months (mean 18 months). Follow-up included history taking, physical examination and repeated semen analysis. Results: There was a statistically significant improvement in all “mean” semen parame-ters following TURED. Furthermore, 42% of the azoospermic (bilateral complete EDO) and 63% of the oligozoospermic patients (partial EDO) showed improvement in their semen parameters after TURED yielding an overall improvement rate of 47% among treated patients. Pregnancy was achieved in about 17% of the azoospermic and in 25% of the oligozoospermic patients. The overall pregnancy rate was 19%. Prolonged hematuria was the only complication, encountered in only 2 patients, and was managed conservatively. Conclusion: TURED is an effective line of treatment for cases of EDO. Used judiciously, this technique can yield satisfactory results with limited morbidity in this challenging patient population. The better response of partial EDO as compared to TURED warrants further studies involving a larger number of patients. Le traitement chirurgical de l\'obstruction des voies éjaculatoires Objectifs: Le but de ce travail est d'évaluer l\'efficacité de la résection transuréthrale (unroofing) des conduits éjaculatoires obstrués (TURED) comme une alternative thérapeutique des cas d\'azoo / oligozoospermie d'origine obstructive. Patients et Méthodes: Trente-deux patients, âgés de 26 à 45 (âge moyen de 34 années), présentant des degrés variables d\'obstruction du conduit éjaculatoire (EDO) ont été sélectionnés parmi une grande population de patients consultant pour stérilité avec un volume éjaculatoire bas à la consultation externe du Département d'Andrologie de l'Hôpital Kasr El Aini. Les patients (24 EDO complète et 8 EDO partielle) ont été transférés au Département d\'Urologie du même hôpital pour traitement chirurgical réalisé par un urologue. Les malades traités ont été renvoyés au Département d'Andrologie pour suivi qui a duré 6 à 30 mois (moyenne 18 mois). Le suivi a inclu un intérrogatoire, un examen physique et une analyse du sperme répétée. Résultats: Il y avait une amélioration statistiquement significative de tous les paramètres du spermogramme en moyenne. En outre, 42% des patients azoospermiques (EDO complet bilatéral) et 63% d\'oligozoospermiques (EDO partiel) ont présenté une amélioration dans leurs paramètres du spermogramme après TURED avec un taux d\'amélioration total de 47% parmi les patients traités. La grossesse a été obtenue dans approximativement 17% des couples avec azoospermie et dans 25% des couples avec oligozoospermie. Le taux de grossesses total était de 19%. Une hématurie prolongée était la seule complication rencontrée dans seulement 2 cas et a été traitée d\'une manière conservatrice. Conclusion: TURED est une alternative efficace dans le traitement des cas d\'EDO. Utilisé judicieusement, cette technique peut donner de bons résultats avec une morbidité limitée dans cette population de patients. La meilleure réponse est notée dans les cas d\'EDO partiel. African Journal of Urology Vol.11(1) 2005: 6-1