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

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

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

Comparison of results and complications of high ligation surgery and microsurgical high inguinal varicocelectomy in the treatment of varicocele

Objectives. To prospectively compare sperm parameters, pregnancy and recurrence rates, and complications after randomized high ligation surgery versus microsurgical high inguinal varicocelectomy (MHIV)

Treatment of idiopathic and postvaricocelectomy oligozoospermia with oral tamoxifen citrate

Objective To identify a subgroup of men who may benefit from tamoxifen citrate (a widely prescribed drug for male infertility) among those with normogonadotrophic and hypergonadotrophic oligozoospermia, either idiopathic or after varicocelectomy

Discrepancy between Gleason scores of biopsy and radical prostatectomy specimens

Objective: The grade of the prostate cancer is an important factor in defining prognosis and deciding on treatment. In this study, we compared the Gleason score determined by 18-gauge core needle biopsies with both the Gleason score and pathological staging of the radical prostatectomy specimens. Patients and Methods: Between July 1992 and September 1998, we performed 144 radical retropubic prostatectomies for clinically localized prostatic carcinoma, after a negative frozen section in bilateral pelvic lymphadenectomy in all cases. Ten patients with pathologic stage T1a and T1b were excluded. The final study group consisted of 134 patients, all of whom had been diagnosed with adenocarcinoma by transrectal needle biopsies with an 18-gauge automated spring-loaded biopsy gun. No patients received neoadjuvant therapy, including androgen deprivation and radiation therapy. All patients had a designated Gleason score on the needle biopsy and prostatectomy specimens. Results: We found that grading error was greatest with well-differentiated (Gleason score 2-4) tumors. The accuracy was 15% for Gleason score 2-4 on needle biopsy. Of the 113 evaluable patients with Gleason score 5-7 on needle biopsy, 110 (97%) were graded correctly. All of the Gleason score 8-10 on needle biopsy was graded correctly. But only 1 patient in our series had Gleason score 8 on needle biopsy. Twenty-seven (25%) of 110 patients with a biopsy grade of Gleason score <7 had the cancer upgraded to 7. Of patients with both Gleason score <7 in the needle biopsy and Gleason score 7 in the prostatectomy specimen, only 3 (11%) had tumor confined to the prostate. Conclusion: The potential for grading error is greatest with well-differentiated tumors and of patients with both Gleason scores <7 in the needle biopsy and Gleason score 7 in the prostatectomy specimen, only 11% had tumor confined to the prostate. This effects treatment policy, especially for watchful waiting criteria. Copyright (C) 2000 S. Karger AG, Basel

Urologic complications of extravesical ureteroneocystostomy in renal transplantation from living related donors

Introduction: Reconstruction of the urinary system during renal transplantation is usually performed with anti-refluxive ureteroneocystostomy techniques and extravesical methods are usually preferred. Material and Methods: Between 1983 and 1997, 241 renal transplantations from living donors were performed at our institution. A variation of the Lich-Gregoir technique was used as the ureteroneocystostomy method in all cases. Results: A total of 12 (4.9%) urologic complications were observed. Urinary fistula developed in 5 (2%) cases and were explored surgically during the early postoperative period. Postoperative vesicoureteral reflux (VUR) to the transplanted kidney was identified in 7 (2.9%) cases. Either endoscopic or surgical interventions resolved VUR in 4 cases while the other 3 did not need further treatment. No ureteral stenosis was observed. There was no loss of graft due to urologic complications. Conclusions: Urologic complications after renal transplantation are reported to be about 7% and ischemia is blamed as the major contributing factor. Preparation of the native ureter during donor nephrectomy and preservation of distal periureteral fatty tissue, anastomosis technique variations in vascular anatomy, rejections and medications are the major factors determining the ischemia. Copyright (C) 2000 S. Karger AG. Basel

Latex allergy in patients with spinal dysraphism: The role of multiple surgery

Objective To investigate whether multiple surgery is responsible for the high prevalence of latex hypersensitivity in patients with spinal dysraphism by comparing the results of a skin-prick test in three groups of patients with different surgical histories