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Background: Systematic reviews and meta‐analyses are instrumental in shaping clinical practice. However, their findings can sometimes be marred by discrepancies and potential biases, thereby diluting the strength of the evidence presented. Umbrella reviews serve to comprehensively assess and synthesise these reviews, offering a clearer insight into the quality of the evidence presented. In the context of the relationship between sperm DNA fragmentation (SDF) and assisted conception outcomes, there is a divergence in the literature. Some reviews suggest a clear cause‐and‐effect linkage, whereas others present conflicting or inconclusive results. Objectives: In this umbrella review we aimed to synthesise the evidence collated in systematic reviews and meta‐analyses summarising the association of SDF with assisted reproductive technology (ART) outcomes. Search strategy: After preregistration (https://doi.org/10.17605/OSF.IO/6JHDP), we performed a comprehensive search of the PubMed, Scopus, Cochrane Library, Web of Science and Embase databases. We conducted a search for systematic reviews on the association between SDF and ART without any restrictions on language or publication date. Selection criteria: Systematic reviews and meta‐analyses assessing the association between SDF and ART outcomes were eligible. Data collection and analysis: We assessed the quality of the included reviews using AMSTAR 2 and ROBIS, and determined the degree of overlap of primary studies between reviews estimating the corrected covered area (CCA), adjusted for structural missingness. We evaluated the most recent reviews assessing the association of SDF with live birth, pregnancy, miscarriage, implantation, blastulation and fertilisation. The synthesis of evidence was harmonised across all included quantitative syntheses, re‐estimating the odds ratio (eOR) in random‐effects meta‐analyses with 95% confidence intervals (95% CIs) and 95% prediction intervals (95% PIs). We categorised the evidence strength into convincing, highly suggestive, suggestive, weak or nonsignificant, according to the meta‐analysis re‐estimated P‐value, total sample size, I2 statistic for heterogeneity, small study effect, excess significance bias and the largest study significance. Main results: We initially captured and screened 49 332 records. After excluding duplicate and ineligible articles, 22 systematic reviews, 15 of which were meta‐analyses, were selected. The 22 reviews showed a moderate degree of overlap (adjusted CCA 9.2%) in their included studies (overall n = 428, with 180 unique studies). The 15 meta‐analyses exhibited a high degree of overlap (adjusted CCA = 13.6%) in their included studies (overall n = 274, with 118 unique studies). AMSTAR 2 categorised the quality of evidence in 18 reviews as critically low and the quality of evidence in four reviews as low. ROBIS categorised all the reviews as having a high risk of bias. The re‐estimated results showed that the association of SDF with live birth was weak in one and nonsignificant in four meta‐analyses. Similarly, the association of SDF with pregnancy, miscarriage, implantation, blastulation and fertilisation was also weak or nonsignificant. The association of high SDF with different ART outcomes was also weak or nonsignificant for different interventions (IVF, ICSI and IUI) and tests. Conclusions: This umbrella review did not find convincing or suggestive evidence linking SDF with ART outcomes. Caution should be exercised in making any claims, policies or recommendations concerning SDF. [ABSTRACT FROM AUTHOR]

Objective: To prepare a set of statements for randomised clinical trials (RCT) integrity through an international multi‐stakeholder consensus. Methods: The consensus was developed via: multi‐country multidisciplinary stakeholder group composition and engagement; evidence synthesis of 55 systematic reviews concerning RCT integrity; anonymised two‐round modified Delphi survey with consensus threshold based on the average percentage of majority opinions; and, a final consensus development meeting. Prospective registrations: (https://osf.io/bhncy, https://osf.io/3ursn). Results: There were 30 stakeholders representing 15 countries from five continents including triallists, ethicists, methodologists, statisticians, consumer representatives, industry representatives, systematic reviewers, funding body panel members, regulatory experts, authors, journal editors, peer‐reviewers and advisors for resolving integrity concerns. Delphi survey response rate was 86.7% (26/30 stakeholders). There were 111 statements (73 stakeholder‐provided, 46 systematic review‐generated, 8 supported by both) in the initial long list, with eight additional statements provided during the consensus rounds. Through consensus the final set consolidated 81 statements (49 stakeholder‐provided, 41 systematic review‐generated, 9 supported by both). The entire RCT life cycle was covered by the set of statements including general aspects (n = 6), design and approval (n = 11), conduct and monitoring (n = 19), reporting of protocols and findings (n = 20), post‐publication concerns (n = 12), and future research and development (n = 13). Conclusion: Implementation of this multi‐stakeholder consensus statement is expected to enhance RCT integrity. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the impact of two stimulation protocols using highly purified human menopausal gonadotropin (HPhMG) on the endocrine profile, follicular fluid soluble Fas levels, and outcomes of intracytoplasmic sperm injection (ICSI) cycles. Methods: This prospective clinical trial included 100 normal-responder women undergoing ovarian stimulation for ICSI; 55 patients received concomitant follicle-stimulating hormone (FSH) plus HP-hMG from the start of stimulation, while 45 patients received FSH followed by HPhMG during mid/late follicular stimulation. The primary outcome was the number of top-quality embryos. The secondary outcomes were the number and percentage of metaphase II (MII) oocytes and the clinical pregnancy rate. Results: The number of MII oocytes was significantly higher in the concomitant protocol (median, 13.0; interquartile range [IQR], 8.5–18.0 vs. 9.0 [8.0–13.0] in the consecutive protocol; p=0.009); however, the percentage of MII oocytes and the fertilization rate were significantly higher in the consecutive protocol (median, 90.91; IQR, 80.0–100.0 vs. 83.33 [75.0–93.8]; p=0.034 and median, 86.67; IQR, 76.9–100.0 vs. 77.78 [66.7–89.9]; p=0.028, respectively). No significant between-group differences were found in top-quality embryos (p=0.693) or the clinical pregnancy rate (65.9% vs. 61.8% in the consecutive vs. concomitant protocol, respectively). The median follicular fluid soluble Fas antigen level was significantly higher in the concomitant protocol (9,731.0 pg/mL; IQR, 6,004.5–10,807.6 vs. 6,350.2 pg/mL; IQR, 4,382.4–9,418.4; p=0.021). Conclusion: Personalized controlled ovarian stimulation using HP-hMG during the late follicular phase led to a significantly lower response, but did not affect the quality of ICSI. [ABSTRACT FROM AUTHOR]

Objective: To assess the outcome of using low-dose aspirin, dopamine agonist and triggering ovulation by low dose of HCG in combination with GnRH agonist in fixed GnRH antagonist protocol in patients at risk of OHSS., Study Design: This prospective cohort study was conducted on 50 infertile women who were at high risk of OHSS. They received low dose aspirin from first day of stimulation, cabergoline 0.5mg daily from the day of HCG for 8days and low dose of HCG (2500 IU) in combination with GnRH agonist for final oocyte maturation in fixed GnRH antagonist protocol., Results: The study was conducted on 50 cases and all of them completed the study protocol. The clinical pregnancy rate was 40% (20 cases of 50) and no cases developed severe or critical OHSS. Only 8% (4 cases) developed moderate OHSS., Conclusion: Combining aspirin, cabergoline, and triggering with low dose of HCG in combination with GnRH agonist produced excellent clinical pregnancy rate, and decreased hospital admissions with severe or critical OHSS., (Copyright © 2017 Elsevier B.V. All rights reserved.)