Efficacy of coenzyme Q10 supplementation for male infertility with high sperm DNA fragmentation index: a protocol for a systematic review and meta-analysis

Introduction
Infertility is a focal issue in public health and affects human reproduction and survival. Notably, an increasing number of studies in recent decades have found that sperm DNA integrity plays a critical role in the development of healthy embryos. Among the multiple pathogenic factors of sperm DNA fragmentation, oxidative stress has proven to be predominant. Coenzyme Q10 supplementation, which has been used for the treatment of male infertility, has shown good clinical efficacy due to its oxidation resistance, but its efficacy as measured by the sperm DNA fragmentation index remains controversial. To address this issue, we will perform a systematic review and meta-analysis to evaluate the efficacy of coenzyme Q10 for male infertility patients with a high sperm DNA fragmentation index.

Methods and analysis
The PubMed, Embase, Cochrane Central Register of Studies and Web of Science databases will be comprehensively searched from inception to 31 December 2022 to identify relevant studies published in the English language using appropriate search strategies. The search terms will be derived from the following concepts: sperm DNA fragmentation, coenzyme Q10 and randomised controlled trials. Two review stages, that is, title and abstract screening and full-text screening, will be performed by two reviewers. The risk of bias, publication bias and evidence grade of the included studies will be assessed using a standardised protocol. Data will be used to calculate effect sizes. Heterogeneity among the studies will be evaluated graphically. Subgroup analysis and sensitivity analysis will be performed if necessary to validate the results.

Ethics and dissemination
No ethical approval will be needed, as there will be no participants in this study. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the findings through publication and conference presentation.

PROSPERO registration number
CRD42022293340.

Leggi
Giugno 2023

Protocol for a systematic review and meta-analysis of the diagnostic test accuracy of host and HPV DNA methylation in cervical cancer screening and management

Introduction
Human papillomavirus (HPV) is necessary but not sufficient for cervical cancer development. During cervical carcinogenesis, methylation levels increase across host and HPV DNA. DNA methylation has been proposed as a test to diagnose cervical intraepithelial neoplasia (CIN); we present a protocol to evaluate the accuracy of methylation markers to detect high-grade CIN and cervical cancer.

Methods and analysis
We will search electronic databases (Medline, Embase and Cochrane Library), from inception, to identify studies examining DNA methylation as a diagnostic marker for CIN or cervical cancer, in a cervical screening population. The primary outcome will be to assess the diagnostic test accuracy of host and HPV DNA methylation for high-grade CIN; the secondary outcomes will be to examine the accuracy of different methylation cut-off thresholds, and accuracy in high-risk HPV positive women. Our reference standard will be histology. We will perform meta-analyses using Cochrane guidelines for diagnostic test accuracy. We will use the number of true positives, false negatives, true negatives and false positives from individual studies. We will use the bivariate mixed effect model to estimate sensitivity and specificity with 95% CIs; we will employ different bivariate models to estimate sensitivity and specificity at different thresholds if sufficient data per threshold. For insufficient data, the hierarchical summary receiver operating curve model will be used to calculate a summary curve across thresholds. If there is interstudy and intrastudy variation in thresholds, we will use a linear mixed effects model to calculate the optimum threshold. If few studies are available, we will simplify models by assuming no correlation between sensitivity and specificity and perform univariate, random-effects meta-analysis. We will assess the quality of studies using QUADAS-2 and QUADAS-C.

Ethics and dissemination
Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.

PROSPERO registration number
CRD42022299760.

Leggi
Giugno 2023