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Fertility and Sterility Jan 2021Can the priorities for future research in infertility be identified?
STUDY QUESTION
Can the priorities for future research in infertility be identified?
SUMMARY ANSWER
The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified.
WHAT IS KNOWN ALREADY
Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems.
STUDY DESIGN, SIZE, DURATION
Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance.
MAIN RESULTS AND THE ROLE OF CHANCE
The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science.
LIMITATIONS, REASONS FOR CAUTION
We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions.
WIDER IMPLICATIONS OF THE FINDINGS
We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda.
STUDY FUNDING/ COMPETING INTEREST(S)
The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form.
TRIAL REGISTRATION NUMBER
Not applicable.
Topics: Consensus; Delphi Technique; Female; Fertility Clinics; Humans; Infertility; International Cooperation; Male; Practice Guidelines as Topic; Pregnancy; Reproductive Medicine; Research
PubMed: 33272617
DOI: 10.1016/j.fertnstert.2020.11.014 -
Journal of Clinical Epidemiology Oct 2022This systematic review aimed to identify the characteristics and application of citation analyses in evaluating the justification, design, and placement of the research... (Review)
Review
OBJECTIVES
This systematic review aimed to identify the characteristics and application of citation analyses in evaluating the justification, design, and placement of the research results of clinical health studies in the context of earlier similar studies.
STUDY DESIGN AND SETTING
We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Methodology Register for meta-research studies. We included meta-research studies assessing whether researchers used earlier similar studies and/or systematic reviews of such studies to inform the justification or design of a new study, whether researchers used systematic reviews to inform the interpretation of new results, and meta-research studies assessing whether redundant studies were published within a specific area. The results are presented as a narrative synthesis.
RESULTS
A total of 27 studies were included. How authors of citation analyses define their outcomes appears rather arbitrary, as does how the reference of a landmark review or adherence to reporting guidelines was expected to contribute to the initiation, justification, design, or contextualization of relevant clinical trials.
CONCLUSION
Continued and improved efforts to promote evidence-based research are needed, including clearly defined and justified outcomes in meta-research studies to monitor the implementation of an evidence-based approach.
Topics: Humans; Research
PubMed: 35793778
DOI: 10.1016/j.jclinepi.2022.06.021 -
Journal of Endocrinological... Dec 2022The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated.
METHODS
All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included.
RESULTS
Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality.
CONCLUSIONS
The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.
Topics: Male; Humans; Adult; Middle Aged; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Prospective Studies; Retrospective Studies; Semen; RNA, Messenger
PubMed: 35527294
DOI: 10.1007/s40618-022-01801-x -
Medical Ultrasonography May 2022Contrast-enhanced ultrasound (CEUS) appears to be a promising application for the diagnosis of parotid gland tumours. We aimed to systematically review and meta-analyse... (Meta-Analysis)
Meta-Analysis Review
AIM
Contrast-enhanced ultrasound (CEUS) appears to be a promising application for the diagnosis of parotid gland tumours. We aimed to systematically review and meta-analyse the ability of CEUS in distinguishing benign from malignant parotid gland tumours.
MATERIAL AND METHODS
PubMed was searched for relevant studies. Data on area under time intensity curve (AUC) in arbitrary unit (AU), and mean transit time (MTT) in seconds (sec) were analysed using the Cochrane Review Manager Software.
RESULTS
Nine studies met the eligibility criteria comprising a total number of 498 parotid gland tumours (benign, number (n)=423; malignant, n=75). Descriptive evaluation of parotid gland tumours following CEUS administration showed overlap characteristics in benign and malignancies. Two publications assessed AUC and MTT in 72 and 60 parotid gland tumours, respectively. AUC was significantly lower in benign compared to malignant tumours following contrast administration (AUC, mean difference (MD) -266.77 AU, 95% confidence intervals (CI) -433.22, -100.33, p=0.002). No significant different in MTT between benign and malignant tumours (p=0.12). Heterogeneity was statistically significant in AUC (p=0.04) and MTT (p<0.00001).
CONCLUSION
Descriptive evaluation of parotid gland tumours showed overlap CEUS characteristics. Perfusion related CEUS parameters analysis is promising in differentiating benign parotid tumours from malignancies.
Topics: Contrast Media; Diagnosis, Differential; Humans; Parotid Gland; Parotid Neoplasms; Perfusion; Ultrasonography
PubMed: 34216453
DOI: 10.11152/mu-3119 -
British Journal of Sports Medicine Dec 2022To investigate cost-effectiveness and costs of fall prevention exercise programmes for older adults. (Review)
Review
OBJECTIVE
To investigate cost-effectiveness and costs of fall prevention exercise programmes for older adults.
DESIGN
Systematic review.
DATA SOURCES
Medline, Embase, Web of Science, Scopus, National Institute for Health Research Economic Evaluation Database, Health Technology Assessment database, Tufts Cost-Effectiveness Analysis Registry, Research Papers in Economics and EconLit (inception to May 2022).
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Economic evaluations (trial-based or model-based) and costing studies investigating fall prevention exercise programmes versus no intervention or usual care for older adults living in the community or care facilities, and reporting incremental cost-effectiveness ratio (ICER) for fall-related outcomes or quality-adjusted life years (QALY, expressed as cost/QALY) and/or intervention costs.
RESULTS
31 studies were included. For community-dwelling older adults (21 economic evaluations, 6 costing studies), results ranged from more effective and less costly (dominant) interventions up to an ICER of US$279 802/QALY gained and US$11 986/fall prevented (US$ in 2020). Assuming an arbitrary willingness-to-pay threshold (US$100 000/QALY), most results (17/24) were considered cost-effective (moderate certainty). The greatest value for money (lower ICER/QALY gained and fall prevented) appeared to accrue for older adults and those with high fall risk, but unsupervised exercise appeared to offer poor value for money (higher ICER/QALY). For care facilities (two economic evaluations, two costing studies), ICERs ranged from dominant (low certainty) to US$35/fall prevented (moderate certainty). Overall, intervention costs varied and were poorly reported.
CONCLUSIONS
Most economic evaluations investigated fall prevention exercise programmes for older adults living in the community. There is moderate certainty evidence that fall prevention exercise programmes are likely to be cost-effective. The evidence for older adults living in care facilities is more limited but promising.
PROSPERO REGISTRATION NUMBER
PROSPERO 2020 CRD42020178023.
Topics: Humans; Aged; Cost-Benefit Analysis; Quality-Adjusted Life Years; Exercise; Exercise Therapy
PubMed: 36302631
DOI: 10.1136/bjsports-2022-105747 -
Environmental Toxicology and Chemistry Mar 2023Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and... (Meta-Analysis)
Meta-Analysis
Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and chemical stress. We targeted metal exposures performed on bivalves under controlled laboratory conditions and selected six transcripts associated with general toxicity for evaluation: catalase, glutathione-S-transferase, heat shock proteins 70 and 90, metallothionein, and superoxide dismutase. Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units, we normalized different metal exposures to a common scale, as a proxy of concentration. Using Bayesian hierarchical random effect models, we then tested the effects of metal exposure on lnRR, both for metal exposure in general and in meta-regressions using toxic unit and exposure time as independent variables. Corresponding analyses were also repeated with transcript and tissue as additional moderators. Observed patterns were similar for general and for transcript- and tissue-specific responses. The expected overall response to arbitrary metal exposure was an lnRR of 0.50, corresponding to a 65% increase relative to a nonexposed control. However, when accounting for publication bias, the estimated "true" response showed no such effect. Furthermore, expected response magnitude increased slightly with exposure time, but there was little support for general monotonic concentration dependence with regard to toxic unit. Altogether, the present study reveals potential limitations that need consideration prior to applying the selected transcripts as biomarkers in environmental risk assessment. Environ Toxicol Chem 2023;42:628-641. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Animals; Bayes Theorem; Bivalvia; Ecotoxicology; Metals; Biomarkers; Water Pollutants, Chemical
PubMed: 36200657
DOI: 10.1002/etc.5494 -
Frontiers in Cell and Developmental... 2020Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impairing fertility dynamics. The three distinct classifications of ovarian...
Reporting on the Role of miRNAs and Affected Pathways on the Molecular Backbone of Ovarian Insufficiency: A Systematic Review and Critical Analysis Mapping of Future Research.
Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impairing fertility dynamics. The three distinct classifications of ovarian insufficiency are poor ovarian response, premature ovarian insufficiency/failure, and advanced maternal age, sharing the common denominator of deteriorated ovarian reserve. Despite efforts to define clear lines among the three, the vast heterogeneity and overlap of clinical characteristics renders their diagnosis and management challenging. Lack of a consensus has prompted an empirically based management coupled by uncertainty from the clinicians' perspective. Profiling of patients in the era of precision medicine seems to be the way forward, while the necessity for a novel approach is underlined. Implicating miRNAs in the quest for patient profiling is promising in light of their fundamental role in cellular and gene expression regulation. To this end, the current study sets out to explore and compare the three pathophysiologies-from a molecular point of view-in order to enable profiling of patients in the context of fertilization treatment and enrich the data required to practice individualized medicine. Following a systematic investigation of literature, data referring to miRNAs were collected for each patient category based on five included studies. miRNA-target pairs were retrieved from the DIANA-TarBase repository and microT-CDS. Gene and miRNA annotations were derived from Ensembl and miRbase. A subsequent gene-set enrichment analysis of miRNA targets was performed for each category separately. A literature review on the most crucial of the detected pathways was performed to reveal their relevance to fertility deterioration. Results supported that all three pathophysiologies share a common ground regarding the affected pathways, naturally attributed to the common denominator of ovarian insufficiency. As evidenced, miRNAs could be employed to explore the fine lines and diverse nature of pathophysiology since they constitute invaluable biomarkers. Interestingly, it is the differentiation through miRNAs and not through the molecular affected pathways that corresponds to the three distinctive categories. Alarming discrepancies among publications were revealed, pertaining to employment of empirical and arbitrary criteria in categorizing the patients. Following bioinformatic analysis, the final step of the current study consisted of a critical analysis of the molecular data sourced, providing a clear and unique insight into the physiological mechanisms involved. It is our intention to contribute to mapping future research dedicated to ovarian insufficiency and to help researchers navigate the overwhelming information published in molecular studies.
PubMed: 33511114
DOI: 10.3389/fcell.2020.590106 -
Journal of Clinical & Translational... Dec 2022Increasing evidence for benefit of early detection of cystic fibrosis related diabetes (CFRD) coupled with limitations of current diagnostic investigations has led to... (Review)
Review
AIMS
Increasing evidence for benefit of early detection of cystic fibrosis related diabetes (CFRD) coupled with limitations of current diagnostic investigations has led to interest and utilisation of continuous glucose monitoring (CGM). We conducted a systematic review to assess current evidence on CGM compared to reference standard oral glucose tolerance test for the detection of dysglycemia in people with cystic fibrosis without confirmed diabetes.
METHODS
MEDLINE, Embase, CENTRAL, Evidence-Based Medicine Reviews, grey literature and six relevant journals were searched for studies published after year 2000. Studies reporting contemporaneous CGM metrics and oral glucose tolerance test results were included. Outcomes on oral glucose tolerance tests were categorised into a) normal, b) abnormal (indeterminate and impaired) or c) diabetic as defined by American Diabetes Association criteria. CGM outcomes were defined as hyperglycemia (≥1 peak sensor glucose ≥ 200 mg/dL), dysglycemia (≥1 peak sensor glucose ≥ 140-199 mg/dL) or normoglycemia (all sensor glucose peaks < 140 mg/dL). CGM hyperglycemia in people with normal or abnormal glucose tolerances was used to define an arbitrary CGM-diagnosis of diabetes. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess risk of bias. Primary outcome was relative risk of an arbitrary CGM-diagnosis of diabetes compared to the oral glucose tolerance test.
RESULTS
We identified 1277 publications, of which 19 studies were eligible comprising total of 416 individuals with contemporaneous CGM and oral glucose tolerance test results. Relative risk of an arbitrary CGM-diagnosis of diabetes compared to oral glucose tolerance test was 2.92. Studies analysed were highly heterogenous, prone to bias and inadequately assessed longitudinal associations between CGM and relevant disease-specific sequela.
CONCLUSIONS
A single reading > 200 mg/dL on CGM is not appropriate for the diagnosis of CFRD. Prospective studies correlating CGM metrics to disease-specific outcomes are needed to determine appropriate cut-points.
PubMed: 36200022
DOI: 10.1016/j.jcte.2022.100305 -
Transfusion and Apheresis Science :... Apr 2021Anti-allergic agents (e.g. dexamethasone, chlorpheniramine or promethazine) are commonly administered to patients prior to blood product transfusions. However, the use... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anti-allergic agents (e.g. dexamethasone, chlorpheniramine or promethazine) are commonly administered to patients prior to blood product transfusions. However, the use of these agents is largely experience-based instead of evidence-based. This meta-analysis aimed to explore the evidence behind using anti-allergic agents to attenuate transfusion reactions.
MATERIALS AND METHODS
The Pubmed, EMBASE, Cochrane Library, Wanfang, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical literature (CMB) databases were all queried for related articles. Data from groups treated with and without anti-allergic agents were collected for meta-analysis using RevMan 5.3. Baseline characteristics and univariate statistics between groups were compared using SPSS 19.0.
RESULTS
Eight eligible articles (six case control studies and two randomized controlled trials, all with high risks of bias) were identified (22060 total cases). Administered anti-allergic agents in these studies only included dexamethasone, chlorpheniramine or promethazine. Baseline characteristics showed no significant age or gender differences between treatment or control groups. There were no significant differences between the pooled experimental or control groups (for each of the three medications) in terms of fever, pruritis, rash, airway spasm or overall transfusion reaction rates.
CONCLUSION
There is no evidence that dexamethasone, chlorpheniramine or promethazine can prevent transfusion reactions. Avoiding the arbitrary use of such anti-allergic agents before blood transfusions may potentially avoid needless adverse drug reactions.
Topics: Adult; Anti-Allergic Agents; Blood Transfusion; Female; Humans; Male; Middle Aged; Transfusion Reaction
PubMed: 33455877
DOI: 10.1016/j.transci.2020.103041 -
Trials Jan 2020Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no 'gold...
A call for consensus in defining efficacy in clinical trials for opioid addiction: combined results from a systematic review and qualitative study in patients receiving pharmacological assisted therapy for opioid use disorder.
BACKGROUND
Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no 'gold standard' measure of treatment effectiveness, and each successive trial measures a different set of outcomes which reflect success in arbitrary or opportune terms. We sought to describe the variation in current outcomes employed across clinical trials for opioid addiction, as well as determine whether a discrepancy exists between the treatment targets that patients consider important and how treatment effectiveness is measured in the literature.
METHODS
We searched nine commonly used databases (e.g., EMBASE, MEDLINE) from inception to August 1, 2015. Outcomes used across trials were extracted and categorized according to previously established domains. To evaluate patient-reported goals of treatment, semi-structured interviews were conducted with 18 adults undergoing methadone treatment.
RESULTS
We identified 60 trials eligible for inclusion. Once outcomes were categorized into eight broad domains (e.g., abstinence/substance abuse), we identified 21 specific outcomes with furthermore 53 subdomains and 118 measurements. Continued opioid use and treatment retention were the most commonly reported measures (46%, n = 28). The majority of patients agreed that abstinence from opioids was a primary goal in their treatment, although they also stressed goals under-reported in clinical trials.
CONCLUSIONS
There is inconsistency in the measures used to evaluate the effectiveness of OSATs. Individual and population level decision making is being guided by a standard of effect considered useful to researchers yet in direct conflict with what patients deem important.
TRIAL REGISTRATION
PROSPERO, CRD42013006507.
Topics: Clinical Trials as Topic; Consensus; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Qualitative Research; Research Design; Treatment Outcome
PubMed: 31907000
DOI: 10.1186/s13063-019-3995-y