Greer, O

Shah, NM

Woon, EV

English

Spiral - Imperial College Digital Repository

PROSPEROInternational prospective register of systematic reviewsTo enable PROSPERO to focus on COVID-19 submissions, this registration record has undergone basicautomated checks for eligibility and is published exactly as submitted. PROSPERO has never provided peerreview, and usual checking by the PROSPERO team does not endorse content. Therefore, automaticallypublished records should be treated as any other PROSPERO registration. Further detail is provided here. CitationEe Von Woon, Orene Greer, Nishel Shah. Natural Killer Cells in Recurrent Miscarriage and RecurrentImplantation Failure : Systematic Review and Meta Analysis. PROSPERO 2020 CRD42020175868 Availablefrom: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020175868 Review question1. What are the levels of pNK and uNK in recurrent miscarriage versus controls?3. What are the levels of pNK and uNK in recurrent implantation failure versus fertile controls? SearchesLiterature search strategies will be developed using medical subject headings (MeSH) and text words relatedto recurrent miscarriage, recurrent implantationf failure and natural killer cells. We will search MEDLINE,EMBASE, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and CochraneDatabase of Systematic Reviews (CDSR). This will be supplemented by searching for trial protocols viametaRegister. Grey literature will be searched in Google Scholar. Types of study to be includedThere are no restriction to the type of study to be included. Our only exclusion criteria is study that involveusage of immunotherapy. Condition or domain being studiedImmunological factor as an aetiology in patients with recurrent miscarriage and recurrent implantation failure. Participants/populationWe will include studies examining all patients with two or more recurrent miscarriages and patients with twoor more implantation failures after IVF. Intervention(s), exposure(s)We will only include studies where NO interventions are given to the patients. Comparator(s)/controlWe will only include studies where there are healthy fertile controls with a history of </= 1 previousmiscarriage (for objectives 1 and 2); and infertile/fertile healthy controls with </= 1 previous implantationfailure ContextThere are no restrictions in the setting for the studies. Main outcome(s)Primary outcome measure is level of NK cells (percentage/number) in women with RM or RIF versus fertilecontrol. Measures of effectStandard mean difference (SMD) of NK cells levels (absolute number/percentage) in RM or RIF versus fertilecontrols Additional outcome(s)                               Page: 1 / 4PROSPEROInternational prospective register of systematic reviewsPeripheral and uterine natural killer cell cytotoxicity in RM/RIF versus fertile controls.Measures of effectAs there is no absolute measure of this effect, we intend to report this as a narrative outcome. Data extraction (selection and coding)Two reviewers will screen titles and abstracts independently and a full report will be obtained for those thatmeet inclusion criteria. Full reports will be further screened to meet inclusion criteria. We will seek furtherinformation from study authors where necessary to resolve questions about eligibility. A data spreadsheetwill be developed and agreed among all authors. The data will be extracted by two reviewers independentlyinto Covidence. Any disagreements will be resolved by discussion or by a senior reviewer. Authors will becontacted to resolve any uncertainties. Data extracted will include :- Year of publication, country of study, author details- study aim- Sample size- patient characteristics- methodology- inclusion and exclusion criteria, - reason for reproductive failure (implantation failure or recurrent miscarriage), - source (pNK or uNK) and method of measurement of NK cell levels/activity and reference range of the test,if applicable, - Levels of NK cells (percentage and/or absolute number)- Cytotoxicity of NK cells (percentage and/or absolute number) Risk of bias (quality) assessmentThe Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool will be used to evaluate riskof bias – this includes bias due to confounding, selection of participants into the study, classification ofinterventions, deviations from intended interventions, missing data, measurement of outcomes, selection ofthe reported result. Two reviewers will independently rate each study and risk will be allocated as low,unclear or high risk. Any differences will be resolved by consensus or referring to a third reviewer. Strategy for data synthesisIf two or more studies within each group of RM or RIF is found, data will be synthesised.Standard mean difference (SMD) of NK cells levels (number/percentage) in RM or RIF versus respectivecontrols will be calculated, with a confidence interval of 95%. SMD will be plotted on a forest plot graph –RM/RIF will be plotted on the right side, and controls plotted on the left side. Heterogeneity will be measured by considering variability of patient characteristics (e.g. age, BMI, pre-existing comorbidities, primary/secondary RIF or RM, fertile/infertile, previous number of RM or RIF, methodof NK cell measurement) and trial factors (randomization concealment, blinding of outcome assessment,losses to follow up) – I²>50% is considered as significant in which case a random effects model will be used.If I² <50%, a fixed effects model (Mantel-Haenszel) will be used.  Analysis of subgroups or subsetsIf significant heterogeneity >50% is found, subgroup analyses into possible sources of heterogeneity will beperformed for :                               Page: 2 / 4PROSPEROInternational prospective register of systematic reviews- Primary vs secondary RIF/RM- Number of previous RM (2 vs >2) or RIF (2 vs >2)- Fertile vs infertile patients - uNK vs pNK - Number vs percentage of NK cells - Methodology of measurement of NK cells (e.g. flow cytometry versus immunohistochemistry) Contact details for further informationEe Von Woone.woon19@imperial.ac.uk Organisational affiliation of the reviewNone Review team members and their organisational affiliationsDr Ee Von Woon. Imperial College LondonDr Orene Greer. Imperial College LondonDr Nishel Shah. Chelsea and Westminster Hospital Type and method of reviewDiagnostic, Meta-analysis, Systematic review Anticipated or actual start date30 March 2020 Anticipated completion date06 July 2020 Funding sources/sponsorsNo external funding has been sought for the purpose of the review.Grant number(s)State the funder, grant or award number and the date of awardNot applicable Conflicts of interest LanguageEnglish CountryEngland Stage of reviewReview Ongoing Subject index terms statusSubject indexing assigned by CRD Subject index termsMeSH headings have not been applied to this record Date of registration in PROSPERO                               Page: 3 / 4PROSPEROInternational prospective register of systematic reviews28 April 2020 Date of first submission22 March 2020 Stage of review at time of this submissionThe review has not started Stage Started CompletedPreliminary searches No NoPiloting of the study selection process No NoFormal screening of search results against eligibility criteria No NoData extraction No NoRisk of bias (quality) assessment No NoData analysis No NoThe record owner confirms that the information they have supplied for this submission is accurate andcomplete and they understand that deliberate provision of inaccurate information or omission of data may beconstrued as scientific misconduct.The record owner confirms that they will update the status of the review when it is completed and will addpublication details in due course. 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Natural killer cells in recurrent miscarriage and recurrent implantation failure : systematic review and meta analysis

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Natural killer cells in recurrent miscarriage and recurrent implantation failure : systematic review and meta analysis

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