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Summary: Health professionals and policymakers rely on evidence synthesized from high quality research studies. Yet, there remain unanswered questions about how to prevent and treat obesity. In this research project, international practice guidelines and Cochrane systematic reviews were examined in order to identify gaps in the synthesized obesity intervention evidence base. One hundred and forty‐two partial or complete gaps were found. Systematic review questions to address these gaps were formulated and subjected to a prioritization consultation process with 36 international obesity expert stakeholders. Forty‐three review questions were priority‐assessed. The top 10 ranked review questions received support from at least 75.0% of stakeholders. The leading questions focused on preventive and community‐based approaches, including those delivered through primary‐care. Children within the context of their families were a highly‐prioritized target group, as were persons with diabetes or disabilities. Experts also prioritized reviews to determine which elements of programs are the most effective, and by which mode they are best delivered. Experts recommended that negative, psycho‐social, and longer‐term outcomes be captured in reviews. We request reviewers and funders to strongly consider addressing the top 10 leading prioritized review questions presented here. [ABSTRACT FROM AUTHOR]

BACKGROUND IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy. OBJECTIVE AND RATIONALE Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility. SEARCH METHODS We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool. OUTCOMES Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81–1.74, I 2 = 42.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41–1.50, I 2 = 0.0%). WIDER IMPLICATIONS There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making. [ABSTRACT FROM AUTHOR]

BACKGROUND In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. OBJECTIVE AND RATIONALE This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. SEARCH METHODS A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. OUTCOMES Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02–1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96–1.54]; OR 1.25 [95% CI 0.99–1.57]; OR 1.26 [95% CI 1.03–1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. WIDER IMPLICATIONS This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties. [ABSTRACT FROM AUTHOR]

Objective: To develop a core outcome set for heavy menstrual bleeding (HMB). Design: Core outcome set (COS) development methodology described by the COMET initiative. Setting: University hospital gynaecology department, online international survey and web‐based international consensus meetings. Population or sample: An international collaboration of stakeholders (clinicians, patients, academics, guideline developers) from 20 countries and 6 continents. Methods: Phase 1: Systematic review of previously reported outcomes to identify potential core outcomes. Phase 2: Qualitative studies with patients to identify outcomes most important to them. Phase 3: Online two‐round Delphi survey to achieve consensus about which outcomes are most important. Phase 4: A consensus meeting to finalise the COS. Main outcome measures: Outcome importance was assessed in the Delphi survey on a 9‐point scale. Results: From the 'long list' of 114, 10 outcomes were included in the final COS: subjective blood loss; flooding; menstrual cycle metrics; severity of dysmenorrhoea; number of days with dysmenorrhoea; quality of life; adverse events; patient satisfaction; number of patients going on to have further treatment for HMB and haemoglobin level. Conclusions: The final COS includes variables that are feasible for use in clinical trials in all resource settings and apply to all known underlying causes of the symptom of HMB. These outcomes should be reported in all future trials of interventions, their systematic reviews, and clinical guidelines to underpin policy. [ABSTRACT FROM AUTHOR]