Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

Background Composite outcomes are increasingly being used in obstetric trials. The aim of this systematic review is to critically appraise the use of composite outcomes in obstetric RCTs with an intention of identifying limitations and providing potential solutions for future research. Methods The study protocol was prospectively registered. Medline, Embase, Cochrane Databases and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) published in English between 1999 and 2019, using search terms related to pregnancy and composite outcomes. Study eligibility criteria: RCTs involving an obstetric condition that reported on a composite outcome. Study appraisal and synthesis methods: Screening and data extraction were performed in duplicate, and a descriptive synthesis and critical appraisal of composite obstetric outcomes, is presented. Results Of the 4170 results screened, we identified 156 RCTs, reporting on 181 composite outcomes. Of these, 158 composite outcomes related to general morbidity and mortality, either exclusively maternal (n=20), fetal-neonatal [perinatal] (n=116) or maternal and perinatal (n=22) were included in the final analysis. Obstetric composite outcomes included between two and 16 components. Components that comprised these composite outcomes were often dissimilar in terms of severity and frequency of occurrence, unlikely to have similar relative risk reductions and sometimes unrelated to the study’s primary objective – important pre-requisites to consider while constructing composite outcomes. In addition, composite adverse obstetric outcomes often do not incorporate the perspectives of pregnant persons, embrace a holistic view of health or consider outcomes related to both members of the mother-fetus dyad. Conclusions Composite outcomes are being increasingly used as primary outcomes in obstetric RCTs, based on which study conclusions are drawn and clinical recommendations made. However, there is a lack of consistency with regard to what components should be included within a composite adverse obstetric outcome and how these components should be measured. The use of novel research methods such as concept mapping may be able to address some of the limitations with the development of composite adverse obstetric outcomes, to inform future research.

The use of preoperative urodynamics as a standard investigation for urinary incontinence (UI) has long been a subject of debate, with a lack of robust evidence to demonstrate improved patients' outcomes. We aim to compare the clinical and cost effectiveness of urodynamics versus office clinical evaluation only, prior to the treatment of UI. We conducted three linked systematic reviews and meta-analyses of randomised controlled trials (RCTs) comparing urodynamics assessment versus clinical evaluation only in women prior to 1) non-surgical treatment of UI, 2a) surgical treatment of stress urinary incontinence (SUI) and 2b) invasive treatment for overactive bladder (OAB). Women with severe pelvic organ prolapse, previous continence surgery and neuropathic bladder were excluded. Primary outcomes were patientreported and objective success post-treatment. Secondary outcomes were adverse events, quality of life, sexual function and health economic measures. We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases for each category, which was last updated on January 2019. Study selection, risk of bias assessment and data extraction were performed independently by two reviewers. The random effects model was used to assess risk ratio and mean difference with 95% confidence interval. Statistical heterogeneity was assessed by I 2 statistics and the quality of evidence by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Four RCTs compared urodynamics versus clinical evaluation only prior to non-surgical management of UI. Treatment consisted of pelvic floor muscle training, with or without pharmacological therapy. Metaanalysis of 150 women showed no evidence of significant difference in the patient-reported and objective success rates between groups (P = 0.520, RR: 0.91, 95% Cl 0.69-1.21, I 2 = 0% and P = 0.470, RR:0.87, 95% Cl 0.59-1.28, I 2 = n/a, respectively). Seven RCTs were identified for surgical management of SUI. The majority of women underwent mid-urethral tape procedures (retropubic or transobturator approach). Metaanalysis of 1149 women showed no evidence of significant difference in patient-reported (P = 0.850, RR:1.01, 95% CI 0.88-1.16, I 2 = 53%) and objective success between groups (P = 0.630, RR:1.02, 95% CI 0.95-1.08, I 2 = 28%). There was no significant difference in incidence of voiding dysfunction, de novo urgency, and urinary tract infection between groups. No RCTs were identified for invasive management of OAB. In conclusion, limited evidence shows that routine urodynamics prior to non-surgical management of UI or surgical management of SUI is not associated with improved treatment outcomes, when compared to clinical evaluation only. Well-designed clinical trials are needed to evaluate the clinical and costeffectiveness of routine urodynamics prior to surgical management of SUI and OAB.

Introduction: Clinical trials provide fundamental evidence used to inform healthcare decisions at patient-and population levels and it is thus important that trials consider outcomes relevant to both patients and stakeholders. Although validated tools assessing other aspects of trial integrity exist, there is no tool for assessing the breadth and completeness of outcomes measured. Our objective was to develop a comprehensiveness of outcome reporting (COR) tool to assess this within trials in pregnancy. Material and methods:We developed a tool that aids in visualizing outcome reporting through the automatic generation of a heatmap, enabling assessment of the range of maternal and fetal/neonatal outcomes included in clinical trials. Outcome reporting and measurement of each study is compared to a context-specific, user-determined, ideal standard set of outcomes, created by initially considering all domains within five core outcome areas. These include mortality, morbidity, functioning/life-impact, resource-use, and adverse events, as identified by the most recent taxonomy for outcomes in medical research. We tested the tool's functionality using trials previously identified as studies on obesity in pregnant patients, and further compared the utility of the COR Tool against Cochrane's Risk of Bias 2.0 Tool using correlational analysis. Results:The pilot heatmap using clinical trials studying obesity in pregnancy (n = 15), illustrated a lack of comprehensiveness of reported outcomes in the majority of studies. Included trials were found to readily report physiological/clinical outcome but consistently neglected outcome areas related to functioning, delivery of care, resource-use, and adverse events. Outcome areas reported and measured were done so with largely varying degrees of quality. When the COR Tool was compared with Cochrane's RoB 2.0 Tool on a scatter plot, only a weak correlation was found (R = 0.2936, R 2 = 0.0862) Conclusions:The COR Tool will promote transparency in clarifying what outcomes a trial's conclusions are based on, encourage trialists to consider outcomes related to all aspects of maternal and fetal/neonatal health, and support reviewers in appraising outcome reporting and measurement in the assessment of trial integrity.