Considerations on implementation of the newest treatment for symptomatic uterine fibroids: Oral GnRH antagonists.

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.

LAparoscopic Versus Abdominal hysterectomy (LAVA): protocol of a randomised controlled trial.

INTRODUCTION: There is uncertainty about the advantages and disadvantages of laparoscopic hysterectomy compared with abdominal hysterectomy, particularly the relative rate of complications of the two procedures. While uptake of laparoscopic hysterectomy has been slow, the situation is changing with greater familiarity, better training, better equipment and increased proficiency in the technique. Thus, a large, robust, multicentre randomised controlled trial (RCT) is needed to compare contemporary laparoscopic hysterectomy with abdominal hysterectomy to determine the safest and most cost-effective technique. METHODS AND ANALYSIS: A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation. A within trial-based economic evaluation will explore the cost-effectiveness of laparoscopic hysterectomy compared with open abdominal hysterectomy. We will aim to recruit 3250 women requiring a hysterectomy for a benign gynaecological condition and who were suitable for either laparoscopic or open techniques. The primary outcome is major complications up to six completed weeks postsurgery and the key secondary outcome is time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation is to be cost per QALY at 12 months' postsurgery. A secondary analysis is to be undertaken to generate costs per major surgical complication avoided and costs per return to normal activities. ETHICS AND DISSEMINATION: The study was approved by the West Midlands-Edgbaston Research Ethics Committee, 18 February 2021 (Ethics ref: 21/WM/0019). REC approval for the protocol version 2.0 dated 2 February 2021 was issued on 18 February 2021.We will present the findings in national and international conferences. We will also aim to publish the findings in high impact peer-reviewed journals. We will disseminate the completed paper to the Department of Health, the Scientific Advisory Committees of the RCOG, the Royal College of Nurses (RCN) and the BSGE. TRIAL REGISTRATION NUMBER: ISRCTN14566195.

Local anaesthesia for office hysteroscopy: A systematic review & meta-analysis.

OBJECTIVE: To compare the effects of different types and routes of administration of local anaesthetic for pain control during and after office hysteroscopy. METHODS: Medline, Embase, CINAHL and the Cochrane library were searched from inception until October 2019, in order to perform a systematic review and meta-analysis of all randomised controlled trials investigating the use of a local anaesthetic compared to a control, for pain relief in women undergoing diagnostic or operative office hysteroscopy. Average pain scores and data regarding side-effects, feasibility, complications, acceptability and satisfaction were collected. RESULTS: The literature search yielded 612 citations. A total of 37 studies were included for systematic review, of which data from 20 studies were used for meta-analysis. Local anaesthesia was associated with significantly reduced pain during (SMD -0.57, 95 % CI -0.79 to -0.34) and after (SMD -0.30, 95 % CI -0.54 to -0.06) office hysteroscopy but did not reduce vasovagal episodes (OR 0.73, 95 % CI 0.50-1.09). A reduction in intra-procedural pain was observed regardless of type or route of administration. Local anaesthesia did not significantly reduce the risk of procedural failure (OR 0.72, 95 % CI 0.47-1.11). Insufficient data regarding complications, acceptability and satisfaction were available for meta-analysis. CONCLUSION: Local anaesthesia via any route of genital tract administration, should be considered when undertaking office diagnostic or operative hysteroscopy to reduce pain during and after the procedure. Further research is needed to understand whether the pain control benefits of local anaesthesia remain apparent with vaginoscopic approaches to office hysteroscopy that avoid genital tract instrumentation.

Local anaesthesia for pain control during outpatient hysteroscopy: systematic review and meta-analysis.

OBJECTIVE: To compare the effects of different types of local anaesthetic for pain control during outpatient hysteroscopy. DESIGN: Systematic review and meta-analysis of randomised controlled trials. SETTING: Outpatient hysteroscopy clinics. PARTICIPANTS: Women undergoing diagnostic or operative hysteroscopy as outpatients-that is, without general anaesthesia. Study selection criteria Medline, Embase, CINAHL, the Cochrane library, and reference lists of relevant studies. Two reviewers independently selected trials. Data were abstracted on quality, characteristics, and results. RESULTS: There were 20 trials (2851 participants). Data from 15 of these were meta-analysed in subgroups defined by type of intervention and study quality. Intracervical (standardised mean difference -0.36, 95% confidence interval -0.61 to -0.10, I(2)=0%) and paracervical (-1.28, -2.22 to -0.35, I(2)=97%) injections of local anaesthetic significantly reduced the pain in women undergoing hysteroscopy as outpatients, whereas transcervical (-0.11, -0.31 to 0.10, I(2)=27%) and topical application (-0.32, -0.97 to 0.33, I(2)= 90%) did not. Meta-regression showed that paracervical injection was superior to the other anaesthetic methods (P=0.04), a finding that was supported by the high quality subgroup of studies. Use of local anaesthetic did not have a significant effect on the incidence of vasovagal episodes (P=0.09). CONCLUSIONS: Paracervical local anaesthetic injection is the best method of pain control for women undergoing hysteroscopy as outpatients.

Hospital recovery following Thermachoice ablation is not dependent on setting (outpatient or daycase) or rescue analgesia: unexpected result.

BACKGROUND: Thermal balloon endometrial ablation (TBEA) is increasingly being performed in the outpatient setting under local anaesthesia (LA) rather than in a daycase setting under general anaesthesia (GA). Our aim was to compare the post operative rescue analgesia requirements and duration of hospital stay in women undergoing outpatient (LA) and daycase (GA) TBEA. METHODS: Prospective observational study of consecutively recruited women who underwent outpatient (LA) TBEA (n=51) and daycase (GA) TBEA (n=50) over the same time period. Analgesia that was provided additional to the standard administered analgesic regimen was considered rescue analgesia. The main outcome measures were requirement for rescue analgesia and duration of hospital stay in both cohorts. RESULT(S): LA compared to GA cohorts had shorter hospital stays (11 h [95% CI 9-13] vs. 17 h [95% CI 14-20]) and lower analgesia requirements. However, multivariate regression, correcting for all known confounders, showed that duration of stay was independent of setting for ablation or amount of rescue analgesia. CONCLUSION(S): Duration of hospital stay is not entirely dependent on whether outpatient or daycase endometrial ablation is considered. This unexpected preliminary finding deserves to be validated in future confirmatory trials that compare outpatient and daycase treatments. We also discuss the confounding factors that should be considered when designing such trials.