Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial.

OBJECTIVES: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain. DESIGN: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial. SETTING: 34 UK hospitals. PARTICIPANTS: 405 women of reproductive age undergoing conservative surgery for endometriosis. INTERVENTIONS: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill. MAIN OUTCOME MEASURES: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment). RESULTS: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). CONCLUSIONS: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some. TRIAL REGISTRATION: ISRCTN registry ISRCTN97865475.

Effectiveness of laparoscopic removal of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women (ESPriT2): protocol for a multi-centre randomised controlled trial.

BACKGROUND: Endometriosis affects 190 million women and those assigned female at birth worldwide. For some, it is associated with debilitating chronic pelvic pain. Diagnosis of endometriosis is often achieved through diagnostic laparoscopy. However, when isolated superficial peritoneal endometriosis (SPE), the most common endometriosis subtype, is identified during laparoscopy, limited evidence exists to support the common decision to surgically remove it via excision or ablation. Improved understanding of the impact of surgical removal of isolated SPE for the management of chronic pelvic pain in women is required. Here, we describe our protocol for a multi-centre trial to determine the effectiveness of surgical removal of isolated SPE for the management of endometriosis-associated pain. METHODS: We plan to undertake a multi-centre participant-blind parallel-group randomised controlled clinical and cost-effectiveness trial with internal pilot. We plan to randomise 400 participants from up to 70 National Health Service Hospitals in the UK. Participants with chronic pelvic pain awaiting diagnostic laparoscopy for suspected endometriosis will be consented by the clinical research team. If isolated SPE is identified at laparoscopy, and deep or ovarian endometriosis is not seen, participants will be randomised intraoperatively (1:1) to surgical removal (by excision or ablation or both, according to surgeons' preference) versus diagnostic laparoscopy alone. Randomisation with block-stratification will be used. Participants will be given a diagnosis but will not be informed of the procedure they received until 12 months post-randomisation, unless required. Post-operative medical treatment will be according to participants' preference. Participants will be asked to complete validated pain and quality of life questionnaires at 3, 6 and 12 months after randomisation. Our primary outcome is the pain domain of the Endometriosis Health Profile-30 (EHP-30), via a between randomised group comparison of adjusted means at 12 months. Assuming a standard deviation of 22 points around the pain score, 90% power, 5% significance and 20% missing data, 400 participants are required to be randomised to detect an 8-point pain score difference. DISCUSSION: This trial aims to provide high quality evidence of the clinical and cost-effectiveness of surgical removal of isolated SPE. TRIAL REGISTRATION: ISRCTN registry ISRCTN27244948. Registered 6 April 2021.

PROSPECT: 4- and 6-year follow-up of a randomised trial of surgery for vaginal prolapse.

INTRODUCTION AND HYPOTHESIS: Our aim was to compare the mid-term results of native tissue, biological xenograft and polypropylene mesh surgery for women with vaginal wall prolapse. METHODS: A total of 1348 women undergoing primary transvaginal repair of an anterior and/or posterior prolapse were recruited between January 2010 and August 2013 from 35 UK centres. They were randomised by remote allocation to native tissue surgery, biological xenograft or polypropylene mesh. We performed both 4- and 6-year follow-up using validated patient-reported outcome measures. RESULTS: At 4 and 6 years post-operation, there was no clinically important difference in Pelvic Organ Prolapse Symptom Score for any of the treatments. Using a strict composite outcome to assess functional cure at 6 years, we found no difference in cure among the three types of surgery. Half the women were cured at 6 years but only 10.3 to 12% of women had undergone further surgery for prolapse. However, 8.4% of women in the mesh group had undergone further surgery for mesh complications. There was no difference in the incidence of chronic pain or dyspareunia between groups. CONCLUSIONS: At the mid-term outcome of 6 years, there is no benefit from augmenting primary prolapse repairs with polypropylene mesh inlays or biological xenografts. There was no evidence that polypropylene mesh inlays caused greater pain or dyspareunia than native tissue repairs.

Summary: 2017 International Consultation on Incontinence Evidence-Based Surgical Pathway for Pelvic Organ Prolapse.

OBJECTIVE: The aim of this article is to summarize the relevant findings that inform the 2017 International Consultation on Incontinence pathway for surgical treatment of pelvic organ prolapse (POP). METHODS: We conducted an evidence-based review of the English-language peer-reviewed literature relating to POP surgery published prior to December 2016. Level 1 evidence (randomized controlled trials [RCTs] or systematic reviews of RCTs) was preferred; however, level 2 (poor-quality RCT, prospective cohort studies) or 3 evidence (case series or retrospective studies) has been included if level 1 data were lacking. The committee evaluated the literature and made recommendations based on the Oxford grading system summarized as follows: grade A recommendation usually depends on consistent level 1 evidence; grade B recommendation usually depends on consistent level 2 and/or 3 studies, or "majority evidence" from RCTs; grade C recommendation usually depends on level 3 studies or "majority evidence" from level 2/3 studies or Delphi-processed expert opinion; grade D, "no recommendation possible," would be used where the evidence is inadequate or conflicting. RESULTS: The recommendations from each chapter of the review are presented and serve to inform an evidence-based pathway for the surgical treatment of prolapse. A Web-based interactive application of the pathway is presented. CONCLUSIONS: The 2017 International Consultation on Incontinence pathway on surgery for POP is designed as an adjunct to transparent consultation and consent relating to POP surgery. The final decision regarding surgical intervention can be made only after a shared decision-making process between the patient and the clinician that will evaluate a variety of individual factors that cannot be assessed in the pathway.

Mesh, graft, or standard repair for women having primary transvaginal anterior or posterior compartment prolapse surgery: two parallel-group, multicentre, randomised, controlled trials (PROSPECT).

BACKGROUND: The use of transvaginal mesh and biological graft material in prolapse surgery is controversial and has led to a number of enquiries into their safety and efficacy. Existing trials of these augmentations are individually too small to be conclusive. We aimed to compare the outcomes of prolapse repair involving either synthetic mesh inlays or biological grafts against standard repair in women. METHODS: We did two pragmatic, parallel-group, multicentre, randomised controlled trials for our study (PROSPECT [PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials]) in 35 centres (a mix of secondary and tertiary referral hospitals) in the UK. We recruited women undergoing primary transvaginal anterior or posterior compartment prolapse surgery by 65 gynaecological surgeons in these centres. We randomly assigned participants by a remote web-based randomisation system to one of the two trials: comparing standard (native tissue) repair alone with standard repair augmented with either synthetic mesh (the mesh trial) or biological graft (the graft trial). We assigned women (1:1:1 or 1:1) within three strata: assigned to one of the three treatment options, comparison of standard repair with mesh, and comparison of standard repair with graft. Participants, ward staff, and outcome assessors were masked to randomisation where possible; masking was obviously not possible for the surgeon. Follow-up was for 2 years after the surgery; the primary outcomes, measured at 1 year and 2 years, were participant-reported prolapse symptoms (i.e. the Pelvic Organ Prolapse Symptom Score [POP-SS]) and condition-specific (ie, prolapse-related) quality-of-life scores, analysed in the modified intention-to-treat population. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN60695184. FINDINGS: Between Jan 8, 2010, and Aug 30, 2013, we randomly allocated 1352 women to treatment, of whom 1348 were included in the analysis. 865 women were included in the mesh trial (430 to standard repair alone, 435 to mesh augmentation) and 735 were included in the graft trial (367 to standard repair alone, 368 to graft augmentation). Because the analyses were carried out separately for each trial (mesh trial and graft trial) some women in the standard repair arm assigned to all treatment options were included in the standard repair group of both trials. 23 of these women did not receive any surgery (15 in the mesh trial, 13 in the graft trial; five were included in both trials) and were included in the baseline analyses only. Mean POP-SS at 1 year did not differ substantially between comparisons (standard 5·4 [SD 5·5] vs mesh 5·5 [5·1], mean difference 0·00, 95% CI -0·70 to 0·71; p=0·99; standard 5·5 [SD 5·6] vs graft 5·6 [5·6]; mean difference -0·15, -0·93 to 0·63; p=0·71). Mean prolapse-related quality-of-life scores also did not differ between groups at 1 year (standard 2·0 [SD 2·7] vs mesh 2·2 [2·7], mean difference 0·13, 95% CI -0·25 to 0·51; p=0·50; standard 2·2 [SD 2·8] vs graft 2·4 [2·9]; mean difference 0·13, -0·30 to 0·56; p=0·54). Mean POP-SS at 2 years were: standard 4·9 (SD 5·1) versus mesh 5·3 (5·1), mean difference 0·32, 95% CI -0·39 to 1·03; p=0·37; standard 4·9 (SD 5·1) versus graft 5·5 (5·7); mean difference 0·32, -0·48 to 1·12; p=0·43. Prolapse-related quality-of-life scores at 2 years were: standard 1·9 (SD 2·5) versus mesh 2·2 (2·6), mean difference 0·15, 95% CI -0·23 to 0·54; p=0·44; standard 2·0 (2·5) versus graft 2·2 (2·8); mean difference 0·10, -0·33 to 0·52; p=0·66. Serious adverse events such as infection, urinary retention, or dyspareunia or other pain, excluding mesh complications, occurred with similar frequency in the groups over 1 year (mesh trial: 31/430 [7%] with standard repair vs 34/435 [8%] with mesh, risk ratio [RR] 1·08, 95% CI 0·68 to 1·72; p=0·73; graft trial: 23/367 [6%] with standard repair vs 36/368 [10%] with graft, RR 1·57, 0·95 to 2·59; p=0·08). The cumulative number of women with a mesh complication over 2 years in women actually exposed to synthetic mesh was 51 (12%) of 434. INTERPRETATION: Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery. FUNDING: UK National Institute of Health Research.

A cost-utility analysis of microwave endometrial ablation versus thermal balloon endometrial ablation.

OBJECTIVE: To evaluate the cost-effectiveness of microwave endometrial ablation (MEA) and thermal balloon endometrial ablation (TBALL) for heavy menstrual bleeding. METHODS: A cost-utility analysis performed alongside a pragmatic RCT in a single hospital within Scotland on women undergoing MEA and TBALL. Resource use data collected from all 314 trial participants were combined with study specific and published unit cost data to estimate a cost per patient. Quality-adjusted life-years (QALYs) were based on EQ-5D responses at baseline, 2 weeks, 6 and 12 months. The incremental cost per QALY of TBALL versus MEA was calculated and bootstrapping was performed to determine the likelihood that a treatment would be cost-effective at different threshold values for society's willingness to pay for a QALY. RESULTS: The mean cost of TBALL (10 years equipment life, 100 uses annually) of reusable equipment was pound181 (95% confidence interval [CI] pound70-434) greater than MEA. There were no statistically significant differences between the total nonhealth costs and health benefits of the two arms. On average, MEA provided more QALYs after adjusting for baseline EQ-5D score (0.017; 95% CI 0.017-0.051). In terms of mean incremental cost per QALY, MEA was, on average, dominant (less costly and at least as effective) and there was over a 90% chance that MEA would be considered cost-effective at a pound20,000 threshold of a cost per QALY. CONCLUSIONS: MEA is likely to be more cost-effective than TBALL at 1 year. Further longer-term follow-up is, however, needed.

Second-generation treatment: microwave.

Microwave endometrial ablation is an effective treatment for heavy menstrual loss that achieves high satisfaction rates, is acceptable to patients, and is recommended by the National Institute of Clinical Excellence. It has been evaluated extensively in randomized trials against first- and second-generation endometrial ablative techniques. Its simplicity of use and short treatment time make it suitable for outpatient treatments, whilst it can also treat larger and irregular cavities. This article reviews the available clinical research and scientific basis of this endometrial ablation technique.

A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs.

OBJECTIVE: To compare outpatient microwave endometrial ablation (MEA) in the postmenstrual phase to standard MEA treatment after drug preparation in a day case theatre environment. DESIGN: A randomised controlled trial. SETTING: A large United Kingdom teaching hospital. POPULATION: Two hundred and ten women complaining of excessive menstrual loss. METHODS: Two hundred and ten women with excessive menstrual loss were randomised. Ninety-seven women were treated as outpatients in the immediate post-menstrual phase and 100 were treated in an operating theatre after hormonal preparation. All procedures were commenced under local anaesthesia with or without conscious sedation. Analysis was by modified intention to treat. MAIN OUTCOME MEASURES: Primary outcome measures were satisfaction with treatment (measured at one year) and acceptability of treatment (measured at two weeks). Secondary outcome measures were menstrual outcome and financial cost. RESULTS: Significantly more women found treatment post-menses acceptable; 86 (89.5%) versus 76 (76.0%) [difference in proportions 13.6%, 95% CI (3.0%, 23.9%)]. Similar numbers in each arm were totally or generally satisfied with the treatment, 86 (92.5%) versus 84 (88.4%) [difference in proportions 4.1%, 95% CI (-4.7%, 12.9%)] while amenorrhoea rates at one year were comparable, 52 (55.9%) versus 60 (61.9%). [difference in proportions -5.9%, 95% CI (-19.8%, 7.6%)]. The mean health service costs were 124 pounds (95% CI 86-194 pounds) lower for the patients in the post-menses group. CONCLUSION: MEA performed under local anaesthesia (with or without conscious sedation) in the post-menstrual phase achieves high levels of satisfaction is very acceptable to patients and results in significantly reduced health service costs. Importantly menstrual outcomes are not affected by omission of drug preparation. There is now good evidence to support the use of MEA, without drug endometrial preparation, in the outpatient setting.

Outpatient endometrial ablation.

The simplicity of use and short treatment times of second-generation ablation techniques have increased the likelihood of acceptable treatment under local anaesthetic. Once treatment under local anaesthesia +/- conscious sedation has become accepted, the next step is to explore the viability of moving ablation out of theatre. Whilst there are many series reports of treatment under local anaesthetic, few well-constructed trials have evaluated acceptability and success rates. A reliable anaesthetic regime is available with low failure rates, although problems exist with unpredictable post-operative discomfort and nausea. The optimal treatment package, which will guarantee acceptable treatment with no failures and a quick recovery time allowing for early discharge, is not known. This, along with equipment requirements, safety issues and the need for well-trained support staff, will make outpatient ablation unattractive at present for all but the most determined gynaecologists who have supportive and dynamic staff.

A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years.

OBJECTIVE: To compare long term outcomes following microwave endometrial ablation (MEA) or transcervical resection of the endometrium (TCRE). DESIGN: Follow up of a randomised controlled trial. SETTING: Gynaecology department of a large UK teaching hospital. POPULATION/SAMPLE: Two hundred and thirty-nine participants in a randomised comparison of MEA with TCRE. METHODS: Collection of patient completed postal questionnaires and operative databank review. MAIN OUTCOME MEASURES: Women's satisfaction with and acceptability of treatment, menstrual symptoms, changes in health-related quality of life and additional treatments received. RESULTS: Two hundred and thirty-six of the original 263 women returned questionnaires (90%) after a minimum of five years post-treatment. Women allocated to MEA were significantly more likely to be totally or generally satisfied with treatment (86% vs 74%; difference 12%, 95% CI 2% to 23%), to find it acceptable (97% vs 91%; difference 6%, 95% CI 1% to 13%) and would recommend it (97% vs 89%; difference 8%, 95% CI 1% to 14%). Bleeding and pain scores were highly significantly reduced following both MEA and TCRE, achieving amenorrhoea rates of 65% and 69%, respectively. The hysterectomy rate after a minimum of five years was 16% in the MEA and 25% in the TCRE arm. CONCLUSIONS: Both techniques achieve significant and comparable improvements in menstrual symptoms, and health-related quality of life. While high rates of satisfaction with treatment and acceptability of treatment are achieved by TCRE, these are significantly lower than levels following MEA. These long term data, when combined with the trials' operative findings and known costs of both procedures, now inform us that MEA is a more effective and efficient treatment for heavy menstrual loss than TCRE.

Is outpatient diagnostic hysteroscopy more useful than endometrial biopsy alone for the investigation of abnormal uterine bleeding in unselected premenopausal women? A randomised comparison.

OBJECTIVE: To formally evaluate the clinical benefit of additional outpatient hysteroscopy over traditional vaginal examination and endometrial biopsy. DESIGN: A prospective randomised controlled trial. SETTING: A large teaching hospital in the northeast of Scotland. SAMPLE Premenopausal women with abnormal uterine bleeding referred to the general gynaecologic clinic and requiring endometrial biopsy. METHODS Women were randomised to either outpatient hysteroscopy and endometrial biopsy or endometrial biopsy alone. PRIMARY OUTCOME: initial surgical intervention rates. SECONDARY OUTCOMES: procedural success and acceptability, intrauterine pathology identified and changes in management. RESULTS: Three hundred and seventy women were recruited to the study. Initial trends in clinical management were comparable in both groups. No woman was advised to have removal of a localised lesion found at outpatient hysteroscopy and a normal uterine cavity at hysteroscopy did not influence the hysterectomy rate, which was similar in both groups. Outpatient hysteroscopy was found to be as acceptable as an outpatient endometrial biopsy and successfully completed in 85% compared with 91% of women who underwent endometrial biopsy alone. No cases of endometrial malignancy were identified. CONCLUSIONS: Outpatient diagnostic hysteroscopy is an acceptable procedure and may give more reassurance. It did not influence clinical management, especially with respect to hysterectomy rate. Outpatient hysteroscopy may be useful in selected cases, but when performed in a non-selective manner, it has little influence on clinical management and increases costs.

Microwave endometrial ablation versus endometrial resection: a randomized controlled trial.

OBJECTIVE: To compare menstrual status, satisfaction, and acceptability of microwave endometrial ablation with transcervical endometrial resection for the treatment of heavy menstrual bleeding. METHODS: Women were randomized to either endometrial ablative method. Menstrual status, satisfaction, acceptability, and changes in health-related quality of life were obtained by a self-completed questionnaire. Case note review and personal communication identified further surgery rates at 2 years after each procedure. RESULTS: Among the original 263 women who underwent endometrial ablation, 249 (95%) returned questionnaires at 2 years. Menstrual status in both groups was similar, although the amenorrhea rate was higher after microwave endometrial ablation. Seventy-nine percent of women were either completely or generally satisfied after microwave ablation compared with 67% after transcervical endometrial resection. Health-related quality-of-life scores remained higher than at recruitment for both treatments. Hysterectomy rates were similar at 2 years (11.6% after microwave endometrial ablation and 12.7% after transcervical endometrial resection), and no repeat endometrial ablative procedures were required. CONCLUSION: Microwave endometrial ablation is an effective alternative to transcervical endometrial resection for dysfunctional uterine bleeding.