Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Hysterectomy, endometrial destruction, and levonorgestrel releasing intrauterine system (Mirena) for heavy menstrual bleeding: systematic review and meta-analysis of data from individual patients.

OBJECTIVE: To evaluate the relative effectiveness of hysterectomy, endometrial destruction (both "first generation" hysteroscopic and "second generation" non-hysteroscopic techniques), and the levonorgestrel releasing intrauterine system (Mirena) in the treatment of heavy menstrual bleeding. DESIGN: Meta-analysis of data from individual patients, with direct and indirect comparisons made on the primary outcome measure of patients' dissatisfaction. DATA SOURCES: Data were sought from the 30 randomised controlled trials identified after a comprehensive search of the Cochrane Library, Medline, Embase, and CINAHL databases, reference lists, and contact with experts. Raw data were available from 2814 women randomised into 17 trials (seven trials including 1359 women for first v second generation endometrial destruction; six trials including 1042 women for hysterectomy v first generation endometrial destruction; one trial including 236 women for hysterectomy v Mirena; three trials including 177 women for second generation endometrial destruction v Mirena). Eligibility criteria for selecting studies Randomised controlled trials comparing hysterectomy, first and second generation endometrial destruction, and Mirena for women with heavy menstrual bleeding unresponsive to other medical treatment. RESULTS: At around 12 months, more women were dissatisfied with outcome with first generation hysteroscopic techniques than with hysterectomy (13% v 5%; odds ratio 2.46, 95% confidence interval 1.54 to 3.9, P<0.001), but hospital stay (weighted mean difference 3.0 days, 2.9 to 3.1 days, P<0.001) and time to resumption of normal activities (5.2 days, 4.7 to 5.7 days, P<0.001) were longer for hysterectomy. Unsatisfactory outcomes were comparable with first and second generation techniques (odds ratio 1.2, 0.9 to 1.6, P=0.2), although second generation techniques were quicker (weighted mean difference 14.5 minutes, 13.7 to 15.3 minutes, P<0.001) and women recovered sooner (0.48 days, 0.20 to 0.75 days, P<0.001), with fewer procedural complications. Indirect comparison suggested more unsatisfactory outcomes with second generation techniques than with hysterectomy (11% v 5%; odds ratio 2.3, 1.3 to 4.2, P=0.006). Similar estimates were seen when Mirena was indirectly compared with hysterectomy (17% v 5%; odds ratio 2.2, 0.9 to 5.3, P=0.07), although this comparison lacked power because of the limited amount of data available for analysis. CONCLUSIONS: More women are dissatisfied after endometrial destruction than after hysterectomy. Dissatisfaction rates are low after all treatments, and hysterectomy is associated with increased length of stay in hospital and a longer recovery period. Definitive evidence on effectiveness of Mirena compared with more invasive procedures is lacking.

The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up.

BACKGROUND: This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. METHODS: In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. RESULTS: Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. CONCLUSIONS: Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.

Endometrial laser intrauterine thermotherapy for the treatment of dysfunctional uterine bleeding: the first British experience.

Forty patients due to undergo endometrial ablation as a treatment for dysfunctional uterine bleeding were recruited to assess the efficacy and safety of endometrial laser intrauterine thermo-therapy using the gynelase. At 12 months the average menstrual score reduction was 88%, the amenorrhoea rate was 70%, and the hypomenorrhoea rate 16%. Four women (10%) have had a hysterectomy for persistent menorrhagia, and one (3%) for pelvic pain. One patient (3%) has had a further endometrial laser ablation. There were no major complications. and 34 patients (85%) were most satisfied with the treatment. The system is easy to use and has a short learning curve.

Intraperitoneal gas drain to reduce pain after laparoscopy: randomized masked trial.

OBJECTIVE: To determine whether a drain placed in the peritoneal cavity during laparoscopy is both a clinical and cost-effective method of reducing postoperative pain. METHODS: Two hundred twenty-five women undergoing diagnostic or minor operative laparoscopic procedures were recruited. Women were assigned to receive either an intraperitoneal gas drain or a dummy drain during surgery. Sample size to detect a two-point difference in visual analogue score was estimated at 158 subjects, with 79 in each arm. The patients and nursing staff were unaware of the position of the drain. A visual analogue score was used to assess pain preoperatively and at 4, 24, and 48 hours postoperatively. Data on the experience of nausea, frequency of vomiting, and site of pain were collected. The analgesic and antiemetic use was recorded. An economic evaluation of the analgesic use and the material costs for the two groups was performed. RESULTS: One hundred sixty-one complete sets of data (72%) were available for analysis. The two groups were well matched for age, parity, previous surgery, body mass index, volume of carbon dioxide used, and operative time. No significant differences were found between the two groups with regard to the overall pain scores preoperatively (8 versus 7) or at 4 (30 versus 34), 24 (40 versus 44), and 48 (26 versus 26) hours postoperatively, after adjusting for multiple point testing. On assessment at different sites, the dummy drain group experienced shoulder pain more frequently at 4 (19 of 79 versus 10 of 82, P =.05) and 48 (16 of 79 versus 7 of 82, P =.03) hours postoperatively compared with the drain group. The placebo group had a 33% greater usage of oral analgesia after discharge, but this was $2.50 cheaper than the use of an intraperitoneal drain. No statistically significant differences were found between the groups with regard to nausea and vomiting postoperatively. CONCLUSION: An intraperitoneal drain after minor gynecologic laparoscopy decreases the frequency of shoulder pain and reduces postoperative analgesia requirements. However, it is less cost-effective to reduce pain using an intraperitoneal gas drain than simple oral analgesia after minor gynecologic laparoscopy.

Modern approaches to management of menorrhagia.

Menorrhagia and its management is a common problem in both the primary health-care setting and in hospitals. There is an increasing number of options for management of menorrhagia and these will be discussed in this article.

The effect of endometriosis and its radical laparoscopic excision on quality of life indicators.

OBJECTIVE: To assess the effect of endometriosis and radical laparoscopic excision on the quality of life of women with this condition. DESIGN: A prospective study. SETTING: The Northern Endometriosis Centre at South Cleveland Hospital, Middlesbrough and St. James's University Hospital, Leeds. POPULATION: Fifty-seven consecutive patients undergoing laparoscopic excision of invasive endometriosis. METHODS: Questionnaires, both pre-operatively and four-month post-operatively, for a number of different symptoms associated with endometriosis were completed by patients. Details of fertility, previous treatments and quality of life as measured by SF12 and EuroQOL (EQ-5D) and sexual activity questionnaire, as well as linear pain scores for several symptoms, were recorded. Details of intra-operative findings was also collected. MAIN OUTCOME MEASURES: Effect of laparoscopic excision on pain scores and quality of life, operative findings, type of surgery, length of surgery and incidence of intra- and post-operative complications. RESULTS: Patients with endometriosis were severely ill with significant pain and impairment of quality of life and sexual activity. Four months after radical laparoscopic excision for deep endometriosis there was significant improvement in all the parameters measured including their quality of life based on EuroQOL evaluation: EQ-5D (0 x 595:0 x 729, P = 0 x 002) and EQ thermometer (68 x 9:77 x 7, P = 0 x 008); SF12 physical score (44 x 8:51 x 9, P = 0 x 015); sexual activity (habit P = 0 x 002, pleasure P = 0 x 002 and discomfort P < or = 0 x 001). Only the mental health score of SF12 failed to show any statistical improvement (47 x 1:48 x 4, P = 0 x 84). Symptomatically, there was a significant reduction in dysmenorrhoea (median 8 x 0:4 x 0, P < or = 0 x 001), pelvic pain (median 7 x 0:2 x 0, P < or = 0 x 001), dyspareunia (median 6 x 0:0 x 0, P < 0 x 001) and rectal pain scores (median 4 x 0:0 x 0, P < 0 x 001). Complications were noted, but were deemed to be acceptable for the extent of the surgery. CONCLUSIONS: This is an early analysis of the first 57 cases studied, but structured evaluation suggests that meaningful improvements in clinical symptoms and quality of life can be obtained with this approach with acceptable levels of operative morbidity. Further follow up of this series is required, but early evidence would suggest that the technique should be further evaluated as part of a randomised trial.

Cavaterm thermal balloon ablation for the treatment of menorrhagia.

Fifty patients due to undergo endometrial ablation as a treatment of dysfunctional uterine bleeding were recruited to assess the efficacy and safety of a new thermal balloon ablation system (Cavaterm). The patients were followed up for a mean of 14 months (range 6-24): 34 (68%) have complete amenorrhoea, 12 (24%) only have spotting, two (4%) are eumenorrhoeic, and two (4%) have had failed treatments. There were no major complications, but two patients have required oral antibiotics for suspected endometritis. Although these preliminary results are encouraging, all patients remain under review to determine long term effect of the procedure. Further evaluation is also underway in the form of a randomised trial against endometrial laser ablation.

Laparoscopic-assisted Doderlein hysterectomy: retrospective analysis of 300 consecutive cases.

OBJECTIVE: To assess the clinical outcomes of the Doderlein laparoscopic-assisted hysterectomy. DESIGN: A retrospective study. SETTING: Women's Endoscopic Laser Foundation at South Cleveland Hospital, Middlesbrough and St James's University Hospital, Leeds. POPULATION: Three hundred consecutive women who had a laparoscopic-assisted Doderlein hysterectomy. METHODS: Patients were identified from the laparoscopic hysterectomy theatre log at both sites. Case notes were requested and examined. MAIN OUTCOME MEASURES: Operative time, uterine weight, associated pelvic pathology, blood loss, hospital stay, intra-operative and post-operative complications. RESULTS: The operations were performed by eight different surgeons, seven of whom were laparoscopic trainees. The mean operating time was 102 minutes (SD 30). Additional surgery including unilateral or bilateral salpingo-oophorectomy, was carried out in 247 patients (82%). The mean uterine weight was 140 g (SD 74). One hundred and thirty-two women (44%) had a normal pelvis at hysterectomy. The mean drop in haemoglobin and haematocrit was 1.46 g (SD 0.95) and 4.4% (SD 2.8), respectively. The overall complication rate was 18%, of which 6.2% were classed as major. The major complications included four cystotomies, five unscheduled laparotomies, seven post-operative blood transfusions, one pulmonary embolus and two re-operations (within six weeks). The mean hospital stay was three days. CONCLUSIONS: Laparoscopic-assisted Doderlein hysterectomy is an alternative to standard laparoscopic hysterectomy techniques. It has the advantage of being easy to learn and is associated with low complication rates, compared with other laparoscopic and traditional techniques for hysterectomy.

Laparoscopic hysterectomy.

The first laparoscopic hysterectomy using only laparoscopic techniques was performed around 10 years ago by Harry Reich. Such total laparoscopic hysterectomy (TLH) approach is surgically elegant but technically difficult. A number of alternative laparoscopic techniques to perform all or some of the hysterectomy have since been introduced to simplify the surgical technique but retain the major advantages of the approach, which is to avoid the use of a large laparotomy wound. The advantages of this approach have been well documented, but so far the laparoscopic route has been little used by the general gynecologic surgical community. Although it has been possible in some units to reduce the laparotomy rate for hysterectomy to 10%, there is evidence from the United Kingdom and the United States that still more than 70% of all hysterectomies are still being performed by the laparotomy approach. This chapter seeks to explain why this should be so and how appropriate training and acquisition of the necessary skills in operative laparoscopy and vaginal surgery can be achieved to ensure that all patients who may benefit by avoiding a laparotomy incision are given the opportunity to do so.

Recurrent pain after hysterectomy and bilateral salpingo-oophorectomy for endometriosis: evaluation of laparoscopic excision of residual endometriosis.

Endometriosis can represent with a variety of symptoms including pelvic pain, dyspareunia and pain with defaecation, up to several years after hysterectomy and bilateral salpingo-oophorectomy. This may occur when all endometriotic tissue is not excised at the time of the initial procedure. Although excision of endometriosis at this time would be preferable, we have found laparoscopic excision of residual endometriosis to be effective in relieving endometriosis associated pain.

The validity of continuous automated fluid monitoring during endometrial surgery: luxury or necessity?

Thirty-four consecutive women undergoing endometrial laser ablation, as a treatment of menorrhagia, were recruited to assess the validity of fluid absorption monitoring by a new continuous automated system (AquaSens). The same group of women also had monitoring of fluid absorption carried out by our standard technique of weighing. The intra-class correlation coefficient for the fluid deficit estimated by AquaSens compared to our standard technique of manually weighing the irrigation bags was 0.98 (95% CI 0.96-0.99). Aquasens therefore provides a valid and non-invasive method of continuously monitoring fluid deficit amongst patients undergoing operative hysteroscopy procedures, thereby reducing the risk of unexpected fluid absorption and its potentially fatal sequelae.

Second trimester serum free beta human chorionic gonadotrophin levels as a predictor of pre-eclampsia.

BACKGROUND: To prospectively assess maternal serum free beta human chorionic gonadotrophin (beta hCG) estimation between 15 and 18 weeks gestation, as a screening test for pre-eclampsia in primigravid women. METHODS: A prospective longitudinal study in a University Teaching Hospital. The study population was 430 primigravid women, who had maternal serum free beta hCG levels measured as part of antenatal serum screening for Down's Syndrome in the second trimester, who booked consecutively within the unit and went on to deliver on the unit's labor ward. These women were followed during their subsequent pregnancy and categorized into those who remained normotensive and those who developed pre-eclampsia on both clinical and biochemical grounds. The beta hCG levels were used to construct a receiver operator characteristics curve (ROC) to assess the screening potential for pre-eclampsia. RESULTS: Nineteen (4.4%) women in the study group developed pre-eclampsia. The median second trimester free beta hCG multiples of the median (MOM) was significantly elevated compared to that of the control group (1.52 vs 1.10, p=0.03). The ROC curve shows that for a sensitivity of 79%, the specificity was only 54%. CONCLUSIONS: Maternal serum free beta hCG alone measured in the second trimester is not clinically useful as a screening test for pre-eclampsia in primigravid women. It has, however, some predictive value.

Fetal growth retardation and second trimester maternal serum human chorionic gonadotrophin levels.

Second trimester maternal serum human chorionic gonadotrophin (hCG) levels in women who remained normotensive but delivered an unexplained growth retarded infant were compared with those from a control group and a group of women who developed pre-eclampsia in a retrospective observational study. Our hypothesis was that the similar placental pathological changes shared by unexplained normotensive IUGR and pre-eclampsia would be reflected by elevated maternal serum hCG levels in the second trimester. Normotensive women delivering unexplained singleton growth retarded infants were identified (n=43) and their second trimester hCG levels, taken as part of antenatal screening for Down's syndrome, were obtained. These were compared with a control group of 625 women, and a group of 48 women who subsequently developed pre-eclampsia. There was no significant difference in the hCG levels expressed as multiples of the median (MOM) between the women who delivered growth retarded fetuses (median MOM 0.96) and the control group (median MOM 0.97). The levels of hCG in the women who subsequently developed pre-eclampsia were significantly higher (median MOM 1.3, P=0.008). There were no significant differences in AFP levels in the three groups; however, the trend was towards a higher level of AFP in the fetal growth retardation group. Maternal serum hCG in the second trimester does not appear to be elevated in normotensive women who later produce a growth retarded fetus, although human chorionic gonadotrophin levels are significantly higher in women who subsequently develop pre-eclampsia.