Risk of Hysterectomy After Endometrial Ablation: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the risk of hysterectomy after nonresectoscopic endometrial ablation in patients with heavy menstrual bleeding. DATA SOURCES: The EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane databases were searched for eligible articles from inception until June 13, 2022. We used combinations of search terms for endometrial ablation and hysterectomy. METHODS OF STUDY SELECTION: Articles included in the review described the incidence of hysterectomy at a specific point in time after ablation with a minimum follow-up duration of 12 months. TABULATION, INTEGRATION, AND RESULTS: The literature search yielded a total of 3,022 hits. A total of 53 studies met our inclusion and exclusion criteria, including six retrospective studies, 24 randomized controlled trials, and 23 prospective studies. A total of 48,071 patients underwent endometrial ablation between 1992 and 2017. Follow-up duration varied between 12 and 120 months. Analyses per follow-up moment showed 4.3% hysterectomy rate at 12 months of follow-up (n=29 studies), 11.1% at 18 months (n=1 study), 8.0% at 24 months (n=11 studies), 10.2% at 36 months (n=12 studies), 7.6% at 48 months (n=2 studies), and 12.4% at 60 months (n=6 studies). Two studies reported a mean hysterectomy rate at 10 years after ablation of 21.3%. Minimal clinically relevant differences in hysterectomy rates were observed among the different study designs. Furthermore, we found no significant differences in hysterectomy rate among the different nonresectoscopic endometrial ablation devices. CONCLUSION: The risk of hysterectomy after endometrial ablation seems to increase from 4.3% after 1 year to 12.4% after 5 years. Clinicians can use the results of this review to counsel patients about the 12% risk of hysterectomy 5 years after endometrial ablation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020156281.

Endometrial ablation plus levonorgestrel releasing intrauterine system versus endometrial ablation alone in women with heavy menstrual bleeding: study protocol of a multicentre randomised controlled trial; MIRA2 trial.

BACKGROUND: It is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation. In these ways, insertion of an LNG-IUS immediately after endometrial ablation might prevent subsequent hysterectomies because of persisting uterine bleeding and cyclical pelvic pain or pain that arises de novo. Hence, we evaluate if the combination of endometrial ablation and an LNG-IUS is superior to endometrial ablation alone in terms of reducing subsequent rates of hysterectomy at two years following the initial ablative procedure. METHODS/DESIGN: We perform a multicentre randomised controlled trial in 35 hospitals in the Netherlands. Women with heavy menstrual bleeding, who opt for treatment with endometrial ablation and without contraindication for an LNG-IUS are eligible. After informed consent, participants are randomly allocated to either endometrial ablation plus LNG-IUS or endometrial ablation alone. The primary outcome is the hysterectomy rate at 24 months following endometrial ablation. Secondary outcomes include women's satisfaction, reinterventions, complications, side effects, menstrual bleeding patterns, quality of life, societal costs. DISCUSSION: The results of this study will help clinicians inform women with HMB who opt for treatment with endometrial ablation about whether concomitant use of the LNG-IUS is beneficial for reducing the need for hysterectomy due to ongoing bleeding and/or pain symptoms. Trial registration Dutch Trial registration: NL7817. Registered 20 June 2019, https://www.trialregister.nl/trial/7817 .

The combined use of endometrial ablation or resection and levonorgestrel-releasing intrauterine system in women with heavy menstrual bleeding: A systematic review.

INTRODUCTION: Despite endometrial ablation/resection being a very successful treatment for women with heavy menstrual bleeding, re-intervention with additional surgery is needed in 12%-25% of cases. Introducing a levonorgestrel-intrauterine system (LNG-IUS) immediately after ablation could preserve the integrity of the uterine cavity and suppress the regenerated or non-ablated endometrial tissue. Therefore, this combined treatment can perhaps lower the re-intervention rate. The aim of this systematic review was to assess the impact of the combined treatment. MATERIAL AND METHODS: The MEDLINE, EMBASE, and Cochrane library were systematically searched. No language restrictions were applied. All types of studies were included reporting on the results of endometrial ablation or resection combined with immediate insertion of LNG-IUS for treatment of heavy menstrual bleeding. The primary outcome was the number of hysterectomies after the ablation procedure. Secondary outcomes included re-intervention rates, removals of LNG-IUS, bleeding pattern, patient satisfaction, adverse effects, and complications. Our protocol was registered in PROSPERO, an international prospective register of systematic reviews under registration number CRD42020151384. RESULTS: Six studies with a retrospective design and one case series with a follow-up duration varying from 6 to 55 months were included. In total, 427 women were treated with the combined treatment. The studies described a lower hysterectomy and re-intervention rate after combined treatment compared with treatment with endometrial ablation/resection alone. Hysterectomy rate varied from 0% to 11% after combined treatment compared with 9.4% to 24% after endometrial ablation/resection alone. Bleeding patterns and patient satisfaction appeared to be in favor of the combined treatment group. No intra- or post-operative complications or complications in the removal of LNG-IUS were described. The most reported adverse effects after combined treatment were weight gain, mood changes, and headaches. An additional 11 studies with only an abstract available substantiated these findings. All the included studies had poor methodological quality. CONCLUSIONS: Based on the available literature, inserting an LNG-IUS immediately after endometrial ablation/resection seems to lower the hysterectomy and re-intervention rates compared with ablation/resection alone. However, as only limited observational studies of low methodological quality are available, high-quality research is necessary to confirm the findings of this systematic review.

Predictive factors for failure of the levonorgestrel releasing intrauterine system in women with heavy menstrual bleeding.

BACKGROUND: This study was conducted to identify factors that are associated with failure of treatment using the levonorgestrel releasing intrauterine system (LNG-IUS) in women with heavy menstrual bleeding. METHODS: For this study, data of a cohort of women treated with an LNG-IUS was used. Women who suffered from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future child wish, were recruited in hospitals and general practices in the Netherlands. Eight potential prognostic baseline variables (age, body mass index, caesarean section, vaginal delivery, previous treatment, anticoagulant use, dysmenorrhea, and pictorial blood assessment score) were analyzed using univariable and multivariable regression models to estimate the risk of failure. The main outcome measure was discontinuation of the LNG-IUS within 24 months of follow up, defined as removal of the LNG-IUS or receiving an additional intervention. RESULTS: A total of 209 women received the LNG-IUS, 201 women were included in the analyses. 93 women (46%) discontinued LNG-IUS treatment within 24 months. Multivariable analysis showed younger age (age below 45) (adjusted RR 1.51, 95% CI 1.10-2.09, p = .012) and severe dysmenorrhea (adjusted RR 1.36, 95% CI 1.01-1.82, p = .041) to be associated with a higher risk of discontinuation. CONCLUSIONS: High discontinuation rates are found in women who receive an LNG-IUS to treat heavy menstrual bleeding. A younger age and severe dysmenorrhea are found to be risk factors for discontinuation of LNG-IUS treatment. These results are relevant for counselling women with heavy menstrual bleeding.

Treatment of women with heavy menstrual bleeding: Results of a prospective cohort study alongside a randomised controlled trial.

OBJECTIVE: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT. STUDY DESIGN: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands. Women suffering from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future fertility desire, were eligible for this trial. Women who declined randomisation were asked to participate in the observational cohort. The outcome measure was reintervention rate at 24 months of follow-up. RESULTS: 276 women were followed in the observational cohort of which 87 women preferred an initial treatment with LNG-IUS and 189 women preferred an initial treatment with endometrial ablation. At 24 months of follow-up women in the LNG-IUS-group were more likely to receive a reintervention compared to the women in the ablation group, 28/81 (35 %) versus 25/178 (14 %) (aRR 2.42, CI 1.47-3.98, p-value 0.001). No differences in reintervention rates were found between women in the observational cohort and women in the RCT. CONCLUSIONS: Women who receive an LNG-IUS are more likely to undergo an additional intervention compared to women who receive endometrial ablation. Reintervention rates of women in the cohort and RCT population were comparable. The results of this study endorse the findings of the RCT and will contribute to shared decision making in women with heavy menstrual bleeding.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. OBJECTIVE: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. STUDY DESIGN: This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. RESULTS: We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. CONCLUSION: Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared with women who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

Prognostic Factors for the Failure of Endometrial Ablation: A Systematic Review and Meta-analysis.

OBJECTIVE: To provide an overview of prognostic factors predicting failure of second-generation endometrial ablation. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched from 1988 until February 2019. The search was conducted without language restrictions using the following search terms: "endometrial ablation," "prognosis," "predict," "long term," "late onset," "outcome." METHODS OF STUDY SELECTION: The literature search provided a total of 990 studies. All types of studies reporting about prognostic factors of second-generation endometrial ablation failure were included. TABULATION, INTEGRATION, AND RESULTS: After screening for eligibility, 56 studies were included in this review, of which 21 were included in the meta-analysis. In these 56 studies, 157,830 women were included. We evaluated 10 prognostic factors: age, myomas, history of tubal ligation, body mass index, parity, preexisting dysmenorrhea, caesarean delivery, bleeding pattern, uterus position, and uterus length. Meta-analysis was performed for the primary outcome (surgical reintervention) to estimate summary treatment effects. Younger age (aged 35 years or younger, odds ratio [OR] 1.68, 95% CI 1.19-2.36; aged 40 years or younger, OR 1.58, 95% CI 1.30-1.93; aged 45 years or younger OR 1.63, 95% CI 1.28-2.07), prior tubal ligation (OR 1.46, 95% CI 1.23-1.73), and preexisting dysmenorrhea (OR 2.12, 95% CI 1.41-3.19) were associated with an increased risk of surgical reintervention. Studies investigating the prognostic factors myomas and obesity showed conflicting results. CONCLUSION: Younger age, prior tubal ligation and preexisting dysmenorrhea were found to be associated with failure of endometrial ablation. Obesity and the presence of large submucous myomas may be associated with failure, as well, though more research is necessary to estimate the influence of these factors. It is important to take the results of this review into account when counselling women with heavy menstrual bleeding. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019126247.

Women's preferences for the levonorgestrel intrauterine system versus endometrial ablation for heavy menstrual bleeding.

OBJECTIVES: Women's preferences for treatment of heavy menstrual bleeding (HMB) are important in clinical decision-making. Our aim was to investigate whether women with HMB have a preference for treatment characteristics of the levonorgestrel intrauterine system (LNG-IUS) or endometrial ablation and to assess the relative importance of these characteristics. STUDY DESIGN: A discrete choice experiment was performed in general practices and gynaecology outpatient clinics in the Netherlands. Women with HMB were asked to choose between hypothetical profiles containing characteristics of LNG-IUS or endometrial ablation. Characteristics included procedure performed by gynaecologist or general practitioner; reversibility of the procedure; probability of dysmenorrhea; probability of irregular bleeding; additional use of contraception; need to repeat the procedure after five years; and treatment containing hormones. Data were analysed using panel mixed logit models. The main outcome measures were the relative importance of the characteristics and willingness to make trade-offs. RESULTS: 165 women completed the questionnaire; 36 (22%) patients were recruited from general practices and 129 (78%) patients were recruited from gynaecology outpatient clinics. The characteristic found most important was whether a treatment contains hormones. Women preferred a treatment without hormones, a treatment with the least side effects, and no need for a repeat procedure or additional contraception. Women completing the questionnaire at the gynaecology outpatient clinic differed from women in primary care in their preference for a definitive treatment to be performed by a gynaecologist. CONCLUSIONS: Whether or not a treatment contains hormones was the most important characteristic influencing patient treatment choice for HMB. Participants preferred characteristics that were mostly related to endometrial ablation, but were willing to trade-off between characteristics.

Bipolar versus balloon endometrial ablation in the office: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of bipolar radiofrequency (Novasure®) ablation and balloon endometrial ablation (Thermablate®). STUDY DESIGN: We performed a multi-center double blind, randomized controlled trial in three hospitals in The Netherlands. Women with heavy menstrual bleeding were randomly allocated to bipolar or balloon endometrial ablation, performed in the office, using a paracervical block. The primary outcome was amenorrhea. Secondary outcome measures were pain, satisfaction, quality of life and reintervention. RESULTS: 104 women were randomized into the bipolar (52) and balloon (52) groups. After 12 months amenorrhea rates were 56% (29/52) in the bipolar group and 23% (12/52) in the balloon group (relative risk (RR) 0.6, 95% confidence interval (CI) 0.4-0.8). The mean visual analog pain score of the total procedure was 7.1 in the bipolar group and 7.4 in the balloon group (P<.577). 87% (45/52) of the patients in the bipolar group were satisfied with the result of the treatment versus 69% (36/52) in the balloon group (RR 0.44, 95% CI 0.2-0.97). The reintervention rates were 5/52 (10%) in the bipolar group and 6/52 (12%) in the balloon group (RR 1.02, 95% CI 0.9-1.2). Quality of life (Shaw score) improved over time (P<.001) and was significantly higher in the bipolar group at 12 months follow-up (P=.025). CONCLUSION: In the treatment of heavy menstrual bleeding, bipolar radiofrequency endometrial ablation is superior to balloon endometrial ablation as an office procedure in amenorrhea rate, patient satisfaction and quality of life.

Diagnosis of heavy menstrual bleeding.

Heavy menstrual bleeding (HMB) is an important health problem. This paper gives an overview of the diagnosis of HMB. For each woman, a thorough history should be taken as one should ascertain whether there are underlying factors that could cause complaints of HMB. Objectively knowing whether or not the blood loss is excessive could also be very beneficial. The pictorial blood assessment chart score can help with diagnosis. Physical examination starts with standard gynecological examination. Imaging tests are widely used in the work-up for women with HMB. The first step in imaging tests should be the transvaginal ultrasound. Other diagnostic tests should only be performed when indicated.

Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial.

BACKGROUND: Heavy menstrual bleeding is an important health problem. Two frequently used therapies are the levonorgestrel intra-uterine system (LNG-IUS) and endometrial ablation. The LNG-IUS can be applied easily by the general practitioner, which saves costs, but has considerable failure rates. As an alternative, endometrial ablation is also very effective, but this treatment has to be performed by a gynaecologist. Due to lack of direct comparison of LNG-IUS with endometrial ablation, there is no evidence based preferred advice for the use of one of these treatment possibilities. METHOD/DESIGN: A multicenter randomised controlled trial, organised in a network infrastructure in the Netherlands in which general practitioners and gynaecologists collaborate. DISCUSSON: This study, considering both effectiveness and cost effectiveness of LNG-IUS versus endometrial ablation may well improve care for women with heavy menstrual bleeding. TRIAL REGISTRATION: Dutch trial register, number NTR2984.

Factors attributing to the failure of endometrial sampling in women with postmenopausal bleeding.

OBJECTIVE: To determine which doctor- and patient-related factors affect failure of outpatient endometrial sampling in women with postmenopausal bleeding, and to develop a multivariable prediction model to select women with a high probability of failed sampling. DESIGN: Prospective multicenter cohort study. SETTING: Three teaching hospitals in the Netherlands. POPULATION: Women presenting with postmenopausal bleeding with an indication for endometrial sampling. METHODS: Multivariable logistic regression was performed to evaluate the impact of doctor's training level and patient's characteristics on failure of sampling. MAIN OUTCOME MEASURES: Failure of endometrial sampling, classified as technical failure or insufficient tissue for diagnosis. RESULTS: In 74 (20.8%) of the 356 included women, sampling technically failed, and in 84 (29.8%) the amount of tissue was insufficient for diagnosis. Nulliparity [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.8-7.9] and advanced age (OR 1.03 per year, 95% CI 1.00-1.06) were associated with technical failure. Advanced age was associated with insufficient sampling (OR 1.04 per year, 95% CI 1.01-1.07), and endometrial thickness >12 mm decreased the chance of insufficient sampling (OR 0.3, 95%CI 0.1-0.8). The prediction model for total failure had an area under the ROC curve of 0.64 (95% CI 0.58-0.70). CONCLUSIONS: In women with postmenopausal bleeding, the failure rate of endometrial sampling is relatively high and is associated with nulliparity and advanced age. Endometrial thickness >12 mm decreased the chance of failure. A multivariable prediction model for total failure based on patient characteristics has a moderate capacity to discriminate between women at high or low risk of failure.

Five-year follow-up after comparing bipolar endometrial ablation with hydrothermablation for menorrhagia.

OBJECTIVE: To evaluate the results of a previous study comparing bipolar radiofrequency endometrial ablation with hydrothermablation for the treatment of menorrhagia at 5-year follow-up. METHOD: A double-blind, randomized, controlled trial was performed in a large teaching hospital in the Netherlands between March 2005 and August 2007. One-hundred sixty women with menorrhagia were randomly allocated to bipolar ablation or hydrothermablation. The results of follow-up at 12 months were previously reported. At 4-5 years of follow-up, a questionnaire was sent to all the participants to register amenorrhea rates, reinterventions, and patient satisfaction. RESULTS: At 5-year follow-up, response rates were 90% and 83% in the bipolar group and hydrotherm group, respectively. Amenorrhea rates were 55.4% and 35.3% in the bipolar group and the hydrotherm group, respectively (relative risk [RR] 1.5, 95% confidence interval [CI] 1.05-2.3). The number of surgical reinterventions was 11 compared with 23 (RR 0.43, 95% CI 0.23-0.80). Overall, more women were satisfied in the bipolar group compared with the hydrotherm group. CONCLUSION: After treatment, bipolar radiofrequency endometrial ablation system is more effective at 5 years than hydrothermablation in the treatment of menorrhagia. LEVEL OF EVIDENCE: II.