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Bhattacharya S, Middleton LJ, Tsourapas A, et al. ; the International Heavy Menstrual Bleeding Individual Patient Data Meta-analysis Collaborative Group Hysterectomy, Endometrial Ablation and Mirena® for Heavy Menstrual Bleeding: A Systematic Review of Clinical Effectiveness and Cost-Effectiveness Analysis. Southampton (UK): NIHR Journals Library; 2011 Apr. (Health Technology Assessment, No. 15.19.)


Heavy menstrual bleeding (HMB) is a common problem1 which affects approximately 1.5 million women in England and Wales.2 The condition causes 1 in 20 women of reproductive age to consult their general practitioners (GPs) and accounts for 20% of gynaecology outpatient referrals. HMB can cause significant distress to women by affecting their performance at work as well as their social activities, and leads to a measurable reduction in quality of life (QoL).3 Surgery has been traditionally used as the definitive treatment of HMB such that, in the past, by the age of 55 years one in five women in the UK had a hysterectomy,4 over half of which were for HMB.5

Definition of heavy menstrual bleeding

Although objectively defined as the loss of > 80 ml of blood per cycle,6 such measurement is impractical in most clinical settings. Between 35% and 60% of women who present with a subjective complaint of HMB have been shown to have normal levels of blood loss.7,8 Conversely, many women with objectively demonstrable high blood loss do not seek help for associated symptoms.9

Of various methods used to measure menstrual blood loss, the alkaline haematin technique has been considered to be the gold standard.10 Despite the introduction of modifications in an effort to simplify it,11 this method remains laborious and involves extraction of haemoglobin from used sanitary wear. As such, it is unsuitable for regular clinical use.

A more practical method of assessing menstrual blood loss is the pictorial blood loss assessment chart (PBAC).12 This takes into account the number of items of sanitary wear used and the degree of staining, which are in turn converted into a score. This technique is now more widely used than the alkaline haematin method although the correlation between actual measured blood loss and the PBAC score has been questioned.13 Another indirect method for estimating menstrual blood loss is the ‘menstrual pictogram’,14 which is similar to the PBAC but additionally requires women to comment on the absorbency of the towel or tampon and any extraneous blood loss.

From a clinical perspective, HMB is defined as excessive menstrual blood loss which interferes with a woman's physical, emotional, social and material QoL, and which can occur alone or in combination with other symptoms.15

Causes of heavy menstrual bleeding

Possible causes of HMB are shown in Table 1. In most cases a definite cause is not found and the condition is labelled as dysfunctional uterine bleeding (DUB).17

TABLE 1. Causes of HMB (from Garside et al.).


Causes of HMB (from Garside et al.).

Estimating the severity of heavy menstrual bleeding

Subjective estimates of menstrual blood loss do not correlate well with objective measures,13,18 and over half of women who have surgery for HMB do not experience a blood loss of 80 ml or more in each cycle.8 Women's expectations of normal menstrual loss can shape their perception of the gravity of their condition, inform their demand for treatment and influence their judgement about treatment success.

The presence of other menstrual symptoms may also have an impact on perceptions of bleeding and account for some of the differences between objective and subjective estimates of menorrhagia. Thus, many women presenting with HMB describe other additional symptoms such as painful periods while associated symptoms are more likely to encourage a diagnosis of HMB by clinicians. The impact of HMB is conventionally measured by means of a number of QoL measures. A systematic review of QoL measures in HMB described 15 generic and two condition-specific scales19 and suggested that there was scope for better ways of assessing the severity of the condition and its impact on women's lives.

Generic scales allow comparison between different clinical conditions in terms of their impact on QoL and may provide a single score or scores across dimensions of QoL, but are relatively insensitive to specifics of a particular condition. Generic measures of QoL used in HMB include the Short Form questionnaire-36 items (SF-36), Nottingham Health Profile, health-status structured history and single global item.16 SF-36 is generally a well-validated measure used to assess health-related QoL19 and includes items on global health perception, physical function, social function, role (physical and mental), pain, mental health and energy/vitality.20 The SF-36 has been considered to be a feasible way of assessing QoL in women with HMB, but it has some limitations in this setting21 as some questions can be inappropriate for these women. In addition, internal reliability, as assessed by Cronbach's statistic, has been shown to be lower in women with HMB, especially for general health perception and mental health scales.

Clark et al.19 have also reported on the use of generic measures that address particular aspects of QoL such as physical (Modified Townsend Score), mental (General Health Questionnaire) and sexual health (Revised Sabbatsberg Sexual Rating Scale) and social function (Lifestyle Index) in studies of women with HMB bleeding.

Condition-specific scales have the advantage of incorporating attributes of QoL that are specifically affected by the condition of interest. They may therefore be more sensitive to small but important changes and may be considered to have greater face validity (that is, they include items that are of importance to sufferers and reflect their experience and concerns). Two condition-specific outcome measures have been developed for women with HMB. These include the Menorrhagia Outcomes Questionnaire22 and the Multi-attribute Questionnaire.23 The Menorrhagia Outcomes Questionnaire includes items on symptoms and satisfaction with care, physical function, psychological and social well-being, global judgement of health and QoL, and personal constructs. The Multi-attribute Questionnaire includes items on practical difficulties, social function, psychological function, physical health, interruption to work and family life.

Preference-based measures elicit preferences for a given health state and, if appropriately scaled, provide weights that can be used in cost–utility analyses.

The EQ-5D™ (European Quality of Life-5 Dimensions; Euro Qol Group, Rotterdam, the Netherlands), which has been used in studies as a measure of QoL in HMB, includes a multi-attribute scale, with dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and a global rating scale for QoL (visual analogue scale).

Measuring patient satisfaction

Patient satisfaction is widely used as a primary outcome measure in studies of treatments for HMB.24 Satisfaction is a subjective and relative concept and represents the extent to which a service meets users' expectations. It is not clear whether satisfaction can be measured on a continuum, from dissatisfied through to satisfied, or whether factors resulting in satisfaction are different from those leading to dissatisfaction.16 Satisfaction is influenced by patient characteristics24 such as age and health status.

The extent to which these potential biases are addressed in the patient satisfaction measures used in studies of HMB is difficult to assess in the absence of detailed accounts of the development and validation of the measures used. While the use of a similar tool to measure subjective satisfaction for women in both arms of an RCT may provide a comparative measure between these groups, it may remain unclear exactly what is being measured for the reasons outlined above.16 In addition, the range of techniques and scales used to elicit a measure of satisfaction across studies can limit any attempts to aggregate data by means of meta-analysis.

Current service provision

Treatment for HMB aims to improve women's quality of life through reducing menstrual loss. The current National Institute for Health and Clinical Excellence (NICE) guideline advocates full gynaecological examination followed by appropriate tests such as a full blood count and recognises the need for endometrial biopsy, ultrasound scan and hysteroscopy in specific cases.15

Medical therapy

According to the recent NICE guideline on HMB,15 medical treatment should be considered where structural and histological abnormalities of the uterus have been excluded or for fibroids < 3 cm in diameter which do not appear to distort the cavity of the uterus. In addition, the contraceptive needs of the woman should be taken into consideration. In addition to being licensed as a contraceptive device, the levonorgestrel-releasing intrauterine system (LNG IUS or Mirena®, Bayer Healthcare Pharmaceuticals, Pittsburg, PA, USA) is an effective non-surgical treatment for HMB which is reversible and fertility sparing. The device, which has to be fitted by a qualified practitioner, has a T-shaped plastic frame and a rate-limiting membrane on the vertical stem which releases a daily dose of 20 μg of LNG. The effects of the LNG IUS are local and hormonal, including prevention of endometrial proliferation, thickening of cervical mucous and suppression of ovulation in a minority of women. It reduces estimated menstrual blood loss by up to 96% by 12 months, with up to 44% of users reporting amenorrhoea,25,26 at a cost which is a third of that for hysterectomy.27 It has been recommended that LNG IUS should be considered before oral medication such as tranexamic acid, non-steroidal anti-inflammatory drugs (NSAIDs) or combined oral contraceptives.15 Mirena can lead to troublesome spotting in some women, causing early discontinuation of the device. There are relatively few randomised trials comparing the relative effectiveness of LNG IUS with that of hysterectomy, as well as endometrial ablation (EA), or long-term follow-up data on Mirena use.

Surgical treatment

Despite the availability of a number of medical options, long-term medical treatment is unsuccessful or unacceptable in many cases and surgical alternatives such as EA techniques and hysterectomy may be required.28 In a randomised controlled trial (RCT) of medical management versus transcervical resection of the endometrium (TCRE) in secondary care, total satisfaction with treatment was higher in women who were treated surgically (39% vs 61%; p = 0.01).28 The current NICE guideline on HMB suggests that EA may be offered to women who do not desire future fertility and in whom bleeding is considered to have a major impact on QoL. The guideline development group felt that ablative surgery could be offered as the initial surgical treatment for HMB after full discussion about the risks and benefits of other options.15

Incidence of surgical operations for heavy menstrual bleeding

Of 51,858 hysterectomies in the public sector in England in 1999–2000, it is likely that half were for HMB.29 Between 1999–2000 and 2004–5, 6500 fewer hysterectomies were performed.30 In contrast there were 826 hysteroscopic EAs in England in 1989, rising to 7173 in 1992–3, before falling to 3847 in 1997–8. In 2004–5, 9701 EAs were performed, of which over half (5457) used second-generation (non-hysteroscopic directed) methods.30 With just 7179 hysterectomies performed for HMB over this period, the predominant operation for HMB was now ablation. The use of LNG IUS has increased concurrently, although the widespread use of this device for contraception as well as for the control of HMB across a number of clinical settings (primary care, sexual reproductive health as well as gynaecology clinics in secondary care) makes it difficult to gather accurate data on uptake rates.


Hysterectomy is defined as the surgical removal of the uterus. It offers a definitive treatment for menorrhagia and guarantees amenorrhoea, but is particularly invasive and carries risk of significant morbidity.31 Hysterectomy can be performed through a number of routes. In abdominal hysterectomy the uterus is approached through the anterior abdominal wall, while vaginal hysterectomy involves surgical removal of the uterus through the vagina. In laparoscopic hysterectomy surgery is accomplished without the need for a laparotomy. Laparoscopic hysterectomy includes three subtypes: (1) laparoscopically assisted vaginal hysterectomy; (2) laparoscopic hysterectomy; and (3) total laparoscopic hysterectomy. In addition, laparoscopically assisted supracervical hysterectomy involves removal of the body of the uterus while the cervix is retained.

Hysterectomy can also be categorised on the basis of the extent of the operation and organs removed. Removal of the uterus and cervix constitutes total hysterectomy, while excision of the body of the uterus while conserving the cervix is defined as subtotal hysterectomy. Removal of the uterus alone is conventionally known as simple hysterectomy, while additional removal of the fallopian tubes and ovaries or ovaries alone is referred to as salpingo-oophorectomy or oophorectomy, respectively. Oophorectomy is usually performed in the presence of ovarian pathology but can also be carried out prophylactically to avoid the risk of cancer. Removal of the ovaries in cases of HMB is incidental.15 Of 37,000 hysterectomies performed in the UK in 1994–5, two-thirds were abdominal (4% of these were subtotal hysterectomies) and 57% were accompanied by removal of tubes and ovaries.5

Hysterectomy is generally performed as an inpatient procedure. The need for general anaesthesia, prolonged hospital stay and delayed recovery makes it a potentially expensive treatment.32 Overall, 1 in 30 women suffers a major adverse event after hysterectomy, and the mortality rate is 0.4–1.1 per 1000 operations. Around 3% of women suffer from perioperative problems such as haemorrhage, trauma to other pelvic organs and anaesthetic problems. Immediate postoperative complications include sepsis, bleeding and venous thromboembolism. Adverse events following hysterectomy are summarised in Table 2. Although delayed complications including urinary incontinence, fatigue, pelvic pain, hot flushes and sexual problems have been reported,5,3335 satisfaction rates following hysterectomy are very high.31

TABLE 2. Complications following hysterectomy (from Garside et al.).


Complications following hysterectomy (from Garside et al.).

Endometrial ablation

Endometrial ablative techniques, which aim to destroy functionally active endometrium along with some underlying myometrium,36,37 offer a conservative surgical alternative to hysterectomy. The first-generation ablative techniques including endometrial laser ablation (ELA),38,39 TCRE40 and rollerball endometrial ablation (RBEA) were all endoscopic procedures. Although none guarantees amenorrhoea, their effectiveness (in comparison with hysterectomy) has been demonstrated in a number of RCTs.4146

National audits47,48 revealed that, although first-generation ablative techniques were less morbid than hysterectomy, they were associated with a number of complications, including uterine perforation, cervical laceration, false passage creation, haemorrhage, sepsis and bowel injury. In addition, fluid overload associated with the use of 1.5% urological glycine (non-ionic) irrigation fluid in TCRE and RBEA resulted in serious and occasionally fatal consequences due to hyponatraemia.49,50 Mortality from these techniques has been estimated at 0.26 per 1000.47,48

Second-generation ablative techniques represent simpler, quicker and potentially more efficient means of treating menorrhagia, which require less skill on the part of the operator. Examples of second-generation ablative techniques are fluid-filled thermal balloon EA (TBEA), radiofrequency (thermoregulated) balloon endometrial ablation, hydrothermal EA, 3D bipolar radiofrequency EA, microwave endometrial ablation (MEA), diode laser hyperthermy, cryoablation and photodynamic therapy. The most common techniques in the UK are TBEA (ThermaChoice®, Ethicon, Livingston, UK and Cavaterm™, Pnn Medical SA, Morges, Switzerland)5153 and MEA,54,55 while the NovaSure® (Hologic Inc., Bedford, MA, USA) device56 is becoming more widely used.

First-generation endometrial ablation techniques

Early methods of EA which require direct hysteroscopic visualisation of the endometrial cavity such as TCRE, RBEA and ELA are known as ‘first-generation’ ablation techniques.57 A national survey demonstrated that 99% of first-generation ablative procedures were performed under general anaesthetic.47 Endometrial thinning agents are conventionally used prior to ablation in order to ensure an adequate depth of destruction. Drugs such as danazol and gonadotrophin-releasing hormone (GnRH) analogues have been shown to improve operating conditions for the surgeon and increase postsurgical amenorrhoea rates.58 GnRHs were found to produce slightly more consistent endometrial thinning than danazol, although both produced satisfactory results.58

Transcervical resection of the endometrium requires a hysteroscope with a fibre optic cable to transmit light from an external power source. The cervix is dilated prior to insertion of the resectoscope, which provides a 12° angle of view. A continuous-flow outer sheath circulates liquid (usually glycine) to provide a clear view of the uterine cavity. A cutting loop is used to remove the endometrial lining. TCRE provides good samples of endometrium for biopsy.16 TCRE may also be used for the excision of small fibroids, and the operation17 is usually done as a day case.

Rollerball EA also requires visualisation and irrigation using a resectoscope. EA is achieved by means of a rollerball (RB) electrode rather than a cutting loop. A current is passed through the ball which is moved across the surface of the endometrium.59 As the RB fits better within the cornua and decreases the chance of perforating this relatively thin-walled part of the uterus,47 some surgeons prefer to use the RB to treat this area. In the UK, it is usual for TCRE to be used to treat the uterine walls while RBEA is used for the fundus and cornua.60

Potential perioperative adverse effects associated with TCRE and RBEA include electrosurgical vaginal and vulval burns, uterine perforation, haemorrhage, gas embolism, infection and fluid overload (which may cause congestive cardiac failure, hypertension, haemolysis, coma and death). Strategies for avoiding fluid absorption include maintaining the minimum intrauterine pressure compatible with safe surgery, using an efficient suction system to retrieve irrigation fluid and maintaining a strict fluid balance.39

Possible adverse effects of first-generation ablation techniques are shown in Table 3.

TABLE 3. Complications of first-generation EA techniques (from Garside et al.).


Complications of first-generation EA techniques (from Garside et al.).

Second-generation endometrial ablation techniques

Since the 1990s, several new methods of EA have been developed. These are often referred to as second-generation techniques. They do not require direct visualisation of the uterine cavity and employ a variety of means to destroy the endometrium – circulation of heated saline within the uterine cavity, use of a diode laser [endometrial laser intrauterine thermo-therapy (ELITT)], punctual vaporising methods, photodynamic methods, radiofrequency, microwaves, a balloon catheter filled with heated fluid and cryotherapy. The treatments are much less dependent on the skill of the surgeon than first-generation techniques, and much more dependent on the reliability of the machines used to ensure safety and efficacy. Complications associated with second-generation techniques include equipment failure, uterine infection, perforation, visceral burn, bleeding and cyclical pain. A limited number of randomised trials indicate that these procedures appear to be as effective as first-generation ablative techniques.61 In addition, some have the added benefit of being performed under local anaesthetic.

Microwave endometrial ablation

Microwave EA uses microwave energy (at a frequency of 9.2 GHz) to destroy the endometrium with a tissue penetration depth of Image ch1fu1.jpg 6 mm. An 8-mm applicator inserted through the cervix delivers the microwaves using a dielectrically loaded waveguide.62 Power is controlled by the surgeon using a footswitch and the temperature inside the uterus is monitored by thermocouples on the surface of the waveguide. Prior to microwave ablation treatment, oral and vaginal thinning agents may be given. Immediately prior to MEA, hysteroscopy is performed to exclude false passages, wall damage and perforation.

Following measurement of uterine cavity length, the cervix is dilated to Hegar 8 or 9 under general or local anaesthetic and the uterine cavity length is measured again. Next, the microwave probe is inserted until the tip reaches the fundus. Graduated centimetre markings on the applicator shaft confirm the length and if these three measurements of uterine length are the same the device is activated.63 When, after a few seconds, the temperature reaches 80 °C, the probe is moved laterally so that the tip is placed in one of the uterine cornua. The temperature briefly falls and rises again and when 80 °C is reached again the probe is moved to the other cornual region and the procedure is repeated.

Maintaining a temperature of 70–90 °C, the probe is withdrawn with side-to-side movements. The temperature measured by the thermocouple is actually the heat transmitted back from the tissue through the plastic sheath to the applicator shaft. Tissue temperature is higher than these measured levels during active treatment. As a marker on the probe appears at the external os, the applicator is switched off to avoid treating the endocervix. The procedure takes 2–3 minutes.62 Postoperative analgesia is provided as required.

Thermal balloon endometrial ablation

Thermal balloon EA aims to destroy the endometrium by means of heated liquid within a balloon inserted into the uterine cavity, which should be of normal size and regular shape. Available devices such as ThermaChoice and Cavaterm have an electronic controller, a single-use latex or silicone balloon catheter with a heating element, thermocouples and an umbilical cable. As the balloon must be in direct contact with the uterine wall, the device is unsuitable for women with large or irregular uterine cavities.

In the case of the ThermaChoice device, following dilatation of the cervix to about 5 mm, the balloon is introduced within the uterus and filled with sterile fluid (5% dextrose in water) which causes it to expand to fit the cavity. Once intrauterine pressure is stabilised to 160–180 mmHg, the temperature of the fluid is raised to 87°C and maintained for 8 minutes. Pressure, temperature and time are continuously monitored and the device is switched off if safety parameters are breached. The heat produced by the device causes destruction of the endometrium. Postoperatively, oral analgesia is prescribed and the treated endometrium sloughs off over the following week to 10 days.

The Cavaterm device acts in a similar fashion. The cervix is dilated to about 6 mm and a silicone balloon is inserted and filled with sterile 5% glucose solution to a pressure of 230–240 mmHg. The liquid is heated at a target temperature of 78°C for 10 minutes.

Endometrial thinning agents are not recommended although curettage immediately prior to the procedure can be used. NSAIDs are given to reduce perioperative cramping.

Impedance-controlled bipolar radiofrequency (NovaSure)

The NovaSure system consists of a single-use bipolar ablation device which is inserted into the uterine cavity transcervically after dilatation to 8 mm. This is connected to a generator which functions at 500 kHz and has a power cut-off limit set at a tissue impedance of 50 Ω. The cavity and cervical length are measured and the difference in centimetres is determined; this setting is selected on the shaft of the device. The device is inserted and the trigger is deployed which delivers the bipolar triangular array into the cavity. With gentle tapping and slight rotation in both directions the array fully deploys with the tips sited in each cornua. The distance between the cornuae is displayed and then entered into the generator, and this determines the energy required. A cavity integrity test is then automatically performed, which must be passed before the energy is delivered. Active treatment times are under 2 minutes, during which time suction pulls the walls onto the device. After completion the array is retracted into the device sheath and withdrawn. While the device is versatile, it cannot effectively treat larger cavities (> 11 cm) or distorted cavities. Pre-treatment endometrial thinning is not required and the procedure can be performed under local anaesthetic. A number of randomised trials has been undertaken, one comparing with RBEA56 and the others with thermal balloon devices.64,65 One of the trials has published follow-up to 5 years.66 A randomised trial comparing NovaSure with microwave ablation has been completed and awaits publication. It has approval from NICE.15 Results have been consistent through the trials, with amenorrhoea rates varying between 42% and 56%, high satisfaction rates of over 90% and low hysterectomy rates. Active treatment times vary between 90 and 120 seconds.

Adverse effects associated with second-generation EA devices include the following:16 uterine infection, perforation, visceral burn, bleeding, haematometra, laceration, intra-abdominal injury and cyclical pain.

Use of local anaesthetic

Use of local anaesthetic (LA) is a potential advantage of second-generation EA techniques, although this may not be suitable for all women. In a partially randomised trial of general anaesthetic (GA) and LA,67 the procedure was considered acceptable under GA in both preferred (100%) and randomised (97%) groups. However, under LA, 97% of those who chose this method and 85% of those allocated to LA found the procedure acceptable.

Selecting an appropriate treatment for heavy menstrual bleeding

The introduction of new EA techniques over the last two decades has been accompanied by a series of randomised clinical trials aimed at evaluating their clinical effectiveness and cost-effectiveness. Initially, first-generation EA techniques such as TCRE and laser EA were compared with hysterectomy.31 Subsequent trials, which compared alternative first-generation techniques such as TCRE, laser EA and RBEA, established TCRE as the gold standard for this group of treatments. As less invasive and more user-friendly second-generation techniques such as MEA became available, these were compared with earlier methods of ablation like TCRE and RBEA.

Although not all techniques have been subjected to head-to-head comparisons in the context of randomised trials, an overview of the literature demonstrates that MEA (second generation) has been shown to be comparable with TCRE (first generation) – which in turn has been shown to be an effective alternative to hysterectomy (gold standard). However, questions about the long-term clinical effectiveness and cost implications of alternative forms of surgical treatment remain unanswered. Published data report no more than 5 years of follow-up.46,68 Inevitably, some women treated by EA will eventually require repeat ablation or hysterectomy. Following hysterectomy, a proportion of women will also develop further complications such as postsurgical adhesions and pelvic floor dysfunction, which may lead to further surgery. The necessity for a head-to-head comparison between the two most common second-generation methods – MEA and TBEA – has been identified.15 Given the widespread use of ablative techniques as first-line surgical treatment for menorrhagia at the present time, it is uncertain whether it is either necessary or feasible to compare second-generation techniques directly with hysterectomy. At the same time, the need to obtain comparative information on long-term outcomes is clearly accepted, as is the need to identify the best technique for individual women.

From a clinical perspective, the most relevant research questions at the present time are:

  1. How do the currently used ablative techniques compare with hysterectomy in the medium to long term?
  2. Which among the commonly used second-generation ablation techniques is the most effective and cost-effective?
  3. Are there subgroups of women who are most likely to benefit from either hysterectomy or specific types of ablation?

In this project we have performed a series of studies in order to address these questions by analysis of data from national data sets and randomised trials. Long-term outcomes following EA and hysterectomy in a national cohort have been explored by means of record linkage, while the effectiveness of Mirena, hysterectomy and EA have been determined by individual patient data (IPD) meta-analysis of existing trials. The output has been used (along with other data from the literature) to create a model for the utilisation and costs of the different treatments.

Project objectives

  1. To determine, using data from record linkage and follow-up of randomised and non-randomised cohorts of British women, the long-term effects of various second-generation ablative techniques and hysterectomy in terms of failure rates, complications, QoL and sexual function.
  2. To determine, using IPD meta-analysis of existing RCTs, the short- to medium-term effects of various second-generation ablative techniques and hysterectomy, including the exploration of outcomes in clinical subgroups.
  3. To undertake a model-based clinical effectiveness and cost-effectiveness analysis comparing various second-generation ablative techniques with hysterectomy using output from the above analyses and to conduct extensive sensitivity analyses to explore the robustness of the results to the assumptions made.
  4. To devise an algorithm for clinical decision making regarding the choice of surgery for women with HMB in whom medical treatment has failed.
© 2011, Crown Copyright.

Included under terms of UK Non-commercial Government License.

Cover of Hysterectomy, Endometrial Ablation and Mirena® for Heavy Menstrual Bleeding: A Systematic Review of Clinical Effectiveness and Cost-Effectiveness Analysis
Hysterectomy, Endometrial Ablation and Mirena® for Heavy Menstrual Bleeding: A Systematic Review of Clinical Effectiveness and Cost-Effectiveness Analysis.
Health Technology Assessment, No. 15.19.
Bhattacharya S, Middleton LJ, Tsourapas A, et al. ; the International Heavy Menstrual Bleeding Individual Patient Data Meta-analysis Collaborative Group
Southampton (UK): NIHR Journals Library; 2011 Apr.

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