Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Fergusson RJ, Lethaby A, Shepperd S, Farquhar C

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 11 http://www.thecochranelibrary.com

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 8. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 1 Woman’s perception (proportion with improvement in bleeding symptoms). . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 2 PBAC score (continuous data). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 3 Proportion requiring further surgery for HMB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 4 Proportion satisfied with treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 5 Adverse events-short term (intraoperative and immediate postoperative). . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.6. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 6 Adverse events-long term (after hospital discharge). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.7. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 7 Quality of life scores (continuous data). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.8. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 8 Quality of life (proportion with improvement). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.9. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 9 Duration of surgery (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.10. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 10 Time to return to work (weeks). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.11. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 11 Time to return to normal activity (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.12. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 12 Duration of hospital stay (days). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .


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[Intervention Review]

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding Rosalie J Fergusson1 , Anne Lethaby2 , Sasha Shepperd3 , Cindy Farquhar4 1 Obstetrics

and Gynaecology, Auckland City Hospital, Auckland District Health Board, Auckland, New Zealand. 2 Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand. 3 Nuffield Department of Population Health, University of Oxford, Oxford, UK. 4 Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand Contact address: Anne Lethaby, Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. [email protected]. Editorial group: Cochrane Menstrual Disorders and Subfertility Group. Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 11, 2013. Review content assessed as up-to-date: 30 October 2013. Citation: Fergusson RJ, Lethaby A, Shepperd S, Farquhar C. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD000329. DOI: 10.1002/14651858.CD000329.pub2. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Heavy menstrual bleeding (HMB), which includes both menorrhagia and metrorrhagia, is an important cause of ill health in women. Surgical treatment of HMB often follows failed or ineffective medical therapy. The definitive treatment is hysterectomy, but this is a major surgical procedure with significant physical and emotional complications, as well as social and economic costs. Several less invasive surgical techniques (e.g. transcervical resection of the endometrium (TCRE), laser approaches) and various methods of endometrial ablation have been developed with the purpose of improving menstrual symptoms by removing or ablating the entire thickness of the endometrium. Objectives The objective of this review is to compare the effectiveness, acceptability and safety of techniques of endometrial destruction by any means versus hysterectomy by any means for the treatment of heavy menstrual bleeding. Search methods Electronic searches for relevant randomised controlled trials (RCTs) targeted but were not limited to the following: the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsycINFO and the Cochrane CENTRAL register of trials. Attempts were made to identify trials by examining citation lists of review articles and guidelines and by performing handsearching. Searches were performed in 2007, 2008 and 2013. Selection criteria Included in the review were any RCTs that compared techniques of endometrial destruction by any means with hysterectomy by any means for the treatment of heavy menstrual bleeding in premenopausal women. Data collection and analysis Two review authors independently searched for studies, extracted data and assessed risk of bias. Risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes were estimated from the data. Outcomes analysed included improvement in menstrual blood loss, satisfaction, change in quality of life, duration of surgery and hospital stay, time to return to work, adverse events and requirements for repeat surgery due to failure of the initial surgical treatment. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Main results Eight RCTs that fulfilled the inclusion criteria for this review were identified. For two trials, the review authors identified multiple publications that assessed different outcomes at different postoperative time points for the same women. An advantage in favour of hysterectomy compared with endometrial ablation was observed in various measures of improvement in bleeding symptoms and satisfaction rates. A slightly lower proportion of women who underwent endometrial ablation perceived improvement in bleeding symptoms at one year (RR 0.89, 95% confidence interval (CI) 0.85 to 0.93, four studies, 650 women, I2 = 31%), at two years (RR 0.92, 95% CI 0.86 to 0.99, two studies, 292 women, I2 = 53%) and at four years (RR 0.93, 95% CI 0.88 to 0.99, two studies, 237 women, I2 = 79%). The same group of women also showed improvement in pictorial blood loss assessment chart (PBAC) score at one year (MD 24.40, 95% CI 16.01 to 32.79, one study, 68 women) and at two years (MD 44.00, 95% CI 36.09 to 51.91, one study, 68 women). Repeat surgery resulting from failure of the initial treatment was more likely to be needed after endometrial ablation than after hysterectomy at one year (RR 14.9, 95% CI 5.2 to 42.6, six studies, 887 women, I2 = 0%), at two years (RR 23.4, 95% CI 8.3 to 65.8, six studies, 930 women, I2 = 0%), at three years (RR 11.1, 95% CI 1.5 to 80.1, one study, 172 women) and at four years (RR 36.4, 95% CI 5.1 to 259.2, one study, 197 women). Most adverse events, both major and minor, were significantly more likely after hysterectomy during hospital stay. Women who had a hysterectomy were more likely to experience sepsis (RR 0.2, 95% CI 0.1 to 0.3, four studies, 621 women, I2 = 62%), blood transfusion (RR 0.2, 95% CI 0.1 to 0.6, four studies, 751 women, I2 = 0%), pyrexia (RR 0.2, 95% CI 0.1 to 0.4, three studies, 605 women, I2 = 66%), vault haematoma (RR 0.1, 95% CI 0.04 to 0.3, five studies, 858 women, I2 = 0%) and wound haematoma (RR 0.03, 95% CI 0.00 to 0.5, one study, 202 women) before hospital discharge. After discharge from hospital, the only difference that was reported for this group was a higher rate of infection (RR 0.2, 95% CI 0.1 to 0.5, one study, 172 women). For some outcomes (such as a woman’s perception of bleeding and proportion of women requiring further surgery for HMB), a low GRADE score was generated, suggesting that further research in these areas is likely to change the estimates. Authors’ conclusions Endometrial resection and ablation offers an alternative to hysterectomy as a surgical treatment for heavy menstrual bleeding. Both procedures are effective, and satisfaction rates are high. Although hysterectomy is associated with longer operating time (particularly for the laparoscopic route), a longer recovery period and higher rates of postoperative complications, it offers permanent relief from heavy menstrual bleeding. The initial cost of endometrial destruction is significantly lower than that of hysterectomy, but, because retreatment is often necessary, the cost difference narrows over time.

PLAIN LANGUAGE SUMMARY A comparison of the effectiveness and safety of two different surgical treatments for heavy menstrual bleeding Review question This Cochrane review concerns women with heavy menstrual bleeding (HMB), which is menstrual blood loss that a woman feels to be excessive and that often interferes with her quality of life. Researchers from The Cochrane Collaboration compared endometrial resection or ablation versus hysterectomy for women with HMB. The main factors (thought to be of greatest importance) were how well each operation was able to treat the symptoms of HMB, how women felt about undergoing each operation and what the complication rates were. Additional factors studied were how long each operation took to perform, how long women took to recover from the operation and how much the operation cost the hospital and the woman herself. Background Surgical treatments for HMB include removal or destruction of the inside lining (endometrium) of the womb (endometrial resection or ablation) and surgical removal of the whole womb (hysterectomy). Both methods are commonly offered by gynaecologists, usually but not always after a non-surgical treatment has failed to correct the problem. Endometrial resection/ablation is performed via the entrance to the womb, without the need for a surgical cut. During a hysterectomy, the uterus can be removed via a surgical cut to the abdomen, via the vagina, or via ’keyhole’ surgery that involves very small surgical cuts to the abdomen (laparoscopy); this last approach is a newer way to perform hysterectomy. Hysterectomy is effective in permanently stopping HMB, but it stops fertility and is associated with all the risks of major surgery, including infection and blood loss. These risks are smaller with endometrial resection/ablation. Search date Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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A systematic review of the research comparing endometrial resection and ablation versus hysterectomy for the treatment of heavy menstrual bleeding was most recently updated in October 2013 by researchers at The Cochrane Collaboration. After searching for all relevant studies, review authors included eight studies involving a total of 1,260 women. Study characteristics Only randomised controlled trials (RCTs) are included in Cochrane reviews. RCTs are studies in which participants are randomly allocated to one of two groups, each receiving a different intervention (in this case, endometrial ablation/resection or hysterectomy). The two groups are then compared. RCTs that compared these two interventions were included in this review if they studied women with HMB who had not gone through menopause and who did not have cancer or precancer of the uterus. Key results and conclusions The review of studies revealed that endometrial ablation/resection is an effective and possibly cheaper alternative to hysterectomy with faster recovery, although retreatment with additional surgery is sometimes needed. Hysterectomy is associated with more definitive resolution of symptoms but longer operating times and greater potential for surgical complications. For both operations, women generally reported that undergoing the procedure was acceptable and that they were satisfied with their experience. Since laparoscopic hysterectomy has become more widely used, several of the previously described disadvantages of traditional types of hysterectomy have improved, and some outcomes such as duration of hospital stay, time to return to work and time to return to normal activities have become more comparable with those of endometrial ablation. However, laparoscopic hysterectomy is associated with longer operating time than other modes of hysterectomy and requires more sophisticated surgical expertise and equipment. Only three of the eight trials included laparoscopic hysterectomy in their comparison. More trials in this area will be needed as this route of hysterectomy becomes more widely available. Identifying harms Both surgical treatments are considered to be generally safe, and low complication rates are reported. However, hysterectomy is associated with higher rates of infection and requirement for blood transfusion. Quality of the evidence Evidence reported in this review was occasionally of low quality, suggesting that further research is likely to change the result. This was the case for outcomes such as a woman’s perception of bleeding and proportion of women requiring further surgery for HMB.


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S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]

Endometrial resection/ablation for heavy menstrual bleeding Patient or population: women with heavy menstrual bleeding Settings: Intervention: endometrial resection/ablation Outcomes

Illustrative comparative risks* (95% CI)

Assumed risk

Corresponding risk

Control

Endometrial resection/ ablation

Relative effect (95% CI)

No of participants (studies)

Quality of the evidence (GRADE)

RR 0.91 (0.8 to 0.97)

650 (4 studies)

⊕⊕

low1,2

68 (1 study)

⊕⊕⊕ moderate1

Woman’s per- 978 per 1,000 ception (proportion with improvement in bleeding symptoms)-within one year of follow-up

890 per 1,000 (783 to 949)

PBAC score (continuous data)-at one year of follow-up

Mean PBAC score (continuous data) at one year of follow-up in the intervention groups was 24.4 higher (16.01 to 32.79 higher)

Adverse events-short 319 per 1,000 term (intraoperative and immediate postoperative)-sepsis

61 per 1,000 (38 to 99)

RR 0.19 (0.12 to 0.31)

621 (4 studies)

⊕⊕⊕ moderate2

Proportion requiring fur- 2 per 1,0003 ther surgery for HMBwithin one year after surgery

36 per 1,000 (13 to 103)

RR 14.94 (5.24 to 42.57)

887 (6 studies)

⊕⊕

low1,4

Comments

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Proportion satisfied with 820 per 1,000 treatment-at one year of follow-up

771 per 1,000 (721 to 820)

RR 0.94 (0.88 to 1)

739 (4 studies)

⊕⊕⊕ moderate1

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio. GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. 1

Lack of blinding (although unfeasible) is likely to bias women’s responses. heterogeneity. 3 Result suggests incomplete operation-rare. 4 Wide confidence interval. 2 Significant

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BACKGROUND

Description of the condition Heavy menstrual bleeding (HMB) is a common presenting complaint for primary care services and a frequent reason for secondary referral, with 5% of women between 30 and 49 years of age seeking medical attention for the problem (Vessey 1992; Cooper 2011). Unacceptably problematic bleeding is most commonly determined by the woman herself if the amount or frequency of blood loss interferes with her physical or psychosocial well-being. This personal perception is often what determines the need for treatment and assessment of outcomes afterwards. Many alternative definitions for HMB are used, including menorrhagia, abnormal menstrual bleeding, abnormal uterine bleeding and disordered uterine bleeding. These terms have not always been universally defined, and considerable overlap and confusion between them have been noted in the existing literature (Woolcock 2008). In response to this confusion, the International Federation of Gynaecology and Obstetrics (FIGO) formally defined HMB as ‘the woman’s perspective of increased menstrual volume, regardless of regularity, frequency, or duration’ (Munro 2011). Intervention for HMB should be aimed at correction of identified underlying causes, control of bleeding, amelioration of anaemia and improvement in quality of life measures, with the woman’s contraceptive requirements or desire for future fertility taken into account, along with individual preferences for treatment.

Description of the intervention Many well-established treatment options for HMB are available, including hormonal and non-hormonal medications, but among women who do not desire future fertility or for whom medical treatment may be problematic, inconvenient or prolonged, surgical management may be preferred. Until the mid-1980s, hysterectomy was the only option for such women, and 60% of women presenting with HMB during this time underwent hysterectomy as a first-line treatment (NICE 2007). Hysterectomy continues to be performed via the more traditional abdominal and vaginal routes, but minimally invasive techniques have been introduced for women with benign disease, and these techniques continue to be developed. Such approaches include the introduction of laparoscopic hysterectomy (total laparoscopic hysterectomy and laparoscopically assisted vaginal hysterectomy) in 1989 (Reich 1989) and single-port laparoscopic hysterectomy in 2009 (Li 2012). Considerable differences between types of approach have been noted with regard to intraoperative complications, duration of hospital stay, length of recovery and cost. However, as this review aims to compare hysterectomy with endometrial resection and

ablation, the results for hysterectomy by all approaches will be pooled. Endometrial ablation is a minimally invasive hysteroscopic surgical intervention for HMB involving removal or destruction of the endometrium. Since it was introduced in the 1990s, its popularity as an alternative to hysterectomy has grown. An examination of the UK National Health Service (NHS) statistics in 2005 revealed that endometrial destruction was being performed more frequently than hysterectomy for benign HMB in the UK (Reid 2007). Since its invention, techniques for endometrial resection and ablation have evolved considerably as technologies have advanced (Sharp 2012). Currently, no clear evidence of differences in effectiveness or safety between ‘first’- and ‘second’-generation techniques has been found (Lethaby 2005; Fernandez 2011). ‘First-generation’ techniques included desiccation of the endometrium by way of rollerball endometrial ablation (REA) and transcervical resection of the endometrium with loop electrode. These techniques require direct hysteroscopic vision throughout the procedure, whereby other endometrial pathology such as polyps and fibroids can be diagnosed and, if necessary, removed. A potential complication of endometrial resection is systemic fluid overload due to absorption of hysteroscopic fluid; therefore careful intraoperative input/output fluid balance requires attention and documentation. The efficacy and safety of first-generation techniques are often operator dependent. Newer technologies were subsequently introduced, including thermal balloon ablation, microwave ablation, free-fluid thermal ablation, radiofrequency ablation and cryotherapy. These ‘secondgeneration’ techniques have allowed widespread use of endometrial ablation, as they require less advanced hysteroscopic skill and do not necessitate intraoperative fluid balance. However, these procedures depend heavily on the surgical equipment itself for efficacy and safety. In some (but not all) instances, they can be performed without the hysteroscope altogether, making these approaches simpler, quicker and safer.

How the intervention might work Hysterectomy is regarded as ‘definitive’ treatment for HMB with guaranteed amenorrhoea and cessation of fertility and little need for future treatment. However, hysterectomy by any route is associated with all the complications of major surgery, including intraoperative bleeding, infection and venous thromboembolism. Other reported complications include urinary incontinence and dyspareunia. Although a successful outcome after endometrial ablation is not guaranteed and further surgery is occasionally required, many women still choose a less invasive surgical option (Nagele 1998; Bourdrez 2004). Endometrial resection/ablation is often chosen because of perceived short hospitalisation, quick return to normal functioning and avoidance of major surgery (Nagele 1998). Vaginal discharge and increased period pain are common complica-


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tions following endometrial resection/ablation. Uncommon complications include intraoperative uterine perforation and associated pelvic organ injury from direct perforation or electrosurgical burns.

Types of participants

Source of recruitment

Primary care, family planning and specialist clinics.

Why it is important to do this review HMB is a common reason for women to seek treatment, and many choose a surgical option as first- or second-line management. Surgical methods for treatment of HMB show a trend in favour of endometrial resection/ablation and towards newer endometrial resection/ablation techniques. In the late 1980s and early 1990s, 60% of women with HMB who were referred to a gynaecologist in the UK were treated with hysterectomy (Coulter 1991), but an examination of NHS statistics in 2005 revealed that endometrial destruction was being performed more frequently than hysterectomy for benign HMB in the UK (Reid 2007). Despite this trend, many women still express a preference for firstline hysterectomy (Kennedy 2002), and rates of different methods of hysterectomy are evolving. As surgical techniques for both hysterectomy and endometrial resection/ablation continue to evolve, corresponding changes in success rates, outcomes and complications will be noted, necessitating regular comparison and review. At the time of the 2008 review, robust evidence in the literature comparing less invasive hysterectomy techniques versus second-generation methods of endometrial ablation was lacking.

Inclusion criterion

1. Women of reproductive years with heavy menstrual bleeding (including both heavy regular periods (menorrhagia) and heavy irregular periods (metrorrhagia)), measured objectively or subjectively. Exclusion criteria

1. Postmenopausal bleeding (> 1 year from the last period). 2. HMB caused by uterine malignancy or endometrial hyperplasia. 3. Iatrogenic causes of HMB (e.g. intrauterine coil devices). Types of interventions 1. Endometrial resection and ablation (including firstgeneration techniques, such as transcervical resection of the endometrium with loop electrode or rollerball, and secondgeneration techniques, such as endometrial ablation by thermal balloon, microwave, thermal free-fluid, radiofrequency and cryotherapy). 2. Hysterectomy (by abdominal, vaginal and laparoscopic/ laparoscopically assisted routes). Types of outcome measures

OBJECTIVES The objective of this review is to compare the effectiveness, acceptability and safety of techniques of endometrial destruction by any means versus hysterectomy by any means for the treatment of heavy menstrual bleeding.

METHODS

Primary outcomes

Effectiveness (improvement in bleeding)

1.1 Woman’s perception (proportion with improvement in bleeding symptoms). 1.2 PBAC (Pictorial Blood Loss Assessment Chart) score: a visual measure of amount of blood loss (clinically significant HMB correlates with a score > 100).* 1.3 Requirement for further surgery. Acceptability

Criteria for considering studies for this review

1.4 Proportion satisfied with treatment. Safety (adverse outcomes)

Types of studies Published and non-published randomised controlled trials (RCTs) were eligible for inclusion. Quasi-randomised trials were excluded.

1.5 Adverse events: short term (intraoperative and immediately postoperative). 1.6 Adverse events: long term (after hospital discharge).


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Secondary outcomes

1.7 Quality of life scores (continuous data). 1.8 Quality of life (proportion with improvement). 1.9 Duration of surgery. 1.10 Duration of hospital stay. 1.11 Time to return to normal activity. 1.12 Time to return to work. 1.13 Total health service cost per woman. 1.14 Total individual cost per woman. *PBAC score: A score over 100 suggests significantly heavy menstrual bleeding. A reduction from over 100 to under 100 would be clinically significant at an individual level.

“Hysterectomy, subtotal” or “Hysterectomy, Vaginal” or Title CONTAINS “Hysterectomy” or “Hysterectomy, abdominal” or “hysterectomy, laparoscopically assisted vaginal” or “Hysterectomy, subtotal” or “Hysterectomy, Vaginal”. (See Review Group details for additional information.) 2. The two review authors then searched MEDLINE (1966 to October 2013; Appendix 1), EMBASE (1980 to October 2013; Appendix 2), PsycINFO (1972 to October 2013; Appendix 3) and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 10, 2013; Appendix 4), using the search strategy developed by The Cochrane Collaboration. Searching other resources

Search methods for identification of studies We searched all publications that would potentially describe RCTs comparing surgical techniques to resect or ablate the endometrium versus hysterectomy for the treatment of heavy menstrual bleeding. Search strategies for identifying potential studies for inclusion were employed in consultation with the Cochrane Menstrual Disorders and Subfertility Group Trials Search Co-ordinator.

1. The principal review author searched all registers of the metaRegister of Controlled Trials in October 2013 to identify ongoing trials, trials that may have been missed by the search of electronic databases and trials that were unpublished. 2. Citation lists of all studies that appeared to meet the inclusion criteria of the review, studies found in the literature review stage of the introduction, other relevant studies and evidence-based guidelines on the management of abnormal bleeding were also searched.

Electronic searches The original search was performed in 1999. Updated searches were performed in 2008 and 2013. 1. The principal and second review authors searched the trial register of the Menstrual Disorders and Subfertility Group using the search strategy developed by the Menstrual Disorders and Subfertility Group as follows: Keywords CONTAINS “menorrhagia” or “heavy bleeding” or “heavy menstrual bleeding” or “heavy menstrual loss” or “dysfunctional uterine bleeding” or “dysfunctional bleeding” or Title CONTAINS “menorrhagia” or “heavy bleeding” or “heavy menstrual bleeding” or “heavy menstrual loss” or “dysfunctional uterine bleeding” or “dysfunctional bleeding”. AND Keywords CONTAINS “Hysterectomy” or “Hysterectomy, abdominal” or “hysterectomy, laparoscopically assisted vaginal” or

Data collection and analysis Statistical analysis was performed in accordance with guidelines from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). When possible, outcomes were pooled statistically. Selection of studies Trials for inclusion in the review were selected by two of the review authors (AL and IC or AL and SS in 2008, and RJF and AL in 2013) after the search strategy described previously was employed. This task was undertaken independently, and the final list of included studies reflected consensus between the two review authors. Details of the screening and selection process are shown in Figure 1.


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Figure 1. Study screening and selection process (2008 to 2013).


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Data extraction and management All assessments of characteristics of the included studies were performed independently by two review authors (AL and IC in 2008, and RJF and AL in 2013) using forms designed according to Cochrane guidelines and described in Higgins 2011 When necessary, additional information on trial methodology or original trial data were sought from the principal or corresponding author of any trials that appeared to meet the eligibility criteria (see Acknowledgements section for details of the study authors who provided clarification of data beyond that reported in the publications). Quality criteria and methodological details were extracted from each study as follows.

1. Type of endometrial destruction technique used and route of hysterectomy performed.

Outcomes

1. Methods used to evaluate menstrual symptoms (e.g. PBAC score, woman-defined ’improvement in symptoms’). 2. Methods used to measure requirement for further surgery for HMB. 3. Methods used to evaluate participant satisfaction and change in quality of life postsurgery. 4. Methods used to record adverse surgical events. 5. Methods used to measure resource and individual costs. 6. Methods used to measure duration of surgery, hospital stay and recovery time.

Trial characteristics

1. Study design. 2. Numbers of women randomly assigned, excluded and lost to follow-up. 3. Whether an intention-to-treat analysis was done. 4. Whether a power calculation was done. 5. Duration, timing and location of the study. 6. Number of centres. 7. Source of funding.

Characteristics of study participants

1. Age and any other recorded characteristics of participants in the study. 2. Other inclusion criteria. 3. Exclusion criteria. 4. Type of surgery. 5. Source of participants. 6. Proportion participating of those eligible.

Interventions used

Assessment of risk of bias in included studies Included trials were assessed for risk of bias using the ’Risk of bias tool’ developed by The Cochrane Collaboration and described in Higgins 2011. 1. Sequence generation (whether the allocation sequence was adequately generated to produce comparable groups). 2. Allocation concealment (whether the allocation was adequately concealed). 3. Blinding of participants, personnel and outcome assessors (whether knowledge of the allocated intervention was adequately controlled during the study). 4. Incomplete outcome data (whether incomplete outcome data were adequately addressed). 5. Selective outcome reporting (whether reports of the study were free of the suggestion of selective outcome reporting). 6. Other sources of bias (whether the study was apparently free of other problems that could put it at high risk of bias, e.g. baseline imbalance, bias related to study design, early termination of the study). Details of the risk of bias for each included study are displayed in Characteristics of included studies and are summarised in Figure 2 and Figure 3.


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Figure 2. Methodological quality graph: review authors’ judgements about each methodological quality item presented as percentages across all included studies.


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Figure 3. Methodological quality summary: review authors’ judgements about each methodological quality item for each included study.


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Measures of treatment effect For dichotomous data (e.g. number of adverse outcomes), we will use the numbers of events in the control and intervention groups of each study to calculate risk ratios (RRs). For continuous data (e.g. PBAC score), if all studies report exactly the same outcomes, we will calculate mean differences (MDs) between treatment groups. If similar outcomes are reported on different scales, we will calculate the standardised mean difference (SMD). We will reverse the direction of effect of individual studies, if required, to ensure consistency across trials. We will treat ordinal data (e.g. quality of life scores) as continuous data. We will present 95% confidence intervals for all outcomes. When data needed to calculate RRs or MDs are not available, we will utilise the most detailed numerical data available that may facilitate similar analyses of included studies (e.g. test statistics, P values). We will compare the magnitude and direction of effect reported by studies versus how they are presented in the review, while taking account of legitimate differences. For dichotomous data (e.g. proportion of participants satisfied with their treatment), results of each study were expressed as a risk ratio. For some dichotomous outcomes (e.g. proportion of participants requiring further surgery), a higher proportion represented a negative consequence of that treatment, and for other outcomes (e.g. proportion with improvement in menstrual blood loss), a higher proportion was considered a benefit of treatment. This approach to the categorising of outcomes should be noted when summary graphs for the meta-analysis are viewed for assessment of benefits as opposed to harms of treatment. Thus, for some dichotomous outcomes, treatment benefit has been displayed as risk ratios and confidence intervals to the left of the centre line, but for others, a treatment benefit has been shown to the right of the centre line. Each outcome was labelled for clarification. For other outcomes for which high values were considered a negative consequence of treatment, for example, duration of surgery, hospital stay and return to work, evaluation of the summary graphs reveals that means and confidence intervals to the left were considered a benefit of endometrial destruction. With one exception, quality of life scores were entered as continuous data-mean plus standard deviation values post-treatment. One study, however, recorded the percentage mean change of Euroqol scores from baseline to four months after treatment. Some scales measured general quality of life summary score; others reported results separately in different categories, representing general quality of life but without a summary score; still others used more specific measurements of aspects of quality of life, such as anxiety, social adjustment and depression. For some outcomes, women were assessed at different periods of follow-up after surgery.

1. Menstrual symptoms were recorded at one, two, three and four years after surgery, PBAC scores at one and two years after surgery, and quality of life at four months and one, two and four years post-treatment. 2. Adverse events were recorded before and after discharge from hospital. 3. Requirement for further surgery was measured separately within the first year and at two, three and four years after treatment.

Unit of analysis issues The unit of analysis was the woman with HMB who was randomly assigned to endometrial resection/ablation or to hysterectomy.

Dealing with missing data Data were analysed on an intention-to-treat basis as far as possible; otherwise only available data were analysed. When data were found to be missing, attempts were made to obtain this information from the original trial authors.

Assessment of heterogeneity Heterogeneity (variations) between the results of different studies was examined by visual inspection of scatter of data points on the graphs and overlap in their confidence intervals and, more formally, by examination of the results of the I2 quantity (a quantity that describes approximately the proportion of variation in point estimates that is due to heterogeneity rather than sampling error; Higgins 2008). When statistical heterogeneity was found to be very substantial (> 90%), calculation of a summary effect measure was not considered appropriate, and study data were not pooled. However, results of these studies can be viewed in forest plots that portray the range of values for comparison in each study.

Assessment of reporting biases Avoidance of reporting bias was attempted by using a robust search strategy with no restrictions on language or publication forum. Multiple publications of the same study were identified for several of the included studies and are referenced as such. The use of funnel plots was planned to explore the possibility of small study effects if 10 or more studies had been included in the analysis.

Data synthesis Combination of data was not always possible, as some outcomes were measured differently (e.g. some trials used PBAC score as a


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measure of improvement in bleeding, whilst others used proportion reporting improvement in bleeding symptoms, proportion with excessive bleeding, etc.). Such data were displayed in the forest plots; however, often only one trial contributed data to each plot. For continuous data (e.g. PBAC score), if all studies reported exactly the same outcomes, mean differences (MDs) between treatment groups were calculated. Continuous outcomes were also displayed differently according to whether benefit or harm was measured. For most quality of life scores, a high score represented a benefit of treatment, but for the Hospital Anxiety and Depression Scale (HAD), a high score represented a greater degree of anxiety or depression. To display on the same graph quality of life scales that differed in this way, HAD scores were displayed as minus values, so that all quality of life continuous outcomes could be included in a single forest plot. Subgroup analysis and investigation of heterogeneity A priori, it was planned to explore the possible contribution of differences in trial design to any heterogeneity identified in the manner described above under ’Assessment of heterogeneity’. As a guide, I2 values ≤ 25%, = 50% and ≥ 75% correspond to low, moderate and high levels of heterogeneity (Higgins 2008). Sensitivity analysis To assess the robustness of pooled estimates, the following sensitivity analyses were conducted. 1. Estimates whereby all types of hysterectomy were combined versus estimates for which each individual surgical approach was used. 2. Estimates based on all relevant trials regardless of evidence of allocation concealment versus estimates based on trials that provided clear evidence that allocation was concealed. The following analysis was planned but was not conducted. 1. Estimates based on all relevant trials regardless of missing data and loss to follow-up versus estimates based on trials in which incomplete outcome assessment was not likely to cause bias. Overall quality of the body of evidence: summary of findings table

Summary of findings for the main comparison was generated using GRADEPRO software. This table evaluates the overall quality of the body of evidence for the main review outcomes, using GRADE criteria. 1. Study limitations (i.e. risk of bias). 2. Consistency of effect. 3. Imprecision. 4. Indirectness. 5. Publication bias.

Judgements about evidence quality (high, moderate, low or very low) were justified, documented and incorporated into reporting of results for each of these main outcomes.

RESULTS Description of studies Eight RCTs comparing techniques of removal or ablation of endometrium versus hysterectomy by any route for the treatment of heavy menstrual bleeding were included. Two of these trials had multiple publications, each based on the same study population but providing assessment of different outcomes and different follow-up times, as well as cost-utility analyses of previously published data (Dwyer 1993; Pinion 1994). Trials comparing different types of endometrial destruction were not considered in this review but are assessed in Lethaby 2009. Details of included studies can be found in the Characteristics of included studies table. Study design All included studies used a parallel-group design. Six of these studies were carried out at a single centre (three in Italy, three in the UK), one study was performed at nine centres throughout the UK and one study was completed at 25 centres in the USA and Canada. Participants Participants in all included studies were premenopausal, had symptomatic heavy menstrual bleeding (regular or irregular prolonged or excessive bleeding) and were eligible for (i.e. had shown no response to medical treatment) or were awaiting hysterectomy. Participants in five of the included studies had received a diagnosis of menorrhagia (heavy regular bleeding), and participants in two of the studies had been given a diagnosis of dysfunctional uterine bleeding (which was defined as both regular and irregular ovulatory heavy bleeding and anovulatory abnormal bleeding not due to pathology). Exclusion criteria included large fibroids, large uterine size, pelvic inflammatory disease (PID) and endometriosis and abnormal pathology. Three studies excluded participants with submucosal fibroids. Interventions Available data mostly compared first-generation ablation techniques (predominantly transcervical resection of the endometrium (TCRE)) versus total hysterectomy. Two trials (Gannon 1991; Dwyer 1993) compared TCRE versus abdominal hysterectomy; the latter trial also included a preoperative procedure (medroxyprogesterone acetate injection four to six weeks before surgery) to


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reduce the thickness of the endometrium for participants undergoing endometrial resection. One trial compared endometrial resection versus vaginal hysterectomy (Crosignani 1997), another trial compared endometrial resection versus hysterectomy (50% abdominal, 50% vaginal) (O’Connor 1997) and another trial compared endometrial destruction after preoperative gonadotrophinreleasing hormone (GnRH) treatment (50% endometrial resection and 50% laser ablation) versus hysterectomy (88% abdominal and 12% vaginal) (Pinion 1994). One study compared endometrial resection or thermal balloon ablation (according to surgeon choice) versus total hysterectomy (vaginal, laparoscopic or abdominal approach, according to surgeon choice) (Dickerson 2007), another study compared endometrial resection after preoperative GnRH agonist (GnRHa) treatment versus laparoscopic supracervical hysterectomy (Zupi 2003) and the final study compared thermal balloon endometrial ablation versus laparoscopic supracervical hysterectomy (Sesti 2011). Sensitivity analysis was undertaken to compare trial results with all types of hysterectomy included in the estimates versus exclusion of the more invasive types of hysterectomy to assess effects in the trials in which solely vaginal hysterectomy surgery or laparoscopic supracervical hysterectomy was performed (Crosignani 1997; Zupi 2003; Sesti 2011).

Outcomes Follow-up after surgery for all included studies ranged from four months to four years. Six studies assessed change in menstrual bleeding patterns; four of these assessed whether menorrhagialike symptoms had resolved (amount and frequency of bleeding), one study (in which participants had a complaint of dysfunctional bleeding) measured separate components of bleeding excess (excessive amount and duration) and another study used PBAC questionnaires. Four studies assessed time to return to normal activities in days. Two studies, in which participants had a diagnosis of dysfunctional bleeding, assessed whether an improvement in overall symptoms had occurred (recorded in one trial as ’problem solved’). Three studies measured costs of treatment. All but three studies assessed satisfaction with surgery (although this was reported at different follow-up times) and return to work, all but two studies assessed postoperative complication rate and duration of surgery and all studies assessed hospital stay and requirement for further surgery. Some outcomes measured time of surgery or recovery time and strictly speaking were time to event outcomes, such as duration of surgery, length of stay in hospital and time to return to normal activities and work. However, these were analysed as continuous data, as all participants had initial and end values representing the time that had elapsed. Time to event analysis is mandatory when censoring is performed and only a subset of participants have an event, but in this review, comparison of means was considered by the review authors to be an acceptable analysis.

Seven studies assessed quality of life after surgery, but several different scales were used. This review has assessed quality of life as measured by the Golombok Rust Inventory of Marital State (one year after surgery), the Short Form-36 Scale (SF-36), the Euroqol Visual Analogue Scale, the Hospital Anxiety and Depression Scale (HAD) and the Sabbatsberg Sexual Rating Scale (all one or two years after surgery). The SF-36 is a generic measure of subjective health in the form of a profile with eight multi-item dimensions (including physical and emotional role limitation, physical and social functioning, mental health, energy, pain and general health perception) developed in the USA and shown to be an acceptable tool when used by women with HMB (Ware 1993; Coulter 1994). The Euroqol health instrument is a generic single index measure of health-related quality of life validated in several European countries, including the UK (Euroqol Group 1990; Brazier 1993). The Golombok Rust Inventory was modified by the investigators to obtain a brief measure of the overall quality of the marital relationship (Rust 1986), and the Sabbatsberg Sexual Rating Scale was designed to provide a self assessment of sexual functioning by women engaging in intercourse (Garrat 1995). The Hospital Anxiety and Depression Scale is a self-assessment mood scale specifically designed to identify states of anxiety and depression and is regarded as a valid measure of the severity of these mood disorders (Zigmond 1983). Several other scales were used to evaluate aspects of quality of life in some of the trials, including the General Health Questionnaire, the Psychosocial Adjustment to Illness Scale, a psychiatric mood scale, a modified social adjustment scale and an unvalidated questionnaire, but these outcomes were not entered into the review because the data were not obtained in a suitable form for inclusion in a meta-analysis (quantitative data provided in graphical form indicated significant skew; data could not be obtained from study authors). Five publications from three trials (Cameron 1996 and Aberdeen 1999 from the Pinion 1994 study; Gannon 1991; and Sculpher 1998 and Sculpher 1996 from the Dwyer 1993 study) compared costs to the health service of the two techniques. Two of these trials had two publications reporting total health resource costs of the procedures (including the need for retreatment) at different follow-up times (Cameron 1996 and Aberdeen 1999 (Pinion 1994); Sculpher 1993 and 1996 (Dwyer 1993)). One trial measured direct costs to the participant after one year (Cameron 1996 (Pinion 1994)). Two trials (Sculpher 1993 and Sculpher 1996 from Dwyer 1993, and Cameron 1996 and Aberdeen 1999 from Pinion 1994) calculated cost per participant based on resource use. The third trial calculated costs by summing the average costs of variable resources and then adding a factor of 100% to allow for fixed costs (Gannon 1991).

Results of the search The search was updated in October 2013 and included 62 addi-


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tional potential references. Titles and abstracts were screened by two review authors (RJF and AL). Full-text copies of two references that appeared to meet the inclusion criteria were obtained; one was the re-publication of a trial already included in the 2008 review (Dickerson 2007), and the other was an additional new trial to be included (Sesti 2011), leading to a total of eight trials in the updated review.

Included studies Eight RCTs of endometrial resection/ablation versus hysterectomy with a total of 1,260 randomly assigned participants met the criteria for inclusion in the review, although not all participants contributed to the assessment of every outcome.

Incomplete outcome data In two studies (O’Connor 1997; Dickerson 2007), withdrawal from the study and/or missing data were greater than 10%, and explanations were not provided to enable judgement of whether this could have biased the results. In the former trial, primary outcomes were analysed by an intention-to-treat method (satisfaction rate, quality of life and bleeding outcomes), but intraoperative and perioperative outcomes (adverse events, requirement for further surgery and hospital stay) were analysed according to surgery received. This trial also reported outcomes at three and four years’ follow-up, but as women who were assigned later during the trial had shorter follow-up, these assessments are likely to be underpowered. The other six studies had withdrawals of less than 10% at the time of calculation of outcomes at the first time point. However, in studies with longer follow-up, additional loss to follow-up increased with the duration of the trial.

Excluded studies In the 2008 update of this review, two studies were retrieved for closer inspection and were excluded from the review (Paddison 2003; Lin 2006). One study had allocation according to date of admission and did not satisfy the criteria for true randomisation, and the other was a review of ablation versus hysterectomy. No further studies were retrieved for closer inspection but subsequently excluded in the 2013 update of the review.

Selective reporting Sufficient information was provided in only one study (Dickerson 2007) to indicate that it was free of selective outcome reporting. Before publication of the study results, an earlier publication provided details of the study protocol and changes made throughout the study (Dickerson 2007: other study cited under this ID). The other studies did not provide any evidence of measures taken to prevent selective outcome reporting.

Risk of bias in included studies All included studies were assessed separately for risk of bias (Higgins 2011). A summary of these assessments is provided in Figure 2 and Figure 3.

Allocation Five of the eight included studies provided sufficient detail on the adequacy of the randomisation method (Crosignani 1997; O’Connor 1997; Zupi 2003; Dickerson 2007; Sesti 2011), all at low risk of bias. The other three studies did not describe how randomisation was undertaken and were therefore at unclear risk of bias in this category. All but two studies (Gannon 1991; Zupi 2003) provided sufficient details of allocation concealment; these two studies were therefore at unclear risk of bias, and all other studies were at low risk of bias in this category.

Other potential sources of bias In all of the studies, groups were balanced at baseline. In three studies (Gannon 1991; O’Connor 1997; Zupi 2003), the prior experience of the operating surgeon was described. However, this was not described in the remainder of the studies and could be a potential source of bias, as a less experienced surgeon for either treatment group could alter results such as duration of surgery, adverse outcomes and, in the case of endometrial ablation, effectiveness.

Effects of interventions See: Summary of findings for the main comparison Endometrial resection/ablation for heavy menstrual bleeding Endometrial resection and ablation versus hysterectomy

Blinding Three of the more recent studies used single blinding for assessment of some outcomes (Zupi 2003; Dickerson 2007; Sesti 2011). The other five studies did not appear to have any blinding of participants, investigators or assessors. All studies were therefore at high risk of bias in this category.

Primary outcomes

Effectiveness


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A significant advantage favoured hysterectomy for improvement of bleeding outcomes. These were assessed in different ways in the trials, and not all outcomes could be pooled.

1.1 Woman’s perception (proportion with improvement in bleeding symptoms) Five trials assessed whether bleeding symptoms were perceived as improved; women randomly assigned to endometrial ablation

were slightly less likely to show improvement in bleeding symptoms when compared with those randomly assigned to hysterectomy at one year (RR 0.89, 95% confidence interval (CI) 0.85 to 0.93, four studies, 650 women, I2 = 31%). Differences were also noted at later stages of follow-up, but these findings were only just within the range of statistical significance: at two years (RR 0.92, 95% CI 0.86 to 0.99, two studies, 292 women, I2 = 53%) and at four years (RR 0.93, 95% CI 0.88 to 0.99, two studies, 237 women, I2 = 79%; Figure 4; Analysis 1.1).

Figure 4. Forest plot of comparison: 1 Endometrial resection/ablation versus hysterectomy, outcome: 1.1 Woman’s perception (proportion with improvement in bleeding symptoms).

1.2 PBAC score One trial assessed menstrual blood loss using the PBAC (Pictorial Blood Loss Assessment Chart) score. Compared with pretreatment scores, the PBAC score was significantly reduced in both groups at one and two years postoperatively; however, this finding overall significantly favoured women randomly assigned to hysterectomy at one year (MD 24.40, 95% CI 16.01 to 32.79, one study, 68 women), and even more so at two years (MD 44.00, 95% CI

36.09 to 51.91, one study, 68 women; Analysis 1.2).

1.3 Requirement for further surgery Risk of repeat surgery for failure of the initial surgical treatment was significantly more likely for TCRE/ablation than for hysterectomy at all follow-up periods (all eight trials contributed data for at least one time point): within the first year (RR 14.9, 95% CI 5.2 to


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42.6, six studies, 887 women, I2 = 0%), at two years (RR 23.4, 95% CI 8.3 to 65.8, six studies, 930 women, I2 = 0%), at three years (RR 11.1, 95% CI 1.5 to 80.1, one study, 172 women) and at four years (RR 36.4, 95% CI 5.1 to 259.2, one study, 197 women; Figure 5; Analysis 1.3). Figure 5. Forest plot of comparison: 1 Endometrial resection/ablation versus hysterectomy, outcome: 1.3 Proportion requiring further surgery for HMB.

Acceptability

1.4 Proportion satisfied with treatment

Satisfaction (very or moderately satisfied) rates were comparable (five trials) although lower amongst those who had endometrial ablation at two years after surgery (RR 0.87, 95% CI 0.80 to 0.95, four studies, 567 women, I2 = 0%). No significant differences were noted between post-treatment


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satisfaction rates in groups at other follow-up times (one and four years), although the trend favoured hysterectomy (Figure 6; Analysis 1.4). Figure 6. Forest plot of comparison: 1 Endometrial resection/ablation versus hysterectomy, outcome: 1.4 Proportion satisfied with treatment.

Safety (adverse events)

1.5 Adverse events: short term (intraoperative and immediately postoperative) Most short-term complications were more frequent after hysterectomy than after endometrial resection and ablation techniques. Women who had a hysterectomy were more likely to experience sepsis (RR 0.2, 95% CI 0.1 to 0.3, four studies, 621 women, I 2 = 62%), blood transfusion (RR 0.2, 95% CI 0.1 to 0.6, four studies, 751 women, I2 = 0%), pyrexia (RR 0.2, 95% CI 0.1 to 0.4, three studies, 605 women, I2 = 66%), vault haematoma (RR 0.1, 95% CI 0.04 to 0.3, five studies, 858 women, I2 = 0%) and

wound haematoma (RR 0.03, 95% CI 0.00 to 0.5, one study, 202 women) before their hospital discharge. However, women who underwent TCRE/ablation were more likely to have fluid overload (RR 9.3, 95% CI 2.2 to 39.6, three studies, 611 women, I2 = 0%) when compared with those who had a hysterectomy. No differences between groups were reported for haemorrhage, anaesthesia, perforation, gastrointestinal obstruction, laparotomy, cystotomy, cervical laceration, cardiorespiratory event, thromboembolic event or return to surgery as causes of postoperative complications, although some of these short-term results were based on the findings of only one study (Pinion 1994 or Dickerson 2007; Figure 7; Analysis 1.5).


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Figure 7. Forest plot of comparison: 1 Endometrial resection/ablation versus hysterectomy, outcome: 1.5 Adverse events-short term (intraoperative and immediate postoperative).


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1.6 Adverse events: long term (after hospital discharge) After hospital discharge, sepsis was more likely following hysterectomy in one study (RR 0.2, 95% CI 0.1 to 0.5, one study, 172 women), but no other significant differences were reported (Figure 8; Analysis 1.6). Figure 8. Forest plot of comparison: 1 Endometrial resection/ablation versus hysterectomy, outcome: 1.6 Adverse events-long term (after hospital discharge).

Secondary outcomes

Quality of life Quality of life was measured by a number of validated scales. It was not possible to combine scales, as the domains differed, measuring different aspects of quality of life.

1.7 Quality of life scores (continuous data) Significant differences were detected in five domains of the SF-36 Scale measured one and two years after surgery. Women randomly assigned to hysterectomy reported significantly higher scores on

the social functioning (one and two years), pain (two years), energy (one year) and general health perception (one and two years) domains (social functioning: one year: MD -21.2, 95% CI -24.7 to -17.7, one study, 181 women; two years: MD -10.1, 95% CI 13.55 to -6.58, three studies, 300 women, I2 = 25%) (pain: two years: MD -9.5, 95% CI -12.8 to -6.2, four studies, 513 women, I2 = 63%) (energy: one year: MD -11.0, 95% CI -14.5 to -7.5, two studies, 211 women, I2 = 0%) (general health perception: one year: MD -7.3, 95% CI -10.7 to -3.8, two studies, 385 women, I2 = 81%; two years: MD -7.4, 95% CI -12.8 to -6.21, four studies, 509 women, I2 = 41%). However, women randomly assigned to TCRE/ablation reported significantly higher scores for emotional role limitation at two years (MD 10.2, 95% CI 5.5 to 15.0, three studies, 300 women,


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I2 = 92%). No statistically significant differences in SF-36 scores were noted between the two interventions in the domains of physical role limitation, mental health and physical functioning (Figure 9; Analysis 1.7).


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Figure 9. Forest plot of comparison: 1 Endometrial resection/ablation versus hysterectomy, outcome: 1.7 Quality of life scores (continuous data).


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1.8 Quality of life (proportion with improvement) Differences between groups were not reported in quality of life dimensions as measured by any of the other scales: Golombok Inventory, Euroqol Scale, Sabbatsberg Scale or HAD Scale. The dichotomous outcome of proportion with improvement in pain at two years was not significantly different between surgical groups. However, a greater proportion of those who had undergone a hysterectomy reported an improvement in their general health one year after surgery when compared with those who had received TCRE/ablation (RR 4.2, 95% CI 1.5 to 11.9, one study, 185 women). At four years, this difference between groups had narrowed and was just outside the level of significance (Analysis 1.8).

1.9 Duration of surgery The duration of surgery was significantly longer for hysterectomy in all seven trials, especially when compared with laparoscopic hysterectomy. A pooled estimate was not included in this analysis, as a high degree of heterogeneity was noted, as discussed below under ’Heterogeneity’ (Analysis 1.9).

1.13. Total health service cost per woman All three trials evaluating costs reported that endometrial resection cost the health service less than hysterectomy for the management of heavy menstrual bleeding. This difference continued over a prolonged follow-up time, but the cost gap narrowed primarily because of the retreatment rate for women who underwent endometrial resection. By four years, ablation techniques cost between 5% and 11% less than a hysterectomy in one study that evaluated longterm follow-up (Aberdeen 1999 (Pinion 1994); Analysis 1.13).

1.14. Total individual cost per woman One trial (Cameron 1996 (Pinion 1994)) measured costs to the women. At one year of follow-up, total personal costs, in terms of travel, loss of pay and child care, were higher for women who had a hysterectomy than for women who underwent endometrial ablation. However, women who had a hysterectomy estimated significantly greater savings in the cost of sanitary protection when compared with those who underwent endometrial ablation (savings of UK £85.10 per year vs UK £58.30 per year; Analysis 1.14).

Funnel Plots 1.10. Duration of hospital stay Seven trials evaluated this outcome, and the results were significantly longer after hysterectomy in all trials. A pooled estimate was not included in this analysis, as a high degree of heterogeneity was noted, as discussed below under ’Heterogeneity’ (Analysis 1.12).

1.11. Time to return to normal activity Time to return to normal activity was significantly longer after hysterectomy in all four trials. A pooled estimate was not included in this analysis, as a high degree of heterogeneity was noted, as discussed below under ’Heterogeneity’ (Analysis 1.11).

1.12. Time to return to work Time to return to work was significantly longer after hysterectomy in four of the five trials (the fifth showed no significant difference). A pooled estimate was not included in this analysis, as a high degree of heterogeneity was noted, as discussed below under ’Heterogeneity’ (Analysis 1.10).

Insufficient studies were included in the review for funnel plots to have sufficient power to distinguish chance from true asymmetry.

Heterogeneity For some outcomes, a high level of heterogeneity was observed. For many outcomes, only one trial contributed data, and analysis of heterogeneity was therefore not applicable. However, for four outcomes, data were contributed from several or all trials, and for these outcomes, the forest plots were visually inspected. The estimate for proportion requiring further surgery showed a low level of heterogeneity (all confidence intervals overlapping and I 2 = 0% at one and two years of follow-up). However, a very high degree of heterogeneity was evident for outcomes such as duration of surgery (I2 = 99%), time to return to work (I2 = 100%) and time to return to normal activities (I2 = 97%). The level of clinical heterogeneity for these outcomes may be explained in part by differences in interventions (most notably, mode of hysterectomy) throughout the trials. Two trials (Dwyer and Gannon) included abdominal hysterectomies only; one trial (Crosignani) included only vaginal hysterectomies; and two trials (Zupi and Sesti) included only laparoscopic hysterectomies. All other studies included two or all modes of hysterectomy. To investigate this further, a sensitivity analysis was conducted as below.


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All trials had similar risk profiles for most measures in the risk of bias table. It is therefore assumed that no significant methodological heterogeneity was present.

Sensitivity Analysis The first analysis was performed to determine whether mode of hysterectomy altered the estimates as compared with estimates when all types of hysterectomy were pooled. TCRE/ablation was compared individually against each mode of hysterectomy. For many of the outcomes, the estimates were largely unchanged when this analysis was conducted. Mode of hysterectomy did not change the estimates of comparisons for bleeding outcomes, requirement for further surgery, quality of life or satisfaction rates. In some instances, this occurred because only one trial contributed data to the particular outcome for the pooled estimate. Mode of hysterectomy appeared to influence some aspects of surgical safety and several secondary outcomes. When laparoscopic hysterectomy was compared against TCRE/ablation, the risk ratios for the following short-term adverse outcomes were no longer statistically significant: blood transfusion (RR 0.20, 95% CI 0.07 to 0.59, to RR 0.21, 95% CI 0.01 to 4.27), pyrexia (RR 0.17, 95% CI 0.09 to 0.35, to RR 0.78, 95% CI 0.18 to 3.37) and vault haematoma (RR 0.11, 95% CI 0.04 to 0.34, to RR 0.21, 95% CI 0.01 to 4.25); however, the trend still favoured TCRE/ablation. All modes of hysterectomy were still associated with longer operating times, but this was most marked for laparoscopic hysterectomy, followed by vaginal hysterectomy, and least so for abdominal hysterectomy (mean difference (MD) for all modes pooled 39.6, 95% CI 55.1 to 24.1; for laparoscopic route comparison MD 75.3, 95% CI 165.4 to 14.8; for vaginal route comparison MD 57.6, 95% CI 60.3 to 54.9; and for abdominal route comparison MD 15.6, 95% CI 26.13 to 4.97). Mean differences in hospital stay remained significantly longer for both abdominal and vaginal hysterectomy when compared with TCRE/ablation (MD 4.9 days, 95% CI 6.5 to 3.2; MD 4.3 days, 95% CI 4.5 to 4.1, respectively), but the mean difference in hospital stay between TCRE/ablation and laparoscopic hysterectomy was only just statistically significant (MD 0.3 days, 95% CI 0.7 to 0.1). Abdominal hysterectomy was associated with the greatest difference in time to return to normal activities and time to return to work when compared with TCRE/ablation (MD 21 days, 95% CI 24.8 to 17.2; MD 8.2 weeks, 95% CI 9.5 to 6.8, respectively). For the same outcomes, when TCRE/ablation was compared against vaginal hysterectomy (MD 5 days, 95% CI 7.3 to 2.7; MD 2.4 weeks, 95% CI 2.7 to 2.1, respectively), the difference was less, particularly when compared against laparoscopic hysterectomy (MD 1.5 days, 95% CI 3.1 to 0.1; MD 0.04 weeks, 95% CI 0.3 to 0.25, respectively). A further analysis was performed to investigate the effect of clear evidence of allocation concealment on estimates. For six of the

eight trials, clear evidence indicated that allocation was concealed, but for two trials (Gannon 1991 and Zupi 2003), this was not the case. When only trials with clear evidence of allocation concealment were included in the meta-analysis, no significant change was seen in the estimates compared with when all trials were included. The following analysis was planned but was not conducted: estimates based on all relevant trials regardless of missing data and loss to follow-up versus estimates based on trials for which incomplete outcome assessment was not likely to cause bias. This analysis was not conducted, as no data were missing from the included trials.

DISCUSSION Summary of main results This review assessed the benefits and harms of two surgical procedures for the treatment of heavy menstrual bleeding. When the primary outcomes of this review-effectiveness (woman’s perception of improvement in bleeding outcomes, PBAC score, requirement for further surgery), acceptability and safety (adverse outcomes)-are considered, this review shows that both hysterectomy and TCRE/ ablation are effective, acceptable and safe surgical treatments for heavy menstrual bleeding. Whilst hysterectomy is more effective at reducing bleeding symptoms and improving quality of life and is associated with less repeated surgery than endometrial ablation, considerable short-term benefits are associated with endometrial ablation techniques when compared with hysterectomy, mainly in the areas of recovery time and cost. Hysterectomy was completely successful in treating bleeding problems and led to very high levels (> 95% in most trials) of participant satisfaction up to two years after surgery. Satisfaction levels were also high for women who underwent endometrial ablation; they were significantly lower for these women when compared with hysterectomy at two years of follow-up, although the trend strongly favoured hysterectomy at earlier follow-up. Endometrial destruction techniques were also highly successful in reducing menstrual blood loss in most participants, but a proportion of participants (ranging from 3% to 18%) showed no improvement in their bleeding complaints. At most periods of follow-up, regardless of how bleeding symptoms were measured, women in the hysterectomy groups showed a significantly greater reduction in symptoms than those in the endometrial ablation groups. For some outcomes, it was suggested that these differences were no longer experienced at longer periods of follow-up, possibly because of reduced numbers and/or retreatment in the TCRE/ablation group. Most quality of life measures were not markedly different between the two types of surgery, although evidence from analysis of SF36 scores shows that women who had a hysterectomy perceived


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greater benefit for their general health, social functioning and energy levels at both one and two years and for pain levels at two years after surgery was completed compared with those having endometrial ablation. All other aspects of quality of life as measured by different instruments did not differ between groups. Both surgical treatments were considered to be safe, with low complication rates reported. However, hysterectomy was associated with higher rates of sepsis, pyrexia, requirement for blood transfusion, vault haematoma and wound haematoma. Duration of surgery, hospital stay, time to return to normal activities and time to return to work were shorter for those who had TCRE/ablation when compared with those who underwent hysterectomy. Although the findings from the included studies could not be pooled, almost all of the individual trials consistently reported a significant benefit for TCRE/ablation in these areas. Likely causes of heterogeneity for duration of surgery were variations in surgical route (e.g. vaginal vs abdominal vs laparoscopic hysterectomy or first-generation vs second-generation endometrial resection/ablation techniques), surgical technique and the expertise of surgeons carrying out the procedures. Duration of hospital stay was likely to be affected by changes outside the control of investigators. Hospital policy for maximum stay can vary significantly between hospitals and could have accounted for the heterogeneity observed in the results for this outcome. Route of surgery (e.g. vaginal vs abdominal vs laparoscopic) partially explains the extreme heterogeneity in the time taken for recovery after discharge from hospital. Many hospitals worldwide are adopting a policy of ’enhanced recovery’ following elective surgery, including shorter times to discharge for major operations such as abdominal hysterectomy. Future updates of this review may include trials that reflect this change. Significant differences in operating time, hospital stay and time to return to normal activities and work can be seen in most of the trials, but the magnitude of these differences varies, depending on which mode of hysterectomy is being compared. Although precise estimates cannot be given, TCRE/ablation for abnormal bleeding takes less time to perform and has a shorter recovery time than hysterectomy. These differences are associated with a reduction in health service costs. Evaluation of comparative costs between the two surgical procedures is affected by the increasing retreatment rate. Initially, treatment costs are much lower for women undergoing endometrial ablation than for those undergoing hysterectomy, but the difference in costs between the groups narrows over time because of the cost of retreatment. In one study with a minimum of four years of follow-up, endometrial ablation was reported to be only 5% to 11% less costly than hysterectomy compared with 24% and 29% less costly at one and two years of follow-up. Again here, ’enhanced recovery’ policies may reflect a narrower difference in duration of hospital stay and therefore a corresponding narrower difference in patient costs. As described previously, outcomes may be altered by the prior ex-

perience of the surgeon for both surgical procedures. A less experienced surgeon for either treatment group could alter results such as duration of surgery, adverse outcomes and, in the case of endometrial ablation, effectiveness.

Overall completeness and applicability of evidence The included studies adequately addressed the review question: to assess the relative effectiveness, acceptability and safety of endometrial resection/ablation by any means and hysterectomy via any route for the treatment of heavy menstrual bleeding, as well as the secondary outcomes described above. The inclusion and exclusion criteria were largely met, and the interventions well described. Unfortunately, the outcomes (particularly measures of improvement in bleeding symptoms) were measured in several different ways, and it was not possible for all estimates to be pooled, making metaanalysis impossible for some outcomes. On the whole, the review findings were consistent with currently accepted clinical advice and are in agreement with current guidelines. National Institute for Health and Care Excellence (NICE) guidelines for menorrhagia (NICE 2007) suggest that hysterectomy should not be used as a first-line treatment for benign HMB and should be considered only when other treatment options have failed, are contraindicated or are declined by the woman; when there is a wish for amenorrhoea; when the woman (who has been fully informed) requests it; and/or when the woman no longer wishes to retain her uterus and fertility. NICE 2007 guidelines are in agreement with the findings of this review with regard to potential complications associated with both modes of surgical treatment.

Quality of the evidence In total, eight studies were included with a total of 1,260 randomly assigned participants. All studies were at high risk of performance/detection bias, as it is not feasible to blind women or the surgeon against the type of operation that was performed. Several of the older studies were at high risk of selection bias. As the studies used many different measurements for the outcomes (particularly for effectiveness of treatment), it was not possible to pool data for every outcome. However, the results were largely comparable; both treatments are considered to be effective and safe, hysterectomy was generally superior in improving symptoms and in leading to less requirement for future surgery and endometrial ablation was superior in terms of fewer adverse outcomes, shorter operating times and faster return to activities/work. For many outcomes, assessment of heterogeneity was not relevant, as only one trial contributed data. For outcomes that displayed a high level of clinical heterogeneity, this was explained in part


26

by differences in outcomes for different modes of hysterectomy (further described under ’Sensitivity analysis’). Quality of evidence was low to moderate, depending on the outcome. PBAC score, adverse events and proportion satisfied with treatment generated a moderate GRADE score, suggesting that further research may change the estimate. Outcomes that generated a low GRADE score included the woman’s perception of bleeding and the proportion of women requiring further surgery for HMB. For these two outcomes, further evidence is likely to change the estimate.

Potential biases in the review process Electronic searches in combination with handsearches performed by the review authors identified all relevant studies known to be available currently. The inability to pool data for particular outcomes is likely to decrease the power of results; this may change if future studies are able to add data to the existing outcomes.

Agreements and disagreements with other studies or reviews Bhattacharya 2011 performed a systematic review that compared clinical effectiveness and cost-effectiveness analyses of hysterectomy, endometrial ablation and Mirena for heavy menstrual bleeding. These findings were in accordance with the findings of this review; satisfaction rates at 12 months were highest for hysterectomy, and rates of further surgery after endometrial resection/ablation were comparable (8.5%). The authors also noted longer hospital stay and longer time to return to normal activities for hysterectomy. Women who have undergone hysterectomy have experienced more postoperative complications than women who have received TCRE/ablation, although for some types of complications, no differences were reported. Because some complications are rare, these rates are best compared with those of large audits, such as the Mistletoe audit in the UK (Overton 1997). The low rate of complications for TCRE/ablation in this review confirms the findings of the Mistletoe study. A comparison of costs of endometrial resection and ablation techniques versus those of hysterectomy cannot adequately provide information on the relative value in terms of money of these two surgical procedures. The availability of TCRE/ablation as a treatment for HMB may result in an earlier recourse to surgery than a woman would have considered if the only surgery available was hysterectomy (Bridgman 1994; Coulter 1994), and this will have a significant impact on costs. Additional studies have provided assessments of cost-effectiveness based on the Dwyer 1993 trial through a cost-utility analysis (Sculpher 1998), preferencebased treatment allocation (woman allocated to the treatment that she prefers) (Sculpher 1998) and four other cost-utility analyses

(Garside 2004; You 2006; Clegg 2007; Roberts 2011). Garside 2004 concluded that abdominal hysterectomy is likely to be more cost-effective than endometrial resection if healthcare purchasers are willing to pay an additional cost of at least UK £6,500 per extra quality-adjusted life-year (QALY) generated by hysterectomy, although an area of uncertainty is attached to this conclusion in the form of variation in the parameters used in the analysis. Clegg 2007 found that a preference-based treatment allocation was more cost-effective than reliance on a single intervention for all women requiring surgery for HMB. Garside 2004 reported that hysterectomy was more expensive than endometrial ablation but accrued more QALYs over 10 years. The incremental cost per QALY of hysterectomy compared with two second-generation endometrial ablation techniques was approximately UK £2,000. You 2006 also confirmed that hysterectomy was a more expensive option than endometrial ablation (cost per woman: US $6,878 vs US $6,185 over five years) but was more effective (4.725 QALYs vs 4.624 QALYs). Roberts 2011 found that hysterectomy produced more QALYs relative to second-generation endometrial ablation, with an incremental cost-effectiveness ratio of £970 per additional QALY. Data from the Clegg 2007 cost-utility analysis contradicted this finding; the authors reported that second-generation methods accrued marginally more QALYs than hysterectomy over five years (4.13 vs 4.01 QALYs). Evaluation of the comparative cost-effectiveness of endometrial destruction techniques and hysterectomy is complex, and the simple conclusion that endometrial destruction is cheaper than hysterectomy, with the difference narrowing over time, may not represent an adequate economic assessment.

AUTHORS’ CONCLUSIONS Implications for practice • Although hysterectomy is more effective at resolving bleeding problems and satisfaction rates are high, endometrial destruction by TCRE or ablation is an alternative to hysterectomy that should be offered to women with heavy menstrual bleeding. • TCRE/ablation techniques have satisfaction rates ranging from 70% to 80% with shorter operation time and hospital stay, earlier recovery and reduced postoperative complications. However, a preoperative discussion should focus on the possibility of further surgery being necessary for those women who choose endometrial destruction techniques for relief of their heavy menstrual bleeding. • The initial cost of endometrial destruction is significantly lower than that of hysterectomy, but because retreatment is often necessary, the cost difference narrows over time.


27

• Laparoscopic hysterectomy represents an improvement of several of the previously described disadvantages of hysterectomy, and some outcomes such as duration of hospital stay, time to return to work and time to return to normal activities have become more comparable with those of endometrial ablation. It should be noted, however, that laparoscopic hysterectomy is associated with longer operating time than is required by other modes of hysterectomy and requires more sophisticated surgical expertise and equipment.

• It is recommended that women be encouraged to play an active role in selecting the type of surgery, based on the personal value that they place on the advantages and disadvantages of each surgical approach.

for HMB, second-generation methods have overtaken firstgeneration methods in the UK and are now the most common operation for HMB (Reid 2007). One further trial in this category was added in the 2013 update (Sesti 2011). • Trials with follow-up of four years or longer to adequately assess the cost differential between the two types of surgery and the requirement for further surgical treatment in women randomly assigned to TCRE or to endometrial ablation. • Trials that incorporate ’enhanced recovery’ programmes. In the future, findings of these trials may reflect shorter hospital stay for women undergoing hysterectomy, and therefore a smaller difference between the two procedures for this particular outcome.

Implications for research Additional trials are needed in the following areas.

ACKNOWLEDGEMENTS • Comparison of more recent types of hysterectomy (supracervical, vaginal and laparoscopically assisted vaginal) versus endometrial ablation techniques. One further trial in this category was added in the 2013 update (Sesti 2011); however, more data are needed to reduce heterogeneity for some outcomes. Results from this trial did not contribute data to cost comparisons, and this is likely to be clinically important.

• Comparison of second-generation ablation methods versus hysterectomy. Evidence suggests that whereas first-generation ablation methods did not have an impact on hysterectomy rates

The review authors acknowledge the helpful comments of those who refereed previous versions of this review. We are especially grateful to Professor Pier Crosignani, Dr Kay Dickerson and Dr Sbracia, who answered queries and provided additional material for this review. Special thanks are also due to Helen Nagels, Managing Editor of the Menstrual Disorders and Subfertility Group, for her professionalism and help with the inevitable problems that arose, and to Marion Showell, Trials Search Co-ordinator, for her assistance in identifying trials. The authors of the 2013 update acknowledge the contribution of Dr Inez Cooke, who wrote the protocol for the 2008 review.

REFERENCES

References to studies included in this review Crosignani 1997 {published data only} ∗ Crosignani PG, Vercellini P, Apolone G, De Giorgi O, Cortesi I, Meschia M. Endometrial resection versus vaginal hysterectomy for menorrhagia: long-term clinical and quality-of-life outcomes. American Journal of Obstetrics & Gynecology 1997;177:95–101. Dickerson 2007 {published data only} Dickerson K, Munro M, Langenberg P, Scherer R, Frick KD, Weber AM, et al.Surgical treatments outcomes project for dysfunctional uterine bleeding (STOP-DUB): design and methods. Controlled Clinical Trials 2003;24:591–609. ∗ Dickerson K, Munro MG, Clark M, Langenberg P, Scherer R, Frick K, et al.Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding.

Obstetrics and Gynecology 2007;110(6):1279–89. Munro M, Dickerson K, Clark M, Langenberg P, Scherer R, Frick K. The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding: summary of an Agency for Health Research and Quality-sponsored randomized trial of endometrial ablation versus hysterectomy for women with heavy menstrual bleeding. Menopause 2011;18(4):451–8.

Dwyer 1993 {published data only} ∗ Dwyer N, Hutton J, Stirrat GM. Randomised controlled trial comparing endometrial resection with abdominal hysterectomy for the surgical treatment of menorrhagia. British Journal of Obstetrics & Gynaecology 1993;100: 237–43. Sculpher M. A cost-utility analysis of abdominal hysterectomy versus transcervical endometrial resection for the surgical treatment of menorrhagia. International Journal


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of Technology Assessment in Health Care 1998;14(2):302–19. Sculpher MJ, Bryan S, Dwyer N, Hutton J, Stirrat GM. An economic evaluation of transcervical endometrial resection versus abdominal hysterectomy for the treatment of menorrhagia. British Journal of Obstetrics & Gynaecology 1993;100:244–52. Sculpher MJ, Dwyer N, Byford S, Stirrat GM. Randomised trial comparing hysterectomy and transcervical endometrial resection: effect on health related quality of life and costs two years after surgery. British Journal of Obstetrics & Gynaecology 1996;103:142–9. Gannon 1991 {published data only} ∗ Gannon MJ, Holt EM, Fairbank J, Fitzgerald M, Milne MA, Crystal AM, et al.A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia. British Medical Journal 1991; 303:1362–4. O’Connor 1997 {published data only} ∗ O’Connor H, Broadbent JAM, Magos AL, McPherson K. Medical Research Council randomised trial of endometrial resection versus hysterectomy in management of menorrhagia. Lancet 1997;349:897–901. Pinion 1994 {published data only} Aberdeen Endometrial Ablation Trials Group. A randomised trial of endometrial ablation versus hysterectomy for the treatment of dysfunctional uterine bleeding: outcome at four years. British Journal of Obstetrics & Gynaecology 1999; 106:360–6. Alexander DA, Naji AA, Pinion SB, Mollison J, Kitchener HC, Parkin DE, et al.Randomised trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects. British Medical Journal 1996;312:280–4. Cameron IM, Mollison J, Pinion SB, Atherton-Naji A, Buckingham K, Torgerson D. Cost comparison of hysterectomy and hysteroscopic surgery for the treatment of menorrhagia. European Journal of Obstetrics and Gynaecology 1996;70:87–92. ∗ Pinion SB, Parkin DE, Abramovich DR, Naji A, Alexander DA, Russell IT, et al.Randomised trial of hysterectomy, endometrial laser ablation, and transcervical endometrial resection for dysfunctional uterine bleeding. British Medical Journal 1994;309:979–83. Sesti 2011 {published data only} Sesti F, Ruggeri V, Pietropolli A, Piancatelli R, Piccione E. Thermal balloon ablation versus laparoscopic supracervical hysterectomy for the surgical treatment of heavy menstrual bleeding: a randomized study. The Journal of Obstetrics and Gynaecology Research 2011;37:1650–7. Zupi 2003 {published data only} Zupi E, Zullo F, Marconi D, Sbracia M, Pellicano M, Solima E, et al.Hysteroscopic endometrial resection versus laparoscopic supracervical hysterectomy for menorrhagia: a prospective randomized trial. American Journal of Obstetrics and Gynecology 2003;188:7–12.

References to studies excluded from this review Lin 2006 {published data only} Lin H. Comparison between microwave endometrial ablation and total hysterectomy. Chinese Medical Journal 2006;119(14):1195–7. Paddison 2003 {published data only} Paddison K. Menorrhagia: endometrial ablation or hysterectomy. Nursing Standard 2003;18(1):33–7.

Additional references Bhattacharya 2011 Bhattacharya S, Middleton L, Tsourapas A, Champaneria R, Daniels J, Roberts T, et al.Hysterectomy, endometrial ablation and Mirena for heavy menstrual bleeding: a systematic review of clinical effectiveness and costeffectiveness analysis. Health Technology Assessment April 2011;19:1–252. Bourdrez 2004 Bourdrez P, Bongers MY, Mol BWJ. Treatment of dysfunctional uterine bleeding: patient preferences for endometrial ablation, a levonorgestrel-releasing intrauterine device, or hysterectomy. Fertility and Sterility 2004;82(1): 160–6. Brazier 1993 Brazier JE, Jones NMB, Kind P. Testing the validity of the Euroqol and comparing it with the SP36 health survey questionnaire. Quality of Life Research 1993;2:169–80. Bridgman 1994 Bridgman SA. Increasing operative rates for dysfunctional uterine bleeding after endometrial ablation (letter). Lancet 1994;344:893. Clegg 2007 Clegg JP, Guest JF, Hurskainen R. Cost-utility of levonorgestrel intrauterine system compared with hysterectomy and second generation endometrial ablative techniques in managing patients with menorrhagia in the UK. Current Medical Research and Opinion 2007;23(7): 1673–48. Cooper 2011 Cooper K, Lee A, Chien P, Raja E, Timmaraju V, Bhattacharya S. Outcomes following hysterectomy or endometrial ablation for heavy menstrual bleeding: retrospective analysis of hospital episode statistics in Scotland. British Journal of Obstetrics and Gyanecology 2011; 118:1171. Coulter 1991 Coulter A, Bradlow J, Agass M, Martin-Bates C, Tullock A. Outcomes of referrals to gynaecology outpatient clinics for menstrual problems: an audit of general practice records. British Journal of Obstetrics & Gynaecology 1991;98:789–96. Coulter 1994 Coulter A. Trends in gynaecological surgery (letter). Lancet 1994;344:1367.


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Euroqol Group 1990 Euroqol Group. Euroqol-a new facility for the measurement of health-related quality of life. Health Policy 1990;16: 199–208.

Nagele 1998 Nagele F, Rubinger T, Magos A. Why do women choose endometrial ablation rather than hysterectomy?. Fertility and Sterility 1998;69(6):1063–6.

Fernandez 2011 Fernandez H. Update on the management of menometrorrhagia: new surgical approaches. Gynaecological Endocrinology 2011;1:1131–6.

NICE 2007 National Collaborating Centre for Women’s and Children’s Health. Heavy Menstrual Bleeding. London: RCOG Press, 2007.

Garrat 1995 Garrat AM, Torgerson DJ, Wyness J, Hall MH, Reid DM. Measuring sexual functioning in premenopausal women. British Journal of Obstetrics & Gynaecology 1995;102:311–6.

Overton 1997 Overton C, Hargreaves J, Maresh M. A national survey of the complications of endometrial destruction for menstrual disorders: the MISTLETOE study. British Journal of Obstetrics & Gynaecology 1997;104:1351–9.

Garside 2004 Garside R, Stein K, Wyatt K, et al.A cost-utility analysis of microwave and thermal balloon endometrial ablation techniques for the treatment of heavy menstrual bleeding. British Journal of Obstetrics and Gynaecology 2004;111: 1103–14. Higgins 2008 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2008;327 (7414):557–60. Higgins 2011 Higgins JPT, Altman DG. Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.0. New York: John Wiley & Sons, 2011. Kennedy 2002 Kennedy ADM, Sculpher MJ, Coulter A, Dwyer N, Rees M, Abrams KR, et al.Effects of decision aids for menorrhagia on treatment choices, health outcomes and costs. JAMA 2002;288(21):2701–8. Lethaby 2005 Lethaby A, Hickey M, Garry R. Endometrial destruction techniques for heavy menstrual bleeding. Cochrane Database of Systematic Reviews. John Wiley, 2005, issue 4. [DOI: 10.1002/14651858] Lethaby 2009 Lethaby A, Hickey M, Garry R, Penninx J. Endometrial resection/ablation techniques for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2009, (4):[DOI: 10.1002/14651858.CD001501.pub3]. Li 2012 Li M, Han Y, Feng YC. Single-port laparoscopic hysterectomy vs conventional laparoscopic hysterectomy: a prospective randomised trial. Journal of International Medical Research 2012;40(2):701–8. Munro 2011 Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. International Journal of Gynaecology and Obstetrics 2011;113(1):3–13.

Reich 1989 Reich H, DeCaprio J, McGlynn F. Laparoscopic hysterectomy. Journal of Gynaecological Surgery 1989;5:213. Reid 2007 Reid PC. Endometrial ablation in England-coming of age? An examination of hospital episode statistics 1989/1990 to 2004/2005. European Journal of Obstetrics and Gynecology 2007;135:191–4. Roberts 2011 Roberts T, Tsourapas A, Champaneria R, Daniels J, Cooper K, Bhattacharya S, et al.Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost effectiveness analysis. BMJ April 2011;342:d2202. Rust 1986 Rust J, Bennum I, Crowe M, Golombok S. The construction and validation of the Golombok Rust inventory of marital state. Sexual & Marital Therapy 1986;1:34–40. Sculpher 1998 Sculpher M. The cost-effectiveness of preference-based treatment allocation: the case of hysterectomy versus endometrial resection in the treatment of menorrhagia. Health Economics 1998;7:129–42. Sharp 2012 Sharp HT. Endometrial ablation: postoperative complications. American Journal of Obstetrics and Gynaecology 2012;206:4. Vessey 1992 Vessey M, Villard-Mackintosh L, McPherson K, Coulter A, Yeates D. The epidemiology of hysterectomy: findings in a large cohort study. British Journal of Obstetrics & Gynaecology 1992;99:402–7. Ware 1993 Ware JE, Snow KK, Kosiniski M, et al.Health survey: manual and interpretation guide. The Health Institute. Boston: New England Medical Centre, 1993. Woolcock 2008 Woolcock JG, Critchley HO, Munro MG, et al.Review of the confusion in current and historical terminology and definitions for disturbances in menstrual bleeding. Fertility and Sterility 2008;90:2269.


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You 2006 You JHS, Sahota DS, Yuen PM. A cost-utility analysis of hysterectomy, endometrial resection and ablation and medical therapy for menorrhagia. Human Reproduction 2006;21(7):1878–83. Zigmond 1983 Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica 1983;67: 361–70. ∗ Indicates the major publication for the study


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CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID] Crosignani 1997 Methods

Randomisation by computer-generated sequence using numbered opaque sealed envelopes Single-centre, parallel-group with no blinding Number of women randomly assigned: n = 92 Number of withdrawals: n = 7 (four in the resection group: one refused treatment, one underwent surgery in another hospital, one did not want further treatments, and one was lost to follow-up before surgery; three in the hysterectomy group: one refused treatment, one had surgery in another hospital and one decided on long-term medical treatment) Power calculation for sample size performed and analysis by intention to treat Source of funding not reported

Participants

Women 42 to 49 years of age, with menorrhagia not responding to medical treatment and requiring hysterectomy, recruited from an outpatient clinic in Milan, Italy Inclusion criteria: ≤ 50 years, mobile uterus with volume < 12 weeks in gestational size and < 380 mL on ultrasound, negative cervical smear, no evidence of atypical hyperplasia at endometrial biopsy, no adnexal tumours at clinical and ultrasound examination Exclusion criteria: known PID or endometriosis, urinary stress incontinence, moderate/ severe genital prolapse, clotting disorders, use of IUD or drugs that may affect MBL, unstable general conditions, submucous myomas > 3 cm in diameter or > 50% intramural extension

Interventions

Rx 1: hysteroscopic endometrial resection Rx 2: vaginal hysterectomy Duration: two years of follow-up Prior experience of the surgeon not mentioned

Outcomes

Participant satisfaction with treatment Improvement in MBL Quality of life Duration of surgery (minutes) Duration of hospital stay (days) Return to work (weeks) Requirement for further surgery

Notes

Author contacted for additional information and reply received

Risk of bias Bias

Authors’ judgement

Random sequence generation (selection Low risk bias)


Support for judgement Computer-generated randomisation sequence

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Crosignani 1997

(Continued)

Allocation concealment (selection bias)

Low risk

Numbered opaque sealed envelopes

Blinding (performance bias and detection High risk bias) All outcomes

Not feasible for a comparison of surgical techniques

Incomplete outcome data (attrition bias) All outcomes

Low risk

Clear reasons given for withdrawal-appeared balanced in numbers between groups

Selective reporting (reporting bias)

Unclear risk

Unclear-no protocol identified. Study did not measure adverse events

Other bias

Low risk

Groups appeared balanced at baseline (although the table did not include dropouts) , and no other biases were identified

Dickerson 2007 Methods

Randomisation by computer-generated permuted blocks of random size stratified by age and site Multi-centre (n = 25), parallel-group, single-blinded (only assessors) Number of women randomly assigned: n = 237 Number of withdrawals: at one year: 16 in endometrial ablation group, 11 in hysterectomy group; at two years: 17 in endometrial ablation group, seven in hysterectomy group Power calculation for sample size (90% power based on quality of life measures) but recruitment did not quite achieve the required sample size Analysis was by intention to treat for primary bleeding and satisfaction outcomes. Analysis was not by intention to treat for assessment of intraoperative and perioperative events Source of funding: AHRQ and Brown Medical School

Participants

Women with dysfunctional bleeding (not explained by pathology, drugs, etc.), most of whom were younger than 45 years of age (85%), recruited from 25 clinical centres in United States and Canada. Inclusion: 18 years of age or older; premenopausal; dysfunctional uterine bleeding for at least six months (defined as one or more of excess duration, amount or unpredictability); refractory to medical treatment for at least three months. Exclusion: postmenopausal; bilateral oophorectomy; pregnant; wishing to retain fertility; refusal to consider surgery

Interventions

Rx 1: resectoscopic endometrial ablation with electrodesiccation/coagulation or vaporisation OR ablation with thermal balloon Rx 2: vaginal, laparoscopic or abdominal hysterectomy under general or regional anaesthesia. In both groups, women > 45 years were allowed oophorectomy Duration of trial: enrolment was staggered, with some women having data for five years Prior experience of the surgeon not mentioned


33

Dickerson 2007

(Continued)

Outcomes

Pain, bleeding and fatigue at one year Other outcomes at different time points: QOL outcomes, sexual function, employment, housework, leisure activities, out-of-pocket costs, health provider visits, surgical complications, additional surgery

Notes

Author contacted for clarification of some points and reply received

Risk of bias Bias


Support for judgement


Randomisation schedule (computer-generated permuted blocks) was developed by the Co-ordinating Centre and was stratified by participating centre


Central allocation

Low risk


Single blinding for interviewers requesting information on bleeding history, quality of life, etc. But women providing this information knew of their assignment


Unclear risk

No reasons given for dropouts


Low risk

Protocol published with details on prespecified outcomes

Other bias

Low risk

Groups appear balanced at baseline. However, some outcomes (intraoperative and perioperative events, including adverse events) reported according to surgery received

Dwyer 1993 Methods

Randomisation by sealed numbered envelopes in variable blocks of 20, 30 and 50 Single-centre, parallel-group, no blinding Number of women randomly assigned: n = 200 Number of withdrawals: n = 4 (three from the hysterectomy group and one from the resection group) Power calculation for sample size performed but intention-to-treat analysis not reported Source of funding: South West Regional Health Authority

Participants

Women with mean age of 40 years, recruited from an outpatient gynaecology clinic at a teaching hospital in Bristol, UK Inclusion criteria: < 52 years of age, complaint of menorrhagia that could not be con-


34

Dwyer 1993

(Continued)

trolled by conservative means, candidates for abdominal hysterectomy Exclusion criteria: uterine size ≤ 12 gestational weeks, additional symptoms or other pathology, making hysterectomy the preferred treatment Interventions

Rx 1: endometrial resection, n = 99 Rx 2: abdominal hysterectomy, n = 97 Duration: four months of follow-up, 2.8 years of follow-up Prior experience of the surgeon not mentioned

Outcomes

Satisfaction with surgery at four months Satisfaction with surgery at 2.8 years Change in menstrual blood loss after surgery (subjective) at four months Change in menstrual blood loss after surgery (subjective) at 2.8 years Quality of life at 2.8 years Postoperative complications Duration of hospital stay (days) Duration of surgery (minutes) Return to work (weeks) Requirement for further surgery within one year Requirement for further surgery at 2.8 years Total health service resource cost at four months Total health service resource cost at 2.8 years

Notes

Three publications used the same study population: Dwyer 1993; Sculpher 1993; Sculpher 1996 Dr Dwyer contacted for additional information but no reply received

Risk of bias Bias



Random sequence generation (selection Unclear risk bias)

Randomisation sequence not described


Sealed numbered envelopes in variable blocks

Low risk




Low risk

Dropouts from trial minimal and not likely to bias results


Unclear risk

No prior protocol identified

Other bias

Low risk

Groups appeared balanced at baseline. No other bias identified


35

Gannon 1991 Methods

Randomisation by sealed envelope Single-centre, parallel-group, no blinding Number of women randomly assigned: n = 54 Number of withdrawals: n = 3 (one from the resection group who wanted hysterectomy, one from the hysterectomy group who wanted resection and one from the hysterectomy group who postponed surgery and was treated elsewhere) Power calculation and intention-to-treat analysis not reported Source of funding: not reported

Participants

Women with median age 40 years and awaiting abdominal hysterectomy for menorrhagia, recruited from the Royal Berkshire Hospital in Reading, UK Exclusion criteria: leiomyomata, endometrial or cervical neoplasia, concomitant ovarian pathology, pelvic inflammatory disease or endometriosis

Interventions

Rx 1: endometrial resection, n = 25 Rx 2: abdominal hysterectomy, n = 26 Duration: 12 months (mean) of follow-up Procedures performed by ’experienced surgeons on routine operating lists’

Outcomes

Change in menstrual blood loss Duration of surgery (minutes) Duration of hospital stay (days) Return to work (weeks) Postoperative complications Requirement for further surgery Resource cost of surgery (theatre and ward) (per woman)

Notes

Endometrial resection women given an intramuscular injection of medroxyprogesterone acetate 150 mg four to six weeks before surgery to reduce endometrial thickness Author contacted but no reply received

Risk of bias Bias






Sealed envelope but no other safeguards described

Unclear risk




Low risk

Dropouts minimal and not likely to cause bias


Unclear risk



36

Gannon 1991

Other bias

(Continued)

Low risk

Groups appeared balanced at baseline, although very few parameters examined

O’Connor 1997 Methods

Randomisation at a ratio of 2:1 from a computer-generated random number sequence, with the code kept at the Royal Free Hospital Multi-centre, parallel-group with no blinding Number of women randomly assigned: n = 202 Number of withdrawals: n = 30 (26 before surgery and four lost to follow-up) Power calculation for sample size performed and analysis by intention to treat Source of funding: Medical Research Council

Participants

Women 30 to 50 years of age who had symptomatic menorrhagia that required hysterectomy were recruited from several centres in the UK (King’s Lynn, Portsmouth, Plymouth, London, Bradford, Chelmsford, Northampton, Birmingham and Exeter) Inclusion criteria: 30 to 50 years of age, decision to have no more children, regular menstrual cycles of between 21 and 35 days, with each period lasting for less than 50% of the cycle, documented evidence of normal endometrial histology within the previous 12 months and normal cervical smear within the previous three years Exclusion criteria: serious intercurrent illness, intermenstrual or postcoital bleeding, uterine size corresponding to pregnancy of greater than 12 weeks of gestation, submucous fibroids larger than 5 cm in diameter, adnexal tenderness that is suggestive of pelvic inflammatory disease or endometriosis, major uterovaginal prolapse or severe urinary symptoms, severe premenstrual syndrome or menopausal symptoms

Interventions

Rx 1: transcervical endometrial resection, n = 116 Rx 2: hysterectomy, n = 46 (n = 28 abdominal, n = 28 vaginal) Duration: two years (median) of follow-up Surgeons performing TCRE required prior experience of at least 20 procedures. Surgeons performing hysterectomy were ’experienced’ or were supervised by an experienced surgeon

Outcomes

Satisfaction rate at two years Quality of life (General Health Questionnaire, Mood scales, Social Adjustment Scale)these were not entered in this review because the data were in graphical form and were not provided in numerical form by the authors Duration of surgery (minutes) Duration of hospital stay (days) Blood loss (this outcome not entered in the review because SD was too large and data were not available for transformation) Difficulty of surgery (this outcome not entered in the review) Complication rate Requirement for further surgery

Notes Risk of bias Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

37

O’Connor 1997

(Continued)

Bias




Computer-generated random number sequence


Code to randomisation kept separate, with telephoning for next assignment

Low risk




Unclear risk

Dropouts greater than 10% and reasons not given


Unclear risk


Other bias

Low risk

Groups appeared balanced at baseline. No other potential bias identified

Pinion 1994 Methods

Randomisation, ratio of 2:1:1 (hysterectomy:resection:ablation), by a series of numbered opaque envelopes in a random order Single-centre, parallel-group, no blinding Number of participants randomly assigned: n = 204 Number of withdrawals: n = 6 (two before surgery and four refused the allocated treatment) Power calculation for sample size performed and analysis by intention to treat Source of funding: Scottish Office Home and Health Dept and ICI (Zeneca)

Participants

Women with mean age of 40 years, eligible to undergo hysterectomy for menorrhagia, recruited from the general gynaecology clinics of the Aberdeen Royal Infirmary in Scotland, UK Inclusion criteria: age < 50 years, weight < 100 kg, clinical diagnosis of dysfunctional uterine bleeding, uterus < 10 weeks of gestational size, normal endometrial histology No exclusion criteria reported

Interventions

Rx 1: laser ablation (n = 53) or endometrial resection (n = 52) Rx 2: hysterectomy (n = 87 abdominal, n = 12 vaginal), n = 99 Duration: four years of follow-up Prior experience of the surgeon not mentioned

Outcomes

Satisfaction rate at one and four years Change in general health Change in MBL Duration of surgery (minutes)


38

Pinion 1994

(Continued)

Duration of hospital stay (days) Return to work (weeks) Complication rate Quality of life (Hospital Anxiety and Depression Scale, Golombok Rust Inventory of Marital State) Quality of life (Psychosocial Adjustment to Illness Scale)-this outcome not entered in the review because not enough information provided about categories Health service costs at one and four years Participant costs at one year Requirement for further surgery Notes

Author contacted for additional data but no reply received This trial has four publications using the same study population and assessing different outcomes Data usually available only for the laser ablation and endometrial resection combined

Risk of bias Bias






Series of numbered opaque envelopes

Low risk




Low risk

Dropouts minimal and unlikely to cause bias


Unclear risk


Other bias

Low risk

Groups appeared balanced at baseline and no other potential bias identified

Sesti 2011 Methods

Randomisation by computer-generated sequence of serially numbered opaque envelopes Single-centre parallel-group with blinding of assessors Number of women randomly assigned: n = 68 Number of withdrawals: n = 0 Power calculation for sample size performed and analysis by intention to treat Source of funding: Italian Ministry of University

Participants

Women 35 to 50 years of age with heavy menstrual bleeding, who had failed appropriate first-line oral medical therapy and required surgical treatment


39

Sesti 2011

(Continued)

Inclusion criteria: PBAC score ≥ 100 (average of two consecutive cycles), completed family, normal smear, pelvic ultrasound scan and endometrial biopsy Exclusion criteria: previous endometrial resection/ablation, previous levonorgestrel intrauterine system, any uterine pathology on pelvic ultrasound scan or hysteroscopy, any pathology whereby hysterectomy was indicated, uninvestigated abnormal bleeding or postmenopausal bleeding Interventions

Rx 1: endometrial ablation via Thermachoice III thermal balloon ablation Rx 2: laparoscopic subtotal hysterectomy Duration of follow-up: 24 months All surgery was performed by the same two surgeons; however, prior experience of the surgeon not mentioned

Outcomes

Primary: Menstrual bleeding (PBAC score) at three, six, 12 and 24 months Secondary: Quality of life (SF-36 score) at 24 months Improvement in bleeding patterns (frequency and duration of bleeding) at three, six, 12 and 24 months Haemoglobin levels at three, six, 12 and 24 months Intensity of postoperative pain Early postoperative complications

Notes

Information included in the study was sufficient for meta-analysis-not necessary to contact authors

Risk of bias Bias




Computer-generated randomisation sequence


Serially numbered, opaque sealed envelopes

Low risk




Low risk

All women accounted for in groups to which they were randomly assigned


Low risk

All prespecified outcomes reported.

Other bias

Low risk

Groups balanced at baseline. No other potential bias identified


40

Zupi 2003 Methods

Computer-generated randomisation number sequence Single-centre, parallel-group, single-blind (assessors of SF-36 results) Number of women randomly assigned: 203 Number of women analysed: 181 Power calculation for sample size (power of 0.8 for difference in satisfaction rate of 50% between groups) Analysis was by intention to treat Source of funding: not reported

Participants

Women with mean age of 43 years with menometrorrhagia unresponsive to medical treatment, recruited between March 1995 and February 1997 from Departmental O and G Clinic in the Tor Vergarta University of Rome, Italy Inclusion: younger than 50 years of age; weight less than 100 kg; not seeking contraception; normal endometrial histology and Pap smear within the previous six months; uterus not greater than 12 weeks of pregnancy in size; without submucosal fibroids, adnexal masses or endometriosis Exclusion: no further exclusion criteria reported

Interventions

Rx 1: pretreatment with GnRHa one month before surgery, then hysteroscopic endometrial resection Rx 2: laparoscopic supracervical hysterectomy Duration: two years (follow-up at three months, at one and two years) All surgeons were proficient in both endometrial resection and laparoscopic hysterectomy

Outcomes

Pain (immediately after surgery and then for a week) Duration of vaginal bleeding Date resumed normal activities, sexual intercourse, work Quality of life (SF-36) Further surgery Operative outcomes (duration of surgery, blood loss, complications, hospital stay)

Notes Risk of bias Bias




Computer-generated random number sequence


Not described

Unclear risk



Not feasible for a comparison of surgical techniques. Single blinding of assessors who administered the SF-36, but women who provided the answers knew of their assignment

41

Zupi 2003

(Continued)


Low risk

Dropouts minimal and unlikely to cause bias


Unclear risk


Other bias

Low risk

Groups appeared balanced at baseline and no other potential bias identified

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Lin 2006

Not an RCT

Paddison 2003

Not an RCT


42

DATA AND ANALYSES

Comparison 1. Endometrial resection/ablation versus hysterectomy

Outcome or subgroup title 1 Woman’s perception (proportion with improvement in bleeding symptoms) 1.1 Within one year of follow-up 1.2 At two years of follow-up 1.3 At four years of follow-up 2 PBAC score (continuous data) 2.1 At one year of follow-up 2.2 At two years of follow-up 3 Proportion requiring further surgery for HMB 3.1 Within one year after surgery 3.2 At two years after surgery 3.3 At three years after surgery 3.4 At four years after surgery 4 Proportion satisfied with treatment 4.1 At one year of follow-up 4.2 At two years of follow-up 4.3 At four years of follow-up 5 Adverse events-short term (intraoperative and immediate postoperative) 5.1 Sepsis 5.2 Haemorrhage 5.3 Blood transfusion 5.4 Pyrexia 5.5 Vault haematoma 5.6 Wound haematoma 5.7 Anaesthetic 5.8 Fluid overload 5.9 Perforation 5.10 Gastrointestinal obstruction/ileus 5.11 Laparotomy 5.12 Cystotomy 5.13 Cervical laceration 5.14 Cardiorespiratory event 5.15 Thromboembolic event 5.16 Readmission/return to surgery

No. of studies

No. of participants

5

Statistical method

Effect size

Risk Ratio (M-H, Fixed, 95% CI)

Subtotals only

4

650


0.89 [0.85, 0.93]

2 2 1 1 1 8

292 237

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.92 [0.86, 0.99] 0.93 [0.88, 0.99] Subtotals only 24.4 [16.01, 32.79] 44.0 [36.09, 51.91] Subtotals only

6

887


14.94 [5.24, 42.57]

6 1 1 5

930 172 197

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

23.36 [8.30, 65.75] 11.10 [1.54, 80.14] 36.32 [5.09, 259.21] Subtotals only

4 4 2 6

739 567 246

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.94 [0.88, 1.00] 0.87 [0.80, 0.95] 0.89 [0.77, 1.03] Subtotals only

4 3 4 3 5 1 1 3 2 1

621 555 751 605 858 202 202 611 430 202

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.19 [0.12, 0.31] 0.69 [0.32, 1.46] 0.20 [0.07, 0.59] 0.17 [0.09, 0.35] 0.11 [0.04, 0.34] 0.03 [0.00, 0.53] 0.18 [0.01, 3.80] 9.27 [2.17, 39.64] 5.05 [0.61, 42.16] 0.46 [0.04, 5.01]

2 1 2 1 1 1

383 228 409 228 228 228

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.39 [0.08, 1.97] 0.21 [0.01, 4.42] 3.16 [0.33, 30.10] 0.15 [0.01, 2.93] 0.21 [0.01, 4.42] 0.15 [0.01, 2.93]

68 68


43

6 Adverse events-long term (after hospital discharge) 6.1 Sepsis 6.2 Haematoma 6.3 Haemorrhage 7 Quality of life scores (continuous data) 7.1 SF-36 at one year-Role Limitation (physical) 7.2 SF-36 at one year-Role Limitation (emotional) 7.3 SF-36 at one year-Social Functioning 7.4 SF-36 at one year-Mental Health 7.5 SF-36 at one year-Energy

2

7.6 SF-36 at one year-Pain 7.7 SF-36 at one year-General Health Perception 7.8 SF-36 at one year-Physical Functioning 7.9 SF-36 at two years-Role Limitation (physical) 7.10 SF-36 at two years-Role Limitation (emotional) 7.11 SF-36 at two years-Social Functioning 7.12 SF-36 at two years-Mental Health 7.13 SF-36 at two years-Energy 7.14 SF-36 at two years-Pain 7.15 SF-36 at two years-General Health Perception 7.16 SF-36 at two years-Physical Functioning 7.17 GR inventory scores at one year after surgery 7.18 Euroqol score within one year after surgery 7.19 Euroqol scores at two years after surgery 7.20 SSR score at two years after surgery 7.21 Total HAD scores at two years after surgery 7.22 Anxiety HAD scores at two and four years after surgery


Subtotals only

1 2 1 6

172 368 196

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

0.27 [0.13, 0.58] 0.59 [0.15, 2.37] 2.94 [0.12, 71.30] Subtotals only

1

181

Mean Difference (IV, Fixed, 95% CI)

-0.80 [-4.99, 3.39]

1

181


-3.90 [-8.21, 0.41]

1

181


2

385


-21.20 [-24.73, -17. 67] -1.53 [-5.06, 2.01]

2

211


2 2

391 385

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-10.99 [-14.45, -7. 53] -1.91 [-5.67, 1.86] -7.27 [-10.72, -3.81]

1

181


-1.20 [-5.34, 2.94]

3

300


-3.09 [-7.94, 1.76]

3

300


10.22 [5.48, 14.96]

3

300


4

509


-10.06 [-13.55, -6. 58] 2.39 [-0.61, 5.40]

4

513


-2.01 [-5.41, 1.40]

4 4

513 509

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-9.50 [-12.80, -6.21] -7.42 [-10.64, -4.20]

3

300


-9.29 [-12.80, -5.78]

1

182


0.0 [-1.75, 1.75]

2

347


-3.24 [-8.35, 1.88]

2

368


-1.96 [-5.60, 1.67]

1

77


-3.70 [-11.17, 3.77]

1

77


-1.5 [-4.32, 1.32]

2

259


-0.67 [-1.64, 0.30]


44

7.23 Depression HAD scores at two and four years after surgery 8 Quality of life (proportion with improvement) 8.1 Proportion with improvement in pain two years after surgery 8.2 Proportion with improvement in general health one year after surgery 8.3 Proportion with improvement in general health four years after surgery 9 Duration of surgery (minutes) 10 Time to return to work (weeks) 11 Time to return to normal activity (days) 12 Duration of hospital stay (days) 13 Total health service cost per woman 14 Total individual cost per woman

2

259

2


-0.00 [-0.10, 0.09]


Subtotals only

1

59


1.60 [0.55, 4.63]

1

185


4.17 [1.47, 11.85]

1

146


2.76 [0.93, 8.17]

7 5 4

Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)

Totals not selected Totals not selected Totals not selected

7

Mean Difference (IV, Random, 95% CI) Other data

Totals not selected No numeric data

Other data

No numeric data


45

Analysis 1.1. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 1 Woman’s perception (proportion with improvement in bleeding symptoms). Review:

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding

Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 1 Woman’s perception (proportion with improvement in bleeding symptoms)

Study or subgroup

TCRE/ablation

Hysterectomy

n/N

n/N

Risk Ratio

Weight

Pinion 1994

80/96

97/97

30.4 %

0.83 [ 0.76, 0.91 ]

Gannon 1991

21/25

26/26

8.1 %

0.84 [ 0.70, 1.01 ]

Dwyer 1993

90/99

97/97

30.8 %

0.91 [ 0.85, 0.97 ]

94/107

96/103

30.6 %

0.94 [ 0.86, 1.03 ]

327

323

100.0 %

0.89 [ 0.85, 0.93 ]

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

1 Within one year of follow-up

Dickerson 2007

Subtotal (95% CI)

Total events: 285 (TCRE/ablation), 316 (Hysterectomy) Heterogeneity: Chi2 = 4.33, df = 3 (P = 0.23); I2 =31% Test for overall effect: Z = 4.92 (P < 0.00001) 2 At two years of follow-up Dickerson 2007

90/106

101/107

71.8 %

0.90 [ 0.82, 0.99 ]

Crosignani 1997

34/35

44/44

28.2 %

0.97 [ 0.90, 1.04 ]

141

151

100.0 %

0.92 [ 0.86, 0.99 ]

Subtotal (95% CI)

Total events: 124 (TCRE/ablation), 145 (Hysterectomy) Heterogeneity: Chi2 = 2.13, df = 1 (P = 0.14); I2 =53% Test for overall effect: Z = 2.39 (P = 0.017) 3 At four years of follow-up Dickerson 2007

40/47

50/51

40.7 %

0.87 [ 0.77, 0.98 ]

Pinion 1994

71/73

66/66

59.3 %

0.97 [ 0.93, 1.02 ]

120

117

100.0 %

0.93 [ 0.88, 0.99 ]

Subtotal (95% CI)

Total events: 111 (TCRE/ablation), 116 (Hysterectomy) Heterogeneity: Chi2 = 4.65, df = 1 (P = 0.03); I2 =79% Test for overall effect: Z = 2.47 (P = 0.014)

0.1 0.2

0.5

Favours hysterectomy

1

2

5

10

Favours TCRE/abl


46

Analysis 1.2. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 2 PBAC score (continuous data). Review:


Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 2 PBAC score (continuous data)

Study or subgroup

Favours experimental

Mean Difference

Hysterectomy

N

Mean(SD)

N

Mean(SD)

34

54 (21.3)

34

29.6 (13)

Weight

IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI

1 At one year of follow-up Sesti 2011

Subtotal (95% CI)

34

100.0 %

34

24.40 [ 16.01, 32.79 ]

100.0 % 24.40 [ 16.01, 32.79 ]

Heterogeneity: not applicable Test for overall effect: Z = 5.70 (P < 0.00001) 2 At two years of follow-up Sesti 2011

Subtotal (95% CI)

34

73.5 (19.6)

34

34

29.5 (13)

100.0 %

34

44.00 [ 36.09, 51.91 ]

100.0 % 44.00 [ 36.09, 51.91 ]

Heterogeneity: not applicable Test for overall effect: Z = 10.91 (P < 0.00001) Test for subgroup differences: Chi2 = 11.11, df = 1 (P = 0.00), I2 =91%

-100

-50

0

Favours TCRE/ablation


50

100


47

Analysis 1.3. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 3 Proportion requiring further surgery for HMB. Review:


Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 3 Proportion requiring further surgery for HMB

Study or subgroup

TCRE/ablation

Hysterectomy

n/N

n/N

Risk Ratio

Risk Ratio

1/41

0/44

3.21 [ 0.13, 76.74 ]

Dwyer 1993

12/99

0/97

24.50 [ 1.47, 408.14 ]

Gannon 1991

4/25

0/26

9.35 [ 0.53, 165.12 ]

9/116

1/56

4.34 [ 0.56, 33.46 ]

28/105

0/97

52.70 [ 3.26, 851.56 ]

5/89

0/92

11.37 [ 0.64, 202.59 ]

475

412

14.94 [ 5.24, 42.57 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

1 Within one year after surgery Crosignani 1997

O’Connor 1997 Pinion 1994 Zupi 2003

Subtotal (95% CI)

Total events: 59 (TCRE/ablation), 1 (Hysterectomy) Heterogeneity: Chi2 = 3.35, df = 5 (P = 0.65); I2 =0.0% Test for overall effect: Z = 5.06 (P < 0.00001) 2 At two years after surgery Crosignani 1997

3/41

0/44

7.50 [ 0.40, 140.91 ]

Dickerson 2007

27/110

0/118

58.96 [ 3.64, 955.12 ]

32/99

0/97

63.70 [ 3.96, 1025.88 ]

19/116

1/56

9.17 [ 1.26, 66.80 ]

Sesti 2011

0/34

0/34

0.0 [ 0.0, 0.0 ]

Zupi 2003

12/89

1/92

12.40 [ 1.65, 93.42 ]

489

441

23.36 [ 8.30, 65.75 ]

23/116

1/56

11.10 [ 1.54, 80.14 ]

116

56

11.10 [ 1.54, 80.14 ]

1/95

36.32 [ 5.09, 259.21 ]

Dwyer 1993 O’Connor 1997

Subtotal (95% CI)

Total events: 93 (TCRE/ablation), 2 (Hysterectomy) Heterogeneity: Chi2 = 2.73, df = 4 (P = 0.60); I2 =0.0% Test for overall effect: Z = 5.97 (P < 0.00001) 3 At three years after surgery O’Connor 1997

Subtotal (95% CI)

Total events: 23 (TCRE/ablation), 1 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 2.39 (P = 0.017) 4 At four years after surgery Pinion 1994

39/102

0.01

0.1


1

10

100


(Continued . . . )


48

(. . . Study or subgroup

TCRE/ablation

Hysterectomy

n/N

n/N

102

95

Subtotal (95% CI)


Continued) Risk Ratio

M-H,Fixed,95% CI

36.32 [ 5.09, 259.21 ]

Total events: 39 (TCRE/ablation), 1 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 3.58 (P = 0.00034)

0.01

0.1

1


10

100


Analysis 1.4. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 4 Proportion satisfied with treatment. Review:


Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 4 Proportion satisfied with treatment

Study or subgroup

TCRE/ablation

Hysterectomy

n/N

n/N

Risk Ratio

Weight

53/107

54/103

18.6 %

0.94 [ 0.72, 1.23 ]

84/99

89/95

30.7 %

0.91 [ 0.82, 1.00 ]

90/104

42/46

19.7 %

0.95 [ 0.84, 1.07 ]

92/96

88/89

30.9 %

0.97 [ 0.92, 1.02 ]

406

333

100.0 %

0.94 [ 0.88, 1.00 ]

M-H,Fixed,95% CI


1 At one year of follow-up Dickerson 2007 Dwyer 1993 O’Connor 1997 Pinion 1994

Subtotal (95% CI)

Total events: 319 (TCRE/ablation), 273 (Hysterectomy) Heterogeneity: Chi2 = 2.11, df = 3 (P = 0.55); I2 =0.0% Test for overall effect: Z = 1.87 (P = 0.062) 2 At two years of follow-up Crosignani 1997

33/38

37/39

16.7 %

0.92 [ 0.79, 1.06 ]

Dickerson 2007

51/106

59/107

26.9 %

0.87 [ 0.67, 1.13 ]

Dwyer 1993

64/81

69/72

33.5 %

0.82 [ 0.73, 0.93 ]

O’Connor 1997

74/86

36/38

22.9 %

0.91 [ 0.81, 1.02 ]

311

256

100.0 %

0.87 [ 0.80, 0.95 ]

Subtotal (95% CI)

0.1 0.2

0.5


1

2

5

10


(Continued . . . )


49


TCRE/ablation

Hysterectomy

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 222 (TCRE/ablation), 201 (Hysterectomy) Heterogeneity: Chi2 = 1.75, df = 3 (P = 0.63); I2 =0.0% Test for overall effect: Z = 3.04 (P = 0.0024) 3 At four years of follow-up Dickerson 2007

23/47

29/51

29.7 %

0.86 [ 0.59, 1.26 ]

Pinion 1994

61/76

64/72

70.3 %

0.90 [ 0.79, 1.04 ]

123

123

100.0 %

0.89 [ 0.77, 1.03 ]

Subtotal (95% CI)

Total events: 84 (TCRE/ablation), 93 (Hysterectomy) Heterogeneity: Chi2 = 0.07, df = 1 (P = 0.79); I2 =0.0% Test for overall effect: Z = 1.54 (P = 0.12)

0.1 0.2

0.5

1


2

5

10


Analysis 1.5. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 5 Adverse events-short term (intraoperative and immediate postoperative). Review:


Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 5 Adverse events short term (intraoperative and immediate postoperative)

Study or subgroup

Favours TCRE/abl

Hysterectomy

n/N

n/N

Risk Ratio

Weight

Dwyer 1993

2/99

29/97

31.3 %

0.07 [ 0.02, 0.28 ]

Gannon 1991

0/25

6/26

6.8 %

0.08 [ 0.00, 1.35 ]

0/116

7/56

10.8 %

0.03 [ 0.00, 0.56 ]

16/105

46/97

51.1 %

0.32 [ 0.20, 0.53 ]

345

276

100.0 %

0.19 [ 0.12, 0.31 ]

M-H,Fixed,95% CI


1 Sepsis

O’Connor 1997 Pinion 1994

Subtotal (95% CI)

Total events: 18 (Favours TCRE/abl), 88 (Hysterectomy) Heterogeneity: Chi2 = 8.00, df = 3 (P = 0.05); I2 =62% Test for overall effect: Z = 7.09 (P < 0.00001)

0.01

0.1


1

10

100


(Continued . . . )


50


Risk Ratio

Weight


Favours TCRE/abl

Hysterectomy

n/N

n/N

O’Connor 1997

0/116

3/56

31.8 %

0.07 [ 0.00, 1.32 ]

Pinion 1994

6/105

5/97

35.1 %

1.11 [ 0.35, 3.52 ]

Zupi 2003

4/89

5/92

33.2 %

0.83 [ 0.23, 2.98 ]

310

245

100.0 %

0.69 [ 0.32, 1.46 ]

2/99

6/97

32.9 %

0.33 [ 0.07, 1.58 ]

O’Connor 1997

0/116

3/56

25.5 %

0.07 [ 0.00, 1.32 ]

Pinion 1994

1/105

5/97

28.2 %

0.18 [ 0.02, 1.55 ]

Zupi 2003

0/89

2/92

13.3 %

0.21 [ 0.01, 4.25 ]

409

342

100.0 %

0.20 [ 0.07, 0.59 ]

4/110

20/118

36.7 %

0.21 [ 0.08, 0.61 ]

Dwyer 1993

2/99

29/97

55.8 %

0.07 [ 0.02, 0.28 ]

Zupi 2003

3/89

4/92

7.5 %

0.78 [ 0.18, 3.37 ]

298

307

100.0 %

0.17 [ 0.09, 0.35 ]

1/110

7/118

22.0 %

0.15 [ 0.02, 1.23 ]

Dwyer 1993

1/99

8/97

26.3 %

0.12 [ 0.02, 0.96 ]

Gannon 1991

0/25

1/26

4.8 %

0.35 [ 0.01, 8.12 ]

Pinion 1994

0/105

11/97

38.9 %

0.04 [ 0.00, 0.67 ]

Zupi 2003

0/89

2/92

8.0 %

0.21 [ 0.01, 4.25 ]

428

430

100.0 %

0.11 [ 0.04, 0.34 ]

0/105

14/97

100.0 %

0.03 [ 0.00, 0.53 ]

105

97

100.0 %

0.03 [ 0.00, 0.53 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

2 Haemorrhage

Subtotal (95% CI)

Total events: 10 (Favours TCRE/abl), 13 (Hysterectomy) Heterogeneity: Chi2 = 3.06, df = 2 (P = 0.22); I2 =35% Test for overall effect: Z = 0.98 (P = 0.33) 3 Blood transfusion Dwyer 1993

Subtotal (95% CI)

Total events: 3 (Favours TCRE/abl), 16 (Hysterectomy) Heterogeneity: Chi2 = 0.86, df = 3 (P = 0.83); I2 =0.0% Test for overall effect: Z = 2.95 (P = 0.0032) 4 Pyrexia Dickerson 2007

Subtotal (95% CI)

Total events: 9 (Favours TCRE/abl), 53 (Hysterectomy) Heterogeneity: Chi2 = 5.86, df = 2 (P = 0.05); I2 =66% Test for overall effect: Z = 4.98 (P < 0.00001) 5 Vault haematoma Dickerson 2007

Subtotal (95% CI)

Total events: 2 (Favours TCRE/abl), 29 (Hysterectomy) Heterogeneity: Chi2 = 1.23, df = 4 (P = 0.87); I2 =0.0% Test for overall effect: Z = 3.89 (P = 0.000099) 6 Wound haematoma Pinion 1994

Subtotal (95% CI)

0.01

0.1


1

10

100


(Continued . . . ) Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

51


Favours TCRE/abl

Hysterectomy

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 0 (Favours TCRE/abl), 14 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 2.41 (P = 0.016) 7 Anaesthetic Pinion 1994

0/105

2/97

100.0 %

0.18 [ 0.01, 3.80 ]

105

97

100.0 %

0.18 [ 0.01, 3.80 ]

1/110

0/118

24.0 %

3.22 [ 0.13, 78.13 ]

12/105

1/97

51.6 %

11.09 [ 1.47, 83.67 ]

5/89

0/92

24.4 %

11.37 [ 0.64, 202.59 ]

304

307

100.0 %

9.27 [ 2.17, 39.64 ]

Subtotal (95% CI)

Total events: 0 (Favours TCRE/abl), 2 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 1.09 (P = 0.27) 8 Fluid overload Dickerson 2007 Pinion 1994 Zupi 2003

Subtotal (95% CI)

Total events: 18 (Favours TCRE/abl), 1 (Hysterectomy) Heterogeneity: Chi2 = 0.47, df = 2 (P = 0.79); I2 =0.0% Test for overall effect: Z = 3.00 (P = 0.0027) 9 Perforation Dickerson 2007

3/110

0/118

48.2 %

7.50 [ 0.39, 143.65 ]

Pinion 1994

1/105

0/97

51.8 %

2.77 [ 0.11, 67.29 ]

215

215

100.0 %

5.05 [ 0.61, 42.16 ]

1/105

2/97

100.0 %

0.46 [ 0.04, 5.01 ]

105

97

100.0 %

0.46 [ 0.04, 5.01 ]

Subtotal (95% CI)

Total events: 4 (Favours TCRE/abl), 0 (Hysterectomy) Heterogeneity: Chi2 = 0.20, df = 1 (P = 0.65); I2 =0.0% Test for overall effect: Z = 1.50 (P = 0.13) 10 Gastrointestinal obstruction/ileus Pinion 1994

Subtotal (95% CI)

Total events: 1 (Favours TCRE/abl), 2 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 0.63 (P = 0.53) 11 Laparotomy Pinion 1994

1/105

3/97

61.3 %

0.31 [ 0.03, 2.91 ]

Zupi 2003

1/89

2/92

38.7 %

0.52 [ 0.05, 5.60 ]

194

189

100.0 %

0.39 [ 0.08, 1.97 ]

2/118

100.0 %

0.21 [ 0.01, 4.42 ]

Subtotal (95% CI)

Total events: 2 (Favours TCRE/abl), 5 (Hysterectomy) Heterogeneity: Chi2 = 0.10, df = 1 (P = 0.76); I2 =0.0% Test for overall effect: Z = 1.14 (P = 0.25) 12 Cystotomy Dickerson 2007

0/110

0.01

0.1


1

10

100


(Continued . . . )


52


Favours TCRE/abl

Subtotal (95% CI)

Hysterectomy

Risk Ratio

Weight

M-H,Fixed,95% CI


n/N

n/N

110

118

100.0 %

0.21 [ 0.01, 4.42 ]

M-H,Fixed,95% CI

1/110

0/118

49.5 %

3.22 [ 0.13, 78.13 ]

1/89

0/92

50.5 %

3.10 [ 0.13, 75.10 ]

199

210

100.0 %

3.16 [ 0.33, 30.10 ]

0/110

3/118

100.0 %

0.15 [ 0.01, 2.93 ]

110

118

100.0 %

0.15 [ 0.01, 2.93 ]

0/110

2/118

100.0 %

0.21 [ 0.01, 4.42 ]

110

118

100.0 %

0.21 [ 0.01, 4.42 ]

0/110

3/118

100.0 %

0.15 [ 0.01, 2.93 ]

110

118

100.0 %

0.15 [ 0.01, 2.93 ]

Total events: 0 (Favours TCRE/abl), 2 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 1.00 (P = 0.32) 13 Cervical laceration Dickerson 2007 Zupi 2003

Subtotal (95% CI)

Total events: 2 (Favours TCRE/abl), 0 (Hysterectomy) Heterogeneity: Chi2 = 0.00, df = 1 (P = 0.99); I2 =0.0% Test for overall effect: Z = 1.00 (P = 0.32) 14 Cardiorespiratory event Dickerson 2007

Subtotal (95% CI)

Total events: 0 (Favours TCRE/abl), 3 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 1.25 (P = 0.21) 15 Thromboembolic event Dickerson 2007

Subtotal (95% CI)

Total events: 0 (Favours TCRE/abl), 2 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 1.00 (P = 0.32) 16 Readmission/return to surgery Dickerson 2007

Subtotal (95% CI)

Total events: 0 (Favours TCRE/abl), 3 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 1.25 (P = 0.21)

0.01

0.1


1

10

100



53

Analysis 1.6. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 6 Adverse events-long term (after hospital discharge). Review:


Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 6 Adverse events long term (after hospital discharge)

Study or subgroup

TCRE/ablation

Hysterectomy

n/N

n/N

Risk Ratio

Weight

9/116

16/56

100.0 %

0.27 [ 0.13, 0.58 ]

116

56

100.0 %

0.27 [ 0.13, 0.58 ]

0/99

2/97

48.3 %

0.20 [ 0.01, 4.03 ]

4/116

2/56

51.7 %

0.97 [ 0.18, 5.11 ]

215

153

100.0 %

0.59 [ 0.15, 2.37 ]

1/99

0/97

100.0 %

2.94 [ 0.12, 71.30 ]

99

97

100.0 %

2.94 [ 0.12, 71.30 ]

M-H,Fixed,95% CI


1 Sepsis O’Connor 1997

Subtotal (95% CI)

Total events: 9 (TCRE/ablation), 16 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 3.40 (P = 0.00068) 2 Haematoma Dwyer 1993 O’Connor 1997

Subtotal (95% CI)

Total events: 4 (TCRE/ablation), 4 (Hysterectomy) Heterogeneity: Chi2 = 0.84, df = 1 (P = 0.36); I2 =0.0% Test for overall effect: Z = 0.74 (P = 0.46) 3 Haemorrhage Dwyer 1993

Subtotal (95% CI)

Total events: 1 (TCRE/ablation), 0 (Hysterectomy) Heterogeneity: not applicable Test for overall effect: Z = 0.66 (P = 0.51)

0.01

0.1


1

10

100



54

Analysis 1.7. Comparison 1 Endometrial resection/ablation versus hysterectomy, Outcome 7 Quality of life scores (continuous data). Review:


Comparison: 1 Endometrial resection/ablation versus hysterectomy Outcome: 7 Quality of life scores (continuous data)

Study or subgroup

TCRE/ablation N

Mean Difference

Hysterectomy Mean(SD)

N

Mean(SD)

92

62.1 (13.9)

Weight

IV,Fixed,95% CI


1 SF-36 at one year Role Limitation (physical) Zupi 2003

Subtotal (95% CI)

89

61.3 (14.8)

89

92

100.0 %

-0.80 [ -4.99, 3.39 ]

100.0 %

-0.80 [ -4.99, 3.39 ]

100.0 %

-3.90 [ -8.21, 0.41 ]

100.0 %

-3.90 [ -8.21, 0.41 ]

100.0 %

-21.20 [ -24.73, -17.67 ]

Heterogeneity: not applicable Test for overall effect: Z = 0.37 (P = 0.71) 2 SF-36 at one year Role Limitation (emotional) Zupi 2003

Subtotal (95% CI)

89

64.2 (14.4)

89

92

68.1 (15.2)

92

Heterogeneity: not applicable Test for overall effect: Z = 1.77 (P = 0.076) 3 SF-36 at one year Social Functioning Zupi 2003

Subtotal (95% CI)

89

67.3 (12.7)

89

92

88.5 (11.5)

100.0 % -21.20 [ -24.73, -17.67 ]

92

Heterogeneity: not applicable Test for overall effect: Z = 11.76 (P < 0.00001) 4 SF-36 at one year Mental Health Dickerson 2007 Zupi 2003

Subtotal (95% CI)

105

67.7 (23.4)

99

66.1 (25.8)

27.2 %

1.60 [ -5.17, 8.37 ]

89

60.5 (14.8)

92

63.2 (13.6)

72.8 %

-2.70 [ -6.84, 1.44 ]

100.0 %

-1.53 [ -5.06, 2.01 ]

194

191

Heterogeneity: Chi2 = 1.13, df = 1 (P = 0.29); I2 =11% Test for overall effect: Z = 0.85 (P = 0.40) 5 SF-36 at one year Energy Dickerson 2007

17

52.8 (25.7)

13

55.1 (25.8)

3.5 %

-2.30 [ -20.90, 16.30 ]

Zupi 2003

89

61 (12.8)

92

72.3 (11.3)

96.5 %

-11.30 [ -14.82, -7.78 ]

100.0 %

-10.99 [ -14.45, -7.53 ]

31.4 %

-2.80 [ -9.53, 3.93 ]

Subtotal (95% CI)

106

105

Heterogeneity: Chi2 = 0.87, df = 1 (P = 0.35); I2 =0.0% Test for overall effect: Z = 6.22 (P < 0.00001) 6 SF-36 at one year Pain Dickerson 2007

107

67.2 (24.5)

103

70 (25.2) -20

-10


0

10

20


(Continued . . . )


55


TCRE/ablation

Zupi 2003

Subtotal (95% CI)

Mean Difference

Hysterectomy

N

Mean(SD)

N

Mean(SD)

89

58.6 (17)

92

60.1 (14)

196

Weight

IV,Fixed,95% CI

Continued)


195

68.6 %

-1.50 [ -6.05, 3.05 ]

100.0 %

-1.91 [ -5.67, 1.86 ]

Heterogeneity: Chi2 = 0.10, df = 1 (P = 0.75); I2 =0.0% Test for overall effect: Z = 0.99 (P = 0.32) 7 SF-36 at one year General Health Perception Dickerson 2007 Zupi 2003

Subtotal (95% CI)

105

65.4 (23.2)

99

66.1 (24.4)

27.9 %

-0.70 [ -7.24, 5.84 ]

89

59.6 (13.7)

92

69.4 (14.2)

72.1 %

-9.80 [ -13.86, -5.74 ]

100.0 %

-7.27 [ -10.72, -3.81 ]

100.0 %

-1.20 [ -5.34, 2.94 ]

100.0 %

-1.20 [ -5.34, 2.94 ]

194

191

Heterogeneity: Chi2 = 5.36, df = 1 (P = 0.02); I2 =81% Test for overall effect: Z = 4.12 (P = 0.000037) 8 SF-36 at one year Physical Functioning Zupi 2003

Subtotal (95% CI)

89

66.4 (15.1)

89

92

67.6 (13.2)

92

Heterogeneity: not applicable Test for overall effect: Z = 0.57 (P = 0.57) 9 SF-36 at two years Role Limitation (physical) Crosignani 1997

38

67.4 (36.3)

39

74.1 (37.9)

8.6 %

-6.70 [ -23.27, 9.87 ]

Dwyer 1993

82

82.7 (33.1)

73

82 (33.6)

21.2 %

0.70 [ -9.82, 11.22 ]

Sesti 2011

34

66.2 (13)

34

70 (11.3)

70.2 %

-3.80 [ -9.59, 1.99 ]

100.0 %

-3.09 [ -7.94, 1.76 ]

Subtotal (95% CI)

154

146

Heterogeneity: Chi2 = 0.74, df = 2 (P = 0.69); I2 =0.0% Test for overall effect: Z = 1.25 (P = 0.21) 10 SF-36 at two years Role Limitation (emotional) Crosignani 1997

38

61.1 (37.8)

39

71.9 (40.7)

7.3 %

-10.80 [ -28.34, 6.74 ]

Dwyer 1993

82

80 (31.6)

73

86.2 (29.8)

24.0 %

-6.20 [ -15.87, 3.47 ]

Sesti 2011

34

59.4 (14.8)

34

41.2 (8.4)

68.7 %

18.20 [ 12.48, 23.92 ]

100.0 %

10.22 [ 5.48, 14.96 ]

Subtotal (95% CI)

154

146

Heterogeneity: Chi2 = 24.07, df = 2 (P

Hysteroscopy and heavy menstrual bleeding (to cover TCRE and second-generation endometrial ablation).

Thermal balloon endometrial ablation in the treatment of heavy menstrual bleeding.

Endometrial Ossification: An Unusual Cause of Heavy Menstrual Bleeding (HMB).

Heavy menstrual bleeding.

Tactile Electrosurgical Ablation: A Technique for the Treatment of Intractable Heavy and Prolonged Menstrual Bleeding.

Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long-Term Follow-Up of a Randomized Trial.

Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long-term Follow-up of a Randomized Trial.

Heavy menstrual bleeding and quality of life.

Cost effectiveness of endometrial ablation with the NovaSure(®) system versus other global ablation modalities and hysterectomy for treatment of abnormal uterine bleeding: US commercial and Medicaid payer perspectives.

Combined Endometrial Ablation and Levonorgestrel Intrauterine System Use in Women With Dysmenorrhea and Heavy Menstrual Bleeding: Novel Approach for Challenging Cases.

Cost-Effectiveness of Global Endometrial Ablation vs. Hysterectomy for Treatment of Abnormal Uterine Bleeding: US Commercial and Medicaid Payer Perspectives.

Comparison of direct and indirect costs of abnormal uterine bleeding treatment with global endometrial ablation and hysterectomy.

Non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women with bleeding disorders.

Levonorgestrel intrauterine system versus thermal balloon ablation for the treatment of heavy menstrual bleeding: A meta-analysis of randomized controlled trials.

Hemostatic abnormalities in young females with heavy menstrual bleeding.

Platelet function defects in adolescents with heavy menstrual bleeding.

No increased systemic fibrinolysis in women with heavy menstrual bleeding.

Heavy menstrual bleeding significantly affects quality of life.

Severe anemia from heavy menstrual bleeding requires heightened attention.

A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia.

[Hysteroscopic morcellation versus bipolar resection for endometrial polyp removal].

Re: endometrial ablation: is tubal ligation a risk factor for hysterectomy.

Hormonal contraception as treatment for heavy menstrual bleeding: a systematic review.

Population screening for von Willebrand disease in adolescents with heavy menstrual bleeding.