Clinical and health service implications of second generation endometrial ablation devices Nazar N. Amso

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1 Clinical and health service implications of second generation endometrial ablation devices Nazar N. Amso Purpose of review This review evaluates the current evidence on the efficacy, safety and cost-effectiveness of the ever-increasing number of second-generation endometrial ablation devices. Recent findings The literature covered by this review includes (1) evidence on long-term benefit, avoidance of hysterectomy and improvement in quality of life, (2) applicability of these techniques in the outpatient environment under local or no anaesthesia, (3) frequency and nature of early and delayed complications associated with these devices, (4) impact on clinical practice and the health service, and (5) implications for research. Summary Where appropriate, second-generation devices are rapidly becoming the first-line surgical choice for the management of heavy menstrual bleeding. This has both cost-savings and negative implications for the health service. There is also emerging evidence that improvement in quality of life is more relevant to women than amenorrhoea rates. What has come to light from this review is the lack of accurate data on adverse events rate, and the urgent need for a better appreciation of the frequency and nature of complications. Keywords complications, effectiveness, endometrial ablation, outpatient, quality of life, second generation Curr Opin Obstet Gynecol 18: ß 2006 Lippincott Williams & Wilkins. Department of Obstetrics and Gynaecology, Wales College of Medicine, Cardiff University, University Hospital of Wales and Vale NHS Trust, Cardiff, UK Correspondence to Nazar N. Amso, FRCOG, PhD, ILTHEM, Senior Lecturer, Department of Obstetrics and Gynaecology, Wales College of Medicine, Cardiff University, Cardiff CF14 4XN, UK Tel: ; fax: ; amsonn@cf.ac.uk Current Opinion in Obstetrics and Gynecology 2006, 18: Abbreviations ELITT endometrial laser intrauterine thermal therapy MEA microwave endometrial ablation TCRE transcervical resection of the endometrium ß 2006 Lippincott Williams & Wilkins X Introduction Menorrhagia remains a common and significant cause of morbidity in premenopausal women in the UK. In the event of a failure of first-line medical treatment, various surgical options are available. Hysterectomy is associated with the possibility of major adverse events and has its own mortality. First-generation endometrial ablation techniques such as rollerball, transcervical resection of the endometrium (TCRE) and laser ablation have largely been superseded by a variety of ingenious equipment commonly referred to as second-generation ablation devices. All these modalities share the concept of aiming to destroy the endometrium including the basalis layer and stop its re-growth. It was argued that they should be easier and safer to perform, have reduced morbidity and mortality, and be as effective as first-generation devices. Furthermore, they do not require general anaesthesia and thus are more suitable to the office environment. All these potential advantages were seen as factors that would result in less hysterectomies being performed and ultimately reduce the overall costs for the management of menorrhagia. Over the past decade, a number of techniques were introduced, and since the previous review [1] many more have been added and some withdrawn! The first of the second-generation devices was the fluid-filled balloon Thermachoice 1 ; this was followed by other balloon devices, the microwave-based technique microwave endometrial ablation (MEA), impedance radiofrequency and laser-based techniques, and others. Several of these devices have been evaluated by the National Institute of Clinical Excellence (Table 1), and evidence of their safety and effectiveness presented, while others are yet to be evaluated. In this review, evidence on longterm effectiveness, suitability for ambulatory and outpatient setting, complications, cost-benefit, and impact on the health service of these techniques will be presented. Patient selection and endometrial preparation Most of the second-generation devices (Cavaterm, Thermachoice, Novasure, Cryoablation) require a relatively normal uterine cavity of a depth under 12 cm to enable the device to complete the treatment satisfactorily. Free fluid ablation (HydroThermAblator) and MEA can be 457

2 458 Reproductive endocrinology Table 1 National Institute of Clinical Excellence publications, where applicable, and their dates in relation to each device Device National Institute of Clinical Excellence publications (date) Balloon thermal ablation: Cavaterm overview (11/02) IPG 006 (08/03) TA 078 (04/04) Balloon thermal ablation: Thermachoice overview (11/02) IPG 006 (08/03) TA 078 (04/04) Cryoablation: Her Option overview (12/05) IPG 157 (03/06) Free fluid endometrial ablation: HydroThermAblator overview (11/02) IPG 051 (03/04) GyneLase overview ( ) IPG ( ) Impedance bipolar radiofrequency ablation: Novasure overview (02/04) IPG 104 (12/04) Microwave endometrial ablation overview (11/02) IPG 007 (08/03) TA 078 (04/04) Thermablate endometrial ablation system overview ( ) IPG ( ) Photodynamic endometrial ablation overview (11/02) IPG 047 (03/04) IPG, Interventional Procedure Guidance; TA, Technology Appraisal. performed when the uterine cavity is irregular, although complete septate or bicornuate uteri are contraindications to undertaking the procedures. In all instances it is recommended to confirm the correct placement of the devices in the cavity with ultrasound especially in a mal-positioned uterus. In the case of cryoablation, the treatment is carried out under ultrasound guidance. Several studies have assessed second-generation ablation devices in women with submucous fibroids. Successful outcomes were reported in randomized controlled studies for Thermachoice 1 [2], MEA [3] and hydrothermablation [4]. Unlike with first-generation endometrial ablation techniques, endometrial thinning is not necessary with most second-generation devices. Several studies have confirmed that success and patient satisfaction are not affected by endometrial preparation [5,6,7 ]. The exceptions are hydrothermablation [8] and the endometrial laser intrauterine thermal therapy (ELITT) system, where pretreatment endometrial thinning with gonadotrophinreleasing hormone analogues was reported to lead to superior amenorrhoea rate (website com/wt/page/press/2002). Type of anaesthesia and location of surgery All manufacturers state that their respective devices can be used in the outpatients or as a day-case and without the need for general anaesthesia; however, the evidence in the literature is variable. Thermachoice under conscious sedation, local or no anaesthesia has been reported [9 12,13 ]. In a prospective observational study [11], patient-controlled sedation was reported to be safe and effective in alleviating pain and discomfort, and was well received by patients. A more recent study [12] evaluated the use of local anaesthesia only in the outpatient setting. The procedure was successfully completed in 94% women (n ¼ 53), 27% of whom required postoperative opiate for pain relief and 4% overnight stay; 67% of women were satisfied at six months. Marsh et al. [13 ] performed the procedure in 24 of 27 women (89%) without local anaesthesia or intravenous sedation safely and successfully without complications. The use of ibuprofen obviated the need for rescue analgesia and most women were discharged within 3 h of the treatment. Two studies evaluated the use of Thermachoice in community [14] and primary care [15] settings, and concluded that the procedure was well tolerated by patients and suitable for these settings. Similarly, a randomized clinical trial comparing MEA treatment under local and general anaesthesia reported local anaesthesia to be acceptable to the majority of women, but almost one in 10 women needed conversion to general anaesthesia because of discomfort [16]. With this in mind, the authors concluded that this treatment remains a day-case rather than an outpatient procedure. The same group [17] reported minimal cost savings to the patient or health service from using MEA under local rather than general anaesthesia in a theatre setting and that in a clinic setting MEA has a similar cost to a theatrebased treatment once re-admissions for general anaesthesia treatments were considered. In a small cohort of 40 patients [8] undergoing hydrothermablation, the anaesthetic regimen comprised of a combination of oral mefenamic acid and cervical/ paracervical block using lignocaine 1% and adrenalin 1 : The authors reported successful completion of the treatment in all subjects with a median pain score of 6.4 during the procedure and 88% of women finding it acceptable. All women were discharged within 2 h and none was readmitted. Techniques and their effectiveness The following techniques and devices will be reviewed in detail. Balloon thermal ablations Fluid-filled balloons were one of the earliest secondgeneration devices. In this section, three widely available devices will be reviewed. A fourth device, MenoTreat (Lina-Medical, Glostrup, Denmark) has been used in Finland and Sweden, but to the author s best knowledge very infrequently elsewhere.

3 Second-generation endometrial ablation Amso 459 Cavaterm (Wallsten Medical, Morges, Switzerland) With this device, a balloon is inserted into the uterine cavity and inflated with glycine solution to a pressure of mmhg. The solution is heated to 758C for 15 min. The balloon size is adjustable to fit different sized uterine cavities. Two randomized controlled studies were published. There was no difference in the amenorrhoea rate between Cavaterm and TCRE, and a significantly shorter operating time for the Cavaterm. At 2 years follow-up, bleeding and pain recurrence were significantly higher with TCRE, while satisfaction and reoperation rates were higher with Cavaterm [18,19]. Thermachoice (Gynecare, Ethicon, Somerville, New Jersey, USA) With Thermachoice, a balloon catheter is inserted into the uterine cavity and inflated with 5% dextrose solution to a pressure of mmhg. The solution is heated to 878C for 8 min. The single-use silicone or latex balloon catheter housing a heating element and two thermocouples is connected through an umbilical cable to an electronic controller device. A large multicentre observational study [9] demonstrated that Thermachoice 1 led to a significant reduction in the severity and duration of menstrual flow and dysmenorrhoea. Fifteen percent of women were amenorrhoeic and 88% had reverted to eumenorrhoea or less by 12 months. In comparison with rollerball [10] and TCRE [20,21], Thermachoice 1 achieved comparable reduction in menstrual loss with the first-generation techniques. Long-term follow-up [22] showed that nearly seven of 10 women were cured of menorrhagia without additional intervention 5 years after ablation, and that hysterectomies were performed because of bleeding and/or pelvic pain; onethird of them were associated with fibroids. Additional evidence [23] showed that 4 6 years after Thermachoice 1, the probability of avoiding hysterectomy was 86% of all women. In the same study, of the women avoiding hysterectomy, 47% were amenorrhoeic, 30% were hypomenorrhoiec, 13.6% were eumenorrhoiec and only 8.5% had heavy periods. Thermablate endometrial ablation (MDMI Technologies, Richmond, British Columbia, Canada) In this technique a disposable cartridge consisting of a silicone balloon, catheter and reservoir is connected to the treatment control unit, and the fluid is heated in the reservoir to 1738C before the treatment commences. The temperature of the fluid in the balloon is approximately 1558C when it first enters the uterus and declines to approximately 1158C by the end of the 128-s treatment period. Once the balloon has been inserted into the uterine cavity and the user depresses the trigger button, a pneumatic pump applies pressure to the reservoir and fluid is forced into the balloon achieving a pressure of mmhg. During treatment the pressure is pulsed periodically to mix the fluid within the balloon and ensure a uniform temperature distribution. Early reports [24,25] indicated amenorrhoea rates of 25 and 90% satisfaction at 6 months with no reported serious complications. No other studies have been reported since the licence to the Thermablate Ablation Technology was acquired in 2003 by Global Precision Medical (Wheatland, Wyoming, USA). Cryoablation: Her Option, uterine cryoablation therapy system (Cryogen, San Diego, California, USA) Endometrial cryotherapy is a nonhysteroscopic technique that uses cold temperatures to freeze and destroy the endometrium. The cryoprobe is inserted into the uterus and a small amount of saline solution may be injected into the cavity to enhance freezing. The cryoprobe is cooled by perfusing it with either liquid nitrogen or a compressed gas mixture. The tip of the probe, where freezing occurs, is placed in one cornua of the uterus, and then moved to the other and the remainder of the uterine cavity in a series of freeze thaw cycles. Ultrasound is used to monitor the position of the probe and depth of tissue freezing. Declared advantages over other techniques include (1) ease of use, (2) quick and safe to perform due to direct ultrasound visualization of the ablation depth, (3) requires less anaesthetic due to the analgesic effect of cold temperatures, and (4) potential for use in the outpatient setting. Efficacy is based on the results of a randomized controlled trial with rollerball ablation [26,27]. At 12 months, return to eumenorrhoea (pictorial blood loss assessment chart score 75 or below) was 67.4% in the cryoablation group and 73.3% following rollerball therapy, 27.6 and 55.5% had amenorrhoea, and 12% and 6.9% had continued menorrhagia (pictorial blood loss assessment chart score above 100) in the respective groups. At 24 months, patient satisfaction and improvement in quality of life was up to 91%. The two groups had similar and nonsignificantly different hysterectomy and re-treatment rates. In addition to minor adverse events that occurred during and in the immediate postoperative period, late events within 12 months included severe abdominal cramping and vaginal pain, prolonged tiredness, and perimenopausal symptoms. Free fluid endometrial ablation: HydroThermAblator (Boston Scientific, Natick, Massachusetts, USA) In this technique circulating hot saline solution is instilled into the uterus under direct hysteroscopic

4 460 Reproductive endocrinology guidance. The saline is heated to 908C and circulated for 10 min. A randomized controlled trial comparing the Hydro ThermAblator with rollerball ablation [28,29] reported a reduction of bleeding to normal or less in 82 and 85% at 12 months follow-up and 94 and 91% at 36 months in the two groups, respectively. The amenorrhoea rates were comparable, 40 and 51% at 12 months and 53 and 46% at 36 months, respectively. Equally, patient satisfaction and the subsequent hysterectomy rate at 12 and 36 months were comparable. Overall, success after 36 months (normal bleeding or less and no repeat ablations, hysterectomy or other interventions) was 81.4% for HydroThermAblator and 81.6% for rollerball. Minor operative or postoperative complications were reported; however, more seriously, first-degree burns on the buttocks and upper thighs due to prolonged contact with tubing connecting the control unit to the inflow channel of the hysteroscopic sheath were reported as well. Since then, the design of the equipment was changed to avert such injury. Impedance bipolar radiofrequency endometrial ablation: Novasure (Novacept, Palo Alto, California, USA) In this technique a sheath containing a bipolar radiofrequency electrode is placed through the cervix into the normal shaped uterine cavity. The sheath is pulled back, allowing the unique gold-mesh electrode to expand and conform to the shape of the uterine cavity, and radiofrequency energy is then delivered into the uterus via the electrode. The treatment usually lasts for approximately 90 s, and the electrode is then retracted back into the sheath and removed from the uterus. Women with fibroids or large polyps inside the uterine cavity are unsuitable for this technique. No endometrial pretreatment is necessary. Efficacy was reported in two randomized controlled trials [30,31] and two case series studies. Amenorrhoea rates in these four studies ranged from 41 to 59% at 12 months, with higher amenorrhoea rates in the impedance controlled procedure. Continuing menorrhagia rates ranged from 3.9 to 14% at 12 months. There was also evidence to suggest that the majority of patients were satisfied following the procedure and that quality of life had improved. At 3-year follow-up [32] hysterectomy was avoided in 97% of women, 65% of whom were amenorrhoeic. A similar but monopolar radiofrequency system was introduced in the mid-1990s called Vestablate and comprised of 12 thin, plate-like electrodes over a distensible balloon attached to an 8-mm catheter. The device is not available at present. Laser hyperthermy: GyneLase endometrial laser intrauterine thermal therapy (ESC/Sharplan Laser, Needham, Massachusetts, USA) In this technique, introduced in 1999, an intrauterine diode laser emits light, which is absorbed and transformed to heat causing controlled tissue coagulation. An observational study [33] of 100 cases, all with pretreatment endometrial thinning, reported an amenorrhoea rate of 70% at 6 and 12 months, satisfaction rates in excess of 90% at 1 year, and no operative or postoperative serious complication. A randomized comparison of ELITT with TCRE [34] reported that both techniques were equally effective, but that ELITT was superior in inducing amenorrhoea at 12 and 36 months. A US Food and Drug Administration premarket approval clinical trial was stopped early in April 2002 (website: as the interim results did not reflect previously reported superior results. No updates appear to have been published to date. Microwave endometrial ablation (Mircosulis, Waterlooville, UK) MEA is another ingenious second-generation endometrial ablation device where low-power, high-frequency microwave energy is used to generate heat and destroy the endometrium. The probe is inserted into the uterine cavity and moved from side to side with the temperature maintained at C to destroy the endometrium. In a well-designed randomized controlled trial, MEA was compared to TCRE [35] and was reported to have significantly shorter mean operative time than TCRE (11.4 versus 15.0 min, P ¼ 0.001), and equally high satisfaction rate, acceptability and improved quality of life 1 year after treatment for both groups. These results were sustained at 2-year follow-up. At 5-year follow-up [36 ] both techniques achieved significant and comparable improvements in menstrual symptoms, and healthrelated quality of life. While high rates of satisfaction with treatment and acceptability of treatment were achieved by TCRE, these were significantly lower than following MEA. These long-term data, when combined with the trials operative findings and known costs of both procedures, led the authors to conclude that MEA is a more effective and efficient treatment for heavy menstrual loss than TCRE. Complications of second-generation ablation devices Minor immediate postoperative complications are common among second-generation ablation devices, and include pelvic pain, endometritis, urinary tract infection, nausea and vomiting, haematometra and pelvic inflammation. To date, these and other minor complications have been reported in the medical literature. The

5 Second-generation endometrial ablation Amso 461 frequency of their occurrence and, in particular, the more serious complications remain difficult to establish, however. Several reports have attempted to address this deficiency. Rogerson and Duffy [37] conducted a European survey of complications among surgeons undertaking Thermachoice ablation and reported a 0.24% incidence of nonmachine-related operative complication, 3.92% postoperative complications rate and emergency additional surgery rate in 0.04% of 5859 cases. These figures compared very favourably with the MISTLETOE study for first-generation ablation devices. Others [38] searched the medical literature, the Cochrane database, MAUDE database of medical device adverse events submitted to the US Food and Drug Administration (website: maude.html) and relevant textbooks. The authors relied on the manufacturers estimated number of procedures in the USA for each device, and calculated complication rates of 0.56, 1.2, 1, and 0.96 per 1000 for Thermachoice, NovaSure, Her Option and HydroThermAblator, respectively. Reported serious complications included sepsis, adnexal/uterine necrosis, lower genital tract thermal injury and one death. Many of these resulted from non compliance with manufacturers instructions and other avoidable factors. A 2005 update of a Cochrane Database of Systematic Review [39 ] concluded that equipment failure, nausea and vomiting, and uterine cramping were more likely with second-generation ablation devices, but these were less likely to be associated with fluid overload, uterine perforation, cervical lacerations and haematometra than conventional ablation and resection techniques. Overall, they compared favourably with TCRE. Other poorly defined risks include the incidence of endometrial cancer [40] and pregnancies after second-generation ablation techniques [41]. The above reports highlight the significant deficiency in structured data gathering. There is an urgent need to establish definitively the true incidence of such complications as reported for firstgeneration devices in the MISTLETOE study [42]. Comparisons between techniques Few studies have compared second-generation ablation techniques with each other. Bongers et al. [43] compared Novasure with Thermachoice 1 in a randomized controlled study, and reported significantly higher amenorrhoea and satisfaction rates with the bipolar device at 1-year follow-up. Another group [44 ] reported that both methods significantly improved health-related quality of life questionnaires and that there was no difference between the two groups despite the menstrual and satisfaction data. A comparison between Novasure and Thermachoice [45] reported significantly less intra and postoperative pain with Novasure; however, all women undergoing Thermachoice had 3-min dilatation and suction curettage, which might have contributed to the pain scores. Abbott et al. [31], in a randomized controlled trial of Novasure and Cavaterm, reported significantly lower pain scores for the Novasure device at 4 h after surgery and higher amenorrhoea rates at 12 months. Patient satisfaction and quality of life questionnaires were comparable between the groups at 12 months follow-up, but Novasure had 16% repeat procedures compared with 0% for Cavaterm. Another group [46] compared clinical outcomes and quality of life questionnaires between three second-generation techniques and laser ablation in a descriptive cohort study. The authors reported nonsignificant differences between the combined amenorrhoea and hypomenorrhoea rates and the quality of life scores at 12 months after treatment. A recent systematic review [47 ] assessed MEA with Thermachoice 1, and concluded that as no head-to-head trials have been performed between the two techniques, there was not enough evidence of differences in terms of clinical effectiveness to recommend one over another. The reader may also seek additional information on first-generation ablation devices from a recent review on the subject [48 ]. Implications for clinical practice Menstrual problems are among the most common reasons for specialist referrals and account for a third of gynaecological outpatient workload with an expanding multitude of treatment options [49 ]. The choice of treatment should be taken jointly by the woman and her clinician after taking all factors into consideration. In England, the trends in the number of hysterectomies performed for menorrhagia between 1989 and 2002/3 showed a substantial fall to just over one-third (36%) of the number of a decade earlier, most notably from 1995 [50 ]. This fall is not due to endometrial ablation alone, however, and other factors such as better patient education, the introduction of clinical guidelines and the use of the MIRENA intrauterine system for the treatment of menorrhagia, although only for such purpose in 2001, may all have added to this decline. Interestingly, the introduction of first-generation techniques in the 1980s did not appear to result in a similar downward trend. Often, the question Which device should I use? is asked. Each device has its relative strengths and weaknesses, and no single device can be preferred over another in all circumstances. The evidence presented above suggests that clinicians should consider the safety and effectiveness figures, applicability to the outpatient environment, and evidence of quality of life improvement applied on an individualized basis after full discussion with the patient and taking her preferences into account as well as surgical skill available at any institution. Implications for the health service An excellent attempt to apply a cost utility economic model to microwave and thermal balloon endometrial

6 462 Reproductive endocrinology ablation for heavy menstrual bleeding and compare their cost-effectiveness [51] concluded that despite limitations in available data, the evidence suggested that secondgeneration techniques were likely to be more cost-effective than first-generation techniques in most cases. Hysterectomy, where a woman finds this option acceptable, continues to be a very cost-effective procedure compared with all endometrial ablation methods. The implications for the UK National Health Service will depend on the number of women suitable for these techniques, and the uptake rates as influenced by patients choice and clinicians preference. Furthermore, the full economic impact of introducing these techniques into the outpatient setting will only be determined by hypothesis-driven, properly designed and powered randomized controlled trials [52 ]. A comprehensive review of thermal balloon ablation and MEA devices and their clinical and health service impact published by the National Institute of Clinical Excellence estimated that if all hysterectomies were replaced by second-generation ablation techniques, the annual cost saving would be in excess of 32 million, and would be less if first and second-generation techniques were used [53 ]. It was also argued that such savings are, however, unlikely to be realized financially as (1) the estimates represent amounts of resources that would remain within the system, but nevertheless be redeployed, and (2) are based on average and fixed costs that would not be saved but could be available for other purposes. Conclusion More evidence has accumulated in the past few years on the long-term efficacy and suitability of second-generation ablation devices in the outpatient and community settings. Evidence is also emerging that improvement in the quality of life is a more important endpoint to women than the occurrence of amenorrhoea. Such findings have informed the debate on the role of these techniques in clinical practice and enabled health economists to assess their true impact on the health service. There are, however, only very few studies comparing these techniques with each other and, equally, more effort should be made to collect reliable data on the frequency of treatmentassociated complications. These deficiencies would only be answered by properly designed and implemented prospective studies. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 470). 1 Jones KD, McGurgan P, Sutton CJG. Second-generation endometrial ablation techniques. Curr Opin Obstet Gynaecol 2000; 12: Soysal ME, Soysal SK, Vicdan K. Thermal balloon ablation in myoma-induced menorrhagia under local anesthesia. Gynecol Obstet Invest 2001; 51: Cooper JM, Anderson TL, Fortin CA, et al. Microwave endometrial ablation vs. rollerball electroablation for menorrhagia: a multicenter randomized trial. J Am Assoc Gynecol Laparosc 2004; 11: Glasser MH, Zimmerman JD. The HydroThermAblator system for management of menorrhagia in women with submucous myomas: 12- to 20-month follow-up. J Am Assoc Gynecol Laparosc 2003; 10: Watermeyer SR, Nix B, Amso NN. A randomised controlled study of two preoperative preparation protocols prior to endometrial balloon ablation in women with menorrhagia. In: Proceedings of the RCOG 6th International Scientific Meeting Improving the Health of Women: Lessons from the Past, Hope for the Future; Cairo Cooper J, Brill A, Fulop T. Is endometrial pretreatment necessary in NovaSure 3-D endometrial ablation? Gynaecol Endosc 2001; 10: Jack SA, Cooper KG, Seymour J, et al. A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs. BJOG 2005; 112: This paper provided strong evidence that endometrial preparation is not necessary for MEA. 8 Farrugia M, Hussain SY. Hysteroscopic endometrial ablation using Hydro- ThermAblation in an outpatient hysteroscopy clinic: feasibility and acceptability. J Minim Invasive Gynecol 2006; 13:in press. 9 Amso NN, Stabinsky SA, McFaul P, et al. Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300 patients from a multicentre study. International Collaborative Uterine Thermal Balloon Working Group. BJOG 1998; 105: Meyer WR, Walsh BW, Grainger DA, et al. Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison. Obstet Gynecol 1998; 92: Lok IH, Chan M, Tam WH, et al. Patient-controlled sedation for outpatient thermal balloon endometrial ablation. J Am Assoc Gynecol Laparosc 2002; 9: Clark TJ, Gupta JK. Outpatient thermal balloon ablation of the endometrium. Fertil Steril 2004; 82: Marsh F, Thewlis J, Duffy S. Thermachoice endometrial ablation in the outpatient setting, without local anesthesia or intravenous sedation: a prospective cohort study. Fertil Steril 2005; 83: The paper describes the suitability of Thermachoice in the outpatient setting. 14 McAllister KF, Bigrigg A. Uterine balloon therapy for menorrhagia: a feasibility study of its use in the community setting. J Fam Plann Reprod Healthcare 2002; 28: Olah KS, Alliston J, Jones J, et al. Thermal ablation performed in a primary care setting: the South Warwickshire Experience. BJOG 2005; 112: Wallage S, Cooper KG, Graham WJ, Parkin DE. A randomised trial comparing local versus general anaesthesia for microwave endometrial ablation. BJOG 2003; 110: Seymour J, Wallage S, Graham W, et al. The cost of microwave endometrial ablation under different anaesthetics and clinical settings. BJOG 2003; 110: Romer T, Muller J. Comparative prospective study of the treatment of recurrent menorrhagias: Cavaterm coagulation versus rollerball ablation. Gynaecol Endosc 1997; 6 (Suppl 2): Pellicano M, Guida M, Acunzo G, et al. Hysteroscopic transcervical endometrial resection versus thermal destruction for menorrhagia: a prospective randomized trial on satisfaction rate. Am J Obstet Gynecol 2002; 187: Gervaise A, Fernandez H, Capella-Allouc S, et al. Thermal Balloon Ablation versus endometrial resection for the treatment of abnormal uterine bleeding. Hum Reprod 1999; 14: Bongers MY, Mol BW, Dijkhuizen FP, Brolmann HA. Is balloon ablation as effective as endometrial electroresection in the treatment of menorrhagia? J Laparoendosc Adv Surg Tech A 2000; 10: Loffer FD, Grainger D. Five-year follow-up of patients participating in a randomized trial of uterine balloon therapy versus rollerball ablation for treatment of menorrhagia. J Am Assoc Gynecol Laparosc 2002; 9: Amso NN, Fernandez H, Vilos G, et al. Uterine endometrial thermal balloon therapy for the treatment of menorrhagia: long-term multicentre follow up study. Hum Reprod 2003; 18: Mangeshikar PS, Kapur A, Yackel DB. Endometrial ablation with a new thermal balloon system. J Am Assoc Gynecol Laparosc 2003; 10:27 32.

7 Second-generation endometrial ablation Amso Douglass B, Yackel DB, Vilos G. Thermablate EAS: a new endometrial ablation system. Gynecol Surg 2004; 1: Duleba AJ, Heppard MC, Soderstrom RM, et al. A randomized study comparing endometrial cryoablation and rollerball electroablation for treatment of dysfunctional uterine bleeding. J Am Assoc Gynecol Laparosc 2003; 10: Townsend DE, Duleba AJ, Wilkes MM. Durability of treatment effects after endometrial cryoablation versus rollerball electroablation for abnormal uterine bleeding: two-year results of a multicenter randomized trial. Am J Obstet Gynecol 2003; 188: Corson SL. A multicenter evaluation of endometrial ablation by Hydro- ThermAblator and rollerball for treatment of menorrhagia. J Am Assoc Gynecol Laparosc 2001; 8: Goldrath MH. Evaluation of HydroThermAblator and rollerball endometrial ablation for menorrhagia 3 years after treatment. J Am Assoc Gynecol Laparosc 2003; 10: Cooper J, Gimpelson R, Laberge P, et al. A randomized, multicenter trial of safety and efficacy of the NovaSure system in the treatment of menorrhagia. J Am Assoc Gynecol Laparosc 2002; 9: Abbott J, Hawe J, Hunter D, Garry R. A double-blind randomized trial comparing the Cavaterm TM and the NovaSure TM endometrial ablation systems for the treatment of dysfunctional uterine bleeding. Fertil Steril 2003; 80: Gallinat A. NovaSure impedance controlled system for endometrial ablation: three-year follow-up on 107 patients. Am J Obstet Gynecol 2004; 191: Donnez J, Polet R, Squifflet J, et al. Endometrial laser intrauterine thermotherapy (ELITT): a revolutionary new approach to the elimination of menorrhagia. Curr Opin Obstet Gynecol 1999; 11: Perino A, Castelli A, Cucinella G, et al. A randomized comparison of endometrial laser intrauterine thermotherapy and hysteroscopic endometrial resection. Fertil Steril 2004; 82: Cooper KG, Bain C, Parkin DE. Comparison of microwave endometrial ablation and transcervical resection of the endometrium for treatment of heavy menstrual loss: a randomised trial. Lancet 1999; 354: Cooper KG, Bain C, Lawrie L, Parkin DE. A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years. BJOG 2005; 112: An important paper describing the long-term follow-up of a second-generation device. 37 Rogerson L, Duffy S. A European survey of the complications of a uterine thermal balloon ablation system in 5800 women. Gynaecol Endosc 2002; 11: Gurtcheff SE, Sharp HT. Complications associated with global endometrial ablation: the utility of the MAUDE database. Obstet Gynecol 2003; 102: Lethaby A, Hickey M, Garry R. Endometrial destruction techniques for heavy menstrual bleeding. An update of Cochrane Database Syst Rev 2002, (2):CD001501, PMID, Cochrane Database Syst Rev 2005; 4:CD An excellent and comprehensive update of the literature on this subject. 40 Neuwirth RS, Loffer FD, Trenhaile T, Levin B. The incidence of endometrial cancer after endometrial ablation in a low-risk population. J Am Assoc Gynecol Laparosc 2004; 11: Hare AA, Olah KS. Pregnancy following endometrial ablation: a review article. J Obstet Gynaecol 2005; 25: Overton C, Hargreaves J, Maresh M. A national survey of the complications of endometrial destruction for menstrual disorders: the MISTLETOE study. BJOG 1997; 104: Bongers MY, Bourdrez P, Mol BWJ, et al. Randomised controlled trial of bipolar radio-frequency endometrial ablation and balloon endometrial ablation. BJOG 2004; 111: Bongers MY, Bourdrez P, Heintz APM, et al. Bipolar radio frequency endometrial ablation compared with balloon endometrial ablation in dysfunctional uterine bleeding: Impact on patients health-related quality of life. Fertil Steril 2005; 83: An excellent assessment of the improvement in the quality of life following secondgeneration treatments that is unrelated to menstrual outcome. 45 Laberge PY, Sabbah R, Fortin C, Gallinat A. Assessment and comparison of intraoperative and postoperative pain associated with NovaSure and ThermaChoice endometrial ablation systems. J Am Assoc Gynecol Laparosc 2003; 10: Abbott JA, Hawe J, Garry R. Quality of life should be considered the primary outcome for measuring success of endometrial ablation. J Am Assoc Gynecol Laparosc 2003; 10: Garside R, Stein K, Wyatt K, Round A. Microwave and thermal balloon ablation for heavy menstrual bleeding: a systematic review. BJOG 2005; 112: A thorough systematic review of two commonly used second-generation ablation devices. 48 Munro MG. 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