The Role of ThermaChoice^TM and MEA^TM in Managing Dysfunctional Uterine Bleeding

Abukhalil I.H. and Raheem M.
West Midland, United Kingdom

Introduction:

Menorrhagia and dysfunctional uterine bleeding are common indications for referral to a gynecologist. One in 20 women aged 30-49 will consult her general practitioner every year complaining of heavy uterine bleeding(1). Over 70,000 hysterectomies are performed annually in the UK with menorrhagia being the commonest indication. In up to 30% of these cases the uterus is anatomically normal. To these women, heavy uterine bleeding brings considerable stress and disruption to their social, domestic and professional lives. In the UK, the cost of primary care prescriptions for the treatment of menorrhagia was estimated in 1998 to be around £7 million⁽²⁾. Gynecologists have looked at less radical but effective alternatives to hysterectomy for the treatment of heavy uterine bleeding. While the MISTLETOE⁽³⁾ audit had demonstrated a pivotal role for less extreme yet successful interventions than hysterectomy for the treatment of bleeding problems, there were some setbacks. Special skills are needed to perform rollerball and diathermy loop resections of the endometrium. As well as the risk of serious intra-operative complications the techniques are relatively time consuming to perform. In the MISTLETOE audit there were two direct deaths as a consequence of the procedure and 1.26% of patients required emergency surgery. This review looks at two new interventions available for clinical use, in the short term they have both proven to be successful and safe in the management of heavy uterine bleeding. Individually, they offer distinct advantages in the successful treatment of heavy uterine bleeding without the disadvantages of major surgery or medical treatment. They are both relatively easy to learn and do not require advanced hysteroscopic skills. A major step forward is the suitability for outpatient setting.

THERMAL BALLOON ENDOMETRAL ABLATION (ThermaChoice, ETHICON^®):

This second-generation endometrial ablation technique uses a 16 cm long and 3 mm wide catheter connected to a latex balloon filled with 5% dextrose heated to 87°C for 8 minutes⁽¹⁴⁾. The pressure inside the balloon is maintained between 150-180 mmHg. These parameters are set and monitored by a control unit (ThermaChoice, ETHICON).

The technique is simple to learn and does not require advanced hysteroscopic skills. The balloon is inserted into the uterine cavity with little or no dilatation of the cervix under a local^(19,20), regional or general anesthesia.

This method is suitable for pre-menopausal women with regular uterine cavity and no cervical or endometrial malignancies⁽⁵⁾. Future child bearing is contraindicated. The latex balloon would not be suitable for patients with a known latex allergy. Endometrial preparation is not always indicated⁽⁵⁾.

A small preliminary, observational study⁽⁴⁾ of 18 patients
treated with ThermaChoice for menorrhagia quoted 83% significant reduction in bleeding. This early result was comparable to the success of hysteroscopic methods of endometrial ablation then in use. Amso et al⁽⁵⁾ published the results of one of the earliest multicentre prospective observational studies (international collaborative uterine thermal balloon working group) of 300 patients treated with ThermaChoice between June 1994 and August 1996. Criteria for inclusion into the study were: failed medical management for intractable uterine bleeding, pre-menopausal, normal uterine cavity and completed family. Patients were excluded if they were known to have a structural uterine abnormality or known endometrial/cervical malignancy. There were no intra-operative complications and post-operative morbidity was minimal. Successful reduction of menses to eumenorrhea or less was 88-91% over the first year. The researchers concluded that thermal balloon endometrial ablation appears to be safe, as well as effective in properly selected women with menorrhagia. Several other observational studies reported similar findings^(6,7,8). A successful outcome was more likely(5) with increasing age, higher balloon pressure, smaller uterine cavity and lesser degree of pre-procedure menorrhagia. Bonger et al⁽⁹⁾ similarly concluded in his prospective study of 130 patients that young age and prolonged duration of menstruation were associated with an increase risk of treatment failure. Additionally, their study identified a retro-verted uterus and endometrial thickness of at least 4 mm to be risk factors for treatment failure. The balloon method of endometrial ablation was formally assessed in a randomized-controlled trial(10) of 255 patients with rollerball endometrial ablation. Menorrhagia was assessed by pre-procedure and post-procedure menstrual diary scores and quality of life questionnaires. Data at 12 months indicated that both techniques were comparable in reducing menstrual blood flow (balloon 80.2% and rollerball 84.3%). Quality of life assessment showed that patients were satisfied with their treatment (balloon 85.6% and rollerball 86.7%). This trial concluded that the balloon technique of endometrial ablation was comparable to the rollerball method. Also, there was a trend towards more intra-operative complications in the rollerball group (3.2%) compared with (0%) in the balloon group. At two years follow up(11) patients in both arms of the trial were highly successful in avoiding hysterectomy and relieving the symptoms of menorrhagia. Only 15 hysterectomies were performed (6 for menorrhagia), 11 in the rollerball and 4 in the balloon group. Additional benefits were reduction in dysmenorrhea and pre-menstrual syndrome. At three years follow up(12), both balloon and rollerball ablations were successful in treating menorrhagia, avoiding hysterectomy, decreasing dysmenorrhea and pre-menstrual syndrome and improving quality of life. The observed trend of more hysterectomies in rollerball(14) compared with balloon⁽⁸⁾ ablation persisted.

Using a heat transfer model for thermal balloon endometrial ablation, the tissue damage depth is calculated at 3 to 6 mm(13). Clinical trials were done in Mexico on 6 and in London on 4 patients undergoing hysterectomy⁽¹⁴⁾. Heating was carried out for 6-12 minutes, with balloon pressure set between 45 and 165 mmHg and temperature at 92°C. The maximum zone of destruction was 10 mm, and with 6 minutes of heating, 5.07 mm. For 6 minutes of heating, the highest recorded serosal temperature was 37°C. The safety of balloon ablation was examined in observational in-vivo and in-vitro study with histopathologic correlation on 23 patients undergoing abdominal hysterectomy(17). The greatest depth of myometrial damage in-vitro was 5.8 mm over the anterior lower uterine segment and in-vivo 3.8mm in the anterior midline. Peak serosal temperatures were within the safe physiological range, (in-vitro <45°C and in-vivo 36.1 +/- 1.6°C). Trans-uterine injury is a highly unlikely scenario. Andserson et al(18) reported on light and electron microscopy assessment of thermal damage in 8 patients after their subsequent hysterectomy. Coagulation of the myometrium adjacent to the endometrium could be demonstrated by light microscopy with a maximum depth of 11.5 mm and 15mm by electron microscopy. Full thickness necrosis or injury from the coagulated myometrium in unlikely.

Vilos et al⁽¹⁵⁾ reported the effects of varying pressure and duration with balloon ablation treatment in a retrospective cohort study of 66 patients with menorrhagia. At 12-24 months follow up, persistent menorrhagia was reported in 56% of women treated at 80 to 150 mmHg compared with 20% treated at 151 to 180 mmHg for 8 minutes (p=0.001) and in 24% treated for 12 to 16 minutes at 151 to 180 mmHg (p=0.1). Therefore, balloon pressure greater than 150 mmHg increased the effectiveness of treatment. Increasing the duration of treatment from 8 to 12 minutes or more did not influence success. Similar findings were reported with pressure and duration of treatment variations in a larger prospective, observational study⁽¹⁶⁾.

Thirty-six patients each were randomized to balloon ablation or Mirena as treatment for heavy menstrual bleeding⁽¹⁹⁾. All balloon ablations were done in an outpatient clinic with local anaesthesia. Both treatments significantly reduced menstrual bleeding. However, patients in the balloon group perceived a higher health related quality of life as they reported fewer side effects.

In an observational study of 46 women with menorrhagia
and high-risk surgical candidates⁽²⁰⁾ for hysterectomy or hysteroscopic endometrial ablation, they were safely and effectively treated with balloon ablation. 40% of patients had the procedure under local anesthesia with or without sedation. No intra-operative complications were reported.

MICROWAVE ENDOMETRIAL ABLATION:

Microwave, as an energy source for endometrial ablation, was developed at the University of Bath in conjunction with the Royal United Hospital, departments of Gynecology and medical physics from 1992⁽²³⁾. The Microwave Endometrial Ablator (MEA^TM) generator in use (MICROSULIS^®, Hampshire, UK) delivers microwave power at 30 W and frequency of 9.2 GHz via an eight (8 mm) applicator as a dielectric waveguide(21). At this frequency tissue necrosis depth is consistently 5-6 mm. There are no earthing problems associated with this applicator. A surgeon operated foot switch controls the release of microwave energy. The temperature achieved inside the uterus is monitored continuously by thermocouples on the exterior surface of the waveguide. A computer displays temperature graphically in real time and generates a hard copy.

                                      

In-vivo experiments were carried out in 17 patients immediately prior to abdominal hysterectomy. No microwave leakage occurred beyond the uterus. Post-hysterectomy histological and histochemical analysis clearly demarcated a 5-6 mm area of necrosis and a further 1-mm zone of transition from cell necrosis to cell death⁽²³⁾.

Patients with heavy uterine bleeding who have completed their family, without endometrial or cervical malignancy are suitable for MEA⁽²³⁾. Patients with slightly enlarged and minor distortion of the uterine cavity may also be suitable candidates. Pre-treatment with endometrial thinning drugs is recommended 4-5 weeks prior to treatment. MEA is not recommended in patients treated with prior rollerball ablation.

The first published observational study examined 23 patients with menorrhagia treated with MEA⁽²¹⁾. Thirteen (57%) patients were amenorrheic at six months and 6 (26%) reported light menstruation. Four (12%) patients failed to respond. After re-treatment, however, these four patients became amenorrheic. Additional observed benefits were a reduction in dysmenorrhea (95%). Other small observational study reported similar findings. In their report of 16 women treated with MEA, Milligan et al⁽²²⁾ found 87.5% satisfaction with significant reduction in menstrual score at one year. Hodgson et al⁽²³⁾ reported on 43 patients treated for 46 cycles with MEA, followed for three years with 83.7% overall satisfaction in reduction of menses. Moderate (55.8%) or severe (27.9%) dysmenorrhea preoperatively had improved (11.6% and 6.8% respectively) at three years. The technique of MEA was assessed in a RCT with TCRE⁽²⁴⁾. The primary outcome measures were patients’ satisfaction with and acceptability of the two procedures. Secondary measures were comparison of effects on menstrual status and health related quality of life, 263 patients were randomized to receive MEA or TCRE. At 12 months follow up 116 of 123 in MEA and 124 of 132 in TCRE group were available for evaluation. Both treatment methods led to significant and equivalent reductions for all variables relating to bleeding (p< 0.001). The proportions of women with dysmenorrhea or pelvic pain were significantly lower than at baseline in both groups (p<0.001), but did not differ between the groups. Similarly, the proportions with pre-menstrual symptoms were much lower with both techniques (p<0.001)

MEATM and MIRENA^®:

A retrospective cohort study of 39 women treated with MEA and 23 patients treated with MIRENA⁽²⁶⁾ concluded that both treatments were acceptable and effective (p<0.0001) management options for heavy menstrual bleeding. The study also recorded a significant reduction in dysmenorrhea (p<0.002) with both treatments.

References:

1. RCOG. The initial management of menorrhagia. National evidence-based clinical guidelines. Jan, 1998.

2. RCOG. The management of menorrhagia in secondary care. National evidence-based clinical guidelines. Jan, 1999.

3. Overton C, Hargreaves J, Maresh M. A national survey of the complications of endometrial destruction for menstrual disorders: The MISTLETOE study. Minimally Invasive Surgical Techniques-Laser, EndoThermal or Endorescetion. Br J Obstet Gynecol. 1997 Dec; 104(12): 1351-9.

4. Singer A, Almanza R, Gutierrez A, Haber G, Bolduc LR, Neuwirth R. Preliminary clinical experience with a thermal balloon endometrial ablation method to treat menorrhagia. Obstet Gynecol. 1994 May; 83(5 Pt 1): 732-4.

5. Amso NN, Stabinsky SA, McFaul P, Blanc B, Pendley L, Neuwirth R. Uterine thermal balloon therapy for the treatment of menorrhagia: The first 300 patients from a multi-centre study. International Collaborative Uterine Thermal Balloon Working Group. Br J Obstet Gynecol. 1998 May; 105(5): 517-23.

6. Buckshee K, Banerjee K, Bhatla H. Uterine balloon therapy to treat menorrhagia. Int J Gynecol Obstet. 1998 Nov; 63(2); 139-43.

7. Vilos GA, Fortin CA, Sanders B, Pendley L, Stabinsky SA. Clinical trial of the uterine thermal balloon for treatment of menorrhagia. J Am Assoc Gynecol Laparosc. 1997 Nov; 4(5): 559-65.

8. Vilos GA, Vilos EC, Pendley L.Endometrial ablation with a thermal balloon for the treatment of menorrhagia. J Am Assoc Gynecol Laparosc. 1996 May; 3(3): 383-7.

9. Bongers MY, Mol BW, Brolmann HA. Prognostic factors for the success of thermal balloon ablation in the treatment of menorrhagia. Obstet Gynecol. 2002 Jun; 99(6): 1060-6.

10. Meyer WR, Walsh BW, Grainger DA, Peacock LM, Loffer FD, Steege JF. Thermal balloon and rollerball ablation to treat menorrhagia: A multicenter comparison. Obstet Gynecol. 1998 Jul; 92(1): 98-103.

11. Grainger DA, Tjaden BL, Rowland C, Meyer WR. Thermal balloon and rollerball ablation to treat menorrhagia: Two-year results of a multicenter, prospective, randomized, clinical trial. J Am Assoc Gynecol Laparosc. 2000 May; 7(2): 175-9.

12. Loffer FD. Three-year comparison of thermal balloon and rollerball ablation in treatment of menorrhagia. J Am Assoc Gynecol Laparosc. 2001 Feb; 8(1): 48-54

13. Baldwin SA, Pelman A, Bert JL. A heat transfer model of thermal balloon endometrial ablation. Ann Biomed Eng. 2001 Nov; 29(11): 1009-18.

14. Neuwirth RS, Duran AA, Singer A, MacDonald R, Bolduc L. The endometrial ablator: A new instrument. Obstet Gynecol. 1994 May; 83(5 Pt 1): 792-6.

15. Vilos GA, Aletebi FA, Eskandar MA. Endometrial thermal balloon ablation with the ThermaChoice system: effect of intrauterine pressure and duration of treatment. J Am Assoc Gynecol Laparosc. 2000 Aug; 7(3): 325-9.

16. Vilos GA, Fortin C, Sanders B, Pendley L, McColl M. Uterine Balloon Therapy for the treatment of menorrhagia. J Am Assoc Gynecol Laparosc 1996 August; 3(4,supp.): S54.

17. Shah AA, Stabinsky SA, Klusak T, Bradley KR, Steege JF, Grainger DA. Measurement of serosal temperatures and depth of thermal injury generated by thermal balloon endometrial ablation in ex vivo and in vivo models. Fertil Steril. 1998 Oct; 70(4): 692-7.

18. Andersen LF, Meinert L, Rygaard C, Junge J, Prento P, Ottesen BS. Thermal balloon endometrial ablation: safety aspects evaluated by serosal temperature, light microscopy and electron microscopy. Eur J Obstet Gynecol Reprod Biol. 1998 Jul; 79(1): 63-8.

19. Soysal M, Soysal S, Ozer S. A randomized controlled trial of levonorgestrel releasing IUD and thermal balloon ablation in the treatment of menorrhagia. Zentralbl Gynakol. 2002 Apr; 124(4): 213-9.

20. Aletebi FA, Vilos GA, Eskandar MA.Thermal balloon endome- trial ablation to treat menorrhagia in high-risk surgical candi- dates. J Am Assoc Gynecol Laparosc. 1999 Nov; 6(4): 435-9.

21. Sharp NC, Cronin N, Feldberg I, Evans M, Hodgson D, Ellis S. Microwaves for menorrhagia: a new fast technique for endometrial ablation. Lancet. 1995 Oct 14; 346(8981):1003-4.

22. Milligan M.P, Etokowo G.A,Microwave Endometrial Ablation for Menorrhagia. J Obst. Gynae(1999) vol. 19, No.5, 496-99.

23. Hodgson DA, Feldberg IB, Sharp N, Cronin N, Evans M, Hirschowitz L. Microwave endometrial ablation: Development, clinical trials and outcomes at three years. Br J Obstet Gynaecol. 1999 Jul; 106(7): 684-94.

24. 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 Nov 27; 354(9193): 1859-63.

25. Bain C, Cooper KG, Parkin DE. Microwave endometrial ablation versus endometrial resection: a randomized controlled trial. Obstet Gynecol. 2002 Jun; 99(6): 983-7.

26. Henshaw R, Coyle C, Low S, Barry C. A retrospective cohort study comparing microwave endometrial ablation with levonorgestrel-releasing intrauterine device in the management of heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2002 May; 42(2): 205-9.