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Keywords:

  • Heavy menstrual loss;
  • microwave endometrial ablation;
  • randomised controlled trial

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

Please cite this paper as: Sambrook A, Jack S, Cooper K. Outpatient microwave endometrial ablation: 5-year follow-up of a randomised controlled trial without endometrial preparation versus standard day surgery with endometrial preparation. BJOG 2010;117:493–496.

The objective was to compare long-term outcomes following outpatient microwave endometrial ablation in the postmenstrual phase with those following day surgery microwave endometrial ablation after standard drug-based endometrial preparation. Of the women originally recruited, 154/197 (78%) returned questionnaires. The primary outcome of satisfaction was high in both groups (71% postmenses versus 65% preparation) as were the amenorrhoea rates (84% versus 87%). There was no significant difference in the hysterectomy rates between the two arms. It can be concluded that microwave endometrial ablation outcomes are not affected in the long term by undertaking the procedure in the postmenstrual phase in an outpatient setting.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

Microwave endometrial ablation (MEA™) has been established as a safe and effective conservative treatment for heavy menstrual bleeding, and has been proven in a randomised trial to be acceptable to women under local anaesthesia with or without conscious sedation.1 The original results from this cohort of patients demonstrated no significant difference in menstrual outcomes between women treated in the postmenstrual phase and those who received a standard endometrial preparation in the form of gonadotrophin-releasing hormone analogues or danazol.1 Endometrial preparation is not only an extra cost with unpleasant adverse effects, but significantly increases cervical resistance, making cervical trauma and false passage formation more likely.2

Significant health service cost savings were found at 1-year follow-up for women undergoing treatment in the postmenstrual phase.1 As with any change to an established technique, it is imperative that adequate long-term follow-up is performed to ensure that short-term outcomes are maintained and that unforeseen and unwanted outcomes do not become evident.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

Full methodological and operative details can be found in the original paper.1 Local ethics committee approval was obtained for long-term follow-up.

Participants

Women were recruited from the general gynaecology clinics of Aberdeen Royal Infirmary. They were considered to be eligible if they had heavy menstrual loss, their family was complete, there was no endometrial atypia and the uterus was not greater than 12 weeks’ size. Preoperative screening to exclude fibroids was not undertaken. Baseline questionnaires were completed by the patient prior to surgery.

Treatments were performed following endometrial preparation [danazol 200 mg twice daily for 4–5 weeks (85% of women in the preparation arm), a single injection of goserelin 3.6 mg subcutaneously 5 weeks pre-operatively (9% of women in the preparation arm) or both (6% of women in the preparation arm)] in the day surgery unit, or as an outpatient procedure in the postmenstrual phase.

Operations were performed under local anaesthetic (3% prilocaine with felypressin four-quadrant cervical block), with or without intravenous sedation (midazolam 2–4 mg). Intravenous fentanyl 25–50 μg was available if intraoperative analgesia was required.

Postal questionnaires were sent at a minimum of 60 months after the original procedure.

Objective/outcomes

The primary objective of this study was to detect any difference in patient satisfaction between postmenstrual treatment and treatment with standard endometrial preparation.

Secondary outcomes assessed at a minimum of 5 years were identical to those reported at 1 year, and included menstrual status, changes in health-related quality of life [Short Form-12 (SF12)] and any further surgery received.1 The questionnaire was sent to the participant. Those who did not respond were sent a postal reminder and, finally, a telephone call to ascertain whether they wished to participate. Data were entered into an SPSS (version 16, SPSS Inc., Chicago, IL, USA) database. Subsequent operations were established from the questionnaires and from the hospital database for all 210 recruits.

Sample size

The original power study determined that 180 recruits were required to give an 80% power of demonstrating a 20% difference in satisfaction with treatment and a 10% difference in satisfaction rate (P = 0.05). Two-hundred and ten women were recruited and treated to allow for a 15% dropout rate at 1 year post-treatment.

Randomisation/blinding

The randomisation sequence was created by an independent statistician using computer-generated random number tables which were in balanced blocks of 20. A series of sealed opaque sequentially numbered envelopes was created revealing the treatment code in an individual randomisation ratio of 1:1. Following informed consent, a secretary at a separate site opened the next envelope in the sequence. Blinding of the patients to their treatment allocations was not performed.

Statistical methods

Statistical analysis of the 5-year data was undertaken on the number of returned questionnaires using SPSS for Windows (version 16). Analysis was performed as intention-to-treat for subjective outcome measures, treating those who did not return their questionnaire as treatment failures. Objective outcomes were calculated only for those women who returned the questionnaire. Subsequent operations were established both from the questionnaires and a hospital database search for all 210 participants.

Independent and paired t tests were used to analyse continuous variables (independent and related) with a normal distribution. The Mann–Whitney U test was used for ordinal or continuous variables that were not normally distributed. Chi-squared or Fisher’s exact test was used for independent nominal data. Confidence intervals for the difference in means were calculated for continuous variables with a normal distribution. Confidence intervals for the differences in proportions were calculated for categorical data using the Confidence Interval Analysis program (C.I.A. v 1.1, BMJ, London, UK), where appropriate.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

Participants

One hundred and fifty-four of the 197 (73.3%) women originally recruited returned completed questionnaires. The baseline characteristics of the 154 women successfully followed up were very similar to those of the total trial group and not statistically significantly different between either group.1

There were no statistically significant differences between the two groups with respect to satisfaction with treatment and menstrual symptoms (Table 1). There was a highly significant and comparable decrease in the bleeding score (postmenstrual, 95%; standard drugs, 97%) and pain score (postmenstrual, 87%; standard drugs, 93%) in both trial groups.

Table 1.   Menstrual outcomes and satisfaction, and recommendation to a friend (%)
 Postmenses (n = 77)Drug preparation (n = 77)Difference in proportions (95% CI)
Amenorrhoea63 (81)66 (86)−0.16, 0.08
Periods light13 (17)11 (14)−0.09, 0.14
Unchanged/heavier1 (1)0−0.01, 0.04
Change in bleeding score23.99 (9.84)24.78 (10.17)−3.98, 2.40
Change in pain score14.59 (9.49)12.33 (9.97)−0.84, 5.36
Intention-to-treat analysisPostmenses (n = 97) (%)Drug preparation (n = 100) (%)Difference in proportions (95% CI)
Totally or generally satisfied69 (71.13)65 (65.00)−0.07, 0.19
Recommend to a friend73 (75.26)73 (73.00)−0.10, 0.15

Both the physical and mental components of SF12 demonstrated significant improvement from the baseline quality of life scores for both categories, and this was not altered significantly from the 12-month follow-up.

Subsequent treatment received or continued at 5 years

At a minimum of 60 months following MEA™, the majority of women had not undergone further gynaecological surgery There was no statistically significant difference in women undergoing hysterectomy, with 11 women (11%) in the postmenses arm and six (6%) in the standard preparation arm (95% CI, −0.03, 0.13). Following MEA™ in the postmenstrual phase, of the 11 hysterectomies, one was for heavy bleeding, seven for cyclical pain, two for irregular bleeding and one for prolapse. Half the hysterectomies demonstrated normal pathology with the other half showing a mixture of adenomyosis, endometriosis and fibroids. In the standard preparation arm, there were three hysterectomies for pain and three for heavy bleeding. Two of these hysterectomies showed normal pathology, with the remaining four demonstrating adenomyosis, endometriosis or fibroids. There were three repeat ablations in the preparation arm and one in the postmenses arm.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

Changes to established practice need to be evaluated carefully before acceptance and introduction. This generally necessitates evaluation in a randomised trial with meaningful outcomes and length of follow-up. The ability to acceptably perform MEATM in the outpatient setting was established by the short-term results of this trial. Long-term follow-up has shown that undertaking the procedure in the postmenstrual phase does not compromise all measured outcomes. Hospital episode statistics have demonstrated a fall in the number of hysterectomies for heavy menstrual bleeding with a rise in the number of endometrial ablations over the last decade.3 It is therefore important to ensure that new ablative techniques or changes in the way in which they are performed are successful in the long term and do not just delay the requirement for hysterectomy.

This is the first long-term follow-up of a randomised study evaluating MEA™ in the postmenstrual phase and in an outpatient setting. Undertaking the procedure in the postmenstrual phase was based on findings from in vitro and in vivo studies, which demonstrated no loss of efficacy in endometrial thicknesses up to 10 mm.4

Follow-up in excess of 70% is in keeping with previous long-term follow-up from ablation trials. The two trial arms remained balanced at the 5-year follow-up despite the dropout of recruits. Those women who did not respond were analysed as treatment failures for the principal outcome measure. This gives the impression of a deterioration in satisfaction with treatment over time, but this is the correct method for the analysis of data within pragmatic randomised controlled trials. It does not lend itself to comparison with results from other trials that have not used this method of analysis.

Women with the subjective complaint of heavy bleeding were eligible for recruitment, with formal menstrual blood loss measurements not being performed. Routine ultrasound and hysteroscopy were not performed unless clinically indicated. This mirrors clinical practice, thereby increasing the generalisability of the results.

Heavy menstrual loss is known to cause significant deterioration in quality of life, and SF-36 has been used previously within the unit as it has proven validation for menstrual complaints.2 This trial chose to use SF-12 as it consists of fewer questions, thereby requiring less time for respondents to complete. It demonstrates good correlation with SF-36, but has not been formally validated for menstrual disorders. The physical component of the SF-12 score demonstrated an overall improvement from baseline at 6 months. This was reduced at 12 months and further reduced at 60 months to the mean normative value (51.07) for the age group.5 The mental component followed a similar pattern, with an overall improvement for both arms at 12 months, and a fall to the normative values (48.01) by 60 months.5 No significant difference was noted between either group.

This study demonstrates that MEA™ in the postmenstrual phase maintains high rates of satisfaction at long-term follow-up, and this is not significantly different from that in the standard drug preparation arm. Endometrial preparation in the form of gonadotrophin-releasing hormone or danazol provides unpleasant adverse effects and a cost burden to the NHS. Scheduling treatment to the postmenstrual phase or inducing a withdrawal bleed with progestogen1 has been demonstrated to be an acceptable and efficacious alternative without detriment to long-term outcomes. Scheduling treatments when there is a flexible dedicated operator, such as a research fellow, is not difficult. In routine practice, with fixed sessions and staff with set commitments, this is more difficult. An alternative way of inducing a predictable withdrawal bleed is to use a 7–10-day course of Provera 10 mg twice daily stopped 10 days prior to the procedure. It does require the woman to take a hormonal medication, although it is for a short time and is inexpensive at £4.94 for the 10-day course (values taken from British National Formulary 2009).

The genuine amenorrhoea rate was in excess of 70% if the hysterectomies were excluded at 5 years. With a mean age of 42 years at recruitment, the majority of women would still have been premenopausal at follow-up. Only one participant described her periods as unchanged or heavier. Again, in keeping with previous work, menstrual pain was reduced significantly in both groups.

Repeat surgery rates in the form of hysterectomy (8.63%) were halved at 5 years in this study in comparison with women participating in an MEA™ versus transcervical resection of the endometrium (TCRE) trial within this unit (16%).6 Repeat endometrial ablation in the form of rollerball was comparable at 4/197 versus 0/129 for those undergoing MEA in the MEA/TCRE trial.6 The reasons behind this reduction in the requirement for further surgery are uncertain. In both trials, the operator had only recently been trained in the MEA™ technique. Cyclical pain was the most common reason for hysterectomy. Of the 11 hysterectomies performed for pain, six had no specific pathology on analysis of the specimen. Only two showed evidence of endometriosis or adenomyosis, and three demonstrated fibroids. Perhaps we are improving our diagnosis of endometriosis and adenomyosis for women with cyclical pain, and these women are opting for Mirena or hysterectomy as a primary procedure.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

This trial has further demonstrated the versatility of MEA™. This is an endometrial ablative technique which can acceptably be performed in the outpatient setting in the postmenstrual phase without compromising outcomes in the long term.

Contribution to authorship

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

AS undertook follow-up of all patients for this study, input the data, undertook statistical analysis and wrote the manuscript.

SJ recruited the patients, undertook the majority of treatments and edited the manuscript.

KC designed the trial and methodology, supervised the original procedures, supervised the statistical analysis, edited the manuscript and is guarantor.

Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

No external funding was provided for this study. Costs were covered by the Gynaecology Endoscopy Research Fund.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References

The original study was funded by a grant awarded by the Chief Scientists Office, Scottish Executive Health Department. This follow-up study was internally funded by the Gynaecology Endoscopy Research Fund. The views expressed are those of the authors.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Disclosure of interest
  9. Contribution to authorship
  10. Details of ethics approval
  11. Funding
  12. Acknowledgements
  13. References
  • 1
    Jack SA, Cooper KG, Seymour J, Graham W, Fitzmaurice A, Perez J. A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs. BJOG 2005;112:110916.
  • 2
    Cooper KG, Pinion SB, Bhattacharya S, Parkin DE. The effects of the gonadotrophin releasing hormone analogue (goserelin) and prostaglandin E1 (misoprostol) on cervical resistance prior to transcervical resection of the endometrium. Br J Obstet Gynaecol 1996;103:3758.
  • 3
    Reid PC. Endometrial ablation in England – coming of age? An examination of hospital episode statistics 1980/1990 to 2004/2005. Eur J Obstet Gynecol Reprod Biol 2007;135:1914.
  • 4
    Wallage S, Cooper KG, Parkin DE. Microwave endometrial ablation: does endometrial thickness or the medium for pre-operative hysteroscopy affect the depth of ablation. Gynecol Endosc 2003;11:1079.
  • 5
    Ware JE, Kosinski M, Turner-Bowker DM, Gandek B. How to Score Version 2 of the SF12 Health Survey (with a Supplement Documenting Version 1). Lincoln, RI: Quality Metric Incorporated, 2002.
  • 6
    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;112:4705.