an initial report in the Lancet by Phipps et al 1 describing the use of radio waves for the treatment of menorrhagia.
Radiofrequency endometrial ablation (RaFEA) used elec- tromagnetic energy at a frequency of 27.12 MHz to heat the endometrium and to destroy the regenerative basalis layer. This report prompted the formation of the research team in Bath, UK, to explore the possibility of using microwaves to achieve the same objective, with the expec- tation that it should potentially have advantages over the use of radiofrequency. Microwave energy lies in the mil- limeter waveband, with a frequency in t he GHz range.
At the same time, RaFEA was trialled in the Bath Royal United Hospital as the first endometrial ablation technique in the department, and considerable experience was obtained with it while the microwave research was being completed.
Despite the two technologies being in adjacent parts of the electromagnetic spectrum, the difference in frequency con- siderably altered how the energy behaved in use, and this was reflected in the safety margins: microwaves are inherently safe; radio waves, we found, are inherently dangerous.
The microwave research turned out to be fruitful, not only living up to the research team's expectations but also exceeding them and making it one of the foremost types of endometrial ablation today.
It is interesting to compare the features of MEA against RaFEA (Table 21.1), to show the differences in the technologies.
Owing to an unacceptably high incidence of complica- tions with RaFEA, it was withdrawn from the market in 1995. MEA, however, was taken through all research stages and initial trials without adverse events, and the first report of a successful clinical study was published in 1995. 2
MICROWAVE THEORY
Microwaves, like most other forms of electromagnetic energy, penetrate tissues, and the depth of penetration is
a function of their wavelength. Microwaves are non-ion- izing, but the absorption in tissues causes heating, largely due to energizing of water molecules. A domestic micro- wave oven uses a frequency of 2.3 GHz to penetrate deeply into the food to be cooked. If the frequency is raised and the wavelength therefore decreased, penetra- tion is reduced, and by choosing the correct frequency, penetration can be restricted to a specific depth. Using a frequency of 9.2 GHz, with a wavelength of approxi- mately 3 cm, tissue penetration is restricted to 5–6 mm. 3 This penetration is determined purely by microwave physics, and is essentially independent of the power setting.
Microwaves can be emitted by an antenna arrange- ment – a variation on a bare wire, or transferred by a waveguide. An antenna arrangement was judged to be an ineffective approach for endometrial ablation, and wave- guide technology was the favored approach. An air-filled waveguide would need to be about 30 mm in diameter to transfer microwaves at 9.2 GHz. 3 The preferred diameter for the microwave device was 8 mm – a compromise between feasible cervical dilation, but adequate ‘blunt- ness’ to avoid uterine perforation. To ‘pipe’ microwaves down an 8 mm waveguide, it was necessary to find an appropriate dielectric filler for the waveguide. Initially, a ceramic rod was used as the dielectric. This was effective, but liable to fracture with rough handling, and further refinements produced a more robust, easily manufactured applicator.
More recently, a disposable waveguide (FemWave) has been introduced (Figures 21.1 and 21.2), and reusable applicators will be phased out.
MICROWAVE RESEARCH
The microwave research was divided into a series of steps (with full Research Ethical Committee approval):
(1) Measurements of ‘permittivity’ of endometrium.
(2) Excised unperfused organ studies.
Microwave endometrial ablation
Nicholas C Sharp
21
(3) Excised perfused organ studies.
(4) Treatment of patients immediately prior to hyster- ectomy.
(5) Clinical trial.
Step 1
Samples of endometrium were obtained by simple curet- tage, and laboratory measurements of tissue permittivity made. It was found that most soft tissues registered simi- lar values and, subsequently, raw animal liver made a very Table 21.1 Comparison of microwave endometrial ablation and radiofrequency endometrial ablation
Characteristic Microwave endometrial ablation Radiofrequency endometrial ablation
Frequency 9.2 GHz 27.12 MHz
Power 22 W (emitted) 200–350 W
Warm-up time None 6–8 minutes
Treatment time 3.5 minutes (average) 12 minutes
Energy used 4.6 kJ (average) 240–420 kJ
Applicator diameter 8.2 mm 10 mm
Earthing No Yes, and capable of ‘earthing’ through electrically
insulated items
Earth return belt required No Yes
Endometrial temperature 100°C 63–68°C
Uterine perfusion Irrelevant Essential to prevent thermal spread to serosa, with
adjacent organ damage
Vaginal contact with applicator Safe Had to be avoided to prevent serious burns due to ‘earthing’
Energy field Confined to 5 mm Filled entire operating theater, affecting
of endometrium anesthetic alarm systems and other electrical equipment
Waveguide Yes No
Antenna No Yes. Patient would emit energy as part of the system.
Simple touch would cause significant warming due to
energy transfer
Figure 21.1 Disposable waveguide (FemWave) of the MEA. Figure 21.2 The MEA Control Unit.
useful trial material, with easily visible and measurable thermal effects.
Step 2
After obtaining informed consent, normal uteri from hys- terectomy (usually for menorrhagia) were instrumented, and the microwaves applied to the cavity before despatch to histology. Serosal temperature measurements con- firmed the absence of serosal heating despite high cavity temperatures. Histology confirmed major thermal effects and tissue destruction of endometrium.
Step 3
Identical to Step 2, but perfusion of the uterus with warm saline at 37°C was undertaken to establish that the ‘coolant’
effect of uterine blood flow would not reduce the micro- wave effects.
To prepare a uterus for this experiment, it was neces- sary to try and leave a bit of uterine artery leading to the specimen – this would then be flushed with heparinized solution as soon as the uterus was removed, to retain the vascular bed. This study confirmed that uterine blood flow had no impact on the microwave effects.
Step 4
After opening the abdomen, prior to hysterectomy, the bowel would be packed clear of the uterus. Thermocou- ples were then secured to the uterine serosa and placed into the myometrium. Microwave energy was then applied using the prototype applicator introduced through the dilated cervix. The uterus was observed directly during this process, in addition to the continuous multiple place- ment thermometry.
It quickly became apparent during this stage that 80 W power was too much: not only because of any serosal heating but also because of loud noises coming from the uterus owing to rapid expansion of pockets of superheated steam and because of very rapid, and diffi- cult-to-control heating of the cavity. A setting of 30 W (lower than anticipated) was found to be very workable.
In fact, at this setting, the actual emitted power at the applicator tip is about 22 W, as a result of power losses in the system.
These studies confirmed that the system behaved entirely as predicted by the microwave theory, and pen- etration was no greater than 6 mm with complete tissue destruction in this narrow zone.
Histologic staining with Nitrazolium tetra-blue gave a good visual representation of the effects of microwave heating. Whereas viable tissue stains blue, as a result of
the activity of the intracellular enzyme succinic dehydro- genase, non-vital tissue does not stain due to thermal degradation of cellular enzymes (Figure 21.3).
MICROWAVE EFFECTS
The rapid heating induced by microwaves has a coagula- tive effect on tissue – there is therefore no bleeding (Figure 21.4). Following treatment, patients have a light watery discharge, which lasts from 1 to 6 weeks. With an effective treatment, there is a hyaline, cicatricil fibrosis of the cavity, with total cavity occlusion (Figure 21.5). The cavity may not occlude entirely but is usually very scarred, much reduced, and lined mainly by fibrous tissue.
MICROWAVE ENDOMETRIAL ABLATION TECHNIQUE
The technique of MEA has been well described elsewhere. 2 , 4–7
A brief description is appropriate, however; MEA is different to all other second-generation ablation systems in that it is iterative, rather than global. All first-genera- tion ablation techniques – transcervical resection of the endometrium (TCRE), rollerball, and laser – treated the endometrium bit by bit, i.e. iteratively. All second-gener- ation systems aim to treat the entire endometrial cavity at once, i.e. global treatment, apart from MEA.
After safely instrumenting the uterine cavity, with hys- teroscopy if necessary, the microwave applicator is inserted until the tip reaches the fundus. It is then activated with a foot switch. The cavity is treated from the fundus down- wards, with lateral side-to-side motions to evenly cover
Section of a uterus from hysterectomy treated with MEA prior to excision.
Staining shows tissue destruction throughout the cavity (light color)
80 mm
Figure 21.3 Tissue distruction from in-vivo trial: white uterus.
the endometrial surface with the microwave energy field.
This process is guided by the continuous thermometry display on the system’s plasma screen. The therapeutic zone is displayed as a band from 70 to 80°C. However, the applicator thermocouple is heat-sunk onto the appli- cator shaft, and covered with a fluoropolymer sheath, and the actual tissue temperature at the applicator–tissue interface is 100°C; this produces micropockets of super- heated steam – the effect of which is cratering in the coagulum seen after MEA (see Figure 21.4).
The system prints a documentary record of the treat- ment profile for inclusion in the patient’s medical record.
The mean treatment time is approximately 3.5 min- utes, but is dependent on cavity length: bigger cavities take longer (Figure 21.6) Significant fibroids tend to lengthen treatment time, as the increased blood flow may have a slight coolant effect. Pretreatment with gonadotro- phin-releasing hormone (GnRH) agonists tends to shorten treatment time by thinning the endometrium and reducing vascularity.
Patient selection
Like all ablation techniques, MEA is a treatment for men- orrhagia. Patients presenting with abnormal uterine bleeding (AUB) must have pathology excluded before simple menorrhagia can be diagnosed. Vaginal ultrasound examination in the outpatient clinic with endometrial biopsy is the preferred assessment protocol. Some practi- tioners may prefer hysteroscopy, but skilled ultrasound examination is less invasive and is more informative in most cases.
Figure 21.4 Coagulative effect or tissue
Figure 21.5 Uterus 6 months after MEA–hysterectomy following ovarian cystadenoma.
>115 mm 111–115 mm 101–105 mm 91–95 mm 81–85 mm
71–75 mm
60–65 mm
0 60 120 180 240 300 360 420 480 540 Seconds
Figure 21.6 MEA: Cavity length vs treatment time
Fibroids
Fibroids are not a contraindication to MEA, provided there is no excessive cavity distortion. If the applicator tip can be placed in contact with the all the endometrium, MEA is feasible. This applies with submucous fibroids, as long as cavity protrusion is less than one-third. Hysteros- copy may be required to evaluate the cavity in such cases.
Very large cavities may be difficult to treat fully within the 8 minutes maximum treatment time, and cavities beyond 11 cm in length are unlikely to get the best response, although treatment of cavities up to 14 cm is feasible with MEA.
Cesarean section
Previous cesarean section is not a contraindication to treat- ment, but the scar integrity must be assessed by ultrasound to ensure safety. The scar is easily visualized on sagittal ultrasound section and is found adjacent to the empty bladder fold (Figure 21.7). Since microwave penetration is limited to 6 mm, a minimum scar thickness of 8 mm has been a safe working minimum. Microsulis protocol now stipulates 10 mm (giving a good margin of safety).
Most patients with a single previous cesarean section will have an adequate scar thickness; the incidence of defective scars increases with the number of cesarean sec- tions, and many women with three cesarean sections will be ineligible, but not all.
Uterine abnormality
Congenital uterine anomalies such as unicornuate, bicor- nuate, subseptate, or didelphys can be safely treated with
MEA. Hysteroscopic control is required to ensure safe instrumentation and proper access. The treatment tech- nique is modified to a simple slow steady withdrawal, and care must be taken not to allow the temperature to rise outside the therapeutic band. MEA is one of the few second-generation techniques applicable to such cases.
Contraindications
• Abnormal endometrial histology.
• Hysterectomy indicated for other reasons.
• Previous uterine surgery.
• Fertility required.
Special precautions
• Uterine retroversion – increased risk of uterine perfo- ration: extra care required.
• Chronic steroid use – increased risk of uterine perforation.
• Connective tissue disorder, e.g. Ehlers–Danlos syn- drome, osteogenesis imperfecta etc. – increased risk of uterine perforation.
RESULTS OF TREATMENT
Initial follow-up of patients after the introduction of MEA into clinical practice was fairly intense, with several visits in the first year, and then annually. It became clear
Figure 21.7 Cesarean scar measurements on vaginal ultrasound assessment.
that there were no major concerns in the follow-up, and patients now receive a simple questionnaire by post 3 months after MEA, the results of which are entered on the database. Those patients unsatisfied with their out- come are offered a review consultation, or may be referred back.
The flow chart (Figure 21.8) shows outcomes at 6 years following introduction of MEA:
• Satisfaction total = 555 (86.6%)
• Hysterectomy total = 86 (13.4%)
Although an initial amenorrhea rate of 57% was reported for an early cohort, the amenorrhea rate has settled to a consistent 41–42% over the longer term.
Apart from incidental causes, the main indication for hysterectomy in this group is regrowth of cornual endo- metrium which has become trapped behind scar tissue in the lower uterine cavity. Such patients typically present about 18 months post-MEA with steadily worsening cyclical pain, despite good menstrual outcome. The pain is unresponsive to analgesics; vaginal ultrasound reveals the cornual pockets with retained menstrual fluid. It is therefore important to warn patients undergoing MEA that avoidance of hysterectomy cannot be guaranteed, although a good outcome may be anticipated.
RANDOMIZED CONTROLLED TRIALS Comparison with endometrial resection
The initial report of Cooper et al 8 compared 123 patients receiving MEA with 132 receiving TCRE. Amenorrhea
results were identical: 40% at 12 months, with satisfac- tion rates of 78% for MEA and 76% for TCRE. Operat- ing times were significantly less for MEA.
Two-year follow-up of this study group 9 showed con- tinuing satisfaction, with 47% amenorrhea for MEA, and 41% for TCRE, with satisfaction rates of 79% and 67%, respectively. Actual acceptability of treatment was greater for MEA (96% vs 88%).
Comparison with rollerball endometrial ablation A comparison with rollerball undertaken for Food and Drug Administration(FDA) approval at eight sites in the UK and USA 10 showed high satisfaction rates with both techniques (MEA 98%, rollerball 99%); amenorrhea rates were 55% for MEA and 46% for rollerball. Treatment times were again significantly shorter for MEA: 3½ min- utes compared with 20½ minutes.
Comparison with Mirena Intrauterine system A recent small randomized controlled trial 11 comparing MEA (43 patients) with the levonorgestrel-releasing intra- uterine device (44 patients) showed a higher satisfaction rate using quality of life questionnaires. Of 38 patients fitted with Mirena for whom 12 months’ follow-up was concluded, six had hysterectomies and seven opted for MEA, compared with three hysterectomies in the micro- wave group.
OUTPATIENT/OFFICE MEA UNDER LOCAL ANESTHETIC
The brevity of the MEA treatment quickly led to the application of a local anesthetic approach. The local anes- thetic technique used is a refinement of that described by Ferry and Rankin. 12
Cervical block
The block required for MEA is an intracervical block – this blocks not only the cervix but also, when correctly established, provides a good uterine blockade. However, the cervix is fairly vascular in a proportion of patients, and intravascular absorption affects the choice of local anesthetic agents that can be used.
Local anesthetic agents to avoid are:
• Those containing epinephrine – patients will fre- quently experience the side effects of intravenous epi- nephrine: palpations, tachycardia, and a very unpleasant feeling of panic, or impending doom.
MEA 660
Follow-up 6 months 641 (97.1%) Lost to follow-up
19 (2.9%)
Satisfied 499 (77.9%)
Dissatisfied 137 (21.3%)
Incidental hysterectomy
5 (0.8%) Repeat MEA
66 (48.2%)
Hysterectomy 71 (51.8%)
Satisfied 56 (84.8%)
Hysterectomy 10 (15.2%)
Figure 21.8 Outcomes at 6 years following introduction of MEA.
• Bupivacaine 0.5% – absorption of which causes mus- cular excitability with twitching and clouding or loss of consciousness, both of which can lead to a ‘grand mal’ seizure.
The anaesthetic agents used are:
• A quick-acting, short-acting agent: for a long time prilocaine 3% with felypressin (Citanest with Octa- pressin; Astra) was used. Now mepivacaine 3% (Scan- donest; Septodont) has been substituted.
• A slow-acting, long-acting agent: either bupivacaine (Marcain; Astra) 0.25%, or levobupivacaine (Chiro- caine; Abbott) 0.25%, administered slowly with
‘draw-back’. Administration is halted if the patient experiences any intravasation symptoms (buzzing in ears, blurring of vision, tingling in lips/face, feeling of floating, etc.).
After positioning the patient, the vagina is cleansed with warmed antiseptic solution and the cervix exposed. Using a dental syringe, a small amount of Citanest or Scandon- est is administered into the anterior cervical lip centrally.
After a few moments, this area may be grasped with vol- sellum forceps and the cervix brought into full view. The cervical block is then initiated with one cartridge of local anesthetic (2.2 ml) administered as deeply as possible into each cervical quadrant – the aim being to establish a ‘ring- block’ at the internal cervical os. This administration can be quick. Next, the slower-acting bupivacaine or levobu- pivacaine 0.25% is administered with a 20 ml syringe and 22 gauge needle, 5 ml per quadrant, starting with the posterior quadrants (the uterosacral ligaments being the most important to block). If the patient develops any symptoms with this phase, further administration is then withheld until completion of the MEA procedure; the main purpose of this second local anesthetic is to enhance postoperative pain relief. This second block is also given to all patients having general anesthetic, to minimize postoperative discomfort.
Drugs
All patients for local anesthesia have diclofenac (Voltarol;
Geigy) 1 hour preoperatively (100 mg suppository, self- administered).
Occasionally, during the MEA treatment, the patient may still experience discomfort despite the local anes- thetic; in such cases Entonox (nitrous oxide/oxygen mix- ture) by inhalation may be sufficient to overcome this, especially if it is only the central fundus that has escaped the blockade, and should therefore be readily available.
For some patients, these measures will be insufficient, and sedation with midazolam (Hypnovel; Roche) and alfentanil (Rapifen; Janssen) intravenously will enable the treatment to be completed. For this reason all patients have an intravenous (IV) cannula sited routinely preprocedure, so that sedation can be readily administered if required.
All patients receiving these agents must have pulse oximetry and supplemental oxygen at 4 L/min. Anexate (Flumazenil; Roche) and naloxone (Narcan; DuPont) must be available as the reversants for midazolam and alfentanil. Atropine should also be available, in case of vagal bradycardia (very uncommon).
In our reported study of outpatient local anesthesia, 13 cavities up to 12 cm were treated. The mean treatment time was about 4 minutes (254 seconds).
Of the 116 patients reported in the study, 94 had local anesthesia alone (81%). Entonox alone was sufficient for a further seven (6.1%), and 15 had IV sedation (12.9%).
All procedures were completed in the Outpatient Depart- ment, and there was no anesthetist in attendance; any sedation was given by the operator, who then regloved to complete the MEA.
Follow-up was completed in 114 patients (two lost to follow-up). Of those, 101 were satisfied, 12 disappointed, and there was one incidental hysterectomy. Of the 12 dissatisfied patients, five had repeat MEA and seven opted for hysterectomy. Following repeat MEA, one patient was satisfied and four were not and had hysterectomy. Overall satisfaction was 89.5%, with a hysterectomy rate of 10.5%
at 4 years.
Before treatment, 74% reported moderate or severe dysmenorrhea. After treatment, this was reduced to 21%, with 61.5% reporting no dysmenorrhea.
Patient selection for outpatient/office treatment Experience has shown that careful patient selection is critical to smooth running of an outpatient treatment ses- sion. Initial selection was unrefined, and difficulties were encountered. The exclusion criteria developed for use in our outpatient clinic are given in Table 21.2.
Practical aspects of outpatient treatment
• Four people are required for an outpatient session:
• surgeon
• assistant – to operate the equipment, connect the cables, generally assist the surgeon
• treatment nurse – to distract the patient with con- versation, administer inhalational agent, or top up IV sedation under surgeon’s instruction