148 INTRODUCTION
Abnormal uterine bleeding (AUB) from benign causes effects 20–25% of premenopausal women. 1 It is one of the most common presenting symptoms for gynecology patients, accounting for 15% of gynecology clinic patients, and is the major indication for 25% of gynecologic oper- ations. 2 Menstrual disorders is listed as the second most common indication for hysterectomy (15–20%) and, together with uterine fibroids, accounts for up to 70% of all hysterectomies. 3–6
First-line treatment for dysfunctional uterine bleeding (DUB) consists of medical management with non-steroidal anti-inflammatory drugs (NSAIDs), 2 , 7–9 antifibrinolytics, 9–11 progestins, 12–14 combined estrogens and progestins, 15 , 16 androgens, 17 or antiprogestational agents. 18 If a patient fails or has a contraindication to medical therapy, surgical therapy is utilized. Up until the 1980s, dilatation and curettage (D&C) had been widely used as a treatment for DUB. However, D&C has since been shown to have diag- nostic value and no therapeutic effect on DUB. Hysterec- tomy was the definitive surgical standard for the treatment of menorrhagia and was associated with a high rate of satisfaction. Hysterectomy can be associated with many potential adverse events, such as death, significant blood loss requiring transfusion, deep venous thrombosis, pul- monary embolism or infarction, myocardial infarction, abscess formation, sepsis, injury to bowel, bladder, or major blood vessels, longer postoperative recovery times, potentially long-term implications, 19–24 and high direct and indirect costs. 25 – 27 Over the last few decades, the trend in gynecology has been towards minimally invasive thera- pies for the treatment of common gynecologic conditions such as menorrhagia. Endometrial ablation has been devel- oped as an alternative to hysterectomy for the manage- ment of menorrhagia. The gold standard for ablation of the endometrium is hysteroscopically directed rollerball ablation or resection. It is safe, effective, and durable but requires significant technical skill. In addition, endome- trial ablation is more cost-effective than hysterectomy as therapy for menorrhagia. 25–27 Global endometrial ablation
or second-generation endometrial ablation technologies (SEATs) were introduced as equally safe and effective as hysteroscopically directed ablation, but are less skill- intensive. 28 –30
HISTORY OF THE THERMABLATE BALLOON
The Thermablate hot liquid balloon system was designed by MDMI Technologies in 1998 (MDMI Technologies Inc, Richmond, BC, Canada). Requirements included portability (light weight, handheld system), user friendli- ness (minimal clinician involvement), and fulfillment of the shortcomings of the existing balloons such as tem- perature gradients, manual balloon control, and duration of the treatment cycle.
MDMI engineers had substantiated uneven tempera- ture distribution using the ThermaChoice balloon. This was done by using both a thermocouple test frame (uter- ine model with 62 thermocouples) and tissue uterine models. The non-circulating liquid of the ThermaChoice device developed significant temperature gradients which affected treatment, particularly if the catheter was resting towards the anterior surface of the uterus or if the uterus was retroverted.
It was also noted that the ThermaChoice and Cava- term balloon technologies required manual inflation and pressure control of the balloon both before and during treatment. As a rule, when the uterus is heated it tends to relax and expand. This results in a significant decrease of intra-balloon pressure during treatment, which can affect clinical outcomes. 33 , 34 However, the fluid pressure in the Thermablate balloon is monitored continuously and adjusted automatically.
The treatment cycle of the existing balloons varied from 8 to 15 minutes. Although this duration of treat- ment is shorter than for the first-generation endometrial ablation technologies (FEATs), clinicians objected because there was not much to do other than hold the device. An important requirement of the Thermablate system was to shorten the duration of treatment.
A heat transfer model of TBEA, taking into account conduction through the uterine wall, cooling due to uter- ine blood perfusion, and metabolic heat generation, pre- dicted a 4 mm burn depth with increased temperature (130°C) and shorter treatment time (1.4 minutes). 35 Reinders et al. also reported on another mathematical model of the Thermablate system. The model predicted that high temperature and pulsed treatment resulted in consistent immediate tissue death (coagulation) of 3.4 + 0.1 mm for uterine cavity volumes of up to 26 ml. Fur- thermore, eventual necrosis (tissue death that would occur 1–5 days postablation) could occur to depths of 6.5 ± 0.2 mm. Similarly, the high-temperature pulsed treatment was less sensitive to blood perfusion rate than the low- temperature treatment. Predicted eventual necrosis depth was 1.5 mm less for the high-temperature pulsed treat- ment than that predicted for a low-temperature treatment
(constant 87°C for 7 min) for the same immediate tissue death depth (3–5 mm), indicating that the new high- temperature treatment may result in less damage to non- targeted tissues. 36
Throughout 1999, progress continued in developing and testing prototypes in various tissue models and, by the beginning of 2000, a final prototype was ready for prehys- terectomy safety trials (Phase 1). Phase 1 safety studies were carried out in seven women undergoing hysterec- tomy at Delta Hospital in Vancouver, Canada, and seven women at the University Hospital in Monterrey, Mexico.
Histopathologic examination of the extirpated uteri con- firmed that the most satisfactory tissue necrosis was obtained with the preheated liquid at 173°C for a treat- ment duration of 128 seconds (2 minutes 8 seconds). 37 , 38 In 2001, a Phase II pilot feasibility/efficacy study was carried out in Bombay, India, in 16 women with menor- rhagia. Following Thermablate treatment, only one woman reported persistent menorrhagia and mild dys- menorrhea. There were no adverse events and the overall satisfaction rate was 94%. 39
From March to July 2003, two pilot feasibility/safety studies were conducted in China. Women (n = 120) with menorrhagia were treated by Thermablate ablation in two centers. Ten patients from each site had hysterectomy immediately after treatment for histochemical evaluation of the thermal effects. Fifty women from each site were followed to determine clinical outcomes. There were no complications or device malfunctions. At 2–3 months of follow-up, menstrual reduction was experienced by 98%
of women at both sites. Based on these studies, the Thermablate was approved for use by the State Drug Administration (SDA) of China in the fall of 2003.
The Thermablate system was approved for use in Canada in May 2003, in the European Union in October 2004, and has since been approved for the treatment of menorrhagia in several other countries. The Food and Drug Administration (FDA) has approved Investigational Device Exemption (IDE) and associated clinical trial/
PMA is pending.
DESCRIPTION OF THE THERMABLATE The Thermablate EAS is a hot liquid balloon system that allows for ablation of the endometrial lining, using ther- mal energy, without the need for direct visualization of the uterine cavity. The device consists of a handheld treat- ment control unit (TCU, weight 700 g); a catheter bal- loon disposable cartridge (weight 110 g), power supply, and TCU stand (Figure 20.1). The TCU is electrically powered, with voltage at an intrinsically safe level to pro- tect the user and the patient from electrical injuries.
The TCU is reusable and controls treatment settings such as time, pressure, and temperature for the heating and pumping/draining subsystems. The treatment is automatically controlled by a microprocessor with no physician input or adjustment required. It also has liquid crystal display (LCD) that provides information and instructions to the user, including warm-up cycle, readi- ness for treatment, leak checks, treatment cycle and com- pletion, and withdrawal of balloon. The TCU preheats 28 ml of glycerine solution to 173°C within 8 minutes.
The unit remains in the treatment-ready mode for 35 min- utes and automatically turns itself off if treatment has not been initiated. The unit can be restarted. The treatment component of the device is the catheter/balloons/car- tridge, which consists of a 6 mm diameter and 12 cm insertional length catheter with a preshaped, single-use, silicone balloon used for treatment on one end and a second reservoir balloon located inside the heating canis- ter at the other end. The catheter is heat shielded to avoid genital tract burns, and has a soft tip to minimize risk of uterine perforation. Once the treatment liquid is heated to 173°C, the balloon is inserted into the uterus to the sounded depth. Treatment is initiated by a finger trigger action on the TCU which is held for 5 seconds. Follow- ing this, a 15-second balloon leak check is automatically performed to confirm balloon integrity. The TCU then pneumatically forces the heated liquid from the reservoir balloon through the catheter into the uterine balloon until a controlled set point of liquid pressure of 180–200 mmHg is reached. The rationale for using these pressures was provided by studies involving the ThermaChoice and Cavaterm balloons.
A geometric uterine model predicted that higher intra- balloon pressures (>166 mmHg) strangulate endometrial capillary vessels by local stress, which in turn decreases
uterine blood circulation allowing deeper penetration of thermal coagulation and necrosis. 40 Clinical data from ThermaChoice balloon ablation also demonstrated that the rate of treatment success was directly related to intrauterine pressure (>160 mmHg) during treatment. 33 ,34 Throughout the Thermablate treatment cycle, fluid pressure in the bal- loon is continuously monitored by two pressure transduc- ers and is automatically controlled via the system pneumatics to remain within a small window of the desired value. In the event that the uterus relaxes, causing the uter- ine volume to increase and fluid pressure to drop, the sys- tem reacts immediately to inject more fluid into the balloon to maintain the fluid pressure at 180 mmHg. In the event of a sudden contraction of the uterus, the system immedi- ately withdraws fluid from the balloon.
As the liquid travels through the catheter, the tempera- ture of the liquid entering the balloon decreases to approxi- mately 150°C and intrauterine treatment temperatures have been measured at 100°C. The TCU maintains a homoge- nized temperature within the balloon during the treatment cycle through a series of pressurization and depressurization 10-second cycles. The amount of heat energy stored within the uterus at any given time is not much greater than that with water-based fluid systems because of glycerine's lower specific heat capacity (2.4 J/g/°C compared to 4.2 J/g/°C for water). A typical Thermablate treatment has 247 J/g available to heat tissue, which is not significantly greater than the 210 J/g for water-based fluid.
The Thermablate EAS achieves a depth of tissue necro- sis into the myometrium of 4–5 mm in the uterine cavity and 2–3 mm at the level of the internal os and cornual region within 128 seconds (2 minutes and 8 seconds). Once the treatment has concluded, the glycerine is automatically withdrawn from the balloon into the canister, and the bal- loon is removed from the uterine cavity. 37
PRETREATMENT ASPECTS Patient assessment
Prior to endometrial ablation, by any technology, women with AUB should be assessed and inclusion and exclusion criteria should be applied in accordance with established clinical practice guidelines, 1 , 41 and manufacturer’s specifi- cations. In addition to the standard history, physical and pelvic examination, Papanicolaou smear, vaginal/cervical swabs and endometrial biopsy, when indicated, the uter- ine cavity should be thoroughly assessed prior to Thermab- late treatment. Imaging by sonography (saline infusion sonography [SIS], transvaginal ultrasound [TVS]) and/or office hysteroscopy is mandatory to assess the shape, size, and condition of the uterine cavity.
Figure 20.1 Thermablate EAS device.
discussed and documented since pregnancies after Ther- mal balloon ablation have been reported to occur at a frequency of approximately 5%. 42 Pregnancies after abla- tion can be dangerous for both mother and fetus due to early pregnancy loss, abnormal placentation, and fetal intrauterine growth restriction. Concomitant laparoscopic or hysteroscopic tubal occlusion should be offered in patients who require contraception. 43 The nature of Thermablate ablation, possible complications, clinical outcomes, and alternative therapies should be outlined.
Specific complications, such as infections, hemorrhage, hematometra, postablation tubal sterilization syndrome (PATSS), cervical and/or uterine perforations, thermal injuries to viscera and/or lower genital tract, should also be disclosed. 41
Patient selection
One of the advantages of Thermablate balloon ablation is that it is a minimally invasive procedure requiring skills similar to those of inserting an intrauterine contraceptive device (IUCD). However, knowledge and training on its application, use, limitations, and safety are mandatory.
The small-diameter catheter/balloon (6 mm) requires minimal cervical dilation and obviates the need for major analgesia/anesthesia and the use of resource-intensive operating rooms. The ideal patients for Thermablate endometrial ablation should be women with menor- rhagia, over 40 years old, normal size and shape of uterine cavity, who have had at least one normal vaginal delivery, and family planning is not an issue.
The pain tolerance of women, their eligibility for out- patient balloon ablation, and their requirements for anal- gesia/anesthesia may be assessed during office visits by pelvic and vaginal speculum examination, particularly by the ease or difficulty of performing endometrial biopsy and/or office hysteroscopy.
Cervical stenosis, due to lack of vaginal deliveries, may be overcome by preoperative misoprostol administration (orally or vaginally) or laminaria inserted in the cervix at least 4 hours prior to treatment. Conscious sedation or general anesthesia would be recommended for women with cervical scarring from previous surgery. 44
Preoperative endometrial preparation
Intuitively, a thin endometrium should allow deeper thermal endomyometrial necrosis and result in better clinical outcomes. However, endometrial thinning prior to Thermablate balloon treatment has not been assessed.
Randomized comparison using the ThermaChoice bal- loon has indicated that pretreatment thinning of the endometrium with gonadotropin-releasing hormone Indications and contraindications
The indications and contraindications for Thermablate endometrial ablation are listed in Tables 20.1 and 20.2, respectively.
Patient counseling, education, and informed consent
Prior to Thermablate ablation, women should be informed that the procedure is irreversible and that the clinical out- come is reduction of menstrual bleeding, not amenor- rhea. However, women should be informed that amenorrhea is a possible outcome. The need for further treatments such as medications, repeat hysteroscopic endometrial ablation, and/or hysterectomy in approximately 20–25%
of women should also be discussed. 41
It must be emphasized that Thermablate ablation should not be performed in women who wish to preserve their fertility, nor should it be used as a means for contra- ception. Additional methods of family planning should be
Table 20.1 Indications for Thermablate Ablation Dysfunctional uterine bleeding (DUB)
Failed traditional therapies (e.g. medical, D&C) Contraindications to traditional therapies
Poor surgical risk for anesthesia, HEA, hysterectomy To preserve the uterus
Table 20.2 Contraindications for Thermablate
• Uterine fundal sounding <7 cm or >12 cm or uterine, cavity
<5 cm
• Genital tract malignancy (cervical, uterine, tubal, ovarian)
• Unresolved endometrial hyperplasia
• Women with anatomic or pathologic uterine anomalies
• Myomas >3 cm distorting the uterine cavity
• Women with history of previous classical cesarean section or transmural myomectomy
• Intrauterine pregnancy
• Acute genital and/or urinary tract infection
• Women wishing to preserve their fertility
• Women expecting amenorrhea as an outcome
• Women with IUCD in place
• Failed previous endometrial ablation
pressure, heart rate) and pulse oximetry are recommended during treatment when patients are given combined medi- cations by any route.
Leyland evaluated the feasibility, safety, and pain tol- erance of Thermablate endometrial ablation in an office setting under local anesthesia. Forty-two women with menorrhagia, who met eligibility criteria, received a preop oral dose of oxycodone/acetaminophen combination and paracervical block immediately before ablation consisting of a 50/50 mixture of Marcaine (bupivacaine) 0.25% and lidocaine 1%. Patient pain tolerance, measured using visual analogue scale (VAS), showed lower pain levels both intra- and postoperatively for Thermablate EAS when compared with 122 women who had been treated with the NovaSure (Cytyc Surgical Products, Palo Alto, CA) system using the same protocol. 47
A study by Laberge and colleagues compared pain asso- ciated with the NovaSure bipoplar radiofrequency system and the ThermaChoice balloon system. Using VAS, the authors reported that the NovaSure system had signifi- cantly lower intra- and postoperative pain than the Ther- maChoice balloon. 48 However, Leyland’s study inferred that pain levels associated with the Thermablate balloon offer a significant improvement over both the NovaSure and the ThermaChoice treatments. 47
PROTOCOL FOR THERMABLATE BALLOON ABLATION
Vilos and associates conducted a pilot study to determine the feasibility, safety, and efficacy in 60 women with men- orrhagia treated under local anesthesia in a clinical setting.
Patient assessment and selection included the presence of menorrhagia for more than three cycles with no intramen- strual bleeding. Since hot liquid balloons tend to decrease rather than eliminate menstrual bleeding, women with menometrorrhagia may express dissatisfaction with treat- ment if they experience spotting between reduced men- struations. The uterine cavity was assessed by SIS. In the absence of contraindications, women were given oral con- traceptives to be taken until the day of treatment. It has been shown that oral contraceptives prior to hysteroscopy maintain a very thin endometrium (mean 4.1 ± 1.6 mm) compared with endometrium observed in the late follicu- lar phase (11 ± 2.0 mm) or luteal phase (12 ± 2.3 mm). 49 All women were prescribed misoprostol 400 µg vaginal suppositories and were instructed to insert into the vagina with a moist tampon the evening before treatment. In addition, they were instructed to take ibuprofen orally (400–600 mg) the evening before and 1 hour prior to treatment. One tablet of Ativan (lorazepam) orally or sub- lingually was also given just before treatment.
agonist GnRH-a vs no treatment 45 and GnRH-a vs suction curettage did not significantly alter the clinical outcomes. 46
ANALGESIA/ANESTHESIA
During a surgical procedure, the goal of the use of analge- sia/anesthesia is to reduce the patient’s anxiety, create amnesia, and control pain. Pain threshold and pain toler- ance may be expressed by interaction of biologic, psycho- logical, and social factors. Pain can be alleviated by a variety of pharmachologic agents and techniques, including anal- gesics, local anesthetics, conscious sedation, general anes- thesia, and possibly acupuncture. Analgesia is defined as the reduction of pain in the conscious patient and can be achieved by a variety of medications, including anxiolytics, opioids, and NSAIDs. Local anesthesia (elimination of sen- sation) from the cervix and uterus can be achieved by a variety of injectable or spray solutions and gels. 44
A suggested cocktail for local anesthesia prior to TBEA is shown in Table 20.3.
Conscious sedation is defined as minimal reduction in the level of consciousness while the patient retains her own airway and responds to physical and verbal stimuli.
Suggested medications for conscious sedation are shown in Table 20.4.
Caution should be exercised when a combination of medications is used. Various drugs, given by different routes, peak at different times, and anxiolytics and narcotics may potentiate each other’s contribution to respiratory and cardiac dysfunction. Cardiopulmonary monitoring (blood Table 20.3 Solution for paracervical block
• 10 ml lidocaine 1% with 1:200 000 epinephrine
• 10 ml bupivacaine 0.2%
• 50 ml (1 ampule) sodium bicarbonate
• 1 ml (1 ampule) atropine (0.5 mg)
• 71 ml total solution; inject 10–20 ml around the cervix
Table 20.4 Medications for conscious sedation
• Fentanyl citrate 1 µg/kg IV
• Atropine 0.5–0.6 mg IV
• Midazolam 4 m IV
• Antiemetic:
• Dimenhydrinate 50 mg IV • Prochlorperazine 10 mg IV or IM
women requiring ‘rescue’ analgesia (n = 4 women) or requesting to terminate treatment (n = 1). Successful 8-minute treatment was achieved in 12 women (86%). A second cohort of 13 women underwent ThermaChoice ablation after taking elective ibuprofen only. Patients were asked to take ibuprofen (600 mg) the evening before treatment, 600 mg 1 hour prior to treatment, and 600 mg 4 hours after treatment. In one woman, the cervix could not be dilated. Eight-minute treatment in the second group was successful in 12 women (92%).
Throughout treatment there was little difference between the two groups with regard to VAS pain scores, with an overall pain score of 3.6. The most uncomfort- able part of the procedure in both groups was the inser- tion of the ThermaChoice, with an average pain score for all women of 4.2. The VAS pain scores for the first cohort gradually increased during the procedure from the initia- tion of therapy to the end of 8 minutes. Nausea was experienced by 42% and 8% (p = 0.059) and vomiting by 25% and 8% (NS) in the first and second group, respec- tively. Overall, ThermaChoice treatment was successful in 24 of 27 (89%) women. Of the 92% of women who replied to a questionnaire, 100% would recommend it to a friend and 77% would have it again. 54
The studies by Marsh and associates, 54 Leyland, 47 and Vilos (unpublished study) indicate that, in properly selected women, balloon endometrial ablation can be safely performed in an outpatient setting without local anesthesia or IV sedation. One could speculate whether the addition of misoprostol (400 µg vaginal suppository) given the evening before treatment would have fascili- tated cervical dilatation and successfully treated the two women in whom the procedure was abandoned due to inability to access the uterine cavity. 54 No other non- hysteroscopic endometrial ablation device has been reported to be feasible under absence of analgesia or oral/
local anesthetic alone.
CLINICAL OUTCOMES
There have been no randomized controlled trials (RCTs) reported to compare clinical outcomes of Thermablate EAS to any other of the first- or second-generation endo- metrial ablation technologies. There have been five cohort studies performed to assess the safety and efficacy of the Thermablate EAS device for the treatment of menorrhagia. 38 , 39 , 47 , 55 , 56
A study in China compared outcomes in 90 women with menorrhagia treated by Thermablate endometrial ablation with 92 women treated by transcervical resection of the endometrium (TCRE) between October 2003 and June 2005. At 6–27 months of follow-up, improvement The treatment protocol included a pelvic examination
to reconfirm the position of the uterus prior to sounding and cervical dilatation. The cervix was infiltrated with 15–20 ml of the solution listed in Table 20.3. After a minimum waiting period of 3–5 minutes, a single-toothed tenaculum was applied, the uterine cavity was sounded, and the cervix was dilated to 7 mm. Hysteroscopy just prior to balloon ablation is desirable but it was not per- formed in this group of women. The balloon/catheter was inserted to the fundus, ensuring that the centimeter mark- ings on the catheter matched the predetermined uterine depth. Currently, we are investigating the introduction of transabdominal sonography for confirmation of correct placement of the balloon prior to initiating treatment.
The use of ultrasound monitoring for other hysteroscopic procedures has been reported. 50
Post-treatment analgesia included the use of mild opi- oids with ibuprofen (400–600 mg) orally every 4 hours.
Adverse events reported within the first 24 hours follow- ing ThermaChoice balloon ablation included nausea and vomiting (25% of women) and cramping abdominal and pelvic pain (92% of women). 51 Therefore, ibuprofen has been chosen as the NSAID of choice for the Thermablate balloon, since it has been shown to be the most effective prostaglandin inhibitor, with a low incidence of side effects, for treating dysmenorrhea. 52
Fifty-nine women were successfully treated in the clinic using the above protocol. In one patient, the cervix could not be accessed due to cervical scarring. There were no adverse events intraoperatively or in the immediate postoperative period. All women were discharged within 2 hours after treatment. Our treatment protocol was similar to those used by other investigators with the ThermaChoice balloon. 53
In 2004, Clark and Gupta reported on 68 women with menorrhagia having treatment with the ThermaChoice balloon under general or local anesthesia. Fifty-three women chose local anesthesia, consisting of indomethacin (100 mg) rectal suppository and intracervical/paracervical block. No intravenous (IV) sedation or narcotic analgesia was given. The treatment was successfully completed under local anesthesia in 50 women (94%); one (2%) woman could not tolerate treatment because of severe dis- comfort, another was not treated due to equipment fail- ure, and in the third woman the balloon/catheter system could not be inserted through the cervix. 53
Marsh et al. reported on ThermaChoice endometrial ablation (n = 27 women) in the outpatient setting, with- out local anesthesia or IV sedation. 54 The first cohort of 14 women underwent ThermaChoice without elective analgesia (i.e. awake, with no premedication, IV sedation, or local anesthetic). Uterine cramping, both during and after ThermaChoice, was most commonly responsible for