H. IVERSEN*, S. LENZ and M. DUEHOLM ABSTRACT

Transcription

1 Ultrasound Obstet Gynecol 2012; 40: Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: /uog Ultrasound-guided radiofrequency ablation of symptomatic uterine fibroids: short-term evaluation of effect of treatment on quality of life and symptom severity H. IVERSEN*, S. LENZ and M. DUEHOLM *Gynecologic Department, Næstved Hospital, University of Copenhagen, Næstved, Denmark; Gynecologic Clinic, Charlottenlund, Denmark; Department of Obstetrics and Gynaecology, Aarhus University Hospital Aaarhus, Denmark KEYWORDS: ablation; fibroid; leiomyoma; radiofrequency; treatment ABSTRACT Objective To evaluate the feasibility of ultrasound-guided radiofrequency ablation (USgRFA) for the treatment of women with symptomatic uterine fibroids in relation to volume of fibroid. Methods Forty-three women with symptomatic fibroids underwent USgRFA for treatment of uterine fibroids. Improvements in fibroid symptoms and quality of life were measured by the Uterine Fibroid Symptom and Quality of Life questionnaire scores at baseline and 3, 6 and 9 months after the intervention, and analyzed in relation to baseline fibroid volume. Volume reduction of fibroids was measured and the frequency of adverse events and re-interventions was recorded. Results Following USgRFA, mean Symptom Severity Scores (SSS) decreased from 60.7 ± 17.8 to31.2 ± 19.5, corresponding to an improvement of 48.6%. The total Health-Related Quality of Life (HRQOL) score improved by 46.4% from 55.6 ± 20.9 to81.4 ± There was no correlation between fibroid volume at baseline and improvement in SSS and HRQOL scores. Fibroid volume was reduced in all patients, by a mean of 69.7 ± 19.4%. Two (4.7%) patients underwent hysterectomy. No adverse events occurred. Conclusion USgRFA reduces fibroid symptom and size even in patients with larger fibroids. USgRFA is a promising new treatment for fibroids in gynecological settings and should be further investigated. Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION Fibroids can be treated by uterine artery embolization (UAE) as an alternative to surgery 1,2. In UAE the vascular supply of the entire uterus, including all fibroids, is impaired, and the resultant ischemia and ischemic fibroid necrosis cause ischemic pain 3. In rare cases, the arterial supply to the ovaries is compromised leading to amenorrhea 4 or loss of ovarian reserve 5.Moreover, there might be an increased risk of miscarriage in future pregnancies 6. This has motivated the development of various imageguided ablative techniques that induce rapid thermal changes in fibroids to achieve necrosis. Treatment alternatives are radiofrequency ablation (RFA), cryotherapy, laser ablation, high-intensity focused ultrasound and magnetic resonance-guided high-intensity focused ultrasound (MRgFUS). MRgFUS is associated with minimal post-procedure pain and successfully improves fibroid symptoms and quality of life 7 9. Limited data on pregnancy outcome after MRgFUS seem encouraging 10. MRgFUS ablation requires 3 4 h in a magnetic resonance imaging (MRI) scanner. It is costly and clinical availability will probably be limited. RFA is an uncomplicated minimally invasive ultrasound-guided needle technique. It uses radiofrequency energy, and the heat generated causes localized coagulation necrosis of fibroid tissue. Similar to MRg- FUS, RFA produces necrosis in a restricted area 11. It has been performed in small series in combination with laparoscopy, with a substantial reduction in the size of fibroids and in related symptoms However, without the support of laparoscopy, the RFA procedure has been performed with only ultrasound guidance in pilot studies To our knowledge, only two ultrasoundguided radiofrequency ablation (USgRFA) studies have published follow-up data; both studies included more than 30 patients 19,20, but only one study involved larger fibroids 20. Correspondence to: Dr H. Iversen, Gynecologic Department, Næstved Hospital, University of Copenhagen, Ringstedgade 61, 4700 Næstved, Denmark ( helene.iversen@dadlnet.dk) Accepted: 18 January 2012 Copyright 2012 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 446 Iversen et al. We performed USgRFA on uterine fibroids in an outpatient setting without the support of advanced medical imaging facilities. The aim of this study was to evaluate the safety, feasibility and outcome at 9 months of outpatient USgRFA treatment of uterine fibroids in relation to baseline volume of treated fibroids, including treatment of larger fibroids. METHODS The study included 46 women aged over 24 years referred with symptomatic fibroids to the outpatient clinic at Herlev Hospital, Denmark, from 1 November 2007 to 1 August All patients underwent standard gynecologic and ultrasound examination (transvaginal and transabdominal). Saline contrast sonohysterography was performed to evaluate the presence of type 0 and 1 submucous fibroids and polyps. Endometrial samples were collected in all patients who were over 45 years of age with abnormal bleeding and no sampling within the last year. Exclusion criteria were: (1) malignant disease; (2) severe chronic disease or diabetes; (3) pregnancy; (4) endometrial pathology; (5) coagulopathy; (6) suspected intra-abdominal adhesions; (7) severe endometriosis or intra-abdominal infection; (8) metal devices implanted in the body including intrauterine devices (metal clips used for sterilization were accepted); (9) inability to speak and understand Danish; (10) receiving gonadotropin-releasing hormone therapy within 1 year; (11) freely movable subserosal fibromas with more than 50% of fibroid tissue on the serosal surface, and fibromas with more than 50% of their volume within the uterine cavity (type 0 and 1), because of their mobility and associated difficulty with needle insertion 21 ; and (12) fibroids not visible on transabdominal ultrasound. Inclusion criteria were a maximum of 500 cm 3 ablation possible in a maximum of three fibroids to be ablated (i.e. maximum size of ablation in a single fibroid, c. 10 cm diameter). The minimum size of fibroids to be ablated was 3 cm. Patients planning a future pregnancy were not treated, unless the benefits of alternative treatments were excluded by advice from a fertility specialist. The benefits and possible risks were extensively discussed with each patient before informed written consent was obtained. The project was approved by The Capital Region Danish National Committee on Biomedical Research Ethics. Primary outcome measures were frequency of adverse events, re-intervention rate for fibroid symptoms, scores from the validated Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL) 22 and changes in fibroid volume. All patients were carefully monitored during and after the procedure. In the first 4 postoperative days, patients registered temperature rectally and reported a daily total pain score using a visual analog scale (VAS) score from All readmissions and unplanned healthcare contacts that led to any treatment or intervention were recorded as complications. The UFS-QOL questionnaire was completed at baseline and at 3, 6 and 9 months after the intervention 22. Answers were transformed to fibroid-related Symptom Severity Score (SSS) and six subscores of health-related quality of life (HRQOL) and HRQOL total. The UFS-QOL questionnaire is designed to assess symptom severity of uterine myomas and health-related quality of life. The level of distress was rated on a 1 5 scale ( Not at All, Slightly, Somewhat, A Great Deal and A Very Great Deal ) regarding 37 questions on symptoms of bleeding, menstrual periods, pelvic tightness or pressure, urination symptoms and quality of life related to the fibroids. The scores for each group of questions were added to create a summary score and the summary score was transformed to a 100-point scale for both the SSS score and the HRQOL score. The SSS score for severity was lower if symptoms were few, and HRQOL score was high if quality of life was satisfactory. Assessment of menorrhagia and bulkrelated symptoms was based on answers to the UFS-QOL questionnaire. Menorrhagia was defined as the presence of more than 3 months duration of menstrual periods with a great deal of or very great deal of heavy bleeding, passing blood clots, or fluctuation in duration compared to previous cycles (a score of > 3 in questions 1 3). A 10-point improvement in SSS was consistent with a moderate effect size 22. A positive treatment effect was taken as a more than 10-point improvement in symptom severity or HRQOL total score 8. The type of fibroid was classified according to the International Federation of Gynecology and Obstetrics (FIGO) classification 23. Gray-scale tone of the fibroids at baseline was evaluated on a 10-point scale and compared to adjacent myometrium (fibroids with a two-point darker gray-scale tone than myometrium were termed + 2, while fibroids with echo-tone one point lighter than myometrium were termed 1). Images of all fibroids in all patients were stored with data on size and location in order to track the fibroids. The total fibroid volume as measured at ultrasound was recorded at the preoperative evaluation and again at clinical follow-up visits at 3, 6 and 9 months. The volume of the fibroids was calculated from three perpendicular diameters (A, B, C) using the formula for a prolate ellipsoid: A B C Percent volume reduction was calculated as difference in fibroid volume in relation to volume at baseline. A few patients did not attend the clinical follow-up; these patients were contacted by phone. Possible adverse events, complications or other gynecological treatments were registered for all patients. USgRFA treatment, pre- and postoperative clinical examination and ultrasonography were performed by a gynecologist (H.I.) with some training in ultrasoundguided puncture. ALOGIQ 9 ultrasound machine (GE Medical Systems, Zipf, Austria) was used to examine the fibroids and to guide the RFA procedure. A radiofrequency delivery system (RITA Model 1500, AngioDynamics, Latham, NY, USA), consisting of a radiofrequency generator

3 Radiofrequency ablation of uterine fibroids 447 (a) Figure 1 (a) Photograph of the StarBurst Talon needle showing tapered cutting tip with central electrode and four prongs deployed laterally. (b) Ultrasound image showing the needle in a fibroid during ablation. connected to a 15-cm long RF StarBurst Talon 14-gauge needle, was used (Figure 1). The radiofrequency generator produces a voltage between the active electrode and two large dispersive electrodes. The generator operates at 460 khz with a maximum power of 150 watts, and a target temperature of 105 C. The target temperature is setat105 C to achieve a cool-down temperature in 30 s after active ablation to beyond 70 C. Each USgRFA procedure was performed under general anesthesia. The skin was prepared as for abdominal surgery and no antibiotics were administered. A 150-mm insufflation needle (Aesculap Ag, Tuttlingen, Germany) was inserted into the umbilicus and approximately 500 ml of Ringer s lactate was instilled intra-abdominally to enable better visualization of the fibroids and to prevent transmission of heat from the surface of the fibroid. The radiofrequency needle insertion was ultrasound guided. In three patients the needle was inserted by the vaginal route, with a needle guide affixed to the vaginal probe. The vaginal route was chosen in cases where the fibroids were closer to the vaginal probe than to the abdominal probe. When vaginal RFA was performed, patients received intravenous prophylactic antibiotics with 1.5 g cefuroxime. In 40 patients the needle was inserted by the abdominal route with a freehand technique until the tip had entered the fibroid. The StarBurst Talon RF ablation needle (Figure 1a) is designed for ablation of solid tissue, with an exposed tapered cutting tip with central electrode and continuous flow of saline through four prongs, which can be deployed laterally to enable ablation from 2 to 4 cm in diameter. The flow of saline reduces the electrical resistance in the tissue, and prevents the prongs from attaching to the dry burnt fibroid following ablation. The temperature in the four prongs is monitored and controlled during ablation, and this can be used to assess the position of the needle as well as the degree of ablation 30 s after active heating. When the cool-down temperature is above 70 C, sufficient ablation has been achieved, as all vital tissue will become necrotic at temperatures higher than 55 C. Monitoring the temperature in the prongs during active heating can also be used as a safety device, as it will be difficult to reach the target temperature in a prong placed in the saline on the serosal surface of the fibroid. In this study, the freehand technique was considered important because it allowed work in two ultrasound planes, to confirm the placement of the tip of the needle before starting spherical ablation and to compensate for occasional movements of the fibroids during puncture. The needle tip is easily seen owing to the obliquely cut sharp edge. Ablation was performed in one to 11 cycles of 2 4 cm in diameter depending on the size of the fibroid, allowing a boundary of 1 cm to either the serosal surface or the endometrium. Ablation was verified through observation of the position of the needle, and concurrent monitoring of the temperature in the prongs of the needle. The site of ablation can be seen as small hyperechogenic foci on ultrasound, probably due to small bubbles of gas from the ablated tissue (Figure 1b). The duration of the procedure depended on the size of the ablation and the time required for insertion of the needle into the fibroid. The procedure time for a 2-cm ablation (4.2 cm 3 ) was 2 min, 3-cm (14.1 cm 3 ) ablation took 5 min and 4-cm (33.5 cm 3 ) ablation lasted 9 min. Additional time was required for antiseptic preparation and instillation of Ringer s lactate. Statistical analysis The transformed scores from the UFS-QOL questionnaire and the volume of the fibroids were normally distributed. Correlation between variables was tested using the Pearson correlation coefficient test. The patients were classified into groups according to initial fibroid volume. Analysis of the effect of fibroid volume group and time from procedure on outcome variables was carried out by three-way ANOVA using a general linear model classified by time (month = 0, 3, 6, 9) and group (defined by volume: A, < 80 cm 3 (< 5.3 cm diameter); B, cm 3 ( cm diameter); C, cm 3 ( cm diameter); D, 280 cm 3 ( 8.1 cm diameter)), with patients nested within groups. P for paired t-tests on differences within groups and one-way ANOVA between groups was calculated. All

4 448 Iversen et al. test results were also confirmed using Friedman s nonparametric analysis. Cuzick s Wilcoxon-type test for trends was used to compare percent volume reduction in fibroids in relation to symptoms, fibroid type and grayscale tone. All data were analyzed using Stata software (Stata/MP 11; StataCorp, College Station, TX, USA), and P < 0.05 was considered statistically significant. RESULTS Forty-six patients were included in the study (Figure 2). Forty-four were premenopausal and two women with fibroids and bulk-related symptoms on hormone replacement therapy were postmenopausal (more than 1 year without bleeding). In three patients treatment could not be completed, as the needle could not be safely placed owing to mobile fibroids or obesity. One patient had experienced chronic pelvic pain for several years. She had no complications, but regretted the treatment and had a hysterectomy within 1 month after USgRFA. These four patients were excluded from further analysis. Thus, 42 patients were left for analysis. Patient characteristics are shown in Table 1. Patients included (n = 46) Treatment failure (n = 3) Patients treated (n = 43) Hysterectomy for other reason (n = 1) Table 1 Baseline characteristics of patients treated by ultrasound-guided radiofrequency ablation for fibroids (n = 42) Characteristic Mean ± SD (range) or n (%) Age (years) 44.6 ± 7.5 (24 55) Premenopausal 40 (95.2) Postmenopausal (hormone replacement) 2 (4.8) Menorrhagia 34 (81.0) Menorrhagia score 56.0 ± 22.0 (0 80) Bulk-related symptoms 32 (76.2) Frequent urination 27 (64.3) Pelvic pain 20 (47.6) Baseline HRQOL score 55.6 ± 20.9 Symptom Severity score 60.7 ± 17.8 Fibroids Load (sum of fibroid volumes) (cm 3 ) ± (28 675) Number of fibroids 1 32 (76.2) 2 4 (9.5) 3 4 (9.5) 4 2 (4.8) Numbers of fibroids treated (total = 51, mean = 1.21) 1 36 (85.7) 2 3 (7.1) 3 3 (7.1) Fibroid type (FIGO classification) Type 2 3 (7.1) Type 3 14 (33.3) Type 4 19 (45.2) Type 5 6 (14.3) Echodensity* 3, 4 7 (16.7) 1, 2 10 (23.8) + 1, (47.6) (11.9) Location of largest fibroid Anterior 28 (66.7) Posterior 12 (28.6) Other 2 (4.8) *Compared with myometrium, using a 10-point scale, indicating a lighter tone and + indicating a darker tone. FIGO, International Federation of Gynecology and Obstetrics; HRQOL (score), Health-Related Quality of Life (score). Patients remaining at 3 months (n = 42) Hysterectomy for other reason (n = 1) Cured by vaginal expulsion (n = 1) Patients remaining at 6 months (n = 40) Patients remaining at 9 months (n = 40) (36 followed-up clinically, 4 by phone) Figure 2 Flow chart of study population. Two patients were only followed up for 3 months. One of the two postmenopausal women on hormone replacement therapy had a hysterectomy after 3 months despite an improved SSS from 93.8 to One patient delivered her single fibroid vaginally and uneventfully at home within 2 months and did not attend for follow-up at 6 months. No other patients requested further treatment for fibroids related to gynecological problems in the study period. At enrollment, 24 patients (57.1%) had both menorrhagia and bulk-related symptoms (Group 1), eight (19.0%) had only bulk-related symptoms (Group 2) and 10 (23.8%) had only menorrhagia (Group 3). A total of 23 patients (54.8%) had menorrhagia at 3 months, 19 (45.2%) at 6 months and 10 (23.8%) at 9 months. Bulk-related symptoms were still present in 12 (28.6%) at 3 months, and in 15 (35.7%) at 6 and 9 months. The mean improvement in SSS score at 9 months was 36.1 ± 17.1

5 Radiofrequency ablation of uterine fibroids 449 Table 2 Symptom severity scores and Health-Related Quality of Life (HRQOL) scores in relation to initial fibroid volume (Groups A, B, C and D) for patients undergoing radiofrequency ablation treatment at baseline and at 3, 6 and 9 months after treatment Baseline Month 3 Change in score 0 3 months Month 6 Month 9 Change in score 0 9 months (n = 42) (n = 42) (n = 40) (n = 40) Parameter (mean ± SD) (mean ± SD) Mean ± SD P (mean ± SD) (mean ± SD) Mean ± SD P Symptom Severity Score All patients 60.7 ± ± ± 20.8 < ± ± ± 17.6 < Group A (n = 7) 65.2 ± ± ± * 40.2 ± ± ± * Group B (n = 16) 57.6 ± ± ± ± ± ± 15.6 Group C (n = 9) 53.5 ± ± ± ± ± ± 15.7 Group D (n = 10) 69.1 ± ± ± ± ± ± 19.7 HRQOL subscores (all patients) Concern 48.5 ± ± ± 24.7 < ± ± ± 28.7 < Activities 59.9 ± ± ± 22.7 < ± ± ± 22.4 < Energy/mood 59.0 ± ± ± 20.6 < ± ± ± 23.5 < Control 60.2 ± ± ± 23.3 < ± ± ± 24.6 < Self-consciousness 48.4 ± ± ± 22.3 < ± ± ± 24.7 < Sexual function 46.4 ± ± ± 23.4 < ± ± ± 24.5 < HRQOL total score All patients 55.6 ± ± ± 19.6 < ± ± ± 21.0 < Group A (n = 7) 56.4 ± ± ± * 70.9 ± ± ± * Group B (n = 16) 57.0 ± ± ± ± ± ± 22.4 Group C (n = 9) 66.0 ± ± ± ± ± ± 13.5 Group D (n = 10) 43.7 ± ± ± ± ± ± 19.0 Fibroid volume (all ± ± ± 79.8 < ± ± ± 98.6 < patients) Change in fibroid volume (%) 55.2 ± ± 19.4 P for t-test. *One-way ANOVA comparison of means (Groups A, B, C and D). Group A, fibroid volume < 80 cm 3 ; Group B, fibroid volume cm 3 ; Group C, fibroid volume cm 3 ; Group D, fibroid volume 280 cm 3. in Group 1, 18.8 ± 15.3 ingroup2and22.7 ± 14.2 in Group3(P = 0.02). Eight patients (19.0%) had a less than 10-point improvement in SSS, but only four (9.5%) had a less than 10-point improvement in total HRQOL score. Thus, 90.5% of the patients experienced a positive treatment effect. Table 2 displays the mean HRQOL total and subscores, SSS and reduction in fibroid volume from baseline to 3, 6 and 9 months follow-up. The mean decrease in SSS represented a 51.7% improvement from baseline. The main improvement was seen during the first 3 months, with a slight, though not significant, improvement from 3 to 9 months. All HRQOL mean subscores improved and the total HRQOL score improved by 46.4% compared to baseline values. The scores were significantly improved at 3 months follow-up and this persisted and slightly, though not significantly, increased at 6 and 9 months follow-up. The volume of the fibroids was also reduced in all patients. Only one patient had a less than 30% reduction in fibroid volume, and only four patients had a volume reduction below 40%. There was no correlation between SSS and HRQOL scores and volume of the fibroids at baseline, nor was there any correlation between improvement in SSS score and reduction in fibroid volume. Mean reductions in scores at 3 months were: 29.5 ± 24.1 in seven patients with 0 40% reduction in fibroid volume, 20.0 ± 22.9 in 10 patients with 41 55% reduction, 22.6 ± 20.1 in 13 patients with 56 65% reduction, and 29.9 ± 18.9 in 12 with > 65% reduction in fibroid volume. Mean reduction in bulk-related SSS was 33.1 ± 21.1, and there was no correlation between decrease in fibroid volume and improvement in bulk-related symptoms. The mean values of improvement in scores were compared in four groups of patients according to initial fibroid volume (Table 2). From analysis of the interaction between group and time there was no difference between the groups in the development of mean values of scores over time in severity and HRQOL total scores. Thus, the effects of treatment did not depend on the size of the fibroid. Moreover, there was no difference in the mean reduction in fibroid volume (% of baseline fibroid volume) between the groups. We could not demonstrate any trend or relation between percent volume reduction of fibroid and type of fibroid (FIGO types 2 5). The gray-scale tone of the dominant fibroid at baseline was lighter than that of the myometrium in 17, with a reduction in fibroid volume at 3 months follow-up of a mean of 49.4 ± 17.6 cm 3, while 25 dominant fibroids with darker color than that of the myometrium had a volume reduction of a mean of 59.1 ± 19.7 cm 3 (P = 0.06). The color score of dominant fibroids changed from baseline to 9 months, and became lighter with a mean score of 1.8 ± 2.5 (range, 2to7), but change in tone score did not relate to percent volume reduction of fibroids.

6 450 Iversen et al. No peri- or postoperative complications occurred, and no patients were readmitted because of fibroid-related problems within the first 3 months. All patients were well enough to have been discharged on the same day, but the first 12 patients were observed until the next day. No fevers or adverse events occurred. VAS pain scores at postoperative days 1 4 showed low pain with a median score of six from a total VAS score of 40 (4 10) (95% CI, 2 9.9; range, 2 14). DISCUSSION In this study, ablation of uterine fibroids was found to be safe, feasible and without complications in almost all patients. The technique is suitable for day-surgery settings because of the low level of reported pain and the absence of adverse events. Both mean SSS and mean HRQOL total scores were significantly improved. The safety and treatment effects were in agreement with those of other studies on USgRFA Even patients with very large fibroids (> 8 cm in diameter) showed a reduction in fibroid volume and SSS to the same extent as patients with smaller fibroids. This was in line with the results of a recent USgRFA study 20 but in contrast to those of another study 19. However, in a third study incomplete ablation was more frequent in larger fibroids 24, indicating that shortcomings of the technique in large fibroids could be due to incomplete ablation. This is supported by findings after UAE 25 and MRgFUS 9, where the treatment effect seemed to depend on cessation of fibroid perfusion and complete infarction visualized by contrast-enhanced MRI. Complete ablation by RFA probably depends mainly on the technique of the person performing the treatment. All previous studies on USgRFA have indicated that there is a learning curve in carrying out the technique, and in large fibroids complete ablation requires systematic handling of the needle with overlapping of targeted regions in order to include all fibroid tissue. In this study the technique was feasible in the hands of a single gynecologist with some experience in ultrasound-guided puncture. One in 10 patients in this study did not experience a positive treatment effect. Previous reports have revealed that insufficient effect of MRgFUS may be present even in completely ablated fibroids 9 and that this is also related to fibroid cellularity and pretreatment perfusion of fibroids 26. The 6-month SSS and HRQOL total outcome scores in this study corresponded to outcomes reported after UAE and MRgFUS 8,27,28. Reductions in fibroid volume after USgRFA were comparable with findings after UAE 29,30, but fibroids seem to be reduced to a greater extent after USgRFA than after MRgFUS 26,31. However, this might be improved in upcoming MRgFUS outcome data for patients in whom the ablation of larger fibroid volumes has been performed 32. MRgFUS has been established as a safe noninvasive method for the ablation of uterine fibroids. The advances in knowledge and expertise in this technologically advanced technique may lead to more accessible ultrasound-guided methods of ablation. We wanted to develop a straightforward treatment protocol in a gynecological day-surgery setting in addition to common endoscopic fibroid treatment options. The main concern is whether USgRFA is sufficiently safe with the modest precautions described in this study protocol. An important precaution may be our use of the intraperitoneal instillation of saline as this may, like other distending media, reduce the risk of accidental injury to other organs 33,34. Ultrasonography is the only imaging technique available in a day-care setting, and further studies, including other imaging techniques, are needed to clarify the safety and efficiency of this approach. Preoperative mapping of all fibroids using MRI may be more beneficial than the use of ultrasound in patients with multiple fibroids 35. Contrastenhanced MRI is the standard technique for the evaluation of treatment effect after RFA 36, and could be implemented in the study protocol. A persistent effect of treatment after UAE and MRgFUS seems to depend on cessation of fibroid perfusion and complete infarction as visualized on contrast-enhanced MRI 9,25.Analternative imaging technique is contrast-enhanced ultrasonography; in future studies this may prove to be comparable with contrast-enhanced MRI for the diagnosis of incomplete ablation 24. Randomized studies with large numbers of patients and long-term follow-up are needed before the widespread implementation of USgRFA in clinical practice. In conclusion, USgRFA is an uncomplicated treatment causing only mild pain when performed by a gynecologist with modest training in ultrasound-guided puncture. In this study, USgRFA showed a promising effect on fibroid symptoms and quality of life scores, even in large fibroids. The method has the potential to become a widely established gynecological procedure in day surgery, but more studies are needed before this technique can be incorporated into clinical practice. REFERENCES 1. Gupta JK, Sinha AS, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev 2006; CD Mara M, Maskova J, Fucikova Z, Kuzel D, Belsan T, Sosna O. Midterm clinical and first reproductive results of a randomized controlled trial comparing uterine fibroid embolization and myomectomy. Cardiovasc Intervent Radiol 2008; 31: Hehenkamp WJ, Volkers NA, Donderwinkel PF, De Blok S, Birnie E, Ankum WM, Reekers JA. Uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids (EMMY trial): peri- and postprocedural results from a randomized controlled trial. Am J Obstet Gynecol 2005; 193: Walker WJ, Barton-Smith P. Long-term follow up of uterine artery embolisation an effective alternative in the treatment of fibroids. BJOG 2006; 113: Hehenkamp WJ, Volkers NA, Broekmans FJ, de Jong FH, Themmen AP, Birnie E, Reekers JA, Ankum WM. Loss of ovarian reserve after uterine artery embolization: a randomized comparison with hysterectomy. Hum Reprod 2007; 22:

7 Radiofrequency ablation of uterine fibroids Homer H, Saridogan E. Uterine artery embolization for fibroids is associated with an increased risk of miscarriage. Fertil Steril 2010; 94: Stewart EA, Gedroyc WM, Tempany CM, Quade BJ, Inbar Y, Ehrenstein T, Shushan A, Hindley JT, Goldin RD, David M, Sklair M, Rabinovici J. Focused ultrasound treatment of uterine fibroid tumors: safety and feasibility of a noninvasive thermoablative technique. Am J Obstet Gynecol 2003; 189: Stewart EA, Rabinovici J, Tempany CM, Inbar Y, Regan L, Gostout B, Hesley G, Kim HS, Hengst S, Gedroyc WM. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril 2006; 85: Stewart EA, Gostout B, Rabinovici J, Kim HS, Regan L, Tempany CM. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol 2007; 110: Rabinovici J, David M, Fukunishi H, Morita Y, Gostout BS, Stewart EA. Pregnancy outcome after magnetic resonanceguided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. Fertil Steril 2010; 93: Lencioni R, Crocetti L, Pina MC, Cioni D. Percutaneous imageguided radiofrequency ablation of liver tumors. Abdom Imaging 2009; 34: Garza Leal JG, Hernandez Leon I, Castillo Saenz L, Lee BB. Laparoscopic ultrasound-guided radiofrequency volumetric thermal ablation of symptomatic uterine leiomyomas: feasibility study using the Halt 2000 Ablation System. J Minim Invasive Gynecol 2011; 18: Ghezzi F, Cromi A, Bergamini V, Scarperi S, Bolis P, Franchi M. Midterm outcome of radiofrequency thermal ablation for symptomatic uterine myomas. Surg Endosc 2007; 21: Milic A, Asch MR, Hawrylyshyn PA, Allen LM, Colgan TJ, Kachura JR, Hayeems EB. Laparoscopic ultrasound-guided radiofrequency ablation of uterine fibroids. Cardiovasc Intervent Radiol 2006; 29: Bergamini V, Ghezzi F, Cromi A, Bellini G, Zanconato G, Scarperi S, Franchi M. Laparoscopic radiofrequency thermal ablation: a new approach to symptomatic uterine myomas. Am J Obstet Gynecol 2005; 192: Recaldini C, Carrafiello G, Lagana D, Cuffari S, Bergamini V, Ghezzi F, Fugazzola C. Percutaneous sonographically guided radiofrequency ablation of medium-sized fibroids: feasibility study. AJR Am J Roentgenol 2007; 189: Carrafiello G, Recaldini C, Fontana F, Ghezzi F, Cuffari S, Lagana D, Fugazzola C. Ultrasound-guided radiofrequency thermal ablation of uterine fibroids: medium-term follow-up. Cardiovasc Intervent Radiol 2010; 33: Kim HS, Tsai J, Jacobs MA, Kamel IR. Percutaneous imageguided radiofrequency thermal ablation for large symptomatic uterine leiomyomata after uterine artery embolization: a feasibility and safety study. J Vasc Interv Radiol 2007; 18: Cho HH, Kim JH, Kim MR. Transvaginal radiofrequency thermal ablation: a day-care approach to symptomatic uterine myomas. Aust N Z J Obstet Gynaecol 2008; 48: Kim CH, Kim SR, Lee HA, Kim SH, Chae HD, Kang BM. Transvaginal ultrasound-guided radiofrequency myolysis for uterine myomas. Hum Reprod 2011; 26: Stewart EA. Uterine fibroids. Lancet 2001; 357: Spies JB, Coyne K, Guaou GN, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and health-related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002; 99: Munro MG, Critchley HO, Fraser IS; FIGO Menstrual Disorders Working Group. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril 2011; 95: , 2208.e Meng X, He G, Zhang J, Han Z, Yu M, Zhang M, Tang Y, Fang L, Zhou X. A comparative study of fibroid ablation rates using radio frequency or high-intensity focused ultrasound. Cardiovasc Intervent Radiol 2010; 33: Kroencke TJ, Scheurig C, Poellinger A, Gronewold M, Hamm B. Uterine artery embolization for leiomyomas: percentage of infarction predicts clinical outcome. Radiology 2010; 255: Lenard ZM, McDannold NJ, Fennessy FM, Stewart EA, Jolesz FA, Hynynen K, Tempany CM. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery imaging predictors of success. Radiology 2008; 249: Spies JB, Myers ER, Worthington-Kirsch R, Mulgund J, Goodwin S, Mauro M; FIBROID Registry Investigators. The FIBROID Registry: symptom and quality-of-life status 1 year after therapy. Obstet Gynecol 2005; 106: Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany C, Hynyen K, McDannold N, Inbar Y, Itzchak Y, Rabinovici J, Kim HS, Geschwind JF, Hesley G, Gostout B, Ehrenstein T. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol 2004; 183: Pron G, Bennett J, Common A, Wall J, Asch M, Sniderman K. The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids. Fertil Steril 2003; 79: Spies JB, Ascher SA, Roth AR, Kim J, Levy EB, Gomez-Jorge J. Uterine artery embolization for leiomyomata. Obstet Gynecol 2001; 98: Funaki K, Fukunishi H, Sawada K. Clinical outcomes of magnetic resonance-guided focused ultrasound surgery for uterine myomas: 24-month follow-up. Ultrasound Obstet Gynecol 2009; 34: Fennessy FM, Tempany CM, McDannold NJ, So MJ, Hesley G, Gostout B, Kim HS, Holland GA, Sarti DA, Hynynen K, Jolesz FA, Stewart EA. Uterine leiomyomas: MR imagingguided focused ultrasound surgery results of different treatment protocols. Radiology 2007; 243: Raman SS, Aziz D, Chang X, Sayre J, Lassman C, Lu D. Minimizing diaphragmatic injury during radiofrequency ablation: efficacy of intraabdominal carbon dioxide insufflation. AJR Am J Roentgenol 2004; 183: Arellano RS, Garcia RG, Gervais DA, Mueller PR. Percutaneous CT-guided radiofrequency ablation of renal cell carcinoma: efficacy of organ displacement by injection of 5% dextrose in water into the retroperitoneum. AJR Am J Roentgenol 2009; 193: Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Olesen F. Accuracy of magnetic resonance imaging and transvaginal ultrasonography in the diagnosis, mapping, and measurement of uterine myomas. Am J Obstet Gynecol 2002; 186: Lencioni R, Cioni D, Della Pina C, Crocetti L. Hepatocellular carcinoma: new options for image-guided ablation. JHepatobiliary Pancreat Sci 2010; 17: