Image-guided therapies for uterine fibroids

Image-guided therapies for uterine fibroids Jordann-Mishael Lewis and Esraa Algurjia are co-first authors. Abstract Uterine fibroids (leiomyomas) and adenomyosis are among the most common benign gynecological conditions affecting women of reproductive age. These disorders are frequently associated with abnormal uterine bleeding, pelvic pain, pressure symptoms on adjacent pelvic organs, and potential infertility. The incidence of fibroids increases as women enter their third and fourth decades of life. In parallel, recent trends in delayed childbearing have further emphasized the need for fertility-preserving treatment options. Notably, fibroids have a higher prevalence in African-American women, highlighting a significant disparity in health needs compared to white women. Historically, hysterectomy and myomectomy were considered definitive treatments. However, these procedures carry inherent surgical risks, longer recovery periods, and, in the case of hysterectomy, a complete loss of reproductive potential. Consequently, there is increasing demand for uterus-sparing, minimally invasive alternatives that provide effective symptom control with lower morbidity and preservation of fertility. Among the evolving treatment options, three image-guided, minimally invasive therapies have gained particular attention: Uterine Artery Embolization (UAE), Radiofrequency Ablation (RFA), and High-Intensity Focused Ultrasound (HIFU). Uterine Artery Embolization (UAE), also known as uterine fibroid embolization (UFE), is a well-established endovascular procedure in which embolic agents are introduced via catheterization of the uterine arteries, inducing ischemia and infarction of fibroids. Performed under conscious sedation or regional anesthesia, UAE has demonstrated significant reductions in fibroid volume and symptom relief in over 80% of appropriately selected patients. All image-guided techniques are especially beneficial for women who desire uterine preservation, have contraindications to surgery, or wish to avoid major operative interventions. In comparison with UAE, Radiofrequency Ablation (RFA) uses targeted thermal energy to induce coagulative necrosis within fibroid tissue. This approach can be delivered via laparoscopic, transcervical, or transvaginal routes, depending on the platform. The Sonata® System integrates intrauterine ultrasound guidance with energy delivery, enabling precise fibroid targeting with minimal myometrial damage. RFA is associated with shorter recovery and less intraoperative blood loss, though it is more suitable for smaller or fewer fibroids and may be less ideal for extensive disease. Together, these advancements reflect a paradigm shift in fibroid management—driven by demographic trends, racial disparities, patient preferences, and technological innovations—toward evidence-based, uterus-preserving therapies tailored to individual patient needs. This article discusses details of each technique including the procedure, benefits and complications and also the impact on particular situations such as pregnancy. Some key points common to each technique are also mentioned. 1 INTRODUCTION Uterine fibroids (leiomyomas) and adenomyosis are among the most common benign gynecological conditions affecting women of reproductive age.1 These disorders are frequently associated with abnormal uterine bleeding, pelvic pain, pressure symptoms on adjacent pelvic organs, and potential infertility.2 The incidence of fibroids increases as women enter their third and fourth decades of life. In parallel, recent trends in delayed childbearing have emphasized the need for fertility-preserving treatment options.3 Notably, fibroids have a higher prevalence in African-American women, highlighting a significant disparity in health needs compared to white women.4, 5 Historically, hysterectomy and myomectomy were considered definitive treatments. However, these procedures carry inherent surgical risks, longer recovery periods, and, in the case of hysterectomy, a complete loss of reproductive potential.6 Consequently, there is increasing demand for uterus-sparing, minimally invasive alternatives that provide effective symptom control with lower morbidity and preservation of fertility.7 Among the evolving treatment options, three image-guided, minimally invasive therapies have gained particular attention: Uterine Artery Embolization (UAE), Radiofrequency Ablation (RFA), and High-Intensity Focused Ultrasound (HIFU). Uterine Artery Embolization (UAE), also known as uterine fibroid embolization (UFE), is a well-established endovascular procedure in which embolic agents are introduced via catheterization of the uterine arteries, inducing ischemia and infarction of fibroids.8 Performed under conscious sedation or regional anesthesia, UAE has demonstrated significant reductions in fibroid volume and symptom relief in over 80% of appropriately selected patients.9 All image-guided techniques are especially beneficial for women who desire uterine preservation, have contraindications to surgery, or wish to avoid major operative interventions. In comparison with UAE, Radiofrequency Ablation (RFA) uses targeted thermal energy to induce coagulative necrosis within fibroid tissue. This approach can be delivered via laparoscopic, transcervical, or transvaginal routes, depending on the platform. The Sonata® System integrates intrauterine ultrasound guidance with energy delivery, enabling precise fibroid targeting with minimal myometrial damage.10 RFA is associated with shorter recovery and less intraoperative blood loss, though it is more suitable for smaller or fewer fibroids and may be less ideal for extensive disease.10, 11 The third modality included in this article is non-invasive HIFU treatment which was first introduced by Lynn et al. in the 1940s.12 However, successful clinical applications awaited the development of technologies capable of accurately targeting the focal area. Today, HIFU is performed under either ultrasound or MRI guidance, enabling precise localization and minimizing trauma to adjacent or surrounding healthy tissue. When leiomyomas are believed to contribute to clinical symptoms, the FIGO classification system can help identify patients who are more suitable candidates for image-guided techniques (Table 1). Together, these advancements reflect a paradigm shift in fibroid management—driven by demographic trends, racial disparities, patient preferences, and technological innovations—toward evidence-based, uterus-preserving therapies tailored to individual patient needs. This article discusses details of each technique including the procedure, benefits and complications and also the impact on particular situations such as pregnancy. Some key points common to each technique are listed here. | FIGO type | Acceptable image-guided treatments | Contraindicated image-guided treatments | |---|---|---| | Type 0a | TV-RFA Risk of fibroid becoming endocavitary and expulsed | UAE (relative) | | Type 1a | HIFU TV-RFA LC-RFA All carry risk of fibroid becoming endocavitary and expulsed | UAE (relative) | | Type 2a | UAE HIFU TV-RFA (easily accessible) TC-RFA LC-RFA | UAE contraindicated if fibroid 24-week size | | Type 3 | UAE HIFU TV-RFA (easily accessible) TC-RFA (easily accessible) LC-RFA | UAE contraindicated if fibroid 24-week size | | Type 4 | UAE HIFU TV-RFA TC-RFA (easily accessible) LC-RFA | UAE contraindicated if fibroid 24-week size | | Type 5 | UAE HIFU TC-RFA (easily accessible) LC-RFA (easily accessible) | UAE contraindicated if fibroid 24-week size TV-RFA | | Type 6 | UAE (caution exercised) HIFU LC-RFA (easily accessible) | TV-RFA TC-RFA | | Type 7 | HIFU (less efficacious) | All routes of RFA UAE | | Type 8 | UAE HIFU LC-RFA (caution exercised) | TV-RFA TC-RFA UAE contraindicated if intracervical | - a Best treated with hysteroscopic myomectomy. 1.1 Key Points—image-guided treatments - Although increasing data report successful pregnancies following leiomyoma treatment with image-guided techniques, the role of these techniques in managing leiomyoma-related infertility—or among women planning future pregnancies—remains uncertain. The outcomes of pregnancy are summarized in Table 2. - Further research is needed to determine which leiomyoma phenotypes are best suited for treatment with image-guided techniques, especially in the context of infertility or anticipated pregnancy. Current knowledge is summarized in Table 1. - The standard treatment for FIGO type 0, 1 and 2 fibroids is usually hysteroscopic myomectomy. - All image-guided treatments have short recovery times and are same day procedures. - Some patients are unsuitable for targeted therapy and UAE. Examples include: - ⚬ Comorbidities such as uncontrolled hypertension, history of cerebrovascular incident, history of myocardial infarction, severe arrhythmia, heart failure and liver failure - ⚬ Acute inflammation of the pelvis or reproductive tract - ⚬ Known or suspected malignancy of the uterine cervix, uterine corpus, ovaries or other elements of the reproductive system | Therapy | Fertility impact | Pregnancy rate | Live birth rate | Miscarriage rate | Complications noted in pregnancy | Recommendations | |---|---|---|---|---|---|---| | UAE18-24, 62-66 | Uncertain: potential risk to ovarian reserve | 15–39% | 60–69% | 22–27% | Preterm birth - 14–28% Malpresentation - 10–17% Postpartum hemorrhage (PPH) - 13–18% Abnormal placentation - 17% | Avoid if fertility is a priority unless no other option | | Myomectomy62, 67-70 | Best pregnancy outcomes over other surgical treatments | 49–75% | 44–85% | 19–43% | Abnormal placentation - <1% Preterm delivery - 5.3% Uterine rupture - <1% | Gold standard to preserve fertility | | HIFU33, 36, 38, 68, 71 | Promising: low risk of uterine rupture, uterus-preserving | 19–69% | 17.3–76% | 11–39% | Retained placenta - 7% Abnormal placentation - 1–5% Hypertensive disease of pregnancy - 2% | Consider for selected patients; more data needed | | RFA62, 69, 72-74 | Limited data; not recommended for women actively trying to conceive | Unclear | 50–71% | 12–41% | TV-RFA: None TC-RFA: Malpresentation - 5% Premature rupture of membranes (PROM) - 5% Hypertensive disease of pregnancy - 5% Fetal Macrosomia - 15% LC-RFA: Abnormal placentation - 3% PPH - 3% | Use with caution; not first-line to preserve fertility | 2 UTERINE ARTERY EMBOLIZATION (UAE) 2.1 The procedure UAE involves the temporary or permanent occlusion of the uterine arteries using biocompatible particles to block the blood supply to fibroids. It is performed typically under local anesthesia and mild sedation and involves temporary occlusion of the arteries supplying the uterus, using biocompatible particles. The particles are injected into the uterine blood vessels through a catheter using fluoroscopy. It causes ischemic infarction from which the uterus usually recovers but the fibroids do not. Various embolic materials have been used for the UAE, each with unique properties including polyvinyl alcohol (PVA) particles, gelatin foam, n-butyl-2 cyanoacrylate and coils among others. Of note, PVA is widely used; however, this is considered permanent along with n-butyl-2 cyanoacrylate, and gelatin foam is considered temporary embolization. UAE has been performed in Africa and Asia with reports of success, even with large and multiple fibroids as are common in Africa. There are several reports of good outcomes such as would be anticipated elsewhere and overall; its introduction has been a positive experience for many women in both Africa and Asia.13-15 UAE is undertaken by an interventional radiologist and many gynecologists the world over, but its uptake has, at times, been hindered by a lack of collaboration between radiologists and gynecologists. 2.2 Patient Selection UAE is best suited for patients with fibroids presenting with symptoms, such as abnormal and heavy bleeding, pain during sex, pelvic pain and pressure, constipation, urinary issues, and erratic menstrual cycles. UAE can be utilized where a patient is not a viable surgical candidate (obesity, bleeding disorders, anemia, etc.), wishes to avoid surgery (although they must be willing to accept hysterectomy in the event of an emergency), wishes to retain her uterus, and where there are other technically challenging issues, e.g. refusal of blood products, multiple prior surgeries, etc. Some women simply wish to have less time away from work. Absolute and relative contraindications include those women who have a fibroid that is already infarcted (based on MRI), is smaller than 1 cm or bigger than 24 weeks size, and where there are fibroids with pedunculated morphology, Intracervical fibroids are also not suitable. Concurrent use of a GnRH agonist renders the vessels smaller and makes the procedure more difficult. Severe contrast allergy is, of course, a contraindication. 2.3 Clinical outcomes UAE has proven effective in reducing fibroid-related symptoms and improving quality of life. UAE involves blocking the uterine arteries leading to fibroid shrinkage and symptom resolution for many women. The expected outcomes following a UAE are summarized in Table 3. When compared with myomectomy, both procedures appear to improve the quality of life of women with symptomatic uterine fibroids. | Therapy | Percentage of patients experiencing improvement in menstrual bleeding at 12 months | Total mean myoma volume reduction at 12 months | Participant satisfaction | Reintervention rate at 12 months | |---|---|---|---|---| | UAE75, 76 | >90% | 50%–60% | 80%–90% | 7% | | HIFU33, 34 | 62% (reduction of symptom severity scores) | 70% | Unclear | 1% | | TV-RFA46, 50 | Unclear | 86% | 98% | 1.5% | | TC-RFA10 | 64.8% | 62.4% | 97% | 0.7% | | LC-RFA45 | 40.2% | 45.1% | 94% | 0.7% | | Myomectomy76, 77 | 89% | Variable (surgical removal) | 82% | 4.2% | For symptom control, the choice is currently unclear and indications and clinical preferences for either modality is varied. Perhaps as a result of the uncertainty of the effect of UAE on fertility, previous RCTs have not generally included women desiring pregnancy. This has meant that some of the studies undertaken are poorly designed and often inconclusive. Concerns around the potential impact of UAE on ovarian and uterine function have resulted in some organizations recommending against UAE for women seeking pregnancy, although the data is very unclear.16 Women undergoing UAE report significant improvement in quality of life, although this might be somewhat less than after myomectomy when assessed at 2 years.17 Menstrual blood loss can be measured using a Pictorial Blood loss Assessment Chart (PBAC) and UAE leads to a significant decrease.18 When compared with myomectomy there is no apparent difference in terms of menstrual regularity, with regular or fairly regular cycles in 88% of the UAE group and 61% of the myomectomy group and the difference was not statistically significant.18 There are also no differences in the bleeding scores, nor in the proportions of women reporting amenorrhea or heavy bleeding; PBAC median scores decreased from 133 (IQR 63–275) to 32 (0–88) at 2 years in the UAE group and from 180 (100–383) to 41 (11–84) in the myomectomy group.18 Pregnancy outcome is uncertain, since many studies have not included women wishing to become pregnant and the recording of pregnancy outcomes has been variable (Table 2). Women desiring pregnancy following UAE for symptomatic fibroids had an overall mean pregnancy rate of 39.4%, live birth rate of 69.2%, and miscarriage rate of 22%.19 The major confounding factor was patient age, with many studies including women over 40 years who already have lower fertility compared to younger cohorts and also the comparison being with a general population of women rather than age-matched women who also have fibroids. However, miscarriage rates and pregnancy rates in the studies analyzed appear comparable to the age-matched population and the other imaging techniques. Thus, since there is a paucity of data regarding the propriety of image-guided interventions, including UAE, on pregnancy rates and outcomes, UAE may not be appropriate for women with infertility or those desiring future pregnancy without very careful counseling.20-22 Ovarian reserve can be measured by assay of Follicle Stimulating Hormone (FSH), Anti-Mullerian Hormone and Luteinizing Hormone (LH) and antral follicle count on ultrasound. There is mixed data as to whether UAE affects ovarian reserve markers, especially depending on age of the participant. A retrospective study in 2016 showed that AMH and AFC were reduced at 12 months after UAE; however, a statistically significant recovery of AMH occurred in women who were <40 years of age but not in those 40 years or older.23 In opposition, more recent studies have shown that there was no effect on AMH or FSH even despite age analysis;18, 24 however, antral follicle count did decline at 3 months after UAE.24 Additionally, the role of the type of embolic agent (temporary versus permanent) and the effect on ovarian reserve has not yet been studied, which could explain the difference in the literature's outcomes. At 3-year follow-up, the overall re-intervention rate among patients who underwent UAE was 14.4%.25 This is in keeping with multiple prior studies which have concluded that UAE has a similar patient satisfaction rate compared with the other surgical alternatives and is associated with shorter length of hospital stay. However, patients undergoing UAE have higher minor complications and higher likelihood of surgical re intervention within 2–5 years. Available data from China suggest that, for example, comparing myomectomy and UAE, the frequency of repeat interventions was similar, and at 5 years an equal proportion of women would recommend their procedure.26 Consequently, all women, including those desiring a future pregnancy, should have the best available evidence before deciding. 2.4 Available adverse outcomes UAE is generally considered safe, although complications can occur. Reported rates vary widely—from 5% to 40%—largely due to differences in study methodology, patient selection, and definitions of adverse events.27 Pelvic pain is a common early complication, experienced by approximately 25% of patients.28 It typically begins 10–20 min after embolization and may persist for several hours. Postembolization syndrome occurs in 19%–35%29 of women and is characterized by a flu-like illness including low-grade fever, malaise, and pelvic discomfort. Symptoms typically emerge within 24–48 h after the procedure, often resolving spontaneously within 2 days, although in some cases they may persist for up to 7 days. Vaginal discharge is also frequently reported, affecting up to 2%–17% of patients.25 Emergency surgical intervention, most often due to complications such as arterial perforation, is required in approximately 2%–3% of cases.27 Pelvic abscess or infection is rare, with an estimated incidence of 1%.27 3 HIGH INTENSITY FOCUSED ULTRASOUND 3.1 Key points - Ultrasound waves can be precisely focused to heat targeted tissue, inducing localized coagulative necrosis while preserving the integrity of surrounding healthy structures. - This technique, known as focused ultrasound (FUS) or HIFU, has been successfully applied to various tissues and tumors using either ultrasound guidance (US-guided focused ultrasound; USgFUS) or magnetic resonance imaging (MR-guided focused ultrasound; MRgFUS). - Several societies have recommended the use of both MRgFUS and USgFUS for the treatment of uterine leiomyomas. - Although increasing data report successful pregnancies following leiomyoma treatment with HIFU, the role of these techniques in managing leiomyoma-related infertility—or among women planning future pregnancies—remains uncertain. - Further research is needed to determine which leiomyoma phenotypes are best suited for treatment with HIFU, especially in the context of infertility or anticipated pregnancy. 3.2 Background Mechanism of Action for HIFU HIFU tissue ablation relies on the deep penetrability of ultrasonic waves in the human body and their ability to be precisely focused on targeted tissues. By concentrating the energy at a specific focal point, tissue temperatures rise to approximately 65°C (149°F), leading to coagulative necrosis as the mechanical energy of the ultrasound waves is converted into heat. 3.3 Patient Selection As stated in Table 1, FIGO Type 0, 1, and 2 lesions, which are best treated hysteroscopically, should be removed via a transcervical approach. Lesions potentially appropriate for HIFU include FIGO Types 1 and 2 that are not amenable to hysteroscopic removal, as well as symptomatic Types 3–6 and Type 8 leiomyomas up to a mean diameter of 20 cm. Type 7 leiomyomas—characterized by a pedicle accounting for less than 10% of the lesion's diameter, or lacking an intramyometrial component—should instead be removed surgically, due to the slow absorption of necrotic tissue and limited reduction in fibroid size following USgHIFU. For fibroids larger than 20 cm in diameter, surgical intervention remains the recommended approach. Patients unsuitable for HIFU include patients who are unable to lie prone for 1 h under analgesic sedation. Patients with severe scars with an acoustic attenuation width of >1.5 cm preventing sonographic visualization of posterior tissue are not candidates for HIFU. Additionally, those with absence of a safe acoustic pathway on imaging. 3.4 Patient preparation Equipment and procedural setup vary between ultrasound-guided (US-HIFU) and MRI-guided (MR-HIFU) systems. When both modalities are available, the choice of technique may be influenced by leiomyoma phenotype and other patient-specific factors. For both MRI and ultrasound-guided procedures, the FUS ablation system converts standard alternating electrical current into mechanical oscillations at ultrasonic frequencies through an ultrasound transducer. The resulting ultrasonic waves are then precisely focused on to the target tissue, raising cellular and tissue temperatures to levels that induce necrosis. Treatment efficacy can be assessed in real time by observing gray-scale changes on ultrasound images, providing immediate feedback for dose adjustments and continuous monitoring of the treatment process. A motion control system maintains patient positioning using a fixation device on the treatment bed and drives the movement of the ultrasound transducer to sequentially treat tissues at different locations. In accordance with the requirements for “Thermal Ablation”, HIFU equipment must enable real-time monitoring and conformal treatment, with the goal of achieving complete ablation of the targeted tissue in a single session.30 Since the gastrointestinal (GI) tract may lie within the acoustic pathway during therapy, a three-day GI preparation is required involving dietary changes and fasting. Proper skin preparation is essential to prevent residual microscopic air bubbles within hair follicles, which could cause skin damage during USgHIFU. The skin is shaved and then cleansed with degassed water and alcohol to degas and degrease the surface. A urinary catheter is inserted prior to treatment to control bladder volume. This ensures a safe acoustic pathway and minimizes the risk of injury to adjacent tissues. 3.5 The Procedure Medications utilized during the procedure HIFU treatment is conducted under intravenous sedation and analgesia. Continuous oxytocin administration (40 units of oxytocin diluted in 500 mL of 5% dextrose solution) during USgHIFU reduces uterine and myometrial blood flow through the stimulation of uterine smooth muscle contractions.31 Targeting The patient is positioned prone. After initial imaging analysis by the integrated system, the patient's position is fixed for treatment. The location, size, and ultrasound imaging characteristics of the fibroid, along with its three-dimensional measurements and relationship to surrounding structures and tissues, are assessed. Pre-treatment imaging evaluates the fibroid's vascularity and helps estimate the necessary treatment dosage, while post-treatment imaging assesses the completeness of ablation, allowing the operator to identify and retreat any inadequately treated areas. Formulation of the ablation treatment plan The scanning range includes the tumor diameter plus an additional 5 mm margin on either end, ensuring accurate delineation of the lesion's boundaries and complete coverage of the treatment area.30, 32 Treatment technique summary The operator selects an appropriate area to initiate treatment, usually starting with the largest cross-sectional plane of the tumor. A trial sonication dose is recommended for each new slice in deeper regions or when applying a higher energy dose. If adverse events occur—such as radiating pain into the lower extremities or perineal discomfort—treatment parameters should be promptly adjusted. Treatment proceeds from deep to superficial regions to ensure complete ablation of the deeper tumor areas with sufficient energy delivery.32 The total treatment time varies depending on the size, number, location, type, and vascularity of the fibroid(s). Most procedures are completed within 2 h. In complex cases, for safety and patient comfort, the total sonication time should not exceed 3500 seconds (approximately 58 min) per session. Endometrial protection For patients desiring future fertility, special precautions should be taken to protect the endometrium during HIFU ablation. The focal point of sonication should be kept at least 1.5 cm away from the endometrial lining. The ablation zone should be dynamically adjusted based on real-time grayscale changes to prevent inadvertent endometrial injury. 3.6 Post-procedure Management For outpatient HIFU treatment, patients who experience no or minimal discomfort can be discharged after a 2-h observation period. Some patients may experience lower abdominal discomfort or vaginal discharge due to uterine contractions and may require a few days of rest at home. Close monitoring is recommended during the first 2 weeks following the procedure, and a structured follow-up plan should be established. 3.7 Available adverse events Skin injury is common in patients who are obese or have abdominal scarring. The risk of skin injury can be reduced by adjusting the intensity of treatment and close monitoring intra-procedural skin response. Intestinal injury from focused ultrasound ablation is rare and can be minimized by ensuring a safe acoustic pathway. Other rare complications include fever, hematuria, and secondary infection. 3.8 Clinical Outcomes According to the literature, the average fibroid shrinkage rates following HIFU treatment are approximately 50% at 6 months, 70% at 12 months, and 80% at 24 months, as seen in Table 3.33 62% of patients had a reduction in their symptom severity scores after HIFU.33 Reintervention is defined as the need for any additional treatment following initial HIFU therapy. In a prospective non-randomized cohort study, the reintervention rate at 12 months after HIFU was reported to be 1.0%.34 An eight-year retrospective follow-up study on recurrent symptomatic uterine fibroids showed reintervention rates of 0%, 3.2%, 9.5%, and 13.7% at 12, 36, 60, and 96 months, respectively.35 Reintervention treatments may include repeat HIFU, myomectomy, or hysterectomy. The precision of HIFU offers optimism for the treatment of leiomyomas in women planning future pregnancies. Several studies have reported reassuring outcomes, suggesting that HIFU may be a suitable option for women with fibroids who are considering pregnancy.33, 36, 37 A systematic review also indicated that HIFU may improve fertility outcomes, with some previously infertile patients achieving pregnancy after treatment.38 Nevertheless, despite encouraging results, most experts advocate caution. Current evidence is not yet sufficient to recommend HIFU—or any other thermal ablation technique—as the first-line treatment for infertility attributed to leiomyomas. Comparison of USg- and MRg-HIFU In the United States, Tempany et al. initially reported the safety and feasibility of MR-guided HIFU (MRg-HIFU) for the treatment of uterine fibroids.39 With its high soft tissue resolution and the capability for real-time temperature mapping, MRg-HIFU theoretically offers more precise ablation of targeted fibroids. Despite the relatively modest ablation volume of around 30%, partial or significant symptom relief was still reported.40 Long-term follow-up studies have shown that patients with greater ablation volumes—referred to as non-perfused volumes (NPV)—experience more substantial symptom relief and lower rates of reintervention.41, 42 To date, little data of clinical comparisons between MRg-HIFU and USg-HIFU have been recorded. 3.9 Guidelines and Recommendations In recent years, several international societies and institutions have recommended HIFU as a treatment option for uterine fibroids. The National Institute for Health and Care Excellence (NICE) in the United Kingdom currently endorses HIFU for the management of uterine fibroids,43 particularly in patients with symptomatic fibroids who wish to preserve fertility and who have not responded to other treatments, such as medication or surgery. NICE further recommends that HIFU should be performed only by experienced practitioners in centers equipped with appropriate facilities and technology. The Society of Obstetricians and Gynecologists of Canada (SOGC) and the European Society for Gynecological Endoscopy (ESGE) recommend HIFU as a surgical alternative for the treatment of uterine fibroids, while also highlighting the necessity for more robust long-term data on its safety and efficacy. 4 RADIOFREQUENCY FIBROID ABLATION 4.1 Key points - Transcervical transvaginal and laparoscopic RFA uses hyperthermic energy to heat soft tissue to greater than 100°C causing coagulation necrosis which in turn leads to volume reduction of the fibroid and hopefully reduction of fibroid-related symptoms. - In practice, FIGO Type 2 and 3 fibroids are easily accessed with transvaginal RFA (TC-RFA). Type 3, 4, 5 fibroids are easily accessed with Transcervical RFA (TC-RFA) and Type 5 and 6 fibroids are easily accessed with Laparoscopic RFA (LC-RFA) (Table 1). - RFA ablation has been shown to have high treatment satisfaction and improvement of heavy menstrual bleeding. However, there is a risk of surgical reintervention such as hysteroscopic myomectomy, uterine artery embolization, endometrial ablation, and hysterectomy. - Depending on the route of RFA, serious adverse events can occur from 1.4% to 3.7% of patients. 4.2 Background Mechanism of Action for Radiofrequency Ablation Transcervical, transvaginal and laparoscopic RFA use a combination of radiofrequency energy with ultrasound. The ultrasound device allows the surgeon to identify and map the fibroids. Once the fibroid is mapped, the physician inserts the handpiece into the fibroid. Conductive needles are then advanced into the fibroid and radiofrequency energy is used to treat the fibroid. Both transcervical and laparoscopic RFA have an array with multiple needle electrodes and transvaginal RFA has a single electrode to treat fibroids. Coagulative necrosis then creates granulation and inflammatory response which results in fibrosis and volume reduction of the fibroid. Factors that determine the volume of ablation include the temperature the tissue reaches, the length of time at that temperature and the shape of the electrode (single electrode, multiple electrodes in array, shape of the electrodes [curved vs. straight]), tissue conductivity and presence of fluid or vascularity.44 The current travels back to the electrode return pads that contain thermocouples which are in place as a safety mechanism to monitor the temperature on the pad. Both Laparoscopic RFA and Transcervical RFA electrode return pads have thermocouples. 4.3 Types/Approaches There are three main approaches to radiofrequency ablation: transvaginal radiofrequency ablation (TV-RFA), transcervical radiofrequency ablation (TC-RFA) and laparoscopic radiofrequency ablation (LC-RFA). The Acessa ProVu© system was FDA approved in 2012 for the treatment of fibroids and it uses a combination of laparoscopy and real time ultrasound guidance to treat fibroids. This system uses a 5 mm laparoscope, a 10 or 12 mm reusable laparoscopic ultrasound probe and a 3.4 mm radiofrequency ablation handpiece with a deployable seven-needle electrode array. Once the myomatous uterus is mapped the RFA handpiece is inserted percutaneously under laparoscopic guidance and advanced into the target fibroid under ultrasound guidance. Depending on the size and shape of the fibroid, the electrode array is deployed according to a proprietary treatment algorithm. After verifying the correct position of the array within the fibroid capsule with the ultrasound transducer and safety of other visceral structures in proximity to the handpiece the surgeon initiates the ablative treatment. Ablation time can occur from 30 s to 12 min at a target temperature of 95°C. After ablation has completed, the handpiece should be allowed to cool in the target tissue for at least 60 s prior to removing it from the tissue. After each ablation, the probe is withdrawn from the fibroid with concurrent coagulation of the probe track. Depending on the size and location of the fibroids, multiple fibroids can be ablated during one serosal puncture. After completion of the ablative treatment, the trocar fascial and skin sites are closed according to the surgeon's standard surgical practice. The STARmed© fibroid radiofrequency ablation was FDA approved in 2018 for the treatment of fibroids using real time transvaginal ultrasound in combination with a vaginally-inserted radiofrequency needle electrode. The ultrasound device with the probe guider attachment is placed into the vagina and leiomyomas are then mapped. Once mapping is complete, the radiofrequency needle can be introduced either transcervically or through the anterior or posterior fornix under ultrasound guidance. After centralization of the needle into a specific myoma, ablation can be performed with care to maintain a safety margin within the fibroid tissue as limits of the ablation are not visualized by the supporting software. This system uses a coolant circulation system of the electrode to maintain suitable impedance at its surface. The core of the target myoma is found to be ablated once the echo-enhanced area on ultrasound reaches 80%–90% of the myoma. Contrast enhanced ultrasound can additionally be used to confirm the absence of vascularization. At this time more myomas can be ablated or the needle electrode is removed. The Sonata© system was FDA approved in 2020 and it uses a combination of radiofrequency ablation and ultrasound guidance in one single handpiece to treat fibroids without abdominal incisions. This system also uses approximately 60 cc of hypotonic fluid to reduce the risk of unintended RF energy dispersion. A 8.75 mm handpiece containing the ultrasound and ablation device is inserted through the cervix. The physician then uses the ultrasound to survey the uterus and map leiomyomas. This system utilizes a SMART (Setting Margins of Ablation in Real Time) Control to adjust the depth and size of the ablation zone. Once the size and location of the ablation zone are determined to be safe for ablation, the trocar tip introducer is advanced into the fibroid. The time of the energy delivered is based on the size of the desired ablation. Depending on the size of the ablation, RF energy delivery times range from 1 to 7 min. The target temperature during ablation is 105°C. Following the radiofrequency ablation cycle, the radiofrequency generator automatically turns off and the needle electrodes and introducer are retracted. The treated fibroids on ultrasound will take on a lighter appearance due to the presence of gas from elevated temperatures. Subsequent ablations can be performed as needed. 4.4 Patient selection RFA is suitable for patients who desire uterine preservation. However, safety and effectiveness regarding fertility have not been established for all routes of RFA and should not be performed in patients who are pregnant. Although case series show no evidence of increased complications, it cannot be recommended for patients actively attempting conception or having a desire for future conception due to the lack of high-level evidence in the literature. In contrast, no RFA routes eliminates the possibility of pregnancy in the future. For preoperatively known or suspected pre-malignant or malignant conditions RFA is contraindicated. If a patient is at risk for endometrial malignancy, tissue sampling of the endometrium should be obtained prior to intervention with RFA. Patients who have active implants such as a cardiac pacemaker, should undergo preoperative consultation with the qualified profession such as cardiologist to determine compatibility with RFA. All RFA routes can treat a variety of fibroids. LC-RFA was designed to treat FIGO Type 1, 2, 3, 4, 5, 6 and hybrid fibroids 2–5.45 TV-RFA was designed to treat FIGO type 0, 1, 2, 3 and 4.46 TC-RFA was designed to treat FIGO type 1, 2, 3, 4, 5 and hybrid fibroids 2–5.10, 47 In practice, FIGO Type 5 and 6 fibroids are easily accessed via the laparoscopic approach, FIGO Type 2 and 3 are easily accessed by TV-RFA and Type 3, 4 and 5 are easily accessed by TC-RFA (Table 1). In FIGO type 2 fibroids where size is >3 cm, complete resection with hysteroscopic myomectomy is low.47 In this clinical situation, the combined two-step approach with hysteroscopic myomectomy with TC-RFA or TV-RFA could lead to further improvement of bleeding, sloughing and passage of tissue. Uterine size of 14 weeks or greater, myomas exceeding 7 cm in diameter or volume greater than 300cm3 may not be suitable and are excluded from studies.46, 48 Further contraindications are outlined in Table 1. 4.5 Patient preparation Informed consent for all RFA procedures should include risk of burns due to overheating of surgical equipment, risk of thermal injury to surrounding structures such as bowel and bladder perforation and risk of allergy. Electrosurgery is not recommended for patients with metal implants near the ablation site or along the radiofrequency path to dispersive electrodes. For transcervical radiofrequency ablation (TC-RFA) the needle electrodes within the handpiece contain nickel and should be used with caution in patients who have a nickel allergy. The risk of infection should be included in the consent for RFA, as the risk of genitourinary (GU) infection with TC-RFA has been reported with 4%–4.8%10, 49 and with LC-RFA 0.74% for pelvic abscess.45 No GU infections have been reported for TV-RFA50 so far. Although ACOG does not recommend antibiotic prophylaxis for aseptic procedures such as laparoscopy without entry into the bowel or vagina and clean contaminated procedures such as diagnostic or operative hysteroscopy, in the pivotal trial for TC-RFA antibiotics were administered in 38.8% of subjects at physician discretion.10 In trials concerning TV-RFA, antibiotics were routinely administered prior to procedure and for 5 days after the procedure. In another LC-RFA trial prophylactic antibiotics were applied preoperatively.51 Antibiotic prophylaxis prior to RFA should therefore be considered at the discretion of the physician. Risk of intrauterine adhesion is a well-documented risk of transcervical surgical procedures such as hysteroscopic myomectomy, curettage and endometrial ablation, respectively.52 Bongers et al. evaluated patients undergoing TC-RFA with a second look hysteroscopy at 6 weeks postoperatively and showed no de novo adhesions after this procedure.53 Risk of intrauterine adhesions after TC-RFA may be minor because the endometrium itself is not the target of the procedure. Patients with known or suspected intra-abdominal adhesions that would interfere with use of the LC-RFA handpiece should not be considered as candidates. The specific risk of adhesions after LC-RFA has not been elucidated or studied. 4.6 Post procedure management All RFA routes can be performed as same day procedures however the following milestones must be completed prior to discharge: bleeding should be monitored in the postoperative phase and should be minimal prior to discharge, pain must be controlled, vital parameters have to be stable. The patient has to be mobile and capable of per os intake. For TC-RFA the mean pain scores (0–10 scale) were 0.2 during the procedure and 2.6 during recovery.10 TC-RFA was completed under conscious sedation and general anesthesia and the mean pain scores were 0.01 for those who underwent general anesthesia and 0.5 for procedures under conscious sedation.10 During recovery 33% of patients were managed with non-steroidal anti-inflammatory drugs and 26.5% received narcotics.10 Return to normal activities was approximately 2 days with more than half of the patients returning to normal activity within 1 day of the procedure.10 Employed patients returned to work in a mean of 4 days postoperatively.10 Patients resumed a normal diet, sleep and bowel function at approximately 1 day after the procedure, and normal urinary function on the same day of the procedure.10 For TV-RFA the mean duration of analgesic use was 4 days and the return to work in a mean of 5 days.46 For LC-RFA the median time to return to normal activity was 9 days (ranging from 2 to 60 days). Those who were employed returned to work in a median of 5 days (range from 0 to 29 days).45 Patients took pain relievers for a median of 4 days.54 There have been no studies looking at postprocedural pain scores and return to normal activities and work comparing routes of RFA. 4.7 Clinical Outcomes A summary of clinical outcomes for all routes of RFA are seen in Table 3. All RFA modalities showed at least a 45% reduction in mean myoma volume with improvements in patient bleeding symptoms with high patient satisfaction.10, 45, 46, 50, 55 Reintervention rates for all RFA were approximately 1%.10, 45, 50 Reintervention rates for Sonata TC-RA and LC-RFA increased at 3 years to 9.2% and 11%.55, 56 Although there are currently no studies that compare outcomes between different RFA modalities, a metanalysis showed that Acessa® carries the lowest reintervention rate (0.3%) after 12 months when compared to other uterine sparing modalities such as myomectomy (1.1%), uterine artery embolization (3.6%) and high intensity focused ultrasound (9.7%).57 Pregnancy and fertility outcomes after RFA are outlined in Table 2. The overall review of pregnancy outcomes for all routes of radiofrequency ablation shows favorable fertility and pregnancy outcomes. More research needs to be performed to evaluate the safety of pregnancy after RFA. As of today, myomectomy still remains the gold standard for patients who desire future fertility with symptomatic fibroids. 4.8 Available adverse outcomes In the Acessa® pivotal trial, 3.7% of patients suffered from device related adverse events including pelvic abscess requiring antibiotics and drainage, 2 cm laceration of sigmoid colon treated with primary repair, mild uterine serosal burns managed expectantly, postoperative vaginal bleeding with intravenous iron supplementation and severe abdominal pain treated with ibuprofen.45 There was 1 serious adverse event related to the procedure due to early postoperative bleeding resulting in an abdominal wall hematoma which resolved without further sequalae.58 10% of patients had adverse events possibly related to the procedure including abdominal pain and a urinary tract infection.58 The overall rate of procedure-related adverse events was 1.78%.59 In comparison to complication rates among surgical interventions for fibroids laparoscopic RFA had the lowest major complication rate of 1.7% when compared to myomectomy (3.5%), uterine artery embolization (2.7%), or hysterectomy (2.1%).60 In the Sonata® pivotal trial, 1.4% of patients had procedure-related serious adverse events, including deep venous thrombosis and pelvic pain, leukorrhea and low-grade fever related to leiomyoma sloughing.10 Non-serious procedure-related adverse events were reported in 74 patients (50.3%) including leiomyoma sloughing (30.6%), cramping or pain (7.5%), leukorrhea (6.1%), uncomplicated genitourinary infection (4.8%), constitutional symptoms (3.4%), expelled leiomyoma (1.4%) and non-gynecologic events such as constipation, high blood pressure, atelectasis and sore throat (5.4%).10 In a separate trial of TV-RFA, the most frequent complication was associated with use of epidural anesthesia (5.08%) and there was one case of intestinal heat injury (1.69%).46 In other trials such as Cho et al. 14.5% of patients had increased vaginal discharge.61 Overall, the rate of adverse event for any RFA procedure for fibroid treatment is low. Depending on the route it ranges from 1.4%–3.7% serious procedure or device-related adverse events.10, 45 Currently there are no studies comparing the outcomes of RFA. Therefore, more research is needed to elucidate effects and risks of these promising techniques. AUTHOR CONTRIBUTIONS MAL, MW, PD, IMH, AS all contributed to the development of the FIGO Fibroid Toolbox and subsequently to the conceptualization of the article. MAL, PD and IMH supported by EA and JML put together the original version of the article and all authors have commented on and developed the manuscript. EA, JML and MAL were responsible for the final text. FUNDING INFORMATION No funding was received by any of the authors. CONFLICT OF INTEREST STATEMENT None of the authors declare any conflicts of interest. DATA AVAILABILITY STATEMENT Data sharing is not applicable to this article as no new data were created or analyzed in this study.