Procedure Overview

TFA is currently performed using an FDA-cleared and CE marked device (Sonata® System; Gynesonics, Redwood City, California) in both the US and Europe. Sonata is a transcervical intrauterine-ultrasound-guided radiofrequency energy device that provides volumetric ablation of the types of myomas that most often cause irregular bleeding (nonpedunculated submucosal, abutting and transmural myomas (FIGO types 1, 2, 3 and hybrid 2–5), but also extends a transcervical approach to the treatment of intramural (Type 4) and subserous (Types 5, 6) myomas and their associated symptoms. Due to the integrated intrauterine ultrasound (IUUS) probe, the Sonata system is not limited to treating only submucous fibroids that would be visible with hysteroscopic methods. In addition, larger fibroids that have dimensions greater than the largest ablation (4.9 cm x 4.2 cm; 45.3 cc) capable with the device can be treated with multiple ablations in a single treatment episode, with small degrees of overlap.

Technology Overview and Procedure Details

The Sonata System has been described in detail previously [10, 14, 15]. The device consists of a reusable intrauterine ultrasound (IUUS) probe and a single-use RFA Handpiece with graphical guidance software (SMART Guide) for diagnosis and targeting (Fig. 1). These components are integrated to provide the surgeon with real-time image-guided treatment that has the benefit of maintaining the intrauterine ultrasound probe, RF needle electrodes and the targeted fibroid all parallel and in-plane. The RFA handpiece couples onto the IUUS probe and contains a 13-gauge introducer and seven thin RF needle electrodes that are deployed during the procedure, as well as interactive controls for controlling the procedural steps. When assembled, the RFA handpiece is 21.3 cm long, 8.3 mm in diameter with a 2.34 cm articulating ultrasound tip. The ultrasound tip can be articulated to 45º and 60° from the vertical axis of the device to target the treatment area and permit visualized deployment of the RFA needles. The IUUS probe image is curvilinear, penetrates a depth greater than 9 cm, has a transmit frequency of 4.8–9.0 Mhz, and provides a 114° field of view from within the endometrial cavity (thus, there is no endometrial stripe as the imaging landmark as the probe is within the stripe). Depending on the size of the ablation, RF energy delivery time ranges from 1 to 7 min after reaching the target temperature of 105 C. While it is not necessary to ablate 100% of a fibroid’s volume to obtain durable symptom relief, it does appear helpful to ablate a majority of a fibroid, volumetrically, for optimal long-term results.

The SMART Guide depicts the location and size of the subsequent Ablation Zone (red ellipsoid), along with a Thermal Safety Border (green ellipsoid) that demarcates a point beyond which there are no significant thermal effects on tissue [11, 14]. This validated safety border, in conjunction with a depiction of the ablation size and location, provides high degree of control and precision for safely ablating targeted tissue without extending beyond the uterine serosa, preventing damage to the surrounding viscera. Ablations may also be constrained within a fibroid’s pseudocapsule if desired by the operator. Multiple overlapping ablations may be performed in one or more fibroids during the same treatment session as determined graphically by the gynecologist; thus, there is no need to stage patients as is often done with hysteroscopic myomectomy. When soft tissue is thermally ablated, it generates water vapor that is visible as “outgassing” on the IUUS image and appears as hyperechoic/echogenic bubbles for several minutes. That helps indicate where the ablation has taken place when deciding whether to make additional ablations in the same fibroid. There is also no need for a fluid management system; only a small amount of fluid (typically sterile water) is instilled into the endometrial cavity for acoustic coupling, rather than uterine distention (Fig. 1).

Fig. 1

While general anesthesia in an operating room is not unusual for TFA procedures, treatment with Sonata is often performed in an ambulatory surgical setting under conscious sedation, regional anesthesia or parenteral general anesthesia with or without oral airway support. In the United Kingdom, TFA is often performed successfully with excellent pain control in a procedure room using multimodal local anesthesia such as oral premedication with paracervical or intracervical blockade [16]. Some procedures in the US are also done in an office setting, either under conscious sedation under the guidance of a certified registered nurse anesthetist or occasionally under paracervical blockade. The smallest ablation size of 2.0 cm x 1.3 cm, which scales up to a maximum 4.9 cm x 4.2 cm allows for a broad range of fibroid sizes and FIGO types to be treated. Patient recovery is similar to that of operative hysteroscopy; mean return to normal activity is 2.2 days, with a median 1.0 days [10]. Patients are generally discharged home within 1–2 h after the procedure on oral nonsteroidal analgesics for cramping and instructed on precautions for follow-up.

Clinical IndicationsClinical Trial Summary

The first clinical trial of the Sonata System, formerly referred to as VizAblate™, was the 50-subject prospective, single-arm, multicenter FAST-EU trial at seven sites in Mexico, the UK and the Netherlands [15]. The FAST-EU was a 12-month study with a primary endpoint of perfused fibroid volume reduction at 3 months. Of note, there was a mean total fibroid volume reduction of 54.7 ± 37.4 and 66.6 ± 32.1% at 3 and 12 months, respectively (all P < .001 compared with baseline). At 12 months post-ablation, mean menstrual pictogram scores improved by 53.8 ± 50.5, while mean symptom severity (SSS) and health-related quality of life (HRQOL) scores improved by 55.1% ± 41.0% and 277% ± 483%., respectively (all P < .001 compared with baseline). There were four surgical reinterventions (8%) within 12 months.

The largest clinical trial to date of the Sonata System was the 147-patient prospective, interventional, multicenter, single-arm SONATA trial that involved 21 clinical sites in the US and one in Mexico [10, 12, 17]. The co-primary endpoints of bleeding reduction and lack of surgical reintervention were both reached at 12 months post-treatment. In all, 64.8% of patients reported ≥ 50% reduction in menstrual bleeding using a pictorial blood loss assessment chart and 99.3% of patients were free from surgical reintervention at one year. Patients were followed through three years, and the cumulative reintervention rate at 36 months was 8.2%.

The OPEN clinical trial was a prospective, multicenter, single-arm, observational study to with the primary endpoint being the incidence of new intrauterine adhesions at 6 weeks post-ablation with the Sonata System [18]. The trial was unusual in that three independent reviewers, rather than the investigators themselves, scored baseline and second-look hysteroscopy videos for intrauterine adhesions, thereby reducing bias. While 37 patients were enrolled, at the conclusion of the study, there were 34 pairs of baseline and second-look hysteroscopy videos that were evaluated (two patients disenrolled and one patient’s video record was inadequate for evaluation). No evidence of intrauterine adhesiogenesis was noted, including among six women with apposing fibroids. The study, while unpowered, suggests there is a low risk for adhesiogenesis after TFA, particularly for women with apposing submucous and transmural myomata.

Patient Selection

The current indication for Sonata in both the US and Europe is for the treatment of symptomatic uterine fibroids. While bulk symptomatology has not been formally studied, results from the FAST-EU study did demonstrate a significant degree of fibroid volume reduction as early as 3 months after treatment [15].

Based on the available evidence and the significant experience among the authors, we maintain that TFA with the Sonata System should be a treatment consideration when counseling any patient with symptomatic uterine fibroids. Indeed, we feel it is the default option for many women until proven otherwise.

In the product labelling, there is no specific guidance regarding the size, number or location of fibroids. That said, there are some sensible recommendations for TFA with the Sonata System. As a volumetric ablation procedure, fibroid size does assume outside importance when considering whether this is an appropriate treatment option for a given patient. Geometrically, the Sonata System can ablate 10-cm fibroids and this has indeed been accomplished, reported in the literature [19]. However, treatment of fibroids ≤ 8 cm in diameter appears optimal. A GnRH analog, preferably without hormonal add-back therapy (as it tends to blunt fibroid volume reduction) for three months may be helpful when considering treatment of fibroids that are 9–10 cm in diameter [20, 21].

A general suggestion of ≤ 10 fibroids to be treated with Sonata also seems appropriate since it can become daunting to keep track of which fibroids have been ablated when dealing with larger numbers of myomata. While there is no harm in doubly ablating the exact same tissue, there is no benefit either.

It is also important to note that Sonata has not been studied in women > 50 years of age or post-menopausally. While admittedly a rare malignancy, the prevalence of uterine sarcoma, specifically in women undergoing myomectomy or hysterectomy for presumptive fibroids, increases nearly fivefold when a woman turns 50 and nearly twelvefold at age 60 [22].

Clinical OutcomesPregnancy

Initial data for pregnancy in women who have undergone TFA for symptomatic uterine fibroids has been promising [23,24,25,26,27,28]. It should be noted that the FDA-cleared and CE marked indications for use of the Sonata System note that safety regarding future pregnancy after undergoing TFA remains to be established, although as a uterus-conserving alternative to hysterectomy, pregnancy is not precluded after treatment with Sonata. Desire for fertility is also not specifically contraindicated in the current labelling [26]. There is a growing body of evidence regarding women who have undergone fibroid ablation, particularly with RF energy or FUS [29].

Pregnancies have been reported after most hyperthermic ablative techniques, with the largest series to date reported in 2024 of 89 pregnancies after TFA with the Sonata System, after a 2022 case series that had reported outcomes of 36 pregnancies [24, 26]. To date, more than 105 pregnancies have been reported to a registry maintained by Gynesonics (communication D Toub). In a more recent report of 89 pregnancies, there were no instances of uterine rupture, intrauterine fetal demise or placenta accreta spectrum, and a single delivery with a five-minute Apgar score under 7 [24]. Pregnancy outcomes included 19 vaginal deliveries, 35 Cesarean sections, 5 therapeutic abortions, 1 ectopic pregnancy, and 1 delivery by an unknown route. These findings represent a limited dataset, and the appropriate route of delivery and optimal timing for subsequent pregnancy has to be determined.

In 2015, the US FDA removed warming from US labeling of magnetic resonance-guided FUS (MRgFUS) after reviewing data from 118 reported pregnancies [11, 14, 30]. While the safety of MRgFUS remains to be established, MRgFUS can be a consideration for women who had not completed childbearing. The current revised pregnancy labeling for MRgFUS is similar to that of the Sonata System, as no explicit warnings or contraindications appear in either device’s labelling.

Selective targeting and treatment of fibroids that aims to constrain each ablation within the fibroid pseudocapsule, could avoid adjacent endometrium and/or myometrium. Importantly, this can be accomplished through the use of a graphical overlay that depicts the ablation size and location (as with the Sonata System’s SMART guide). This may have fertility implications in that preservation of the endometrium and adjacent myometrium might reduce the theoretical risks of uterine rupture prior to, or during, labor, as well as theoretical concerns about blastocyst implantation and the placental interface in pregnancy [25]. Patients should be fully counseled that the specific probabilities of abnormal outcomes after any hyperthermic fibroid ablation remain unknown at this time, although the emerging data for both FUS and RFA remain encouraging.

Adenomyosis

Adenomyosis is a chronic disease of the myometrium and involves the implantation or differentiation of glandular epithelium resembling endometrium in lakes or bundles of tissue that are activated by ovarian hormones, principally estrogen [31]. Much like endometriosis (and in fact referred to as endometriosis of the uterus), adenomyosis causes pelvic inflammation, pelvic pain, irregular menstrual cycles and has a known negative influence on fertility [32]. Adenomyosis is often found coincidentally with myomas and pelvic endometriosis and lesions can often be singular, multifocal, borderless and diffuse [31].

Classification of various types of adenomyosis has been proposed. Focal or circumscribed adenomyosis, diffuse adenomyosis, cystic adenomyosis (cystic areas within the endometrium), polypoid adenomyosis (circumscribed endometrial masses) have all been described. Adenomyosis is characterized on ultrasound as cystic, hypervascular and often quite heterogeneous with linear striations noted on transvaginal sonography. In comparison to myomas that display peripheral vasculature and are hypoechoic compared to surrounding myometrium, adenomyosis often has central vascularity and appears hyperechoic.

Currently, there is no medication or standard treatment protocol that is indicated for the treatment of adenomyosis. Traditionally, the disease is treated medically for patients with a desire for uterine preservation using estrogen modulating or receptor blocking drugs such as progestins (oral and injectable), oral contraceptive pills, GnRH agonists or antagonists and selective estrogen receptor modulators). These treatments have demonstrated limited efficacy in alleviating the full spectrum of adenomyosis symptoms. Definitive treatment of adenomyosis remains a hysterectomy for those patients with treatment refractory symptoms.

Uterus-sparing techniques for adenomyosis requires highly complex surgical skills and is associated with significant perioperative risks. Uterine reconstruction and complete excision is challenging, due to a lack of clear demarcation between affected and healthy tissue has been difficult to standardize because adenomyotic tissue invades the uterine muscle later in a way that distorts the borders [33]. Surgical “debulking” of lesions with wedge metroplasty or adenomyomectomy has been reported for uterine preservation and is most successful in patients with focal disease but has also been done for diffuse disease and cystic lesions. There is no strong evidence to point to a technique that secures the best clinical and reproductive results. Improvement in symptoms for dysmenorrhea and menorrhagia have been documented with both laparoscopic and laparotomy approaches, 54.6–84.6% and 50-68.8%, respectively, depending on the degree of resection. Pregnancies have been reported in women after excisional procedures, with concern for uterine rupture being as high as one in eight women [34, 35].

As the majority of studies evaluating RFA has been in fibroids, adenomyosis treatment has been considered investigational. RFA has gained recognition in Asia with an initial report on treatment in 2017 both transcervically and transvaginally with abdominal ultrasound guidance. RFA has been as a feasible treatment consideration for patients who wish for a uterus-sparing procedures, with less morbidity and potentially more specificity in lesion identification due to directed imaging based focal treatment [36, 37]. While literature on the effectiveness of RFA on adenomyosis remains sparse, prior studies have demonstrated a decrease in dysmenorrhea and a reduction in uterine volumes [36,37,38,39]. Published reports of transcervical RF ablation of adenomyosis using different devices than the Sonata system also show outcomes with reduction in lesion size and overall menstrual symptom reduction [36,37,38,39]. However, none of these previous methods involve an integrated transcervical ultrasound probe, with the ultrasound monitoring conducted transabdominally.

A systematic review from Dedes et al. evaluated 7 studies on 396 patients who underwent RFA for symptomatic adenomyosis [38]. Of the studies, 4 studies were conducted with transcervical approach, 2 studies were laparoscopic and 1 study involved percutaneous approach, and all were performed with ultrasound guidance. However, only 4 studies were deemed as ‘good’ according to the NIH quality assessment guidelines. These studies were notable for a mean age of 39. Data on lesions and uterine volume were incomplete, and pretreatment with GnRH agonist occurred in one study and post treatment with levonorgestrel containing IUD was performed in another study. Adenomyosis was diagnosed by imaging in these cases; and none had histology- proven adenomyosis.

TFA with the Sonata system can more easily be incorporated into gynecologic surgery due to its transcervical approach and integrated RF energy and imaging. As it is guided by ultrasound, it allows the adenomyosis lesion to be more precisely targeted than laparoscopic or open surgery. By basing treatment on ultrasonographic mapping, this can lead to a more specific approach and minimize thermal effects to uninvolved tissue. The transcervical approach also has the advantage of leaving the outermost myometrial layer intact. Two recent case reports and a small case series of 13 patients detail the first reported treatments of image-identified adenomyosis with the Sonata system [40,41,42]. Each of these reports demonstrated a reduction in adenomyosis volume and overall corpus uterine volume and improvements in dysmenorrhea and menorrhagia.

TFA with the Sonata system shows great promise as a uterine-sparing treatment for patients with adenomyosis. However, additional data are required to confirm the safety and long-term efficacy for this condition. It is also essential to conduct further evaluations to ensure the safety of this treatment for women seeking to preserve their fertility and for its effects on the uterus during pregnancy.

Safety and Complications

The safety of the procedure (currently with over 10,000 cases performed worldwide since 2011) has been documented. The thermal safety border as displayed on the graphical interface provides real-time visual clarity for the surgeon to safely perform volumetric ablation with confidence to safely ablate the fibroid and stay within the serosa, thereby avoiding proximity to the bowel, bladder and other viscera.

The most common post-procedure side effects include cramping and vaginal spotting. In the SONATA pivotal trial, no device related adverse events were noted, although two procedure related adverse events were reported in the first year of follow-up and resolved without sequelae. These consisted of a deep venous thrombosis at 15 days post-ablation that was managed with oral anticoagulants on an outpatient basis, and an overnight admission for noninfectious leukorrhea and pelvic pain 28 days after TFA. The 3 most frequent non-serious procedure related adverse events in the original trial consisted of fibroid sloughing (30.6%), cramping/pain (7.5%) and leukorrhea (6.1%) [10]. In the Sage Clinical registry, a global post market registry of 160 patients (still ongoing) was published in 2021 by Christoffel et al., reported no serious device related adverse events [24]. There was one case of endometritis (0.6%) and one second degree skin burn at the site of the dispersive electrode, resulting from human error in placement of the pad on the anterior thigh.

A review of the MAUDE database over 6 years using search terms reveals 6 reports of anterior thigh burns, of which 4 were thought to be device related due to inappropriate contact/application of the return electrodes to the skin [43]. The other two reports included a reaction to the adhesive and a burn that was more likely the result of a light cord burn from the coincidental hysteroscopy. Three other reports are listed specifically for the Sonata system including a failed handpiece with inability to deploy the secondary needles after four prior successful ablations and then loss of part of the central needle. This needle fragment was not noted to be visible in the fibroid on subsequent imaging, and the patient had no complaints. One intraprocedural uterine hemorrhage that required an emergent supracervical hysterectomy in a uterus over 1000 g and a post-procedure prolapsing fibroid that occurred about one week after treatment also requiring hysterectomy. The company estimates over 30,000 myomas have been treated to the date of this publication with no reports of visceral injuries.

A case report of Enterococcus faecalis sepsis and Asherman’s syndrome was reported in 2023 after treatment of 3 fibroids measuring 7 cm, 6 cm, and 5 cm, respectively. This patient presented 3 days after her procedure with pain, fever and tachycardia. She received IV antibiotics and had persistent fevers on day 7, and therefore underwent a laparoscopic myomectomy with excision of 6 myomas and surrounding hemorrhagic and infected myometrium [44]. In this author’s experience of over 250 cases, we have experienced one case of endometritis, one case of GBS endometritis with bacteremia, and 1 case of hematocolpos caused by cervical blockage due to expulsion of necrotic tissue.

Gynesonics internal data on file notes endometritis occurring in 16/10,000 cases, or 0.16%. The rare reports of endometritis are infrequent and are not surprising given the placement of the device via the vagina/cervix and are similar in nature to those reported in endometrial ablation and less frequent than those reported with operative hysteroscopy [45]. The majority of patients treated in the SONATA trial did not receive prophylactic antibiotics. More data is needed to assess whether prophylaxis is needed or should be performed for patients at greater risk for infection, which may include obesity, number or volume of fibroids treated, immune suppression, and diabetes.

QOL

European guidelines support the use of the SONATA as first line therapy for the treatment of symptomatic myomas [13]. ACOG has also published support for the RF treatment of myomas, endorsing transcervical RF treatment of fibroids as equally efficacious in reducing leiomyoma volume and improving quality of life [46]. Significant improvements measured in the symptom severity score (SSS) and health-related quality of life (HRQOL) subscales of the UFS-QOL questionnaire demonstrated durability at 3 months and through a mean follow-up of 64 months as shown in the studies, SONATA, FAST-EU, and VITALITY [15, 17]. As additional patient types and fibroid number are expanded in normal clinical use of Sonata, these durability scores will continue to be assessed.

New Developments and Areas of InterestHigh Risk Patients

The advantage of a transcervical procedure in the treatment of myomas in patients with co-morbidities such as inherited or medical coagulopathies, obesity, previous abdominal surgeries, anesthesia related issues for ventilation and Trendelenburg positioning are obvious. As the procedure becomes more available for these patients the opportunity to avoid more risky procedures such as laparoscopic and laparotomic fibroid therapies and hysterectomy will be available.

Early Fibroid Intervention

Fibroids remain a major source of gynecologic and reproductive dysfunction. Growth prevention strategies have been explored, but to date, there have been no noninvasive surgical therapies that currently exist for uterine fibroid prevention. Consideration of early treatment for small myomas, with targeted intrauterine transcervical ablation, may provide a method of fibroid growth arrest, which could reduce the overall burden of fibroid disease over a woman’s lifetime.

Bridge to Hysterectomy

Undergoing a hysterectomy is a significant life event that requires considerable time and planning, which can be particularly challenging for women balancing the demands of work and family responsibilities. For many women, taking time off work for the surgery, followed by weeks of recuperation, can disrupt their professional life, potentially leading to stress or financial strain. Simultaneously, the demands of managing household responsibilities, caring for children, and fulfilling other family roles can create additional pressure. The combined burden of work and family obligations makes finding a suitable time for such a procedure even more complex.

Sonata can act as a bridge therapy, which would allow a patient to have symptomatic improvement, until a time where hysterectomy is feasible and convenient. Sonata fibroid ablation offers symptom relief with a significantly shorter recovery period and less disruption to daily life.

Pretreatment with GnRh Agonists/Antagonists

Optimizing fibroid response to TFA treatment may be improved with a short course of pretreatment to reduce blood flow to the uterine fibroids. Elagolix, Relagolix and Lupron all demonstrate decreased menstrual bleeding in women with uterine fibroids. There is a potential for a synergistic effect of reduced hormonal input to fibroids in combination with TFA. In addition, pretreatment can improve hemoglobin and reduce anemia, optimizing patients for a surgical procedure.

TFA as an Alternative to Hysterectomy in Markedly Symptomatic Patients

Many women are deeply committed to preserving their uterus, even if it means enduring a significantly reduced quality of life. Often, they are rightly informed that hysterectomy is their best option, yet they are prepared to continue with the resultant health consequences, such as severe AUB, anemia, iron infusions, and transfusions. Even in uteri that are markedly enlarged with numerous fibroids and adenomyosis, and where hysterectomy is the most ideal treatment, transcervical ablation offers a less invasive alternative, potentially providing these patients with moderate symptom relief while preserving their uterus. Sonata can reduce symptoms of heavy bleeding and pelvic pain, potentially leading to significant improvements in quality of life without the need for more invasive surgical options.