Could Transcervical Radiofrequency Ablation Become a Therapy Option for Focal Adenomyosis?

Thirty patients with focal adenomyosis were treated with transcervical RFA with the Sonata System. The age range was from 27 to 54 years. Hypermenorrhea was the main symptom. Twenty-five patients had one area of focal adenomyosis, and six patients had at least one additional fibroid. We treated 43 findings in total, which included 36 focal adenomyosis and seven fibroids. Three patients underwent operative hysteroscopy, with two patients undergoing endometrial resection and another patient undergoing fibroid resection. The size of the area of focal adenomyosis ranged from 2 cm to 9.6 cm in diameter, with an average size of 4.4 cm. Table I presents the patients' characteristics and preoperative findings. We performed all surgeries without any complications. The average surgery's time was 30.7 min. Only two cases exceeded 36 min due to simultaneous laparoscopy and excision of endometriosis lesions in one case (98 min) and concurrent operative hysteroscopy and fibroid resection in another (56 min). In the majority of patients, more than one ablation cycle was necessary. The shortest ablation time was 1 min 58 s (ablation in one step), while the longest ablation time was 17 min 54 s (ablation in four steps). Table II presents the intraoperative parameters. Follow-up was performed after the treatment. At the time of this report, 27 patients had returned for follow-up, while three patients were unreachable. Seven patients had follow-ups to assess the improvement of their bleeding symptoms 6-12 months after the procedure, while 21 patients had follow-ups ≥12 months. Of the 27 patients, 24 reported symptom improvement, including 23 who experienced significant improvement and one who reported mild improvement. No patient reported a worsening of their symptoms. The procedure reduced the average focal lesion size from 4.4 cm to 2.8 cm (Table II). No postoperative complications were observed. All patients reported satisfaction with the procedure. Table III displays the postoperative outcomes.

This was a retrospective study, and according to the 15§ of the professional code of the North Rhine Medical Association, neither prior consultation nor ethical approval is required for such studies. Transcervical RFA was initially developed for the treatment of fibroids. This procedure is performed by a gynecologist, using a device equipped with a small ultrasound probe, which is inserted into the uterus ( 17 ). Prior to the ablation, the fibroid is detected sonographically. There are two zones, the red zone (ablation zone) and the green zone (safety zone), which must be adjusted depending on the size of the fibroid ( Figure 1 ). Usually, general anesthesia is required for transcervical RFA. The diameter of the device is 8.3 mm. After graphical visualization of the fibroid, the ablation is carried out. In this phase, a safety zone guarantees no thermal injury in the surrounding organs ( e.g. , bladder and bowel). Transcervical access to the fibroid eliminates the need for serosa puncture. The measurements are registered graphically. The ablation time is 1-7 min depending on the size of the fibroid. The temperature of the electrode is about 105˚C. A thorough understanding of vaginal ultrasonography and proficiency in other endoscopic fibroid therapies are essential, as these techniques can be combined with transcervical RFA when necessary ( 17 , 19 ). Ablation and safety zones. Red arrows indicate the uterine border. Black arrows show the fibroid border. Green zone is the safety zone. Red zone is the ablation zone. This was a retrospective analysis of patients treated with the Sonata ® System. In total, 574 cases were analyzed, all performed at two centers in Germany (Academic Hospital Cologne Weyertal and Hospital Böblingen). In this study, only patients who were treated with sonographic-detected focal adenomyosis and bleeding disorders were included ( Figure 2 ). To differentiate focal adenomyosis from fibroids using transvaginal sonography the following criteria were used: 1) compared to fibroids, adenomyosis lacks distinct margins, as it does not have pseudocapsules or other clear demarcations. It may also contain small cysts that are highly suggestive of adenomyosis; 2) on Doppler imaging, blood vessels cross through focal adenomyosis, whereas fibroids typically demonstrate peripheral blood flow ( 12 ). We compared the largest diameter between the preoperative and postoperative evaluations. An ultrasound follow-up was the routine procedure in each case. If the findings were reduced and/or the symptoms improved, the ablation was rated as successful. Figure 3 presents an example of ultrasound imaging of focal adenomyosis. Overview of patients. Ultrasound imaging of focal adenomyosis. *Red stars show the border of focal adenomyosis. A total of 30 patients with 36 areas of focal adenomyosis were treated. We established the following inclusion criteria for this analysis: 1) patients with bleeding disorders, 2) those with sonographically diagnosed focal adenomyosis, and 3) individuals seeking an organ-preserving method. All patients provided their standard informed consent for the treatment with the Sonata System. We informed them that, although this method is safe and well-established for fibroid treatment, its safety and effectiveness for treating adeno-myosis have not yet been fully established. We performed the ablation of focal adenomyosis in the same manner as for fibroids, and it was successful in all cases without any complications. After placement of the Sonata System intrauterine, areas of focal adenomyosis were detected using the sonography probe integrated within the device. We introduced the central spike, adjusted the ablation and safety zones, and inserted the electrodes. After rechecking the safety zone, the ablation could be performed after reaching 105˚C. All patients were discharged in good condition. Ultrasound follow-up was performed at six-twelve months after the procedure. The last follow-up to assess improvements in bleeding symptoms was performed either by phone contact or during the last ultrasound examination. Patients were asked about their subjective assessment of the improvement of bleeding symptoms and their satisfaction with this method of treatment. Statistical analyses were conducted using a two-tailed Fisher's exact test, descriptive statistics, and confidence intervals of the mean. Results are presented as the mean±standard deviation.

EP: Article writing, data management, data analysis. AD: data management. SS, SR and TR: project development and administration.

RFA appears to be an effective approach for treating adenomyosis. However, there is a lack of data, highlighting the need for further prospective studies. Owing to the advantages of transcervical RFA with the Sonata ® System mentioned above, this system may be a promising therapeutic alternative method to conventional procedures, such as hysterectomy and tissue excision for the treatment of adenomyosis, and may enable a minimally invasive, uterine-preserving option.

The majority of patients with adenomyosis are symptomatic, and because of the progressive nature of the disease, the symptoms can worsen ( 13 , 20 , 21 ). Combined oral contraceptives, gonadotropin-releasing hormone antagonists/agonists, progestin-only pills, levonorgestrel intrauterine devices, and other hormonal options may help treat adenomyosis in patients without fertility desire ( 14 ). However, treatment becomes particularly challenging if patients wish to conceive, prefer to avoid hormone therapy, or when hormone therapy is contraindicated. In such cases, a surgical approach may be required ( 15 ). Nowadays, many patients prefer uterine-preserving treatment options over hysterectomy. For a long time, the only uterine-sparing surgical approach available was the excision (usually through laparotomy) of the adenomyosis-affected uterine tissue ( 15 ). However, it should be emphasizes that this technique necessitates advanced surgical skills. Uterine reconstruction and hemostasis during the procedure can lead to increased bleeding and a long surgery time ( 22 ). Furthermore, as adenomyosis is characterized by a lack of clear demarcation between affected and healthy tissue, excision may result in incomplete or overly extensive removal ( 22 ). Moreover, reports have already indicated the risk of uterine rupture during pregnancy following surgery ( 16 ). These reasons have led to the exploration of new surgical approaches for the treatment of adenomyosis ( 22 ). There are two main directions for adenomyosis treatment that are considered alternatives to hysterectomy and excision of the adenomyotic tissue: uterine artery embolization (UAE) and hyperthermic approaches. However, the UAE is very limited in patients with fertility desire ( 23 ). The most commonly used hyperthermic methods are high-intensity focused ultrasound (HIFU), percutaneous microwave ablation (PMWA), and RFA ( 22 ). A recent review considered all three methods as effective options for treating adenomyosis ( 24 ). The review revealed a significant reduction in mean uterine and adenomyosis volumes in the PMWA and RFA groups compared to the HIFU group: 46.8%, 44%, and 33.6% and 74.9%, 61.3%, and 45.1%, respectively. The average ablation time for RFA was significantly shorter than that for HIFU (31.93 min vs. 92.18 min) and only slightly longer than that for PMWA (24.15 min). The rate of minor adverse events was significantly lower in the RFA group compared to the HIFU and PMWA groups (3.6%, 39.0%, and 51.3%, respectively) ( 24 ). Liu et al. described the postoperative risk for uterine adhesions after performing RFA in patients with adenomyosis to be 2.5% ( 25 ). In the present case series, we achieved a significant reduction in the size of focal adenomyosis. RFA has similar symptom improvements as conventional uterus-sparing surgeries ( 22 ). Improvement of hypermenorrhea in our case series was achieved in 89% of patients (Table II). Nam has reported the outcomes of RFA in patients with adenomyosis and fertility desire. He used transcervical RFA with a monopolar Cool-tip RF ablation system and transabdominal ultrasound guidance to treat 81 patients with adenomyosis and fertility desire. 91% (74) of these patients had been diagnosed with infertility for at least one year ( 26 ). There were reports of 39 pregnancies in 29 patients, leading to 24 deliveries in 22 patients. In addition, 25 of the 59 patients who attempted natural conception achieved 34 pregnancies, representing a clinical pregnancy rate of 42.7%. Four out of twenty-two patients who attempted IVF successfully achieved five pregnancies. Overall, the clinical pregnancy rate was 35.8%. A total of 23 patients did not actively try to conceive or discontinued attempts at conception, resulting in an overall pregnancy success rate of 50%. Furthermore, 15 patients underwent cesarean sections, while nine delivered vaginal. No uterine ruptures were reported ( 26 ). In our case series, five patients had a desire for fertility, with four of them expressing a desire for future conception. There were no pregnancies at the time of this report. In our case series, we employed a transcervical RFA using the Sonata ® System. When compared to other RFA techniques, the Sonata ® System offers several significant advantages ( 17 ). 1) The device is to be inserted transcervically, thus there is no need for incision (neither abdominal nor vaginal). 2) The device incorporates an ultrasound probe at its top, allowing for a lifetime demonstration. 3) Graphical demonstration of ablation and safety zones enables, on the one hand, more precise ablation of the affected uterus tissue and, on the other hand, guarantees the safety of the ablation. 4) Seven electrodes, introduced into the tissue, achieve more volumetric ablation compared to the single needle. 5) Automatic measurement of the ablation's duration simplifies the process, eliminating the need for personal evaluation of the ablated tissue during surgery. The favorable outcomes regarding symptom alleviation and the reduction of adenomyosis lesion size found in our study suggest that this strategy may serve as a viable therapeutic alternative for the treatment of focal adenomyosis, a condition with limited treatment options. There is a difference between performing the RFA in uterine fibroids and adenomyosis. Fibroids usually do not infiltrate healthy uterine tissue, and after performing RFA on fibroids, the uterine tissue remains "untouched". In contrast, adenomyosis penetrates the uterine tissue, necessitating the ablation of the uterus wall during the procedure. This can cause abdominal discomfort, lower abdominal pain, and a stronger, albeit less frequent, vaginal discharge during the first weeks compared to fibroids. Study limitations . Limitations of this report include the small number of patients, absence of prespecified clinical protocol, and absence of histological proof of adenomyosis. A prospect clinical trial to assess safety and effectiveness of transarterial ablation for the treatment of focal adenomyosis is warranted.

Adenomyosis is a common gynecological disease characterized by the presence of ectopic endometrial tissue (endometrial stroma and glands) within the myometrium. Even though adenomyosis is closely related to endometriosis, it is not considered a form or subtype of endometriosis ( 1 , 2 ). Rokitansky described the presence of endometrial glands in the myometrium in 1860 and called this condition “cystosarcoma adenoids uterinum” ( 3 ). Von Recklinghausen and Cullen used the terms “adenomyomata, cystoadenomyomata, adenomyoma, and diffuse adeno-myoma” for describing the similar pathology ( 4 , 5 ). The current definition of adenomyosis was suggested by Bird et al. in 1972 ( 6 ). There are two main types of adenomyosis: diffuse and focal. When focal adenomyosis is entirely surrounded by hyperplastic/hypertrophic smooth muscle, it is referred to as an adenomyoma, and such true adenomyomata are uncommon ( 7 , 8 ). Adenomyosis is generally not considered to be premalignant, although rare cases of malignancy associated with adenomyosis have been reported ( 9 , 10 ). Previously, adenomyosis was diagnosed through histopathological examination following a hysterectomy or adenomyomectomy, with prevalence rates ranging widely from 8.8-61.5% ( 11 ). However, the recent development of imaging tools, such as transvaginal sonography and magnetic resonance imaging (MRI), enable diagnosis without surgical interventions ( 12 ). Approximately 70% of patients with adenomyosis develop symptoms such as heavy bleeding, severe dysmenorrhea, chronic pelvic pain, and pressure on the bladder and bowel. These symptoms are often linked to an enlarged uterus and can also contribute to impaired fertility ( 13 ). Treatment options for adenomyosis are limited. Symptoms attributable to adenomyosis may often be managed with medical therapy ( 14 ). The LNG-IUS 52 mg is one of the most effective medical therapies, but its efficacy is limited for long-term treatment ( 14 ). However, the effectiveness and feasibility of medical therapy are not always guaranteed ( 15 ). A surgical approach is required when the patient desires to preserve fertility or when medical treatment proves ineffective or causes serious adverse side effects ( 15 ). The most used surgical approach is laparoscopic or open abdominal surgery. To deal with adenomyosis, conservative uterus-sparing surgical methods such as Osada Plastic have been established, which involve the excision of adenomyotic tissue ( 15 ). However, these require excellent surgical proficiency and carry increased perioperative risks and morbidity, including the potential for uterine rupture during pregnancy ( 15 , 16 ). Therefore, new surgical methods are currently being attempted for treating adenomyosis ( 16 , 17 ). Transcervical intrauterine ultrasound-guided radio-frequency ablation (RFA) is a focal volumetric image-guided RFA procedure ( 17 ). In a single integrated device, the system combines intrauterine sonography with radiofrequency energy delivery. The system provides real-time visualization of fibroids with graphical imaging, demonstrating the location of the ablation, and a thermal safety border beyond which there is no material thermal effect. Depending on the ablation size, the duration of the ablation typically ranges from 1-7 min. This system is approved by the Food and Drug Administration (FDA) and is Conformite Europeenne (CE)-marked for the treatment of uterine fibroids ( 17 ). Our previous report presented pilot results from a small case series of transcervical adenomyosis ablation using the Sonata System ( 18 ).

EP and AD have no conflicts of interest in relation to this work. SS, SR, and TR are consultants for the Sonata System. The Authors report no other conflicts of interest in relation to this work.