Ultrasound-guided high-intensity focused ultrasound ablation for uterine arteriovenous fistula: a case series

Abstract

Purpose

To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in the treatment of uterine arteriovenous fistula (UAVF).

Materials and methods

This case series included three patients diagnosed with acquired UAVF. All patients underwent routine laboratory tests, electrocardiography (ECG), chest X-ray, ultrasound, and pelvic contrast-enhanced magnetic resonance imaging (MRI). HIFU treatment was performed under sedation and analgesia using a Model JC Focused Ultrasound Tumor Therapeutic System (made by Chongqing Haifu Medical Technology Co. Ltd., China) with a B mode ultrasound device for treatment guidance. The treatment time, sonication power, sonication time, and complications were recorded. Follow-up evaluations were scheduled at 1-, 3-, 6-, and 12-month to assess symptom improvement and evaluate the post-treatment imaging.

Results

All patients completed HIFU treatment in a single session without any major complication. All patients complained of mild lower abdominal and sacrococcygeal pain. Typically, no special treatment is required. Following HIFU treatment, there was a significant relief in clinical symptoms, particularly abnormal uterine bleeding. Ultrasound examinations conducted one month after the treatment revealed a notable reduction in the volume of the lesion, ranging from 57% to 100%. Moreover, the efficacy and safety of HIFU treatment remained consistent during the 12-month follow-up period.

Conclusion

HIFU ablation appears to be an effective and safe treatment modality for UAVF. It provides a noninvasive approach with favorable clinical outcomes.

Keywords:

• Ultrasound-guided high-intensity focused ultrasound
• uterine arteriovenous fistula
• ablation
• treatment
• efficacy
• safety

Introduction

Uterine arteriovenous fistula (UAVF) was first described by Dubreuil and Loubat in 1926 [1]. It is also known as uterine arteriovenous malformation [2]. O'Brien reported an incidence of UAVF approximately 4.5% [3]. A prospective study from Japan found that among 995 patients, UAVF was found in 5.2% (4/77) after abortion, 0.22% (1/458) after delivery, 0.24% (1/424) in outpatients [4]. UAVF is characterized by presenting mainly as arteriovenous fistulous connections into the myometrium supplied by uterine arteries, resulting in vascular pathological lesions with direct communication [3].

UAVF can be classified as congenital or acquired, with the latter being more common and often was caused by trauma, gestational trophoblastic disease, infection, or tumors. The symptoms of UAVF typically include vaginal bleeding, lower abdominal pain [5]. Irregular vaginal bleeding is the most common presentation, but some patients may experience paroxysmal massive bleeding or ‘on-off’ bleeding. In severe cases, UAVF can lead to hemorrhagic shock [6].

Currently, various treatment options are available for UAVF, including medical treatment, uterine artery embolization (UAE), lesion resection, and hysterectomy [7]. However, traditional surgical approaches have their limitations. Surgical lesion resection and hysterectomy are primarily used for patients who do not require future fertility or when other treatments have failed. Retaining the uterus with uterine artery embolization carries the risk of ovarian function damage, and its effects on recurrent vaginal bleeding remain unclear [8–10]. Medical treatment can be used for managing patients with minimal vaginal bleeding, but significant vaginal bleeding often requires repeated treatment due to the short half-life and suboptimal results [11].

With the increasing demand for less invasive and more effective treatments to preserve fertility, HIFU ablation has emerged as a noninvasive therapy for solid tumors and gynecological diseases [12–14]. In this case series, we report the therapeutic results of HIFU for patients with UAVF. Our findings suggest that HIFU is a promising and secure treatment approach for UAVF, leading to improved symptomatology, significant reduction in lesion size, and preservation of fertility in patients.

Cases presentation

This study included three patients who underwent HIFU treatment at Liuzhou Maternal and Child Health Care Hospital. The subjects were analyzed with respect to the etiology, clinical manifestations, diagnosis, treatment, and prognosis. Follow-up was conducted until ultrasonographic examination shows the uterus returned to normal. The protocol for this case series was approved by the ethics committee of our institute (NO KSKY 2023011) and the requirement for informed consent was waived.

HIFU treatment was performed using the Model JC Focused Ultrasound Tumor Therapeutic System (Chongqing Haifu Medical Technology, Chongqing, China). Before HIFU treatment, the patients were asked to complete specific bowel preparation and routine skin preparation. The patients were asked to ingest semi-liquid or liquid food 2 days prior HIFU treatment, with an enema on the morning of the HIFU treatment day after a 12 h fasting. Every patient was asked to shave her abdominal wall from the lower edge of the umbilicus to the upper margin of the pubic symphysis, and then degreasing and degassing the skin with 70% of ethanol and degassed water. Before the procedure of HIFU, a urinary catheter was inserted to adjust the bladder volume by infusing normal saline during the procedure of HIFU treatment to obtain a safe acoustic pathway.

The HIFU procedure was described previously [15,16]. Briefly, every patient was first carefully positioned prone on the HIFU table with the anterior abdominal wall was in contact with degassed water in the reservoir under HIFU table. Then, a degassed water balloon was placed between the abdominal wall and the transducer. HIFU treatment was performed under conscious sedation. During the procedure, all the procedures were performed under conscious sedation (midazolam hydrochloride at 0.02 mg/kg, propofol at 0.02 mg/kg, fentanyl at 1 mg/kg, repeated administration of each at 40-min intervals if needed). The sagittal view of the ultrasound scanning mode was selected, and the treatment plan was made by dividing the treated lesion into different slices with a thickness of 5 mm each. Oxytocin (120 units/500 ml) was administered intravenously at a rate of 15 drops/minute before and during the course of treatment. Real-time ultrasonography was used to determine the location of the target area and to monitor the response to HIFU. The ablation procedure began from the innermost slice. A point sonication was used with the treatment power of 300–400 watts. We compared the ultrasound grey-scale values of the target image before and after ablation to determine whether the lesion was presented with coagulation necrosis. The treatment was terminated when the increased grayscale covered the treated lesion, and a contrast-enhanced ultrasound was performed immediately after HIFU. One day post-HIFU, MRI was performed to evaluate treatment efficacy. The patients were scheduled for follow-up at 1-, 3-, 6-, and 12-month to evaluate symptom improvement, imaging evaluation after treatment.

Case 1

A 24-year-old woman, gravida 2 para 1, presented with persistent vaginal bleeding for 60 days following a vaginal delivery. Laboratory examination found a beta-human chorionic gonadotropin (β-hCG) level of <1.2mIU/mL. Ultrasound examination revealed a hyperechoic mass measuring 29 × 28 × 24 mm in the fundus of the uterus (Figure 1A and 1B). Further evaluation with MRI revealed an abnormal myometrial mass measuring 31 × 25 × 24 mm (Figure 1C).

Figure 1. Image profile of a 24-year-old patient with UAVF. (A) Ultrasound images of the patient with uterine arteriovenous fistula. (B) Grayscale ultrasound showed thickening of the myometrium, and no echo in local pipe-like/honeycomb shape. Color Doppler showed multicolored blood flow signals in the anechoic region. (C) The pre-HIFU MR image showed a lesion located at the bottom of the uterus. (D) The post-HIFU MR image showed no perfusion in the lesion located at the anterior wall of the uterus. (E) Ultrasound image of uterus 1 month after HIFU showed that the lesion reduced. (F) Ultrasound image of the uterus 12 month after HIFU showed good endometrial continuity and good triple line endometrial pattern.

After the diagnosis was made, the patient underwent HIFU treatment on 9 January 2021. The treatment utilized a sonication power of 350 W, with a total treatment time of 66 min and a sonication time of 888 s. Post-treatment MRI revealed a non-perfusion area with a visible size of approximately 28 × 30 × 21 mm (Figure 1D). No serious complications occurred during the HIFU treatment, and the patient was discharged from the hospital 1 day after HIFU treatment.

Following HIFU treatment, the patient experienced a significant improvement of symptoms, with cessation of vaginal bleeding 10 days after the procedure. Ultrasound examination performed one month later showed no blood flow in the mass, with the mass measuring 12 × 4 × 9 mm, and the mass volume reduced by 99% (Figure 1E). Ultrasound at 12 months post-HIFU showed a relatively normal uterine cavity (Figure 1F). The patient was still in the lactation period after treatment, and menstruation resumed after 8 months of lactation, and the volume and the cycle of menstrual recovered as before.

Case 2

A 33-year-old woman, gravida 6 para 2, presented with irregular vaginal bleeding. She experienced vaginal bleeding for 29 days following a miscarriage, with the amount of bleeding being less than the usual menstrual blood volume. Lab test showed the β-hCG level of 20.22mIU/mL, and ultrasound examination revealed a heterogeneity mass with a size of 15 × 12 × 10 mm at the left anterior wall of the uterus (Figure 2A and B). Further evaluation with pre-HIFU MRI showed an abnormal myometrial mass measuring 27 × 16 × 23 mm (Figure 2C).

Figure 2. Image profile of a 33-year-old patient with UAVF. (A) Color Doppler ultrasonography of a longitudinal section of the patient’s uterus before HIFU treatment. (B) Color Doppler showed multicolored blood flow signals in the anechoic region. (C) The pre-HIFU MR image showed a lesion located at left anterior wall of the uterus. (D) The post-HIFU MR image showed no perfusion in the lesion located at the anterior wall of the uterus. (E) Ultrasound examination performed one month later showed no blood flow, with the lesion measuring 19 × 17 × 13 mm and a reduction rate of 57%. (F) Ultrasound image of the uterus 12 month after HIFU showed a relatively normal uterine cavity.

The procedure of HIFU treatment was performed on 7 June 2021. The treatment utilized a sonication power of 350 W, with a total treatment time of 60 min and a sonication time of 802 s. Post-HIFU MRI after HIFU revealed a satisfactory ablation volume (Figure 2D)

Following HIFU treatment, the patient reported cessation of vaginal bleeding in 5 days. Ultrasound examination performed one month later showed no blood flow in the mass, with the size measuring 19 × 17 × 13mm and a reduction rate of 57% (Figure 2E). Ultrasound findings at 12 months post-HIFU showed a relatively normal uterine cavity (Figure 2F). The patient reported her menstrual volume returned to normal.

Case 3

A 32-year-old woman, gravida 2 para 1, presented with persistent vaginal bleeding for 42 days following a vaginal delivery. Laboratory examination revealed β-hCG level of 1.45mIU/mL. Ultrasound examination showed a hyperecoic mass measuring 18 × 18 × 10mm at the anterior wall of the uterus (Figure 3A and 3B). Further evaluation with MRI revealed a myometrial mass measuring 15 × 17 × 15mm, displaying an abnormal signal (Figure 3C)

Figure 3. Image profile of a 32-year-old patient with UAVF. (A and B) Color Doppler ultrasonography of the patient’s uterus before HIFU treatment. (C) The pre-HIFU MR image showed a lesion located at the anterior wall of the uterus. (D) The post-HIFU MR showed non-perfusion in the lesion immediately after HIFU treatment.

The procedure of HIFU treatment was performed on 19 August 2022. The treatment utilized a sonication power of 350 W, with a total treatment time of 35 min and a sonication time of 268 s. Post-HIFU contrast-enhanced ultrasonography demonstrated a satisfactory ablation volume (Figure 3D).

Following HIFU treatment, the patient reported a cessation of vaginal bleeding in 5 days. Subsequent ultrasound examination at 3 months post-HIFU showed complete disappearance of the mass and a relatively normal uterine cavity. During a 12-month follow-up after HIFU treatment, the patient did not resume menstruation due to lactation.

Discussion

The case series presented in this study highlights the use of HIFU as a noninvasive treatment modality for UAVF. By focusing high-energy ultrasound waves on target lesions inside the body, HIFU raises the tissue temperature in the focal region, causing protein degeneration and irreversible coagulative necrosis. Importantly, HIFU minimizes damage to surrounding tissues and ensures the safety of adjacent structures.

Yoon examined 54 patients who underwent UAE, reporting a success rate of 91% [17]. Similarly, Peitsidis reviewed 59 patients who underwent UAE for uterine AVM, with an initial success rate of 71% (42 patients), while 17 required additional treatment such as re-embolization, medical therapy, or surgery [6]. A meta-analysis of 121 UAVF patients treated with medical therapy indicated an overall success rate of 88% [11]. Medical therapy offers the advantage of lower cost and mitigates the risk of embolism, thus preserving future fertility. Surgery remains the primary option for patients experiencing hemodynamic instability or significant vaginal bleeding. Uterine artery embolization carries inherent risks, including hypomenorrhea, premature ovarian failure, intrauterine adhesion, spontaneous abortion, and fetal intrauterine growth restriction or placental abnormalities.

In the context of treating myometrial lesions such as UAVF, HIFU offers several significant advantages. Frist, in contrast to traditional surgical approaches or endovascular procedures, HIFU presents a noninvasive or minimally invasive alternative. Secondly, unlike surgical interventions, which entail incisions and potential tissue trauma, HIFU administers focused ultrasound energy to the target area without invasive procedures, potentially reducing the risk of complications, shortening recovery times, and lessening post-treatment discomfort. Lastly, its site-specific and precise site ablation disrupts communication branches between arteries and veins without affecting the blood supply to the uterus and ovaries, while preserving the structural integrity of surrounding tissues and the acoustic pathway. This makes it an ideal choice for patients who wish to retain their reproductive function without significant impact on ovarian function.

This case series represents the report on the use of ultrasound-guided HIFU for the treatment of acquired UAVF. Clinical observation and follow-up demonstrated significant relief of symptoms in the patients, confirming the effectiveness, safety, and clinical value of ultrasound-guided HIFU in treating UAVF. Based on our findings, we propose that HIFU could be integrated into current treatment algorithms or guidelines for UAVF. Further research and collaboration among experts are warranted to establish standardized protocols and criteria for the appropriate selection of patients and the optimal timing of HIFU treatment in the management of UAVF.

However, it is important to acknowledge the limitations of this case series. The small number of cases and the lack of subsequent pregnancy and pregnancy outcome data limit the conclusions that can be drawn regarding fertility preservation. Additionally, the risk of embryo and placenta residue after HIFU treatment requires further investigation to determine the necessity of routine uterine clearance. Furthermore, the efficacy of HIFU treatment in patients with hemodynamic instability remains unclear and warrants further exploration.

Conclusions

This case series demonstrated the successful use of HIFU treatment for patients with acquired UAVF and provided evidence for the efficacy and safety of HIFU in the treatment of this condition. By utilizing HIFU, the researchers were able to achieve positive outcomes in terms of symptom relief and clinical improvement in the patients with UAVF. This highlights the potential of HIFU as a treatment option for UAVF. Further studies with large number of subjects are needed to validate these findings.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data presented in this study are available on request from the corresponding authors.

Additional information

Funding

This work was funded by the Guangxi Science and Technology Plan Project (Guangxi Clinical Research Center for Obstetrics and Gynecology), grant #GuiKe AD22035223, and Liuzhou Science and Technology Plan Project, grant #2020NBAB0825. Also was supported by Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering [Grant No.2021KFKT020].