Synergistic Efficacy and Safety Evaluation of Focused Ultrasound Ablation Surgery Combined with Thermal Balloon Endometrial Ablation in Treating Adenomyosis: A Prospective Controlled Study

Abstract

Objectives:

The objective of this study was to evaluate the synergistic efficacy and safety of focused ultrasound ablation therapy (FUAS) combined with thermal balloon endometrial ablation (TBEA) in treating adenomyosis.

Materials and Methods:

A total of 103 patients diagnosed with adenomyosis admitted to Nanchuan District People’s Hospital of Chongqing from July 2022 to December 2023 were randomized into two groups. The experimental group (n = 36) received FUAS combined with TBEA, whereas the control group (n = 67) underwent FUAS alone. All patients were followed up for 12 months. Clinical symptoms, serological markers, imaging parameters, and adverse events were compared between groups.

Results:

At 12 months posttreatment, both groups showed significant improvements in key outcomes. The experimental group exhibited superior outcomes in reducing pictorial blood loss assessment chart scores, improving health-related quality of life scores, lowering CA₁₂₅ levels, and elevating hemoglobin levels compared to the control group (all P < 0.05). No significant differences in follicle-stimulating hormone (FSH) levels were observed between groups. No severe complications occurred.

Conclusion:

FUAS combined with TBEA effectively reduces uterine volume, alleviates dysmenorrhea, decreases menstrual flow, improves anemia, and preserves ovarian function (as evidenced by stable FSH levels) with minimal adverse effects. This combined therapy demonstrates enhanced efficacy and safety over monotherapy, providing a promising comprehensive treatment for adenomyosis.

INTRODUCTION

Adenomyosis is a prevalent condition affecting the reproductive system, predominantly observed in women of reproductive age. The etiology of adenomyosis remains ambiguous; however, some researchers propose that it results from the infiltration of endometrial glands with proliferative capacity into the myometrium, categorizing it as a distinct form of endometriosis.[1] The clinical manifestations of adenomyosis are contingent upon the disease type and primarily include alterations in menstrual patterns and progressive dysmenorrhea, among other symptoms.[2] The management of adenomyosis presents a global challenge. Pharmacological interventions can alleviate symptoms, yet issues such as poor patient adherence and high recurrence rates upon cessation of medication persist.[3] Conventional surgical excision of lesions carries risks including hemorrhage, tissue damage, infection, and suboptimal symptom relief.[4] In some cases, patients undergo hysterectomy, which can adversely impact their physical and psychological well-being. Consequently, a comprehensive and individualized therapeutic approach is predominantly employed in clinical settings.[5]

Focused ultrasound ablative surgery (FUAS) is a noninvasive therapeutic modality characterized by its safety, absence of bleeding, and rapid patient recovery posttreatment. It is extensively utilized in obstetrics, gynecology, and various other medical disciplines. The underlying mechanism involves leveraging the high penetrability of ultrasound waves within the human body to concentrate these waves on specific target tissues. This process converts the mechanical energy of ultrasound into thermal energy, thereby elevating the temperature of the target tissues to 60°C–100°C, resulting in coagulative necrosis.[6] Empirical studies indicate that FUAS effectively alleviates dysmenorrhea symptoms associated with adenomyosis. However, the long-term efficacy of FUAS in reducing menstrual bleeding in patients with concurrent abnormal uterine bleeding (AUB) exhibits variability.[7]

Thermal balloon endometrial ablation (TBEA) is an innovative approach to endometrial ablation, wherein a balloon filled with high-temperature fluid is introduced into the uterine cavity. This process induces thermal denaturation of the endometrial tissues in contact with the device, thereby facilitating the removal of the endometrium.[8] Research indicates that TBEA can alleviate symptoms of menorrhagia. However, due to its limited penetration depth, which is confined to the basal layer of the endometrium, it poses challenges in ablating lesions within the myometrium. Consequently, there remains a potential for the continued proliferation of ectopic endometrial tissue, minimal alleviation of dysmenorrhea, and a possible resurgence in menstrual flow.[9]

This study aims to examine the clinical outcomes of utilizing FUAS in conjunction with TBEA for the treatment of adenomyosis by integrating these two therapeutic approaches to simultaneously ablate the adenomyotic lesions and excise the endometrium.

MATERIALS AND METHODS

This study included 103 patients diagnosed with adenomyosis at Nanchuan District People’s Hospital in Chongqing between July 2022 and December 2023. The study protocol was conducted in accordance with the Declaration of Helsinki and received approval from the hospital’s Medical Ethics Committee (approval number: YXYJ-2022-003-01), and all participants provided written informed consent. .

Inclusion and exclusion criteria

Inclusion criteria are as follows: (1) Patients diagnosed with adenomyosis accompanied by AUB-A; (2) Hemoglobin (HGB) levels below 110 g/L; (3) Married women aged between 40 and 55 years who desire uterine preservation and have no intention of future childbearing; (4) Individuals who are either unable to tolerate medication or have not responded to medical treatment; (5) A uterine cavity depth of ≤12 cm as determined by hysteroscopy; and (6) Successful localization using on-board imaging equipment with an established safe acoustic channel. A power analysis (α = 0.05, β = 0.20), based on preliminary data regarding the expected reduction in pictorial blood loss assessment chart (PBAC) scores, indicated a minimum requirement of 30 patients per group. The final enrollment in our study (experimental group n = 36, control group n = 67) met and exceeded this requirement.[8]

Exclusion criteria include: (1) Individuals who are menstruating, pregnant, or lactating; (2) Cases where the nature of the lesion is indeterminate; (3) Presence of pelvic inflammatory disease; (4) A history of multiple lower abdominal surgeries resulting in significant scarring; (5) Inability to communicate effectively or to tolerate the prone position; and (6) Instances where prepositioned ultrasound intestinal intervention in the injection channel cannot be displaced. Individuals meeting any of these exclusion criteria will not be included in the study.[8]

Utilizing the randomized numerical table method, participants were allocated into two distinct groups: (1) the experimental group, which underwent FUAS in conjunction with TBEA (n = 36); and (2) the control group, which received only FUAS (n = 67).

Treatment

FUAS was administered to both patient groups using the JC200 D-type focused ultrasound tumor therapy system. All FUAS procedures were performed by a single attending physician with over 5 years of experience, and all TBEA procedures were conducted by a single associate chief physician also with over 5 years of experience, to minimize operator-related variability. Prior to the procedure, patients underwent bowel and skin preparation, and a urinary catheter was inserted. An appropriate volume of saline was introduced into the bladder. Patients were positioned prone on the treatment bed, with the abdominal wall submerged in degassed water within the treatment bed sink. A degassed water-infused pusher water bladder was then placed between the treatment head and the abdominal wall to establish an optimal acoustic channel. The treatment was performed under sedation and analgesia, with intravenous infusion of oxytocin administered. Treatment commenced following the development of a detailed plan. The treatment power ranged from 300 to 400 watts, and energy was applied along the lesion within a safe range, ensuring an appropriate distribution point shape. Upon achieving satisfactory gray-scale diffusion, a sulfur hexafluoride microbubble contrast agent was administered.[10] The procedure concluded once it was confirmed that no imaging was present within the lesion.

The experimental group underwent treatment with a thermal balloon-type endometrial heat balloon therapy device for endometrial ablation within 48 h following FUAS treatment. Under intravenous general anesthesia, an initial hysteroscopic examination was conducted. After completing the device’s self-check and preheating procedures, the balloon was inserted to match the depth of the uterine cavity, and treatment commenced. Following an automatic cessation of the procedure after 128 s, the device was removed, and the hysteroscope was reinserted for further examination. The treatment could be repeated 2–4 times, if necessary, until the endometrium exhibited a burnt yellow coloration.

Observation and evaluation indicators

The enhancement of clinical symptoms (as measured by visual analogue scale [VAS], PBAC, and health-related quality of life [HR-QOL] scores), imaging parameters (including uterine volume, adenomyoma blood flow grading, and endometrial thickness), serological markers (such as HGB, CA₁₂₅, and follicle-stimulating hormone [FSH]), and the incidence of adverse reactions were systematically assessed at 3-, 6-, and 12-months posttreatment.

The evaluation indices encompassed the following components: (1) Menstrual Flow Assessment: The PBAC was employed, with scoring conducted after conversion based on the number of fully saturated sanitary napkins.[11] (2) Dysmenorrhea Evaluation: The VAS was utilized, allowing patients to score their pain according to their personal descriptions of its intensity.[12] (3) Quality of Life Assessment: The health-related quality of life questionnaire specific to uterine fibroids (HR-QOL) was used, where a higher score indicates greater patient satisfaction with daily life.[13] (4) Uterine Volume: This was measured using color Doppler ultrasonography, with volume calculated as V = 0.523 × anterior–posterior diameter × transverse diameter × longitudinal diameter (cm³).[14] (5) Uterine Adenomyoma Blood Flow Grading: This was assessed and graded through color Doppler ultrasonography, categorized into grades 0-III, corresponding to scores of 0–3, with the average score recorded.[15]

Statistical analysis

Data processing was conducted using SPSS version 25.0 (SPSS Inc., Chicago, IL, USA). Initially, measurement data were assessed for normality. Data following a normal distribution were represented as mean ± standard deviation (x ± s), and intergroup comparisons were performed using the t-test. Categorical data were presented as frequencies and percentages (n[%]), and comparisons between groups were carried out using the Chi-square (χ²) test. P < 0.05 indicates a statistically significant difference.

RESULTS

No statistically significant differences were observed between the two groups concerning age, disease duration, body mass index, and other baseline characteristics (P > 0.05), indicating their comparability, as presented in Table 1.

Table 1.

Comparison of baseline data between the two groups of patients

Group	n	Age (years)	Duration	BMI (kg/m2)
Experimental group	36	46.35±3.17	5.8±3.0	24.59±3.34
Control group	67	45.14±3.85	6.3±2.7	24.15±2.88
t	-	0.550	0.841	0.948
P	-	0.583	0.402	0.348

BMI: Body mass index

Following a 12-month treatment period, both PBAC and VAS scores in the patient cohorts exhibited a statistically significant reduction (P < 0.05), whereas HR-QOL scores demonstrated a significant increase (P < 0.05) compared to baseline values. Notably, the experimental group showed a significantly greater improvement in PBAC and HR-QOL scores compared to the control group (P < 0.05). However, the intergroup difference in VAS scores did not reach statistical significance (P > 0.05), as detailed in Table 2.

Table 2.

Comparison of pictorial blood loss assessment chart scores, Visual Analogue Scale scores, and health-related quality of life scores between patients in the two groups before treatment and after 12 months of treatment

Group	n	VAS scores		PBAC scores		HR-QOL scores
		Before treatment	12 months after treatment	Before treatment	12 months after treatment	Before treatment	12 months after treatment
Experimental group	36	7.26±1.37	2.45±1.06*	191.37±38.23	10.18±4.24*	71.68±5.05	89.12±3.22*
Control group	67	7.65±2.44	2.56±1.37*	185.52±40.33	35.31±5.47*	67.90±3.87	76.12±4.45*
t	-	0.522	0.831	1.125	5.345	0.877	15.525
P	-	0.602	0.415	0.286	<0.001	0.391	<0.001

*Comparison with this group before treatment, P<0.05. PBAC: Pictorial blood loss assessment chart, HR-QOL: Health-related quality of life, VAS: Visual Analogue Scale

After 12 months of treatment, both uterine volume and adenomyoma blood flow grading scores showed a statistically significant reduction in both groups compared to pre-treatment values (P < 0.05). However, the intergroup difference was not statistically significant (P > 0.05). In the experimental group, endometrial thickness was significantly reduced after 12 months of treatment compared to both pre-treatment values and the control group, with the difference being statistically significant (P < 0.05). Conversely, in the control group, the change in endometrial thickness compared to pretreatment values was not statistically significant (P > 0.05). Refer to Table 3 for detailed data.

Table 3.

Comparison of uterine volume, adenomyoma blood flow grading score, and endometrial thickness between the two groups of patients before treatment and after 12 months of treatment

Group	n	Uterine volume (cm3)		Adenomyoma blood flow grading scores		Endometrial thickness (mm)
		Before treatment	12 months after treatment	Before treatment	12 months after treatment	Before treatment	12 months after treatment
Experimental group	36	183.03±23.44	122.78±45.20*	2.41±0.28	0.43±0.58*	8.04±3.56	4.58±2.45*
Control group	67	170.22±18.25	118.74±14.68*	2.05±0.41	0.72±0.33*	9.10±2.11	8.11±1.37†
t	-	0.871	3.215	1.122	2.054	0.511	3.122
P	-	0.190	0.331	0.135	0.378	0.254	<0.001

*Comparison with this group before treatment P<0.05, ^†Comparison with this group before treatment P>0.05

After 12 months of treatment, both groups exhibited an increase in HGB levels and a decrease in CA₁₂₅ values. The experimental group demonstrated a statistically significant improvement compared to the control group (P < 0.05). In contrast, FSH levels showed no significant change in either group before and after treatment, with the difference not reaching statistical significance (P > 0.05). Refer to Table 4 for detailed data.

Table 4.

Comparison of hemoglobin, CA₁₂₅, and follicle-stimulating hormone indexes between the two groups of patients before treatment and after 12 months of treatment

Group	n	HGB (g/L)		CA125 (U/mL)		FSH (mIU/mL)
		Before treatment	12 months after treatment	Before treatment	12 months after treatment	Before treatment	12 months after treatment
Experimental group	36	92.12±6.18	122.18±9.54*	116.56±88.13	38.72±12.11*	15.32±2.32	17.85±2.32†
Control group	67	87.38±5.86	106.27±7.83*	135.38±91.39	63.18±24.67*	14.38±3.57	16.68±3.58†
t	-	0.267	10.018	1.667	3.324	0.261	7.557
P	-	0.411	<0.001	0.037	<0.001	0.654	0.185

*Comparison with this group before treatment P<0.05, ^†Comparison with this group before treatment P>0.05. FSH: Follicle-stimulating hormone, HGB: Hemoglobin

No statistically significant differences were observed in postoperative fever rates or pain duration between the two groups (P > 0.05). However, the experimental group experienced significantly longer hospitalization and vaginal drainage times compared to the control group (P < 0.05), as detailed in Table 5. Importantly, no serious complications were reported in either group.

Table 5.

Comparison of the treatment of patients in the two groups

Group	n	Hospitalization time (days)	Postoperative fever, n (%)	Pain duration (days)	Vaginal drainage time (days)
Experimental group	36	5.18±0.88	1 (3.22)	2.45±0.70	18.66±5.37
Control group	67	3.43±2.37	2 (3.13)	1.77±0.43	9.35±4.84
t	-	2.036	3.029	0.228	9.344
P	-	0.000	0.026	0.604	0.000

DISCUSSION

Adenomyosis is a multifaceted condition necessitating a chronic disease management approach, characterized by personalized treatment and sustained management strategies. Clinical interventions encompass pharmacological therapy, surgical procedures, and interventional techniques, among others. The efficacy of nonsurgical treatments varies among individuals, and the protracted nature of the disease frequently imposes significant psychological distress on patients, adversely impacting their daily lives and occupational functioning.[16] Consequently, some patients opt for hysterectomy, which can result in both physical and psychological trauma. Thus, the development of an integrated treatment regimen that amalgamates various modalities holds substantial clinical research potential.

AUB associated with adenomyosis is prevalent and is characterized by excessive menstrual flow and extended menstrual periods, often resulting in anemia and significantly impacting patient health. The etiology is primarily attributed to increased uterine size, expanded endometrial area, and enhanced vascularization of the endometrial basal layer.[17] Pharmacological interventions, such as GnRH agonists, pose risks of recurrence upon discontinuation, induce bone loss, and do not effectively resolve the underlying lesion. Similarly, the levonorgestrel-releasing intrauterine system is associated with a high expulsion rate and potential for gonorrhoea,[18] prompting some patients to opt for hysterectomy. Studies have demonstrated that TBEA for AUB offers advantages such as ease of operation and minimal complications, facilitating rapid improvement in anemia and reducing the need for blood transfusions.[19] However, its efficacy is confined to the basal layer of the endometrium, and it does not ablate deep myometrial foci or the abnormally proliferated blood vessels and nerves, resulting in limited improvement in dysmenorrhea symptoms. Shadha Nasser’s research demonstrated that the progressive reduction in menstrual flow observed in patients with AUB associated with adenomyosis (AUB-A) treated with focused ultrasound ablation surgery (FUAS) was correlated with a decrease in uterine volume following the ablation of adenomyotic lesions.[20] Consistent with our findings, a recent systematic review and meta-analysis confirmed that ultrasound-guided high-intensity focused ultrasound (HIFU) significantly reduces uterine volume and alleviates dysmenorrhea in patients with adenomyosis, with a relatively low incidence of severe adverse events.[21] Based on the follow-up of over 1000 cases of adenomyosis treated at our institution, patients experienced significant alleviation of dysmenorrhea symptoms. However, the long-term effectiveness in improving menstrual flow was limited, necessitating the continued use of adjunctive pharmacological therapies.

Secondary progressive dysmenorrhea is a prevalent symptom associated with adenomyosis, significantly impacting patients’ quality of life, with an incidence rate ranging from 30% to 40%. This condition is typically attributed to a combination of factors, such as increased uterine volume, which leads to impaired uterine contraction and inefficient menstrual blood discharge.[22] In addition, ectopic endometrial tissue secretes elevated levels of prostaglandins and other nociceptive substances, contributing to the onset of dysmenorrhea.[23] While pharmacological interventions are frequently employed to alleviate dysmenorrhea, their effectiveness varies considerably, and symptoms often recur upon cessation of treatment. Consequently, surgical interventions aimed at reducing uterine volume and ablation of adenomyotic lesions are considered more effective in ameliorating dysmenorrhea in affected patients.[7] Baraa demonstrated that TBEA alone was ineffective in alleviating dysmenorrhea.[9]

The synergistic mechanism of combined FUAS and TBEA lies in addressing both the myometrial and endometrial components of adenomyosis. FUAS targets the deep myometrial lesions, reducing uterine volume and ablating abnormal vasculature and nerves within the adenomyotic foci, which contributes to pain relief and potentially reduces bleeding from deep lesions. TBEA, on the other hand, directly ablates the superficial endometrial lining responsible for heavy menstrual flow. This dual approach ensures a more comprehensive treatment: FUAS manages the underlying adenomyotic disease burden and pain generator, while TBEA provides immediate and effective control of menorrhagia by removing the endometrium. This explains the observed superior outcomes in reducing PBAC scores and improving anemia in the combined therapy group compared to FUAS alone.

In this study, the VAS scores for patients in both cohorts demonstrated a significant reduction at 12 months post-treatment compared to baseline, with a marked improvement in dysmenorrhea (P < 0.05). Nonetheless, there was no statistically significant difference in VAS scores between the two groups following treatment (P > 0.05), suggesting that the combined TBEA treatment did not confer a significant advantage in alleviating dysmenorrhea. This outcome may be attributed to the low correlation between normal endometrial conditions and the occurrence of dysmenorrhea.

Guorui identified a potential risk of endometrial damage and uterine cavity adhesion associated with the FUAS treatment of adenomyosis.[24] In the present study, a uterine color Doppler examination conducted on the FUAS-only group 12 months posttreatment revealed no significant change in endometrial thickness (P > 0.05), and no instances of uterine cavity adhesion were observed (0%). These findings suggest that, when administered with controlled energy and standardized procedures, FUAS may prevent endometrial damage; however, further evaluation using multiple indicators is necessary. In addition, there was no statistically significant change in FSH levels 12 months after treatment in either group (P > 0.05), indicating that both treatment modalities did not significantly impact ovarian function. This aligns with emerging evidence suggesting that FUAS is a fertility-sparing option. A recent study comparing HIFU with laparoscopic excision indicated that HIFU might offer superior outcomes regarding spontaneous pregnancy rates and delivery outcomes for women with fertility desires.[25] Blood CA₁₂₅, as a non-specific marker for adenomyosis, holds clinical significance for both disease diagnosis and efficacy evaluation.[26] In this study, the CA₁₂₅ levels, uterine volume, and adenomyoma blood flow grading scores in both patient groups showed significant reductions 12 months posttreatment, with statistical significance (P < 0.05). These findings suggest that FUAS is effective in decreasing the blood supply to adenomyosis and reducing uterine volume. Notably, the reduction in CA₁₂₅ levels was more pronounced in the experimental group (P < 0.05), indicating a superior effect on the management of adenomyosis. However, the underlying mechanism remains unclear and warrants further investigation.

In this study, a comparison of hospitalization duration and vaginal discharge time between the two patient groups revealed that the experimental group experienced a statistically significant longer duration than the control group (P < 0.05). This extended hospitalization period, which was prolonged by 1–2 days in the experimental group, was attributed to the necessity for split treatment and was deemed acceptable by the patients. In the experimental group, treatment combined with TBEA resulted in the discharge of necrotic endometrial tissue through the natural uterine lumen, presenting as a slight reddish-brown secretion lasting 17–28 days. This discharge typically did not require special intervention and resolved naturally, although some patients experienced improvement with hemostatic medication. There was no statistically significant difference in the incidence of postoperative fever or the duration of pain between the two groups (P > 0.05), and no serious complications were observed during follow-up.

This study has several limitations. First, it is a single-center study with a relatively small sample size, which may affect the generalizability of the results. Second, the maximum follow-up duration was 12 months, lacking long-term efficacy data. Third, the study primarily focused on symptomatic improvement and safety, without assessing potential impacts on fertility. Future multicenter studies with larger sample sizes and longer follow-up periods are needed to further validate the long-term outcomes of this combined therapy and its effects on reproductive function.

CONCLUSION

The integration of FUAS with TBEA in the management of adenomyosis demonstrates superior efficacy in diminishing menstrual flow, alleviating dysmenorrhea, reducing uterine volume, and restoring HGB levels without compromising ovarian function. This approach is characterized by enhanced safety, minimal complications, and satisfactory outcomes achievable within a single hospitalization. Consequently, it represents a comprehensive treatment strategy conducive to uterine preservation, symptom relief, quality of life improvement, and reduction in recurrence rates.

Author contributions

Conceptualization, Ren Yingqiang and Pu Yuanfang.; Methodology, Hu Zhonglian.; Software, Yin Li.; Validation, Ren Yingqiang and Pu Yuanfang.; Formal Analysis, Wang Jinwei.; Investigation, Ren Yingqiang; Resources, Gao Jun.; Data Curation, Chen Jinyun.; Writing – Original Draft Preparation, Ren Yingqiang.; Writing – Review and Editing, Ren Yingqiang and Pu Yuanfang.; Visualization, Li Yuan and Gao Jun.; Supervision, Hu Zhonglian.; Project Administration, Pu Yuanfang.; Funding Acquisition, Pu Yuanfang. All authors have read and agreed to the final version of the manuscript.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

This work was supported by the Open Project of the National Key Laboratory of Ultrasound Engineering in Medicine, Chongqing Science and Technology Bureau (Grant No. 2022KFKT016).