The clinical efficacy and influencing factors of uterine artery embolization in the treatment of different types of uterine adenomyosis

On conventional MRI images, adenomyosis of uterus was significantly enhanced on sagittal enhanced T1WI, and diffused low signal to myometria on sagittal T2WI, with scattered dot high signal, showing “drifting snow sign”. No enhancement was observed in the patient’s lesion area after treatment (Figs. 1 and 2 ). Fig. 1 Representative MRI images of focal adenomyosis before and after UAE treatment. Case 1 (A,B,E,F): ( A ) Pretreatment sagittal T2WI; ( B ) Pretreatment contrast-enhanced sagittal T1WI showing lesion enhancement; ( E ) Sagittal T2WI at 3-month follow-up; ( F ) Contrast-enhanced sagittal T1WI at 3-month follow-up demonstrating complete necrosis without enhancement. Case 2 (C,D,G,H): ( C ) Pretreatment sagittal T2WI; ( D ) Pretreatment contrast-enhanced sagittal T1WI; ( G ) Sagittal T2WI at 5-month follow-up; ( H ) Contrast-enhanced sagittal T1WI at 5-month follow-up showing reduced lesion size with persistent enhancement and no obvious necrosis. Representative MRI images of focal adenomyosis before and after UAE treatment. Case 1 (A,B,E,F): ( A ) Pretreatment sagittal T2WI; ( B ) Pretreatment contrast-enhanced sagittal T1WI showing lesion enhancement; ( E ) Sagittal T2WI at 3-month follow-up; ( F ) Contrast-enhanced sagittal T1WI at 3-month follow-up demonstrating complete necrosis without enhancement. Case 2 (C,D,G,H): ( C ) Pretreatment sagittal T2WI; ( D ) Pretreatment contrast-enhanced sagittal T1WI; ( G ) Sagittal T2WI at 5-month follow-up; ( H ) Contrast-enhanced sagittal T1WI at 5-month follow-up showing reduced lesion size with persistent enhancement and no obvious necrosis. Fig. 2 Representative MRI images of diffuse adenomyosis before and after UAE treatment. Case 1 (A,B,E,F): ( A ) Pretreatment sagittal T2WI; ( B ) Pretreatment contrast-enhanced sagittal T1WI showing lesion enhancement; ( E ) Sagittal T2WI at 3-month follow-up; ( F ) Contrast-enhanced sagittal T1WI at 3-month follow-up showing necrosis without enhancement in anterior wall lesions while posterior wall lesions remain enhanced. Case 2 (C,D,G,H): ( C ) Pretreatment sagittal T2WI; ( D ) Pretreatment contrast-enhanced sagittal T1WI; ( G ) Sagittal T2WI at 4-month follow-up; ( H ) Contrast-enhanced sagittal T1WI at 4-month follow-up showing significant uterine volume reduction and diffuse lesion complete necrosis without enhancement. Representative MRI images of diffuse adenomyosis before and after UAE treatment. Case 1 (A,B,E,F): ( A ) Pretreatment sagittal T2WI; ( B ) Pretreatment contrast-enhanced sagittal T1WI showing lesion enhancement; ( E ) Sagittal T2WI at 3-month follow-up; ( F ) Contrast-enhanced sagittal T1WI at 3-month follow-up showing necrosis without enhancement in anterior wall lesions while posterior wall lesions remain enhanced. Case 2 (C,D,G,H): ( C ) Pretreatment sagittal T2WI; ( D ) Pretreatment contrast-enhanced sagittal T1WI; ( G ) Sagittal T2WI at 4-month follow-up; ( H ) Contrast-enhanced sagittal T1WI at 4-month follow-up showing significant uterine volume reduction and diffuse lesion complete necrosis without enhancement. Before operation, there was no statistical significance in Hb level between the two groups ( P  > 0.05), indicating comparability (Fig. 3 A). Before operation, the CA125 level in group B was significantly higher than that in group A, the difference was statistically significant ( P  < 0.05). 2d after operation, CA125 levels in both groups were lower than before treatment, with statistical significance ( P  < 0.05) (Fig. 3 B). Fig. 3 Preoperative Hb level and postoperative CA125 level of patients in the two groups. ( A ) Comparison of preoperative Hb levels between the two groups; ( B ) Comparison of CA125 levels before and after treatment in both groups. ****P<0.0001 indicates significant difference between groups A and B at baseline; #P<0.05, ###P<0.001 indicate significant differences compared with pretreatment values within the same group. Preoperative Hb level and postoperative CA125 level of patients in the two groups. ( A ) Comparison of preoperative Hb levels between the two groups; ( B ) Comparison of CA125 levels before and after treatment in both groups. ****P<0.0001 indicates significant difference between groups A and B at baseline; #P<0.05, ###P<0.001 indicate significant differences compared with pretreatment values within the same group. Before interventional treatment, there was no significant difference between the two groups in percentage of symptoms and percentage of health ( P  > 0.05). After 3 months of interventional treatment, the two groups of patients were compared with those before interventional treatment, and the symptoms were significantly reduced and the health status was greatly improved, with statistical significance ( P  < 0.05) (Fig. 4 A, B). Fig. 4 Comparison of UFS-QOL scores before and after treatment between the two groups. ( A ) Comparison of symptom percentage results between the two groups before and 3 months after interventional therapy; ( B ) Comparison of health percentage results before and 3 months after interventional therapy between the two groups. Compared with the group before treatment, ## P  < 0.01, ### P  < 0.001. Comparison of UFS-QOL scores before and after treatment between the two groups. ( A ) Comparison of symptom percentage results between the two groups before and 3 months after interventional therapy; ( B ) Comparison of health percentage results before and 3 months after interventional therapy between the two groups. Compared with the group before treatment, ## P  < 0.01, ### P   0.05). The VAS pain score of the two groups was significantly reduced 3 months after interventional treatment, and the above difference was statistically significant ( P  < 0.05) (Fig. 5 ). Fig. 5 Comparison of VAS pain scores before and 3 months after interventional therapy between the two groups. Compared with before treatment, #### P  < 0.0001. Comparison of VAS pain scores before and 3 months after interventional therapy between the two groups. Compared with before treatment, #### P  < 0.0001.

The methods used in this retrospective research were carried out according to the guidelines as per the latest revision of the Declaration of Helsinki (2013). The protocols have been approved by the Ethics Committee of Guangdong Second Provincial General Hospital(2024-KY-KZ-062-02). Due to the retrospective nature of the study, the Ethics Committee of Guangdong Second Provincial General Hospital waived the need of obtaining informed consent. 666 patients with adenomyosis who underwent uterine artery embolization in our hospital from May 2017 to September 2023 were retrospectively analyzed. In the end, 382 patients were enrolled based on the inclusion and exclusion criteria. Inclusion criteria are given as (a) typical clinical symptoms (prolonged menstruation, pain, organ compression symptoms including frequent urination, constipation and abdominal distension, and increased menstrual volume), (b) uterine volume of ≥ 56 cm3 28 (c) at-least two diagnostic criteria for adenomyosis 29 , (d) desire for uterine preservation without future fertility requirements. The exclusion criteria include (a) pregnancy or lactation, (b)gynecological malignancy, (c) severe coagulation or immune disorders, (d)severe cardiac, hepatic, or renal insufficiency, (e) patient didn’t follow up postoperative 22 . According to MRI, there were 202 cases of focal type (group A) and 180 cases of diffuse type (group B). Patients in group A ranged in age from 27 to 50 years, with an average age of (40.16 ± 4.64) years, 0–12 pregnancies, an average number of pregnancies (2.97 ± 1.75), 0–5 deliveries, an average number of deliveries (1.49 ± 0.82), and an average duration of dysmenorrhea (5.69 ± 5.32) years. The average degree of dysmenorrhea was (8.08 ± 2.33) points, and the average duration of menorrhagia was (2.94 ± 3.80) years. Patients in group B ranged in age from 28 to 55 years, with an average age of (41.53 ± 5.09) years, 0–10 pregnancies, an average number of pregnancies (3.13 ± 1.91), 0–5 deliveries, an average number of deliveries (1.35 ± 0.91), and an average duration of dysmenorrhea (5.22 ± 4.35) years. The average degree of dysmenorrhea was 8.36 ± 2.40 points, and the average duration of menorrhagia was 3.29 ± 3.72 years. In group A, 74 patients had adenomyosis with uterine myoma; In group B, 53 patients had adenomyosis with uterine myoma. The general data and clinical baseline characteristics of the two groups were shown in Table 1 , and there was no significant difference between the two groups ( P  > 0.05). These patients were included, who had typical clinical symptoms: prolonged menstrual period, pain, pressure on surrounding organs secondary to frequent urination, constipation and abdominal distension, and increased menstrual volume, those who were diagnosed with adenomyosis by clinical and MRI examination, those who have no childbearing requirements but require the preservation of their uterus, those without contraindications for interventional therapy; and those who had complete imaging and clinical data. The following patients were excluded, the pregnant and lactating women, those who were complicated with gynecological malignancy, those who had severe coagulation and immune function disorders, those who had severe heart, liver and renal insufficiency and those are allergic to contrast media and cannot tolerate interventional procedure. Table 1 Comparison of general data between the two groups. Group A( n  = 202) Group B( n  = 180) P Age 40.16 ± 4.64 41.53 ± 5.09 0.2057 Number of Pregnancies 2.97 ± 1.75 3.13 ± 1.91 0.2117 Number of deliveries 1.49 ± 0.82 1.35 ± 0.91 0.1606 duration of dysmenorrhea 5.69 ± 5.32 5.22 ± 4.35 0.8014 degree of dysmenorrhea 8.08 ± 2.33 8.36 ± 2.40 0.7756 duration of menorrhagia 2.94 ± 3.80 3.29 ± 3.72 0.8007 Combined with fibroids 74 53 0.1365 Comparison of general data between the two groups. Patients had the preoperative preparation. They were given routine preoperative examination and asked to fill in the quantitative evaluation form for dysmenorrhea, assess the level of menstrual volume. The patients would receive a procedure 3 ~ 15d before and after their period time. UAE was carried out as follow. The patient was placed in a supine position and the catheter was inserted. The modified Seldinger method was given 2% lidocaine under local anesthesia to puncture the left/right femoral artery or the left radial artery/distal radial artery and 5 F-size catheter sheath was placed. The 5 F-size Cobra catheter or MPA1 multifunctional catheter was selectively inserted into the left internal iliac artery under fluoroscopy. The tortuously thickened uterine artery is seen in the angiography, and then the micro-catheter is inserted into the distal end of the uterine artery, and Embosphere of 100–300 μm, 300–500 μm, 500–700 μm and other embolic particles are sequentially injected into the large diameter particles from small to large diameter particles with an appropriate amount of contrast agent (Ioversol Injection,Hengrui). After embolization was completed, the contralateral operation was repeated, and angiography was selected until the bilateral uterine artery was completely occlusive at the distal end. After UAE, the catheter was removed and the puncture point of the femoral artery/radial artery/distal radial artery was compressed with pressure. After the operation, patients would receive pressure dressing, braking for 12 h. They took bed rest for 6 h, during which continuous ECG monitoring was given. Meanwhile, they were given symptomatic treatment such as PCA pain-relieving pump and fluid rehydration. Enhanced MRI was the main method for UAE preoperative and postoperative follow-up uterine examination, and the recurrence and therapeutic effect of patients were observed specifically through T1WI and T2WI sequences. Hemoglobin (Hb) value and serum CA125 value were determined. Hb value was measured before treatment, and serum CA125 value was measured before treatment and 2d after treatment. Patients filled out the Uterine fibroid Symptom and Quality of Life Questionnaire (UFS-QOL) and visual analogue scale (VAS) sent through wechat preoperation and postoperation. Pain was assessed by visual analogue Scale (VAS), and the pain score was divided into three levels: mild: 1 ~ 3 points; Moderate: 4 ~ 6 points; Heavy: 7 ~ 10 points. Menstruation related conditions was obtained. The degree of dysmenorrhea was determined based on VAS (0 ~ 10 points). 0 points means no pain; less than 3 points means slight pain which can tolerate, 4 to 6 points mean pain which affect sleep, 7–10 points mean gradually increased and unbearable pain which seriously affect appetite and sleep. Pictorial blood loss assessment chart (PBAC) was used to compare menstrual volume, and the number of fully soaked pads of the same sanitary napkin was used. During the observation period, patients should use unified sanitary napkin. excessive menstruation was determined with menstrual volume > 80mL per menstrual cycle, that is, more than 20 sanitary napkins used in a menstrual cycle. The patient was treated with our hospital’s Philips Ingenia3.0T nuclear magnetic resonance instrument (Philips Health Tech, Netherland) and phased array surface coil before and after operation. Scanning sequence: Fast spin echo sequence (TSE) T1WI sagittal position and axial position: TR 530 ms, TE 10 ms, layer thickness 5 mm, layer spacing 1 mm, matrix 300 × 236, 268 × 204. TSE T2WI axis: TR 3000 ms, TE 70 ms, layer thickness 4 mm, layer spacing 1 mm, matrix 300 × 236. MRI enhanced scanning uses a 3D-THRIVE dynamic enhanced scan sequence. The contrast medium was meglumine gadopenate injection, which was injected 12 mL at a rate of 2 mL/s. SPSS20.0 software was used for statistical analysis of data. Continuous variables were represented by mean ± standard deviation and analyzed by Studentt test or Mann-WhitneyU test. The categorical variables were expressed in terms of frequency and percentage, and analyzed using the χ2 test and Fisher precision test.

UAE, as a minimally invasive treatment, has the greatest advantage of strong repeatability and is an important alternative treatment for adenomyosis. Previous studies have confirmed its safety and efficacy, and it has similar efficacy and fewer adverse reactions than surgical resection. The results of this study indicate that UAE is effective in treating uterine adenomyosis, which is consistent with previous studies. Moreover, the % reduction of the values of CA125 levels and UAE therapeutic effect after treatment in each groups in comparison to before treatment was statistically insignificant and revealing UAE effectiveness in both the conditions.

Adenomyosis is a common gynecological hormone-dependent disease. Although adenomyosis is a benign lesion, it is known as “chronic cancer” and has a great impact on patients’ quality of life and psychological state 30 . The disease is a diffuse or focal hyperplasia of the surrounding smooth muscle and fibrous connective tissue caused by the invasion of the basal layer of the endometrium by glands and interstitium into the muscular layer. The lesion has a relatively rich neovascular network and poor tolerance to ischemia and hypoxia 31 . The treatment of adenomyosis of uterus has always been a difficult clinical problem due to its easy recurrence and difficult to cure 32 . At present, the treatment methods are mainly divided into medical drug therapy, surgical therapy and interventional therapy 33 . Although the drug treatment is effective and can preserve the fertility function, it is prone to serious adverse reactions 34 . Surgical treatment has a definite effect on abnormal bleeding and can significantly alleviate dysmenorrhea symptoms. In clinical practice, hysterectomy is the most commonly used surgical treatment for adenomyosis, but the operation has great physical and mental damage to patients and the opportunity of repregnancy is lost 35 . In recent years, with the development of interventional technology and the proposal of precise treatment model for diseases, UAE has been applied more and more widely in clinic 36 . The theoretical basis for UAE treatment of uterine adenomyosis is that normal uterine myometrium is different from adenomyosis lesions and has a strong tolerance to ischemia and hypoxia. Through bilateral uterine arterial blood network embolization, the blood supply of the lesions is blocked, resulting in ischemic necrosis of the lesions, and then dissolved and absorbed, thus reducing the size of the uterus and the lesions safely and effectively and reducing menstrual volume. Alleviate or cure patients’ pain, promote or improve patients’ fertility treatment infertility, reduce or eliminate recurrence to achieve therapeutic effect 37 , 38 . UAE may cause mild necrosis of the normal endometrial functional layer, but after vascular revascularization or the establishment of collateral circulation, the basal layer can gradually transition and grow back to normal function, which is suitable for patients with the desire to preserve the uterus 39 . Preoperative MRI can facilitate the classification of adenomyosis and a fine understanding of the distribution of adenomyosis lesions and the degree of disease, so as to facilitate differential management 40 . Therefore, this study classifies the disease types of patients by MRI, aiming to explore the clinical efficacy and influencing factors of UAE in the treatment of different types of uterine adenomyosis. CA125 is a tumor-associated carbohydrate antigen secreted by coelomic epithelial cells 41 . Previous studies have shown that CA125 concentration is closely related to endometrial development, and CA125 secretion increases in patients with adenomyosis 42 . Therefore, this study evaluated the effectiveness of UAE therapy by detecting serum CA125 levels in two groups of patients. The results of this study showed that before UAE, CA125 level in patients in group B was significantly higher than that in patients in group A, and 2d after UAE, CA125 level in patients in both groups was lower than that before treatment, indicating that the serum CA125 level of patients may be related to the type of adenomyosis. However, UAE has good therapeutic effect on both localized and diffuse adenomyosis. In the comparison of symptom percentage results, health percentage results and VAS pain score, symptoms were significantly reduced, health status was significantly improved and VAS pain score was significantly decreased in both groups 3 months after intervention compared with before intervention. The results showed that UAE could significantly improve the clinical symptoms of patients with adenomyosis. Bilateral uterine artery embolization was performed in both groups. Although the UAE has been reported to have acute (pain, postembolisation syndrome, sepsis, bleeding etc.) and subacute or chronic complications (Transient or permanent amenorrhoea, pain, endometritis and etc.) 43 but no acute serious complications occurred during the operation, and the technical success rate reached 100%. Since it is a retrospective study, hence almost all its limitation can be attributed to this study also, be it Biasness (more likely to be affected by bias and confounding variables), Selection bias (the controls being not a representative complete population), Recall bias, missed data, incomplete design to conclude cause and effect, reproducibility is not expected, lower evidence level than prospective studies and so forth 44 . Other limitations of this study include the inability to follow-up for long term outcomes and further analysis of re-intervention rate. The study has not included immediate operation parameters like amount of bleeding, recovery time after operation etc.

As a common benign gynecological disease, uterine adenomyosis has a high incidence in different co-morbidities. For example, in a study ~ 42% of patients undergone hysterectomy, ~ 23% postmenopausal patients, ~ 59% in patient with bleeding disorders & dysmenorrhea and 6.0% in uterine rupture situation during surgical treatment reported to have the uterine adenomyosis 1 , 2 . Its mainly affecting women aged 30–50 years old 3 . The main pathogenesis of adenomyosis is that the endometrial glands and interstitium enter the myometrium. This entry is stimulated by estrogen which causes the proliferation of peripheral myometrium cells, uterine enlargement and aggravated dysmenorrhea 4 , 5 . Although the final confirmation of adenomyosis can be confirmed with histopatological examination which is only be possible after hysterectomy. Hence the adenomyosis can be confirmed as incidence retrospectively and cannot be diagnostic confirmation during complaints 6 . Morphological Uterus Sonographic Assessment (MUSA) guidelines on understanding the ultrasound images to conclude the severity has been has been gaining wide acceptance 7 . With the wider application of imaging means such as ultrasound & magnetic resonance examination, followed by its interpretation with MUSA, more and more young women have been found to possibly be suffered from adenomyosis. In recent years, the incidence of adenomyosis has been increasing year by year, and it has a tendency to occur to younger people 8 , 9 . As adenomyosis is a benign disease, conservative treatment and surgical treatment are commonly used in clinical practice 10 . There are non-surgical palliative treatments for the cases when the patients want to retain the fertility. These mainly include the hormonal treatments e.g. combined oral contraceptive pills, progestins, the levonorgestrel-releasing intrauterine system, and gonadotropin-releasing hormone (GnRH) agonists and antagonists and danazol 11 . The limitation of the hormonal therapy is the side effects like mood instability, genital atrophy, and vasomotor syndrome, breast discomfort with long term treatment and not being curative 12 . While the conservative surgery has also shown the high rate of recurrence i.e. 39% 13 , 14 . According to the physical conditions of different patients, surgical treatment is proposed, but surgical resection of the lesion generally causes great trauma to the patient’s body, and a better treatment plan should be selected According to the physical conditions of different patients, conservative surgery has been recommended and practices. Since, adenomyotic lesion doesn’t have a clear boundary from the normal myometrium, and there are many small vessels in the lesion that can cause bleeding, thus this surgical practice may lead to the uterine rupture during pregnancy 15 , 16 . With the extensive application of interventional medicine in clinical practice, a new treatment scheme, uterine artery embolization (UAE), has been provided for patients with adenomyosis 17 . UAE means that under the guidance of medical imaging equipment, by embolizing the uterus and focal blood supply, the ectopic endometrium is in a state of hypoxia and ischemia, resulting in acute necrosis, necrosis dissolution and absorption of proliferative cells and connective tissue, so as to achieve the purpose of treatment and relieve or disappear of clinical symptoms 18 . With the popularity of UAE in the treatment of uterine adenomyosis, it has the advantages of less trauma, rapid recovery, uterine preservation, etc., and has achieved good results in reducing uterine volume, adjusting menstrual volume and relieving dysmenorrhea 19 . At present, gelatin sponge particles, polyvinyl alcohol (PVA), Embosphere and other particles embolization was adopted for embolization. And embolization strategy also includes 300 ~ 500 μm, 500 ~ 700 μm granule equal diameter embolization, there are also 300 ~ 500 μm, 500 ~ 700 μm, 700 ~ 900 μm granule, embosphere, etc. Sequential embolization from small to large diameter particles 20 , 21 . UAE has already been proven to be the sparing treatment option for the failed conservative treatments for the management for adenomyosis. In this study no other treatment was taken as control as a treatment standard for comparison. While a protocol has been found in the literature for the comparison of effectiveness of two intervention for the indication of adenomyosis but no result has been given in this study to find the difference of procedure effectiveness 22 . In a prospective clinical trial study on 64 eligible patients, the two interventions were compared i.e. UAE and hysterectomy. The outcome revealed the higher % with respect to number of complications in UAE however the % of major complications were observed higher in case of hysterectomy. The spent mean days of hospital stay was 1.71 ± 1.59 days for UAE while the hysterectomy group patent’s stay was 5.28 ± 2.52 days with significant difference of 4.14 days ( p < 0.001). None of patients for the UAE group were required to give hysterectomy surgery in this study which would be expected due to UAE related complications. In nutshell this prospective clinical trial study expressed the UAE as better opportunity for the treatment of adenomyosis in comparison to conservative treatment (hysterectomy more specifically) 23 . Imaging diagnosis is an important part of the comprehensive diagnosis of adenomyosis and plays an indispensable role in the diagnosis and differential diagnosis, outlining the scope of the lesion, assisting in pre-treatment planning, and evaluating the therapeutic effect 24 . Imaging methods for adenomyosis mainly include transvaginal ultrasound, pelvic MRI, CT, hysterosalpingography, etc 14 . With better understanding of adenomyosis and the need for morphological classification, MRI has become the most valuable imaging diagnostic method for adenomyosis 25 . MRI has advantages such as high soft tissue resolution, clear and intuitive image, multi-parameter and multi-plane imaging, no operator dependence, no radiation, good repeatability, and no complications, etc., and has been increasingly applied in the diagnosis and classification of uterine adenomyosis and continuous monitoring after drug treatment 26 , 27 . Focal adenomyosis is pathological state when endometrial tissue observed as distinct and isolated nodules within the myometrial layer of uterine wall while in case of diffused type the earlier is found spread throughout in the later. Since the pathophysiology of two types of adenomyosis is different thus the distinctive effect of UAE on two types is missing in the literature. By reviewing the imaging and clinical data of UAE patients with uterine adenomyosis in our hospital, this study aims to explore the clinical efficacy and influencing factors of uterine artery embolization in the treatment of different types of uterine adenomyosis (diffusion vs. focal type more specifically) of uterine adenomyosis, and also provide more basis and guidance for the clinical treatment of uterine adenomyosis in hospitals.