Preliminary clinical observation on the treatment of adenomyosis by partial embolization of uterine artery with novel material combination: a case series

The patient is a 33-year-old woman who presented with heavy vaginal bleeding during menstruation and severe abdominal pain. These symptoms persisted for half a year, leading to anemia, dizziness, and sallow complexion. CDUS examination at another hospital suggested adenomyosis. The patient underwent diagnostic curettage, and the pathological results indicated that most of the submitted specimens were endometrium with menstrual cyclic changes. The patient received treatment with leuprorelin acetate sustained-release microspheres, and experienced amenorrhea for 3 months. During this period, she also underwent the insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS). However, when menstruation resumed during the 4th month, the patient still had abdominal pain, with heavy menstrual flow accompanied by numerous blood clots. Worse still, the LNG-IUS was dislodged due to the flushing of heavy menstrual flow. Doctors from another hospital recommended hysterectomy, but the patient refused. CDUS and MRI indicated adenomyosis and uterine adenomyoma (with the maximum cross-sectional area of 59 mm × 50 mm). CBC indicated mild anemia: the RBC count was 3.61 × 10¹²/L (normal range: 3.8–5.1 × 10¹²/L), and the hemoglobin level was 93 g/L (normal range: 115–150 g/L), as shown in Supplementary Table 3. The patient received UAE treatment in October 2023. Menstruation occurred about 10 days after the operation; although the menstrual flow was still heavy, the dysmenorrhea was markedly relieved. Starting from the second menstrual period after the operation, the patient’s menstrual flow decreased dramatically. Three months after UAE, the patient’s menstrual period was shortened to 6–8 days, down from 8 to 9 days preoperatively (Supplementary Table 2). Currently, the patient’s menstrual function has basically returned to the normal state with a menstrual period of 5–6 days, and she is no longer anemic (as shown in Table  2 and Supplementary Table 3). The uterine volume is smaller than that before UAE, as shown in Fig.  3 and Supplementary Table 3. Table 2 Changes in relevant indicators of the patients before and after UAE Indicators Before or after UAE Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Days of menstruation (day) Before 8–9 7–20 10–13 10–15 7–8 7 After 5–6 7* 6–7 5–6 4 7 The number of SPs or PPs used per menstrual period Before 25–30 (SPs) 30 (SPs) 50–65 (SPs) 60–80 (SPs) 5 (PPs) 10 (PPs) After 10 (SPs) 7 (SPs) 30 (SPs) 20–25 (SPs) 5 (SPs) 7 (PPs) Abbreviations: SPs sanitary pads, PPs  period pants. *Note: Case 2 experienced amenorrhea 7 months after UAE. During the first 7 months after UAE, the patient’s menstrual period lasted 7 days. The time points at which the follow-up data in this Table were obtained are shown in Supplementary Table 1 Changes in relevant indicators of the patients before and after UAE Abbreviations: SPs sanitary pads, PPs  period pants. *Note: Case 2 experienced amenorrhea 7 months after UAE. During the first 7 months after UAE, the patient’s menstrual period lasted 7 days. The time points at which the follow-up data in this Table were obtained are shown in Supplementary Table 1 A 50-year-old woman experienced prolonged menstrual periods in 2018, with the longest duration lasting 20 days, and heavy menstrual flow. She had low blood pressure, accompanied by headaches, dizziness and chest tightness. In addition, she experienced abdominal pain, low back pain and anal tenesmus. CBC indicated anemia, and gynecological CDUS at another hospital showed adenomyosis and endometrial polyps. The patient was advised to undergo hysterectomy but refused surgery due to concerns about surgical risks. She only received hemostatic and iron-supplementing treatments. In 2021, the patient underwent hysteroscopic endometrial polypectomy. Postoperative pathological findings revealed endometrial polyps and proliferative endometrium. The symptoms had not improved postoperatively, but the patient refused further treatment. In February 2024, the patient could no longer endure the suffering caused by heavy menstrual flow, so she came to the Vascular Surgery Department of our hospital for consultation on treatment options. Both MRI and CDUS confirmed the diagnosis of adenomyosis. Eventually, the patient underwent UAE treatment. The patient had menstruation 1 month after the procedure, with a significant reduction in menstrual flow and the disappearance of abdominal pain. Three months after UAE, the number of sanitary pads used by the patient during menstruation decreased from the original 30 to 12–18, as shown in Supplementary Table 2. Her menstruation remained normal for 7 months, after which she developed amenorrhea. MRI indicated that the thickness of the posterior uterine wall had significantly decreased, as demonstrated in Fig.  3 . The patient is a 43-year-old female who presented to our clinic with heavy menstrual bleeding for 4 years. Her main symptoms include prolonged menstrual periods (lasting 10–13 days), increased menstrual flow with blood clots, occasional low back pain, and anal tenesmus. She was diagnosed with adenomyosis in another hospital. She received traditional Chinese medicine treatment 2 to 3 times a year and took ferrous sulfate tablets after each menstrual period, but her symptoms were not significantly relieved. MRI and CDUS revealed adenomyosis and adenomyoma (with the maximum cross-sectional area of 46 mm × 31 mm). CBC indicated moderate anemia: the RBC count was 3.41 × 10¹²/L, and the hemoglobin level was 78 g/L. After the UAE procedure, the patient’s menstrual period was shortened to 6–7 days, and menstrual flow was markedly reduced. The number of sanitary pads used during menstruation decreased from previously 50–65 to 30, as shown in Table  2 . In addition, the degree of anemia improved significantly: the RBC count increased to 3.72 × 10¹²/L, and the hemoglobin level increased to 98 g/L, as shown in Supplementary Table 3. MRI indicated a certain degree of reduction in uterine volume, as shown in Fig.  3 and Supplementary Table 3. Two days after the UAE procedure, the patient experienced increased vaginal discharge. No treatment was administered, and this condition gradually resolved after 8 days. The patient is a 37-year-old woman. Due to prolonged menstrual bleeding (menstrual period lasting 10–15 days), she underwent a CDUS examination in another hospital, which indicated adenomyosis. The patient received uterine curettage and was implanted with an LNG-IUS. Then, the symptom of irregular vaginal bleeding was relieved. However, one and a half months after the operation, the patient experienced irregular vaginal bleeding again, with a relatively large amount of blood and blood clots. She also had abdominal pain along with low back pain. MRI and CDUS showed adenomyosis and adenomyoma. The hemoglobin level was slightly low (113 g/L), but the RBC count was normal (4.04 × 10¹²/L). Three days after the UAE procedure, increased vaginal discharge occurred. No treatment was administered, and the condition gradually returned to normal after approximately 10 days. As the patient had no menstrual flow for more than 7 weeks after UAE, an abdominal CDUS examination was performed, and the result showed that the patient was pregnant. Based on the gestational sac, it was inferred that the patient had become pregnant within 1 week after receiving UAE treatment. She has since given birth to a healthy baby boy at full term. Up to now, the patient’s menstrual flow has dramatically decreased compared with before; her menstrual period is normal (5–6 days), as shown in Table  2 ; there is no dysmenorrhea; the hemoglobin level (127 g/L) and the RBC count (remaining at 4.04 × 10¹²/L) are normal, as demonstrated in Supplementary Table 3. The patient is a 36-year-old female with clinical manifestations including heavy menstrual flow with a large number of blood clots, accompanied by severe abdominal pain and low back pain. The menstrual period lasts about 7–8 days. These symptoms have persisted for 2 years. CDUS showed: the uterus is slightly enlarged with a full shape; the myometrial echo is inhomogeneous, slightly coarse and enhanced, with local mass-like changes; a 0.8 cm × 0.5 cm hypoechoic nodule is seen in the posterior uterine wall; uterine adenomyosis and fibroid are suspected. In February 2023, the patient underwent LNG-IUS insertion. Due to amenorrhea for 1 year after insertion, the patient received LNG-IUS removal. Subsequently, the patient had menstruation, but still with dysmenorrhea and heavy menstrual flow. Pre-UAE MRI shows that the patient’s uterus is full, the myometrium is slightly thickened, and there is a patchy hyperintense lesion on T2-weighted imaging (T2WI) in the uterine fundus, as illustrated in Fig.  3 . Combined with CDUS, MRI and clinical manifestations, the diagnosis of focal adenomyosis is confirmed. Three months after the patient received UAE, the menstrual period was shortened to 4 days (as shown in Table  2 or Supplementary Table 2), the menstrual flow was significantly reduced, and abdominal pain and low back pain were markedly relieved (The VAS score decreased from 9 preoperatively to 4, as shown in Supplementary Table 3). The patient developed moderate abdominal pain after UAE, and an analgesic drug was administered, as shown in Table  3 . Table 3 Adverse events after UAE and the corresponding treatments Patients Adverse events after UAE Treatment Case 1 None No treatment administered Case 2 Mild abdominal pain; amenorrhea No treatment administered Case 3 Mild abdominal pain; increased vaginal discharge No treatment administered Case 4 Mild abdominal pain; increased vaginal discharge No treatment administered Case 5 Moderate abdominal pain Bucinnazine hydrochloride injection Case 6 Moderate abdominal pain; nausea and vomiting Paracetamol and dihydrocodeine; ondansetron and metoclopramide Adverse events after UAE and the corresponding treatments The patient is a 44-year-old female with a 23-year history of adenomyosis. She was diagnosed with adenomyosis in 2001, presenting with heavy menstrual flow and severe dysmenorrhea. In 2007, she underwent resection of adenomyotic lesions, with postoperative relief of symptoms. In 2008, the symptoms of heavy menstrual flow and lower abdominal pain recurred, so she received placement of an LNG-IUS. However, the postoperative symptom relief was not significant. In 2012, she received 3 injections of gonadotropin-releasing hormone (GnRH) therapy, with poor efficacy. In 2013, the LNG-IUS was replaced, but the symptom relief remained unsatisfactory. In 2015, the LNG-IUS was removed due to its displacement. Since then, the patient continued to experience heavy menstrual flow and persistent severe dysmenorrhea (manifested as lower abdominal distension and pain, and low back pain), accompanied by anal tenesmus and occasional nausea. CDUS and MRI confirmed the diagnosis of adenomyosis, adenomyoma, and uterine fibroid. CBC indicated a hemoglobin level of 99 g/L, which was classified as mild anemia. In January 2024, the patient underwent partial embolization of the uterine artery with new embolic materials. One month after the procedure, she received GnRH injection therapy (2 injections) at a local hospital. After the above treatments, her symptoms of dysmenorrhea and heavy menstrual flow were pronouncedly alleviated. However, the patient experienced a recurrence of heavy menstrual flow and severe dysmenorrhea after June 2024. In July 2024, she underwent a second UAE with new embolic materials. Since then, the patient has experienced significant relief from dysmenorrhea, a marked reduction in menstrual flow, and improvement in anemia with a hemoglobin level of 107 g/L. One year after the second UAE, a follow-up MRI showed a significant reduction in uterine volume, as illustrated in Fig.  3 and Supplementary Table 3. After each UAE procedure, the patient’s VAS score for abdominal pain reached 5 points, and paracetamol and dihydrocodeine was administered for pain relief on each occasion, as shown in Table  3 . After the second UAE procedure, she developed nausea and vomiting, and was given ondansetron and metoclopramide for symptomatic treatment (Table  3 ). Fig. 3 The MRI images of all 6 patients before and after UAE (Sagittal T2-weighted images) The MRI images of all 6 patients before and after UAE (Sagittal T2-weighted images) We conducted statistical analysis on the following indicators before and after UAE in 6 patients: VAS score during menstruation, RBC count, hemoglobin level, SSS score, HRQOL score, JZmax, JZdiff, and uterine volume. The paired t-test results showed that there were statistically significant differences in the above indicators between the preoperative and postoperative levels, as shown in Fig.  4 . We also calculated the percentage change in uterine volume, and all patients had a reduction in uterine volume (Supplementary Table 3). The above data indicate that the UAE using new materials can significantly improve the clinical symptoms of patients. Fig. 4 Changes in patients’ relevant indicators: before versus after UAE. All indicators of the 6 patients showed statistically significant differences before and after UAE: VAS score ( A ), RBC count ( B ), hemoglobin level ( C ), SSS ( D ), HRQOL ( E ), JZmax ( F ), JZdiff ( G ), and uterine volume ( H ). Abbreviations: VAS = Visual Analogue Scale; RBC = red blood cell; JZmax = Maximal junctional zone thickness; JZmin = Minimal junctional zone thickness; JZdiff = Junctional zone differential; SSS = symptom severity score; HRQOL = health-related quality of life. A value of P  ≤ 0.05 indicates that the difference is statistically significant. The relevant data have been listed in Supplementary Table 3 Changes in patients’ relevant indicators: before versus after UAE. All indicators of the 6 patients showed statistically significant differences before and after UAE: VAS score ( A ), RBC count ( B ), hemoglobin level ( C ), SSS ( D ), HRQOL ( E ), JZmax ( F ), JZdiff ( G ), and uterine volume ( H ). Abbreviations: VAS = Visual Analogue Scale; RBC = red blood cell; JZmax = Maximal junctional zone thickness; JZmin = Minimal junctional zone thickness; JZdiff = Junctional zone differential; SSS = symptom severity score; HRQOL = health-related quality of life. A value of P  ≤ 0.05 indicates that the difference is statistically significant. The relevant data have been listed in Supplementary Table 3

The start and end dates of the recruitment period for this study are from June 1, 2023 to June 1, 2025. A total of 7 patients with adenomyosis underwent bilateral UAE in the Vascular Surgery Department of the Second Affiliated Hospital of Shandong First Medical University. However, 1 patient was lost to follow-up. Therefore, the remaining 6 patients were included as the research subjects, and their basic information is shown in Table  1 . These 6 patients were married and had children, with an average age of 40.5 years (ranging from 33 to 50 years). The follow-up time for these patients ranged from 3 to 21 months, as shown in Table  1 and Supplementary Table (1). Three months after UAE, we conducted a follow-up on menstruation-related indicators and menopause symptoms, as shown in Supplementary Table (2). All patients fully understood the benefits and adverse reactions of UAE and other treatment options. The patients agreed to use the embolic materials employed in this study after being informed of the risks and benefits, and all signed the written informed consent form. The study was approved by the Ethics Review Committee of the Second Affiliated Hospital of Shandong First Medical University (Approval number: 2023-072). Table 1 The basic information of the patients Patients Age (years) Preoperative main symptoms Reproductive history Diagnosis Previous treatment VAS score during postoperative hospitalization Follow-up duration time (months) Case 1 33 Heavy vaginal bleeding accompanied by numerous blood clots during menstruation; severe abdominal pain, dizziness, and sallow complexion. G3P3L3A0 Diffuse adenomyosis; adenomyoma; without concurrent endometriosis. Treatment with leuprorelin acetate sustained-release microspheres; LNG-IUS insertion. 0 21 Case 2 50 Prolonged menstrual periods, heavy menstrual flow, low blood pressure, headaches, dizziness, chest tightness, abdominal pain, low back pain and anal tenesmus. G2P2L2A0 Diffuse adenomyosis; without concurrent endometriosis. Hemostatic and iron-supplementing treatments; hysteroscopic endometrial polypectomy. 1 17 Case 3 43 Prolonged menstrual periods, increased menstrual flow with blood clots, occasional low back pain, and anal tenesmus. G2P2L2A0 Diffuse adenomyosis; adenomyoma; without concurrent endometriosis. Traditional Chinese medicine treatment; iron supplementation therapy. 1 18 Case 4 37 Prolonged menstrual bleeding, increased menstrual flow with blood clots; abdominal pain along with low back pain. G3P3L3A0 Diffuse adenomyosis; adenomyoma; without concurrent endometriosis. Uterine curettage; LNG-IUS insertion. 2 18 Case 5 36 Heavy menstrual flow with a large number of blood clots; severe abdominal pain and low back pain. G2P2L2A0 Focal adenomyosis; uterine fibroid; without concurrent endometriosis. LNG-IUS insertion. 5 3 Case 6 44 Heavy menstrual flow, severe dysmenorrhea (lower abdominal distension and pain, and low back pain), anal tenesmus, and occasional nausea. G1P1L1A0 Diffuse adenomyosis; adenomyoma; uterine fibroid; without concurrent endometriosis. Resection of adenomyotic lesions; LNG-IUS insertion; hormonal therapy (GnRH). 5 18 Abbreviations: G Gravidity, P Parity, L Living children, A Abortus, LNG-IUS levonorgestrel-releasing intrauterine system, GnRH gonadotropin-releasing hormone, VAS Visual Analogue Scale The basic information of the patients Diffuse adenomyosis; without concurrent endometriosis. Abbreviations: G Gravidity, P Parity, L Living children, A Abortus, LNG-IUS levonorgestrel-releasing intrauterine system, GnRH gonadotropin-releasing hormone, VAS Visual Analogue Scale We mainly collected the following data of patients before and after UAE: uterine volume; maximal junctional zone thickness (JZmax); minimal junctional zone thickness (JZmin); Uterine Fibroid Symptom and Quality of Life (UFS-QOL) scores; Visual Analogue Scale (VAS) score during menstrual period; duration of menstrual period; usage of sanitary pads or period pants during menstruation; hemoglobin level and red blood cell (RBC) count. The above data are shown in Table  2 and Supplementary Tables 2 and 3. The uterine volume was measured from magnetic resonance imaging (MRI) images and calculated using the prolate ellipsoid formula: Volume = longitudinal diameter × transverse diameter × anteroposterior diameter × 0.523 [ 5 , 11 , 33 ]. The measurement of JZmax and JZmin, as well as the calculation of junctional zone differential (JZdiff), were all referenced from previous studies [ 15 ]. The VAS score was used to assess the degree of dysmenorrhea and postoperative abdominal pain in patients [ 5 , 16 ]. A score of 0 indicates no pain; a score of 1–3 indicates mild pain; a score of 4–6 indicates moderate pain; a score of 7–10 indicates severe pain [ 34 ]. The number of sanitary pads or period pants used by patients before and after UAE was collected through questionnaires, and the degree of the patients’ anemia was evaluated via complete blood count (CBC) tests. The UFS-QOL questionnaire was originally designed to assess symptoms related to uterine fibroids, but it can also be used to evaluate symptoms associated with adenomyosis [ 35 ]. The UFS-QOL includes the Symptom Severity Score (SSS) and the Health-Related Quality of Life (HRQOL) score [ 11 , 35 ]. The specific content of the questionnaire and the conversion of raw scores refer to previous literature [ 36 ]. Among them, a higher SSS score indicates more severe symptoms, while a higher HRQOL score means a better quality of life [ 11 , 37 ]. Women with an HRQOL score > 80 and an SSS score < 20 are considered asymptomatic [ 11 ]. Inclusion criteria [ 11 ]: diagnosis of adenomyosis, or adenomyosis combined with adenomyoma and/or uterine fibroids, confirmed by medical history, clinical manifestations, MRI, and gynecological color Doppler ultrasound (CDUS); patients who had received other forms of treatment with poor results but wished to preserve the uterus; no surgical contraindications found in examinations such as coagulation function tests, electrolyte tests, liver and kidney function tests, CBC, and electrocardiogram before UAE. Exclusion criteria [ 11 , 17 , 38 , 39 ]: patients under 18 years of age, or those with pelvic infection, or those with suspected or confirmed malignant tumors, or those with deeply infiltrating endometriosis requiring surgery; patients with known allergies to contrast agents used during the procedure; patients who have a future desire to conceive; patients with confirmed pregnancy or suspected pregnancy; patients with acute cardiovascular and cerebrovascular diseases or autoimmune diseases. All patients underwent right femoral artery puncture. After disinfecting the right inguinal region and laying sterile surgical drapes, local infiltration anesthesia was administered with 2% lidocaine. The right femoral artery was punctured using the Seldinger technique, and a 5 F vascular sheath was inserted. A Cobra catheter or Headhunter catheter, with a guidewire guiding it, was first placed in the distal segment of the left uterine artery (close to the uterine body). If catheter insertion was difficult, a microcatheter could be used to reach the target area. Then, digital subtraction angiography (DSA) was performed to confirm whether the left uterine artery is the dominant artery (As shown in Fig.  1 A, the dominant artery in Case 1 is the left uterine artery). Mix 10 ml of liquid sclerosing agent (lauromacrogol) and 10 mg of gelatin sponge particles (with particle sizes of 150–350 μm) uniformly in advance, as shown in Figs. 2 A and B. During embolization, the lauromacrogol, which contained gelatin sponge particles, was first injected slowly. Inject 2–3 ml of the mixture into the non-dominant artery, and 3–4 ml into the dominant artery. Then, a temperature-sensitive liquid embolic agent (TempSLE) was injected slowly. When TempSLE (containing the contrast agent iohexol) was injected, the initial injection proceeded smoothly, and under DSA, its flow rate was found to be relatively fast. After injecting a certain amount of TempSLE (Generally, 1–2 ml of TempSLE was injected into the non-dominant artery, and about 2–3 ml of TempSLE into the dominant artery), the flow rate of TempSLE decreased significantly under the same pushing force, and there was even a slight reflux sign. At this point, the embolization was terminated. Angiography of the uterine artery was performed again, showing a significant reduction in the visualization of peripheral blood vessels, and the uterine artery presented a “pruned tree” appearance (as shown in Fig.  1 B), but there was still antegrade blood flow. The right uterine artery was embolized using the same method. The composition, dosage, and application sequence of the embolic materials have been listed in Supplementary Table 4. Fig. 1 The DSA images of the left uterine artery in Case 1. ( A ) Before embolization, DSA confirmed that the left uterine artery was the dominant artery. ( B ) After completion of embolization, DSA showed a significant reduction in the visualization of peripheral blood vessels, while the main trunk and major branches of the uterine artery were preserved. The uterine artery presented a “pruned tree” appearance. (DSA: digital subtraction angiography) The DSA images of the left uterine artery in Case 1. ( A ) Before embolization, DSA confirmed that the left uterine artery was the dominant artery. ( B ) After completion of embolization, DSA showed a significant reduction in the visualization of peripheral blood vessels, while the main trunk and major branches of the uterine artery were preserved. The uterine artery presented a “pruned tree” appearance. (DSA: digital subtraction angiography) Fig. 2 The embolic materials used in this study. ( A ) Gelatin sponge particles with particle sizes of 150–350 μm. ( B ) After the mixture of gelatin sponge particles and liquid sclerosing agent (lauromacrogol) is left to stand, precipitation of the gelatin sponge particles occurs; therefore, it is necessary to gently shake and mix it thoroughly before injection. The white arrow indicates the precipitation of gelatin sponge particles. ( C ) When the temperature of TempSLE is lower than its phase transition temperature (such as 25℃), it is in a liquid state. ( D ) When the temperature of TempSLE is higher than the phase transition temperature (such as 37℃), it forms a gel-like substance. (TempSLE: Temperature-sensitive liquid embolic agent.) The embolic materials used in this study. ( A ) Gelatin sponge particles with particle sizes of 150–350 μm. ( B ) After the mixture of gelatin sponge particles and liquid sclerosing agent (lauromacrogol) is left to stand, precipitation of the gelatin sponge particles occurs; therefore, it is necessary to gently shake and mix it thoroughly before injection. The white arrow indicates the precipitation of gelatin sponge particles. ( C ) When the temperature of TempSLE is lower than its phase transition temperature (such as 25℃), it is in a liquid state. ( D ) When the temperature of TempSLE is higher than the phase transition temperature (such as 37℃), it forms a gel-like substance. (TempSLE: Temperature-sensitive liquid embolic agent.) After UAE, during the patients’ hospital stay, we closely monitored their vital signs, blood oxygen saturation, and urine output; details are provided in Supplementary Table 5. None of the patients received iron supplementation after UAE. When the patients experienced pain of moderate intensity or higher, analgesic medication was administered. When the patients experienced nausea and vomiting, antiemetic medication was administered for treatment. During the patients’ hospitalization, any adverse events were recorded. After discharge, we conducted non-scheduled follow-ups with patients via phone calls and WeChat to collect information on adverse events. The adverse events occurring after UAE and the corresponding treatments administered are listed in Table  3 . Additionally, the follow-up time points for blood tests and MRI scans are listed in Supplementary Table 1. SPSS 20.0 for Windows statistical software was used for data processing and analysis. A Student’s two-tailed t-test for paired samples was applied to compare the relevant indicators before and after UAE treatment. The differences in uterine volume before and after UAE did not follow a normal distribution, so the Wilcoxon matched-samples rank sum test was used. A value of P  ≤ 0.05 was considered statistically significant.

In this study, we propose for the first time that favorable clinical outcomes can be achieved in the treatment of adenomyosis through partial embolization of the uterine arteries using gelatin sponge particles, liquid sclerosing agent and temperature-sensitive liquid embolic agent. After the UAE, all patients experienced remarkable improvement in symptoms, with a certain degree of reduction in JZmax, JZdiff, and uterine volume, a marked decrease in SSS scores, and a significant increase in HRQOL scores. Lauromacrogol (polyoxyethylene laurel alcohol ether) is a kind of liquid sclerosing agent that can cause damage to vascular endothelial cells and release procoagulant substances [ 40 , 41 ], thereby promoting vascular fibrosis and thrombosis [ 42 ]. It is characterized by low allergenicity, low toxicity, and mild anesthetic properties [ 41 ]. According to the package insert, lauromacrogol is mainly used for emergency hemostasis of esophageal variceal bleeding and sclerotherapy of varicose veins. However, it has been reported to be used in the treatment of other diseases such as cesarean scar pregnancies [ 43 ], ovarian endometrial cysts [ 44 ], abdominal wall endometriosis [ 45 ], lymphatic malformations [ 46 ], and varicoceles [ 47 ]. TempSLE is a liquid embolic agent approved for marketing in China in 2020, with its main component being a copolymer of N-isopropylacrylamide and N-propylacrylamide [ 48 , 49 ]. TempSLE has temperature-sensitive properties, with a phase transition temperature of 30–35 °C [ 50 ]. When the temperature of TempSLE is below 30 °C, it is in an aqueous solution state; when its temperature is higher than the phase transition temperature (such as body temperature), it forms a gel-like substance [ 51 ], Fig. 2 C and D. Due to the addition of iohexol in TempSLE, it can be visualized during the operation, allowing real-time observation of the embolization effect. In addition, studies have shown that TempSLE can diffuse into blood vessels with diameters of 100–200 μm [ 51 , 52 ], so theoretically, it can embolize the blood-supplying arterioles (with diameters of 200–500 μm) of adenomyotic lesions. At present, there are no clinical reports on the use of the combination of lauromacrogol, gelatin sponge particles and TempSLE for UAE in the treatment of adenomyosis. We innovatively used this combination of embolic agents for UAE for the first time and achieved favorable therapeutic effects. Lauromacrogol has good flow and diffusion properties, enabling it to penetrate into the peripheral blood vessels of diseased tissues, damage vascular endothelial cells, and cause vascular occlusion. However, lauromacrogol is easily washed away by blood flow, which significantly impairs the therapeutic efficacy. Therefore, in this study, a method using gelatin sponge particles (of 150–350 μm particle sizes) and lauromacrogol was employed for embolization. After adsorbing the lauromacrogol, the gelatin sponge particles become softened and can more easily reach the distal artery. In addition, the gelatin sponge particles continuously release the lauromacrogol, achieving a continuous damaging effect on the endothelial cells of the terminal blood vessels. Subsequently, TempSLE was used for further embolization of the terminal blood vessels to augment the embolization efficacy. Since TempSLE has fluidity before reaching the phase transition temperature, it can theoretically fill blood vessels of any shape, thus enabling tight embolization of terminal blood vessels. It has been reported that due to the richer blood vessels in uterine fibroids compared to the surrounding tissues, blood flows preferentially to uterine fibroids [ 20 , 38 ]. Pathological examinations after UAE have shown that embolic materials are more likely to accumulate in uterine fibroid lesions and their adjacent blood vessels [ 6 , 20 , 21 ]. This phenomenon of blood flow redistribution also occurs in other abnormal tissues, such as hepatocellular carcinoma. Hepatocellular carcinoma tissues have abundant blood supply, and the tumor-feeding arteries dilate to meet the blood supply needs of the tumor. The tumor vessels exert a “siphon effect” on these hepatic arteries, drawing blood towards the tumor itself, resulting in a markedly higher local blood flow compared with normal liver tissue [ 53 , 54 ]. Interestingly, there are studies indicating that ectopic endometrial tissues, similar to the functional layer of the endometrium, have a higher degree of vascularization than the basal layer of the endometrium [ 55 ]. Schindl et al. [ 56 ] found through immunohistochemical examinations that, compared with normal endometrium, the microvessel density in ectopic endometrial tissues in adenomyosis is significantly increased. This may be because ectopic endometrium has the effect of promoting angiogenesis within and around it [ 56 ]. Based on the above research results, we have reason to speculate that blood may preferentially flow to vascular-rich adenomyotic lesions, producing a “siphon effect”. In this study, we used liquid sclerosing agent and liquid embolic agent for UAE. Due to their easy fluidity, they may preferentially flow to adenomyotic lesions to achieve precise embolization. Admittedly, there is currently no direct evidence to confirm this, and we will conduct relevant pathological examinations to explore this issue in the future. It is worth noting that some studies have shown that pathological examinations after adenomyosis embolization revealed embolic particles to be randomly distributed in the myometrium [ 6 , 21 ], with few particles found near adenomyotic lesions [ 6 ]. This indicates that embolic particles do not preferentially flow to the lesions to achieve precise embolization. However, this does not mean that liquid sclerosing agents and liquid embolic agents cannot preferentially flow to the lesions, because the physical properties and hemodynamics of solid and liquid substances are different. In the future, we will conduct experiments to explore the precise embolization effects of liquid and solid embolic agents. In addition, the sizes of embolic particles used in the above studies are 500–700 μm or 700–900 μm [ 6 , 21 ], which is much larger than the feeding arteries of adenomyotic lesions (with diameters of 200–500 μm) [ 17 ]. This may be another reason for the failure of precise embolization. Of course, even if the lesions are not precisely embolized, the embolic particles can significantly affect the blood perfusion of the uterus, which may also lead to ischemic necrosis of some lesions [ 20 ]. However, in such cases, some lesions may still survive continuously. One of the reasons is that the uterus has an abundant collateral arterial blood supply, such as the inferior mesenteric artery, the uterine round ligament artery and branches of the ovarian artery [ 12 ]. Even if the main trunk and branches of the uterine artery are completely embolized, the aforementioned collateral arteries can still provide partial blood supply to the uterus. If the embolic particles do not reach the adenomyotic lesions, it will be impossible to accurately embolize the feeding arteries of the lesions. At this time, the collateral circulation enables the ectopic endometria to survive through the feeding arteries of these lesions, resulting in treatment failure or poor therapeutic effect, as demonstrated in Fig. 5 A. In addition to the abundant collateral circulation, vascular recanalization may also be a reason for the persistent survival of adenomyotic lesions [ 57 ]. For example, gaps between embolic particles may allow blood flow to resume, leading to embolization failure [ 5 ]. During the UAE procedure, lauromacrogol can directly damage the vascular endothelial cells of the lesions, and TempSLE can achieve gapless embolization of their vessels, which prevents recanalization. Moreover, since the feeding arteries of the adenomyotic lesions are embolized, even if there is still collateral circulation in the uterus, it cannot provide blood supply to the lesions, ensuring the ischemia and necrosis of the lesions, as shown in Fig. 5 B. However, we currently lack pathological data to support this speculation. Another related issue is that when the feeding arteries of the lesions are precisely embolized, the embolization of the main trunk and branches of the uterine artery becomes less necessary. Fig. 5 Schematic diagrams of adenomyotic lesion embolization with different embolic materials. ( A ) If the embolic particles do not reach the adenomyotic lesions, it will be impossible to accurately embolize the feeding arteries of the lesions. Collateral circulation can still provide blood supply to the lesions, resulting in the survival of the lesions. (White pellets represent embolic particles). ( B ) If the feeding arteries of adenomyotic lesions can be precisely embolized, embolization of the main trunk of the uterine artery and its major branches is unnecessary. (White color indicates that the feeding arteries have been embolized). Note: These schematic diagrams are speculations on the embolization effects of different embolic materials based on limited literature; however, they still lack support from data such as pathology and hemodynamics Schematic diagrams of adenomyotic lesion embolization with different embolic materials. ( A ) If the embolic particles do not reach the adenomyotic lesions, it will be impossible to accurately embolize the feeding arteries of the lesions. Collateral circulation can still provide blood supply to the lesions, resulting in the survival of the lesions. (White pellets represent embolic particles). ( B ) If the feeding arteries of adenomyotic lesions can be precisely embolized, embolization of the main trunk of the uterine artery and its major branches is unnecessary. (White color indicates that the feeding arteries have been embolized). Note: These schematic diagrams are speculations on the embolization effects of different embolic materials based on limited literature; however, they still lack support from data such as pathology and hemodynamics The Expert Consensus on UAE Treatment for Uterine Fibroids and Adenomyosis , released in China in 2018, points out that to achieve better clinical efficacy, the embolization degree for adenomyosis must be significantly higher than that for uterine fibroids, and complete embolization is mandatory [ 10 ]. That is to say, the vascular networks of the lesions and the main trunk of the branch arteries that mainly supply the lesions should be completely embolized, and the DSA shows that the staining of the lesions disappears completely, with the main trunk of the uterine artery only partially visualized or completely invisible [ 10 ]. However, we hold a different view on this. Given that the small arteries and arterioles supply blood to adenomyotic lesions, these feeding arteries should be targeted as precisely as possible, without the need to embolize the main trunk of the uterine artery and its large branches. Studies have pointed out that pelvic pain after UAE is mainly caused by ischemia of the uterine myometrium, which is also a common postoperative symptom [ 9 , 20 , 58 ]. When the main trunks of the uterine arteries and their branches were embolized, the blood flow was completely blocked, and the acute and severe ischemia of the uterus would cause severe spasm of small arteries, making patients suffer from severe pain. In this case, the uterus cannot establish collateral circulation in a short time, so there may even be serious consequences such as uterine necrosis. In cases of incomplete uterine artery embolization, the branches of the uterine artery, along with the unembolized small arteries and arterioles, will continue to nourish the uterus, facilitating the reconstruction of uterine blood circulation. This incomplete embolization, on the one hand, results in relatively mild uterine ischemia and thus relatively less pain for patients; on the other hand, it is beneficial to protect the uterine function and prevent severe uterine ischemia from affecting the function of the normal endometrium. Case 4 in this study, despite indicating no desire for childbearing before UAE, became pregnant within 1 week after UAE and gave birth to a full-term baby boy. This indicates that the novel UAE surgical method causes minimal damage to the endometrium, or at least does not severely affect its function. Furthermore, another advantage of preserving the main trunks and branches of the uterine arteries is that patients can undergo re-embolization in the future if necessary. If the main trunks and branches of the uterine arteries are completely embolized, there will be few opportunities for re-UAE. For example, in Case 6 of this study, due to the severity of the patient’s condition, she underwent two sessions of UAE. It has been reported that when the embolization endpoint is set to blood flow being nearly static rather than completely static, the postoperative pain will be milder [ 12 ]. We agree with this perspective. Regarding the embolization endpoint, we do not take the duration of complete cessation of uterine artery blood flow as a determining factor. At the beginning of the injection of TempSLE, we will observe the injection to be relatively smooth. When the embolization reaches a certain degree, the flow rate of the TempSLE will decrease under the same pushing force, and there may even be slight reflux. At this point, embolization is terminated. DSA will show that the main trunk and branches of the uterine artery remain visualized (Fig. 1 B), presenting a “pruned tree” appearance [ 20 ], but the staining of their peripheral vascular network is remarkably reduced. Then, the goal of partial embolization of the uterine artery is achieved. Another issue requiring attention in UAE is that patients may experience temporary or permanent amenorrhea [ 20 ]. This may be caused by non-targeted embolization of the ovaries by embolic particles via the anastomotic vessels between the ovarian artery and the ascending uterine artery [ 21 , 39 ]. It is unclear whether liquid sclerosing agents and liquid embolic agents are more likely to reach the ovaries through the anastomoses between the uterine arteries and ovarian arteries, resulting in accidental embolization. However, it has been reported that reducing the delivery speed of embolic agents can reduce or prevent accidental ovarian embolization [ 22 ]. In this study, the injection of embolic agents was performed slowly in all cases. Case 2 had normal menstrual cycles for 7 months after UAE, followed by amenorrhea. However, the patient was 50 years old, and her amenorrhea may be due to natural menopause. This is because the patient had menopausal symptoms such as hot flashes, sleep disorders, and memory decline before UAE, as shown in Supplementary Table 2. The other patients had regular menstrual cycles after the UAE without amenorrhea. Postoperative hormone level tests indicated that the ovarian reserve of Case 2 was decreased, while that of the other patients was normal (as shown in Supplementary Table 6). However, the number of clinical cases in this study is limited, and more clinical cases will be needed in the future to evaluate the impact of the new embolic materials on ovarian function. In conclusion, we propose for the first time the use of a combination of gelatin sponge particles, lauromacrogol and TempSLE for UAE treatment of adenomyosis. During the procedure, partial embolization of the uterine arteries is performed, while preserving the main trunks and branches of the uterine arteries. Furthermore, we have also proposed a potentially appropriate embolization endpoint. Eventually, the symptoms of 6 patients improved significantly, and no severe complications occurred after UAE. However, it should be noted that although the 6 patients achieved good therapeutic effects, this does not mean that the new UAE method is superior to the conventional UAE. This study has limitations, mainly including a small number of patients, lack of pathological results to provide theoretical support, and short follow-up time. In the future, we will conduct randomized controlled studies with a larger number of patients and longer follow-up periods, and collect uterine tissue samples after embolization for pathological examination to further determine the efficacy and safety of the novel UAE method.

Adenomyosis is a common gynecological disease, characterized pathologically by the invasion of stroma and endometrial glands into the myometrium, with localized or diffuse growth [ 1 , 2 ]. Patients may experience menorrhagia, dysmenorrhea, anemia, infertility, chronic pelvic pain, dyspareunia, as well as compressive symptoms caused by an enlarged uterus (such as frequent urination or pelvic heaviness) [ 3 , 4 ]. Hormonal therapy can be used for adenomyosis, but it may have drawbacks such as poor efficacy, recurrence of symptoms after discontinuation, and long-term side effects (e.g., changes in hormone levels, osteoporosis) [ 5 , 6 ]. After the failure of conservative treatment, many patients are advised to undergo hysterectomy, which has long been regarded as the gold standard for the treatment of symptomatic adenomyosis [ 7 ]. Uterine artery embolization (UAE) provides a safe and effective alternative treatment option for adenomyosis patients who have failed conservative treatment but still wish to maintain their fertility or preserve the uterus [ 4 , 8 , 9 ]. Although UAE shows encouraging prospects in the treatment of symptomatic adenomyosis, there still exist challenges. In 2018, China issued the Expert Consensus on UAE Treatment of Uterine Fibroids and Adenomyosis [ 10 ]. The consensus points out that there are still many inconsistencies in the application of UAE at present, resulting in varying therapeutic effects [ 10 ]. There remains a lack of consensus on key issues such as the selection of embolic materials (in terms of material type and size), whether the uterine artery should be completely or partially embolized, and the determination of embolization endpoints. Currently, the embolic materials used in UAE include gelatin sponge particles, sodium alginate microspheres, Bead Block, tris-acryl gelatin microspheres, and polyvinyl alcohol (PVA) particles [ 11 – 13 ], with microsphere diameters ranging from 100 μm to 900 μm [ 2 , 5 , 11 , 14 – 16 ]. The arterial supply to adenomyotic lesions is provided by arterioles of the same size as those in the uterine myometrium (with diameters of 200–500 μm) [ 17 ]. The size of embolic particles selected for UAE is related to the diameter of the artery to be occluded [ 13 ]. Therefore, in embolization procedures, smaller particles are required to reach distal small vessels, aiming to induce ischemic necrosis of ectopic endometrial tissue [ 3 , 11 , 14 , 18 ]. However, studies have indicated that the use of smaller embolic particles may lead to the serious consequence of uterine necrosis and exacerbate post-embolization pain [ 3 , 13 , 14 , 17 , 19 ]. Reportedly, the diameters of anastomotic vessels between the uterine artery and ovarian artery are less than 500 μm [ 20 ]; thus, the risk of accidental ovarian embolization appears to be remarkably reduced when using particles with sizes larger than 500 μm [ 21 ]. Possibly due to the above concerns, some surgeons still only use larger-particle embolic agent s (with particle sizes of 500–900 μm) in UAE procedures [ 5 , 16 , 22 ]. In addition to the controversy over the selection of embolic particle sizes, there are other issues with embolic materials: (1) PVA particles tend to aggregate together to form larger clusters, resulting in inaccurate embolization [ 20 , 21 , 23 ]. (2) Extravascular dispersion of PVA particles may occur after UAE, leading to damage (such as inflammatory reaction) to adjacent organs [ 23 ]. This highlights the necessity of exploring other potential and feasible embolic materials to provide more options for UAE treatment. Furthermore, there is currently no unified clinical standard for the degree to which the uterine artery needs to be embolized in the treatment of adenomyosis. A study has reported that the distal bilateral uterine arteries are completely occluded during UAE procedures [ 8 ]. Other studies indicate that the embolization procedure is continued until the blood flow in the ascending branch of the uterine artery ceases completely, while there remains residual blood flow in the descending branch [ 5 , 13 , 24 – 26 ]. Some surgeons also embolize the main trunk of the uterine artery, resulting in complete cessation of blood flow, with it not visualized at all on imaging or only its stump visualized [ 2 , 27 – 30 ]. Additionally, some studies do not describe which part of the uterine artery is embolized, but regard the complete stagnation of uterine artery blood flow as the criterion for the end of embolization [ 11 , 31 ]. Since the blood supply of adenomyosis lesions is provided by arterioles, appropriate embolic materials should be considered to accurately embolize these feeding arteries, without the need to embolize the main trunk of the uterine artery and its large branches. When it comes to the endpoint of embolization, there is currently no fully unified consensus nor a mandatory standard. It is generally considered appropriate to take the complete cessation of uterine artery blood flow lasting for 5–10 cardiac cycles as the embolization endpoint [ 12 ]. Some scholars have proposed other standards, taking the occlusion of vessels in the lesions, the stagnation of distal blood flow (with reduced proximal flow) in the uterine artery, and the continued patency of the uterine artery as signs indicating the end of embolization [ 32 ]. For UAE, the key issue is how to fully embolize the diseased tissues while minimizing ischemic damage to the normal myometrium, which helps reduce post-operative pain and preserve uterine function. To solve this problem, efforts should be made, including the selection of embolic materials and the adjustment of embolization strategies, to optimize the embolization approach. In this study, we used embolic materials that differ from those used in previous studies in partial uterine artery embolization for the treatment of adenomyosis. We reported the improvement of clinical symptoms in all 6 patients and attempted to explore the potential mechanism of action of the novel embolic materials. This study can provide some insights and ideas for the treatment of adenomyosis with UAE.

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