Efficacy and ovarian preservation of combined uterine and ovarian artery embolization in adenomyosis with significant collateral supply

In this small, single-center cohort of relatively young adenomyosis patients with significant ovarian artery collateral supply, combined UAE + OAE was associated with symptom relief without long-term compromise of ovarian reserve at 12 months. Nevertheless, these findings are preliminary and do not allow us to draw definitive conclusions regarding safety in younger patients. More patient data from larger, multicenter cohorts and randomized trials, with longer follow-up and broader inclusion of older patients, those with bilateral ovarian collaterals, and those with lower baseline ovarian reserve, are required to establish the safety and efficacy profile of combined UAE + OAE.

Adenomyosis, characterized by the presence of ectopic endometrial tissue within the myometrium, [ 1 , 2 ] has an unknown exact prevalence. Among women undergoing hysterectomy for menorrhagia or abnormal uterine bleeding, the prevalence of adenomyosis confirmed by histopathology ranges from 26% to 49%. [ 3 ] This disease primarily affects women aged 30 to 50 years. [ 4 , 5 ] It causes debilitating symptoms, including severe pelvic pain and menorrhagia, significantly impairing quality of life (QOL). [ 6 – 8 ] Crucially, it adversely impacts reproductive outcomes by increasing the risks of preterm delivery and premature rupture of membranes. [ 9 ] Adenomyosis is categorized into diffuse and localized forms. [ 10 ] Diffuse adenomyosis involves widespread infiltration of the myometrium by endometrial tissue, often leading to an enlarged uterus, and is characterized by translesional vascularity, where blood vessels cross through the lesion. Localized adenomyosis (adenomyoma) appears as a localized mass and is characterized by circumferential vascularity, where blood vessels surround the lesion. Uterine artery embolization (UAE), a cornerstone minimally invasive therapy for adenomyosis, induces targeted ischemic necrosis of pathological lesions. Despite high initial efficacy, symptom recurrence occurs in approximately 24% of patients within 18 months. [ 11 ] This recurrence strongly correlates with residual perfusion through ovarian collateral vessels, observed in 10% of cases. [ 12 – 15 ] Robust evidence indicates that supplemental ovarian artery embolization (OAE) is imperative when ovarian artery collateral supply exceeds 10% of ipsilateral uterine perfusion. [ 16 ] Although combined UAE + OAE may reduce recurrence by ablating these collaterals, its impact on ovarian function remains contentious. Current literature is confined to small case reports, [ 17 – 19 ] lacking rigorous assessment of dynamic hormonal changes and ovarian reserve – a critical evidence gap hindering risk-stratified patient selection. To address this unmet need, we conducted a retrospective study. Using longitudinal profiling of reproductive hormones, ovarian reserve biomarkers, and patient-reported outcomes, we evaluated the safety and efficacy of combined UAE + OAE in adenomyosis patients with ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion. Given the exploratory design with a limited sample size and the absence of a control group, these findings constitute preliminary evidence to inform future validation studies.

Conceptualization: Tenghui Zhan. Data curation: Jianfeng He. Formal analysis: Jianfeng He. Methodology: Jianfeng He. Project administration: Tenghui Zhan. Supervision: Tenghui Zhan. Validation: Jianfeng He. Visualization: Jianfeng He. Writing – original draft: Jianfeng He. Writing – review & editing: Jianfeng He, Tenghui Zhan.

This single-center retrospective study was conducted at Fujian Maternity and Child Health Hospital between June 2021 and April 2023. The study was approved by the Institutional Ethics Committee (No. 2023KY063-02) in accordance with the Declaration of Helsinki. Due to its retrospective design and complete data anonymization, the study obtained a waiver for individual informed consent. We consecutively screened 257 symptomatic adenomyosis patients undergoing UAE. All participants underwent post-procedural aortography to evaluate ovarian artery collateralization to the uterus. Two senior interventional radiologists (each with ≥ 8 years’ experience) independently quantified the percentage of ipsilateral uterine perfusion contributed by ovarian collaterals through visual estimation. Following standardized consistency training, discrepancies exceeding 5% were adjudicated by a third blinded physician, with final values determined by averaging measurements (Fig. 1 details the screening algorithm). Patient screening and enrollment flowchart. Among the 257 screened patients, 195 (75.9%) had no ovarian collateral supply, 52 (20.2%) had unilateral ovarian collateral supply, and 10 (3.9%) had bilateral ovarian collateral supply. Among the 52 patients with unilateral ovarian collateral supply, 23 had collateral supply exceeding 10% of ipsilateral uterine perfusion and met the inclusion criteria. Among these 23 patients, 2 refused OAE treatment, 3 were lost to follow-up, and 18 completed combined UAE + OAE treatment and the 12-month follow-up, and were included in the final analysis. Other patients included 29 with unilateral ovarian collateral supply <10% and 10 with bilateral supply (both <10%), who underwent UAE alone. All eligible consecutive patients during the study period were included. Data were derived from electronic medical records and follow-up information, covering demographics, clinical manifestations, imaging studies, laboratory tests, and surgical records. Health-related QOL compromised due to menorrhagia, dysmenorrhea, and/or mass-related symptoms (such as urinary system symptoms), defined as limitations in daily activities, decreased energy or mood, altered self-perception, and sexual dysfunction, and who had failed conservative treatments; MRI-confirmed adenomyosis; expressed desire for uterine preservation without future pregnancy plans; angiographic documentation of ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion, confirmed via post-UAE angiography; complete pre- and post-procedural follow-up documentation. Age <18 years; active malignancy; acute pelvic infection; severe contrast allergy or contraindications to angiography/embolization; prior UAE; nonovarian collateral arterial supply to the uterus; or incomplete follow-up data. Comprehensive outcome assessment encompassed 3 domains: serum reproductive hormones – follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) – quantified on menstrual cycle day 3 at baseline and 3, 6, and 12 months postoperatively. Blood samples were collected from a peripheral vein and then centrifuged at 3000 rpm for 15 minutes at room temperature. The serum was subsequently separated and stored in a refrigerator at–80°C. The levels of FSH and LH in the serum were measured using the chemiluminescence method (Architect Alinity, Abbott, Longford, Ireland). The serum level of AMH was measured using an enzyme-linked immunosorbent assay (Motive Biosciences Inc., Webster). All samples were processed in a blinded manner to laboratory technicians. Ovarian reserve evaluated via transvaginal color Doppler ultrasound-derived antral follicle count (AFC) on cycle day 3 (baseline, 3, 6, and 12 months), with AFC defined as the cumulative count of 2 to 10 mm follicles in bilateral ovaries; clinical outcomes assessed using standardized questionnaires measuring symptom severity scores (SSS), QOL, and numerical rating scale (NRS) pain scores at baseline and 12 months. Uterine volume was calculated as length × width × height × 0.52. Partial response required either ≥50% reduction in SSS without full normalization or patient-reported symptom improvement ≥50%. All assessments were independently conducted by researchers blinded to procedural details. Covariates included age, body mass index, uterine volume, parity, prior cesarean delivery, and baseline symptoms. Post hoc power analysis confirmed 80% statistical power (α = 0.05) to detect ≥2.0 ng/mL differences in AMH decline, based on thresholds for clinically significant changes in hormonal interventions. Missing data (<3%) were managed through complete-case analysis. All procedures were performed by an interventional radiology team with over 8 years of experience under local anesthesia, following a standardized protocol. The modified Seldinger technique was used to access the right femoral artery. Bilateral uterine arteries were selectively catheterized using 4-Fr Cobra catheters (Cordis Corporation) for angiographic assessment and subsequent UAE. All patients underwent abdominal aortography using a 4-Fr PIG catheter (Cordis Corporation) to evaluate collateral supply to the uterus. When unilateral ovarian artery enlargement extending into the pelvis was observed, a 2.4-Fr coaxial microcatheter (Merit Medical Systems) was advanced to the proximal to mid-segment of the ovarian artery for selective angiography. In cases with collateral supply exceeding 10% of ipsilateral uterine perfusion, flow-directed embolization was performed for unilateral OAE. The embolic agent was slowly injected while real-time monitoring was conducted to prevent reflux. This technique, based on hemodynamic principles, allows embolic particles to preferentially enter the high-flow pathological uterine vasculature while protecting the low-flow, high-resistance ovarian capillary branches. [ 20 ] The endpoints of embolization included [ 21 ] : disappearance of pathological uterine staining, slowed but patent arterial main trunk flow, and contrast agent retention in distal vessels for 10 cardiac cycles (Fig. 2 ). Combined UAE + OAE in a 43-year-old woman with progressive menorrhagia and dysmenorrhea (5-yr history, exacerbated over the past 9 mo). (A–D) Hypertrophied bilateral uterine arteries with pathological uterine blush. Post-UAE imaging demonstrates preserved main arterial trunks and complete devascularization of adenomyotic lesions. (E and F) Aortography reveals right ovarian artery hypertrophy supplying pathological uterine blush (exceeding 10% ipsilateral uterine perfusion, red arrow), in contrast to the absence of abnormal perfusion from the left ovarian artery (blue arrow). (G and H) Right OAE achieves targeted lesion devascularization while maintaining patency of the main trunk and perfusion to ovarian branches (white arrow). OAE = ovarian artery embolization, UAE = uterine artery embolization. Both UAE and OAE were performed using 300 to 500 μm Embosphere microspheres (merit medical systems). Standardized post-procedural monitoring included vital signs, pain assessment, and bleeding surveillance. Pain management utilized NSAIDs or patient-controlled analgesia pumps, supplemented with antiemetics. Early ambulation was encouraged 6 to 8 hours post-procedure. All patients were monitored postoperatively for menstrual resumption and perimenopausal symptoms (such as hot flashes and night sweats). Given the lack of validated QOL instruments specific to adenomyosis, the Uterine Fibroid Symptom and QOL (UFS-QOL) questionnaire was used to assess symptoms both before and after embolization, generating 2 primary outcome measures: the SSS and the QOL score. [ 22 , 23 ] The questionnaire includes an 8-item symptom severity scale and 29 items related to health-related quality of life. Items are rated on a 5-point Likert scale, with symptom severity items ranging from “not at all” to “very severe,” and health-related quality of life items ranging from “none of the time” to “all of the time.” A higher SSS indicates more severe symptoms, while a higher health-related quality of life subscale score signifies better quality of life. Women with an SSS of 80 were classified as asymptomatic. [ 24 ] The intensity of pelvic pain was quantified using the NRS, [ 25 ] an 11-point scale where 0 represents 1 pain extreme (e.g., “no pain”) and 10 signifies the other pain extreme (e.g., “the worst pain imaginable”). Post-procedural symptoms and complications were categorized in accordance with the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Quality Improvement Guidelines for Percutaneous Catheter Embolization. [ 26 ] Data normality was assessed using the Shapiro–Wilk test. Continuous variables were presented as mean ± standard deviation for normally distributed data or median [interquartile range (IQR)] for non-normally distributed data, and categorical variables as frequencies (%). For longitudinal analysis of normally distributed variables, repeated-measures ANOVA with Greenhouse-Geisser correction was applied, followed by Bonferroni-adjusted paired t-tests for significant pairwise comparisons. Wilcoxon signed-rank tests were used for non-normally distributed variables. Effect sizes (Cohen d) were calculated for significant differences. The missing data rate was <3%, and complete-case analysis was performed. Statistical significance was set at a 2-tailed P -value <.05. All analyses were performed using SPSS 28.0 (IBM Corp., Armonk).

This case series included 18 patients with adenomyosis and significant ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion. The cohort had a mean age of 39.4 ± 6.4 years and body mass index of 23.7 ± 3.1 kg/m². Baseline uterine volume was significantly enlarged (251.6 ± 134.8 cm³; Table 1 ). Obstetrical history indicated a mean gravidity of 2.4 ± 1.1 and 1.1 ± 0.9 prior cesarean deliveries. Preprocedural symptoms were prevalent: dysmenorrhea (77.8%, 14/18), menorrhagia (83.3%, 15/18), and bulk-related symptoms (e.g., urinary compression; 66.7%, 12/18). Technical laterality demonstrated right-sided OAE predominance (66.7% vs 33.3% left-sided). Baseline characteristics of study participants (n = 18). Continuous variables presented as mean ± standard deviation; categorical variables as n (%). BMI = body mas index. Longitudinal assessment of ovarian function revealed distinct patterns in hormonal parameters and reserve markers (Table 2 ). Serum FSH and LH levels remained stable throughout the follow-up period. No significant differences were observed among baseline (FSH: 9.21 ± 1.04 mIU/mL; LH: 7.12 ± 1.12 mIU/mL), 3-month (FSH: 8.99 ± 1.34 mIU/mL; LH: 7.01 ± 0.97 mIU/mL), 6-month (FSH: 8.63 ± 1.11 mIU/mL; LH: 7.07 ± 1.85 mIU/mL), and 12-month (FSH: 8.95 ± 1.31 mIU/mL; LH: 7.45 ± 1.69 mIU/mL) measurements (repeated-measures ANOVA, P  = .548 for FSH; P  = .800 for LH). Similarly, AFC demonstrated no significant variation over time (Baseline: 13.22 ± 3.39; 3 months: 11.96 ± 3.08; 6 months: 13.19 ± 3.40; 12 months: 11.82 ± 3.11; ANOVA P  = .400). Longitudinal changes in hormonal parameters and ovarian reserve markers at different time points (N = 18). Data are presented as mean ± standard deviation. 3M/6M/12M = 3/6/12 mo post-procedure, AFC = antral follicle count, AMH = anti-Müllerian hormone, B = baseline, FSH = follicle-stimulating hormone, LH = luteinizing hormone. P -values derived from repeated-measures ANOVA with Greenhouse-Geisser correction. Significant decrease from baseline (adjusted P  <.05). AMH at 3 mo was significantly lower than baseline, 6 mo, and 12 mo ( P  <.01). Significant pairwise comparisons identified by Bonferroni-adjusted paired t-tests (α = 0.05); only statistically significant results are shown. In contrast, serum AMH levels exhibited a significant transient decline. Baseline AMH was 3.91 ± 1.50 ng/mL, which markedly decreased to 1.86 ± 0.90 ng/mL at the 3-month post-embolization assessment (ANOVA P  <.001). However, AMH levels subsequently recovered to near-baseline values (4.01 ± 1.91 ng/mL at 6 months and 4.18 ± 0.97 ng/mL at 12 months). post hoc pairwise comparisons with Bonferroni correction confirmed that the 3-month AMH value was significantly lower than baseline ( P  = .006), the 6-month value ( P  = .004), and the 12-month value ( P  <.001). No significant differences in AMH levels were detected between baseline, 6 months, and 12 months (Fig. 3 ). Temporal changes in serum AMH levels over 12 mo. AMH = anti-Müllerian hormone. Combined UAE + OAE resulted in substantial clinical improvements at the 12-month follow-up (Table 3 ). SSS demonstrated a marked decline from a baseline median of 57 [IQR 35–77] to 12 [4–50] ( P  <.001), representing a 79% median reduction. Concurrently, QOL scores increased significantly from 40 [20–52] to 78 [54–96] ( P  <.001), reflecting a 95% median improvement. Pain intensity, assessed by the NRS, decreased significantly from 7 [5–10] to 2 [0–6] ( P  <.001). Symptom relief analysis revealed complete resolution in 10 patients (55.6%), partial relief in 6 (33.3%), and no improvement in 2 (11.1%). Clinical outcomes at baseline and 12-mo follow-up. Data are presented as median (IQR) or n (%). Between-timepoint comparisons were performed using Wilcoxon signed-rank tests for continuous variables. Statistical significance was set at P  <.05. IQR = interquartile range, QOL = quality of life, SSS = symptom severity score. No major complications occurred, including infection, hemorrhage, nontarget organ embolization, or premature ovarian failure. Minor complications were observed in 16 patients (88.9%), classified as Grade 1 (self-limiting post-embolization syndrome) per CIRSE criteria. These manifested as low-grade fever (median 37.8°C) within 72 hours post-procedure, dull lower abdominal pain, and mild nausea/vomiting controlled with antiemetics, resolving spontaneously within 7 days without intervention. All patients resumed regular menstruation within 1 to 3 months, with no reports of perimenopausal symptoms, including hot flashes, night sweats, insomnia, vaginal dryness, or irritability. Given the low sample size, the data cannot be generalized to the population.

This single-center retrospective study systematically evaluated reproductive hormone levels, ovarian reserve function, and clinical symptoms in symptomatic adenomyosis patients with ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion undergoing Combined UAE + OAE treatment. Despite the limited sample size due to consecutive patient enrollment (n = 18), the reliability of the study results was enhanced by blinded outcome assessment, complete 12-month follow-up, and standardized measurement methods. The primary findings showed significant clinical improvements at the 12-month follow-up: the median SSS decreased by 79% (from 57 to 12), and the QOL score increased by 95% (from 40 to 78). There were no statistically significant differences in FSH, LH, AMH, and AFC compared to baseline values. All patients resumed their menstrual cycles postoperatively, and no perimenopausal symptoms (such as hot flashes and night sweats) were reported, supporting the notion that ovarian function was not permanently compromised. This safety profile may be related to the following mechanisms: unilateral OAE strategy: All patients underwent unilateral OAE only, with the contralateral ovary providing sufficient functional compensation; age factor: with a mean age of 39.4 years, younger patients have a stronger capacity for ovarian vascular regeneration and functional recovery; technical factors: The flow-directed embolization technique, which utilizes hemodynamic principles to direct embolic particles preferentially into the high-flow pathological uterine vasculature while protecting the low-flow, high-resistance ovarian capillary branches, may have contributed to the safety profile; embolic material: The 300 to 500 μm microspheres used have an appropriate size to effectively embolize the pathological uterine vasculature without excessively affecting the ovarian capillary bed. AMH is secreted by granulosa cells of preantral and small antral follicles; primordial follicles do not show detectable AMH expression, and expression declines in larger antral follicles. [ 27 ] Its circulating level reflects ovarian reserve and the number of developing follicles. [ 27 ] The ovary receives dual arterial inflow from the ovarian artery and the ovarian branch of the uterine artery, forming a utero-ovarian arcade that permits collateral perfusion. [ 16 , 20 ] After UAE or OAE, embolic particles delivered to the uterine circulation may traverse these collaterals and transiently reduce ovarian perfusion, producing ischemic stress and functional suppression of AMH secretion from preantral/small antral follicles. [ 27 , 28 ] This effect is expected to be temporary: human folliculogenesis requires approximately 3 to 4 months for follicles to progress to the small antral stage that contributes most to circulating AMH, and collateral channels can remodel over time; therefore, a 3‑month AMH nadir with subsequent recovery is biologically plausible. [ 28 – 30 ] Consistent with this interpretation, FSH, LH, AFC, and menstrual regularity remained overall stable in our cohort. A study on the impact of UAE on ovarian reserve in women [ 29 ] demonstrated that postoperative AMH levels decreased on average, but this decline was not significantly different from that observed during natural aging, with no substantial effect on fertility. Among women under 40 who desired pregnancy, 48% achieved term pregnancies following the procedure. A meta-analysis by El Shamy et al., [ 31 ] with follow-up durations ranging from 3 to 12 months, revealed no significant impact of UAE on serum AMH levels (weighted mean difference of–0.58 ng/mL; 95% CI–1.5 to 0.36, I2 = 95%), supporting our findings. Hu et al., [ 32 ] in a 2011 study comparing patients with uterine fibroids who underwent concurrent OAE with UAE versus UAE alone, found no significant differences in the incidence or severity of menopause between the 2 groups. Notably, 6 patients who underwent bilateral OAE maintained regular menstrual cycles, indirectly indicating no impact of OAE on ovarian function or menstrual regularity. This study reported the dynamic changes in AMH following combined UAE + OAE: a transient significant decline at 3 months, complete recovery at 6 months, and long-term stability at 12 months. This pattern suggests that the embolization procedure induces a temporary ischemic stress on the ovaries rather than permanent follicle loss, and does not result in permanent damage in younger patients. The flow-directed technique, by protecting physiological branches, allows the microcirculation to reestablish within 6 months. This phenomenon is akin to the impact of uterine artery occlusion on ovarian reserve. [ 33 ] As demonstrated in Kim study, [ 34 ] at the 3-month follow-up, AMH levels in UAE patients decreased by 1.46 ± 1.23 ng/mL. Among patients under 40 years of age, serum AMH levels showed significant recovery between the 3-month and 12-month follow-ups, aligning with the recovery pattern we observed. However, Hehenkamp et al. [ 35 ] reported in their randomized controlled trial that, compared to the expected age-related decline in AMH, AMH levels in the UAE group immediately dropped postoperatively and did not recover to the expected levels in subsequent follow-ups. This suggests that UAE caused more persistent damage to ovarian reserve, which contrasts with our findings. Notably, the patients in their study were older (mean age 44.6 ± 4.8 years), had poorer ovarian reserve, and the study focused on uterine fibroids rather than adenomyosis. These differences in patient demographics and study subjects, along with potential variations in hemodynamics, could be significant factors influencing the results. The clinical success rate of our study (88.9%) was higher than that reported in the prospective cohort study by Trommelen et al. [ 36 ] UAE significantly improved symptoms and QOL in adenomyosis patients (SSS decreased by 45 points, QOL increased by 32.8 points, NRS decreased by 4.5 points), with a satisfaction rate of 73% at 1-year follow-up, suggesting the superiority of combined treatment in selected patients. This study demonstrates that combined UAE + OAE can achieve a high rate of symptom relief in adenomyosis patients with ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion, without compromising ovarian function. Based on our data and the literature, we propose preliminary, conditional recommendations. For symptomatic adenomyosis patients seeking uterine preservation and demonstrating angiographic unilateral ovarian collateral supply >10% of ipsilateral uterine perfusion, UAE plus unilateral, flow‑directed OAE with 300 to 500 μm microspheres can be considered. Prefer younger patients with preserved ovarian reserve; counsel that AMH may transiently decline at 3 months and typically recovers by 6 to 12 months, with FSH/LH/AFC remaining stable. These are conditional suggestions pending multicenter validation. This study has the following limitations. First, although all eligible patients during the study period were included, the sample size remains limited (n = 18), which restricts the power of statistical tests and the feasibility of subgroup analyses. Second, this study did not include a control group receiving UAE alone. The ethics committee deemed that withholding effective treatment (combined UAE + OAE) from patients with a high risk of recurrence due to ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion, as confirmed by DSA, would not be in the best interest of the patients. This design limitation is rooted in clinical reality but can be indirectly validated by comparison with historical studies. Third, the relatively young age of the patients in this study (mean age 39.4 ± 6.4 years) likely contributes to their stronger ovarian recovery capacity after embolization. The safety of the procedure in older patients, those with bilateral ovarian artery supply, or those with poorer ovarian reserve still needs to be verified. Fourth, the assessment of ovarian artery collateral supply exceeding 10% of ipsilateral uterine perfusion by DSA still involves some subjectivity, even with double-blind evaluation. More objective quantitative assessment methods should be developed in the future. Fifth, although a 12-month follow-up was sufficient to observe complete recovery of AMH, longer-term follow-up (24–36 months) is still necessary to assess the long-term stability of ovarian function. Sixth, this study is a single-center, retrospective study, and caution should be exercised when generalizing the findings to other populations.