Matthew Henry
Wayne State University SOM ’22

Christine Lin
Pennsylvania State University SOM ’23

Vimal Gunasekaran
Medical College of Wisconsin ’22

Anushree Rai
SIR MSC Reserves Member

Uterine fibroids are a common occurrence in middle aged females that can cause painful and heavy menstrual bleeding.  With a prevalence of uterine fibroids estimated to be 65% in women greater than 50, successful treatment of these patients is crucial [1].  One of the growing treatment options include uterine fibroid embolization (UFE) performed by an Interventional Radiologist.

While embolizations were first described in the 1970’s for treatment of postpartum hemorrhage, vascular malformations, or devascularization of tumors, it was not until 1995 that Ravina et al. proposed embolization for treatment of uterine fibroids [2]. With 16 patients under neuroleptic analgesia, access of the right femoral artery with subsequent catheterization of the right and left uterine arteries and embolization with inert particles of Ivalon was performed until fibroid blood flow was completely interrupted. 75% of patients had a 20-80% reduction in fibroid volume and 64% of patients had symptom resolution. Additionally, in 1997 Goodwin et al. reported successful reduction of fibroid related symptoms in 88% patients treated with UFE. To date, over 40,000 UFE’s have been performed [3].

Historically, alternative treatment options for uterine fibroids include hormonal/oral contraceptive medical and surgical approaches–however, these options are not without risks. Oral contraceptive side effects include venous thromboembolism and a 20-40% increased risk of stroke. Furthermore, hormonal therapies can cause recurrence of symptoms and fibroid size after cessation. Hysterectomy is a definitive therapy of uterine fibroids and while it has the highest rate of symptom relief compared to UFE in nonrandomized controls, it carries significant major complications such as deep venous thrombosis (5%), surgical wound abscess (15%), intraabdominal abscess (5%) and transfusion (20%) [4-5].

Current Applications
Uterine fibroid embolization (UFE) is a uterus-sparing procedure performed by interventional radiologists through a transcutaneous femoral artery approach to treat symptomatic uterine fibroids [6].  Since 2008, UFE has been endorsed by the American College of Obstetricians and Gynecologists (ACOG) as a safe and effective alternative to hysterectomy to treat fibroids [7].  In this procedure, transcutaneous femoral artery approach is used to access the uterine artery, which is then embolized using embolic agents, including polyvinyl alcohol particles, trisacryl gelatin microspheres, and gelatin sponge [8]. Contraindications to this procedure include pregnancy, pelvic malignancies, and uterine or adnexal infection. Preparing for this procedure requires close collaboration among the patient, interventional radiologist, and gynecologist to assess preferences, benefits and risks [9]. As this is a minimally invasive procedure, patients often have shorter hospital stays compared to patients who undergo hysterectomies, on average by 4 days [10]. A recent single institutional study has found that same-day discharge with low rate of patient return is possible [11].

Current literature reviews of effect on fertility identify limitations in current data with small sample sizes and lack of randomization, but emphasizes that pregnancy is attainable after UFE with an approximate pregnancy rate of 38.3%, but compared to myomectomy, may have increased risk of preterm delivery and spontaneous abortion [12]. Similarly, a systematic review studying this same question found low quality of evidence and highlights the need for higher quality prospective randomized studies [13].

Patient symptom control and post-procedure satisfaction are highest in “ideal” candidates, which are women with no contraindications to UFE and with all of the characteristics like heavy regular menstrual bleeding or dysmenorrhea associated with intramural fibroids, Premenopausal and no desire for future pregnancy [14]. But the majority of women report high satisfaction with the procedure and improved quality of life. Ten year results of the randomized  Embolization vs Hysterectomy (EMMY) trial showed that close to 80% of women who received UFE were satisfied with their treatment. Eighty-one percent would suggest a friend undergo the procedure, and 74% of women who underwent UFE preferred their treatment modality compared to hysterectomy [15]. Several other studies also report sustained improvement in symptom severity and overall quality of life. [16, 17].

After UFE, patients can reasonably expect resolution of symptoms such as menorrhagia (90 – 92% of patients), pelvic pressure, and pelvic pain (88 – 96% of patients). Although infrequent, major adverse events can occur and include ovarian failure and future amenorrhea (7.5% of patients in FIBROID Registry), fibroid expulsion, and rarely venous thromboembolism with possible pulmonary embolism[18]. However, at one year post-embolization, UFE significantly improves all aspects of sexual function measured by Female Sexual Function Index (FSFI) and quality of life [19].

UFE is generally safe in patients with symptomatic fibroids. Obese patients (BMI > 30) and those with large volume uteri (> 1000cm3) are at slight increased risk of developing infection and require appropriate pre-procedural counselling, as well as careful post-UFE follow-up. BMI and uterine volume may be useful to assess before the procedure to help to determine post-UFE infection risk [20].

Impact and Future Directions
While uterine artery embolization (UAE) has demonstrated short term advantages, such as shorter and less painful recovery compared to surgery, the long-term outcomes are not as clear. The 10-year results of the EMMY trial, which was a randomized controlled trial of UAE versus hysterectomy for the treatment of symptomatic leiomyomas, showed that 31% of patients who received successful UAE underwent secondary hysterectomy [21]. Similarly, a meta-analysis examining UAE compared to surgical procedures for the treatment of symptomatic leiomyomas reported increased risk of re-intervention in the UAE group after both two and five years [22]. Incomplete infarction of the leiomyoma, which subsequently results in the growth of the non-infarcted tissue, may lead to symptom recurrence and the indication for additional intervention [23].

Future innovations of UAE are looking to address the current inadequacies of the treatment modality. For example, a recent study explored the use of a convolutional neural network (ResNet) model to predict UAE outcomes using routine magnetic resonance imaging [24]. ResNet is a deep learning model that learns hierarchical representations of imaging data. Using T1-weight contrast-enhanced (T1C) sequence images, the model demonstrated a better test accuracy, sensitivity, and specificity than four radiologists. Similar to other machine learning technologies, this model is unlikely to replace radiologists. Instead, it is likely that in the not-so-distant future that both diagnostic and interventional radiologists will use machine learning models to aid in the selection of patients that are most likely to benefit from UAE.

In addition to utilization of imaging models to improve clinical outcomes of UAE, the continued advancement of embolic materials deployed in UAE will likely also improve patient outcomes. A recent randomized controlled trial published by Han et al. investigated pain following UAE for symptomatic leiomyomas with either non-spherical polyvinyl alcohol particles (PVA) or tris-acryl microspheres (TAGM) [25]. Although patients who received PVA and TAGM showed equivalent pain scores and fentanyl dose, the two groups were not completely equivalent. The authors concluded that the utilization of PAV led to a greater inflammatory response and subsequently higher analgesic use, and more frequent transient global uterine ischemia.

Uterine artery embolization has significantly advanced the treatment of uterine fibroids. Nonetheless, there are still advances to be made. Additional research in all aspects of UAE will result in identification of variables that interventional radiologists can address in order to improve clinical outcomes.

1. Ghant MS, Sengoba KS, Recht H, Cameron KA, Lawson AK, Marsh EE. Beyond the physical: a qualitative assessment of the burden of symptomatic uterine fibroids on women’s emotional and psychosocial health. J Psychosom Res. 2015 May;78(5):499-503. doi: 10.1016/j.jpsychores.2014.12.016. Epub 2015 Feb 2. PMID: 25725565.

2. Ravina JH, Herbreteau D, Ciraru-Vigneron N, Bouret JM, Houdart E, Aymard A, Merland JJ. Arterial embolisation to treat uterine myomata. Lancet. 1995 Sep 9;346(8976):671-2. doi: 10.1016/s0140-6736(95)92282-2. PMID: 7544859

3. Raikhlin A, Baerlocher MO, Asch MR. Uterine fibroid embolization: CME update for family physicians. Can Fam Physician. 2007;53(2):250-256.

4. Silberzweig JE, Powell DK, Matsumoto AH, Spies JB. Management of Uterine Fibroids: A Focus on Uterine-sparing Interventional Techniques. Radiology. 2016 Sep;280(3):675-92. doi: 10.1148/radiol.2016141693. PMID: 27533290.

5. Pinto I, Chimeno P, Romo A, Paúl L, Haya J, de la Cal MA, Bajo J. Uterine fibroids: uterine artery embolization versus abdominal hysterectomy for treatment–a prospective, randomized, and controlled clinical trial. Radiology. 2003 Feb;226(2):425-31. doi: 10.1148/radiol.2262011716. PMID: 12563136.

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7. ACOG Practice Bulletin No. 96: Alternatives to Hysterectomy in the Management of Leiomyomas. Obstet Gynecol. 2008;112(2 Part 1):387-400. doi:10.1097/AOG.0b013e318183fbab

8. Goodwin SC, Spies JB. Uterine Fibroid Embolization. doi:10.1056/NEJMct0806942

9. Bulman JC, Ascher SM, Spies JB. Current Concepts in Uterine Fibroid Embolization. RadioGraphics. 2012;32(6):1735-1750. doi:10.1148/rg.326125514

10. Silberzweig JE, Powell DK, Matsumoto AH, Spies JB. Management of Uterine Fibroids: A Focus on Uterine-sparing Interventional Techniques. Radiology. 2016;280(3):675-692. doi:10.1148/radiol.2016141693

11. Sher A, Garvey A, Kamat S, et al. Single-System Experience With Outpatient Transradial Uterine Artery Embolization: Safety, Feasibility, Outcomes, and Early Rates of Return. AJR Am J Roentgenol. Published online February 3, 2021:1-6. doi:10.2214/AJR.20.23343

12. Ludwig PE, Huff TJ, Shanahan MM, Stavas JM. Pregnancy success and outcomes after uterine fibroid embolization: updated review of published literature. Br J Radiol. 2019;93(1105):20190551. doi:10.1259/bjr.20190551

13. Karlsen K, Hrobjartsson A, Korsholm M, Mogensen O, Humaidan P, Ravn P. Fertility after uterine artery embolization of fibroids: a systematic review. Arch Gynecol Obstet. 2018;297(1):13-25. doi:10.1007/s00404-017-4566-7

14. Young M, Coffey W, Mikhail LN. Uterine Fibroid Embolization. 2020 Jul 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID: 30085558.

15. de Bruijn, A. M., Ankum, W. M., Reekers, J. A., Birnie, E., van der Kooij, S. M., Volkers, N. A., & Hehenkamp, W. J. (2016). Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 10-year outcomes from the randomized EMMY trial. American journal of obstetrics and gynecology, 215(6), 745-e1.

16. Goodwin, S. C., Spies, J. B., Worthington-Kirsch, R., Peterson, E., Pron, G., Li, S., & Myers, E. R. (2008). Uterine artery embolization for treatment of leiomyomata: long-term outcomes from the FIBROID Registry. Obstetrics & Gynecology, 111(1), 22-33.

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19. Kovacsik HV, Herbreteau D, Bommart S, Beregi JP, Bartoli JM, Sapoval M; French Society of Interventional and cardiovascular Imaging (SFICV) research group. Evaluation of Changes in Sexual Function Related to Uterine Fibroid Embolization (UFE): Results of the EFUZEN Study. Cardiovasc Intervent Radiol. 2017 Aug;40(8):1169-1175. doi: 10.1007/s00270-017-1615-3. Epub 2017 Mar 20. PMID: 28321542.

20. Mollier J, Patel NR, Amoah A, Hamady M, Quinn SD. Clinical, Imaging and Procedural Risk Factors for Intrauterine Infective Complications After Uterine Fibroid Embolisation: A Retrospective Case Control Study. Cardiovasc Intervent Radiol. 2020 Dec;43(12):1910-1917. doi: 10.1007/s00270-020-02622-2. Epub 2020 Aug 26. PMID: 32851424; PMCID: PMC7649153.

21. de Bruijn, A. M., Ankum, W. M., Reekers, J. A., Birnie, E., van der Kooij, S. M., Volkers, N. A., & Hehenkamp, W. J. (2016). Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 10-year outcomes from the randomized EMMY trial. American journal of obstetrics and gynecology, 215(6), 745-e1.

22. Fonseca, M. C., Castro, R., Machado, M., Conte, T., & Girao, M. J. (2017). Uterine artery embolization and surgical methods for the treatment of symptomatic uterine leiomyomas: a systemic review and meta-analysis followed by indirect treatment comparison. Clinical therapeutics, 39(7), 1438-1455.

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24. Luo, Y. H., Xi, I. L., Wang, R., Abdallah, H. O., Wu, J., Vance, A. Z., … & Shlansky-Goldberg, R. (2020). Deep learning based on mr imaging for predicting outcome of uterine fibroid embolization. Journal of Vascular and Interventional Radiology, 31(6), 1010-1017.

25. Han, K., Kim, S. Y., Kim, H. J., Kwon, J. H., Kim, G. M., Lee, J., … & Kim, M. D. (2020). Nonspherical Polyvinyl Alcohol Particles versus Tris-Acryl Microspheres: Randomized Controlled Trial Comparing Pain after Uterine Artery Embolization for Symptomatic Fibroids. Radiology, 201895.