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ORIGINAL RESEARCH |
From the Image Guided Surgery Associates, Philadelphia, Pennsylvania; Department of Radiology, Georgetown University Medical Center, Washington, DC; Department of Obstetrics and Gynecology and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina; Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Department of Public Health Sciences, University of Toronto, Ontario, Canada; Department of Medicine, Duke University Medical Center, Durham, North Carolina; and Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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Methods: Examining the FIBROID Registry, a multicenter prospective voluntary registry of patients undergoing uterine embolization for leiomyomata, we studied the frequency of adverse events and predictors of adverse events within 30 days of the procedure. We also report on the technical aspects of the procedure, including details of periprocedural care, technique, and short-term recovery. All adverse events were recorded and classified using standard definitions, both in terms of type and severity. Summary statistics were used to describe the data set, and univariate and multivariate analyses were used to determine which factors might influence the incidence of adverse events.
Results: Of the 3,160 patients enrolled at 72 contributing sites, major in-hospital complications occurred in 0.66%, and postdischarge major events occurred in 4.8% within the first 30 days. The most common adverse event after discharge was inadequate pain relief requiring additional hospital treatment (2.4%). Thirty-one patients required additional surgical intervention within 30 days after treatment, 3 of whom required hysterectomy (0.1%). There were no deaths. Multivariate analysis showed modest increased odds for an adverse event for African Americans, smokers, and those with prior leiomyoma procedures. There were no differences in outcome based on the practice site experience, practice type, or any procedure-related factors.
Conclusion: Uterine embolization for leiomyomata is a low-risk procedure with little variability in short-term outcome based on either patient demographics or practice setting.
Level of Evidence: II-3
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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Registry was designed as a prospective multicenter study to evaluate the short- and long-term outcome of uterine embolization practice throughout the United States.
Sites participated in the Registry on a voluntary basis. In total, 72 sites, 26 core and 46 participating sites, contributed patients to the registry. All sites obtained institutional review board approval and were expected to submit demographic, procedural, and 30-day outcome data on all patients consenting to participate. Procedure-related data included length of procedure, type and amount of embolic material used, number of vessels successfully embolized, type of analgesia used, use of antibiotics, deep vein thrombosis prophylaxis, length of hospitalization, and in-hospital complications.
At 30 days after therapy, follow-up data on recovery were obtained from each patient, preferably during an office visit. These data included any additional reinterventions received since the procedure, unanticipated office or emergency room visits, unanticipated hospitalizations, time to return to work, and time to return to normal activities. Thirty-day follow-up was obtained for 2,729 patients of the 3,005 patients enrolled (90.8%).
Uterine artery embolization is a fluoroscopically guided, catheter-based intervention. After arterial access is obtained, usually through a right common femoral artery approach, the uterine arteries are selectively catheterized. The uterine arteries are embolized with particulate embolic materials. This occludes the blood flow to the leiomyomata and results in their infarction and shrinkage, with of a reduction or resolution of symptoms.
For the Registry, an adverse event was defined as any event that was unexpected and resulted in unanticipated physician office or emergency room visits, or unanticipated therapy (medical or surgical). Whether the adverse event resolved by 30 days after treatment was recorded.
The categories of adverse events are listed in Table 1. Adverse events were scored according to the Society of Interventional Radiology scale for severity.7 In addition, adverse events were classified using a system of complication definitions derived from the American College of Obstetricians and Gynecologists (ACOG) quality indicators, which have been used previously to classify complications of hysterectomy, myomectomy,9 and more recently, uterine embolization.2 Society of Interventional Radiology Class A and B adverse events, requiring no or nominal therapy, were considered to be minor complications, and Class C, D, E, or F (requiring either unplanned increase in care, additional hospitalization or causing permanent adverse sequelae) were considered to be major complications. With each report of a major complication, the site was requested to provide additional details of the adverse event, including its nature, duration, treatment provided, preliminary classification of the adverse event, and whether the adverse event had resolved. All major adverse events were reviewed by an Adjudication Committee consisting of 3 physician members of the Registry Steering Committee, 2 interventional radiologists (J.B.S. and R.L.W.K.) and a gynecologist–epidemiologist (E.R.M.), and final assignment as to Society of Interventional Radiology and ACOG classification was reached by consensus.
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For event rate calculations, denominators included all patients with adverse event reports during hospitalization and 30 days, even if all baseline data were not complete (N = 3,041 for in-hospital events, N = 2,729 for 30-day events). Rates were also calculated including those with missing adverse event data (no definite indication of whether an adverse event occurred), assuming that lack of adverse event reporting indicated no adverse event.
Because the combined major and minor 30-day events were very low, we examined the combined adverse events for predictors. For the descriptive analysis, mean or median values were used to describe continuous variables, and percentages were reported for categorical variables. The Wilcoxon rank-sum test for continuous variables and the 
2 test for categorical variables were used to test for differences. To determine factors that predict "any (one or more) adverse event at 30 days" a stepwise Generalized Estimating Equations (GEE) method was used.9 Nonsignificant variables were eliminated sequentially, resulting in a predictive model for any adverse event at 30 days, containing significant variables only.
The variables considered for determining significance as predictors were patient demographic variables (age, body mass index, race, parity, uterine volume), medical history variables (smoking history, other comorbidities, prior medical and invasive therapies for leiomyomata), presenting signs and symptoms, number of leiomyomata, size, location and morphology of largest or symptom-causing leiomyoma), medications used (prophylactic antibiotics, deep vein thrombosis prophylaxis), procedure-related variables (duration of procedure, material used, which vessels were embolized), and site level variables (core, academic, experience).
A value of P < .05 was established as the level of statistical significance for all tests. All statistical analyses were performed using SAS 8.2 software (SAS Institute, Cary, NC).
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RESULTS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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The average procedure time was 56 minutes, with an average fluoroscopy time of 16.7 minutes. Technical success was achieved in 96.2% of patients. In 92.7% there was embolization of both uterine arteries, and in another 3.5% of patients there was embolization of 1 uterine artery and a contralateral ovarian artery in patients with an anatomic variant. Of the 4% of cases that were technical failures, there were 25 cases where only 1 uterine artery was identified and no second vessel (uterine, ovarian, or other) was identified, and only unilateral embolization was completed. In the remaining cases 2 uterine arteries were present but 1 or both could not be successfully catheterized. A total of 18 patients had no embolization.
The primary embolic agent used was calibrated microspheres in 73% of cases (either Embosphere or Embosphere Gold, Biosphere Medical, Rockland, MA), particulate polyvinyl acetate (Contour, Boston Scientific/Medi-Tech, Natick, MA, Biodyne, Cook, Inc, Bloomington, IL, or Tru-Fill, Cordis, Inc, Hialeah, FL) in 31% of cases, and gelatin sponge (usually Gelfoam, Pharmacia Upjohn, Kalamazoo, MI) in 3% of cases. In some cases more than 1 primary embolic agent was used. Embolization was supplemented in 6% of cases by either gelatin sponge (5%) or embolic coils (1%; eg, Gianturco Embolic Coils, Cook, Inc, Bloomington, IL).
Most patients (94.1%) were kept in the hospital overnight and discharged the next day, with a mean stay of 1.68 days (95% confidence interval [CI] 1.21–2.15) from preprocedure admission to the hospital discharge. There were 94 adverse events in 90 patients during the hospitalization for uterine embolization (3% of the total population). Five patients experienced 2 adverse events. Adverse events are classified by Society of Interventional Radiology and ACOG definitions in Table 1 and by type in Table 2. Of these, 74 (78.7%) were Society of Interventional Radiology Class A or B (minor). There were 20 major adverse events, 11 of which required the patient to stay longer than 48 hours. Most of the major adverse events (10 events) were for prolonged pain or nausea. All resolved without sequelae but one. A single Class E complication occurred, which was a femoral nerve injury resulting in leg pain that was judged permanent. There were no deaths (Class F). Because of the low number of serious adverse events, power to detect predictors was limited. At the bottom of Table 1, the complications meeting the definitions of the ACOG quality indicators are listed. Because these descriptors are not inclusive of all potential complications, the number listed is smaller than the total in the upper section of the table.
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In univariate analyses, there were few predictors of an adverse event. These included length of procedure (odds ratio [OR] 1.012, 95% CI 1.005–1.019), core site status (OR 0.334, 95% CI 0.15–0.76), and size of leiomyoma (OR 1.073, 95% CI 1.013–1.138). Patient presenting symptoms, demographic factors, and the type of embolic material used did not predict adverse events.
Multivariate analysis demonstrated a relatively small alteration in odds of an adverse event in hospital compared with univariate analysis. These included length of procedure (OR 1.10, 95% CI 1.005–1.01), size of leiomyoma (OR 1.11, 95% CI 1.028–1.20) and uterine volume (OR 0.999, 95% CI 0.998–0.999).
Patients returned to normal activities in a mean of 13.86 days (95% CI 13.52–14.20). Of those women who worked outside the home (N = 2,404), the mean number of days lost from work (including the day of the procedure) was 9.63 (95% CI 9.38–9.88).
Adverse events occurring between discharge from the hospital and 30 days after uterine embolization were reported in 710 women (26%), of whom 191 (7%) had more than 1 adverse event. These are summarized by type in Table 2, and they are classified by severity in Table 1. Major events occurred in 111 patients (4%). The most common was emergency room care or readmission for recurrent pain in 65 (2.1%), followed by evaluation for possible infection in 19 (0.62%). The most common minor adverse events were hot flushes (5.7%) and pain requiring additional therapy (9.6%). The classification of minor events at 30 days was limited by incomplete data in 228 cases; it was unclear from the submission whether these required any therapy, and thus their status as Class A or B complications could not be distinguished. These are listed separately in Table 1.
There was 1 Class E complication at 30 days. A patient developed pelvic pain while on vacation abroad 10 days after embolization. The cause was unclear, and exploratory laparotomy was performed. There was inflammation involving both ovaries, although the uterus was normal. Bilateral oophorectomy was performed. The patient had an uncomplicated subsequent recovery. The pathologic report was not available for review.
During the period between discharge and 30 days after uterine embolization, 31 (1.1%) patients had a surgical intervention, and 1 patient had a repeat embolization (for initially failed procedure). Of the 31 surgical interventions, 1 involved bilateral oophorectomy (discussed above), 3 were myomectomies, 5 were hysteroscopic resections or removal, 9 were dilation and curettage for sloughing leiomyomata, and 3 were hysterectomies. The intervention for 10 other patients was not specified. Of these interventions, the majority were for management of a sloughing leiomyoma or passage of leiomyoma tissue. Indications for hysterectomy were not recorded.
The results of univariate analysis for any 30-day event is presented in Table 3. The primary presenting symptoms before uterine embolization did not influence the likelihood of any adverse event, nor did the position of the dominant leiomyoma. Those with prior procedures or prior medical therapy, African Americans, smokers, and those with comorbidities were at increased risk. Use of DVT prophylaxis decreased the odds of an adverse event, whereas longer procedures had a small associated increase in risk. Thirty-day major complications had no clear relationship with site experience or site type (academic compared with others). Again, embolic material and other procedure-related factors did not influence risk nor did operator experience.
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Results of multivariate analysis is presented in Table 4. After adjustment for potential confounding, only smoking status (OR 1.14, 95% CI 1.007–1.293), African American (OR 1.129, 95% CI 1.019–1.251), history of prior procedures (OR 1.23, 95% (CI) 1.02–1.38), and duration of procedure (OR 1.004, 95% CI 1.001–1.006) were associated with an increased risk of 30-day adverse events. Use of DVT prophylaxis decreased risk (OR 0.757, 95% CI 0.622–0.919).
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DISCUSSION |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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The incidence of all adverse events was low, and major complications either in hospital (0.66%) or 30-day postdischarge (4.8%) were infrequent. These low rates were obtained despite a conservative definition of major complication in the Society of Interventional Radiology classification system of adverse events. Any patient with an initial hospitalization longer than 2 days, or postdischarge reevaluation in the emergency room or readmission were considered to have a major complication, even if the reevaluation did not result in admission or if the admission was for only 1 night. Only 3 patients underwent a hysterectomy in the first month after the procedure (0.09%), and only 31 patients had additional surgical interventions of any type (1.1%). The current study reinforces the results of earlier, smaller studies that major interventions are quite rare.
The findings of this study also differ from those that have assessed the risk of leiomyoma surgery. For hysterectomy, increasing uterine size is associated with increasing risk of complications after hysterectomy, particularly blood loss.10,11 Febrile morbidity after hysterectomy is associated with abdominal approach and blood loss greater than 750 mL.12 Similar findings have been noted with myomectomy, with increased odds of an adverse event for uterine size (OR 1.86), number of leiomyomata (OR 1.83), and comorbidities (OR 2.77).13 The lack of an effect of these same factors for uterine embolization suggests that embolization may be an attractive alternative to surgical therapies for leiomyomata for patients who may be at increased risk of operative complications. However, because the incidence of adverse events was very low, we ultimately had limited power to determine reliable predictors of complications.
Although these findings are reassuring regarding uterine embolization safety, there are limitations to the data provided by the Registry. First, because of the voluntary nature of the Registry, formal site monitoring, and data verification was not performed. Principal investigators and study coordinators were not funded for their time for data entry, and funds were not available for on-site monitoring, as would be typical in a phase III trial of new medications submitted for FDA approval. This resulted in higher proportions of missing variables than would be seen in a phase III trial; however, these values are similar to those seen in other voluntary registries.14 In addition, it is possible that some adverse events were not recorded, or that rates were higher in those patients for whom these data were not recorded. However, given that hospital performance results were confidential and not linked to public reporting or reporting to other Registry investigators, sites did not have a strong incentive for underreporting of adverse events in the registry.
We are also limited in our ability to compare results with other treatments for leiomyomata. Obviously, a randomized trial would be ideal, but any such trial would likely be powered on the ability to detect a difference in symptomatic outcomes, rather than adverse events, because of the large sample sizes needed to detect differences in rare adverse outcomes. Comparison with other published studies is possible, but these comparisons must be undertaken with extreme caution because of variability in reporting of potential predictors of outcome.15,16 Finally, although there was a diversity of sites, a large number of the cases (31%) were represented by 2 sites with extensive experience with uterine embolization before the start of the registry. Although analysis of the data with and without these sites did not reveal any substantive differences, it is possible that some effects related to site characteristics could not be observed because of the large volume from these sites.
Based on the data presented here, it can be concluded that embolization is safe, with complication rates that compare favorably with those reported for surgical interventions for leiomyomata, and that, for the majority of patients, the procedure requires only limited hospitalization and a short recovery period.
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APPENDIX |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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Anne Roberts, MD, University of California San Diego Medical Center, La Jolla, CA; Jeffrey Dieden, MD, Kaiser Medical Center, Oakland, CA; Mahmood Razavi, MD, Stanford University Hospital, Palo Alto, CA; Michael Hines, MD, Kaiser Permanente Hospital, Vallejo, CA; James Spies, MD, Georgetown University Hospital, Washington, DC; James Benenati, MD, Miami Cardiac and Vascular Institute, Miami, FL; Gerald Niedzwiecki, MD, Mease Countryside Hospital, Safety Harbor, FL; John Lipman, MD, Radiology Associates of Atlanta, Atlanta, GA; Robert Vogelzang, MD, Northwestern Memorial Hospital, Chicago, IL; Steven Smith, MD, LaGrange Memorial Hospital, LaGrange, IL; Karen Ehman, MD, Methodist Hospital, Indianapolis, IN; Moises Yoselevitz, MD, Ochsner Clinic Foundation, New Orleans, LA; David Brophy, MD, Mount Auburn Hospital, Cambridge, MA; Rajinder Sharma, MD, Henry Ford Hospital, Detroit, MI; William Romano, MD, William Beaumont Hospital, Royal Oak, MI; David Hovesepian, MD, Mallinckrodt Institute of Radiology, St. Louis, MO; Mark Garcia, MD, Christiana Care Health Services, Newark, NJ; Gary Siskin, MD, Albany Medical Center, Albany, NY; Robert Min, MD, Cornell Vascular-New York Presbyterian Hospital New York, NY; James Newman, MD, Cleveland Clinic Foundation, Cleveland, OH; Robert Worthington-Kirsch, MD, Delaware Valley Imaging, Philadelphia, PA; Joseph Bonn, MD, Thomas Jefferson University Hospital, Philadelphia, PA; Richard Schlansky-Goldberg, MD, Hospital of the University of Pennsylvania, Philadelphia, PA; Keith Sterling, MD; INOVA Alexandria Hospital, Alexandria, VA.
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Footnotes |
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No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Address reprint requests to: Evan R. Myers, MD, MPH, DUMC 3279, 244 Baker House, Duke University Medical Center, Durham, NC, 27710; e-mail: myers008{at}mc.duke.edu.
Financial Disclosure
Funded by the Society of Interventional Radiology Foundation through unrestricted grants from Biosphere Medical, Boston Scientific Corporation, COOK, Inc, and Cordis Endovascular; additional support for analysis was provided by the Agency for Healthcare Research and Quality and the Food and Drug Administration Office of Women’s Health.
See related article on page 44. 
doi:10.1097/01.AOG.0000165828.68787.a9
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REFERENCES |
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2. Spies J, Spector A, Roth A, Baker C, Mauro L, Murphy-Skrynarz K. Complications after uterine artery embolization for leiomyomata. Obstet Gynecol 2002;100:873–80.
3. Walker WJ, Pelage JP. Uterine artery embolisation for symptomatic fibroids: clinical results in 400 women with imaging follow up. Br J Obstet Gynaecol 2002;109:1262–72.
4. Pron G, Bennett J, Common A, Sniderman K, Asch M, Bell S, et al. Technical results and effects of operator experience on uterine artery embolization for fibroids: the Ontario Uterine Fibroid Embolization Trial. J Vasc Interv Radiol 2003;14:545–54.[Medline]
5. Pron G, Mocarski E, Cohen M, Colgan T, Bennett J, Common A, et al. Hysterectomy for complications after uterine artery embolization for leiomyoma: results of a Canadian multicenter clinical trial. J Am Assoc Gynecol Laparosc 2003;10:99–106.[Medline]
6. Hutchins F, Worthington-Kirsch R, Berkowitz R. Selective uterine artery embolization as primary treatment for symptomatic leiomyomata uteri. J Am Assoc Gynecol Laparosc 1999;6:279–84.[Medline]
7. Goodwin S, Bonilla S, Sacks D, Reed RA, Spies JB, Landow WJ, et al. Reporting standards for uterine artery embolization for the treatment of uterine leiomyomata. J Vasc Interv Radiol 2001;12:1011–20.[Medline]
8. Liang KY, Zeger S. Longitudinal data analysis using generalized linear models. Biometrika 1986;73:13–22.
9. Sawin S, Pilevsky N, Berlin J, Barnart K. Comparability of peri-operative morbidity between abdominal myomectomy and hysterectomy for women with uterine leiomyomas. Am J Obstet Gynecol 2000;183:1448–55.[Medline]
10. Unger J, Paul R, Caldito G. Hysterectomy for the massive leiomyomatous uterus. Obstet Gynecol 2002;100:1271–1275.
11. Hillis S, Marchbanks P, Peterson H. Uterine size and risk of complications among women undergoing abdominal hysterectomy for leiomyomas. Obstet Gynecol 1996;87:539–43.[Abstract]
12. Peipert J, Weitzen S, Cruickshank C, Story E, Ethridge D, Lapaine K. Risk factors for febrile morbidity after hysterectomy. Obstet Gynecol 2004;103:86–91.
13. Roth T, Gustilo-Ashby T, Barber M, Myers E. Effects of race and clinical factors on short-term outcomes of abdominal myomectomy. Obstet Gynecol 2003;101:881–4.
14. Jacobs J, Mavroudis C, Jacobs M, Lacour-Gayet FG, Tchervenkov CI, William Gaynor J, et al. Lessons learned from the data analysis of the second harvest (1998–2001) of the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database. Eur J Cardiothorac Surg 2004;26:18–37.
15. Matchar DB, Myers ER, Barber MW, Couchman GM, Datta S, Gray RN, et al. Management of uterine fibroids. Evid Rep Technol Assess (Summ) 2001;34:1–6.
16. Myers E, Barber M, Gustilo-Ashby T, Couchman G, Matchar D, McCrory D. Management of uterine leiomyomata: what do we really know? Obstet Gynecol 2002;100:8–17.
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