AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Clinical Background
• Rationale
• Preprocedure Evaluation
• Technique
• Recovery
• Results
• Potential Complications
• Multimedia
• References

CLINICAL BACKGROUND

Section 2 of 10  

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• Clinical Background
• Rationale
• Preprocedure Evaluation
• Technique
• Recovery
• Results
• Potential Complications
• Multimedia
• References

Uterine leiomyomas, better known as uterine fibroids, are benign smooth muscle tumors of the uterus. As the most common tumor found in the female reproductive system, uterine fibroids are seen in 20-25% of all women and are estimated to occur in 40% of menstruating women older than 50 years. In addition, uterine fibroids occur twice as frequently in black women as in either white or Asian women. Uterine fibroids can be seen at any time between menarche and menopause but most commonly occur in those aged 35-49 years. They typically resolve after menopause.

Uterine fibroids can be classified by their location.

• Submucosal fibroids are the least common. Because they are in the submucosa and near the endometrial cavity, they are associated with heavy and prolonged menstrual periods and an increased miscarriage rate. Submucosal fibroids may be pedunculated and may prolapse into the cervix.
• Intramural fibroids grow within the uterine wall. Their growth may be associated with mass-related symptoms such as abdominal distension due to mass or urinary frequency due to bladder compression.
• Subserosal fibroids develop in the outer portion of the uterus. They may be pedunculated, can potentially grow into the abdomen or in the ligaments of the uterus, and are associated with bladder compression and abdominal distension.

Most patients are asymptomatic. Fibroids typically are discovered incidentally during routine gynecologic examination. Presenting symptoms most commonly include the following:

• Abnormal uterine bleeding
• Pelvic pain, possibly resulting from intramural degeneration, torsion of a pedunculated fibroid, or uterine contractions
• Pelvic pressure
• Abdominal distension
• Genitourinary dysfunction, which may manifest as the following:
  • Increased urinary frequency resulting from bladder compression
  • Flank pain resulting from ureteral compression and hydronephrosis
• Infertility
• Rarely, lower extremity edema, constipation, or intestinal obstruction

For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education articles Fibroids and Amenorrhea.

RATIONALE

Section 3 of 10  

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• Results
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The rationale for the use of uterine artery embolization, or uterine fibroid embolization (UFE), to treat uterine fibroids can be traced to several known indications for embolotherapy.

• As a palliative treatment for endstage cancer patients, embolotherapy successfully addresses symptoms attributed to the presence of a tumor (eg, bone pain resulting from bony metastases arising from renal cell carcinoma, abdominal pain resulting from inoperable liver tumors). This includes symptoms related to mass.
• Embolotherapy reduces the vascularity of tumors prior to surgical excision, thereby reducing intraoperative blood loss (eg, renal cell carcinomas, spinal tumors prior to resection).
• Embolotherapy controls tumor-related bleeding throughout the body (eg, bleeding secondary to renal cell carcinoma, bladder tumors, angiomyolipoma, hepatic adenomas).
• Embolotherapy controls abnormal uterine bleeding caused by gynecologic malignancies, postpartum hemorrhage, bleeding from an ectopic pregnancy, and bleeding caused by congenital arteriovenous malformations.

In light of the success of embolization in reducing solid tumors and diminishing associated symptoms, UFE is performed to reduce uterine as well as fibroid volume and their associated symptoms.

PREPROCEDURE EVALUATION

Section 4 of 10  

• Authors and Editors
• Clinical Background
• Rationale
• Preprocedure Evaluation
• Technique
• Recovery
• Results
• Potential Complications
• Multimedia
• References

Imaging

Prior to embolization, it is important to document the presence of fibroids. This can be accomplished using either pelvic ultrasound (US) or MRI. While US may be effective at determining enlargement of the uterus and denoting if fibroids are present or if other pathology can explain a patient's presenting symptoms, its imaging is dependent on machinery used and the body habitus of the patient. MRI is preferred because of its greater ability to demonstrate individual fibroids and denote their size, location, and number within the uterus. MR also allows easier determination of internal characteristics of individual fibroids as well as their vascularity. In a preliminary report, Jha et al attached prognostic significance to both the location and vascularity of fibroids. Mizukami et al also have reported a possible prognostic value for preprocedural MRI by demonstrating better response to embolization in patients with intermediate or high-signal intensity within their fibroids on T2-weighted images.

Pelvic MRI also can determine if coexisting pathology is present within the uterus. For example, menorrhagia and other symptoms commonly associated with uterine fibroids may be similar to those of patients with adenomyosis. Adenomyosis, a benign uterine disease, is characterized by the ectopic growth of endometrial glands and stroma into the myometrium, and by diffuse enlargement of the uterus. MRI is the best imaging tool for the diagnoses of adenomyosis using criteria that include diffuse or focal widening of the junctional zone as well as bright foci or linear striations within the myometrium on T2-weighted images. On MRI, a focal adenomyoma may appear as a localized low-signal myometrial mass with poorly defined margins that often contain high-signal foci.

MRI is also helpful in assessing the results of embolization several months after the procedure.

Technically, one should obtain measurements of the uterus and of each fibroid in three planes, then calculate the volume measurements using the formula for the volume of a sphere (length x width x height x 0.5233). These measurements help the radiologist determine the degree of postprocedural fibroid and uterine volume reduction. After embolization, the signal intensity of the fibroids usually decreases on both T1-weighted and T2-weighted images. Embolization seems to have little effect on the volume or enhancement characteristics of normal myometrium and endometrium.

Other testing

In addition to pelvic MRI, evaluate the patient's renal function (ie, blood urea nitrogen level, creatinine level) and coagulation profile (ie, platelet count, prothrombin time, partial thromboplastin time). At the author's institution, a normal Papanicolaou (Pap) smear is required within 6 months of embolization, and an endometrial biopsy is recommended within 12 months for all patients presenting with menorrhagia. These tests evaluate the patient for both endometrial hyperplasia and endometrial malignancy.

Other procedures

Gonadotropin-releasing hormone (GnRH) agonists often are used as a medical treatment for uterine fibroids, most often before myomectomy or hysterectomy to reduce the potential morbidity of these procedures. Withhold GnRH agonist therapy before patients undergo the procedure since these medications can lead to constriction of the arteries supplying the uterus, which can add to the technical difficulty of the UFE procedure. Since fibroids have been shown to return to normal size within 12 weeks of the cessation of GnRH agonist therapy, UFE should be performed after GnRH agonists have been stopped for at least 12 weeks.

TECHNIQUE

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• Preprocedure Evaluation
• Technique
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• Results
• Potential Complications
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Prior to embolization, an intravenous (IV) line and Foley catheter are placed in all patients. Prophylactic antibiotics usually are given prior to the procedure. At the author's institution, all patients receive 1 g cefazolin IV (Ancef) for prophylaxis; 500 mg of vancomycin is administered to patients with a history of penicillin allergy. The choice of antibiotics and other premedications (eg, use of corticosteroids, antiemetics, analgesics) vary.

UFE typically is performed as follows:

1. A sheath is placed into either the right or left common femoral artery.
2. Under fluoroscopic guidance, a flush catheter is advanced into the abdominal aorta.
3. A pelvic angiogram is performed to identify the right and left uterine arteries. Ovarian, lumbar, or other collateral parasitic supplies to a large myomatous uterus may be seen (see Image 1). The uterine arteries, which typically arise from the anterior division of the internal iliac artery, are responsible for most of the uterine blood supply. A selective arteriogram of the uterine artery reveals the terminal branches, known as the spiral arteries, which dilate and uncoil in response to changes in hormonal levels and endometrial thickness. In the presence of fibroids, arteriography of the uterine arteries shows these vessels as dilated, tortuous, and laterally displaced (see Images 2-3). One can confirm the hypervascular nature of the fibroid by noting the extensive network of intrinsic arteries within the fibroid.
4. Once identified, the uterine arteries should be selectively catheterized.
5. An embolic agent, such as polyvinyl alcohol (PVA) or Embospheres, is injected directly into the uterine arteries to induce thrombosis. Both uterine arteries should be embolized because the spiral arteries arising from them anastomose across the midline. Unilateral embolization caused one of the earliest reported cases of a UFE treatment failure. In some patients, a 4Fr or 5Fr catheter may be occlusive within one or both uterine arteries. If this occurs, a coaxial microcatheter may be used to administer the embolic agent. If a microcatheter is used, some difficulty may be encountered if 500-710 micron PVA is used as the embolic agent. Diluting the agent appropriately along with frequent catheter flushing may minimize the risk of catheter occlusion in this setting.
6. After embolization of both uterine arteries, a complete angiogram (see Image 4) should be performed to confirm that arterial occlusion has occurred. It will also allow a search for collateral vessels (eg, ovarian arteries, vaginal arteries) that may represent a significant source of collateral blood supply to the fibroids.

Polyvinyl alcohol

PVA is the most commonly used embolic agent for UFE. The biocompatibility of PVA was established prior to its first medical use in 1949 as a filling material following pneumonectomy. The first successful use of PVA as an embolic agent was reported by Tadavarthy et al in two studies that included patients with cervical carcinoma, hemangiosarcoma of the liver, hemangioendothelioma of the neck and forehead, and arteriovenous malformation of the spine. Since then, PVA has been used to embolize patients with abnormal bleeding caused by arteriovenous malformations, tumors, and other disorders such as hemoptysis due to cystic fibrosis.

The desired level of occlusion (ie, proximal, distal) determines the particle size selection for each embolization procedure. Generally, using small particles results in a more distal occlusion, increasing the risk for end-organ infarction. However, the tendency of PVA particles to clump often makes the effective size larger than that of individual particles, which may account for the proximal occlusion often seen during PVA embolization. The optimum particle size for UFE is not established; most centers use particles measuring 350-500 or 500-710 micrometers in diameter.

Histologically, PVA particles adhere to the vessel wall, causing slow flow within that vessel. The result is intraluminal thrombus formation, inflammatory reaction, foreign body reaction, and focal angionecrosis of the vessel wall. The foreign body reaction induced by PVA is reported to persist up to 28 months after embolization.

PVA is not biodegradable, thus is considered by many to be a "permanent" embolic agent; however, the reported duration of PVA-induced vascular occlusion has varied. A persistent occlusion will occur with organization of the thrombus, disappearance of the inflammatory infiltrate, and ingrowth of connective tissue into the particles, resulting in fibrosis. Luminal recanalization has been reported and may be caused by angioneogenesis and capillary regrowth either because of vascular proliferation inside the organized thrombus or resorption of the thrombus found between clumps of PVA.

RECOVERY

Section 6 of 10  

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UFE postembolization syndrome is similar to solid tumor postembolization syndrome. It affects most patients undergoing UFE and lasts approximately 2-7 days. Symptoms may include the following:

• Pelvic pain and cramping
• Nausea and vomiting
• Low-grade fever
• General malaise

Most patients experience these symptoms to some degree; however, the variation in severity has prompted the development of different strategies to increase patient comfort during recovery. Regimens involve oral, IV, epidural, and/or patient-controlled analgesia in both an inpatient and outpatient setting. Based on several reports, it seems that most centers admit patients for 1-2 days to aggressively manage these constitutional symptoms. At the author's institution, the outpatient protocol calls for a medication regimen as follows:

• Opioid analgesics (ie, oxycodone [OxyContin], acetaminophen and oxycodone [Percocet], meperidine, hydrocodone with acetaminophen): Currently, the authors administer OxyContin at 10-20 mg orally every 12 hours, with 1-2 tabs of Percocet 5/235 orally every 6 hours for pain not relieved with OxyContin.
• Nonsteroidal anti-inflammatory medications (ie, ketorolac, celecoxib [Celebrex], ibuprofen): Currently, the authors administer Celebrex at 100 mg orally every 12 hours for the first 7 days after embolization, followed by ibuprofen at 200 mg every 4-6 hours as needed.
• Antinausea medications (ie, prochlorperazine): Supply the patient with 25-mg suppositories for relief of nausea associated with embolization and the medications provided above for pain relief.

At the author's institution patients are offered the opportunity to recover at home following the embolization procedure. In the author's experience, most patients are best managed at home when the following conditions are met:

• Patients are provided with the medication regimen detailed above.
• Patients are ambulated as soon as possible (to prevent potential pulmonary embolus).
• Patients are given adequate education.
• Patients are given diligent follow-up care.
• The care provider is readily available to the patient.
• Family or friends can provide home support.

Once discharged, recommend patient activity as follows:

• On the day of the procedure, the patient should observe bedrest with only limited activity.
• The next day, the patient may engage in limited activity around her home.
• After 2 days, normal activity is permitted. At this point, individual tolerance for activity and reliance on pain medication are the best indicators of the patient's capabilities.
• After 6-10 days, most of the author's patients are able to return to work.

RESULTS

Section 7 of 10  

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• Preprocedure Evaluation
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• Results
• Potential Complications
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• References

Clinical Results

Embolization was first used by Ravina et al in patients with fibroids to reduce operative blood loss during myomectomy. As of 2001, it is estimated that over 10,000 UFE procedures have been performed in the United States. The procedure is not considered investigational and is reimbursed by most insurance companies.

Ravina also reported a study in which 16 patients underwent UFE as primary treatment for uterine fibroids. With a mean follow-up time of 20 months, 14 of 16 patients reported resolution or improvement of presenting symptoms; 2 patients required surgery because of symptoms that persisted after embolization. Since then, Ravina's published experience in 88 patients demonstrated improvement in menorrhagia in 89% who underwent embolization as their primary treatment for symptomatic uterine fibroids. In addition, embolization resulted in a 69% reduction in the volume of dominant fibroids. Recently, the same group presented their findings in 243 patients with follow-up care ranging from 6 months to 7 years and cited an 83% rate of improvement in abnormal bleeding after embolization.

Goodwin et al were the first in the United States to publish his experience with UFE. Since their initial article, Goodwin et al have published results in 59 patients followed for a mean period of 16.3 months. Significant improvement was noted in the presenting symptoms of 89%, and 92% had reductions in both uterine and dominant fibroid volumes. Mean uterine and dominant fibroid volume reductions were 42.8% and 48.8%, respectively.

Worthington-Kirsch et al reported their experience with UFE in 53 patients in 1998. Of patients presenting with menorrhagia and those presenting with bulk-related symptoms, 88% and 94% noted improvement after UFE, respectively. The mean uterine volume reduction noted was 46%. Of the patients in that study, 94% stated that they would either choose or consider embolization again if an additional procedure were required. Follow-up data on 305 patients, reported by Hutchins and Worthington-Kirsch in 1999, demonstrated significant improvement in abnormal bleeding in 92% of patients.

Spies et al published results in 61 patients undergoing UFE for symptomatic fibroids during a 16-month period. With a mean of 8.7 months of follow-up care, 89% of patients demonstrated an improvement in menstrual bleeding. Pelvic pain and pressure improved in 96% of patients. One year after UFE, the median uterine volume reduction was 48%, and the median dominant fibroid volume reduction was 78%. A significant improvement in quality of life was noted in this patient population. In a follow-up study, Spies et al reported data on 169 patients with a mean of 11.7 months of follow-up care. One year after UFE, improvement in menorrhagia and pelvic pain as well as pressure was noted in 86% and 88% of patients, respectively. Also, at that time, uterine volume was noted to have decreased 35% and dominant fibroid volume 69%.

Based on the above results, clinical success after embolization can be demonstrated in 81-96% of patients. This implies that 4-19% will not demonstrate a significant clinical benefit, although most patients do experience decreases in both uterine and fibroid volume.

Spies et al published another series of 200 consecutive UFE patients in 2001. After treatment, follow-up data were obtained by written questionnaire mailed to the patients at intervals of 2 weeks, 3 months, 6 months, and 12 months after treatment. Follow-up imaging was obtained at 3 months and 12 months after therapy. With a mean follow-up of 21 months, heavy menstrual bleeding improved in 87% of patients at 3 months and in 90% at 1 year after therapy. Bulk symptoms improved in 93% of patients at 3 months and in 91% at 1 year after treatment. They concluded that "uterine artery embolization is safe and controls the symptoms caused by leiomyomata in most patients."

Treatment failure can be defined as the absence of demonstrable clinical benefit after successful embolization of both right and left uterine arteries.

Possible explanations for treatment failure include the following:

• Incomplete embolization
• Luminal recanalization
• Extremely large uterine fibroids
• Presence of uterine leiomyosarcoma
• Presence of a coexisting disorder (eg, adenomyosis)
• Persistence of collateral sources of arterial blood supply to fibroids (eg, ovarian artery, round ligament artery)

Preprocedure imaging is routinely performed to assess the true size of the uterus and fibroids and to determine the presence of a coexisting disorder. While success has been observed after UFE in patients with large fibroids and in patients with adenomyosis, the potential for persistent postembolization symptoms must be discussed with these patients. Suspect the possibility of a leiomyosarcoma if the expected decrease in fibroid or uterine volume is not observed after embolization.

Pathologic results

Siskin et al, Aziz et al, and McLucas et al specifically studied the histologic effects observed after UFE with PVA particles. Administration of PVA into the lumen of the uterine arteries initiates a foreign body reaction, which leads to platelet aggregation and thrombus formation within the intraluminal PVA particles. Thrombus formation results in arterial occlusion and, ultimately, leads to interstitial edema within the fibroid, followed by ischemic necrosis and hyalinization. The myometrium adjacent to a fibroid embolized with PVA particles has been noted to be viable but edematous and chronically inflamed.

POTENTIAL COMPLICATIONS

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• Results
• Potential Complications
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Immediate complications

• Complications related to iodinated contrast material administration (not unique to UFE, thus familiar to most practicing interventional radiologists)
• Complications related to femoral arterial catheterization (not unique to UFE, thus familiar to most practicing interventional radiologists)
• Complications related to postembolization syndrome (see Recovery)
• Complications related to nontarget or inadvertent embolization of vessels other than the uterine artery. Branches of the anterior division of the internal iliac artery are at risk for nontarget embolization during UFE. In particular, inadvertent embolization of the vesical artery, which sometimes arises from a common trunk with the uterine artery, may increase the risk of bladder necrosis. It may be possible to prevent nontarget embolization by performing the following:
  • Ensure a thorough knowledge of pelvic arterial anatomy and potential variants.
  • Proceed carefully, using an angiographic technique that includes the following:
    • Position the catheter into the descending segment of the uterine artery and confirm this position with an arteriogram prior to embolization.
    • Inject embolic materials under fluoroscopic guidance to prevent reflux into other arteries.
    • Flush the embolization catheter before performing additional arteriograms.
• A fatal pulmonary embolus, which occurred 20 hours after UFE, was reported in a 65-year-old patient. The source of the thrombus was believed to be the deep pelvic veins, and it may have occurred either secondary to the mass effect of the fibroid or from diminished arterial flow after embolization, which resulted in stasis and thrombosis within pelvic veins. To reduce the risk of PE after UFE, patients should ambulate as soon as possible to prevent the development of lower extremity diverticulitis (DVT) and possible pulmonary embolism (PE). In addition, compression stockings have been recommended for patients with a history of smoking or oral contraceptive use since these patients are at increased for thrombotic events. While these measures are important to reduce the risk of DVT and PE in many patients, they will not help if the source of a PE is from the pelvic veins.
• Inadvertent end-organ damage (ie, uterus) can result in ischemic injury or infection, both of which may require hysterectomy for treatment.
• Infection, or more specifically, pyometrium with acute endometritis was one of the earliest reported complications of UFE. High fever and persistent pain led to hysterectomy in an early case report. Since then, infection has been reported in less than 1% of patients. Some infected patients have been successfully treated with antibiotics, while others required hysterectomy. In one patient, infection resulted in multiorgan failure and death. All patients with prolonged fever (>7-10 d) should be evaluated for possible uterine infection. Diagnosis may be aided by the performance of a pelvic examination, lab tests (including CBC, blood and urine cultures), and pelvic CT scan.
• Ischemic injury of the uterus has been reported in less than 1% of patients. These patients presented with pelvic pain persisting several weeks beyond the expected postembolization syndrome. Classic teaching states that the uterus receives approximately two thirds of its blood supply from the uterine arteries and approximately one third from the ovarian arteries, which originate from the abdominal aorta distal to the renal arteries. One possible explanation for this complication is that embolization of the uterine arteries places the uterus at risk for ischemic injury and infarction in cases in which there is potentially inadequate collateral blood flow from the ovarian arteries. Patients experiencing this complication may require further treatment (eg, hysterectomy) to relieve associated pain and discomfort.
• Postprocedure amenorrhea has been reported in approximately 2-14% of patients. Transient amenorrhea may occur in the presence of normal hormone levels secondary to endometrial atrophy. Often, a spontaneous return to normal menstruation occurs within 3-6 months.
  • The existence of collateral pathways between the uterine and ovarian arteries also makes it possible for the embolic materials injected into a uterine artery to enter ovarian arterial circulation.
  • Aziz et al found that PVA particles may be found in the mesovarium and mesosalpinx after UFE. This may contribute to potential ovarian and tubal dysfunction by reducing blood flow to the adnexa. This may result in thrombosis of the ovarian artery, ovarian ischemia, or ovarian infarction.
  • These events provide one possible explanation for permanent amenorrhea after UFE. However, most women do not demonstrate a change in their basal follicle-stimulating hormone levels and, in the absence of this change, the true cause-and-effect relationship between UFE and permanent amenorrhea remains unproved.
• Submucosal fibroids, particularly if pedunculated, are at increased risk for expulsion from the uterus after embolization-induced infarction. This particular complication has been reported in approximately 1-2% of patients. While this may occur spontaneously without clinically significant sequelae, a hysteroscopic resection or other treatment may be required to remove tissue retained within the uterus to prevent subsequent infection.

Technical failure

Technical failure in UFE can be defined as an inability to successfully catheterize and embolize both right and left uterine arteries. While not considered a true complication by some, an inability to successfully complete this procedure is certain to be perceived as a complication by both the patient and referring gynecologist, since it will likely necessitate surgical intervention for definitive treatment. Based on published and presented reports, the technical failure rate for UFE is 1-2%.

Possible explanations for technical failure include the following:

• Anatomic variation
• Anatomic deviation secondary to the mass effect produced by large uterine fibroids
• Operator inexperience
• Persistent effects of GnRH agonist (eg, leuprolide acetate) at the time of embolization (as described below)

Hormonal changes

Fibroids depend on ovarian steroids such as estrogen for growth. GnRH agonists act at the level of the pituitary gland to down-regulate GnRH receptors. This results in a decrease in luteinizing hormone and follicle-stimulating hormone levels, which in turn induces a hypoestrogenic state. With a reduction in serum estrogen levels, hyaline degeneration is induced and leads to a reduction in the uterus of 52-77% after 3 months of therapy. Doppler US studies of uterine and fibroid blood flow have documented a decrease in arterial blood flow and an increase in the arterial resistance index after several months of GnRH agonist therapy.

In addition, a decrease in arterial size and an increase in atherosclerotic changes are seen in uterine and fibroid vessels after therapy. Since a decrease in uterine vasculature is associated with GnRH agonist therapy, the effectiveness of embolization therapy may be diminished during therapy because of decreased particle delivery to the distal uterine vasculature.

Within 3 months after discontinuing GnRH agonist therapy, the uterus returns to 88% of pretreatment size.

To avoid potential UFE failure in patients on GnRH agonist therapy, patients should have their GnRH agonist therapy withheld for a minimum of 3 months before undergoing UFE.

MULTIMEDIA

Section 9 of 10  

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• Clinical Background
• Rationale
• Preprocedure Evaluation
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• Results
• Potential Complications
• Multimedia
• References

Media file 1:  Nonselective pelvic angiogram demonstrating the tortuous and dilated uterine arteries supplying a hypervascular uterine fibroid.
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Media file 2:  Selective angiogram of the left uterine artery prior to embolization.
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Media file 3:  Selective angiogram of the right uterine artery prior to embolization.
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Media file 4:  Nonselective angiogram of the pelvis after embolization demonstrating occlusion of both the right and left uterine arteries.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Clinical Background
• Rationale
• Preprocedure Evaluation
• Technique
• Recovery
• Results
• Potential Complications
• Multimedia
• References

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Article Last Updated: Dec 2, 2005