Current Concepts in Uterine Fibroid Embolization

LEARNING OBJECTIVES

After completing this journal-based CME activity, participants will be able to:

•.	List the indications and contraindications for UFE in patients with uterine fibroids.
•.	Describe the optimal technique for successful UFE of uterine fibroids.
•.	Discuss the expected outcome of UFE in patients with infertility secondary to uterine fibroids.

Introduction

Uterine fibroids are the most common tumor of the reproductive tract in women, occurring in over one-half of American women of reproductive age, according to an ultrasonographic (US) survey (1). Although often asymptomatic, leiomyomas can cause severe symptoms, including pain, menorrhagia, pelvic pressure, and reproductive problems such as infertility and increased rates of cesarean section (2). Among women with fibroids, 50% of black women and 25% of white women will eventually require therapy.

Uterine fibroid embolization (UFE) was introduced in the United States as a treatment option for fibroids in 1997 (3).

UFE has been shown to reduce pain, bulk symptoms (pressure and abdominal wall distortion), and menorrhagia in most cases (5). Although hysterectomy has long been considered the definitive treatment for symptomatic fibroids and remains the most common intervention for fibroids, there is growing interest in less invasive therapies and treatments that avoid removal of the uterus, including medical management, abdominal or laparoscopic myomectomy, endometrial ablation, focused US, and UFE (6). Uterine embolization has emerged as one of the most important of these uterine-sparing options.

In this article, we provide a review of UFE for diagnostic radiologists, including preprocedure patient evaluation, indications, contraindications, technique, and patient care after treatment. We also present the reported outcomes of the procedure, focusing on the recently published outcomes from randomized trials. Finally, complications of UFE and its effect on fertility are discussed.

Patient Evaluation

Ideally, the evaluation of patients considered for UFE should be a collaborative effort between an interventional radiologist and a gynecologist. At a minimum, women considering UFE as a treatment option should be evaluated by an interventional radiologist to determine whether UFE is an appropriate treatment choice. That consultation should include a gynecologic history, a general medical history to identify comorbidities, and a physical examination. The gynecologic history includes the reproductive history, interest in future pregnancy, prior gynecologic conditions and surgeries, and a menstrual history.

A menstrual history is important because uterine fibroids are often associated with menorrhagia, which is defined as heavy or prolonged bleeding (“gushing”) lasting longer than 7 days or requiring more than seven sanitary pads per day (2). The menstrual history should include the length of the cycle, the number of heavy-flow days, and the frequency of change of sanitary protection. The consultation also allows the interventional radiologist to discuss UFE in the context of the patient’s preferences for treatment outcomes. It is important that a gynecologist also evaluate a candidate for UFE before treatment to rule out other pathologic conditions and to discuss other options, such as myomectomy and hysterectomy.

As discussed later, uterine evaluation with MR imaging allows identification of patients who may not be optimal candidates for embolization or those in whom UFE is associated with a higher likelihood of complications, such as fibroid expulsion. MR imaging is also more sensitive than US in detection of adenomyosis (7), identification of which may have an effect on outcome (Fig 1).

Figure 1

Download as PowerPointOpen in Image Viewer

The utility of MR imaging in clinical decision making in uterine embolization has been studied, and its effect on case management has been confirmed, including increased diagnostic confidence and immediate change in treatment plan (8). MR imaging can demonstrate the vascularity of fibroids and allow determination of whether embolization is a reasonable treatment option. (See the article by Deshmukh et al [9] in this issue for further information.) Contraindications to preprocedural MR imaging are the same as those for routine MR imaging, and most patients tolerate the examination well. For claustrophobic patients, conscious sedation may be induced.

US is an acceptable alternative to MR imaging if carefully performed with quality equipment. Specifically, both transvaginal and abdominal US may be needed for a comprehensive evaluation, depending on the size of the uterus. Static US is less sensitive for detection of some pathologic conditions and may be inferior to contrast-enhanced MR imaging for determination of fibroid infarction rates. However, US allows capable evaluation of the endometrium, particularly when combined with sonohysterography. It also has the advantages of being less expensive and, in some areas, more readily available than MR imaging.

Indications

Symptomatic fibroids typically cause heavy menstrual cycles, with an increase in the length of the cycle and the number of days of heavy bleeding. Bleeding between menstrual periods (metrorrhagia) is less typical and raises the possibility of other diagnoses, such as a cervical lesion, endometrial polyp, or carcinoma.

Other symptoms include pain, pressure, and urinary symptoms, such as urinary frequency or retention related to hydronephrosis. These symptoms are usually proportional to the size and location of the fibroid. For example, a patient may have pain and tenderness over a prominent fibroid at the time of her cycle. Rarely, patients with fibroids may seek UFE for hydronephrosis caused by mass effect from a large fibroid or fibroid uterus on the ureter. A recent study suggested that fibroid-associated hydronephrosis nearly always resolves after embolization due to fibroid and uterine shrinkage (10).

Fibroid-induced infertility is defined as infertility due to structural distortion of the uterus or reproductive tract due to submucosal fibroids (2); intramural and subserosal fibroids have not been associated with decreased fertility. One systematic review showed that after removal of submucosal fibroids, women’s clinical pregnancy rates improved compared with those of women with untreated submucosal fibroids; however, there was no statistical significance when pregnancy rates were compared with those in a control group of infertile women without uterine fibroids (11). Women with fibroid-induced infertility who are not candidates for surgery may also be considered for UFE, but the decision as to whether uterine embolization is the best choice in any given patient is complex. The role of UFE in women who are seeking to become pregnant is discussed in detail in a later section.

There are some anatomic considerations in patient selection, although both single and multiple fibroids can be treated with UFE and all fibroid locations (submucosal, intramural, and subserosal) are eligible for embolization. However, patients with very large uteri and fibroids who undergo UFE will likely have less uterine and fibroid shrinkage (12) and less long-term satisfaction (13) than others and tend to have less symptom improvement (14), although there is no evidence that these patients are more likely to experience a complication (15,16).

Intracavitary fibroids are more likely to be expelled in the weeks and months after embolization. Although many patients tolerate fibroid expulsion well, expulsion of larger fibroids may be complicated by lower abdominal pain, increased cramping, or infection associated with the necrotic fibroid. These patients may require analgesia, antibiotics, or further gynecologic intervention.

Pedunculated subserosal fibroids, particularly those with a narrow attachment to the uterus (Fig 2), have been suggested as a contraindication to UFE because of the potential risk of detachment (17). At least two studies have addressed this concern (18,19). These investigators found no instances of fibroid detachment in patients with pedunculated subserosal fibroids, and the clinical outcomes in study patients were similar to those in patients with other fibroid subtypes.

Another class of fibroids, cervical fibroids, has also been investigated. In comparison with other fibroid subtypes, cervical fibroids appear to be resistant to complete hemorrhagic infarction after UFE, although the data are limited (20). Incomplete infarction may be a function of additional or alternative blood supply to the cervix (20) (Fig 3).

Contraindications

There are a few absolute and relative contraindications to UFE (Table 1). The first absolute contraindication is current pregnancy. Every patient undergoing UFE needs to have pregnancy excluded. This may be achieved with a urine or serum pregnancy test. In our practice, this test is performed the morning of the procedure.

Another absolute contraindication is a known or suspected gynecologic malignancy. Therefore, complex cystic masses suspicious for ovarian malignancy need to be diagnosed before UFE. Diagnosis of such masses may require surgery. Similarly, in a patient with irregular bleeding, an endometrial malignancy or premalignant condition should be considered and appropriate testing performed (Fig 4).

Figure 4

Download as PowerPointOpen in Image Viewer

Although rare (21), leiomyosarcoma does occur and can be difficult to distinguish from a fibroid (Fig 5). Usually, leiomyosarcoma manifests as a large heterogeneous mass in the uterus, often with areas of hyper- and hypoenhancement (22). Unfortunately, there is overlap with the MR imaging appearance of fibroids, and definitive diagnosis may require biopsy or surgical resection.

Finally, current uterine or adnexal infection is also a contraindication to UFE, at least until treated. Once the infection has been treated, there should not be any barrier to UFE.

There are also relative contraindications to consider. These include contrast material allergy, coagulopathy, and renal failure. Contrast material allergy can be pretreated with corticosteroids and antihistamines. Unless a severe allergy is present, pretreatment is often sufficient to avoid a reaction. In a patient with coagulopathy, a femoral artery closure device can be used to avoid bleeding complications.

Renal failure is a relative contraindication to UFE. Contrast material angiography associated with the performance of UFE can result in further deterioration of renal function unless proper prophylaxis is used. However, the risk of progressive deterioration in preexisting renal dysfunction must also be considered for general anesthesia when surgical management of fibroids is performed. Therefore, careful preparation with intravenous hydration in the periprocedural period, consideration of the use of acetylcysteine, and strict limitation of contrast agent use will certainly limit the risk for exacerbation of renal dysfunction.

Procedure

UFE is an angiographic procedure that is typically performed by using a unilateral femoral artery approach. Some operators use a bilateral femoral artery approach (23). Regardless of access, in almost all cases, bilateral uterine artery catheterization and embolization are needed, since most uterine fibroids, whether single or multiple, receive blood supply from both uterine arteries.

The most common catheterization method is unilateral. However, the bilateral approach has the advantages of allowing simultaneous imaging of the uterine arteries and simultaneous embolization by two operators, which can substantially reduce the fluoroscopy time and has the potential to reduce the radiation exposure. It is also easier to catheterize across the aortic bifurcation to the opposite side, a technique that can also reduce fluoroscopic exposure time. Finally, bilateral catheterization allows global assessment of uterine flow and enables better technical control of the procedure (Fig 6) (23).

Under fluoroscopy, the left internal iliac (hypogastric) artery is accessed with a catheter. Thereafter, many operators catheterize the uterine artery with a microcatheter. After uterine arteriography, embolic material is injected into the uterine artery to occlude the vessels of the fibroid. This procedure is repeated in the contralateral uterine artery as well, since blood supply to a fibroid is rarely unilateral (Fig 7).

Because there are enlarged vessels feeding the fibroid, there is preferential flow to these vessels early in the embolization process. The goal is to occlude the vessels of the fibroid but not to completely occlude the uterine artery. Commonly, there is still sluggish flow in the uterine arteries at the conclusion of the embolization procedure (24).

From a technical perspective, the choice of embolic material and the end point of embolization have been a subject of great interest to interventionalists in this field. In the United States, the vast majority of embolizations are performed with particulate embolic material. Usually, trisacryl gelatin microspheres (Embosphere, Merit Medical Systems, South Jordan, Utah) or polyvinyl alcohol particles (Contour, Boston Scientific, Natick, Mass; or Ivalon, Cook, Bloomington, Ind) are used. There is a vast literature on the various embolic materials currently available for use in UFE, including comparative outcomes, but a detailed discussion of the technical considerations is beyond the scope of this article.

Postprocedure Management

A well-planned protocol for postprocedure care is important to ensure that patients have a positive experience recovering from the embolization. Most patients will have moderate pain for several hours after UFE. The pain is due to ischemia (25), but if not properly controlled, it can progress to severe pain and can be difficult to manage.

A detailed analysis of the level of pain that occurs after UFE has been published (26). In that study, patients were treated with a routine protocol of nonsteroidal anti-inflammatory drugs and intravenous narcotics (administered via a patient-controlled analgesia pump). In the first 24 hours, the mean pain score was 3.03 (on a scale of 0–10, where 0 = no pain and 10 = the worst imaginable pain). The average peak score in the 1st week was 4.83. Less than 18% of the women experienced a pain score greater than 7 in the 1st week after embolization.

The study also found that the major symptom in the postprocedure period after the first 3 days was fatigue. Many patients also experienced loss of appetite, nausea, and malaise, and one-third had a low-grade fever. These symptoms are collectively known as the postembolization syndrome, a common occurrence after the procedure that results in readmission of up to 10% of patients (6). A planned and actively managed postprocedure protocol by the interventional team allows most women to leave the hospital on the day after UFE.

Outcomes

After more than 15 years of study and clinical experience, UFE outcomes have been well documented. There are now several hundred publications on the procedure and dozens of case series and comparative studies. There have been several large multicenter registries. In this section, we focus on the key studies that have best characterized the anticipated results of the treatment.

Early studies showed technically successful procedures with menorrhagia control in 90%–92% of patients after 12 months and improvement in bulk symptoms in 88%–96% of patients at 12 months (27–29). More recently, several randomized studies that compared UFE outcomes and surgical outcomes after long-term follow-up have been published. Two of the more important are the EMbolization versus hysterectoMY (EMMY) trial and the Randomized Trial of Embolization versus Surgical Treatment for Fibroids (REST) trial. The EMMY trial was a multicenter randomized control trial in the Netherlands that compared UFE with hysterectomy in 177 women (30). The REST trial was a multicenter randomized control trial in the United Kingdom in which 149 women were randomly assigned to surgery (myomectomy or hysterectomy) or embolization (31).

Both the REST and EMMY studies reported similar symptom relief, quality of life, and patient satisfaction in both treatment arms. The REST trial found that UFE was associated with quicker recovery but more reintervention than surgery. Both UFE and surgery improved symptoms and quality of life at 1- and 5-year follow-up, with no significant difference in quality of life improvement between the two groups at 5 years (32). Secondary outcomes included symptom improvement, which was measured on a scale of −5 (significantly worse) to +5 (significantly improved). At 5 years, symptoms improved by +4.5 in the UFE group and +4.8 in the surgery group (P = .08). Patients were very satisfied with their treatment (would recommend the treatment to a friend), with scores of 90% for UFE and 87% for surgery.

In the first 2 years after treatment, the EMMY investigators found that quality of life measures substantially improved for both groups, with no significant differences (33). There was a greater degree of satisfaction with the outcome among hysterectomy patients at 2 years. The study also found that recovery was faster after embolization and that there was less pain after embolization (34).

The REST trial found that UFE was associated with a 13% reintervention rate at 12 months and a 32% rate at 60 months (32), while the EMMY trial showed a 28% hysterectomy rate 5 years after initial UFE. Reintervention in the 1st year was usually due to persistent symptoms, but five patients in the REST trial underwent hysterectomy (n = 3), endometrial ablation (n = 1), or dilation and curettage (n = 1) for complications related to UFE. Longer term, reintervention is often related to recurrent fibroids, a problem also seen with myomectomy and other uterine-sparing therapies. Repeat embolization can be performed in cases of recurrence, and at least one study suggests that outcomes of the second procedure are similar to those of the first (35).

There have been two major randomized trials of embolization versus myomectomy. The first took place in Prague, Czech Republic, and was reported in two publications (36,37). This study focused primarily on reproductive outcomes; its results are discussed in a later section. The second study, called the Fibroids of the Uterus: Myomectomy versus Embolization trial, is the largest randomized controlled trial to compare quality of life outcomes of myomectomy with those of UFE. This trial included 163 women with symptomatic fibroids who were randomly assigned to myomectomy or embolization. All were significantly symptomatic before treatment.

Both groups experienced substantial improvement in both symptoms and quality of life after therapy. However, the myomectomy patients experienced a greater degree of symptom relief and greater improvement in quality of life than the embolization patients. The posttreatment mean symptom score was 18.3 for myomectomy versus 29.5 for UFE (P = .002). (Symptom scores were on a scale of 0–100, with a lower score indicating reduced symptoms.) UFE was also associated with a higher reintervention rate (14.8%) than myomectomy (4%). The average length of hospital stay was 2.0 days for UFE versus 6.0 days for surgery, a result indicative of a more rapid recovery with UFE (38).

Persistent symptoms after UFE can be due to incomplete fibroid infarction (Fig 8). The subsequent regrowth of an incompletely treated fibroid contributes to earlier symptom recurrence (39,40). The extent of fibroid infarction can be affected by the choice of embolic particle, the embolization end point of the procedure, and collateral blood supply.

There are other reasons why a patient may not show improvement after UFE. Heavy menstrual bleeding may not improve due to the presence of comorbidities such as adenomyosis, endometrial polyps or other endometrial disease, or coagulation defects such as von Willebrand disease. Some of these conditions that produce symptoms similar to those attributed to fibroids can be detected by using a combination of a structured menstrual history (41) and quality imaging. This emphasizes the need for a careful preprocedure evaluation. Similarly, pelvic pain initially attributed to fibroids can be due to endometriosis, and urinary symptoms can be secondary to intrinsic bladder disease, conditions that may be difficult to discern at initial presentation (Figs 9, 10).

A number of analyses have been performed to identify factors associated with a better outcome. One of the largest such analyses is that of the FIBROID Registry, a multicenter prospective cohort study sponsored by the Society of Interventional Radiology Foundation. Over 3000 patients were enrolled in the initial phase of this study, with 2100 of them entered in long-term follow-up. Multivariable analyses were performed at 1- and 3-year follow-up (5,13).

In that study, the best predictor of a positive outcome was successful embolization of both uterine arteries; in most cases, this is the minimum requirement for a technically successful procedure. On average, patients with multiple smaller fibroids had better outcomes than patients with single large fibroids in equivalently sized uteri. Successful outcomes are also associated with submucosal location of the dominant fibroid, smaller overall fibroid size, and menorrhagia as the primary presenting symptom.

Adverse Events

Given the broad range of practice settings in which UFE is performed, it has proved to be remarkably safe. The FIBROID Registry noted an in-hospital major complication rate of 0.66% and an overall 30-day major complication rate of 4.8%, with a major complication defined as one requiring a return to the emergency department, readmission, prolonged hospitalization to 48 hours, or surgical intervention (42) (Table 2). Most of these complications involved pain requiring a lengthened hospital stay, emergency department visit, or readmission. There were no deaths, and the hysterectomy rate for complications in the first 30 days was 0.1%.

Among the most serious potential adverse events is venous thromboembolism, with a rate of pulmonary embolus of one in 400 patients in one study (43) (Fig 11). There has been one published report of a death due to pulmonary embolus (44), but other deaths due to pulmonary embolus have been informally reported at scientific meetings. It is known that patients undergoing uterine embolization have temporary elevation of procoagulant factors (45). This hypercoagulability is similar to that occurring after abdominal surgery, although not as severe, but its occurrence suggests that risk factors for venous thromboembolism need to be considered in patients who are candidates for uterine embolization. In our practice, we use automated sequential venous compression devices routinely and use low-molecular-weight heparin prophylactically in high-risk patients.

Figure 11

Download as PowerPointOpen in Image Viewer

The most troublesome complication that occurs after uterine embolization is fibroid expulsion, which can result in substantial pain, vaginal discharge, bleeding, and infection. Overall, it occurs in about 5% of patients, although the frequency depends on the location of the fibroid (46). Fibroid expulsion needs careful management, since infection is frequently associated and can lead to sepsis if not adequately treated. It is perhaps the most common reason why gynecologic intervention is needed after UFE. Hysterectomy may be necessary if the fibroid cannot be removed transvaginally or if infection cannot be cleared.

We usually counsel patients about the risk of fibroid expulsion if a fibroid is intracavitary or has a significant endometrial interface (Fig 12).

Another important although infrequent adverse outcome of UFE is ovarian failure, with amenorrhea the result. In the FIBROID Registry, this occurred in 7.5% of patients (5), with the overwhelming majority of cases occurring in women over 45 years of age. It is believed to be caused by occlusion of ovarian vessels via tubal branches fed by the uterine arteries (47).

Other complications have been reported, including but not limited to arterial injury, misembolization of other pelvic organs, and abdominal adhesions, but these are all rare when UFE is performed by a skilled operator. Overall, there are fewer serious complications after this procedure than after treatment with surgical alternatives, although adverse events are infrequent with all of these treatments (48).

Fertility

For women who wish to become pregnant after treatment of fibroids, the choice of therapies is more difficult. There are few studies that have compared treatment options for fibroids in women seeking to become pregnant after therapy. However, a randomized study of 121 patients compared myomectomy with UFE for treatment of fibroids, with the initial report showing similar levels of improvement in symptoms and quality of life and no difference in ovarian function 6 months after treatment (36).

In a subsequent report 2 years after treatment, myomectomy had better reproductive outcomes, as 78% of myomectomy patients became pregnant compared with 50% of UFE patients (37). UFE was associated with a greater likelihood of not becoming pregnant (relative risk = 2.22), of not delivering (relative risk = 1.54), and of spontaneous abortion (relative risk = 2.79). Longer-term data from this study are not yet available, but these findings suggest a clear advantage of myomectomy for patients seeking to become pregnant.

A systematic review of pregnancy outcomes and complications after UFE from 2009 also concluded that UFE is associated with increased rates of miscarriage. However, this study was limited by its use of asymptomatic infertile women as controls, who likely had less extensive fibroids (49).

Although the evidence is still limited, in sum, UFE should not be first-line treatment for women with infertility due to fibroids or who have a strong desire to become pregnant. However, it is still an option for patients who are poor surgical risks due to comorbidities, prior surgery, or the extent of the fibroids. The evidence also suggests that successful pregnancy is possible after UFE; for those who choose not to have surgery, that option is not foreclosed. Women should be appropriately counseled about their choices at the time of the consultation, when the extent of fibroids, patient preferences, and reproductive status can be considered as a whole.

Conclusions

UFE has been demonstrated to be a safe and effective treatment for uterine fibroids and at this time can be considered a first-line therapy. UFE produces symptom relief similar to that of surgery with fewer major complications. Treatment recommendations need to be based on the patient’s status as a whole, considering the extent of the fibroids, the patient’s suitability for surgery, her interest in future childbearing, and her preferences.

Clearly, uterine embolization is an attractive option for patients who are finished with childbearing and interested in a minimally invasive uterine-sparing therapy. Patients interested in pregnancy after therapy may be considered for UFE, but only after careful consideration of the patient’s needs and preferences. In any case, the ultimate decision on treatment is best made by the patient after consultation with her interventional radiologist and gynecologist, during which there is consideration of all of her options.