Mr. Wong is a medical student at Northwestern University Medical School, Chicago, IL . Dr. Goodwin is Chief of Vascular and Interventional Radiology in the Department of Radiological Sciences, UCLA Medical Center, Los Angeles, CA.

Uterine fibroids are benign tumors that are estrogen responsive and occur in 40% of women, making fibroids the most common tumor in the female reproductive tract. ¹ Patients with fibroids commonly present with dysmenorrhea and/or menorrhagia, and may have compressive symptoms including urinary frequency, abdominal distention, and constipation.

The definitive treatment for fibroid disease is hysterectomy. Approximately 600,000 hysterectomies are performed annually in the United States, and 25% to 35% of these hysterectomies are for treatment of symptomatic fibroids. ² Although this surgical treatment is relatively safe and completely cures the disease, it is a major surgical procedure with a major complication rate of 1% to 2% and a death rate of 0.1%. ³ It also guarantees infertility, since the uterus is removed entirely.

In order to preserve the uterus, numerous alternative therapies have been developed and investigated. These include myomectomy, endometrial resection and ablation, and medical therapy with progestational compounds and gonadotropin-releasing hormone (GnRH) agonists. However, each alternative treatment has associated problems. Myomectomy is the most invasive treatment second only to hysterectomy. It carries the risk of excessive intraoperative blood loss, ⁴ postoperative adhesions, and decreased fertility (postmyomectomy fertility rate is approximately 40%). ⁵ Endometrial resection is associated with hematoma formation, ectopic pregnancies, and cyclical pelvic pain ⁶ and has a 6-month postprocedure failure rate of 24%. ⁷ Use of GnRH agonists is limited to 6 months due to its tendency to cause osteoporosis ⁸ and symptoms of a hypo-estrogenic state, such as hot flashes, vaginal dryness, decreased libido, and mood changes. ⁹ Once discontinued, rapid regrowth of fibroids to their original size is often noted. ⁶

Uterine artery embolization (UAE) has been developed as an additional treatment option. Embolization in the pelvis is a well-established technique that has been employed in a variety of clinical situations. The first reported use of embolization in the pelvis for obstetrical-gynecological hemorrhage appeared in the literature in 1979 to control postpartum hemorrhage. ¹⁰ Since then, the technique has been used to treat postpartum, ^10-22 postcesarean, ^12,17,23-27 and postabortion bleeding, ²⁸ ectopic pregnancy, ^{16,20,25,29-31} postsurgical bleeding, ^12,22,32,33 arteriovenous malformations, ^34,35 and for presurgical prophylaxis against excessive hemorrhage. ^31,36,37 Uterine artery embolization for the treatment of fibroids is a more recent development. Success rates for this treatment have ranged between 85% and 94%. ^38-40 UAE works by causing infarction of the fibroids because fibroid arteries are essentially end arteries. The myometrium is spared because of the rich collateral network in the pelvis. Figure 1 shows a computed tomography (CT) scan of a woman's pelvis the day of embolization. Contrast administered intra-arterially during the embolization is retained in the fibroid (along with the embolic material) while no contrast is seen in the myometrium because it has washed out.

Patient selection

A complete history and physical examination is necessary, as well as ultrasonographic or magnetic resonance imaging (MRI) documentation of fibroids to allow planning of optimal approach for treatment. Malignancy must be ruled out before selection for UAE. Rapidly enlarging fibroids must be investigated, and women older than 40 years of age or with intermenstrual bleeding usually undergo endometrial biopsy to rule out endometrial hyperplasia or neoplasia. Contraindications include pregnancy, active pelvic infection, active vasculitis, history of pelvic irradiation, life-threatening contrast allergy, uncontrollable coagulopathies, and renal insufficiency. In our experience, laboratory studies can usually be limited to a hematocrit in bleeding patients. We have not found routine cultures to be necessary.

UAE technique

UAE is performed under conscious sedation and involves selective catheterization of both uterine arteries with 4Fr to 5Fr visceral selective catheters or with co-axial microcatheters. Particulate emboli are used, especially polyvinyl alcohol (300 to 700 µm). Angiography is used to determine complete embolization of both uterine arteries. Figure 2 illustrates pre- and postembolization angiograms of the left uterine artery in a woman with a large myomatous uterus. The procedure time is 45 to 135 minutes with 90% of the procedures lasting from 50 to 75 minutes. There is an average procedural exposure of 20 rads to the ovaries. Most patients are discharged within 24 hours; however, hospitalization for up to 48 hours is sometimes required for the management of postoperative pain. ⁴¹ The majority of patients return to normal activities within 1 week. ⁴¹

Side effects and complications

Postembolization syndrome (symptoms of pain, fever, vomiting, nausea, and anorexia) occurs in most women undergoing UAE. This syndrome occurs in patients undergoing em-bolization procedures in general and has been well documented, especially in the liver chemoembolization literature. ⁴² The symptoms usually resolve in 7 days and may be difficult to differentiate from infection. Differential features include leukocytosis without a left shift and negative cultures. Infection is characterized by delayed pain and fever with leukocytosis with a left shift, particularly when associated with purulent discharge. Broad spectrum antibiotics will be effective in most patients, although approximately 1 in 200 patients will require a hysterectomy because of infection. Approximately 5% of patients will pass tissue vaginally in the months following embolization. This is not a significant problem if patients are aware of the possibility, unless the cervical os opens and the tissue becomes stuck, leading to infection. A D&C and/or hysteroscopy may be necessary to address this problem in a small number of women.

Crampy postembolization pain occurs frequently. Pain usually peaks the first day following the procedure, but occasionally on the second day, and rarely the third day postprocedure. Resolution of pain can be expected in 1 week. Pain syndromes lasting longer than 2 weeks are rare. The pain is probably due to the ischemia produced by the embolization procedure. Strong analgesics and, particularly, patient-controlled analgesia (during hospitalization) is extremely helpful during this period. The severity of pain is unrelated to the size of fibroid and is unpredictable. We believe that an overnight admission is desirable, but others have advocated embolization on an outpatient basis.

Exposure of the ovaries to radiation is a concern, especially if the patient desires future fertility. Ravina ⁴³ reported the radiation dose to be negligible, which is in contrast to our calculation of 20 rads to the ovaries. A study of 11 patients who underwent UAE estimated the absorbed ovarian dose to be an order of magnitude more than for barium enema or for hystero-salpingogram, and several orders less than for radiation treatment of Hodgkin's disease. Based on the well-established risks of pelvic radiation for Hodgkin's disease, the study concluded that there is no risk for acute/long-term radiation injury or to fertility. ⁴⁴ Low-dose fluoroscopy units with pulsed fluoroscopic capability will keep fluoroscopy dose to a minimum. Avoidance of detailed fluorography as well as strict coning down to the catheter tip to keep the ovaries out of the primary field will also aid in minimizing exposure.

Premature menopause has been documented in 1% to 2% of patients after UAE ^40,45,46 and is believed to result from non-target embolization of the ovaries via the collateral bed between the ovarian and the uterine arteries. This is a risk that must be considered in a premenopausal woman who desires future fertility.

Sexual dysfunction is an unusual complication following UAE. In those women who experience strong uterine contractions during orgasm (internal orgasm) those contractions can be lost following UAE, although clitoral orgasm is not lost. This complication may be related to embolization of the cervical vaginal branch resulting in cervical ischemia or ischemia of the neural plexus adjacent to the cervix. Other nontarget embolization complications are rare with damage to the rectum, bladder, buttocks, and sciatic nerve occurring at much <1 in 1000 cases.

Two deaths have been reported in patients undergoing UAE in Europe: one patient had sepsis and multi-organ failure and the other had pulmonary embolism. ^47,48 No deaths have been reported in more than 4000 cases performed in the United States. ⁴⁹ Finally, complications related to angiography are rare and include 0.2% hematoma, 0.2% to 0.4% arterial thrombosis, and 0.05% false aneurysm. ⁴⁵

Literature review

Transcatheter uterine artery embolization for the treatment for fibroids was first reported in the English literature in 1995 by Ravina et al, ⁴³ and soon thereafter, by investigators including Goodwin et al ³⁸ and Worthington-Kirsh et al ³⁹ from the United States, and, from the United Kingdom, Bradley and colleagues. ⁴⁰ Currently, worldwide technical success rates reported for UAE are 98% to 100%. ^38-40 The overall success rate, defined as marked or complete resolution of the primary fibroid-related symptoms requiring no further surgical treatment, is 85% to 94%. ^38-40,45 In women who are treated with UAE for menorrhagia, reported success rates are 86% to 92% ^{38-41,43,45,46,50} and symptomatic relief occurs as early as the first cycle in the majority of patients. Bulk-related symptoms (for example, urinary incontinence and abdominal distention) improved in 85% to 96% of patients. Six-month pelvic ultrasound follow-up demonstrated an average size reduction in dominant uterine leiomyomata of approximately 60% in comparison to preprocedural volume. ^38,40,45,51 The ultrasound image in Figure 3 shows a reduction in maximum uterine cross-sectional diameter from 9.5 to 4.9 cm, representing >75% reduction in volume, at 6-month follow-up.

In the early 1990s, Ravina ⁵² first noticed unexpected fibroid shrinkage in patients who underwent embolization for premyomectomy or hemorrhagic conditions in the pelvis. In 1995, his group reported using UAE as a primary treatment for fibroids in 16 patients. ⁴³ At a mean follow-up of 20 months, 11 of the 16 patients reported complete resolution of their symptoms, three had partial improvement, and only two failed UAE and required subsequent surgery. Ultrasound demonstrated fibroid volume reduction of 20% to 80% at 3-month follow-up. One of their patients subsequently became pregnant. In 1998, they reported data on a subsequent 184 patients who underwent UAE for symptomatic fibroids. The average fibroid volume reduction was 66% at a 10-month follow-up. ⁵³ At 30-month follow-up, 93% of patients reported substantial improvement (with improvement in menorrhagia in 91% of patients) while 7% did not improve. One patient underwent hysterectomy 8 days after UAE due to fibroid necrosis. Seven pregnancies, one unsuccessful, followed the UAE procedure.

Goodwin et al ³⁸ studied 11 patients who underwent bilateral uterine artery embolization in 1996 and had a mean follow-up of 5.8 months. All patients underwent technically successful embolization. Eight of the nine patients who completed the follow-up questionnaire reported noticeable symptomatic improvement, including three women with complete resolution of symptoms. One women had no clinical response and another developed endometritis and pyometria 3 weeks after the procedure necessitating hysterectomy. Ultrasound confirmed that uterine volumes decreased an average of 40% and dominant fibroid size decreased 60% to 65%.

These promising results led to a subsequent study of 59 patients who underwent bilateral UAE with a mean follow-up of 16.3 months. ⁵⁴ Fifty-six patients presented with bleeding and 47 presented with pain. Of all patients who underwent bilateral UAE, 81% had moderate or better improvement in their symptoms. Ninety-two percent had reductions in their uterine and dominant fibroid volumes with an average decrease of 42.8% and 48.8%, respectively. One patient had permanent amenorrhea following uterine artery embolization.

Six patients eventually elected to have hysterectomy after having undergone UAE. Three of the six patients were diagnosed with adenomyosis by postsurgical histopathology, which suggests that adenomyosis is a condition that predisposes a patient to fail UAE therapy. Of these three patients, one also had cervical squamous carcinoma and another had chronic hematometra concurrent with adenomyosis. A fourth patient had an infectious complication that necessitated hysterectomy. A fifth patient developed renal cell carcinoma and underwent hysterectomy for reasons unrelated to her fibroids. A sixth patient was lost to follow-up.

In 1998, Worthington-Kirsch et al ⁵⁵ studied 53 patients who underwent UAE and had excellent clinical outcomes. Menorrhagia secondary to fibroids was controlled in 88% of patients and bulk-related symptoms were controlled in 94% of patients. Complications in this study were low and included severe abdominal pain in two patients.

In a Canadian multicenter trial of 24 premenopausal women in 1998, Pron et al ⁵⁶ reported successful UAE with no procedural complications. The majority of patients were admitted for management of postprocedural pain (average <48 hours). Many experienced persistent pelvic pain that lasted up to 1 week. Postprocedural vaginal spotting and vaginal discharge for several days were common. Postdischarge, five women returned to the Emergency Department, three for pelvic pain and two for menorrhagia. Generally, the majority of women reported being able to return to work, or their usual activities, 1 week after the UAE. Several women (5 of 24) required longer recovery periods of up to 3 weeks.

Walker et al ⁵⁷ studied 91 patients following UAE; 80% of the patients reported that the procedure was completely successful. One patient required hysterectomy due to an E coli-infected tubo-ovarian abscess. Another patient had a perforated myometrium secondary to attempted expulsion of an infected fibroid. Another patient required a blood transfusion 4 weeks postprocedure for anemia. Finally, one patient suffered transient amenorrhea and another two had permanent amenorrhea.

Spies et al ⁵¹ studied 50 patients with a mean follow up of 12.3 months. Using MRI, a median decrease in uterine and dominant uterine volume of 48% and 78% was achieved, respectively. Menstrual bleeding was improved by 89%, with 81% of patients moderately to markedly improved. Pelvic pain and pressure was improved in 96% of patients, with moderate to marked improvement in 79%. One 50-year-old patient had permanent amenorrhea after one normal menstrual cycle postprocedure. In this patient, it was difficult to differentiate between normal menopause and procedure-induced amenorrhea.

Discussion

In recent years, UAE has become increasingly popular. In the United States, the number of UAE procedures performed increased from 50 in 1996 to more than 4,000 in 1999 ⁴⁹ and a proliferation of literature in the lay press has indicated strong patient demand for this nonsurgical treatment.

The advantages of UAE compared with hysterectomy include avoidance of surgical risks, shorter hospitalization, and the potential for maintaining fertility. However, one must remember that, unlike hysterectomy, UAE is palliative rather than curative.

UAE patients can expect excellent short-term and mid-term results with regards to menorrhagia, pelvic pain, bulk-related symptoms, and reductions in uterine volume. Longer term results are not known. In the near future, randomized controlled studies comparing UAE with myomectomy, as well as studies of UAE regarding preservation of fertility, will further delineate its role in the treatment of uterine fibroids. AR