Uterine fibroid embolization
Clinical issues
Uterine fibroids are one of the most common tumors of the female reproductive tract in premenopausal women. In a study that included women aged 17 to 44 years who underwent tubal sterilization, uterine fibroids were seen in 9% of whites and 16% of blacks,1 although pathologic examination after hysterectomy showed a higher prevalence.2 The overall incidence of the disease was reported to be 29.7 cases/1000 patient-years, with considerable variation between age groups.3 Most studies show that the highest incidence is seen in women aged 40 to Most studies show that the highest incidence is seen in women aged 40 to 45 years.4,5 Blacks are at three times the risk of developing uterine fibroids compared to whites.6
Although uterine fibroids are benign, they can cause a considerable number of symptoms. The most common symptom is heavy menstrual flow and often the resultant iron deficiency anemia. Dysmenorrhea, pelvic pain and pressure, painful intercourse, urinary frequency, urgency, and other pelvic symptoms can also occur. These symptoms are often severe enough to require surgical intervention. In the United States, uterine fibroids are the most common indication for hysterectomy, with 300,000 hysterectomies performed annually to remove fibroids. in 2000, the total cost of treating fibroids was estimated at $2.1 billion.7 More than 70% of these costs are directly related to hysterectomy.
Strategies and evidence
Uterine fibroids are benign monoclonal tumors of the uterus, consisting of smooth muscle cells and the extracellular matrix of collagen, fibronectin, and proteoglycan.8 Although we now know that the growth of fibroids is influenced by estrogen, progesterone, and multiple growth factors, we do not know what factors initiate fibroid production.9 Uterine fibroids are not seen in children, and there is a tendency for fibroids to recede in women after menopause , these facts suggest a role for gonadal steroids.
The growth of fibroids leads to an enlargement of the uterus. Fibroids located in the submucosal area of the uterus and intermural fibroids adjacent to the endometrial layer are associated with excessive menstrual bleeding4 , while the presence of large fibroids or an overall enlargement of the uterus is associated with local pressure, pain or compression effects.
Treatment
Treatment of uterine fibroids is usually indicated when symptoms are present and severe enough to be unacceptable to the patient. There is no evidence that patients who are asymptomatic or have only mild symptoms may benefit from interventional therapy. Exceptions may include patients presenting with severe anemia, or ureteral obstruction leading to hydronephrosis26,27.
Pharmacologic therapy is useful in some patients with symptoms of uterine fibroids. Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are often effective in relieving the pain associated with fibroids, although these drugs do not reduce bleeding. Various hormonal therapies, including androgenic steroids, mifepristone, and gonadotropin-releasing hormone agonists and antagonists, have been shown to reduce uterine volume and blood loss. However, most of these treatments have not been evaluated in randomized clinical trials, and in many cases, the benefits of hormone therapy do not appear to be sustained over time.26,27 In addition, many patients do not want to consider hormone therapy or do not tolerate it well.
For patients requiring intervention, the main current treatment options include hysterectomy, myomectomy, endometrial ablation (when menorrhagia is the primary indication and the anatomic status of the endometrium is appropriate), and myomectomy embolization. The choice among these procedures depends on the patient’s age, symptoms, co-morbidities, and reproductive plans, as well as the characteristics of the fibroids.26,27 When selecting the most appropriate treatment option for a particular patient, it is important to have a thorough discussion of treatment options with an experienced specialist.
Uterine fibroid embolization is a reasonable option for the majority of patients considered appropriate for intervention.
There are few contraindications to uterine fibroid embolization.
All women must undergo a thorough gynecologic evaluation and pelvic examination prior to the procedure. In addition, uterine imaging using ultrasound or MRI is required to assess the size, location and number of fibroids. Laboratory tests performed prior to the procedure usually include a complete blood count, coagulation tests, metabolic markers, and pregnancy tests.
The operator of uterine fibroid embolization should be a properly trained and experienced specialist, usually an interventional radiologist.29,30 This procedure is a percutaneous angiographic technique performed in a radiologic setting using fluoroscopic television imaging methods. The patient is usually sedated during the procedure. The operator inserts a small-bore basal angiographic catheter into the patient’s common femoral artery and advances it with a guidewire across the (abdominal) aortic bifurcation and into the contralateral internal iliac artery. The operator then pushes the basal catheter or a smaller caliber microcatheter placed within the basal catheter into the uterine artery and usually positions it distal to the transverse artery. An arteriogram is obtained to visualize the anatomy of the arterial plexus supplying the uterine myoma (Figure 2A). Embolization is then performed with granular embolic material. The most commonly used embolic agents include polyvinyl alcohol pellets, trisacryl gelatin microspheres, and gelatin sponges. The embolic material is injected and carried by arterial blood flow to the trophoblastic vessels of the myxoma. These vessels are first obstructed because they are thicker and have higher blood flow than the branches of the normal myometrium. When the blood supply to the myometrium is blocked but slow blood flow remains in the uterine artery, the operation is stopped (Figure 2B). The catheter is then moved to the ipsilateral internal iliac artery and the procedure is repeated in the other uterine artery. After the procedure, the patient is usually kept overnight in a specialized interventional radiology unit of the hospital.
A few hours after the procedure, most patients have moderate to severe pelvic pain that requires intravenous narcotics and treatment with an NSAID. One study showed that patients had a pain severity score of 3 in the first 24 hours after treatment and a pain severity score of 4.9 in week 1, as judged by the mean pain severity score shown on a visual analog scale of 0 to 10 (higher numbers indicate more severe pain).31 However, severity can vary considerably, with approximately 20% of women having a visual analog scale score of more than 7 during week 1.
Patients also usually have general malaise, fatigue, and myalgia that persist for multiple days. About one-third of patients have a mild fever, and only 2% have a temperature above 38.5°C. Most patients return to work and other normal activities within 7 to 14 days after surgery.
Many patients have mild vaginal bleeding, dripping blood, or brown vaginal discharge that persists for many days, often into the first (postoperative) menstrual cycle. Patients may have short-term menstrual disorders, but most women return to regular menstrual cycles within 2 to 3 months after treatment. In patients with preoperative menorrhagia, menstrual bleeding usually decreases by the 2nd or 3rd (postoperative) menstrual cycle.32 The time course of pelvic pain, dysmenorrhea, pressure, and urinary tract symptom relief is usually similar to the former, and most patients experience symptom relief by 3 months postoperatively.19,33
In a study that collected information from several national insurance claims databases in the United States, the average cost of uterine fibroid embolization was $8,293, a figure that included inpatient and physician costs.34 The average total cost in year 1 was $13,270, a figure that included follow-up, imaging, medications, and inpatient and outpatient costs.
Adverse effects
In a registry study enrolling 3160 women who underwent uterine fibroid embolization, the incidence of major complications (as defined by the Society of Interventional Radiology clinical practice guidelines) among registrants was 0.66% during the initial hospitalization and 4.8% in the first postoperative month.21 Persistent or recurrent pain and nausea combined accounted for more than 50% of these complications. In a single-center study that included 400 consecutive patients, the incidence of major complications was 4.3% in year 1.35
The most common symptom cluster in the recovery period is the post-embolization syndrome consisting of pelvic pain, fever, and general malaise. This syndrome is usually managed with analgesics and antipyretics, although patients may require prolonged hospitalization or readmission when more severe symptoms develop. It is important to differentiate this syndrome from infection, a less common but potentially serious complication.
Areas of uncertainty
The main unresolved issue with embolization therapy for uterine fibroids is the impact on future pregnancies. As already mentioned, ovarian function may rarely be compromised after the procedure. Embolization may affect the endometrium and embryo implantation as well as the gestational process, which is to be expected. In a series of 56 pregnancies reported after embolization, 17 pregnancies ended in miscarriage. Of the 33 live births, 24 were cesarean deliveries. There were 6 cases of postpartum hemorrhage.47 Placental abnormalities such as placenta praevia or placental implantation may lead to an increased risk of hemorrhage and, in some cases, to hysterectomy.48
Data from a recently published randomized study involving women in Prague, Czech Republic, provide a basis for comparing the effects of embolization with hysterectomy on fertility. The investigators included 121 patients, of whom 63 were randomly assigned to undergo myomectomy and 58 were assigned to undergo embolization.49 At the time of the investigators’ report, 40 women had intended to conceive after myomectomy and 26 women intended to conceive after embolization. Those who underwent embolization had a higher relative risk of not conceiving (relative risk of embolization 2.22) and a higher relative risk of spontaneous miscarriage (relative risk 2.79) compared with women who underwent myomectomy. For women who want to conceive in the near future (within 2 years after surgery), these results suggest that myomectomy is preferable. Information on long-term regression in fertility is not yet available.
Guidelines
The American College of Obstetricians and Gynecologists (ACOG) concluded “based on good and consistent evidence (Level A)” that “uterine artery embolization is a safe and effective option for women who have undergone appropriate selection and wish to preserve the uterus. “50 The ACOG also recommends caution when considering embolization in women who wish to preserve their ability to conceive, as age-related amenorrhea may occur in a small number of patients and there is a possibility of placental abnormalities. The Society of Interventional Radiology and the European Society of Cardiovascular and Interventional Radiology state that uterine artery embolization is indicated “when the symptoms caused by fibroids are causing significant changes in the patient’s lifestyle, particularly if the fibroids are having a mass effect on the bladder or bowel and/or the patient has prolonged dysfunctional uterine bleeding with severe dysmenorrhea, or is causing severe anemia.”
Conclusions and Recommendations
The patient described in the small medical record at the beginning of this article had clear symptoms of uterine fibroids and her fibroids were anatomically suitable for treatment with embolization. She does not have any contraindications for this operation. She does not want to have any more children and is looking for a treatment that is less invasive than hysterectomy.
It is important that the patient has the opportunity to discuss her treatment options with a physician (preferably a clinically experienced specialist) who can explain the relative risks and benefits of the procedure. Since her symptoms have been worsening for 10 years, conservative treatment is unlikely to be acceptable to her, but this option should be presented. Hormonal therapies may also be appropriate to discuss, although it is unclear whether they will provide sustained benefit. When choosing between hysterectomy and embolization, the patient must be informed of the faster recovery and fewer early complications with embolization, but there is an approximately 20-25% chance that she will need to undergo subsequent invasive interventions. Uterine fibroid embolization may be an appropriate option for this patient who does not want to undergo hysterectomy.