Any living tissue in the body requires an intact blood supply to remain viable. If the blood supply is cut off and not rapidly restored the tissue infarcts (dies) and is partially reabsorbed by the body. In Uterine Fibroid Embolization (UFE) the blood supply to the fibroids is intentionally cut off (embolized), the fibroids infarct and shrink, with resolution of symptoms.
History of UFE
Embolization is a procedure that is commonly performed by interventional radiologists and has been successfully applied to arteries in every part of the body to stop bleeding, block abnormal vessels, and treat tumors. Uterine artery embolization (UAE=UFE) has been used for over 20 years to stop life threatening bleeding after childbirth.
In the early 1990s Dr. Ravina, a French gynecologist who specialized in fibroid surgery began a clinical trial to study the effectiveness of adjunctive preoperative UAE in minimizing intra- and post procedural bleeding. Patients were embolized and then scheduled for surgery a few weeks to months later. In those patients who went on to surgery a reduction in blood loss was noted. Interestingly, several patients experienced relief of their fibroid symptoms following UAE and canceled their surgery. Based on this serendipitous discovery he began offering UAE as a primary treatment for symptomatic fibroids.
In 1997 Dr. Goodwin, at UCLA, first reported on early experience with UFE in the U.S. Since then the procedure has rapidly expanded and as of Jan. 2005 it was estimated that over 50,000 patients have been treated worldwide. Published data continues to accumulate with all series reporting an excellent response rate with few complications.
Uterine fibroids, also known as leiomyomata or myomas, are benign (noncancerous) tumors of the muscular wall of the uterus. They are the most common tumor of the female genital tract and affect 20-40% of all women of childbearing age. Fibroids are classified based on their location within the uterine wall. Submucous (or submucosal) fibroids occur just under the endometrial lining of the uterine cavity. Intramural fibroids occur in the muscular wall. Subserosal fibroids occur under the outside covering of the uterus. As fibroids enlarge, the distinction between the types becomes blurred. Pedunculated fibroids occur on a stalk, project from the surface of the uterus, and can be confused with ovarian masses. They can project from the inner lining of the uterus and even extend through the cervix.
Each fibroid develops from a single cell, in the uterine wall, that undergoes transformation. The cause of this transformation is unknown but a genetic link has been established. The subsequent growth of the fibroid appears to be related to the female hormones estrogen and progesterone, as well as other growth factors.
Fibroids are common in all women but are particularly common in African-American women where the incidence is 2-3 times higher than the general population. They also tend to develop fibroids at an earlier age and to a greater extent. The incidence of fibroids is also increased in obese women. A lower incidence is noted in women who exercise and have lean bodies, smokers, those bearing more children, and those bearing children later in life.
Studies estimate that 60-90% of all fibroids do not cause any symptoms. When symptoms develop they tend to occur in the late 30s and 40s, often with an increase in symptoms in the perimenopausal period. Though most fibroids are smaller than a golf ball they can grow to the size of a melon. While some women have only one fibroid others can have dozens, on average six to seven. A combination of the size, number, and location of fibroids may determine the extent and type of symptoms.
Fibroid symptoms can be grouped into abnormal bleeding, pelvic pain, and those caused by mass effect by the enlarged uterus (bulk-type symptoms). Women may develop one or more of the following symptoms:
Abnormal bleeding - submucous and intramural fibroids can both cause menorrhagia (prolonged and/or profuse menstrual bleeding) sometimes leading to severe anemia. Gushing, or flooding, and passage of large clots can occur. In some cases there can be bleeding between periods (metrorrhagia).
Pelvic pain - typically associated with heavy menstrual flow with cramping (dysmenorrhea). An uncommon cause of fibroid related pain is acute degeneration where the blood supply is spontaneously disrupted and the fibroid infarcts (dies) and then shrinks. Carneous or red degeneration is an unusual complication where there is bleeding into the substance of the fibroid, occasionally occurring during pregnancy. The pain can be quite severe but is usually self-limited.
Bulk-type symptoms - those caused by individual fibroids, or the enlarged uterus, compressing adjacent structures.
Pelvic pressure or discomfort - a generalized feeling of heaviness/pain caused by displacement of nearby structures. If nerves are compressed there can be pain in the lower back, flank, or legs.
Abdominal distortion - as the fibroids enlarge the uterus it can extend above the pelvic bone and cause from a small paunch to a very distended abdomen with an appearance suggestive of pregnancy. In fact, gynecologists frequently size the enlarged uterus by referencing it to a comparably sized pregnant uterus (# of weeks gestational size).
Frequent urination - caused by compression of the bladder leading to decreased capacity. This can be disruptive to sleep and daytime activities. Occasionally compression of the bladder can result in stress incontinence (leakage of urine during straining) or bladder outlet obstruction. Rarely, the ureter (connecting the kidney to the bladder) can be compressed and compromise kidney function.
Constipation or bloating can occur when there is compression of the rectum.
Pain during sexual intercourse (dyspareunia) can have a variety of causes including fibroids that distort the vagina.
Reproductive dysfunction - including infertility, recurrent miscarriages, premature labor, and complications of labor. While controversial, and not well studied, these complications are thought to occur when fibroids distort the uterine cavity. Infertility caused by fibroids is thought to represent only 2-3% of all infertility cases. Fibroids can block the cervix or opening to the fallopian tubes thus causing infertility. A submucosal fibroid can distort the cavity enough to prevent implantation of the fertilized ovum and result in recurrent miscarriages. It is less clear whether intramural or subserosal fibroids cause reproductive dysfunction.
Premenopausal women with symptomatic uterine fibroids, without extensive adenomyosis, endometriosis, or other causes for their symptoms, who wish to avoid surgery.
Women who have completed childbearing. Desire for future fertility doesn't preclude UFE, as described below.
Ideally, <24 weeks gestational size uterus. While larger uteri have been treated, a 50% reduction in volume may be inadequate for symptom relief.
Since there is virtually no blood loss, or need for transfusion, UFE may be an ideal treatment for women who wish to avoid transfusion for health or religious reasons.
Side Effects and Complications
In general, UFE is safe and well tolerated. While side effects and complications can occur, they are considerably less frequent than with the surgical alternatives of myomectomy or hysterectomy.
Almost all patients have some degree of crampy pelvic pain for the first 6-8 hours following the procedure, managed with a morphine PCA (patient controlled analgesia) pump that allows delivery of IV pain medications by pushing a button. The cramping is much improved by the next morning and patients are discharged home. Cramping may persist for a few days but is usually well controlled with NSAIDs (motrin) and oral narcotics as needed. Most patients are back to their usual activities in 7-10 days.
Spotting or a brown discharge may occur for days to weeks after the procedure. In ~5% of cases a submucous fibroid may detach from the uterine wall, fall into the cavity, and pass out the vagina. If the fibroid is too large to pass it may require assisted removal by a gynecologist. Fibroid expulsion can occur days to several months after the procedure.
While UFE is much less invasive than the surgical alternatives, there remains the possibility of complications. Minor complications related to angiography occur in <5% of cases. These include bleeding or bruising at the catheter entry site. Rarely (<1%) the femoral artery can be damaged or may develop clot, compromising flow to the leg. Allergic reactions to the xray dye may occur and can be treated. Those patients with a history of allergic reaction to xray dye should be pre-medicated prior to the procedure.
Serious complications are very uncommon. The most serious are four deaths following UFE. A patient in England developed a serious infection following the procedure. She underwent hysterectomy but developed infection in her bloodstream and died from multi-system failure, two weeks later. A patient in the Netherlands recently died from infection following UFE. A 65 year old woman in Italy (she would not have been treated with UFE in this country due to her age) and a patient from the USA each developed a blood clot in the leg that moved to the lungs (pulmonary embolism) and caused death. These are the only deaths reported worldwide following an estimated 50,000 UFE procedures, for an incidence of 1:12,500. For perspective, the risk of death following an elective hysterectomy is 1:1,000.
Injury to the uterus from infection or ongoing ischemia (inadequate collateral blood supply to the normal part of the uterus) requiring hysterectomy occurs in <1%. Non-target embolization of particles to unintended vessels can occur but is unusual. The significance of this complication depends on the particular vessel embolized. This is very unlikely to occur with careful fluoroscopic monitoring by an experienced Interventional Radiologist.
The measured average dose of radiation from the procedure is comparable to that of several barium enemas or pelvic CT scans. This is well below the threshold for developing any expected adverse effects to the patient or her future offspring. While there have been scattered reports of radiation induced skin injury, these have occurred following prolonged (3-4 hour) procedures. We have not observed any radiation injuries in our seven year experience at the Center.
Most women will resume normal periods within a few months of UFE. For patients under 45 years of age there has been a 1-2% incidence of amenorrhea (no more periods) following UFE. For perimenopausal women >45yo the incidence is up to 15-20%. When amenorrhea is accompanied by menopausal symptoms of hot flashes, irritability, and vaginal dryness hormone replacement therapy can be considered.
Fibroids are usually diagnosed on internal pelvic examination by finding an enlarged or irregularly shaped uterus. Once fibroids are suspected it is advisable to confirm the diagnosis with some type of imaging study. Ultrasonography , either externally through a fluid distended bladder, or internally by a vaginally inserted probe, is usually the first imaging test. MRI is a very useful study to confirm the diagnosis of fibroids, exclude fibroid mimics such as adenomyosis, or ovarian masses.
In women with abnormal uterine bleeding assessment of the uterine cavity is important because a submucous fibroid can be missed on traditional ultrasound. Hysterosonography involves passing a small tube through the cervix and injecting fluid into the uterine cavity to serve as a contrast agent during trans-vaginal ultrasonography. Hysteroscopy is an office-based procedure, performed by a gynecologist, where a small, lighted scope is inserted through the cervix and allows direct visualization of the uterine lining. This can be used to direct biopsy when necessary.
Laparoscopy requires general anesthesia and allows visualization of the outer surface of the uterus and surrounding pelvic structures by passing a lighted scope (laparoscope) into the abdominal cavity. This procedure is more commonly performed in the evaluation of pelvic pain and is very useful in diagnosing endometriosis.
Fibroid Basics: Treatment
The most appropriate treatment for uterine fibroids depends on the severity and type of symptoms, size, number, and location of fibroids, and the patient's desire for preservation of fertility. Treatment options include:
Watchful waiting - Fortunately, most fibroids do not cause symptoms and can be managed with observation, an annual physical exam and ultrasound to check for growth.
Medications - usually tried first for patients with symptoms, especially those with abnormal bleeding.
NSAIDs - Non steroidal anti-inflammatory drugs such as motrin (ibuprofen) or naprosyn. These drugs can be effective in reducing heavy menstrual bleeding and cramping. Little if any effect on uterine size and bulk related symptoms.
Iron supplements for those with anemia.
Birth Control Pills / Progestins - hormonal treatments that can be effective in controlling bleeding by diminishing the endometrium (endometrial atrophy). Birth control pills can also help regulate dysfunctional uterine bleeding due to anovulation. Little effect on bulk related symptoms.
GnRH agonists - ex. Lupron, induce a chemical menopause with a low estrogen state. Since fibroid growth is estrogen dependent this therapy decreases the size of individual fibroids and the overall uterine size by ~50%. Also stops menstrual flow (amenorrhea). Potential side effects include menopausal symptoms of hot flashes, vaginal dryness, and irritability. Long term use can lead to bone loss (osteoporosis) and therefore treatment is usually limited to 3-6 months. Unfortunately, rapid regrowth of fibroids occurs within six months of cessation. Typically used prior to planned hysterectomy or myomectomy.
Herbal and Nutritional alternatives - Blue cohosh, black cohosh, milk thistle, wild yam, bee pollen, and shark cartilage have all been suggested to be helpful in managing fibroid symptoms. While there is certainly a high level of interest in these alternatives, there is no published data supporting their use for the treatment of fibroids.
MR Guided Focused Ultrasound – A new, non-invasive, outpatient procedure that uses high doses of focused ultrasound waves to destroy uterine fibroids, without affecting the other tissues around the fibroid. The procedure is conducted in an MRI scanner which helps the physician "see" inside the body to guide and continuously monitor the treatment.
The focused ultrasound energy is directed at a small volume of the fibroid, raising its temperature high enough to cause thermal ablation (killing of the cells) without impacting other tissues. Pulses of energy are repeated until the entire volume is treated. Because the heated volume of tissue is small, multiple pulses are required and the procedure lasts three-four hours depending on the size and number of fibroids treated. The FDA approved the treatment on 10-22-04. Although promising for the treatment of fibroids, and other tumors, the availability is quite limited in the US at this time. The treatment is not intended for women wishing to preserve fertility.
Uterine Fibroid Embolization (UFE) - Medical therapy fails to control symptoms in up to 2/3 patients with abnormal bleeding and a higher percentage in those with bulk type symptoms. A now well established alternative to surgical therapy is uterine fibroid embolization. Using imaging guided angiographic techniques an Interventional Radiologist blocks (embolizes) the blood supply to the fibroids which shrink, causing the symptoms to resolve. This treatment preserves the uterus and potential fertility.
Surgery - Patients who fail medical management, and are not candidates for UFE, may be offered more invasive surgical treatments, typically hysterectomy or myomectomy.
Hysterectomy - the surgical removal of the uterus and is the predominant invasive treatment for fibroids, accounting for 177,000 -366,000 operations per year in the U.S. While this is the only definitive cure for fibroids many have suggested that hysterectomy is radical therapy and should be a last resort for a benign condition such as fibroids. The uterus is most commonly removed through an abdominal incision-abdominal hysterectomy. When feasible a vaginal hysterectomy is preferable, allowing a more rapid recovery. Laparoscopically assisted vaginal hysterectomy (LAVH) uses a laparoscope to facilitate removal of the uterus through the vagina. Laparoscopic supracervical hysterectomy (LSH) spares the cervix and allows removal of the uterus through small incisions. All types of hysterectomy involve removal of the uterus and are obviously only an option for women not planning future pregnancies.
Myomectomy - the removal of one or more fibroids while leaving the uterus intact and is frequently used in those women desiring to preserve their fertility. Estimates range from 37-45,000 myomectomies per year in the U.S. Different techniques are available including using a hysteroscope to remove fibroids under the inside uterine lining (submucous). A laparoscope can sometimes be used to remove fibroids under the outside lining (subserosal) of the uterus. An abdominal myomectomy is performed through an abdominal incision with removal of the fibroids followed by suturing of the defect in the uterine wall. In general, myomectomies are effective in about 80% of patients with abnormally heavy bleeding (menorrhagia). Over time fibroids can recur in 25-50% of cases and require an additional major procedure in 10% of patients.
Myolysis - the obliteration of fibroids by delivering electric current, laser, or thermal energy through needles inserted into the fibroids during laparoscopy. Reserved for perimenopausal or postreproductive women as uterine rupture during pregnancy has been reported following myolysis, due to weakening of the uterine wall.
Endometrial ablation - the intentional destruction of the inner lining (endometrium) of the uterus performed to eliminate abnormal menstrual bleeding. This can be accomplished using a hysteroscope to cut away and cauterize the endometrium (rollerball), or by applying heat (hot water balloon or microwave energy). These techniques can be useful for treating dysfunctional uterine bleeding, but are ineffective for bleeding caused by fibroids.
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