Uterine Artery Embolization

Uterine artery embolization (UAE), also referred to as uterine fibroid embolization (UFE), is a minimally invasive treatment for uterine fibroids. (The term ablation, as in endometrial ablation, and the term embolization sound similar and can be easily confused.)

The principle behind embolization treatment is that by temporarily blocking off the blood supply to the uterus, the fibroids are destroyed and the normal myometrium is able to recover.

This embolization technique has been used for many years to treat emergencies of uterine bleeding, including bleeding after childbirth or with certain kinds of abnormal pregnancies. It was first used specifically for uterine fibroids in 1995. The original study by Ravina and associates treated women prior to planned hysterectomy.  Because a significant proportion of the women had symptom relief without undergoing surgery, the technique was explored as an alternative to hysterectomy. Because the catheters and embolic agents used for UAE treatment were widely used for the treatment of other diseases, UAE was rapidly incorporated into practice. (There was not a “new” device introduced that would have required clinical trials supervised by the U.S. Food and Drug Administration [FDA] before the device could be used.) However, since that time, clinical trials have been conducted, and several embolic agents have received approval from the FDA specifically to treat symptomatic uterine fibroids. (Prior to this time, use for fibroid treatment was what is termed “off-label” use.)

The Procedure

As a procedure, embolization is very similar to a cardiac catheterization. UAE takes place in a room with fluoroscopy equipment to take X-ray pictures throughout and have them available on a screen to guide the procedure. An incision less than a half an inch in size is made where the leg meets the trunk. This allows the artery to be identified, and a long skinny tube called a catheter is then put into the blood vessel under X-ray guidance. Instead of taking the catheter up to the heart and using a balloon to open up a blood vessel, the catheter is used to go to both the right and left uterine arteries and uses tiny sandlike pellets (embolic agents) to block off the blood supply to the uterus.

uterine artery embolization for uterine fibroids picture of procedure

The pellets are normally made of polyvinyl alcohol (PVA) or trisacryl gelatin microspheres (TGM) and are designed to stay in the blood vessels permanently. “Dissolving” embolic agents are available, but most of the time fibroid embolization is done with one of the permanent agents.

Many women are concerned that the particles will move at some later date and possibly injure another organ. Once they are in the uterine blood vessels, however, this is unlikely. There have been rare complications with pellets going to other places in the pelvis and causing injury to the labia or buttocks, but these complications probably occurred because the pellets were released too early and went down other branches of the major blood vessels in the pelvis and not just the uterine arteries. Finding a physician who does a lot of pelvic embolization is essential.

uterine artery embolization for uterine fibroids picture of pellets in artery

Many people have the impression that the blood supply to a specific fibroid can be targeted, since some academic papers discuss things such as “superspecific UAE.” This is not possible, however, and that is why some gynaecologists prefer the older term UAE to UFE. Uterine artery embolization is a global therapy: it targets the whole uterus, including normal myometrium and endometrium. Two things help optimize placement of the pellets. First, placing the catheter deeply into the uterine artery so that the flow is forward into the uterus is crucial. Second, the size and shape of the embolic agent used determine whether you block the vessel closer to the origin or closer to the fibroid. The smaller and rounder the embolic agents are, the farther they flow. Just as if you were trying to block off the branch of a creek, you are better off using big logs than little branches and better off using logs than beachballs the same size.

The procedure generally takes about an hour. Patients receive local anesthesia, or numbing medication similar to what you get in the dentist’s office, for the small incision as well as intravenous medication for relaxation and pain relief during the procedure. The goal is to be awake but relaxed. In most institutions, patients are hospitalized the first night after the procedure. UAE is associated with a high chance of fever and pain postoperatively. This combination of symptoms is commonly referred to as postembolization syndrome. The pain of postembolization syndrome can be quite severe and can be like “having a heart attack in your uterus.” Heart attack pain is caused when the heart muscle has its blood supply cut off, so it makes sense that cutting off the blood supply to the uterus produces similar pain. Pain medications are provided to minimize the pain, and experiencing significant pain is now rare following UAE.

Most women are discharged from the hospital the next morning, and most women require a narcotic pain medication while at home. Early studies documented that women return to work in 7 to 10 days; more recent studies suggest that many women may return to work after less than a week, with the full range being about 4 to 14 days.

The Results of UAE

Most studies reveal that more than 80 percent of women have a reduction in their fibroid-related bleeding; a similar percentage have a reduction in the symptoms related to the size of their fibroids. Many women erroneously assume that this means that UAE reduces the volume of the uterus by 80 percent. In fact, the average uterine volume reduction is about 30 percent, which is a disappointment for many women. Translating this volume reduction into the expected size of the fibroid following embolization is complex.

One of the major issues is the relationship between diameter and volume. The formula for calculating the volume of a sphere is 0.525D3 , where D is the diameter of the sphere. (Most fibroids are not spherical but are really ellipsoids, more like a baking potato than an orange, with several different diameters.) This formula also works in those cases using D1*D2*D3 (representing the diameter in each dimension) instead of D3

Table 1

Pre UAE

Pre UAE

Post UAE (30% decrease in volume)

Post UAE (30% decrease in volume)

Diameter (cm)

Volume (cm3)

Diameter (cm)

Volume (cm3)

1

0.5

0.8

0.4

2

4.2

1.7

2.9

3

14.2

2.7

9.9

5

65.6

4.4

45.9

10

525.0

8.9

367.0

15

1,814.0

13.4

1,270.0

In table 1, the first two columns show the diameter and the volume for several different sizes of spherical fibroids. (Although most fibroids are not spheres, using a single value for all three dimensions makes the concept easier to grasp.) In the last two columns we see the diameter and volume of those same fibroids if the typical 30 percent volume reduction occurs following UAE.

The first thing to note is that the volume rises quickly as the diameter increases. The volume of a 10-cm fibroid is 1,000 times greater than a 1-cm fibroid. Most people erroneously assume that with a 30 percent volume reduction (i.e., the volume is reduced by about a third), the diameter will be decreased by about a third. But that is not the case, and so, instead of the diameter of a 15-cm fibroid shrinking by 5 cm, it shrinks only by 1.6 cm. Thus many women with big fibroids who expect to have a flat stomach following UAE are disappointed with their results.

The other way in which to relieve symptoms is to change the pressure or composition of the mass. Fibroids are typically firm and rubbery. Following embolization, the fibroids typically become soft and squishy. This change is like the difference between having a firm rubber ball sitting on your bladder and then having a Nerf (soft foam) ball of the same size sitting on your bladder. Studies describing early results of UAE suggested that the amount of volume reduction following UAE does not correlate with the amount of symptom relief. In other words, women experience greater relief in their symptoms than would be expected from how much the volume of the uterus decreased, suggesting that this composition change is important.

Even so, studies examining long-term outcomes suggest that volume reduction is critical for achieving symptom relief. In a series of women treated in the United States and followed for 5 years, more than 70 percent were happy with their results at 5 years. Women with symptom control at 1 year were more than five times as likely to have symptom control at 5 years. In this study, UAE failed to control symptoms more than twice as often in women with a larger uterus. Taking all the uterine volumes and ranking them by size and looking at the larger group versus the smaller group, the midpoint (median) was 717 cm3 , or the size the uterus would be with about a 10- to 11-cm fibroid or several fibroids equivalent to this volume (as in table 1, which shows that a 10-cm fibroid has a volume of 525 cm3, and a 15-cm fibroid has a volume of 1,814 cm3, so 717 cm3 appears consistent with a little bigger than 10).

A study from France found that not only increased volume but also an increased number of fibroids led to less success. A rule of thumb emerged from this study which says that for each 1 cm in a leiomyoma’s diameter at baseline, the chance of failure increased by a factor of about one and a half. Similarly, for each additional fibroid present prior to treatment, the chance of failure increased by about one and a third.

Several other factors influence the success of UAE. First, if only one uterine artery can be embolized, the procedure often will not work. The uterus easily establishes its blood supply from the remaining artery. Second, if the fibroid receives its major blood supply from another blood vessel, such as the ovarian or cervical artery, then embolizing the uterine arteries does not produce good results. The appearance of the fibroids on magnetic resonance imaging (MRI) generally predicts success; fibroids that appear dark on T2 weighted images appear to respond best. Finally, degenerated fibroids (fibroids that have previously lost their blood supply) do not respond to UAE; these fibroids have had a “natural UAE.”

Together these results suggest that, like laparoscopic and hysteroscopic myomectomy, UAE is best performed in women who have a limited number of fibroids and fibroids that are smaller. We clearly need interventions with fewer side effects to treat women earlier than we do now. Many diseases in the past were treated surgically at a very advanced state and can now be treated earlier. Breast cancer has been transformed from a disease in which a large mass in the breast was the first sign, to a disease frequently treated when there is an abnormal mammogram and the cancer is too small to feel. Likewise, hernias used to be treated when there was a big bulge in the abdominal wall, and now they are repaired at the first sign of abdominal wall weakness. We have a long way to go with fibroids.

Pregnancy and Childbearing after UAE

Uterine artery embolization generally is recommended for women who do not wish to have future pregnancies. A number of women have had successful pregnancies following UAE, however, and many of them were in their forties when they had the UAE, meaning they already had an increased risk of infertility and pregnancy complications based on their age.

One reason for this recommendation is that the UAE procedure affects the blood supply to the ovaries. If the main blood supply to the uterus is cut off via the uterine arteries, then the uterus tries to get a blood supply from the smaller blood vessels that supply it, called the collateral blood vessels,to keep itself alive. The most important collateral blood supply to the uterus is the ovarian arteries. Although some people argue that ovarian function should be affected only if the embolic particles are incorrectly targeted and hit the ovaries, understanding the blood supply to the uterus tells us that even with correct targeting, blood flow to the ovaries can be interrupted. The uterus is a smart organ; if one area of blood supply is cut off, another will be recruited to replace it.

This effect on ovarian function is seen most clearly in women who stop having periods following UAE (again, technically this is called amenorrhea). Early studies described rates of amenorrhea of 5 to 8 percent following UAE and reported that, like women undergoing chemotherapy, sometimes women would resume having regular periods later. The largest study (consisting of more than 500 women) suggests that the risk of amenorrhea is age-related. For women under age 40 the risk of amenorrhea is only 3 percent, whereas for women over 50 the risk is 40 percent. In several cases the woman’s level of the hormone FSH rose, like it does in menopause when the periods stop, suggesting that the procedure caused a transient menopause-like state.  

This finding makes sense, since older women have less “ovarian reserve” as they approach the age of natural menopause. Since the average age of menopause is 51 in the United States, women still menstruating after that age likely are close to menopause anyway. For women who desire fertility, however, the number of women who have such severe ovarian damage that they stop having periods is only the tip of the iceberg. A major cause of infertility in women as they age is decreased ovarian reserve, having fewer eggs, or a less good quality egg, which makes getting pregnant harder. Thus, the number of women with ovarian damage may be significantly underestimated by concentrating only on those who stop having periods. I think of the risk of ovarian damage like a triangle (or iceberg): the top is women who stop having periods, but the base is women with normal cycles who have trouble getting pregnant.

Although there have been reports of women who got pregnant following UAE-induced amenorrhea, no one has followed a large group of women attempting pregnancy after UAE. Therefore we do not know whether failing to become pregnant or having difficulty getting pregnant is a major issue or not. However, if 3 percent of young women have enough of a shock to the ovary to stop having periods, even temporarily, how many may have fertility problems later due to lost eggs? Longer-term studies are necessary. There has been a report of one woman who stopped having periods after UAE but who nevertheless had normal ovarian function. In this case the endometrium (uterine lining) appeared to be affected by the UAE.

Each individual and her doctor need to make a decision together regarding UAE and plans for pregnancy. For women with an increased risk of surgical complications, like someone with a previous myomectomy, the risks of UAE may be very acceptable. Or, for some women, the benefit of a quicker recovery may be more important than a possible decrease in fertility. Finally, deciding whether optimizing the chance of pregnancy is the critical point or instead just making sure the door to pregnancy is left open is an important dis-tinction when deciding on newer therapies such as UAE, in which the longer-term results are unknown. Only with more and longer studies will we have real answers.

In addition to a number of reports of normal pregnancy, cases have been reported of significant pregnancy complications following UAE. Again, because large series of women have not been followed from UAE through pregnancy, we do not know whether this is a rare event or a common one. We need to know both the numerator (the number of women having pregnancy complications) and the denominator (the total number of women undergoing UAE and attempting pregnancy) of this important fraction.

There is also a bias toward reporting pregnancy complications; medical journals are not interested in normal pregnancies following a procedure. If a woman has an unusual complication, her doctor has greater motivation to write about this rare event. Nonetheless, because some of the embolic particles likely end up damaging the normal uterus, there is reason to believe that pregnancy complications could be increased after UAE.

In one large study in Canada in which women were followed as a cohort following UAE (so we get both numerator and denominator), again healthy pregnancies did occur, but there were also a greater than expected number of problems with the placenta. Twelve percent of women had abnormal placentation, either placenta previa (whereby the placenta implants over the cervical opening, blocking vaginal delivery and putting the woman at risk for severe bleeding) or placenta accreta (whereby the placenta embeds itself too deeply in the uterine wall and does not separate easily following delivery). This is a high percentage of women having this problem, and none of these women had had previous pregnancies (abnormal placentation more often occurs in women who have had prior deliveries or cesarean sections or both). These placenta problems also fit what we know about the risks, in theory, of the procedure; if the normal uterine wall is partially embolized, then damage may occur to the wall like it does during C-section. Clearly women contemplating pregnancy following UAE and their obstetricians need to be aware of this risk.

It has been argued that UAE has long been done for women shortly after delivery for problems such as postpartum hemorrhage and that the results are good. Although the procedure is similar, the situations are entirely different. Bleeding immediately after pregnancy is usually caused by an abnormality of the placenta, an inability of the uterus to contract normally, or a change in blood-clotting factors due to excessive bleeding. These events are transient, and the situation would not be the same a week or a month later. Having a 6- to 10-cm mass in the uterine wall (a fibroid) is a stable cause of bleeding, however, and thus comparing the two situations may not be valid. The blood supply to the uterus is also enhanced during pregnancy. All the collateral blood supply we discussed earlier is recruited during pregnancy and is ready and better able to support the uterus following blockage of the uterine arteries when UAE is performed during or following pregnancy.

Read more about pregnancy after UAE on this site

Potential Complications

Life-threatening complications have been reported following UAE, but they are rare. In an initial series of studies comparing patients undergoing surgery and patients undergoing UAE, the risk of major complications following UAE appeared to be lower than with traditional surgeries. There are now four randomized clinical trials comparing UAE with hysterectomy (two studies), myomectomy (one study), or both (one study), which together suggest that the rate of major complications is the same. A Cochrane Review (the authoritative source for evidence-based medicine) of these studies concludes that UAE is associated with a shorter hospital stay and a faster return to work. It is also associated with more minor complications, unscheduled visits, and higher readmission rates. UAE and surgery have similar rates of complications, but the type and timing of complications differ.

The study that randomized women to UAE or surgery (with 15 percent of women having myomectomy and 85 percent hysterectomy) has reported outcomes one year following treatment. Although both groups had equivalent quality of life at one year, 9 percent of women in the embolization group required another procedure (a second embolization or a hysterectomy).

These studies will continue to give us important information as women are followed longer and additional information is reported in the scientific literature. It will be important to learn whether UAE treatment failures mainly occur during the first year or whether 9 percent of women have additional procedures every year. It will also be critical to know whether symptomatic relief is equivalent with myomectomy and UAE. (Although the symptom scores were lower in the surgery group in the reported trial, this may not be a fair comparison; it is hard to have fibroid symptoms when you no longer have a uterus.)

It is important to note that all these trials took place outside the United States, so all the information may not be applicable to women in the US. With universal health care systems in Europe, women may have less freedom to choose their therapy. Most important, black women may not be well represented in these trials. The racial make-up of the participants in the study reporting one-year outcomes was not described, but given the study sites, it is likely that they were mainly Caucasian.

It will be important as new treatments are introduced that funding is available for trials here and that women participate in trials that allow them to be randomly assigned to a treatment option. Although it is hard to decide to enter a trial and to lose control of deciding on your own treatment, if incomplete information is available on which to make your decision, this is a reasonable option that will also benefit others in the future.

In addition to postembolization syndrome (discussed above), another well-known minor complication is that women with submucosal fibroids frequently expel the necrotic (dead) fibroids through the cervix and vagina. It is not possible to predict the timing of when women will experience this complication. It can occur several days following the UAE or even a year later. This outcome can be beneficial because it increases the volume reduction following UAE, but women often experience labor-like pain when the fibroid dilates the cervix, and the risk of infection is increased. Thus, most experts consider hysteroscopic myomectomy to be a better technique for treatment of a Type 0 or I fibroid, and UAE and hysteroscopic myomectomy complementary, and not competing, techniques.

Encouraged by the success of UAE for the treatment of fibroids, gynecologists are performing several new procedures that try to surgically mimic the effect of UAE. These include surgeries such as laparoscopy, which tie off the uterine arteries, and approaches that use a clamp on the cervix to compress the arteries for several hours. The drawback of these approaches is that there are other vital structures near the uterine arteries, particularly the ureters, that can be damaged. Although UAE causes a small risk of damage to the blood vessels, it does not carry risk of injury to adjacent structures in the way that these other techniques may. Also, since some of these techniques require surgery, the standard surgical risks are added to the risk of vascular occlusion. Clearly, these approaches require further study. Many gynaecologists believe UAE will continue to be a treatment used for the near future. Although its use for women who desire future fertility is controversial, for a woman with no plans for pregnancy, it gives relief of both bleeding and bulk symptoms in a minimally invasive fashion. There is also a small subgroup of women who view the ovarian impairment as an advantage. For women in their fifties who have been trying to temporize until menopause for years, having UAE bring on menopause can be desirable rather than a drawback.

 

tags: