Uterine Fibroid Embolization


Article Author:
Michael Young


Article Editor:
Lyree Mikhail


Editors In Chief:
Tod Aeby


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
6/17/2019 6:46:56 PM

Introduction

Embolization of uterine leiomyomata (fibroids) has been performed since 1995. Because the embolization is either solely or primarily performed through the uterine artery, the procedure is often referred to as uterine artery embolization (UAE).

Technical success (as opposed to clinical success/symptom recurrence) for bilateral UAE by experienced physicians is about 95%. A retrospective review of 84 fibroids over one year showed an average decrease in the size of 60%. Submucosal showed the greatest shrinkage while subserosal showed the least. Ten percent of the fibroids increased in size.[1][2][3]

Anatomy

The uterine artery derives from the internal iliac artery (IIA). The IIA has two divisions, each with multiple branches:

Anterior Division

  • Obturator artery
  • Superior vesical artery
  • Vaginal (females)/inferior vesical (males) artery
  • Middle rectal artery
  • Internal pudendal artery
  • Inferior gluteal artery
  • Uterine artery (UA)
  • The vaginal artery may arise from the uterine artery

Posterior Division

  • Superior gluteal artery
  • Lateral sacral artery
  • Iliolumbar artery 

The uterine artery is typically the first branch of the IIA anterior division, whereas the dominant branch of the IIA anterior division is usually the inferior gluteal artery. Five distinct IIA branching patterns have been described. The most common is as described above. The second most common is a trifurcation of the IIA into the UA, the IIA anterior division, and the IIA posterior division.

The uterine artery has three segments. It first descends along the pelvic sidewall to the broad ligament. There it turns and courses transversely toward the abdominal midline. As it reaches the uterus, it again turns and ascends the uterine sidewall. Thus, the segments are termed the descending, transverse, and ascending segments. The descending segment has no side branches. A cervicovaginal branch usually arises from the mid to distal transverse segment but can arise from the ascending segment. The ascending segment sends numerous branches coursing over the surface of the uterus and that in turn give rise to numerous perforating arterioles. The arterioles supplying individual fibroids are usually too small either to be seen or to be catheterized.

Communication (anastomosis) between the uterine artery and the ovarian artery (OA) can be demonstrated in almost 50% of women in cadaver studies, but during angiography, this anastomosis is visible about 1 in 10 times. A classification for ovarian artery-uterine artery anastomoses has been proposed. Flow from the ovarian artery into the descending or transverse uterine artery is the most common (type 1). An ovarian artery branch can bypass the main uterine artery to an ascending uterine artery branch supplying a fibroid (type 2). In about 1 out of 20 women, an ovarian artery is absent, and the ovary itself is supplied by the uterine artery (type 3).

Conversely, the ovarian artery (instead of the IIA) rarely supplies the uterus directly with no uterine artery from the IIA (not given a type number but similar to type 1). There are other rare variants as well. The ovarian artery typically arises from the aorta a few centimeters below the origins of the renal arteries. Their courses are often too tortuous to catheterize very far.

Indications

The success of UAE depends on appropriate patient selection, which requires an investigation of multiple pertinent positive and negative factors. [4][5] Patient symptom control and post-procedure satisfaction are highest in "ideal" candidates, which are women with no contraindications to UAE and with all of the following characteristics:

  • Heavy regular menstrual bleeding or dysmenorrhea associated with intramural fibroids
  • Premenopausal
  • No desire for future pregnancy

Fibroids characteristically cause heavy bleeding cycles, not irregular bleeding. Increased frequency of bleeding (fewer than 21-day cycles) and increased duration of bleeding (greater than 10 days) are more likely to be related to endometrial pathologies such as polyps or cancer.

Instead of or in addition to bleeding, fibroids can cause "bulk-related" symptoms:

  • The sensation of pressure in the lower abdomen, legs, and back
  • Dysuria (i.e., nocturia, polyuria, incontinence)

Prospective cohort studies and randomized controlled trials (RCT) of women who have undergone UAE have found a long-term improvement in bulk-related symptoms.[5][6]

There are other indications for UAE.

Adenomyosis

A review of 511 women having undergone UAE reported significant improvement in 76%, and other studies with smaller patient groups have also claimed high rates of improvement. However, there has not yet been a study that has included a control group to even account for a placebo effect.  Some patients in published reports have complained of worsened pain after UAE.

Postpartum Hemorrhage (PPH)

Whether UAE is used as first or second line treatment (i.e., after incomplete/ineffective surgical ligation) tends to be institution dependent. Factors predicting the need for UAE as the first line before surgery include abnormal placentation and clotting function (i.e., fibrinogen/INR). UAE after a failed uterine artery ligation is more difficult. Persistent bleeding after surgical treatment can indicate an extrauterine arterial source for bleeding that may be better identified with arteriography. In one study, arterial embolization was successful in 10 of 11 cases after failed surgical ligation therapy..

In some institutions, gynecologists request UAE as a prophylactic measure in an attempt to reduce operative hemorrhage, for example, resection of uterine tumors, before fetal delivery in the setting of placenta accreta.

Failed Medical Therapy for Pain or Bleeding 

UAE also becomes a relevant consideration if a patient without contraindications declines or has already attempted alternative proposed therapies to treat bleeding or pelvic bulk symptoms (e.g., hysterectomy, myomectomy, endometrial ablation, gonadotropin-releasing hormone agonists, or focused ultrasound).

An in-depth discussion of medical treatment for fibroids and abnormal uterine bleeding is beyond the scope of this article, but a brief overview is included here. A meta-analysis of randomized trials concluded that nonsteroidal anti-inflammatory drugs are more effective than placebo with placebo at decreasing menstrual pain and heavy menstrual bleeding but are less effective in reducing bleeding than tranexamic acid or the levonorgestrel-releasing IUD.

Gonadotropin-releasing hormone analogues (GnRHa) can shrink fibroids and limit menorrhagia but usually initially worsen symptoms and can only be used for 2 to 6 months when there is a clear therapeutic goal such as scheduled surgery or when menopause is incipient because they cause osteopenia (Friedman 1991).  Gonadotropin-releasing hormone antagonists avoid the symptom flare associated with GnRHa but also cause osteopenia. Randomized trials have shown that the progesterone-receptor antagonist mifepristone and ulipristal acetate decrease fibroid symptoms and reduce fibroid volume but prevent pregnancy. Rebound fibroid growth occurs after cessation of both kinds of GnRH-based therapies.

Contraindications

Different organizations have different lists of "absolute" and "relative" contraindications. The following list roughly orders contraindications from strongest to weakest.[4]

  • Viable pregnancy
  • Active endometritis
  • Malignancy of the uterus/cervix without concurrent surgical treatment planned
  • Postmenopausal patient with bleeding of undiagnosed etiology
  • Fibroid already infarcted (based on MRI)
  • Fibroid smaller than 1 cm
  • Fibroid morphology of peduncles greater than 50% (stalk width less than 50% of the maximum width; some people use different percentage cutoffs)
  • Fibroid of cervix
  • Concurrent use of GnRH agonist
  • Prior pelvic radiation therapy
  • Immunocompromised state
  • Fibroid induced uterus size to the equivalent of greater than 24 weeks gestation (uterus craniad aspect at umbilicus)
  • Severe contrast allergy
  • Severe renal insufficiency not receiving dialysis
  • Uncorrectable coagulopathy

Of some controversy:

  • Patient desire for future pregnancy
  • Adenomyosis

For both topics, the 2014 SIR guidelines state that in the absence of further evidence, neither should be seen as a contraindication but only as a point of discussion. The 2009 SIR guidelines listed patient desire for future pregnancy as a relative contraindication and were ambivalent on adenomyosis, only stating that "extensive endometriosis or adenomyosis" could result in UAE failure.  Evidence regarding these issues is discussed elsewhere in this article.[7][8][9]

Gonadotropin-releasing hormones that may have been prescribed as medical therapy for the pelvic condition should be stopped at least three months before UAE because they constrict the uterine arteries and may preclude their catheterization. Indications for GnRH agonists also include in vitro fertilization and breast cancer. 

If the stalk of a pedunculated fibroid is much less than the overall fibroid diameter, then laparoscopic resection can avoid the chance of the fibroid sloughing and the formation of a loose necrotic tissue mass in the abdomen creating a potential abscess nidus. A fibroid that is too large is unlikely to be successfully embolized, whereas a fibroid that is too small is unlikely to be the source of symptoms. Fibroids of the cervix are often able to be removed via a vaginal approach operation.

Equipment

In general, tumors are embolized with particles, which are more likely than coils or glue to reach arterioles and capillaries and induce necrosis. There are several types of particles, including tris-acryl gelatin (TAG) microspheres, non-spherical polyvinyl alcohol (PVA), and spherical PVA.

No clinical difference was found between use of less than 500 micron PVA, and 500 to 700 micron PVA particles were found in an RCT. However, it is generally believed that smaller particles result in better infarction rates. This can be good or bad depending on the situation because particles can reflux within an artery and cause "inadvertent" embolization of other arterial beds (such as the ovary). Therefore, large (700 to 900 micron) particles may be chosen if there is a visualized ovarian artery anastomosis, whereas small (300 to 500 micron) particles may be chosen when the microcatheter has been successfully placed deep within the uterine artery without visualized uterine artery-ovarian artery anastomosis to attempt better fibroid infarction.

An RCT comparing TAG microspheres to nonspherical PVA particles found no difference in short-term clinical outcomes. A follow-up RCT by the same physicians then found a statistically significant increase in fibroid infarction rates with TAG compared to PVA with a trend toward improved short-term clinical outcome with TAG.[10][11][12]

A third RCT comparing PVA and TAG had eight treatment failures in 27 patients with PVA and one treatment failure in 26 patients TAG, but the physicians used smaller particle sizes for TAG than for PVA, and there was a conflict of interest in that the TAG manufacturers paid for the study. There has not been an RCT comparing clinical symptoms after using TAG and PVA of the same size particles.[13][14]

Preparation

The possible causes of the symptoms should be investigated to exclude pathologic or anatomic contraindications to UAE (as discussed above).

Cancer Screening 

The patient should be current in her gynecologic screening for cervical cancer. ACOG recommendations include HPV testing at age 30 then every 3 years if HPV-positive and every 5 years if HP- negative. Papanicolaou smears are not recommended after age 65 unless there is a special reason to continue. Women with any endometrial abnormalities on imaging, particularly women over age 45, should undergo endometrial biopsy before UAE. 

Serum Parameters to Evaluate

  • Electrolytes, glomerular filtration rate (eGFR)
  • Complete blood count (CBC)
  • Platelet count greater than 50,000 per microliter
  • International normalized ratio (INR) less than or equal to 1.5
  • Beta-human chorionic gonadotropin for pregnancy exclusion

Imaging

MRI provides a significant amount of additional information compared with ultrasound (size and position of fibroids, adenomyosis status) and should be performed prior to UAE.

Informed Consent

The 2009 SIR guidelines (Hovsepian 2009) stress the importance of informed consent before UAE:

"Any and all treatment options should be presented with the understanding that, for patients interested in gynecologic alternatives, additional consultation will be required. Choice of embolic agents, routes of vascular access, and the anticipated use of an arterial closure device should be discussed. Descriptions of the expected process of admission to the hospital (and by whom), the immediate post-uterine artery embolization recovery period, convalescence and medications at home, and the time expected away from work should also be made.[15]

Written materials given at the time of consultation can enhance this process. Contact information should be given to patients so they can access a responsible physician on a 24-hour availability basis if they perceive that a problem has arisen."

The 2014 SIR guidelines state:

"Interventional radiologists should inform patients about...the possibility of a missed diagnosis of cancer and a delay in definitive treatment."

This recommendation is given knowing that the risk is less than 1% (as discussed further in that article). In this manner, the recommendations preserve patients' rights of autonomy in the face of a severe risk.

Pre-Procedure Care

Blood-borne pathogens can colonize UAE-induced necrotic tissue. The SIR recommends antibiotics to reduce the chance of abscess development.

  • Antibiotics: 1 g cefazolin or 500 mg levofloxacin intravenously (IV)
  • There is no consensus about prophylactic antibiotics in this setting.

Some physicians prescribe pain medication (e.g., ketorolac 30 mg IV) prior to the procedure. If the patient has risk factors for a difficult airway (e.g., screens positive on a sleep apnea questionnaire), then precautions should be taken (e.g., having the patient monitored by capnography at all times) to prevent arrest from respiratory depression from sedation.

Post-Procedure Care

There are a number of clinical factors that may need to be addressed after the procedure. 

Pain

Options include NSAIDs and opioids.

One regimen includes:

  • Ketorolac 30 mg before the procedure and after, then 30 mg every 6 hours intravenously (IV) as an inpatient
  • Ibuprofen scheduled and opioid of choice PRN after discharge

Puncture site pain or leg pain is common, which can be from injury of medial femoral cutaneous nerve. It usually responds to NSAIDs and time. For severe pain, gabapentin. 

If a patient has persistent (longer than 1 week) abdominopelvic pain, imaging workup for non-target embolization should be considered.

Chronic pain syndromes (such as inflammatory bowel disease) may worsen after UAE.

Pulmonary Emboli Prevention

Sequential compression devices and prophylactic enoxaparin should be considered.

Bleeding

Vaginal bleeding in the first week could indicate a developing endometrial infection. The patient should have flu-like symptoms/fever. Bleeding after the first week with cramping could indicate sloughing fibroid. 

Nausea

Consider ondansetron 4 mg IV after the procedure and every 6 hours until discharge. 

Hypertension

Blood pressure often increases in the short term after embolization. Potential sequelae of hypertension include pulmonary edema, myocardial infarction, and stroke. 

After discharge, communication between patient and the physician or physician representative should continue during the first week. Physicians may wish to schedule a return clinic visit at 1 to 3 months.

Technique

  • Access the common femoral artery and insert a 5 or 6 French sheath.
  • Obtain an arteriogram to demonstrate the arterial anatomy and find the origins of uterine arteries.
  • Place a catheter with a selective tip shape into the internal iliac artery anterior division.
  • Advance a smaller catheter (a microcatheter) coaxially through the selective tip catheter and then into the uterine artery horizontal segment beyond any cervicovaginal branch(es).
  • Obtain another arteriogram through the microcatheter to identify any collateral branch(es) to the ovaries/bladder/vagina that might affect decisions regarding the particle delivery.
  • Perform embolization.
  • Obtain final images showing the state of intra-arterial contrast flow to the uterus.
  • Repeat the procedure on the contralateral side.
  • Obtain hemostasis at the site(s) of the arterial puncture(s).

Variables are many and include:

  • Bilateral femoral artery punctures (to decrease procedure time) vs. single femoral artery puncture (to decrease the likelihood of access site complication)
  • Initial or final overview arteriogram from the aorta (to identify ovarian artery contribution/variant anatomy) versus only selective common iliac arteriograms (to reduce contrast load)
  • Delivery of medications during the procedure (such as nitroglycerin to prevent/treat arterial spasm, lidocaine intra-arterially or ketorolac intravenously to reduce post-procedure pain)
  • Embolization endpoint (contrast stasis in the uterine artery for 5 to 10 heartbeats versus the beginning of visualization of contrast reflux toward the uterine artery origin versus the pruned appearance of the uterine artery)

Complications

The overall complication rate differs by author and can be as high as 40% to as low as about 5%.[15][16][17]

Major Complications

  • Death (less than 1/1000)
  • Need for surgery due to a complication of the procedure such as arterial perforation (2 to 3 in 100)
  • Abscess/other serious intrauterine infection (1 in 100)
  • Pulmonary embolism
  • Subsequent pregnancy-related complications: spontaneous uterine rupture at the mid-posterior wall during subsequent pregnancy, placenta accreta
  • Premature ovarian failure
  • Buttock/leg ischemia

Death

Deaths have occurred from UAE via uterine infection/sepsis and pulmonary embolism.

Infection-Spectrum Findings

Postembolization syndrome is the most common adverse event and includes pain, low-grade fever, malaise, nausea, and appetite loss. Symptoms and signs of bacterial endometritis include pain, fever, vaginal discharge, and/or leukocytosis. Initial therapy includes intravenous antibiotics and medications to reduce pain and inflammation. Noninfectious endometritis can manifest as watery vaginal discharge, fever, and/or leukocytosis and occurring days to weeks after the procedure. Imaging findings do not reliably differentiate infected fibroids from non-infected fibroids immediately after UAE.

Amenorrhea Spectrum Findings

Amenorrhea of any kind occurs in less than 10% of cases when considering all comers and is much more likely in patients older than 45 to 50 years old. It is usually limited to a few cycles and is not typically associated with increased FSH levels or menopausal symptoms. Premature ovarian failure is defined as the presence of persistent amenorrhea, increased FSH levels, and symptoms of menopause (night sweats, mood swings, irritability, and/or vaginal dryness).

Expulsion of Fibroids

Transcervical leiomyoma expulsion is defined as a detachment of leiomyoma tissue from the uterine wall and subsequent transvaginal passage, most commonly occurring with submucosal leiomyomata that have thin points of attachment. This process may occur with uterine contractions, abdominal pain, fever, nausea, vomiting, and vaginal bleeding or discharge.  Surgical intervention may be necessary to relieve persistent discomfort and remove the tissue predisposing to infection.

Angiography Complications

These include hematoma, dissection, pseudoaneurysm, and contrast-induced nephropathy.

Complications Other

  • Patients may have persistent pain. Contrast-enhanced CT or MRI may be used in these circumstances to assess for findings of non-target embolization or fibroid sloughing into the pelvis.
  • The radiation doses for UAE are an order of magnitude less than those required to produce radiation burns.
  • There have been reports of petechial rash on the torso and limbs (1% to 7%).

Clinical Significance

For women with ideal characteristics, a high symptom control rate, satisfaction, and quality of life can be achieved for up to 10 years after treatment, as discussed below.

The SIR data indicate that about 90% of women should experience a reduction in bulk symptoms and more than 90% should expect the elimination of abnormal uterine bleeding.

Causes of UAE failure:

  • Poor patient selection
  • Large fibroids
  • Technical limitations
  • Inability to catheterize the uterine arteries
  • Incomplete embolization
  • Spasm leading to the poor flow of embolic arterial 
  • Clumping of embolic material leading to false endpoint
  • Anatomic variants
  • Presence of important collaterals (e.g., ovarian arteries)
  • Coexisting adenomyosis or leiomyosarcoma
  • Physiologic
  • Recanalization of embolized arteries

Trials and Guidelines for Treatment of Fibroids

There have been seven RCTs comparing UAE versus surgery for fibroids including 793 women. Three trials compared UAE against abdominal hysterectomy, two against myomectomy, and two against either type of surgery. In a meta-analysis of these patients, Gupta et al. (2014) found no significant difference between UAE and any type of surgery concerning patient satisfaction or major adverse events. UAE had a higher rate of minor complications and needed for additional surgical interventions. Gupta calculated that within 2 years of initial therapy, 7% of women require further surgery after hysterectomy or myomectomy, whereas 15% to 32% require further surgery after UAE. UAE patients were found to have a lower likelihood of requiring a blood transfusion, shorter procedural time, shorter length of hospital stay, and faster resumption of usual activities.[18]

The first randomized controlled trial (RCT), Embolization versus Hysterectomy for Symptomatic Uterine Fibroids (EMMY), enrolled patients between 2002 and 2004. This multicenter trial has the longest follow-up to date of ten years. Enrolled patients had both fibroids and menorrhagia and were all eligible for hysterectomy.  One hundred seventy-seven patients were randomized to UAE (n = 88) or hysterectomy (n = 89). Ten years after treatment, 33% of UAE patients had undergone secondary hysterectomy for recurrent symptoms (8% of initial hysterectomy patients also required a second procedure), but there were no significant differences between hysterectomy and UAE in pain, bulk-specific complaints, complications, or overall satisfaction. The study authors concluded that hysterectomy is better to achieve a certain cure for bleeding problems but that patients with the appropriate combination of indications and lack of contraindications should be allowed to choose UAE instead of a hysterectomy.[19]

The Randomized Controlled Trial of Embolization versus Surgical Treatment for Fibroids (REST) is the largest study to date. It was a multicenter RCT comparing all surgical interventions to UAE and achieved 80% power with 1-year follow-up. It found no statistically significant difference between UAE and surgery in quality of life or major complications. UAE had a higher minor complication rate (34% versus 20%) but also had a statistically significant reduced length of hospitalization, 24-hour pain score, and cost.[20]

In one study, patients having intramural fibroids larger than 4 cm to UAE (n = 58)  were randomized to myomectomy (open or laparoscopic according to surgeon preference; n = 63) and followed them for two years. This is the primary study used as the rationale for making myomectomy first-line invasive therapy in women who still wish to conceive, as 50% of UAE versus 78% of myomectomy patients were able to conceive. UAE in this study had an increased calculated relative risk compared to myomectomy for (1) inability to conceive and (2) miscarriage (95% CI of [1] 1.11 to 4.44 and of [2] 1.25 to 6.22). However, Gupta (2014), included Mara's patients with others having undergone myomectomy in RCTs and deemed the evidence that myomectomy provides a fertility benefit over UAE to be "low-quality evidence" that "should be regarded with extreme caution." Another systematic review on myomectomy concluded that there is currently insufficient evidence that myomectomy improves fertility whether by the laparoscopic or open approach.[18]

A systematic review of 15 prospective cohort studies and RCTs found that loss of ovarian function after UAE occurred primarily in women older than 45 years of age..

Despite the conclusions of Gupta (2014), guidelines by gynecological societies in France, the United States recommend myomectomy over UAE for symptomatic intramural and subserosal fibroids in women who wish to have a subsequent pregnancy. The Royal College of Obstetricians and Gynecologists does not have guidelines on the subject; the British National Institute for Health and Care Excellence guidelines do not favor UAE or surgery over the other.

Trials and Guidelines not for the Treatment of Fibroids

There are no RCTs comparing UAE to other treatments and almost no society or national guidelines regarding the use of UAE over other therapies outside of the setting of treatment of fibroids.

For the control of PPH, emergent UAE has about a 90% to 95% success rates (with failures usually requiring hysterectomy), and morbidity is less than with emergent laparotomy.

Enhancing Healthcare Team Outcomes

Healthcare Team

Uterine artery embolization is usually performed by an interventional radiologist, but the gynecologist and obstetrician should also be able to educate the patient about pros and cons of this technique compared to surgical and/or medical treatments that the gynecologist can offer. The patient should be informed that infertility may result and that current or subsequent pregnancy may be complicated, such as by premature birth. [21][22](Level V and see above section, Level I).  The nurse taking care of the patient post-procedure may have to administer physician-prescribed analgesics and other medications and observes for signs of complications, primarily those resulting from arterial puncture. In addition, team members may assist each other in performing the procedure and providing appropriate follow-up care.

Outcomes Summary

Most randomized (Level I, see above section) and non-randomized series report high odds of clinical success and subsequent pregnancy success for UAE, although UAE is not necessarily always superior to surgical techniques.  UAE is best suited for women who prefer a minimally invasive procedure to surgery or other methods of treatment and are willing to accept the risks of UAE [23][24](Level V).


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Uterine Fibroid Embolization - Questions

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Uterine Fibroid Embolization - References

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