18.1 Introduction

Uterine fibroids are the most common benign tumour in premenopausal women, with a lifetime prevalence of almost 70% in Caucasian women and more than 80% in women of Afro-Caribbean descent. About half of these women experience symptoms, with the most common being menorrhagia, dysmenorrhoea, pressure symptoms and infertility. Whilst hysterectomy is still the most commonly offered and performed operation to treat uterine fibroids, over the last 20 years minimally invasive therapies have been gaining popularity and uterine fibroid embolization is now a mainstream option for most women who wish to preserve their uterus. Since its introduction, a strong body of evidence has built demonstrating safety and efficacy with low rates of complication. Uterine fibroid embolization (UFE) was first described as a treatment for symptomatic leiomyomas in 1995 by Ravina et al. and has proved so popular that in the last year there were over 25,000 uterine fibroid embolization procedures performed worldwide [1].

18.2 Background/History

UFE was first performed as an adjunct to myomectomy. One of the significant complications of myomectomy was (and remains) bleeding. In a number of areas of the body, embolization was known to be a useful tool for limiting the blood loss at the time of surgery (e.g. nephrectomy and spinal fusion for tumour). In an attempt to reduce the risk of significant intraoperative bleeding, Ravina et al. performed embolization [1]. Subsequently, it was found that a significant proportion of those treated by embolization no longer required the intended myomectomy, and this was notably so in those whose surgery was delayed. On the basis of this observation, the concept of UFE as a standalone treatment was born, trials were performed, and then UFE was introduced to mainstream clinical practice.

18.3 Anatomy and Patient Selection

Almost all patients with uterine fibroids who are suitable for hysterectomy and/or myomectomy are suitable for UFE; in fact there are very few anatomical configurations that are considered unsuitable for fibroid embolization in modern practice. Interventional radiologists are best placed to make the assessment on suitability, but this should not be in isolation and the patients should benefit from a multi-disciplinary approach, having already discussed the surgical options with a gynaecologist, preferably in a clinic with the benefit of both specialties. The most common indications for UFE in the United Kingdom are menorrhagia, dysmenorrhoea, pressure-type symptoms and infertility.

An analysis of available practice guidelines [2] states that the absolute contraindications for UFE are consistent across most bodies, and are active pregnancy or active infection. Relative contraindications include endovascular technical considerations such as renal impairment, coagulopathy and contrast allergy. Previous surgery that may lead to altered fibroid blood supply or visible utero-ovarian arterial anastomoses are also quoted as relative contraindications, although in practice these can often be seen and treated at the time of embolization and a safe treatment performed. Razavi et al. describe three types of common anastomoses, and it is important for the operator to recognize these, and to understand the effect that UFE may have on the ovarian artery and that the anastomoses may have with regard to clinical failure of the treatment [3]. Non-visualization of these anastomoses does not exclude small underlying connections and there is very little evidence that they are linked to ovarian failure, with many authors questioning the clinical importance, quoting other factors such as the patient’s age as far more likely to contribute to early menopause.

Over time, the indications for UFE have grown to include all fibroid types and characteristics. Some guidelines suggest patients with pedunculated and/or submucosal and/or subserosal fibroids should not be offered embolization, but as experience with the technique has grown, most practitioners will offer UFE to almost all fibroid types, with areas of uncertainty being discussed on an individual basis. The reasoning behind the reticence is the fear that pedunculated subserosal and pedunculated submucosal fibroids may detach into the peritoneum or uterine cavity, respectively, after embolization and cause complications. The Society of Interventional Radiology (SIR) USA guidance (2014) cites evidence that these fibroids cause no more complications than fibroids in other anatomical locations [4]. This area is important, because as part of the consent process, patients who have a pedunculated submucosal fibroid must be aware that there is a risk of vaginal expulsion after embolization, although in practice this is rare. One common misconception is that once they have been embolized, fibroids will be passed PV. This is highly unlikely, unless the previous imaging has indicated a pedunculated submucosal fibroid. Once the patient is fully aware of the relative merits of the treatment options, she can make an informed decision as to whether UFE is the most suitable for her.

The size of the fibroid burden often is included in the decision making. Whilst there are definitive limits to the size of fibroid that can be treated by UFE, common sense would say that the larger the fibroid, the more embolic agent it will require to treat and the longer the procedure, with an increase in the radiation dose. Recently, however, there been a number of reports demonstrating the efficacy and safety of UFE to treat fibroids as large as 10 cm.

18.4 Clinic and Consent

The majority of interventional radiologists (IRs) in the United Kingdom will consult with patients who are considering UFE in clinic prior to intervention. They will assess the patient’s symptoms, age, wish for future fertility, previous interventions and understanding of the surgical and conservative options. They will review the risks and benefits of embolization including the risks of the procedure and what happens if the patient opts for no treatment at all. The positive aspects of UFE are its effectiveness in dealing with the symptoms caused by fibroids, its safety profile and minimally invasive nature. The advantages of UFE over surgery are a short hospital stay with a quick return to normal activities (usually 1–2 weeks), fewer major complications and the preservation of the patient’s uterus and fertility in most cases. The disadvantages are that these patients, especially if young, may require reintervention at some point, and that the end result is not immediate and it often takes a few months before the symptoms stabilize. Patients are all counselled that whilst the procedure itself is relatively painless, over the first 24–48 hours after the procedure, they can experience some significant discomfort. However, this is usually relatively easily managed.

The patients are warned about the risks of the UFE, which include induction of an early menopause (very uncommon in young women under 40 years), infection, post-embolization syndrome, and the potential need for hysterectomy at some point. The patients are also told about the rare complication of non-target embolization.

The therapeutic effect of UFE peaks at 6 months post treatment, with most exhibiting a significant reduction in fibroid size and related symptoms. However, if the patient wants an immediate and final result then she should be advised towards hysterectomy. If the patient wishes to watch and wait, then she should be informed that the symptoms caused by fibroids are likely to subside after menopause.

Whilst most fibroids involute after menopause, there is a subset of postmenopausal women who continue to suffer with symptoms. Obesity and hormone replacement therapy have been associated with continuing symptoms. UFE for the treatment of pressure or bulk-type fibroid symptoms has been shown to be safe but postmenopausal women presenting with bleeding symptoms need to be thoroughly investigated for malignancy prior to consideration of UFE.

Patients should also be informed that the speed of symptom resolution and efficacy of embolization depend on the symptoms with which they present. It is the authors’ experience that women who present with menorrhagia tend to benefit from a relatively quick resolution of symptoms, whereas those presenting with pressure-type symptoms may need to be more patient for the final results as the fibroids take time to shrink.

18.5 Imaging

Most patients will at some point have undergone pelvic ultrasound investigation which confirms the presence of uterine fibroids, but it has become the standard of treatment to perform contrast-enhanced MRI. This has been shown to be more accurate in characterizing lesions as it provides accurate information on fibroid location, fibroid enhancement or blood supply and the presence of other disorders that may mimic the symptoms of fibroids, such as adenomyosis [5]. MRI will also help identify the feared complication of leiomyosarcoma and differentiate between a benign fibroid and malignant lesion. The standard MRI sequences used are fairly universal with non-contrast T1 and T2 imaging to assess characteristics, size and position. This is followed by post-gadolinium T1 imaging to assess the enhancement of the fibroids and blood supply (Figure 18.1). After treatment, most centres will follow these patients with further imaging (Figure 18.2).

Figure 18.1 T1-weighted MRI images pre- (a) and post-gadolinium (b) contrast showing the enhancing fibroids prior to embolization.

Figure 18.2 Post-embolization. Pre-contrast (a) and post-contrast (b) after embolization T1-weighted images showing that the fibroids are no longer enhancing, and have been successfully treated.

Many centres are using magnetic resonance angiography (MRA) time-resolved imaging to assess the enhancement and blood supply of the patient’s fibroids. This gives an angiogram type of picture which is also very useful for identifying the presence of ovarian artery supply to the fibroid (Figure 18.3).

Figure 18.3 A single MRA image from the time-resolved sequences (at 19.3 seconds after contrast injection) showing left ovarian artery supply to a fibroid.

18.6 Technique

There are two considerations to plan for prior to intervention. Firstly, it has been traditionally considered a potential risk of postoperative infection if a woman has an intrauterine contraceptive device (IUCD) in situ. Studies have shown the risk of performing UFE with an IUCD in situ is very low (less than 1 in 1,300) and so it is very much a matter of preference of the operator whether they consider it important to remove any device prior to embolization. The second consideration surrounds those patients on gonadotrophin-releasing hormone (GnRH) agonists for short-term symptomatic relief from menorrhagia. GnRH agonists have been associated with a reduction in the vascularity of uterine fibroids (indeed that is their mode of action) and may reduce the efficacy of UFE. Some units will stop these medications 3 months prior to embolization to ensure that the uterine arteries have returned to normal prior to treatment. Kim et al. reported a study using GnRH agonists to reduce the size of large fibroids prior to embolization showing this was safe and did not compromise the embolization [6].

The standard technique for UFE is relatively uniform across most centres; however, the finer points of the technique can vary widely between operators. The choice of embolic material, for example, depends on operator preference as a rule, with no strong evidence that one embolic material is superior to another.

Prior to the intervention, the patients are given pre-medications, often including antibiotics and anti-inflammatories. Usually a patient-controlled analgesia system is established and the patients familiarized in its use. This allows access to either opiate or opioid medicines in a controlled fashion. During the procedure, the patients are also given intravenous (IV) paracetamol (acetaminophen).

Prior to the procedure starting, some centres use a superior hypogastric nerve block (SHNB) to reduce the ischaemic pain experienced by the patient. This technique is performed under fluoroscopic guidance with a long 21 gauge skinny needle, under local anaesthetic and aseptic conditions, placed through the anterior abdominal wall down to the level of the L5 vertebral body [7]. The aortic bifurcation is often marked with an arterial catheter to avoid inadvertent puncture of the aorta or aortic bifurcation. Once the bone is reached, a small amount of contrast is injected to delineate the nerve sheaths (Figure 18.4). Once in position, 10 mL of bupivacaine is injected. This has been shown to be safe and to decrease the need for opiate analgesia at 4 hours post embolization. Yoon et al. performed a prospective, double-blinded RCT comparing SHNB with a placebo and showed this reduced the opioid analgesia and antiemetic requirements in the immediate post-embolization period but failed to demonstrate a reduction in the hospital inpatient stay [8].

Figure 18.4 Fluoroscopic image taken in the lateral aspect showing the correct needle position in SHNB with injected contrast showing the nerve sheath. There is an angiographic catheter demonstrating the aortic bifurcation.

The arterial system is accessed most commonly via the common femoral arteries (CFA) under local anaesthetic using ultrasound guidance with a small arterial sheath (4 or 5 Fr.). Some units will access both CFAs with sheaths as bilateral access allows simultaneous bilateral uterine artery embolization, reducing the radiation burden to the patient. However, arterial bleeding from the puncture sites is probably the most common minor complication of UFE and bilateral punctures increase this risk, and the authors prefer a single-puncture protocol. Some units have adopted unilateral radial artery access as the primary access point as there is growing evidence that this is preferred by patients and leads to quicker recovery time [9, 10]. Most units will give unfractionated heparin depending on weight to prevent peri-catheter thrombus formation.

The fixed image intensifier and imaging equipment are all set to a low-dose protocol with the majority of the imaging performed with digital image grabs rather than the traditional subtraction angiography, which has a much higher radiation dose. Digital zoom rather than image magnification also reduces patient dose. The ALARA (as low as reasonably achievable) principle is practised with all these young patients to minimize dose.

The uterine arteries are commonly the first branch from the anterior division of the internal iliac artery (IIA). Once identified, the uterine arteries have a characteristic appearance with a vertical segment followed by a horizontal one and then a corkscrew appearance. The uterine arteries are susceptible to spasm, and many units will give medication to treat or prevent this. The uterine arteries can be accessed (sequentially) with a standard imaging catheter (4 or 5 Fr.) of the operator’s choice. Some operators choose to use a micro-catheter system to embolize the uterine arteries with the intention of reducing the risk of spasm (Figure 18.5). If the artery does go into spasm, this will reduce the efficacy of the embolization. The catheter or micro-catheter is placed in the horizontal segment of the uterine artery to decrease the risk of reflux of embolic agent into non-target branches of the IIA or the cervicovaginal branches.

Figure 18.5 Right and left uterine arteries selectively catheterized using a 4f catheter and micro-catheter combination. The tip of the micro-catheter has a radio-opaque marker on it and the tip is located in the horizontal portion of the uterine artery.

The most commonly used embolic agents are calibrated particles, with the accepted method being to start with smaller particles to allow distal embolization followed by gradual upsizing of particle size (typically in the region of 500 μm or larger). All embolic agents are combined with a radio-opaque contrast agent to allow their progress to be tracked. It is important to monitor the progress of the embolic agents carefully to ensure there is no significant shunting through the fibroid into the venous system and to ensure that there is no reflux of embolic agent backwards into any of the other branches of the IIA, or ovarian communications (Figure 18.6).

Figure 18.6 Catheter angiogram showing left ovarian artery supply to a large fibroid. Note this is a low-dose digital image acquisition and not standard digital subtraction angiography (DSA).

There is often a misunderstanding by non-interventional radiology medical professionals and patients that the fibroids are selectively embolized. The uterine arteries are embolized to near-stasis, and so the unaffected uterus will receive some embolic agent. The fibroids are preferentially supplied by the uterine arteries, whereas the uterus has a rich collateral supply of other vessels, and as a result uterine necrosis is very rare. As embolization progresses, the fibroids can be seen to enhance as the embolic material preferentially collects within the capillaries of the fibroid. Occasionally, the uterus has a single uterine artery supply, and rarely it is possible to access only one of the uterine arteries due to technical issues. In these cases, there is good evidence that the patients can still derive a good symptomatic improvement from single uterine artery embolization.

If significant fibroid supply is noted from an ovarian artery (OA) source, there is evidence that direct embolization of the OA has very little effect on ovarian function. Hu et al. compared standard UFE with UFE plus OA embolization and found there was no effect on ovarian function or symptoms of menopause. However, most operators will avoid embolization of the ovarian supply if possible [11].

Once the uterine artery has been embolized to near-stasis, which is very sluggish flow in a patent uterine artery, many clinicians will pause and wait a few minutes before checking for further antegrade flow or near-stasis again. A slow infusion of intra-arterial lidocaine, when uterine artery flow is slow, has been used to decrease postoperative pain [12]. Once both arteries have been embolized to stasis, the procedure is complete and the groin puncture is closed with either direct pressure or an arterial closure device. Most patients will remain in hospital overnight and go home the next day if well. The patients are often discharged home on antibiotics, although there is no consensus on a prophylactic regime in the literature or in the guidelines.

Clinical outcomes from UFE have been described in multiple papers – the patients can expect a 50–60% reduction in the size of the fibroids with a similar reduction in uterine size. A 90% reduction in pressure-related symptoms and a greater than 90% reduction in menorrhagia have been reported, with 80–90% of patients being satisfied with the early results [13]. At 3 years, the overall reintervention rate is about 14%, and the number of embolization patients who remain satisfied is approximately the same as among those who underwent surgery.

Follow-up varies between clinicians and units; however, most patients are reviewed in the clinic between 6 weeks and 3 months with the benefit of a repeat MRI to assess reduction in uterine and fibroid size as well as degree of infarction. If there is residual perfusion of fibroids following UFE, there is a higher risk of clinical recurrence in time (depending upon the timing of other factors such as menopause) [13].

18.7 Potential Complications

Major complications from UFE are rare and patient satisfaction rates are high post procedure. Major complications are less common than for the surgical alternatives; however, minor complications are more common than in surgery. The most common complication of UFE is a groin haematoma from the arterial access in the CFA. Active arterial bleeding is very rare. The infection rate post-UFE is around 2%, with 0.5% of patients requiring hysterectomy. Pain post embolization should not be considered as a complication as it is an expected result.

One of the most feared complications is non-target embolization, which occurs either due to an anatomical anastomosis between the uterine arteries and the ovarian arteries across the broad ligament or from a technical complication/failure of the procedure. Shunts through the fibroids into the venous system can sometimes be seen on preoperative MRA imaging and should be suspected during the procedure if there is failure to slow the arterial flow with introduction of the embolic agent. If the embolic agent’s progress is not carefully monitored, then it is possible for it to reflux back up the uterine artery into any of the branches of the IIA and into the pelvis or buttock blood supply or the external iliac artery and down the leg. This is a very rare complication, less than 1 in 1,000, particularly with the use of careful technique and high-quality imaging chains.

18.8 College/NICE Guidance

The current guidance and body of literature robustly demonstrates the safety and efficacy of UFE in providing symptomatic relief. Clinical trials have shown UFE patients to have a shorter length of stay and operative blood loss compared to patients after surgery, and similar quality of life and satisfaction rates. There is paucity of data looking at comparison of outcomes such as complications and cost-effectiveness of UFE versus other surgical procedures, and further large multicentre prospective studies comparing the two are required before more definite recommendations can be made. There is especially very low evidence and a paucity of data looking at conception, fertility and pregnancy post procedure, and caution must be exercised when drawing any conclusions. These outcomes have been recognized by NICE, RCOG, CIRSE and Cochrane.

18.9 Clinical Trials Overview

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