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Saturday 19 January 2019
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Radiological treatments for uterine fibroids

Uterine fibroids (also known as myomas or leiomyomas) are benign tumours characterised by the proliferation of uterine smooth muscle cells and associated collagen matrix. They are the most common benign tumours in women of reproductive age. They are estimated to be symptomatic in 50% of women who have them, with the peak incidence of symptoms occurring among women in their 30s and 40s.1 Uterine fibroids are thought to result from increased mitotic activity within the myometrium under the influence of female hormones; however, what initiates the fibroid growth is not yet clear. Symptoms from fibroids depend on size and position of the fibroids. 
 
Symptoms include bleeding disturbances (usually heavy and prolonged periods, sometimes frequent and unpredictable bleeds), pressure symptoms (bladder and bowel symptoms, bloating, chronic pelvic pain and dyspareunia) and subfertility.2 While bleeding disturbances are more suggestive of submucosal or intramural fibroids which distort the endometrial cavity, pressure symptoms depend on the fibroid size and the extent to which fibroids encroach on the surrounding pelvic structures. The impact of fibroids on fertility remains controversial but most clinicians recommend surgical removal of fibroids distorting the endometrial cavity to improve chances of conception.
 
Asymptomatic women with small fibroids may benefit from expectant management, especially those approaching the menopause. Surgical treatments such as hysterectomy and myomectomy have been the traditional ‘gold standard’ definitive therapies for symptomatic fibroids. However, not all women wish to have a surgery and might like to consider non-surgical alternatives such as medical management or radiological interventions. 
 
Over the last few decades, new medical and minimally invasive treatments have become available for symptomatic uterine fibroids. The choice of treatment needs to be individualised depending on underlying symptoms, fibroid size and location, impact on fertility, history of previous treatments and the possible need for repeat interventions. 
 

Radiological interventions 

Over the last two decades, uterine artery embolisation (UAE) and magnetic resonance imaging-focused high intensity ultrasound (MRgFUS) are two modalities that have emerged as viable alternatives to surgical treatments for uterine fibroids.
 

UAE

UAE involves the placement of an angiographic catheter into the uterine arteries via a common femoral artery approach and injection of embolic particles, such as polyvinyl alcohol particles, until the flow becomes sluggish in both uterine arteries. The fibroids shrink as a result of ischaemic necrosis but blood supply to the uterus is preserved via collateral vessels. 
 
Because the technique aims to achieve fibroid shrinkage rather than removal, it is less effective in the case of large fibroids associated with pressure symptoms. Most patients experience moderate to severe ischaemic pain up to 12 hours after the procedure, which then gradually decreases over the next 12 hours. 
 
Patients can usually return to normal activities within one to two weeks. Main complications of UAE include ‘post embolisation syndrome’ (fever, nausea, vomiting and pain), vaginal expulsion of an infarcted fibroid (approximately 10% of cases) and intrauterine infection (<1% of procedures).3,4 Other concerns associated with UAE are its effects on the reproductive system. The use of the procedure needs to be balanced against the possible loss of ovarian reserve with scarce data on pregnancy outcomes. It has been suggested that UAE could reduce blood flow to the normal uterine tissue and ovaries resulting in reduced ovarian reserve, impaired placentation and increased risks of miscarriage/post-partum haemorrhage.3
 
Although the rates of induction of premature ovarian insufficiency following UAE remain very infrequent, there are concerns about subclinical diminution of ovarian functional reserve. Data from randomised trials and prospective case series suggest that degradation of ovarian function may occur after UAE, and is concentrated in women older than 45 years, with little evidence of impact in women younger than 40 years of age.5
 

Evidence

A Cochrane review assessed the benefits and risks of UAE versus other medical or surgical interventions for symptomatic uterine fibroids.6 Seven randomised controlled trials (RCTs) including 793 women were included in this review. Three trials compared UAE with abdominal hysterectomy, two trials compared UAE with myomectomy, and two trials compared UAE with either type of surgery (53 hysterectomies and 62 myomectomies). 
 
Patient satisfaction rates were up to 41% lower or up to 48% higher with UAE compared with surgery within 24 months of having the procedure (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.59–1.48; six trials, 640 women, moderate quality evidence). Findings were also inconclusive at five years of follow-up (OR 0.90; 95% CI 0.45–1.80, two trials, 295 women, moderate quality evidence). There was some indication that UAE may be associated with less favourable fertility outcomes than myomectomy, but it was very low quality evidence from a subgroup of a single study and should be regarded with extreme caution (live birth: OR 0.26; 95% CI 0.08–0.84; pregnancy: OR 0.29; 95% CI 0.10–0.85, one study, 66 women).6
 
Similarly, for several safety outcomes there was evidence of a substantially higher risk of adverse events in either arm or of no difference between the groups. This applied to intra-procedural complications (OR 0.91; 95% CI 0.42–1.97, four trials, 452 women, low quality evidence), major complications within one year (OR 0.65; 95% CI 0.33–1.26, five trials, 611 women, moderate quality evidence) and major complications within five years (OR 0.56; CI 0.27–1.18, two trials, 268 women). However, the rate of minor complications within one year was higher in the UAE group (OR 1.99; CI 1.41–2.81, six trials, 735 women, I(2)=0%, moderate quality evidence) and two trials found a higher minor complication rate in the UAE group at up to five years (OR 2.93; CI 1.73–4.93, two trials, 268 women).6
 
UAE was associated with a higher rate of further surgical interventions (re-interventions within two years: OR 3.72; 95% CI 2.28–6.04, six trials, 732 women, moderate quality evidence; within five years: OR 5.79; 95% CI 2.65–12.65, two trials, 289 women). The evidence suggested that women in the UAE group were less likely to require a blood transfusion than women receiving surgery (OR 0.07; 95% CI 0.01–0.52, two trials, 277 women). UAE was also associated with a shorter procedural time (two studies), shorter length of hospital stay (seven studies) and faster resumption of usual activities (six studies) in all studies that measured these outcomes.6
 
The authors concluded that patient satisfaction rates at up to two years following UAE versus surgery (myomectomy or hysterectomy) were not different. Findings at five-year follow-up were similarly inconclusive. There was very low quality evidence to suggest that myomectomy may be associated with better fertility outcomes than UAE. There was no clear evidence of a difference between UAE and surgery in the risk of major complications, but UAE was associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. This increase in the surgical re-intervention rate may balance out any initial cost advantage of UAE.6
 
UAE is an option for women with symptomatic fibroids, who are not planning a pregnancy in the future and wish to avoid surgery or have a high risk of surgical or anaesthetic complications. However women need to be made aware about the high rates of further intervention required following the procedure.
 

MRgFUS

MRgFUS scanning to locate the fibroid and focus high intensity ultrasound beams on to a point within the fibroid results in tissue heating and subsequent necrosis. Its advantages are that it is low cost, non-invasive and requires no general anaesthesia or hospitalisation. Because it is an ambulatory procedure, recovery time is approximately one to two days. Large or multiple fibroids and pedunculated fibroids are considered relative contraindications to this treatment. The presence of bowel loops or abdominal wall scars in the projected pathway of the ultrasound beam may preclude use of the technique. Common symptoms during the procedure are lower abdominal pain, leg pain and buttock pain. 
 
The main drawback of the technique is high rates of further surgical or radiological interventions required. There have been a number of reports of pregnancies following MRgFUS with reassuring pregnancy outcomes; however, further evidence is needed before recommending the procedure to women planning to conceive.
 

Evidence

A pilot, randomised, placebo-controlled trial evaluated the feasibility of a full-scale placebo-controlled trial of magnetic resonance-guided focused ultrasound for fibroids in premenopausal women with symptomatic uterine fibroids.7 Twenty women with a mean age of 44 years (± standard deviation 5.4 years) were enrolled, and 13 were randomly assigned to MRgFUS and seven to placebo. Four weeks after treatment, all participants reported improvement in the uterine fibroid symptoms and health-related quality of life score (UFS-QOL): a mean of 10 points in the MRgFUS group and 9 points in the placebo group (for difference in change between groups). By 12 weeks, the MRgFUS group had improved more than the placebo group (mean 31 points and 13 points, respectively). The mean fibroid volume decreased 18% in the MRgFUS group with no decrease in the placebo group at 12 weeks.
 
Two years after MRgFUS, 4 of 12 women who had a follow-up evaluation (30%) had undergone another fibroid surgery or procedure.7
 
A study compared the long-term outcomes after UAE versus MRgFUS for symptomatic uterine fibroids.8 Seventy-seven women (median age, 39.3 years; range, 29.2–52.2 years) with symptomatic uterine fibroids, equally eligible for UAE and MR-g high-intensity focused ultrasound underwent treatment (UAE, n=41; MRgFUS, n=36) from 2002 to 2009. Re-intervention was significantly lower after UAE (12.2%) than after MRgFUS (66.7%) at long-term follow-up (p<0.001). Improvements in symptom severity and quality of life scores was significantly better after UAE resulting in a significant lower re-intervention rate compared to MRgFUS.8
 
Another study of 119 women comparing outcomes of treatment between volumetric MRgFUS and UAE for uterine fibroids.9 Both procedures resulted in significant symptom relief and quality of life improvement. UAE had a stronger positive effect on the clinical outcomes. Re-intervention rate after MRgFUS was significantly higher than after UAE.9
 

Other minimally invasive techniques

Ultrasound-guided high-intensity focused ultrasound ablation is a new non-invasive treatment of uterine fibroids. The technique allows a check on the immediate efficacy of the procedure and if viable residual tissue is detected, there is the option to repeat the ablation immediately.3 Transcervical intrauterine sonography with radiofrequency ablation of the fibroids is yet another novel approach being investigated. A graphical interface delineates the boundaries of ablation and thermal spread so that thermal injury to the serosa as well as adhesions and injury to bowel or bladder can be minimised. 
 
A recent study looked into the effectiveness in day clinics of microwave endometrial ablation (MEA) on transcervical microwave myolysis for patients with menorrhagia caused by submucosal fibroids.10 Thirty-five outpatients (average age 44.8 ± 5.2 years (mean ± SD), range 34–58) with a single submucosal fibroid that was 4–7cm (5.5 ± 2.1cm) in size underwent MEA with transcervical microwave myolysis using a specifically developed transabdominal ultrasound probe attachment for transcervical puncture. The mean operation time was 27.9 ± 13.6 min. The fibroids had shrunk by 56.2% at three months and 73.8% at ≥six months after the operation. Blood haemoglobin levels had increased significantly at three months (10.2 ± 2.0 vs. 12.7 ± 1.2; p<0.001).10 Further clinical trials are needed to better define the role and limitations of these techniques for treatment of symptomatic uterine fibroids. 
 

Conclusions

Many uterine fibroids are asymptomatic and require no intervention. While myomectomy and hysterectomy have been the traditional definitive treatments for symptomatic uterine fibroids, not all women wish to have a surgery and many would like to retain their uterus. Non-surgical treatment options for symptomatic fibroids include pharmacologic as well as radiologically guided interventions. Radiologically guided procedures such as UAE and ablation by high-intensity focused ultrasound are newer treatment modalities that should be tailored to women’s age, general health, fibroid size/symptoms, fertility and their individual wishes. 
 

References

1 Wise LA et al. Age-specific incidence rates for self-reported uterine leiomyomata in the Black Women’s Health Study. Obstetrics Gynecol 2005;105:563–8. 
2 Talaulikar VS, Manyonda I. Progesterone and progesterone receptor modulators in the management of symptomatic uterine fibroids. Eur J Obstet Gynecol Reprod Biol 2012;165(2):135–40.
3 Pérez-López FR et al; EMAS. EMAS position statement: management of uterine fibroids. Maturitas 2014;79(1):106–16.
4 Tropeano G, Amoroso S, Scambia G. Non-surgical management of uterine fibroids. Hum Reprod Update 2008;14:259–74.
5 Kaump GR, Spies JB. The impact of uterine artery embolization on ovarian function. J Vasc Interv Radiol 2013;24(4):459–67. 
6 Gupta JK et al. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev. 2014;(12):CD005073. 
7 Jacoby VL et al. PROMISe trial: a pilot, randomized, placebo-controlled trial of magnetic resonance guided focused ultrasound for uterine fibroids. Fertil Steril 2016;105(3):773–80. 
8 Froeling Vet al. Outcome of uterine artery embolization versus MR-guided high-intensity focused ultrasound treatment for uterine fibroids: long-term results. Eur J Radiol 2013;82(12):2265–9. 
9 Ikink ME et al. Volumetric MR-guided high-intensity focused ultrasound versus uterine artery embolisation for treatment of symptomatic uterine fibroids: comparison of symptom improvement and reintervention rates. Eur Radiol 2014;24(10):2649–57. 
10 Tsuda A, Kanaoka Y. Outpatient transcervical microwave myolysis assisted by transabdominal ultrasonic guidance for menorrhagia caused by submucosal myomas. Int J Hyperthermia 2015;31(6):588–92.

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