Uterine artery embolisation: fertility, adenomyosis and size - what is the evidence?

Some earlier reports of UAE cited as suggesting that larger fibroid size and overall uterine volume are associated with poorer clinical outcomes and increased risk of complications only describe a single case each of complication, both of single large fibroids causing septic necrosis post UAE and requiring hysterectomy (Pelage et al. 2000 ; Worthington-Kirsch et al. 1998 ). The EMMY trial, a multicentre randomised controlled trial (RCT) of 81 patients, showed that larger uterine volume (> 500cm 3 ) and larger dominant fibroid volume (> 100 cm 3 ) were associated with an increased risk of major complications (Volkers et al. 2006 ). Closer study of the paper shows these comprised of minor increased hospital stay, readmission for pain management or antibiotic treatment for a variety of infective causes and 12 cases of fibroid expulsion were recorded in total, but no emergency hysterectomies were required. The FIBROID registry in 2005 reported greater symptomatic improvement in smaller leiomyomas at 1 year (Spies et al. 2005 ). At 3 years, larger leiomyoma size remained a predictor of poorer symptomatic improvement (Goodwin et al. 2008 ). Although many subsequent studies have refuted these conclusions of higher complications and poorer outcomes, large fibroid size remains a somewhat contentious issue in UAE practice. Table  4 summarises the papers studied in this section. Table 4 Assessment of complications post UAE in patients with large fibroids compared with a control group (Parthipun et al., 2010 ; Katsumori et al., 2003 ; Prollius et al., 2004 ; Firouznia et al., 2008 ; Choi et al., 2013 ; Bérczi et al., 2015 ; Mollier et al., 2020 ) Study, year Study design Period Cohort size (n) Giant fibroids / large volume uterus (n) Non giant fibroids (n) Giant Fibroid size Uterine volume Follow up (months) Increased risk of major complications in giant fibroid group Increased risk of major complications in large volume uterus group Katsumori et al., 2003 Retrospective cohort NR 152 47 105 > 10 cm NR 17.5 No No Prollius et al., 2004 Prospective cohort NR 64 12 (18.8%) 52 NR >780cm 3 12 No No Firouznia et al., 2008 Retrospective cohort 2001–2006 101 NR NR NR NR 12 No No Parthipun et al., 2010 Prospective cohort 2004–2008 121 30 91 > 10 cm >750cm 3 12 No No Choi et al., 2013 Retrospective cohort 2005–2011 323 63 260 > 10 cm >700cm 3 12–84 No No Berczi et al., 2015 Retrospective cohort 2008–2012 303 41 262 > 10 cm NR 8 No No Mollier et al., 2020 Retrospective cohort 2013–2018 333 NR NR > 10 cm > 1000 cm 3 NR No Yes UAE uterine artery embolisation, NR not reported Assessment of complications post UAE in patients with large fibroids compared with a control group (Parthipun et al., 2010 ; Katsumori et al., 2003 ; Prollius et al., 2004 ; Firouznia et al., 2008 ; Choi et al., 2013 ; Bérczi et al., 2015 ; Mollier et al., 2020 ) UAE uterine artery embolisation, NR not reported In contrast to these early reports, a retrospective analysis of 152 patients showed that women with larger fibroids (> 10 cm) experienced less symptomatic improvement at 1 year but this difference did not persist at 2 years (Katsumori et al. 2003 ). The same study also demonstrated no increased risk of complications based on fibroid size. Similarly, a study of 61 patients showed that larger uterine volume (> 780 cm 3 ) is not associated with reduced symptomatic improvement or higher rate of complications at 12 months (Prollius et al. 2004 ). Furthermore, a retrospective analysis of 101 patients found no correlation between size of the dominant fibroid and clinical effectiveness or complication rate at 1 year (Firouznia et al. 2008 ). Subsequently, further publications echoed the findings of these studies that refuted the exclusion of patients based on fibroid and uterine volume. A prospective case control study of 121 women compared outcomes of patients grouped according to diameter of largest fibroid and uterine volume. The authors found no increased incidence in complications in women with large-diameter fibroids (> 10 cm) or large uterine volumes (>750cm 3 ) at 12 months (Parthipun et al. 2010 ). Similarly, a retrospective analysis of 71 patients with large fibroid burden (dominant fibroid > 10 cm +/− uterine volume > 700 cm 3 ) showed satisfactory imaging outcomes in terms of fibroid volume reduction and infarction rate with no incidence of severe complications at 4 years (Smeets et al. 2010 ). The authors concluded that large fibroid burden should not be considered a contraindication for UAE. Of note however, the authors reported 10 patients (14%) underwent subsequent hysterectomy for inadequate symptom control, suggesting clinical improvement may be somewhat limited in this group of patients. One of the largest retrospective comparative studies involving 323 patients compared UAE outcomes based on dominant tumour dimension and uterine volume. There were no differences in outcome including volume reduction of uterus or dominant tumour, infarction rate of dominant tumour, or symptom scores at 3 months and beyond 12 months. Similarly, no differences were found in major complications and the authors concluded that outcomes in large fibroid tumours are comparable to those in smaller tumours and without an increased risk of significant complications (Choi et al. 2013 ). A similarly large retrospective analysis of 303 women compared two groups based on the diameter of the dominant fibroid ( 10 cm). Clinical effectiveness and incidence of complications were similar in both groups, although the mean follow-up was somewhat limited at less than 8 months (Bérczi et al. 2015 ). Interestingly, the two most recent studies on fibroid size suggest an increased risk of complications in women with greater fibroid burden. A large retrospective case control study reviewed 333 patients with respect to intra-uterine infection post UAE and identified large uterine volume > 1000 cm 3 to be a risk factor for infective complications although the statistically significance was relatively low ( p  = 0.049, OR 2.94 [1.15–7.54] (Mollier et al. 2020 ). A systematic review and meta-analysis of four retrospective cohort studies (Katsumori et al. 2003 ; Prollius et al. 2004 ; Choi et al. 2013 ; Bérczi et al. 2015 ) was carried out incorporating total of 839 total patients. There was a greater prevalence of major complications ( p  < 0.01, OR 4.7 [1.5–14.6]) and re-interventions ( p   10 cm +/− uterine volume > 700 cm 3 . The major complications related to fibroid expulsion, uterine infection and one patient with sexual dysfunction post UAE. The data supports the effectiveness of the technique as a viable treatment option with appropriate counselling in this patient group. The potential for described complications is higher, and more rigorous follow up of patients and closer collaboration with gynaecology colleagues would be recommended to anticipate and deal with potential complications promptly. This includes expedient management of infections and transvaginal resection of devascularised fibroids in an elective manner to avoid the need for emergency surgery (Llewellyn et al. 2020 ).

We performed separate electronic literature searches for each topic using the Pubmed/Medline, Google scholar, Cochrane and EMBASE databases in July 2022. Medical subject headings (MeSH) and keywords (for example – ‘uterine artery embolisation’ and ‘fertility’) were utilised with searches performed in turn using each database. The reference list of relevant papers was also reviewed for additional studies. Our Pubmed search strategy is included in Additional file  1 . Titles and abstracts were screened, and the remaining full text articles were reviewed by two authors for each topic, with any discrepancies resolved by discussion with a third author. We included clinical studies with ranging levels of evidence– randomised controlled trials (RCT), controlled clinical trials (CCT), comparative studies, prospective/retrospective cohort studies, case-control studies and case series. Populations, interventions and outcomes are outlined in Table  1 . The exclusion criteria included papers which were not published in English, measured different outcomes (e.g., AMH levels rather than actual pregnancy rates), single case reports, patients who underwent UAE for indications other than symptomatic fibroid disease/adenomyosis and papers in which complete outcomes/results were not available (e.g., the number of women who desired to preserve fertility was not clearly reported or if birth and miscarriage rates were not provided). Data extraction was performed on the remaining studies to identify study design, sample size, mean follow up and the desired outcomes for each research question. Table 1 Population, interventions, outcomes assessed for each topic Fertility Adenomyosis Large fibroids (> 10 cm diameter +/− uterine volume > 750 cm 3 ) Population Women desiring fertility following UAE for symptomatic fibroids Women who underwent UAE for symptomatic adenomyosis +/− fibroids Women with large symptomatic fibroids who underwent UAE Intervention Uterine artery embolisation with any embolic material Uterine artery embolisation with any embolic material Uterine artery embolisation with any embolic material Primary outcome Pregnancy rate in women who underwent UAE and expressed a desire to preserve fertility Symptomatic improvement following UAE Symptomatic improvement following UAE Secondary outcome(s) Percentage of live births and miscarriages Symptomatic improvement between adenomyosis alone or adenomyosis + fibroids Complication/re-intervention rate following UAE Population, interventions, outcomes assessed for each topic Formal ethical/institutional board review is not required for this type of study.

Our review found pooled rates of pregnancy of 39.4%, live birth of 69.2% and miscarriage of 22% following UAE. Given the mean age of women included in the analysis was 35.9 years, these rates are comparable to the age-matched background population and we suggest that UAE should be considered in younger patients who desire to preserve fertility. Following UAE in the context of adenomyosis, we found an overall rate of symptomatic relief of 83% with no major differences in outcome between patients with pure adenomyosis and adenomyosis combined with fibroids. UAE is a viable alternative to hysterectomy in achieving symptomatic relief while seeking uterus preservation and fertility potential. In particular, data suggests there is good short-term improvement - an important consideration in patients approaching menopause. We found limited early evidence reporting UAE in large fibroids (> 10 cm or uterine volume > 700 cm 3 ) to be less effective and associated with increased complication rates. More recent data is contrasting, confirming that UAE is effective in treating the symptoms of uterine fibroids in large volume uteri. However, there is some evidence to suggest a higher risk of infective complications in patients with a significantly larger fibroid burden (uterine volume > 1000 cm 3 ) as well as a higher rate of reintervention. Therefore, although UAE should not be contraindicated in this group, patients should be counselled appropriately prior to treatment.

Uterine artery embolisation (UAE) is a safe and effective therapeutic option for symptomatic uterine fibroids (Gupta et al. 2014 ). Originally described for the management of post-partum haemorrhage, Ravina et al. ( 1995 ) were the first to describe UAE for the treatment of symptomatic fibroids (Ravina et al. 1995 ; Pelage et al. 1998 ). Subsequently, UAE has grown in popularity as a well-tolerated, minimally invasive alternative to existing surgical methods (Gupta et al. 2014 ; Pelage et al. 2000 ; Walker and Pelage 2002 ). However, there are specific aspects surrounding UAE which remain a source of debate and uncertainty. The effect of UAE on future fertility remains controversial. Joint guidelines by the Royal College of Obstetricians and Gynaecologists and the Royal College of Radiologists of the United Kingdom (UK) ( 2013 ) acknowledge there is little high-quality evidence available to help draw conclusions in this matter. They recommend UAE should only be offered to women of childbearing age who wish to preserve fertility after an informed discussion (The Royal College of Obstetricians and Gynaecologists and the Royal College of Radiologists 2013 ), whereas many other international guidelines recommend avoiding UAE altogether in this cohort (Marret et al. 2012 ; Carranza-Mamane et al. 2015 ; Stokes et al. 2010 ). This illustrates the difficulties faced by operators in dealing with patients seeking UAE while wishing to maintain fertility. Many patients with symptomatic adenomyosis also have uterine fibroids, and whilst there are publications outlining the use of UAE to treat these patients with encouraging results (de Bruijn et al. 2017a ), the evidence for this is not as clear, or as established as it is for UAE for the treatment of fibroids alone. Finally, many operators consider the use of UAE to be relatively contraindicated in patients with large volume uteri and large fibroids > 10 cm in diameter due to perceived increased complication or failure rates (Parthipun et al. 2010 ). The aim of this review is to present the evidence base for tackling these three challenging aspects surrounding UAE, to assist operators in patient selection and management and having informed discussions with clinicians and patients.

The available evidence supports the use of UAE as a viable management option in women seeking to preserve fertility, those with symptomatic adenomyosis and those with large fibroids. However, there remains alack of high-quality robust data addressing these three areas. Whilst well designed randomised controlled trials remain the gold standard of evidence, the consistent use of validated quality of life questionnaires for outcome assessment in studies would enable effective comparison of outcomes from different studies. In the area of adenomyosis, the results of the QUESTA trial are awaited, which may address the issue of lack of RCT data. From a practical perspective, Standards of Practice documents from Interventional Radiology societies should also be updated to reflect the growing role, indications and suitability of UAE in these difficult clinical areas.

Additional file 1. Pubmed search terms used for each outcome which were then adapted for each database. Additional file 1. Pubmed search terms used for each outcome which were then adapted for each database.