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Long‐term durability of uterine artery embolisation for treatment of symptomatic adenomyosis

Background Failing conservative therapies, uterine artery embolisation (UAE) has been proposed as a uterine‐sparing option for treatment of symptomatic adenomyosis. UAE appears effective at short‐term; however long‐term durability is less well established. Aims To evaluate the long‐term clinical efficacy of UAE for treatment of adenomyosis. Materials and Methods One hundred and four women with initial clinical success following UAE for adenomyosis (results previously published) were further followed with a two‐part online survey. Part one inquired about menopause, symptom recurrence, need for further intervention and overall satisfaction. Part two comprised the Uterine Fibroid Symptom and health‐related Quality of Life (UFS‐QOL) questionnaire. Maintenance of clinical success was defined as remaining ‘happy’ or ‘very happy’ with overall outcome, no recurrence of symptoms, or need for further intervention. Results Of those women with initial success, 91/104 (88%) participated in this long‐term study at mean 52 months following UAE. Maintenance of clinical success was demonstrated in 82/91 (90%) women. For the remaining 9/91 (10%) women, mean time to failure was 31 months. There were 53/91 (58%) women who reached menopause at mean age of 51.5 years, occurring at mean 30 months post‐UAE. UFS‐QOL demonstrated significant decrease in symptom severity from 58.9 to 20.0 (P < 0.001); and significant increase in QOL from 40.3 to 86.3 (P < 0.001). Conclusions Long‐term durability of UAE for treatment of adenomyosis was demonstrated, with cumulative success rate of 80% at mean 52 months. UAE did not appear to bring forward menopause. UAE should be considered as an alternative to hysterectomy to treat adenomyosis.


INTRODUCTION
gynaecological conditions including fibroids and endometriosis. 1,2,7 The greatest symptomatic burden is seen in women aged 40-50 years. 8 Conservative treatment options for adenomyosis, aimed at relieving HMB and pain, include non-steroidal anti-inflammatory drugs, tranexamic acid, oral contraceptive pills, levonorgestrelreleasing intrauterine system (LNG-IUS) and short-term use of gonadotropin-releasing hormone (GnRH) agonists. 3,9 Failing conservative therapies, many women are advised to undergo a hysterectomy, which is deemed the only definitive treatment for adenomyosis. 10 Uterine artery embolisation (UAE) has been proposed as a less invasive alternative to hysterectomy to treat adenomyosis. 5,9,11 UAE is an angiographic procedure whereby an embolic agent is injected into uterine arteries to induce ischaemic infarction of adenomyotic foci. 12,13 The efficacy of UAE for treatment of adenomyosis has been established in the short-term, 5,[14][15][16] but mid-to long-term durability is less clear. While some studies demonstrated high rates of symptom recurrence, with only 45-57% women remaining symptom free at 2-3 years, 10,17 others reported maintenance of clinical success in 70-76% at 3-5 years. 12,13,18,19 The aim of the present study is to evaluate the long-term clinical efficacy of UAE for treatment of adenomyosis to address this discrepancy.

Study design
This study is a long-term follow-up of our previously published cohort study evaluating short-term outcomes of UAE in 115 women with adenomyosis. 20 The follow-up period for the initial study was a mean of 22.5 months (median 18, range 6-84 months) and clinical success was achieved in 104/115 (90%) women, including two women requiring a repeat UAE. The 104 women who achieved initial success formed the cohort for this long-term outcome study (Fig. 1).
Women were contacted by SMS, email or phone and invited to participate in the study on a voluntary basis. For those who consented to participate, unique links to a two-part secure online survey were sent via SMS or email. Women who had already reached menopause at the time of initial short-term study were not contacted.

Study measures
The first part of the survey was a questionnaire inquiring about menopause, recurrent symptoms of adenomyosis and need for F I G U R E 1 Study population. The study population for this long-term study was derived from a previously evaluated cohort of women who demonstrated initial clinical success at 22.5 months, following uterine artery embolisation (UAE) for treatment of adenomyosis. Short-term outcomes have previously been published. 20 further intervention in case of recurrent symptoms. Women were asked if they had entered menopause and if so, when it occurred and whether they were unhappy about it. They were asked to rate their periods, currently or just before they entered menopause, as either: (1) lighter than normal; (2) back to normal; (3) still heavy; or (4) heavier than before UAE. Women with dysmenorrhoea at baseline were asked to rate their pain as either: (1) gone; (2) much better; (3) slight improvement; (4) same; or (5) worse than before UAE. Pain was further quantified using a visual analogue scale (VAS). Women were asked to rate their overall satisfaction with the procedure as: (1) very happy; (2) happy; (3) not sure; (4) not happy; or (5) very unhappy. Finally, women were asked about the need for further intervention for ongoing symptoms.
The second part of the survey comprised the Uterine Fibroid Symptom and health-related Quality of Life (UFS-QOL) questionnaire which provides two scores, the health-related quality of life score (HRQOL) and symptom severity score. Although the UFS-QOL was developed as an objective measure of the impact of fibroids, it has also been used to evaluate adenomyosis. 12,18,21 Symptoms of fibroids and adenomyosis are similar and the two conditions often coexist. 20 HRQOL score > 80 and symptom severity score < 20 may be considered asymptomatic. 22 The UFS-QOL was implemented in our clinical follow-up from mid-2009. Long-term clinical success was defined as patient satisfaction rated as either 'happy' or 'very happy' with overall outcome, no recurrence of symptoms and no need for further interventions.
For those women who indicated undesirable outcomes, telephone contact was made to clarify the nature of clinical failure, and further clinical assessment and treatment offered.

RESULTS
Of the 104 women with initial success following UAE from our previous short-term outcome study, five women declined participation and eight women were unable to be contacted. Thus, 91/104 (88%) women were included in this long-term outcome study. Mean follow-up duration was 52 months from UAE (median 50, range 5-117 months). Patient demographics are included in Table S1.
In this long-term study, 82/91 (90%) women remained 'happy' or 'very happy' with the overall long-term outcome, reported no recurrence of symptoms, or need for further interventions. Maintenance of clinical success over time is illustrated in Figure 2.
Of those with pain before UAE, 6/74 (8%) women developed recurrence of dysmenorrhoea. Of those with HMB before UAE, 8/91 (9%) women developed recurrent HMB. Long-term symptomatic control was achieved in the remaining patients. A significant decrease in pain and symptom severity score and a significant increase in HRQOL compared to baseline was observed at longterm ( Table 1).
By long-term follow-up, 53/91 (58%) women had reached menopause, at mean age of 51.5 years (95% CI 50. 6-52.4) and at mean period of 30 months (median 26, range -12-100 months) after UAE. None of the women who reached menopause experienced recurrence of symptoms of adenomyosis prior to the onset of menopause. Of those who developed menopause, only one patient was unhappy about the onset of menopause due to hot flushes.
Sensitivity analyses showed results remained robust with respect to outliers and missing data; however, varying rates of clinical success (ranging from 82% to 93%) were observed with the application of alternative criteria for clinical success. The total re-intervention rate from short-and long-term is 13/102 (13%). This is comprised of three cases of repeat UAE (3%) from short-term: one further hysterectomy in addition to the six hysterectomies reported at short-term, giving a total hysterectomy rate of 7/102 (7%); two cases of LNG-IUS (2%) and one case of laparoscopy (1%) reported at long-term.

DISCUSSION
Our findings support the long-term durability of UAE for treatment of adenomyosis. This is consistent with several studies   13 The observed significant increase in HRQOL and decrease in symptom severity are consistent with other studies utilising the UFS-QOL questionnaire. 12,18,19 Other long-term studies of UAE for treatment of adenomyo- term. This is consistent with our findings. The meta-analyses also noted that those with adenomyosis with fibroids had better outcomes following UAE compared to those with pure adenomyosis.
While this was not directly examined in our study, we note seven of the nine long-term clinical failures had pure adenomyosis.
The application of UAE for treatment of adenomyosis remains novel in comparison to its use in the treatment of fibroids.
Whereas several randomised controlled trials and a Cochrane review have demonstrated no difference in patient satisfaction with UAE compared to surgery for treatment of fibroids, this level of evidence is lacking for adenomyosis. 25 The ongoing QUESTA trial seeks to address this by directly comparing UAE to hysterectomy for treatment of adenomyosis. 26 By long-term follow-up, 58% of women reached menopause, which occurred at mean age of 51.5 years (95% CI 50. 6-52.4 Previously, failure of conservative therapy for treatment of adenomyosis necessitated hysterectomy for management of debilitating symptoms. Hysterectomy remains a major surgical procedure requiring general anaesthesia, with inherent surgical risks and longer-term side effects. 7 By contrast, UAE is less invasive and allows preservation of the uterus as is desired by many women. 7,16,24 This long-term study has confirmed that UAE is a durable, definitive treatment for adenomyosis in 80% of women.
Hysterectomies were avoided in 93% of women. UAE did not bring forward menopause. UAE should be offered to women in whom conservative management for adenomyosis has failed, as a less invasive alternative to hysterectomy.