A Hirst,¹ S Dutton,¹ O Wu,² A Briggs,² C Edwards,³ L Waldenmaier,¹ M Maresh,⁴ A Nicholson⁵ and K McPherson^1*

¹ Nuffield Department of Obstetrics and Gynaecology, University of Oxford, UK
² Section of Public Health and Health Policy, University of Glasgow, UK
³ Student Support and Learning Centre, University of Leicester and Qualitative Focus, UK
⁴ Department of Obstetrics and Gynaecology, St Mary's Hospital for Women and Children, Manchester, UK
⁵ Department of Radiology, Leeds General Infirmary, Leeds, UK

* Corresponding author

Background

The standard treatment for symptomatic uterine fibroids is hysterectomy. During the mid-1990s a minimally invasive uterus-conserving treatment was described known as uterine artery embolisation (UAE). Evidence from a few small randomised controlled trials comparing the two treatments suggested that UAE is a safe, effective treatment up to 12 months. Long-term safety and efficacy remain unknown. HOPEFUL is a pragmatic observational study that has investigated and compared the two treatments in the medium term.

Objectives

The medium-term results of hysterectomy and UAE as a treatment for symptomatic uterine fibroids were examined and compared with regard to

• safety
• efficacy
• special issues in UAE group
• cost-effectiveness
• women's own perspectives on the treatments.

Design

HOPEFUL is a multi-centre retrospective cohort study. Inherent biases were minimised by rigorous design, protocol and analyses. Data were collected locally from patients' hospital records and also from patients themselves by postal questionnaire. Questionnaire data included free-text comments and this qualitative material was analysed using constant comparison. A two-stage probabilistic decision model was designed to estimate UK NHS costs and health outcomes in terms of quality-adjusted life-years (QALYs).

Setting

The setting was 18 NHS hospital trusts, 17 in England and one in Scotland. The UAE cohort included patients treated in both NHS and private hospitals, reflecting UK practice at the time of treatment. The entire hysterectomy cohort was NHS patients.

Participants

Patients were eligible for inclusion if they had received one of the treatments under comparison specifically for symptomatic fibroids. We identified 1734 eligible women (972 UAE, 762 hysterectomies). The hysterectomy cohort underwent their index treatment in the 12 months beginning October 1994 as part of a national audit of hysterectomies (VALUE study). The UAE patients were treated by interventional radiologists who had pioneered its use since 1996 and all received their index UAE prior to the end of 2002, ensuring a minimum follow-up of at least 2 years. The average length of follow-up was 8.6 years [standard deviation (SD) 3.4] for the hysterectomy cohort and 4.6 years (SD 2.0) for the UAE cohort.

Interventions

The majority of the HOPEFUL patients had total abdominal hysterectomies (86.7%). All UAE centres used poly(vinyl alcohol) (PVA) embolic particles and in addition some used gelfoam or coils.

Main outcome measures

Primary outcome measures were complication rates to assess the comparative safety of the two interventions. Complications were defined as unintended consequences of treatment categorised according to the severity of their impact on health and the interventions required to rectify their impact. Categories were agreed a priori by the project team into severe, major or minor complications. The general side-effects of treatment in the UAE cohort including post-embolisation syndrome and vaginal discharge were considered a normal consequence of the embolisation process.

Secondary outcome measures related to treatment efficacy including resolution of symptoms and patient-reported satisfaction with treatment. Both quantitative and qualitative analyses were undertaken. Further efficacy outcome measures obtained in the UAE group included fibroid/uterine size shrinkage and further treatments required for unresolved fibroid symptoms. Data were also gathered on pregnancies post-UAE.

Results

Data were available for 1108 women (649 UAE and 459 hysterectomy). As expected, the cohorts presented a different baseline profile for many confounders including educational level (UAE higher), ethnicity (UAE more ethnically diverse) and parity (more UAE women nulliparous).

After adjusting for confounders, clustering by centre and missing values, fewer complications were experienced by women in the UAE cohort compared to the hysterectomy cohort – raw data, hysterectomy n = 120 (26.1%), UAE n = 114 (17.6%), adjusted odds ratio 0.48 [95% confidence interval (CI) 0.26 to 0.89]. When only the severe/major complications were considered, this odds ratio was reduced to 0.25 (95% CI 0.13 to 0.48). Expected general side-effects of UAE occurred in 32.7% of the UAE cohort, of which 8.9% also experienced complications. Obesity and medical co-morbidity predisposed women to complications whereas prophylactic antibiotics appeared to protect against both complications and the expected side-effects of UAE.

More women in the hysterectomy cohort reported relief from fibroid symptoms (89% versus 80% UAE, p < 0.0001) and feeling better (81% versus 74% UAE, p < 0.0001), but only 70% (compared with 86% UAE, p = 0.007) would recommend their treatment to a friend.

In the UAE cohort, 18.3% of the women went on to receive one or more further fibroid treatments including hysterectomy (11.2%). After adjusting for differential time of follow-up, the UAE women had up to a 23% (95% CI 19 to 27%) likelihood of requiring further treatment.

Twenty-seven women (average age 38 years, SD 3.3) reported 37 pregnancies post-UAE. There were 15 miscarriages, two ectopic pregnancies, one termination and 19 live births observed in this study. Some 79% of the live births were delivered by Caesarean section, six for complications of pregnancy or delivery.

The free-text data indicated that many women, in both cohorts, felt that their treatment had been a complete success. In the UAE cohort there were several areas where expectations were apparently high and outcome had not fulfilled their expectations. Disappointment was expressed mainly about continuation or return of symptoms or failure to become pregnant. Many continued to have remaining questions about their treatment.

The economic analysis indicated that UAE is less expensive than hysterectomy even after further treatments for unresolved or recurrent symptoms are taken into account, with little difference in QALYs between the two treatments. Younger women are exposed to the risk of recurrent fibroids and subsequent additional procedures over a longer period and consequently UAE may no longer be cost-effective, although this would depend on the quality of life placed by an individual woman on uterine preservation.

Conclusions

This study provides comparable medium-term follow-up for the two treatments.

Safety

Our results suggest that both UAE and hysterectomy are safe. No unexpected problems were detected following UAE after a long follow-up period (average 5 years). Complications are less common for UAE than hysterectomy, particularly severe/major complications.

One-third of women experienced general expected side-effects post-UAE. The likelihood of requiring further fibroid treatment after UAE was 23%. However, for women wishing to retain their uterus these risks may be worth taking.

Cost-effectiveness

The cost-effectiveness analysis favours embolisation even after taking account of complications, expected side-effects associated with the procedure and subsequent re-treatments for women with a preference for uterus preservation. For younger women the cost to the NHS may become slightly more than for hysterectomy due to the longer period prior to the menopause and thus the increased potential requirement of further fibroid treatment.

Communication/information

Our results provide reliable evidence of short- and medium-term outcomes, and of treatment failure, needed to inform decision-making. The way in which women described their experiences showed that, for them, the intervention was not an event, but a process, and this needs to be reflected in the communication strategy in this area. Radiologists practising UAE should see patients in outpatients both before and after treatment.

It is important to improve the management of expectations following UAE, particularly regarding fertility. Our data suggested that fertility and miscarriage rates are consistent with those of age-matched women with fibroids.

Impact on NHS

UAE is an effective treatment for some women with fibroids and our trial supports the National Institute for Health and Clinical Excellence guidance that it should be made available as one of the options for treatment, with a possible reduction in the need for hysterectomy as the first-line treatment.

Recommendations for research

In addition to confirming the medium-term safety of UAE, this study has generated hypotheses of great importance for women with symptomatic fibroids.

• Who will benefit from UAE?
  Conclusions regarding which subgroups of women will be treated most successfully by UAE (size, position and number of fibroids) were not possible from this study. Further research on these areas will have important implications for advising patients, and for health economics.
• What UAE techniques are the most successful?
  The best method of achieving effective embolisation is also still not clear, with a number of different agents being used at varying cost. All the centres in HOPEFUL used PVA particles. Since then, a range of different embolic materials and techniques have become available. Randomised studies would determine the optimal materials and techniques for UAE.
• What advice can be given to women who desire future fertility?
  Our observations suggest that live births after UAE are possible, but the actual probabilities and factors that determine who conceives, miscarries or achieves a live birth remain poorly understood. Randomisation between myomectomy and embolisation may determine the more cost-effective and successful option particularly in the infertile patient and those who are undergoing in vitro fertilisation therapy.
• What role does prophylactic antibiotics have in UAE?
  The role of antibiotics in the prevention of complications and side-effects has strong support from this study, but the results should be viewed with caution. Antibiotic use was highly confounded with collaborating centre. The uncertainty that remains warrants randomised trials.
• What are the effects of HRT use after UAE on recurrence of fibroid symptoms?
  Our free-text analysis suggested that a common question amongst women after UAE is whether using HRT will lead to recurrent fibroid symptoms. Currently patients are advised against the use of HRT, as its effects after embolisation are unknown. Further research is warranted to help clarify this question.

Publication

Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al. A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study. Health Technol Assess 2008;12(5).

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