Abstract
Introduction
Between 50% and 77% of women may have fibroids, depending on the method of diagnosis used. Fibroids may be asymptomatic, or may present with menorrhagia, pain, mass and pressure effects, infertility, or recurrent pregnancy loss. Risk factors for fibroids include obesity, having no children, and no long-term use of the oral contraceptive pill. Fibroids tend to shrink or fibrose after the menopause.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of surgical/interventional radiological treatments in women with fibroids? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
Five studies were included. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: magnetic resonance-guided focused ultrasound surgery versus no/sham treatment; magnetic resonance-guided focused ultrasound surgery versus other interventions (hysterectomy, myomectomy, hysteroscopic resection, rollerball endometrial ablation, thermal balloon ablation, thermal myolysis with laser); uterine artery embolisation versus no/sham treatment; uterine artery embolisation versus hysterectomy; uterine artery embolisation versus myomectomy; uterine artery embolisation versus other interventions (magnetic resonance-guided focused ultrasound surgery, hysteroscopic resection, rollerball endometrial ablation, thermal balloon ablation, thermal myolysis with laser).
Key Points
Between 50% and 77% of women may have fibroids, depending on the method of diagnosis used. Fibroids may be asymptomatic, or may present with menorrhagia, pain, mass and pressure effects, infertility, or recurrent pregnancy loss.
Risk factors for fibroids include obesity, having no children, and no long-term use of the oral contraceptive pill. Fibroids tend to shrink or fibrose after the menopause.
Myomectomy maintains fertility.
We searched for RCT evidence. Overall, we found a limited number of trials with relatively small numbers of participants in the assessment of some outcomes. There is a need for further high-quality RCTs in this field.
We don't know whether magnetic resonance-guided focused ultrasound surgery is beneficial in women with fibroids compared with no treatment/sham treatment, or other procedures (uterine artery embolisation, hysteroscopic resection, rollerball endometrial ablation, myomectomy, hysterectomy, thermal balloon ablation, or thermal myolysis with laser) as we found no studies.
We found no RCT evidence on uterine artery embolisation (UAE) compared with no treatment/sham treatment.
UAE may reduce procedure time, hospital stay, and recovery time compared with hysterectomy, and may reduce the need for blood transfusion.
Satisfaction rates may be similar between the two procedures at up to 5 years.
However, UAE seems to be associated with an increased need for future treatment compared with hysterectomy.
UAE may reduce procedure time, hospital stay, and recovery time compared with myomectomy.
Satisfaction rates may be similar between the two procedures at up to 2 years.
However, UAE may be associated with an increased need for future treatment compared with myomectomy.
Myomectomy may increase pregnancy rates compared with UAE in women with fibroids who wish to retain fertility, but evidence was limited, and came from a small sample of women in one RCT.
We don’t know how UAE compares with magnetic resonance-guided focused ultrasound surgery, hysteroscopic resection, rollerball endometrial ablation, thermal balloon ablation, or thermal myolysis with laser, as we found no studies.
Clinical context
General background
Fibroids (uterine leiomyomas) are benign tumours of the smooth muscle cells of the uterus. Women with fibroids can be asymptomatic, or may present with menorrhagia, pelvic pain with or without dysmenorrhoea, or pressure symptoms, infertility, and recurrent pregnancy loss. Fibroids are the most common gynaecological tumour.
Focus of the review
To date, open surgery has been the mainstay of treatment. There are now minimally invasive surgical as well as interventional radiological treatment options. This review will focus on the evidence surrounding the radiological interventions of magnetic resonance-guided focused ultrasound surgery and uterine artery embolisation.
Comments on evidence
For four of the six comparisons, no evidence was identified for the specified outcomes. For the other two comparisons (uterine artery embolisation [UAE] v hysterectomy and UAE v myomectomy), only one systematic review was identified with three and two RCTs. None of the trials were blinded, which may have influenced some of the outcome estimates. Additional quality concerns included potential selection bias for one trial included in the UAE v hysterectomy comparison and difficulties in generalisability for the UAE v myomectomy comparison (with different participants in the two relevant trials). Where evidence was found, it was generally of low quality.
Search and appraisal summary
The update literature search for this review was carried out from the date of the last search, June 2009, to May 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 186 studies. After deduplication and removal of conference abstracts, 68 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 46 studies and the further review of 22 full publications. Of the 22 full articles evaluated, two systematic reviews and three RCTs were added at this update.
About this condition
Definition
Fibroids (uterine leiomyomas) are benign tumours of the smooth muscle cells of the uterus. Women with fibroids can be asymptomatic, or may present with menorrhagia (30%), pelvic pain with or without dysmenorrhoea or pressure symptoms (34%), infertility (27%), and recurrent pregnancy loss (3%). Much of the data describing the relationship between the presence of fibroids and symptoms are based on uncontrolled studies that have assessed the effect of myomectomy on the presenting symptoms. One observational study (142 women) undertaken in the USA suggested that the prevalence of fibroids in infertile women can be as high as 13%, but no direct causal relationship between fibroids and infertility has been established.
Incidence/ Prevalence
The reported incidence of fibroids varies from 5.4% to 77.0%, depending on the method of diagnosis used (the gold standard is histological evidence). It is not possible to state the actual incidence of fibroids, because some women with fibroids will not have symptoms, and will therefore not be tested for fibroids. Observational evidence suggests that, in premenopausal women, the incidence of fibroids increases with age, reducing during menopause. On the basis of postmortem examination, 50% of women were found to have these tumours. Gross serial sectioning at 2 mm intervals of 100 consecutive hysterectomy specimens revealed the presence of fibroids in 50/68 (73%) premenopausal women and 27/32 (84%) postmenopausal women. These women were having hysterectomies for reasons other than fibroids. The incidence of fibroids in black women is three times greater than that in white women, based on ultrasound or hysterectomy diagnosis. Submucosal fibroids have been diagnosed in 6% to 34% of women having a hysteroscopy for abnormal bleeding, and in 2% to 7% of women having infertility investigations.
Aetiology/ Risk factors
The cause of fibroids is unknown. Each fibroid is of monoclonal origin and arises independently. Factors thought to be involved include the sex steroid hormones oestrogen and progesterone, as well as the insulin-like growth factors, epidermal growth factor, and transforming growth factor. There may also be genetic factors associated with development; certain genes may be switched on or off making an individual more likely to develop these tumours. Risk factors for fibroid growth include nulliparity and obesity. Risk also reduces consistently with increasing number of term pregnancies; women with five term pregnancies have one quarter of the risk of nulliparous women (P <0.001). Obesity increases the risk of fibroid development by 21% with each 10-kg weight gain (P = 0.008). The combined oral contraceptive pill also reduces the risk of fibroids with increasing duration of use (women who have taken oral contraceptives for 4 to 6 years compared with women who have never taken oral contraceptives: OR 0.8, 95% CI 0.5 to 1.2; women who have taken oral contraceptives for at least 7 years compared with women who have never taken oral contraceptives: OR 0.5, 95% CI 0.3 to 0.9). Women who have had injections containing 150 mg depot medroxyprogesterone acetate also have a reduced incidence compared with women who have never had injections of this drug (OR 0.44, 95% CI 0.36 to 0.55). It is not known if other hormonal contraception, such as the hormone-releasing intrauterine device (IUD), decreases risk.
Prognosis
There are few data on the long-term untreated prognosis of these tumours, particularly in women asymptomatic at diagnosis. One small case control study reported that, in a group of 106 women treated with observation alone over 1 year, there was no significant change in symptoms and quality of life over that time. Fibroids tend to shrink or fibrose after the menopause.
Aims of intervention
To reduce menstrual bleeding; reduce pressure symptoms; reduce pelvic pain; and induce a change in fertility status, with minimal adverse effects.
Outcomes
Menstrual blood flow (assessed objectively [mL/cycle] or subjectively); haemoglobin concentration and haematocrit; fibroid-related symptoms, including pelvic pain, pressure, or both (measured by a validated scale or subjective report); reduction in fibroid and uterine volume; pregnancy rate; postoperative recovery, including blood loss during procedure; duration of procedure; length of hospital stay; rate of blood transfusions; probability of transverse versus vertical incisions during surgery; probability of vaginal versus abdominal hysterectomy; ease of procedure as assessed by the surgeon; complication rates during and after procedure; recurrence rate; patient satisfaction rate; quality of life; adverse effects.
Methods
BMJ Clinical Evidence search and appraisal May 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2014, Embase 1980 to May 2014, and The Cochrane Database of Systematic Reviews 2014, issue 5 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. An information specialist identified titles and abstracts in an initial search, which an evidence scanner then assessed against predefined criteria. An evidence analyst then assessed full texts for potentially relevant studies against predefined criteria. Two expert contributors were consulted on studies selected for inclusion. An evidence analyst then extracted all data relevant to the review. Study design criteria for inclusion in this review were published RCTs and systematic reviews of RCTs in the English language, at least single-blinded, and containing 20 or more individuals (10 in each arm), of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs, where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we used a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Fibroids (uterine myomatosis, leiomyomas).
| Important outcomes | Complication rates before and after procedure, Complication rates during and after procedure, Fibroid-related symptoms, Menstrual blood flow, Patient satisfaction rates, Postoperative recovery, Pregnancy rate, Quality of life, Recurrence rate, Reduction in fibroid and uterine volume | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of surgical/interventional radiological treatments in women with fibroids? | |||||||||
| 2 (209) | Recurrence rate | Uterine artery embolisation versus hysterectomy | 4 | –2 | 0 | 0 | 1 | Moderate | Quality points deducted for weak methods (all 3 RCTs unblinded, high-risk random sequence allocation and allocation concealment in 1 RCT) and for participants in 1 RCT being told of procedures and being allowed to choose treatment; effect size point added for OR >2 |
| 3 (at least 247) | Postoperative recovery | Uterine artery embolisation versus hysterectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for weak methods (all 3 RCTs unblinded, high-risk random sequence allocation and allocation concealment in 1 RCT) and for participants in 1 RCT being told of procedures and being allowed to choose treatment |
| 3 (at least 271) | Complication rates during and after procedure | Uterine artery embolisation versus hysterectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for weak methods (all 3 RCTs unblinded, high-risk random sequence allocation and allocation concealment in 1 RCT) and for participants in 1 RCT being told of procedures and being allowed to choose treatment |
| 3 (at least 266) | Patient satisfaction rates | Uterine artery embolisation versus hysterectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for weak methods (all 3 RCTs unblinded, high-risk random sequence allocation and allocation concealment in 1 RCT) and for participants in 1 RCT being told of procedures and being allowed to choose treatment |
| 2 (242) | Recurrence rate | Uterine artery embolisation versus myomectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for lack of blinding and high attrition rates in 1 RCT |
| 1 (66) | Pregnancy rate | Uterine artery embolisation versus myomectomy | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and lack of blinding; directness point deducted for issues of generalisability (subgroup of total trial population, short follow-up for specified outcome) |
| 2 (223) | Postoperative recovery | Uterine artery embolisation versus myomectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for lack of blinding and high attrition rates in 1 RCT |
| 2 (242) | Complication rates before and after procedure | Uterine artery embolisation versus myomectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for lack of blinding and high attrition rates in 1 RCT |
| 1 (110) | Patient satisfaction rates | Uterine artery embolisation versus myomectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for lack of blinding and sparse data |
| 1 (122) | Quality of life | Uterine artery embolisation versus myomectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for lack of blinding and sparse data |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Menorrhagia (many women with fibroids experience symptoms of heavy menstrual bleeding). See Menorrhagia.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Anne Lethaby, Cochrane Menstrual Disorders and Subfertility Group, Auckland, New Zealand.
Dr Beverley Vollenhoven, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
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