Funding
None.
IntroductionUterine fibroids are benign
tumours of the uterine muscle, and are the most common type of tumour
amongst women of reproductive age[1]. Symptomatic
uterine fibroids are a common and significant health problem affecting
as many as 1 in 3 women in the UK, and have a lifetime prevalence of
around 30%[2]. Fibroids can cause severe symptoms
such as menorrhagia, pelvic pressure, pain, and also impact upon the
mental health and sexual functioning of those who have them. Fibroids
can also cause infertility. In cases like these, treatment is often
required to improve symptoms[3] .
Two common uterine-conserving treatments for uterine fibroids are UAE
and myomectomy. UAE is a comparatively newer technique and is limited to
tertiary centres with the appropriate expertise. The British Medical
Journal (BMJ) recommends both UAE and myomectomy as first-line
treatments for fibroids where uterine preservation is desired. According
to this algorithm, UAE is only recommended for those not desiring future
fertility[4]. Other studies such as Vercellini et
al., 1998[5] also favour myomectomy for fertility
preservation. However, in 2013, the Royal College of Obstetricians and
Gynaecologists (RCOG) stated that there is no robust evidence comparing
the two for fertility and pregnancy outcomes[6] .
There are a few randomised controlled trials (RCTs) comparing UAE with
hysterectomy[7, 8, 9, 10, 11]. There are some
recent systematic reviews that compare UAE with surgical treatment as a
whole[12, 13] , however it is hard to assess the
differences between UAE and myomectomy specifically where generic
‘surgery’ headings are used. At the time the current RCOG guidance was
created for fibroids, only two RCTs had been undertaken that directly
compared UAE and myomectomy [14, 15], since then
another RCT has been published, the FEMME 2020
trial[16]. The decision between UAE and myomectomy
can have a significant effect on the quality of life of those who suffer
with uterine fibroids, including symptom control, fatigue, and feeling
of general health. This study aims to review and meta-analyse the data
to assess whether there are any significant differences in outcomes
which may help guide future management algorithms. Methods Core outcome setsNo core outcome sets were used in this study.Patient and public involvementNo patients or public were involved in this study.Data sourcesThe protocol for this systematic review was developed in line with
PRISMA-P guidance[17] and prospectively registered
on the Prospero database (Reference number CRD42021259347). Ethical
approval was not required to undertake this review.
A systematic search of The Cochrane Library, Medline, and EMBASE
databases was conducted using a pre-defined search strategy (Appendix
S1) to gather all studies comparing UAE versus myomectomy in patients
with symptomatic uterine fibroids. Study SelectionArticles were screened by two independent reviewers. Any discrepancies
were resolved by consensus. Articles were included if they were
published in a peer-reviewed journal, published in English from 1995
onwards, and were comparing UAE with myomectomy as treatment for women
with symptomatic fibroids. Papers were excluded if they were abstracts,
letters, opinion pieces or reviews. RCTs, cohort studies, and
case-controlled studies were included. A citation search of the selected
articles was performed to identify any further relevant studies. Data extractionData from each paper was entered into a bespoke designed data extraction
table. This included data such as the type and size of fibroid, as well
as patient demographic data. Outcome data was extracted which included:
Technical failure, re-intervention rates, haemorrhage, infection, length
of stay in hospital, mental health/mood, sexual functioning, resolution
of symptoms , improvement in menorrhagia, post-procedural quality of
life score, time taken to return to normal activities, number of
patients who had complicationsAssessment of Study Quality/BiasThe papers were assessed for risk of bias using the Newcastle-Ottawa
scale (NOS) for cohort studies[18] and Cochrane
RoB2 tool for RCTs [19] . The NOS compares across
three domains: selection, comparability, and exposure. The Cochrane RoB2
tool assesses for bias across six domains: randomisation, assignment to
an intervention, adherence to an intervention, missing outcome data,
measurement of the outcome, and selection of reported result. Data analysis Dichotomous data were presented as odds ratio with 95% confidence
intervals (CIs) and continuous outcome measures by weighted mean
differences and 95% CIs. Meta-synthesis of raw data was performed using
Review Manager 5.4.1 from the Cochrane
Collaboration[20].
Weighted mean scores were undertaken for ‘length of stay in hospital’
and ‘time taken to return to activities’ as these were continuous
outcomes for which both papers gave no information on CIs. The
I2 test was used to test for heterogeneity between
studies and sensitivity analyses were undertaken for results which gave
an I2 of over 50%.ResultsAn electronic search of The Cochrane Library, Medline, and EMBASE
databases was conducted on August 21st 2021. This
produced 485 results, 180 from Medline, 253 from Embase, and 52 from The
Cochrane Library. (Table S1)
There were 15 papers included for full-text review and four were removed
as they did not report myomectomy data separately from
hysterectomy[8, 10, 11, 21], one was removed as it
was a sub-analysis of the REST trial that focused on imaging outcomes[22], and four papers were removed as they were
systematic reviews [12, 23, 24, 25]. Two more
papers were added from citation reviews [26, 27].
In total there were eight studies included in this meta-analysis and
systematic review. There were five cohort studies[26, 27, 28, 29, 30] and three RCTs[14, 15, 16]. The characteristics of the included
studies are shown in Table 1. Bias assessments are shown in Appendices
S2 and S3.
Three of the cohort studies were undertaken at a single institution[26, 27, 30] and two were undertaken as
multi-centre studies [28, 29] . There were a total
of 625 women in the cohort, and 489 in the myomectomy cohort.
Inclusion criteria were similar across the eight studies, with all of
them requiring symptomatic uterine fibroids. Siskin et al., 2006; Mara
et al., 2007 and Goodwin et al., 2006 all specified maximum FSH levels
for their participants, to ensure that they were not already menopausal
at the time of the study. Manyonda et al., 2012 also specified that only
pre-menopausal women were to be included. However, Razavi et al., 2003
specified that for inclusion in the study the women must be seeking
symptomatic relief, not seeking treatment for fertility problems.
All of the studies reported key demographic data such as age of the
participants. For two of the papers [14, 15] it
was possible to perform comparison, and there was found to be no
significant difference in age between the UAE and myomectomy cohorts
[OR=-0.76, 95% CI (-1.99, 0.47)] (Appendix S4).
There were 12 outcomes that were deemed comparable between the papers,
five of these were related to technical aspects of the procedure, such
as infections and need to re-intervene at a later date. The remaining
seven were related to the quality of life of the women in the respective
studies, such as mental health and sexual functioning. These are
outlined below.
Technical failure
Technical failure did not significantly differ between groups
[OR=0.67, 95% CI (0.30, 1.50)] (Figure 1, A). Five papers commented
on rates of failure [14, 15, 26, 27, 29] however
Narayan et al., 2010 gave their results as an adjusted OR and this could
not be meta-analysed with the other data. None of the studies gave a
specific definition for ‘technical failure’ however they did give
examples of what was considered to be a failed procedure. In this
review, the need for conversion for hysterectomy mid-procedure, and any
repeat surgery to correct immediate complications were also considered
under this outcome.2. Re-intervention rates
Re-intervention rates varied significantly between groups [OR=5.16,
95% CI (2.41, 11.04)] (Figure 1, B), with myomectomy having lower
rates of re-intervention post-procedurally compared with UAE. Four
studies reported on this [14, 15, 27, 30]. One
study, Razavi et al., 2003, did show lower re-intervention rates in its
UAE cohort, with there being five out of 62 patients in the UAE cohort,
and four out of 40 in the myomectomy cohort. Manyonda et al., 2012
found that there was unsuspected adenomyosis in three of the six
patients who underwent a hysterectomy at re-intervention in the UAE
group, which offers a potential explanation for the need for
re-intervention in these cases.
3. Haemorrhage
There was a significantly lower rate of haemorrhage in the UAE cohorts
compared with the myomectomy ones [OR=0.22, 95% CI (0.06, 0.77)]
(Figure 1, C), this was demonstrated in all three studies that commented
on this outcome.
4. Infection
Infection rates did vary significantly between UAE and myomectomy
cohorts [OR=0.20, 95% CI (0.06, 0.72)] (Figure 1, D), with the data
favouring the UAE group.
5. Length of stay in hospital
A weighted mean was calculated for the number of days spent in hospital
for both the UAE and myomectomy cohorts across the five studies which
recorded this in their study (Figure 2, K). It was found that the UAE
group had a mean number of 1.28 days (range 0-2.5) in hospital, whereas
the myomectomy group had a mean number of 3.49 days (range 2.5-6) in
hospital. 6. Mental health/mood
Changes in mental health/mood post-procedurally did not vary
significantly between UAE and Myomectomy [OR=-0.13, 95% CI (-5.3,
5.04)] (Figure 2, F) This data included two studies reporting their
results at 6 months post-op and at 12 months. [14,
29]).
7. Sexual functioning
There was no significant difference in sexual functioning between UAE
and myomectomy [OR=-6.33, 95% CI (-12.93, 0.27)] (Figure 2, G).
This data included two studies [14,
29]).8. Resolution of symptoms
Resolution of symptoms did not vary significantly between groups
[OR=1.72, 95% CI (0.91, 3.27)] (Figure 2, H). Three papers reported
on this [15, 28, 30]. All these papers used
different scoring systems, however, the result had little statistical
heterogeneity (I2 0%) implying consistency in the
finding.
9. Improvement in menorrhagia
There was a significant difference in improvement of menorrhagia between
UAE and myomectomy groups [OR=1.61, 95% CI (1.07, 2.43)] (Figure 2,
I). Siskin et al.,2006 found a reduction in mean menorrhagia bleeding at
6 months of 52.1% with UAE, and 43.7% with myomectomy. Razavi et al.,
2003 found a reduction in menorrhagia was 64% for their myomectomy
group and 92% for their UAE group.
10. Post-procedural quality of life score.
Post-procedural quality of life scores 12 months post-operatively were
significantly higher in the myomectomy cohort in comparison to the UAE
cohort [OR=-10.56, 95% CI (-15.34, -5.79)] (Figure 2, J).
11. Time taken to return to normal activities
UAE group took a weighted mean of 7.7 days (range 7.5-8) to return to
normal activities, whereas the myomectomy group took 36.6 days (range
36-37) (two studies [27, 28] (Figure 2, L)).
12. Complications
It was found that there was a significantly higher rate of complications
in the myomectomy group in comparison to the UAE group [OR=0.56, 95%
CI (0.40, 0.79)] (Figure 1, E). Five papers provided data on the
number of participants experiencing complications[14, 15, 27, 28]. ‘Complications’ included events
such as infections, haematomas, post-embolisation syndrome, bowel
obstructions, rash, transfusions, pain, readmissions, and adhesions. DiscussionMain findingsBoth UAE and myomectomy are uterine-sparing treatment options for
fibroids. UAE offers a minimally invasive approach, however myomectomy
is generally favoured as first line treatment for fibroids that require
further treatment than hormonal or analgesic medications[4].
There are several studies that compare UAE to all surgical managements
of fibroids [10, 11, 12, 13, 23, 24, 25] . But
very few of these papers separate results for different surgical
techniques, so they could not be included in this review. A few
literature reviews that do compare UAE and myomectomy do not include
more recent RCT data that would have an impact on the findings. A review
by Jun et al., 2012 that compared UAE with surgical treatments only
included one RCT that had myomectomy data. Since then, there have been
two large RCT trials with more data specifically for UAE versus
myomectomy [14, 16]. Further to this, the 2014
Cochrane review for outcomes of different treatments for uterine
fibroids included only two studies that compared UAE and myomectomy[23]. In this review we included eight studies,
which to the best of our knowledge means it is the largest meta-analysis
of UAE versus myomectomy.
There were no significant differences found between the UAE and
myomectomy groups for numbers of technical failures, mental health
scores, and sexual functioning. UAE was associated with lower
complication rates (OR 0.56; 95% CI 0.40-0.79), increased improvement
in bleeding (OR 1.61 95% CI 1.07-2.43) and a shorter total recovery
time (7.7 days versus 36.6 days). Whilst myomectomy was associated with
a higher post-procedure quality of life (mean difference -10.56; 95% CI
-15.34 - -5.79) and lower re-intervention rate (OR 5.16; 95% CI
2.41-11.04). No significant difference in procedural failure rate was
seen (OR 0.67; 95% CI 0.30-1.50).
It was expected that UAE is associated with a lower risk of haemorrhage,
infection, stay in hospital, and recovery time. This is because it is
less invasive, and similar results have been reported in UAE vs surgery
meta-analyses [11, 23]. Furthermore, ‘surgery’
(including myomectomy) has been associated with a lower rate of
re-interventions [11, 25], and higher
post-procedural quality of life score [21].
In our review we found that UAE had a lower risk of complications
compared with myomectomy, however, other papers have found that UAE is
associated with higher numbers of complications compared with ‘surgery’[10, 25]. Whereas Jun et al.,2012 found no
difference in complications incidence, and less ‘major complications’ in
UAE cohorts. These differences are also likely to be explained by
separating out myomectomy from other surgical procedures.
The ‘improvement in menorrhagia’ outcome had high heterogeneity
(I2=71%). So a sensitivity analysis was undertaken
(Appendix S5) where Razavi et al., 2003’s paper was removed, which
improved the heterogeneity. This may be because each author measured the
outcome differently, with Goodwin et al., 2006 and Siskin et al., 2006
measuring a reduction in bleeding score, and Razavi et al., 2003
measured the percentage of patients that had a ‘successful’ reduction in
menorrhagia. Strengths and limitationsThe RCTs included within this study did not blind patients to the
intervention, increasing their risk of bias. However, this is a
limitation which was found to be acceptable given that patients needed
to be able to give informed consent to the procedure. Furthermore,
Manyonda et al., 2012 and 2020 had some deviations from the initial
randomisation with some patients receiving a different intervention.
Four of the cohort studies were deemed to have issues with comparability
between UAE and myomectomy groups (Table S1). These included problems
such as a large difference in cohort sizes [29],
and the presence of potential confounding variables such as obesity and
smoking [26]. Siskin 2006 evaluated the
gynaecological histories between the cohorts as well as looking at
demographic information and surgical histories. Overall, there were no
papers that presented a significant risk of bias, and therefore all
eight were included in the data analysis.
In regards to bias assessment, two of cohort studies had a low risk of
bias (Goodwin et al., 2006 and Siskin et al., 2006), and three had a
medium risk of bias (Narayan et al., 2010, Broder et al., 2002, and
Razavi et al., 2003). One RCT was determined to have a low risk of bias
(Mara et al., 2007), and the other two were found to have a medium risk
(Manyonda et al., 2012 and 2020). The aspects of bias that were most
prevalent in the studies was in the study selection and availability of
follow-up data for all participants.
Although four of the eight papers did use the Uterine Fibroid Symptom
and Quality of Life (UFS-QOL) score[31][14, 16, 28, 29] , to assess quality of life
outcomes, most studies reported their results in different formats, and
some papers did not give data for each outcome on the UFS-QOL scoring
framework.
There were some outcomes that could not be meta-analysed and this was a
limitation of our study. Two studies did give data for patient
satisfaction [26, 29] , although Narayan et al.,
2010 gave their results in odds ratio and Broder et al., 2002 gave
theirs in percentages of participants satisfied. This meant it was not
possible to meta-analyse.
Three papers did report on pain [27, 28, 29] ,
Siskin et al., 2006 reported pain scores as a change from baseline, and
Goodwin et al., 2006 reported it as a mean score. Although both used the
UFS-QOL framework they presented their results differently and because
of this they could not be meta-analysed. Razavi et al., 2003 reported on
pain as a percentage of patients with resolution of pain.
There was difficulty in assessing post-procedural complications between
the papers. Some gave complication rates as ‘early’ or ‘late’[15, 28], whilst others gave ‘occurrence of
adverse events’ [14, 27] without indication of
when they occurred. Some papers elaborated on specific complications
such as ‘infection’ or ‘haematoma’ [14, 28] ,
however others just reported how many patients had a ‘complication’, and
gave examples within the text. Because of this, in this review outcomes
were reported both under a generic ‘complication’ heading and specific
ones where possible.InterpretationMara et al., 2007 and Siskin et al., 2006 gave data on pregnancies,
labours, and miscarriages . With Mara et al., 2007 also giving data on
live birth. They found five births in the UAE group (out of 26 who tried
to conceive) and 19 births in the Myomectomy group (out of 40 who tried
to conceive). Some of the papers noted that they did not include women
who wanted to get pregnant in the UAE cohort due to ethical reasons[14, 28, 29] . Therefore, pregnancy and fertility
outcomes could not be compared. Current NHS treatment algorithms for
fibroids do suggest that there are hesitations for use of UAE in those
who may wish to become pregnant [3,5]. Therefore,
this is a key comparator for the two treatment modalities that needs to
be explored further, especially given that fibroids do largely affect
pre-menopausal women.
The findings of this study suggest that guidelines for the treatment of
uterine fibroids should be based upon the individual preferences of the
patients. It would be hard to make a treatment algorithm based on the
findings, as there is no clear ‘better’ treatment. Rather, there are
risks associated with both treatments that need to be balanced with the
goal of reducing symptoms and increasing the quality of life of the
patient. There is a hesitancy for use of UAE over myomectomy within
current guidelines that may need to be re-assessed to ensure the best
options are offered to those seeking treatment for uterine fibroids.
Patients should be given the data in a clear format that shows which
outcomes are associated with each treatment option, and healthcare
professionals should aid the patient in this decision using an
appropriate evidence-base. ConclusionsBoth UAE and myomectomy are safe and effective treatment options for
uterine fibroids. They both offer a high rate of technical success, and
offer significant improvement in sexual functioning, mental health, and
general quality of life. However, there is a higher chance of requiring
re-interventions if UAE is chosen. UAE offers lower rates of haemorrhage
and infection, and allows for patients to leave hospital faster, and
return to activities of daily life faster than those who have
myomectomy. More research needs to be undertaken to compare fertility
and birth outcomes, as there is a mixed picture in the literature and
few studies have explored these outcomes. Future research on this topic
could potentially benefit from a standardised method of reporting
outcomes, including follow-up times, so that more accurate comparisons
can be made.