Uterine-sparing minimally invasive interventions in women with uterine fibroids: a systematic review...

AOGS REVIEW ARTICLE

Uterine-sparing minimally invasive interventions in womenwith uterine fibroids: a systematic review and indirecttreatment comparison meta-analysisNIKOLETTA PANAGIOTOPOULOU1, SHANKARALINGAIAH NETHRA2, STAMATIOS KARAVOLOS3,GAITY AHMAD2, ANDREAS KARABIS4 & AMANDA BURLS5

1Obstetrics & Gynaecology Department, Leigh Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust, Leigh,2Obstetrics & Gynaecology Department, Royal Oldham Hospital, Pennine Acute Hospitals NHS Trust, Oldham, 3Newcastle

Fertility Centre at Life, Newcastle, UK, 4Mapi Group, Houten, the Netherlands, and 5School of Health Sciences, City

University London, London, UK

Key words

Uterine sparing surgery, fibroids, uterine

artery embolization, uterine artery occlusion,

myomectomy, indirect treatment comparison

Correspondence

Nikoletta Panagiotopoulou, Obstetrics &

Gynaecology Department, Leigh Infirmary,

The Avenue, Leigh, Lancashire, WN7 1HS,

UK.

E-mail: [email protected]

Conflicts of interest

The authors have stated explicitly that there

are no conflict of interest in connection with

this article.

Please cite this article as: Panagiotopoulou N,

Nethra S, Karavolos S, Ahmad G, Karabis A,

Burls A. Uterine-sparing minimally invasive

interventions in women with uterine fibroids:

a systematic review and indirect treatment

comparison meta-analysis. Acta Obstet

Gynecol Scand 2014; 93: 858–867.

Received: 9 October 2013

Accepted: 2 June 2014

DOI: 10.1111/aogs.12441

Abstract

Objective. To evaluate the effectiveness of uterine-sparing interventions for

women with symptomatic uterine fibroids who wish to preserve their uterus.

Design. Systematic review and indirect comparison meta-analysis. Meth-

ods. MEDLINE, EMBASE, CENTRAL, conference proceedings, trial registers

and reference lists were searched up to October 2013 for randomized con-

trolled trials. Main outcome measures. Outcome measures were patient satisfac-

tion, re-intervention and complications rates, reproductive outcomes, and

hospitalization and recovery times. Results. Five trials, involving 436 women

were included; two compared uterine artery embolization with myomectomy

and three compared uterine artery embolization with laparoscopic uterine

artery occlusion. Indirect treatment comparison showed that myomectomy and

uterine artery embolization resulted in higher rates of patient satisfaction (odds

ratio 2.56, 95% credible interval 0.56–11.75 and 2.7, 95% credible interval 1.1–7.14, respectively) and lower rates of clinical failure (odds ratio 0.29, 95% cred-

ible interval 0.06–1.46 and 0.37, 95% credible interval 0.13–0.93, respectively)than laparoscopic uterine artery occlusion. Myomectomy resulted in lower re-

intervention rate than uterine artery embolization (odds ratio 0.08, 95% credi-

ble interval 0.02–0.27) and laparoscopic uterine artery occlusion (odds ratio

0.08, 95% credible interval 0.01–0.37) even though the latter techniques had an

advantage over myomectomy because of shorter hospitalization and quicker

recovery. There was no evidence of difference between the three techniques in

ovarian failure and complications rates. The evidence for reproductive out-

comes is poor. Conclusion. Our study’s results suggest that laparoscopic uterine

artery occlusion is less effective than uterine artery embolization and myomec-

tomy in treatment of symptomatic fibroids. The choice between uterine artery

embolization and myomectomy should be based on individuals’ expectations

and fully informed discussion.

Abbreviations: CrI, credible intervals; GRADE, Grades of Recommendation

AssessmentDevelopment and Evaluation Working Group; HIFU, high-intensity

focused ultrasound; ITC, indirect treatment comparison; LUAO, laparoscopic

uterine artery occlusion; MRgFUS, magnetic-resonance-guided focused

ultrasound surgery; OR, odds ratio; RCTs, randomized controlled trials; UAE,

uterine artery embolization.

ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 858–867858

A C TA Obstetricia et Gynecologica

Introduction

Uterine fibroids are benign smooth muscle tumors of the

uterus. They are seen in approximately one in four

women and cause significant symptoms in at least half of

them (1). Moreover, uterine fibroids are important from

a health-economic perspective. The direct cost of fibroid

treatments exceeds $2.1 billion per annum in the USA (2)

and the indirect cost, consisting of disability and absen-

teeism expenses, reaches that of the direct cost (3).

Despite the clinical and economic implications of uter-

ine fibroids, evidence gaps remain with regards to thera-

peutic options for fibroid-related symptoms (4). Medical

treatments appear ineffective or cause unacceptable side

effects (5) and they are considered inappropriate for

women with reproductive plans because of their contra-

ceptive action (6). The traditional treatment options for

uterine fibroids have been myomectomy and hysterec-

tomy. However, new minimally-invasive alternatives to

hysterectomy have been developed over the last decades

in response to women’s resistance to hysterectomy and

clinicians’ quest for more cost-effective treatments. Rea-

sons that drive women to avoid hysterectomy include

their wish for fertility preservation (7), their conceptions

about hysterectomy’s impact on sexual expression and

function and their extended professional and personal

responsibilities that require minimal recovery time (8).

Two of these alternative uterine-sparing surgical treat-

ment modalities for uterine fibroids – uterine artery

embolization (UAE) and magnetic-resonance-guided

focused ultrasound surgery (MRgFUS) – have been

approved by the USA Food and Drug Administration.

Moreover, UAE has been recommended by the UK,

National Institute for Health and Clinical Excellence as

an alternative to hysterectomy for women with symptom-

atic uterine fibroids who want to retain their uterus (9).

Reports of efficacy of the new, minimally invasive,

uterine-sparing surgical techniques in improving fibroid-

related symptoms have been published (10–16). However,

cumulative data on their safety and efficacy have not yet

been reported, with the exception of UAE. A recent

meta-analysis of randomized controlled trials (16) com-

pared UAE to surgery and concluded that UAE has an

overall patient satisfaction rate similar to hysterectomy

and myomectomy and offers an advantage with regards

to a shorter hospital stay and recovery time. However, it

was shown to be associated with a higher rate of minor

complications and an increased re-intervention rate. Yet

with the lack of direct comparison between UAE and

myomectomy gaps remain in the evidence for efficacy of

these two uterine-sparing surgical techniques. Although

there are numerous studies comparing the different uter-

ine-sparing surgical techniques for uterine fibroids with

each other, direct evidence for their safety and effective-

ness is lacking due to low statistical power. Therefore,

there was a need for a comprehensive systematic literature

review with the aim to find and summarize trials compar-

ing different uterine-sparing surgical treatment modalities

for symptomatic uterine fibroids with each other.

Material and methods

Data sources

We systematically searched MEDLINE (from 1948 to

October 2013), EMBASE (from 1969 to October 2013),

and Cochrane Central Register of Controlled Trials

(CENTRAL) in the Cochrane Library (issue 9, 2013) to

identify all reports of uterine sparing surgical treatment

modalities for women with symptomatic uterine fibroids.

There were no language, publication date, or publication

status restrictions. In addition, we performed a cross-ref-

erence search of all included studies and relevant reviews

that were identified during the search process. Moreover,

to identify unpublished studies and studies in progress,

we searched clinical trials registers, conference proceed-

ings, relevant internet sources, and clinical guidelines. We

also requested additional information on any published,

unpublished or ongoing data by e-mail from authors of

completed trials included in this review or ongoing trials.

An electronic search strategy was developed and adapted

to ensure high sensitivity in the expense of specificity.

Combinations of text words and thesaurus terms that

included uterine embolization, magnetic guided or

focused ultrasound, MRgFUS, uterine and fibroid and

occlusion or ligation or coagulation or high-intensity

focused ultrasound (HIFU), myolysis and myomectomy

were used. Search terms were modified accordingly in

different databases (full details of search strategy available

from corresponding author).

Inclusion criteria

Studies were included if they: (i) were randomized con-

trolled trials (RCTs) comparing any two of the following

Key Message

Laparoscopic uterine artery occlusion appears to be

less effective than uterine artery embolization and

myomectomy in the treatment of women with

fibroids who wish to retain their uterus. The choice

between uterine artery embolization and myomecto-

my depends on individual expectations.

ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 858–867 859

N. Panagiotopoulou et al. Uterine-sparing procedures for fibroids

treatment modalities for symptomatic uterine fibroids:

myomectomy, UAE, laparoscopic uterine artery occlusion

(LUAO), myolysis, temporary transvaginal uterine occlu-

sion, HIFU and MRgFUS or no treatment; (ii) included

premenopausal women with symptomatic fibroids of sig-

nificant size (≥2 cm) who wished to preserve their uterus;

(iii) reported at least one of the outcomes of interest

(patient satisfaction, re-intervention rate, ovarian failure,

clinical failure, hysterectomy rate, complications, length

of hospital stay, recovery time, fertility and obstetric out-

comes). All studies failing to meet these criteria or studies

that included women with exclusively subserosal, pedun-

culated or submucosal fibroids or pregnant or with pelvic

inflammatory disease or with suspected malignancy as

well as studies employing temporal use of any one uter-

ine-sparing treatment modality as an intervention were

excluded.

Data extraction

Data were extracted independently by two reviewers using

a standardized data collection sheet. Disagreements were

resolved by consensus. The methodological quality of the

included studies was evaluated independently by two

reviewers. In case of uncertainty, consensus was reached

by discussion. The risk of bias for RCTs was assessed

using the Cochrane tool (17) and all studies were found

to be well performed with low risk of bias (Figure 1).

The overall methodological quality of the included studies

was assessed using the Grades of Recommendation,

Assessment, Development and Evaluation Working Group

(GRADE) approach (17) (Table 1).

Data synthesis

None of the studies directly compared all three identi-

fied minimally-invasive procedures for fibroids, so an

indirect treatment comparison (ITC) within a Bayesian

framework was carried out (18–21). Indirect (“net-

work”) meta-analyses are based on differences between

treatment group outcomes within each study. The effi-

cacy and safety of myomectomy was compared with that

of UAE and the efficacy and safety of LUAO was com-

pared with that of UAE. The differences in patient satis-

faction, clinical failure re-intervention and hysterectomy

rates as well as minor and major complications between

myomectomy and UAE, and differences between LUAO

and UAE were used to make indirect treatment compar-

isons between myomectomy and LUAO. To estimate

posterior densities for unknown variables we used Mar-

kov Chain Monte Carlo methods through WINBUGS

software (version 1.4.3; MRC Biostatistics Unit, Cam-

bridge, UK).

A hierarchical model was used to examine the four

clinical outcomes of interest (22). For each outcome, the

total number of events in the jth study for intervention k

is denoted by rjk, and the corresponding number of par-

ticipants is given by njk. Together, these data provide

information on the probability of an event (pjk) for each

intervention group in each included study. A logistic

regression model was used wherein each study is assigned

a reference intervention arm, bj, and a corresponding log-

odds for the outcome denoted by lj. Based on this set-

up, we assumed a log-odds ratio (denoted by φj,k) for

intervention k relative to intervention bj to follow a nor-

mal density with mean log-odds ratio (dk � dbj), and

between study standard deviation, s, where dk is the mean

log-odds ratio of outcome for intervention compared

with usual care (so that d1 = 0). The model can be

expressed as log-odds(pj,k) = lj if intervention bj, and

log-odds(pj,k) = lj if intervention k; φj,k ~Normal[(dk-

dbj), s2]. The between-study variability of treatment

effects was assigned a uniform (0, 2) prior density and

assumed to be the same for all pairwise comparisons.

The results of the ITC are presented as odds ratios

(OR). Point estimates of the OR were derived from the

median of the posterior distribution while their 95%

credible intervals (CrI) were estimated from the 2.5th and

97.5th centiles of the posterior distribution. At each end-

point probability of being the best treatment is presented

for each treatment. We estimated the average ranking of

each treatment, the probability of each OR being >1, and

Figure 1. Methodological characteristics of the five included trials.


Uterine-sparing procedures for fibroids N. Panagiotopoulou et al.

the probability of a treatment being associated with the

lowest risk of harm. To present the respective probabili-

ties for each combination of outcome and intervention

we used bar plots and cumulative probability plots. To

assess model convergence we used trace plots and the

Brooks–Gelman–Rubin statistic. For each analysis we fit-

ted three chains, each employing 80 000 iterations, with a

burn-in of 20 000 iterations. We assessed model fit using

the Deviance Information Criterion (23) for the fixed and

random effects model and the model with the lower

Deviance Information Criterion value was selected.

Results

Trials and patients

We identified 10 051 citations through the electronic lit-

erature searches (Figure 2) and excluded 9940 after

screening titles and abstracts. A further 105 were excluded

for being duplicate publications or not being RCTs or

not involving direct comparisons of uterine-sparing sur-

gery for fibroids or not presenting the outcome measures

of our focus. After detailed evaluation of the citations,

five primary articles met the inclusion criteria for the evi-

dence synthesis. These consisted of three studies compar-

ing UAE with LUAO (24–27) (182 women) and two

comparing UAE with myomectomy (28,29) (284 women).

Figure 3 presents the network diagram based on these five

studies. Despite some differences in terms of study design

and patient characteristics, the studies included in this

analysis are considered to be broadly comparable.

Patient satisfaction

The ITC of satisfaction rate at the first year after treat-

ment is presented in Table 3. The results showed that

UAE had the greatest probability (53%) for being the best

treatment on improving short-term patient satisfaction,

followed by myomectomy (46%), and LUAO (1%). None

of the studies reported on satisfaction with treatment at

5 years (Table 2) and hence the difference of long-term

Figure 2. Study selection process for systematic review and meta-

analysis of uterine-sparing surgical treatment modalities for women

with symptomatic uterine fibroids.

Table 1. Quality of evidence across included studies.

Outcomes No of participants (Studies) Quality of evidence (GRADE) Comments

Patient satisfaction 278 (4 studies) moderate Studies with no blinding

Re-intervention 404 (4 studies) moderate Studies with no blinding

Ovarian failure 178 (2 studies) very low Imprecision of results

Hysterectomy 314 (3 studies) moderate Studies with no blinding

Major complications 430 (5 studies) moderate Studies with no blinding

Pregnancies 66 (1 study) very low Evidence is based on a single trial

Only included women who wanted

to conceive

Early pregnancy complications 66 (1 study) very low Evidence is based on a single trial

Late pregnancy complications 24 (1 study) very low Evidence is based on a single trial

GRADE Working Group grades of evidence: high-quality, further research is very unlikely to change our confidence in the estimate of effect;

moderate, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low,

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; very

low, any estimate of effect is very uncertain.



patient satisfaction between the treatments could not be

assessed.

Re-intervention, clinical failure, and hysterectomyrates

The ITC showed that LUAO had the least probability

for being the best treatment on reducing short-term re-

intervention (<1%) and clinical failure (<1%) rate, fol-

lowed by UAE (<1% and 36%, respectively) and

myomectomy (>99% and 63%, respectively). Compared

with myomectomy, UAE was associated with summary

average effects that represented increase in the risk of

hysterectomy [OR 0.16, 95% CrI 0.01–0.85, P(better)

2%]. Similarly, the risk of hysterectomy appeared to be

higher after LUAO in comparison with myomectomy

[OR 0.15, 95% CrI 0–8.74, P(better) 16%], however no

firm conclusion can be drawn due to wide CrIs

(Table 3).

Medium-term (to 5 years) clinical failure rate between

myomectomy and UAE was not assessed in any of the

included studies (Table 2). Hald et al. (25,26) reported

clinical failure and hysterectomy rates in the two groups

at 5 years when comparing UAE and LUAO (Table 2).

The study showed that patients undergoing LUAO had

a higher clinical failure rate and higher chance of having

a hysterectomy in the long term in comparison to those

undergoing UAE. Hysterectomy rate at 5 years between

myomectomy and UAE was not assessed in any of the

included studies (Table 2). None of the studies reported

on re-intervention rate at 5 years (Table 2).

Complications

Myomectomy and UAE demonstrated comparable results

in terms of minor (OR 0.70, 95% CrI 0.29–1.62) or

major (OR 1.52, 95% CrI 0.72–3.36) complications, and

so did LUAO and UAE (minor complications OR 0.60,

95% CrI 0.22–1.62; major complications OR 0.43, 95%

CrI 0.09–1.67] (Table 3).

Length of hospital stay and recovery time

Mara et al. (29) showed that patients undergoing myom-

ectomy stayed longer in hospital than those undergoing

UAE and required significantly longer recovery time

(Table 2). Duration of hospitalization was also compared

between the LUAO and UAE groups (Table 2) but data

were not suitable for pooling; Hald et al. (25,26) showed

that women in the LUAO stayed at hospital for signifi-

cantly less time in comparison to the UAE group while

Ambat et al. (24) reported that there was no difference in

the length of hospital stay between the two groups.

Reproductive and perinatal outcomes

The ITC for ovarian failure risk assessment was not possi-

ble due to convergence problems of the Markov Chain

Monte Carlo algorithm. However, traditional meta-analy-

sis revealed no difference (p > 0.05) between myomecto-

my and UAE (29) and between LUAO and UAE (25,26)

in the proportion of women with symptomatic fibroids

who developed ovarian failure following these uterine-

sparing surgical interventions (Table 2).

Reproductive and perinatal outcomes were only

reported by the Mara et al. (29) study, which compared

UAE to myomectomy. Mara et al. (29) showed that the

pregnancy and live-birth rates were higher among women

undergoing myomectomy in comparison to women

undergoing UAE (Table 2). There was no evidence of dif-

ference in terms of early pregnancy complications, pre-

term delivery, intrauterine growth restriction or

postpartum hemorrhage between the two groups

(Table 2).

Discussion

Of the three most popular uterine-sparing minimally

invasive surgical treatment modalities (myomectomy,

UAE, and LUAO) examined in this study, LUAO seem to

have a disadvantage over myomectomy and UAE in terms

of lower patient satisfaction rate, increased short-term re-

intervention, clinical failure and hysterectomy rates in

women with symptomatic uterine fibroids. The ITC sug-

gested that women undergoing myomectomy had a

reduction in the rate of re-intervention within the first

year in comparison to those undergoing UAE. However,

the similar clinical failure rate as well as the shorter hos-

pital stay and quicker recovery time associated with UAE

make this procedure neutral in terms of patient satisfac-

tion and cost-effectiveness. This may vary in different

Figure 3. Network of studies evaluating uterine-sparing surgical

treatment modalities for uterine fibroids. Number of women

randomized to each treatment is shown in parentheses.



Table

2.Resultsoftrialsincluded

insystem

atic

review

andeviden

cesynthesis.

Patien

t

satisfaction

Re-

interven

tion

Ovarian

failure

Clinical

failure

Hysterectomy

Complications

Length

of

hospital

stay

[mean,(ran

ge)]

Recovery

time

Preg

nan

cy

Live

birth

Early

pregnan

cy

complications

Preterm

delivery

PPH

IUGR

Short

term

Long

term

Short

term

Long

term

Short

term

Long

term

Short

term

Long

term

Minor

Major

Ambat

etal.(24)

LUAO

(n=10)

6/10b

––

––

4/10b

––

–1/10b

0b

3.5

days

(2–1

0)

––

––

––

–

UAE(n

=10)

10/10b

––

––

0b

––

–2/10b

0b

3.5

days

(2–7

)

––

––

––

–

Haldet

al.(25,26)

LUAO

(n=29)

24/29

–6/29b

–0/29b

6/29

14/29a

1/29b

8/29

10/29b

2/29b

46h(24–7

2)a

––

––

––

–

UAE(n

=29)

27/29

–7/29b

–1/29b

2/29

5/29a

1/29b

2/29

13/29b

6/29b

57h(24–1

08)a

––

––

––

–

Helal

etal.(27)

LUAO

(n=45)

36/45

–6/45b

––

6/45

––

––

1/45b

––

––

––

––

UAE(n

=45)

39/45

–5/45b

––

5/45

––

––

0/45b

––

––

––

––

Man

yondaet

al.(28)

Myomectomy

(n=73)

––

1/73b

––

1/73b

–8/73

6/73

6days(NS)

a–

––

––

––

UAE(n

=74)

––

3/63b

9/63

–6/63b

–2days(NS)

a–

––

––

––

Maraet

al.(29)

Myomectomy

(n=63)

51/58

–2/62a

–0/62

5/58

–0/58

–3/63b

12/63b

86.1

�40.4

h

(48,192)a

22.1

�12.3

(7,65)a

31/40b

19/40a

7/40b

5/19b

0/19b

2/19b

UAE(n

=58)

46/52

–19/58a

–2/58

6/58

–0/58

–5/58b

11/58b

60.2

�32.3

h

(36,216)a

11.9

�5.9

(3,30)a

13/26b

6/26a

10/26b

0/5

b1/5

b0/5

b

nconsistsofwomen

withsymptomaticuterinefibroidsat

baseline.

IUGR,intrau

terinegrowth

restriction;LU

AO,laparoscopicuterineartery

occlusion;NS,

notstated

;PPH,postpartum

hem

orrhag

e;UAE,

uterineartery

embolization.

aStatisticalsignificantdifference;p<0.05.

bpvaluenotstated

.



clinical settings, especially in the presence of effective

enhanced recovery programs. All three most popular

uterine-sparing surgical procedures for women with

symptomatic fibroids were associated with similar risks of

complications.

The evidence of fertility and pregnancy outcomes after

myomectomy, UAE and after LUAO is poor. Reproductive

outcomes were reported in the minority of included studies

(25,26,29). Myomectomy appeared advantageous over

UAE with regards to increased number of pregnancies and

live births. No significant difference with regards to perina-

tal outcomes was noted. The validity though of the above

observation is hampered because of the lack of sufficient

power to detect differences and the clinical heterogeneity

of the studied population. It is therefore impossible to

draw firm conclusions from such sparse data.

The findings of this review are in agreement with

the results of a Cochrane systematic review comparing

UAE to myomectomy and hysterectomy (30), which

concluded that UAE had similar satisfaction rate to

hysterectomy or myomectomy with the advantage of

reduced hospital stay and quicker recovery and the dis-

advantage of up to five times higher re-intervention

rate and worse fertility outcomes. Moreover, several

observational studies comparing UAE to myomectomy

(31–37) concluded that both uterine-sparing surgical

treatment modalities are equally successful and with

comparable clinical outcomes, while a prospective

cohort study (31) focusing on re-intervention rates con-

cluded that women undergoing UAE were more likely

to need further invasive treatment. Furthermore, obser-

vational studies comparing UAE to LUAO (38–41)concluded that both treatments have comparable effects

on women’s symptoms but UAE is more effective in

causing complete ischemia.

Data on reproductive outcomes following uterine-spar-

ing surgery for symptomatic uterine fibroids continue to

accumulate and show that pregnancies and live births do

occur following the above procedures. An observational

study comparing LUAO to myomectomy concluded that

there is no difference in ovarian reserve (42). However,

reports from observational studies comparing UAE to

myomectomy (43,44) concluded that UAE is associated

with increased risk of complications in pregnancy such as

preterm delivery and malpresentation and with a trend

towards higher rates of miscarriages and postpartum

hemorrhage and hence the joint Standards of Practice

Committee of the Cardiovascular and Interventional

Radiological Society of Europe and the Society of Inter-

ventional Radiology suggested that future reproductive

plans are a relative contraindication to UAE (45). Finally,

observational studies were inconclusive in terms of repro-

ductive outcomes following UAE or LUAO, with one

reporting equal pregnancy outcomes between the two

groups (39) and another reporting higher risk of miscar-

riage following UAE (46).

Strengths of this review include the fact that it was

conducted according to the standards of The Cochrane

Collaboration and reported according to the PRISMA

standards for reporting systematic reviews and meta-

analyses (47). An extensive literature search was carried

out without any language or publication status restric-

tions, so minimizing the risk of missing relevant studies.

Moreover, published or unpublished research material

not available commercially or not indexed by major data-

bases, including conference proceedings, trial registers

and reference lists, were also searched to minimize the

risk of introducing publication bias. Limitations of this

review include the relatively low number of included

studies and total number of patients despite the fact that

the quality of included studies is satisfactory. Hence, the

results of the ITC should be interpreted with caution.

Moreover, as in all evidence synthesis studies, limitations

associated with the combination of estimates from differ-

Table 3. Outcome measures: indirect treatment comparison (ITC)

results.

LUAO Myomectomy

OR (95% CrI) P(better) OR (95% CrI) P(better)

Patient satisfaction rate at 12 months

UAE 0.37 (0.14–0.90) 1.4% 0.94 (0.28–3.11) 46%

LUAO – 2.56 (0.56–11.75) 89%

Re-intervention rate at 12 months

UAE 1.00 (0.44–2.27) 50% 0.08 (0.02–0.27) >99%

LUAO – 0.08 (0.01–0.37) >99%

Ovarian failure at 12 months

UAE NAa NAa

LUAO – NAa

Clinical failure at 12 months

UAE 2.72 (1.07–7.65) 2% 0.81 (0.21–2.94) 63%

LUAO – 0.29 (0.06–1.46) 93%

Hysterectomy rate at 12 months

UAE 1.00 (0.03–39.98) 50% 0.16 (0.01–0.85) 2%

LUAO – 0.15 (0.00–8.74) 16%

Minor complications

UAE 0.60 (0.22–1.62) 84% 0.70 (0.29–1.62) 80%

LUAO – 1.16 (0.31–4.34) 41%

Major complications

UAE 0.43 (0.09–1.67) 89% 1.52 (0.72–3.36) 14%

LUAO – 3.57 (0.75–19.61) 6%

Figures are mean odds ratios (OR); 95% credible intervals (CrI) and

probability that treatment modality in column is better. Odds ratio >1

indicate increased rate with surgical treatment modality in column.

LUAO, laparoscopic uterine artery occlusion; NA, not available;

P(better), probability that treatment in column is better than treat-

ment in row; UAE: uterine artery embolization.aITC was not possible due to convergence problems.



ent clinical studies should be considered. Different clinical

studies have different populations of patients and

therefore, even with statistical adjustments in the analysis,

clinical heterogeneity may still exist. For example, the

pilot study by Ambat et al. (24) that compared LUAO

with UAE seemed to show much lower satisfaction rate

and much higher clinical failure rate following LUAO

than the other two relevant RCTs. This could be due to

specific characteristics of this particular study that differ-

entiate it from the others, such as the higher menorrhagia

score of the LUAO group at baseline. However, in the

absence of individual patient data, this could not be

investigated any further. Furthermore, due to the limited

amount of data with several comparisons consisting of

only one study, subgroup analyses (such as by polyvinyl

alcohol particle size for UAE or by the myomectomy

route) and adjustment (such as by means of a covariate

analysis) were not feasible.

New uterine-sparing surgical treatments are being

developed in an attempt to improve cost-effectiveness of

available treatment options for uterine fibroids and to

improve women’s quality of life. Therefore, there is a

need for further RCTs providing longer follow up and

assessing the safety and efficacy of novel interventions.

Indeed, there are at least five ongoing registered RCTs

with these objectives and their results are highly antici-

pated. Pending additional data, uterine-sparing surgery

for women with symptomatic fibroids and future repro-

ductive plans should be used with caution and after care-

ful counseling.

To summarize, the current evidence does not support

the effectiveness of LUAO as a treatment option for

women with symptomatic fibroids. However, the early

and medium-term (to 5 years) results for UAE are good;

it is as effective as myomectomy for symptom control

with the caveat of increased risk of second intervention

by 5 years. The evidence for reproductive outcomes after

any of the studied uterine-sparing interventions is poor.

Hence, an evidence-based recommendation about treat-

ment for fibroids in women with future fertility plans

cannot be made and treatment decisions should only be

made after fully informed discussion.

Funding

No benefits of any form have been or will be received

from any commercial party directly or indirectly related

to the topic of this article.

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Uterine-sparing minimally invasive interventions in women with uterine fibroids: a systematic review...

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