DOI: 10.1111/tog.

12223 2016;18:33–42
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

A review of evidence-based management of

uterine fibroids
Kinza Younas MBBS MRCOG MD,a Essam Hadoura MRCOG MB ChB,
b
Franz Majoko MBBS MRCOG PhD,
c

Adnan Bunkheila BSC MBChB M(ART) MD FRCOGd,*

a
Consultant in Reproductive Medicine, Fertility and Minimal Access Surgery, Singleton Hospital, Sketty Lane, Swansea SA2 8QA, UK
b
Consultant Obstetrician and Gynaecologist, Honorary Senior Lecturer (University of St Andrews), Victoria Hospital, Hayfield Road, Kirkcaldy, Fife
KY2 5AH, UK
c
Consultant Obstetrician and Gynaecologist, Singleton Hospital, Sketty Lane, Swansea SA2 8QA, UK
d
Consultant in Gynaecology, Minimal Access Surgery and Fertility, Professor of Reproductive Medicine & Surgery (Hon), CoM, Swansea
University; Director, Wales Fertility Institute, Neath Port Talbot Hospital, Baglan Way, Port Talbot SA12 7BX, UK
*Correspondence: Kinza Younas. Email: Kinzayounas@yahoo.co.uk

Accepted on 13 June 2015

Key content  To create awareness of radiological techniques, such as uterine

 Fibroids are the most common uterine growth and there is an artery embolisation and magnetic resonance imaging-guided
increasing range of options for their management. focused ultrasonography, that preserve the uterus.
 Management options are affected by the woman’s symptoms, age,  To understand the use of pharmacological agents in the reduction
desire to conceive and local resources. of menstrual blood loss and fibroid size.
 Pharmacological agents are effective in alleviating symptoms and
Ethical issues
may improve women’s quality of life.
 Is it ethical to offer new minimally invasive treatment options for
 Interventional radiology procedures may prevent the need
fibroids to older women who wish to retain potential fertility?
for hysterectomy.
 Conventional surgical procedures and minimal access surgery are Keywords: fibroid / infertility / leiomyomata / leiomyoma /
important in management of fibroids. menorrhagia due to fibroids
Learning objectives
 To understand the options available for the management of
uterine fibroids.

Please cite this paper as: Younas K, Hadoura E, Majoko F, Bunkheila A. A review of evidence-based management of uterine fibroids. The Obstetrician &
Gynaecologist 2016;18:33–42. DOI: 10.1111/tog.12223

after menopause.3,4 They can cause concern in women of

Introduction
Uterine fibroids (leiomyomata) are the most common benign
tumours in women, with a lifetime prevalence of around
30%. These tumours are overgrowths of smooth muscle and
connective tissue that are hormone dependent. Each fibroid
arises from a single cell. Fibroids may be solitary, multiple or
diffuse. There is a genetic predisposition to the development
of leiomyomata; they are more common in black women
than in white women, with a ratio of between 3 and 9:1.
Other risk factors for developing fibroids include being
overweight and nulliparity.1,2 The majority of fibroids do not
cause any symptoms but one in four women with fibroids are
symptomatic.2 The symptoms depend on the location and
size of the fibroid and include heavy menstrual bleeding, pain
during periods and intercourse, a dragging sensation in the
lower abdomen and urinary or defecation problems.3
Fibroids rarely present before menarche and usually regress
reproductive age because of heavy, irregular menstrual
bleeding and pain, which can have a negative impact on a
woman’s life and warrants intervention.3,4 Treatment options
include nonsurgical methods (pharmacological, uterine
artery embolisation [UAE], magnetic resonance imaging
[MRI]-guided focused ultrasound [MRgFUS]), minimally
invasive surgery (hysteroscopic myomectomy, laparoscopic
myomectomy), and open surgery (myomectomy or
hysterectomy). The choice of treatment has to be tailored
for each patient according to their wishes, the type and
location of the fibroid, and associated symptoms and
availability of service.5 Figure 1 shows the locations where
fibroids can be found in the uterus.
In women who are asymptomatic or with bearable
symptoms, expectant management may be acceptable.
Many women with fibroids have successful pregnancies.6
Median fibroid growth of 9% over 6 months of observation

ª 2016 Royal College of Obstetricians and Gynaecologists 33

 Fibroid management
Figure 1. A description of fibroids in relation to their location in
the uterus.
has been reported.7 Treatment options for fibroids have been
the subject of Cochrane reviews, but research is still needed to
determine the most appropriate treatment options for
women with fibroids.
The aim of this review was to assess the clinical
effectiveness of treatments for symptomatic uterine fibroids
in premenopausal women. We focused on the effectiveness of
treatment in reducing menstrual loss and fibroid size as well
as improvement in symptoms.
Methods
In defining our question for the review we used the PICO
(participants, intervention, comparison and outcome) tool.8
We searched the Medline, PubMed, Ovid and Cochrane
Library databases using the following keywords: ‘fibroid’,
‘leiomyomata’, ‘leiomyoma’, ‘leiomyofibromas’,
‘menorrhagia due to fibroids’, ‘menometrorrhagia,
symptomatology and management’, ‘treatment of fibroids’,
and ‘medical and surgical management of fibroid uterus’.
Studies of premenopausal women in which the outcome
measures were either change in menstrual loss, uterine or
fibroid size (volume) or improvement in quality of life were
included. All studies from 1990 onwards were included and
we placed no limits on language of publications. Relevant
papers in foreign languages were translated into English
through the library services. When considering procedures
that are current standard practice, we included only
randomised controlled trials, meta-analyses and systematic
reviews. For newer treatments, we included all the available
literature, including case series. We also looked for
unpublished work discussed in international and national
34
conference abstract books. The subsequent bibliographies
were cross-referenced and duplicates were removed.
Articles were screened by titles and abstracts and then full
papers were obtained for assessment. Two reviewers (KY
and AB) independently assessed the articles for inclusion in
the review. A third reviewer (EH) resolved disagreements
about study eligibility for inclusion. The keywords search
yielded 18 278 articles. Screening of titles and then abstracts
identified 96 potential papers for which full texts were
reviewed and CASP checklists were used for critical
analysis.9 A total of 44 papers were considered eligible for
inclusion in the review. Figure 2 shows a flowchart of the
study selection process.
Pharmacological treatment
Pharmacological options are available for short-term use to
treat problems associated with fibroids. These options were
used more frequently in the following situations:
 in perimenopausal women whose problems were likely to
resolve with the onset of the menopause
 in women who were not suitable for surgery and in some
women receiving fertility treatment
 preoperatively to reduce the size of the fibroid and to
reduce menstrual bleeding to improve haemoglobin levels
before surgery. Ulipristal acetate (UA) and
gonadotrophin-releasing hormone (GnRH) analogues
may be used prior to surgery for a fibroid uterus.
In Table S1, we provide a descriptive summary of available
medical treatment options for uterine fibroids and their
effects on menstrual loss, fibroid size and quality of life.
Nonhormonal treatment for heavy periods
associated with fibroids
Tranexamic acid is frequently used in treating heavy
menstrual bleeding in women who have uterine fibroids.
Tranexamic acid is an antifibrinolytic drug that reduces
menstrual loss. A review of the use of tranexamic acid in
women with fibroids concluded that it may reduce
menorrhagia as well as perioperative blood loss in
myomectomy.10 Necrosis and infarcts in fibroids (especially
in large fibroids) have been reported following use of
tranexamic acid.10,11
Hormonal treatments
Published data for the outcome of treatment with the
combined pill or progesterone-only pill in women with a
fibroid uterus are inconclusive. Fibroids have estrogen
and progesterone receptors and both estrogen and
progesterone may promote their growth.12 These hormonal
ª 2016 Royal College of Obstetricians and Gynaecologists

Figure 2. Flow diagram of the study selection process.
treatments can also induce endometrial atrophy, which can
result in reduced menstrual loss.12 A small observational
study reported a reduction in menstrual blood loss and
fibroid volume after 6 months of treatment with depot
medroxyprogesterone acetate.13
Levonorgestrel intrauterine system
The levonorgestrel intrauterine system (LNG-IUS) has been
widely accepted as an effective treatment of heavy menstrual
bleeding. There is general agreement among several reviews
that use of the LNG-IUS in women with fibroids is successful
in reducing menstrual blood loss, increasing haemoglobin
and relieving symptoms.14–17 There are conflicting results
regarding its effect on fibroid or uterine volume and device
expulsion rates. Jiang et al.17 reported no effect on fibroid
volume but a decrease in uterine volume; however,
Sangkomkamhang et al.16 and Kim and Seong15 reported
no change in both uterine and fibroid volume. Zapata et al.14
and Kim and Seong15 reported higher device expulsion rates
that appear to increase with uterine volume. However, Jiang
ª 2016 Royal College of Obstetricians and Gynaecologists
Younas et al.
et al.17 reported low expulsion rates. An online survey for the
Uterine Bleeding and Pain Women’s Research Study found
that 10.3% of women in the UK and France used the
LNG-IUS for menorrhagia associated with fibroids.4
The LNG-IUS reduces menstrual blood loss from
fibroids by inducing endometrial atrophy. A review by
Sangkomkamhang et al.16 included a randomised controlled
trial of 58 women assigned to either a combined oral
contraceptives treatment group (n = 29) or a LNG-IUS
(n = 29) treatment group. The trial showed that the LNG-IUS
was more effective than combined oral contraceptives in
reducing menstrual blood loss and improving haemoglobin
levels.18 The LNG-IUS group showed an increase in
haemoglobin levels from 9.7  1.9 g/dL to 11.7  1.2 g/dL
(P <0.001) and a reduced number of days of menstrual loss.18
Gonadotropin-releasing hormone analogues
GnRH analogues were approved by the Food and Drug
Administration in 1995 for preoperative management of
uterine fibroids. GnRH analogue treatment induces a
35
 Fibroid management
menopausal state with low estrogen levels that may result in
intolerable side effects and bone loss. The hypoestrogenic side
effects could be minimised by adding low dose estrogen and
progestin or tibolone after initial phase of downregulation.
GnRH analogue treatment is therefore limited to a maximum
of 6 months. A Cochrane review that evaluated the role of
preoperative GnRH analogue treatment in women
undergoing hysterectomy or myomectomy suggested a 36%
reduction in leiomyoma size and an improvement in
symptoms after 12 weeks.19 After discontinuation of
treatment, menstruation returned in 4–8 weeks and fibroid
size returned to pretreatment levels within 4–6 months.19,20
Preoperative use of a GnRH analogue may reduce fibroid
volume sufficiently to make vaginal hysterectomy or
transverse incision for the abdominal approach feasible.
Preoperative treatment with a GnRH analogue appears to
make hysterectomy easier, with reduced operating time and a
shorter hospital stay.
There have been concerns about difficulties during
myomectomy in obtaining an appropriate plane for
dissection between the fibroid capsule and myometrium
and that small fibroids were often poorly defined and
therefore were missed in women pretreated with GnRH
analogues. Deligdisch et al.21 reported the blurred interface
between myoma and myometrium and obliteration of
cleavage plan on anatomical and histopathologic findings
with GnRH analogue use before the surgery.
Progesterone-mediated medical treatment
Progesterone binds to progesterone receptors to mediate its
effects in tissues. It has been established that progesterone
acting through its receptors enhances the proliferative activity
of fibroids. Antiprogestins and agents that modulate
progesterone receptor activity, collectively termed selective
progesterone-receptor modulators (SPRMs), could be useful
in the treatment of fibroids. Several SPRMs, including
mifepristone, telapristone, asoprisnil and UA, have been
used in clinical trials for the treatment of uterine
fibroids.22–29
Selective progesterone-receptor modulators
Mifepristone
Mifepristone, a synthetic steroid, works by modulating
progesterone receptors and has been used to alleviate the
symptoms of fibroids. In one double-blind, randomised
clinical trial comparing 10 mg of mifepristone with placebo
there was a reduction in uterine and fibroid volume as well as
decreased menstrual blood loss in the mifepristone group.22
The reduction in menstrual loss and improvement in
symptoms in women treated with mifepristone appears to
be a consistent finding.23–25 However, there is no consensus
about the effect of mifepristone on fibroid volume and the
36
endometrium. Some reports suggest no effect on fibroid
volume23 while others show a reduction in fibroid or uterine
volume.24,25 A systematic review of three clinical trials
including 112 women treated with 5–50 mg of mifepristone
for 3–6 months reported a significant reduction in menstrual
blood loss and an improvement of symptoms (OR 17.84;
95% CI 6.72–47.38), but no change in uterine volume.23
Mifepristone has been associated with development of
endometrial changes in some reports22–25 and its use in
treatment of fibroids is currently restricted to research
settings.22–24
Ulipristal acetate
UA is a new SPRM that is considered effective in the
treatment of uterine fibroids. It induces apoptosis in uterine
fibroid cells and inhibits proliferation of cells.27 In the first
trial (PEARL I),27 5 mg and 10 mg UA doses were compared
with placebo for 13 weeks. Both doses of UA were effective in
reducing menstrual blood loss in over 90% of patients after
13 weeks of treatment.27 Amenorrhoea was noted within 10
days in three-quarters of patients receiving UA. The median
change in uterine fibroid volume was 41% compared with
18% (P = 0.0100) and this reduction was maintained for at
least 6 months after discontinuation of treatment.27
The PEARL II trial28 was a noninferiority, double-blind 13
weeks comparison of UA with a GnRH analogue (monthly
injection of leuprolide acetate). There was no difference in
the control of menstrual bleeding between UA and
leuprolide. However, UA was tolerated better and
controlled bleeding more rapidly than leuprolide. Uterine
volume change was greater with leuprolide than UA, but
ultrasound assessment showed no difference in fibroid
volume change.28 UA use was associated with benign
endometrial changes termed progesterone-receptor-
modulator-associated endometrial changes. These changes
were noted in up to two-thirds of women during treatment
and resolved within 6 months of discontinuation
of treatment.
The PEARL III and extension trials were performed to
investigate long-term use of UA with repeated treatment
cycles. In PEARL III, 209 patients used 10 mg of UA for 12
weeks and results were similar to those of PEARL I and II. In
the PEARL III extension, a subsample of 107 women received
four courses of UA as well as norethisterone acetate between
courses.29 The use of norethisterone acetate between courses
of UA had no effect on progesterone-receptor-modulator-
associated endometrial changes.
Progesterone plays an important role in normal
physiological function of reproductive organs, mammary
glands, and bone, brain and endothelial cells in vessels and
the central nervous system. Studies are needed to evaluate the
effects of SPRMs on other body systems, especially after
prolonged use.
ª 2016 Royal College of Obstetricians and Gynaecologists

Selective estrogen-receptor modulators
Estrogens are known to promote fibroid growth. Anti-
estrogens, like tamoxifen or raloxifene that block estrogen
activity, have the potential for therapeutic activity against
fibroids.30 A meta-analysis including three randomised
controlled trials with 215 participants who used raloxifene
reported inconsistent trial results regarding relief of
symptoms and decrease in fibroid size. In one of the trials,
women received a GnRH analogue in addition to raloxifene.
The authors concluded that there was limited evidence for
the use of selective estrogen-receptor modulators in
fibroid management.30
Aromatase inhibitors
Aromatase is an enzyme that converts androgens to estrogen.
Several small studies have investigated the use of aromatase
inhibitors to reduce uterine fibroid size. A review based on
one trial with 70 women comparing letrozole to a GnRH
agonist (triptorelin) reported equal effectiveness in reducing
fibroid volume; however, GnRH agonists had more adverse
effects.31 Use of aromatase inhibitors in the treatment of
fibroids is still at an experimental stage and is not
recommended for wider clinical use until more information
is available on their effectiveness and safety.31
In Table S1, we provide a descriptive summary of available
medical treatment options for uterine fibroids and their
effects on menstrual loss, fibroid size and quality of life.
Uterine artery embolisation
UAE was introduced in 1994 and is considered an effective
alternative to hysterectomy.32,33 A randomised controlled
trial (UAE versus hysterectomy) of 177 patients from 28
Table 1. Uterine artery embolisation in treatment of fibroids
Author Study design Participants Interventions
Gupta et al.35 Review 7 studies UAE versus abdominal
793 women hysterectomy
UAE versus myomectomy
UAE versus either
myomectomy or
hysterectomy
Hirst et al.37 Retrospective UAE 972
cohort (HOPEFUL) Hysterectomy 762
UAE = uterine artery embolisation.
ª 2016 Royal College of Obstetricians and Gynaecologists
Younas et al.
Dutch hospitals showed a lower rate of major complications
and shorter hospital stay, but an increase in readmission rate,
after UAE.34 An updated Cochrane review in 2014 reporting
on 793 women showed that patient satisfaction with UAE
was similar to that with surgery (myomectomy and
hysterectomy) with quicker recovery and early return to
work. However, UAE was associated with more minor
complications and an almost five-fold increase in the
likelihood of further interventions within 2–5 years. The
long-term follow-up showed no significant difference in
ovarian failure rates.35
One study of 66 women, 26 treated with UAE and 40 with
myomectomy, demonstrated no difference in live birth
rates.35 The most common side effects reported were
postprocedure pain and vaginal discharge but major
complications were rare. Out of more than 100 000
procedures, 12 deaths have been reported worldwide for
UAE, demonstrating an estimated UAE mortality rate of 1 in
10 000 women compared with 3 in 10 000 women
for hysterectomy.36
The HOPEFUL study, which included a 5-year follow-up
after UAE or hysterectomy, showed that both treatments
were safe.37 A meta-analysis including randomised and
nonrandomised clinical trials also suggested that UAE was
associated with a lower rate of major complications
compared with surgery. However, UAE had an increased
risk of reintervention (OR 10.45; 95% CI 2.65–41.14).38 The
results of these studies are summarised in Table 1.
MRI-guided focused ultrasonography
MRgFUS for symptomatic uterine fibroids is an ambulatory,
safe and effective treatment option with the advantage of
preserving the uterus.39,40 High-frequency ultrasound waves
Main results
Higher rate of minor complications in UAE group.
No difference in major complications.
UAE associated with higher rate of need for further interventions.
Insufficient evidence on fertility outcomes but suggestion that
myomectomy may have advantage over UAE.
UAE had shorter hospital stay, reduced need for blood transfusion.
No difference in satisfaction between the interventions at 2 years.
Fewer complications with UAE
Further interventions required in 23% women after UAE.
More information needed on fertility prospects after UAE to
enable expectations to be managed.
37
 Fibroid management
produce heat to denature proteins leading to cell death and
shrinkage of fibroids. MRI is used to target the fibroids and
treatment is monitored by assessing the temperature of
treated tissue. The major advantages of MRgFUS are quick
recovery and very low morbidity. This treatment is not yet
recommended for women wishing to preserve fertility.40 The
Food and Drug Administration approved this treatment in
2004 but the National Institute for Health and Care
Excellence advises its use only in research and
audit settings.32
In one study, 91.5% of 54 patients who completed a fibroid
symptom and quality of life questionnaire, both before and
after MRgFUS treatment, reported satisfaction with
treatment and a significant reduction in fibroid-related
symptoms at 12 months.41
Machtinger et al.42 reported the outcome of telephone
interviews at 33 months ( 15 months) with 81 women
treated with MRgFUS. Most women (69%) did not need
further surgical intervention, but 24% needed further
treatment, especially women with hyperintense fibroids (on
ultrasound the fibroid is whiter than the myometrium); the
OR was 2.96 (95% CI 1.01–8.71).42 Less vascular fibroids
with low signal intensity on MRI were more likely to
respond to treatment than high signal intensity vascular
fibroids.41,42 The incidence of side effects was generally low.
Transient adverse effects included mild skin burn, nausea,
short-term buttock or leg pain and transient sciatic nerve
palsy.41–43 One case of severe skin burn needing skin graft
has been reported.43 A systematic review including 2500
patients in 38 studies concluded that MRgFUS was a safe,
cost-effective, minimally invasive technique for treatment of
fibroids. Further research is needed regarding its effect
on fertility.43
A small clinical trial comparing MRgFUS with UAE in
fibroid treatment found no difference in relief of symptoms;
(a) (b)
Figure 3. Saline sonography for submucous fibroids. (a) Grade 0, (b) Grade 1, (c) Grade 2.
Reproduced with permission from Professor A Abdel-Gadir, www.gynaecologist4u.com.
38
however, MRgFUS was associated with a seven-fold need for
reintervention within 12 months.44
The newer uterus-preserving fibroid treatments need
further research to determine their safety for future child
bearing. Around a quarter (21–28%) of women needed
further intervention after treatment of fibroids with
MRgFUS.41–44
Surgical treatments of fibroids
Surgical management of uterine fibroids may be required in
women with severe pressure symptoms, unresponsiveness to
other therapies (medical, UAE) or in large pedunculated
subserosal or submucous fibroids. Surgical treatment can be
either hysterectomy or myomectomy. The size and location
of the fibroid in the uterus and the desire for future fertility
affects the choice of surgical procedure. Hysteroscopic,
laparoscopic, vaginal or laparotomy routes may be used to
remove fibroids. Myomectomy may alleviate symptoms in
most women with uterine fibroids but complications (e.g.
severe haemorrhage that is difficult to control), may lead to
hysterectomy. The need for careful counselling prior to
surgical interventions cannot be overemphasised.45,46
Myomectomy
Hysteroscopic myomectomy
Hysteroscopic myomectomy for submucous and intracavity
fibroids is an established procedure for heavy menstrual
bleeding, recurrent miscarriages and infertility.45,47
Submucous fibroids have been reported in 6–34% of
women with abnormal uterine bleeding, in 2–7% of
women undergoing infertility investigations and in 1–5% of
asymptomatic women who had hysteroscopic sterilisation.45
Classification systems have been devised to enable accurate
(c)
ª 2016 Royal College of Obstetricians and Gynaecologists

Table 2. ESGE and FIGO classifications for submucous myomas
ESGE classification
Type 0: no myometrial involvement, entirely in endometrium (pedunculated)
Type 1:
<50% myometrial extension (sessile)
<90° angle of myoma surface to uterine wall
Type II:
≥50% myometrial extension (sessile)
≥90° angle of myoma surface to uterine wall
ESGE = European Society of Gynaecological Endoscopy; FIGO = International Federation of Gynaecology and Obstetrics.
description of submucous fibroids (Figure 3) and assist
clinicians in determining the likelihood of successful
hysteroscopic surgery. The most widely used classification
is that adopted by the European Society of Gynaecological
Endoscopy (ESGE);48 the International Federation of
Gynaecology and Obstetrics (FIGO) have a more extensive
classification system for fibroids49 (Table 2 contains details of
the FIGO and ESGE classification systems). There are
limitations in using these classifications to predict operative
outcomes; therefore, another classification was introduced to
improve the outcome in hysteroscopic myomectomy. This is
called STEPW (size, topography, extension, penetration and
lateral wall);50 one multicentre study comparing this
classification system with the ESGE classification system for
hysteroscopic myomectomy indicated that the former system
was better at predicting successful myoma resection and
minimising surgical complications.51 Grade 0 and Grade 1
fibroids can be easily removed hysteroscopically, but
difficulties are likely to be encountered with Grade 2
fibroids as most of the fibroid is in the myometrium. The
thickness of the myometrium between the fibroid and the
Figure 4. Hysteroscopic resection of Grade 0 submucous fibroid using resectoscope.
Reproduced with permission from Professor A. Abdel-Gadir, www.gynaecologist4u.com.
ª 2016 Royal College of Obstetricians and Gynaecologists
Younas et al.
FIGO classification
Submucosal 0 Pedunculated (intracavity)
1 <50% intramural
2 ≥50% intramural
Others 3 Contact endometrium (100% intramural)
4 Intramural
5 Subserosal ≥50% intramural
6 Subserosal <50% intramural
7 Subserosal pedunculated
8 Others (cervical or parasitic)
serosa is an important factor in determining the safety of
hysteroscopic resection in Grade 2 cases.
When fertility is not a concern, the combination of
hysteroscopic fibroid resection with endometrial ablation
may be performed. In one study, 90% of women showed a
decrease in menstrual blood loss at 1-year follow-up.52
One review of different techniques used for hysteroscopic
myomectomy has suggested that resectoscopic slicing is the
gold standard for intracavity fibroids (Grade 0), although there
is no single proven technique for fibroid treatment with an
intramural component (Grades 1 and 2).53 Figure 4 shows a
resection of a Grade 0 submucous fibroid using a resectoscope.
Traditional methods of fibroid resection may be partly
replaced by myolysis (in which an electric current is passed
through a needle to destroy the fibroid) or cryomyolysis
(in which a freezing probe is used in a similar manner).
These techniques can be used for all types of fibroids
through laparoscopic or hysteroscopic routes. They are
associated with less blood loss but have the disadvantages
of providing no tissue for histology, an increased risk of
postoperative adhesions and the need for
39
 Fibroid management

reintervention.52,53 Myolysis can be an alternative to
myomectomy in selected cases.
Laparotomy/laparoscopic myomectomy
Myomectomy can be performed either by the laparoscopic
route or open laparotomy. Myomectomy may reduce
menstrual blood loss and can be considered for women
who want to preserve the uterus.54
Women who have laparotomy for hysterectomy or
myomectomy show similar surgical complications, such
as haemorrhage, unintended repeat surgery and
rehospitalisation, while bladder and bowel injuries are more
frequent with hysterectomy.54 One systematic review showed
that laparoscopic occlusion of the uterine artery is less effective
for the treatment of symptomatic uterine fibroids compared
with myomectomy and uterine artery embolisation.55
Techniques for reducing blood loss during myomectomy
include a preoperative course of GnRH analogue or SPRM, use
of vasoconstriction agents (vasopressin) and tourniquets
during surgery. Laparoscopic myomectomy is considered
the best treatment option for symptomatic uterine fibroids in
women who wish to retain childbearing capacity.56 A
systematic review comparing laparoscopic myomectomy and
open myomectomy showed that laparoscopic procedures were
associated with less postoperative pain or fever and shorter
hospital stay.46 One meta-analysis showed that the
laparoscopic approach is associated with longer operating
times, less blood loss, less postoperative pain and fewer
complications than open conventional myomectomy.57
The choice of open laparotomy or laparoscopic
myomectomy depends upon the availability of facilities and
expertise of surgeons. The size and number of fibroids may
make laparoscopic myomectomy inappropriate.
Conventional open myomectomy has advantages in the
presence of huge, multiple fibroids where a laparoscopic
approach is not possible.58
Hysterectomy
Hysterectomy remains the definitive surgical intervention for
uterine fibroids.58,59 It is the permanent treatment that shows
the highest satisfaction regarding heavy menstrual bleeding
symptoms. In the USA, uterine fibroids are the indication for
one-third of all hysterectomies.59 Hysterectomy is a major
surgical procedure associated with longer hospital stay and
increased time off work. Open conventional hysterectomy,
vaginal hysterectomy and total laparoscopic hysterectomy
can be performed when there is a fibroid uterus. Walsh
et al.60 compared open conventional hysterectomy with total
laparoscopic hysterectomy and reported that the latter
resulted in shorter hospital stay, fewer perioperative

Table 3. Surgical interventions for fibroids

Study
Intervention Author design Participants Intervention details Main results

Hysteroscopic Sardo et al.53 Review of Hysteroscopic resection for

myomectomy surgical submucous fibroids is a gold
techniques standard.
Myomectomy Pundir et al.59 6 studies No difference in major complications.
versus 1520 women Higher blood loss with hysterectomy
Hysterectomy but no difference in blood transfusion
rates.
Min access Bhave et al.46 Review 9 trials 4 trials laparoscopic myomectomy Laparoscopic myomectomy group had
versus open 808 women versus unmodified open myomectomy lower postoperative pain, postoperative
myomectomy 4 trials laparoscopic myomectomy fever and shorter hospital stay
versus mini-laparotomy myomectomy compared with all types of open
1 trial laparoscopy versus myomectomy.
laparoscopically-assisted
mini-laparotomy

Laparoscopic Jin et al.57 Review 6 trials Laparoscopic myomectomy was

versus open 576 women associated with less haemoglobin
myomectomy drop, reduced operative blood loss,
more patients. Fully recuperated at
day 15, diminished postoperative pain
and fewer overall complications, but
longer operating times compared with
open myomectomy for patients with
fibroids. Major complications,
recurrence and pregnancy were similar
between treatments.

40 ª 2016 Royal College of Obstetricians and Gynaecologists


complications and reduced intraoperative blood loss.
However, feasibility of total laparoscopic hysterectomy for
fibroids depends on the size of the fibroids and may be
associated with a longer operating time.60 Surgical
interventions are shown in Table 3.
Conclusion
There is good evidence to support the following suggestions
for fibroid uterus management:
 Medical management and noninvasive techniques (UAE,
MRgFUS) are effective in alleviating the symptoms
associated with uterine fibroids.
 New technologies that have been recently introduced
without adequate assessment require further research
regarding long-term outcomes, especially in the context
of future fertility.
 The surgical options can be considered after careful
selection of patients with informed choice.
 For hysteroscopic myomectomy, traditional resection is
still the gold standard for submucous fibroids.
 There have been reports of successful pregnancies after
UAE and MRgFUS, but further randomised trials are
needed to prove the safety of these treatments in young
women where future fertility is desired.
Contribution to authorship
Two authors (KY and AB) independently reviewed the articles
for relevant evidence and this was cross-checked by EH to
resolve disagreement about a few papers. KY prepared the
initial draft with EH; FM helped with corrections to prepare it
according to the TOG guidance. All four authors were involved
in all the stages of preparation of the final draft.
Disclosure of interests
All authors confirm that we have no conflicts of interest
to disclose.
Acknowledgements
We are thankful to the library staff at Singleton hospital,
Swansea, for their help in obtaining full articles, contacting
authors for further information and translating papers from
other languages.
Special thanks to Professor Ahmed Abdel-Gadir for his
kind permission to use saline sonography images and
hysteroscopic images for submucous fibroids from his
website: www.gynaecologist4u.com.
Supporting Information
Additional supporting information may be found in the
online version of this article at http://wileyonlinelibrary.com/
journal/tog:
ª 2016 Royal College of Obstetricians and Gynaecologists
Younas et al.
Table S1. Pharmacological interventions for treatment of
fibroids.
Single Best Answer questions are available for this article at
https://stratog.rcog.org.uk/tutorial/tog-online-sba-resource
References
1 Parazzini F. Risk factors for clinically diagnosed uterine fibroids in women
around menopause. Maturitas 2006;55:174–9.
2 Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. Best
Pract Res Clin Obstet Gynaecol 2008;22:571–88.
3 Zimmermann A, Bernuit D, Gerlinger C, Schaefers M, Geppert K.
Prevalence, symptoms and management of uterine fibroids. An
international internet-based survey of 21,746 women. BMC Womens
Health 2012;12:6.
4 Ryan GL, Syrop CH, Van Voorhis BJ. Role, epidemiology, and natural
history of benign uterine mass lesions. Clin Obstet Gynecol
2005;48:312–24.
5 Morita Y, Ito N, Hikida H, Takeuchi S, Nakamura K, Ohashi H. Non-invasive
magnetic resonance imaging-guided focused ultrasound treatment for
uterine fibroids–early experience. Eur J Obstet Gynecol Reprod Biol
2008;139:199–203.
6 Qidwai GI, Caughey AB, Jacoby AF. Obstetric outcomes in women with
sonographically identified uterine leiomyomata. Obstet Gynecol
2006;107:376–82.
7 Peddada SD, Laughlin SK, Miner K. Growth of uterine leiomyomata among
premenopausal black and white women. Proc Natl Acad Sci U S A
2008;105:19887–92.
8 Sackett DL, Strauss SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-
Based Medicine: How to Practice and Teach EBM. London: Churchill
Livingstone; 2000.
9 Critical Appraisal Skills Programme (CASP). Making sense of evidence. CASP
UK; 2012 [www.casp-uk.net].
10 Peitsidis P, Koukoulomati A. Tranexamic acid for the management of
uterine fibroid tumors: A systematic review of the current evidence. World J
Clin Cases 2014;2:893–98.
11 Ip PP, Lam KW, Cheung CL, Yeung MC, Pun TC, Chan QK, et al. Tranexamic
acid-associated necrosis and intralesional thrombosis of uterine
leiomyomas: a clinicopathologic study of 147 cases emphasizing the
importance of drug-induced necrosis and early infarcts in leiomyomas. Am J
Surg Pathol 2007;31:1215–24.
12 Rackow BW, Arici A. Options for medical treatment of myomas. Obstet
Gynecol Clin N Am 2006;33:97–113.
13 Venkatachalam S, Bagratee JS, Moodley J. Medical management of uterine
fibroids with medroxyprogesterone acetate (Depo Provera): a pilot study. J
Obstet Gynaecol 2004;24:798–800.
14 Zapata LB, Whiteman MK, Tepper NK, Jamieson DJ, Marchbanks PA, Curtis
KM. Intrauterine device use among women with uterine fibroids-a
systematic review. Contraception 2010;82:41–55.
15 Kim M, Seong SJ. Clinical applications of levonorgestrel-releasing
intrauterine system to gynaecologic diseases. Obstet Gynecol Sci
2013;56:67–75.
16 Sangkomkamhang US, Lumbiganon P, Laopaiboon M, Mol BWJ.
Progestogens or progestogen-releasing intrauterine systems for uterine
fibroids. Cochrane Database Syst Rev 2013;(2):CD008994.
17 Jiang W, Shen Q, Chen M, Wang Y, Zhou Q, Zhu X, et al. Levonorgestrel-
releasing intrauterine system use in premenopausal women with symptomatic
uterine leiomyoma: a systematic review. Steroids 2014;86:69–78.
18 Sayed GH, Zakherah MS, El-Nashar SA, Shaaban MM. A randomized clinical
trial of a levonorgestrel-releasing intrauterine system and a low-dose
combined oral contraceptive for fibroid-related menorrhagia. Int J Gynaecol
Obstet 2011;112:126–30.
19 Lethaby A, Vollenhoven B, Sowter M, et al. Preoperative GnRH analogue
therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane
Database Syst Rev 2006;(2):CD000547.
20 Flierman PA, Oberye JJ, van der Hulst VP, de Blok S. Rapid reduction of
leiomyoma volume during treatment with the GnRH antagonist ganirelix.
BJOG 2005;112:638–42.
41
 Fibroid management
21 Deligdisch L, Hirschmann S, Altchek A. Pathologic changes in gonadotropin
releasing hormone agonist analogue treated uterine leiomyomata. Fertil
Steril 1997;67:837.
22 Bagaria M, Suneja A, Vaid NB, Guleria K, Mishra K. Low-dose
mifepristone in treatment of uterine leiomyoma: a randomised double-
blind placebo-controlled clinical trial. Aust N Z J Obstet Gynaecol
2009;49:77–83.
23 Tristan M, Orozco LJ, Steed A, Ram
ırez-Morera A, Stone P. Mifepristone for
uterine fibroids. Cochrane Database Syst Rev 2012;(8):CD007687.
24 Steinauer J, Pritts EA, Jackson R, Jacoby AF. Systematic review of
mifepristone for the treatment of uterine leiomyomata. Obstet Gynecol
2004;103:1331–6.
25 Shen Q, Hua Y, Jiang W, Zhang W, Chen M, Zhu X. Effects of mifepristone
on uterine leiomyoma in premenopausal women: a meta-analysis. Fertil
Steril 2013;100:1722–6.
26 Horne FM, Blith DL. Progesterone receptor modulators and the
endometrium: changes and consequences. Hum Reprod Update
2007;13:567–80.
27 Donnez J, Tatarchuk TT, Bouchard P, Puscasiu L, Nataliya F, Zakharenko T,
et al. Ulipristal acetate versus placebo for fibroid treatment before surgery.
N Engl J Med 2012;366:409–20.
28 Donnez J, Tomaszewski J, V
azquez F, Bouchard P, Lemieszczuk B, Bar
o F,
et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J
Med 2012;366:421–32.
29 Donnez J, Vazquez F, Tomaszewski J, Nouri K, Bouchard P, Fauser BC, et al.
Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril
2014;101:1565–73.
30 Deng L, Wu T, Chen XY, Xie L, Yang J. Selective estrogen receptor
modulators (SERMs) for uterine leiomyomas. Cochrane Database Syst Rev
2007;(4):CD005287.
31 Song H, Lu D, Navaratnam K, Shi G. Aromatase inhibitors for uterine
fibroids. Cochrane Database Syst Rev 2013;(10):CD009505.
32 National Institute for Health and Care Excellence. Uterine artery
embolization for fibroids NICE interventional procedure guidance 367.
London: NICE; 2011.
33 Committee on Gynecologic Practice. American College of Obstetricians and
Gynecologists. ACOG Committee Opinion. Uterine artery embolization.
Obstet Gynecol 2004;103:403–04.
34 Hehenkamp WJ, Volkers NA, Donderwinkel PF, de Blok S, Birnie E, Ankum
WM, et al. Uterine artery embolization versus hysterectomy in the treatment
of symptomatic uterine fibroids (EMMY trial): peri- and postprocedural
results from a randomized controlled trial. Am J Obstet Gynecol
2005;193:1618–29.
35 Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for
symptomatic uterine fibroids. Cochrane Database Syst Rev 2014;(12):
CD005073.
36 Spies JB, Myers ER, Worthington-Kirsch R, Mulgund J, Goodwin S. Mauro
M; FIBROID Registry Investigators. The FIBROID registry: symptom and
quality-of-life status 1 year after therapy. Obstet Gynecol 2005;106:
1309–18.
37 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;12:1–248.
38 Martin J, Bhanot K, Athreya S. Complications and reinterventions in uterine
artery embolisation for symptomatic uterine fibroids: a literature review and
meta analysis. Cardiovasc Intervent Radiol 2013;36:395–402.
39 Stewart EA, Gostout B, Rabinovici J, Kim HS, Regan L, Tempany CM.
Sustained relief of leiomyoma symptoms by using focused ultrasound
surgery. Obstet Gynecol 2007;110:279–87.
40 LeBlang SD, Hoctor K, Steinberg FL. Leiomyoma shrinkage after MRI-guided
focused ultrasound treatment: report of 80 patients. AJR Am J Roentgenol
2010;194:274–80.
41 Kamp JE, David M, Scheurig-Muenkler C, Hengst S, Beck A. Clinical
outcome of magnetic-resonance-guided focused ultrasound surgery
42
(MRgFUS) in the treatment of symptomatic uterine fibroids. Fortschr
R€ontgenstr 2013;185:136–143.
42 Machtinger R, Inbar Y, Cohen-Eylon S, Admon D, Alagem-Mizrachi A,
Rabinovici J. MR-guided focus ultrasound (MRgFUS) for symptomatic
uterine fibroids. Hum Reprod 2012;27:3425–31.
43 Gizzo S, Saccardi C, Patrelli TS, Ancona E, Noventa M, Fagherazzi S, et al.
Magnetic resonance-guided focused ultrasound myomectomy: safety,
efficacy, subsequent fertility and quality-of-life improvements, a systematic
review. Reprod Sci 2014;21:465–76.
44 Ikink ME, Nijenhuis RJ, Verkooijen HM, Voogt MJ, Reuwer PJM, Smeets AJ,
et al. Volumetric MR-guided high-intensity focused ultrasound versus
uterine artery embolisation for treatment of symptomatic uterine fibroids:
comparison of symptom improvement and reintervention rates. Eur Radiol
2004;24:2649–57.
45 Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol
1990;94:435–8.
46 Bhave Chittawar P, Franik S, Pouwer AW, Farquhar C. Minimally invasive
surgical techniques versus open myomectomy for uterine fibroids.
Cochrane Database Syst Rev 2014;(10):CD004638.
47 Goodwin SC, Bradley LD, Lipman JC. UAE versus Myomectomy Study
Group. Uterine artery embolisation versus myomectomy: a multicenter
comparative study. Fertil Steril 2006;85:14–21.
48 Wamsteker K, Emanuel MH, de Kruif JH. Transcervical hysteroscopic
resection of submucous fibroids for abnormal uterine bleeding: results
regarding the degree of intramural extension. Obstet Gynecol
1993;82:736–40.
49 Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification
system (PALM-COEIN) for causes of abnormal uterine bleeding in non-
gravid women in the reproductive years. Int J Gynaecol Obstet 2011;
113:3–13.
50 Lasmar RB, Barrozo PR, Dias R, Oliveira MA. Submucous myomas: a new
presurgical classification to evaluate the viability of hysteroscopic
surgical treatment–preliminary report. J Minim Invasive Gynecol
2005;12:308–11.
51 Lasmar RB, Lasmar BP, Celeste RK, da Rosa, DB, Depes Dde, B, Lopes, RGC.
A new system to classify submucous myomas: a Brazilian multicentre study.
J Minim Invasive Gynecol 2012;19:575–80.
52 Sabbah R, Desaulniers G. Use of the NovaSure Impedance Controlled
Endometrial Ablation System in patients with intracavitary disease: 12-
month follow-up results of a prospective, single-arm clinical study. J Minim
Invasive Gynecol 2006;13:467–71.
53 Sardo ADS, Mazzon I, Bramante S, Bettocchi S, Bifulco G, Guida M, et al.
Hysteroscopic myomectomy: a comprehensive review of surgical
techniques. Hum Reprod Update 2008;14:101–19.
54 Sawin SW, Pilevsky ND, Berlin JA, Barnhart KT. Comparability of
perioperative morbidity between abdominal myomectomy and
hysterectomy for women with uterine leiomyomas. Am J Obstet Gynecol
2000;183:1448–55.
55 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;93:858–67.
56 Agdi M, Tulandi T. Endoscopic management of uterine fibroids. Best Pract
Res Clin Obstet Gynaecol 2008;22:707–16.
57 Jin C, Hu Y, Chen X, Zheng FY, Lin F, Zhou K, et al. Laparoscopic versus open
myomectomy - a meta-analysis of randomized controlled trials. Eur J Obstet
Gynecol Reprod Biol 2009;145:14–21.
58 Mukhopadhaya N, De Silva C, Manyonda IT. Conventional myomectomy.
Best Pract Res Clin Obstet Gynaecol 2008;22:677–705.
59 Pundir J, Walawalkar R, Seshadri S, Khalaf Y, El-Toukhy T. Perioperative
morbidity associated with abdominal myomectomy compared with total
abdominal hysterectomy for uterine fibroids. J Obstet Gynaecol
2013;33:655–62.
60 Walsh CA, Walsh SR, Tang TY, Slack M. Total abdominal hysterectomy
versus total laparoscopic hysterectomy for benign disease: a meta-analysis.
Eur J Obstet Gynecol Reprod Biol 2009;144:3–7.
ª 2016 Royal College of Obstetricians and Gynaecologists