JOURNAL OF GYNECOLOGIC SURGERY

Volume 40, Number 1, 2024 Special Topic

ª Mary Ann Liebert, Inc.
DOI: 10.1089/gyn.2023.0080

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Surgery for Fibroids in Infertile Women:

The How, the When, and the When Not

Simone Ferrero, MD, PhD,1,2 Fabio Barra, MD,3,4 Giulio Evangelisti, MD,5
Michele Paudice, MD,1,6 and Valerio Gaetano Vellone, MD, PhD7
Downloaded by 200.3.144.15 from www.liebertpub.com at 03/04/24. For personal use only.

Abstract

Uterine fibroids may impact fertility and the outcomes of infertility treatments negatively, depending on the
fibroids’ positions in the uterine wall, their sizes, and their numbers. This article reviews the available data on
managing uterine fibroids in infertile patients. Subserosal fibroids do not affect fertility negatively and generally
do not require treatment. It is advisable to remove submucosal fibroids before infertility treatment or in patients
who have recurrent miscarriages. It is challenging to counsel infertile women with intramural fibroids because of
the lack of a consensus about what should be done. The choice of treating intramural fibroids depends on the
characteristics of the fibroids (such as numbers, sizes, and distances from the endometrial cavity), the repro-
ductive history of the patient, and her willingness to wait until the appropriate time for myometrial healing before
receiving infertility treatments. ( J GYNECOL SURG 40:4)

Keywords: fibroid, hysteroscopic myomectomy, infertility, laparoscopic myomectomy, myomectomy

Introduction wall, their positions (such as in the proximity of the fallopian

D uring the last 10 years, great attention has been gi-
ven to the impact of fibroids on fertility and the out-
comes of in-vitro fertilization (IVF). It is estimated that
fibroids are the only cause of infertility in <3% of couples.1
Data on the impact of uterine fibroids on fertility are obtained
mainly from studies performed in infertile women undergo-
ing IVF. Therefore, the effect of fibroids on natural concep-
tion is mainly unknown. For example, studies conducted in
patients undergoing IVF cannot investigate the impact of fi-
broids on the motility of spermatozoa and on tubal function.
Furthermore, fibroids are heterogeneous gynecologic condi-
tions, and they may have different effects on fertility, de-
pending on the fibroids’ locations in the depth of the uterine
tube), their sizes, and their numbers.
This review describes the potential impact of uterine fi-
broids on fertility and infertility treatment outcomes. The
most-recent evidence on the indications for surgery is de-
scribed.
Assessment of Fibroids in Infertile Patients
A precise assessment of uterine fibroids is required to
determine if surgery is needed and how it should be per-
formed (by hysteroscopy, laparoscopy, or robotic surgery, or
by laparotomy in cases of numerous and large fibroids).
Because of its availability, effectiveness, and cost, trans-
vaginal ultrasound (TVUS) is the first-line tool for assessing

1
Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, Genova, Italy.
2
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of
Genova, Genova, Italy.
3
Unit of Obstetrics and Gynecology, P.O. ‘‘Ospedale del Tigullio’’—ASL4, Metropolitan Area of Genoa, Genova, Italy.
4
Department of Health Sciences (DISSAL), University of Genoa, Genova, Italy.
5
San Paolo Hospital, Savona, Italy.
6
Department of Integrated Diagnostic and Surgical Sciences (DISC), University of Genova, Genova, Italy.
7
Pathology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy.

4
 SURGERY FOR FIBROIDS IN INFERTILE WOMEN
FIG. 1. Transvaginal ultrasonography. The gray box high-
lights the distance between the fibroid and the endometrium.
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the myometrium and diagnosing uterine fibroids. TVUS
enables the surgeon to establish the position of the fibroids
within the uterine wall, identifying subserosal, intramural,
and submucosal fibroids. TVUS also enables the surgeon to
estimate the sizes and volumes of the fibroids. For infertile
women and for those wishing to conceive, TVUS can be
used to calculate the distance between the intramural fibroid
and the endometrium (Figs. 1 and 2). In addition, TVUS can
be used to estimate the distance between the fibroid and the
uterine serosa in patients with submucosal fibroids under-
going hysteroscopic myomectomy. Transabdominal ultra-
sound can be used to measure large subserosal fibroids that
FIG. 2. Transvaginal ultrasonography used to estimate the
distance between the fibroid and the endometrium (top) and
between the fibroid and the uterine serosa (bottom).
5
may be difficult to visualize fully with TVUS. Three-
dimensional–TVUS may be used to define the characteris-
tics of submucosal fibroids better, but it is essential to
determine the degree of protrusion of the fibroids into the
endometrial cavity.2
Saline infusion sonohysterography (SIS) and hystero-
scopy can be equally useful for diagnosing submucosal fi-
broids.3,4 SIS can simultaneously define the extent to which
submucosal fibroids protrude into the uterine cavity and the
depth of myometrial penetration. Therefore, SIS provides
information similar to those obtained by combining hys-
teroscopy and TVUS. In infertile patients, hysteroscopy has
the advantage of showing intracavitary pathologies (such as
synechiae and endometritis).
Magnetic resonance imaging shows the presence and
characteristics of uterine fibroids effectively,5 but its routine
use is not cost-effective.
A detailed preoperative evaluation enables identification
of the correct surgical procedure, decreases the risk of
complications, and contributes to successful completion of
the surgery. The objectives of the preoperative assessment
are: to identify all uterine fibroids; to record the locations
and positions of the fibroids; for submucosal fibroids, to
estimate the distance between the nodule and the uterine
serosa; and, for intramural fibroids, to estimate the distance
between the nodule and the endometrium (Fig. 2).
How Do Fibroids Affect Fertility and Implantation?
Fibroids that distort the endometrial cavity affect im-
plantation and pregnancy adversely by primarily mechanical
mechanisms. They may thin the endometrium immediately
above the fibroid and modify the blood flow to the endo-
metrium.6 Sometimes, fibroids distorting the uterine cavity
can hamper sperm migration through the cervix and to the
ostia of the fallopian tubes. Fibroids can alter uterine peri-
stalsis,7,8 thus, influencing gamete and embryo transport.
Fibroids produce cytokines and growth factors that affect
the adjacent endometrium. Basic research studies have
demonstrated that paracrine signals from fibroids may have
a negative impact on implantation.9 HOXA10, HOXA11, and
basic transcriptional element-binding protein 1 (BTEB1),
molecular markers of endometrial receptivity, may have
decreased expression in patients with uterine fibroids. No-
tably, endometrial expression of these molecules is modified
not only in the portion of the uterus above the fibroid but in
the whole endometrium.10
In addition, leukemia inhibitory factor (LIF) has de-
creased levels in the endometria of patients with uterine
fibroids.11 Bone morphogenetic protein–2 (BMP-2) belongs
to the transforming growth factor–b (TGF-b) superfamily of
proteins and is crucial in preparing the endometrium for
implantation. BMP-2 regulates the expression of HOXA10
and LIF in endometrial stromal cells. TGF-b3 is a growth
factor involved in controlling the growth and proliferation
of cells. Fibroids produce a significantly higher quantity of
TGF-b3 than normal myometrium. Furthermore, the
amount of TGF-b3 produced by fibroids is correlated with
their volume. Therefore, in patients with large fibroids
adjacent to the uterine cavity, higher quantities of TGF-b3
reach the endometrium. TGF-b3 reduces the receptivity
of human endometrium to BMP-2 by decreasing the
 6 FERRERO ET AL.
expression of BMP receptors.12 TGF-b3 blockade in
myoma-exposed endometrial stromal cells restores BMP-2
signaling and restores BMP’s upregulation of HOXA10 and
LIF expression.13
Submucosal fibroids
There is evidence that submucosal fibroids are associ-
ated with lower pregnancy, implantation, and live birth
rates in patients undergoing IVF.14,15 The standard of care
is to remove, by hysteroscopy, intracavitary fibroids and
fibroids that project into the uterine cavity. However, a
Cochrane review found that it is uncertain if surgical ex-
cision of submucosal fibroids improves pregnancy rates.16
Hysteroscopic myomectomy is minimally invasive, and, in
some cases, it is possible to confirm the diagnosis and treat
the myoma during the same procedure in an outpatient
setting.17 Furthermore, hysteroscopic myomectomy mini-
mizes the damage to the uterine wall; therefore, patients
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are allowed to try to conceive quickly after surgery
(in general, 3 months after hysteroscopic myomectomy).
Finally, during hysteroscopic myomectomy, it is possible
to treat additional pathologies of the uterine cavity (such
as polyps and uterine septa) and obtain endometrial bi-
opsies (such as for the diagnosis of endometritis or to
exclude malignancy).
Submucosal fibroids can be excised by different hystero-
scopic techniques—slicing; morcellation; and cutting the
pedicle—in an office setting. The classical hysteroscopic
resection with the slicing technique (Fig. 3) is accomplished
by performing repeated passages of the cutting loop through
the lesion. It is advisable to start the excision at the top of the
fibroid and then progress toward its base. The loop must be
placed beyond the lesion, and the cutting should be performed
during the return movement toward the lens18 (Fig. 3).
A cold loop and resection combination can be used
(Fig. 4) when part of the fibroid infiltrates the myome-
trium.19,20 Initially, the intracavitary portion of the fibroid is
removed using the conventional slicing technique. When the
cleavage plane between the fibroid and the myometrium is
identified, the cold loop is inserted into the cleavage plane
and repeatedly applied along the surface of the fibroid to
perform blunt dissection. After detachment, the intramural
part of the fibroid is excised by the slicing technique. Al-
ternatively, submucosal fibroids may be excised by intra-
uterine morcellation performed with tissue-removal
systems, which may be superior regarding the learning curve
and operative time.21
Complications are rare during hysteroscopic myo-
mectomy. They include uterine perforation, bleeding, in-
fection, and venous intravasation. In addition, intrauterine
adhesions may occur after hysteroscopic myomectomy.
Therefore, a diagnostic hysteroscopy should ideally be
performed before infertility treatment. The duration of
endometrial-wound recovery varies according to the com-
plexity of the surgery. In general, fertility treatments can be
performed 3 months after surgical interventions.
Intramural fibroids
There is growing evidence that intramural fibroids have a
negative effect on conception and the outcome of IVF in
infertile women.14,15 In addition, intramural fibroids, al-
though not distorting the uterine cavity, decrease the preg-
nancy and live birth rates after IVF.22,23 Intramural fibroids
comprise a heterogeneous category because they have var-
iable numbers, sizes, distances from the endometrial cavity,
and positions in the uterus. Because of these characteristics
of intramural fibroids, performing studies with homoge-
neous populations is challenging.
FIG. 3. Hysteroscopic re-
section of International Fed-
eration of Gynecologists and
Obstetricians (FIGO) type
1 fibroid using the classic
slicing technique. The exci-
sion starts at the top of the
fibroid and then progresses
toward its base.
 SURGERY FOR FIBROIDS IN INFERTILE WOMEN
FIG. 4. Hysteroscopic re-
section of International Fed-
eration of Gynecologists and
Obstetricians (FIGO) type 2
fibroid, using a combination
of an electric cutting loop
and a mechanical cold loop.
The cold loop is inserted into
the cleavage plane along the
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surface of the fibroid, and
blunt dissection is performed.
The demonstration that fibroids can affect IVF outcomes
negatively is insufficient to prove that myomectomy improves
fertility or infertility treatment outcomes. The choice of ex-
cising intramural fibroids in infertile patients is complex be-
cause there is no clear guideline. Several variables must be
considered. The patient’s symptoms (in particular menorrha-
gia) must be considered. The number of previous reproductive
failures (both failed implantation or early miscarriage) may
induce a surgeon to perform surgery. However, the time to
perform surgery (including the waiting list, if present) and the
time required after surgery for myometrial healing (at least 6
months) must be balanced with the patient’s age and ovarian
reserve. Per this perspective, oocyte or embryo cryopreserva-
tion may be considered before performing myomectomy.
Finally, considering that fibroids produce cytokines and
growth factors that may affect the adjacent endometrium
and the implantations, the sizes of the fibroids, and the
distances between the fibroids and the endometrial cavity
should be considered in the decision to perform myo-
mectomy. Small fibroids remote from the uterine cavity are
unlikely to have a significant reproductive effect. In con-
trast, large fibroids close to the endometrium may affect
endometrial receptivity significantly.24
When surgery is judged to be required, the choice of the
surgical approach should be similar to the approach used for
noninfertile patients, and the surgeon should consider the
following variables: numbers and sizes of fibroids; the sur-
7
geon’s experience; and the patient’s preference. Ideally,
laparoscopic or robotic-assisted myomectomy should be
preferred to minimize the risk of postoperative adhesions that
may affect fertility negatively. Minimally invasive surgery
has several advantages over laparotomic myomectomy, in-
cluding less postoperative pain, a shorter hospital stay, and
faster recovery. However, no difference has been seen be-
tween laparoscopic and laparotomic myomectomy regarding
reproductive outcomes.25
The most-frequent complications of laparoscopic/robotic
myomectomy include myometrial hematoma, excessive
blood loss, and morcellation accidents.26 A minimally in-
vasive approach is contraindicated when there is a suspicion
of malignancy. In all other patients, the decision to perform
a laparoscopic/robotic myomectomy depends on the skill of
the surgeon and his/her ability to suture the myometrial
defect quickly. In general, it is advisable to perform a la-
parotomic myomectomy when there are more than 4 fibroids
at different uterus sites, requiring numerous incisions, and
when there is a fibroid with a diameter >10–12 cm.25
Subserosal fibroids
Subserosal fibroids do not affect fertility negatively be-
cause they are remote from the uterine cavity,14 and,
therefore, in general, they do not need to be treated in in-
fertile patients. However, huge subserosal fibroids can cause
 8 FERRERO ET AL.
abdominal pain during pregnancy. In addition, if large pe-
dunculated fibroids become torted during pregnancy, the
patient may experience severe acute abdominal pain and
require surgery during pregnancy. Therefore, surgical
treatment of large subserosal fibroids may be considered
before conception. These fibroids can usually be treated
easily by laparoscopic or robotic surgery; however, in-bag
morcellation may be time-consuming because of the large
volume of these fibroids.
Conclusions
When a clinician must decide to treat fibroids in infertile
women, the decision depends on several variables, including
symptoms (such as heavy menstrual bleeding and pain),
characteristics of the fibroids (such as locations, numbers,
and sizes), and features of the patients (such as age, ovarian
reserve, and reproductive history). Potential benefits of
surgery must be balanced with possible complications of
surgery and scarring of the uterine wall after myo-
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mectomy.26 During surgery, it is crucial to identify the
correct dissection plane, the fibroid pseudocapsule
(a neurovascular bundle surrounding the fibroid that sepa-
rates the fibroid from the normal myometrium).26 Pre-
servation of the pseudocapsule may be relevant for
myometrial healing.27
It is well-established that subserosal fibroids do not affect
fertility negatively and do not require treatment. In con-
trast, all submucosal fibroids should ideally be treated in
women wishing to conceive (independently from the his-
tory of infertility).
It is advisable to remove submucosal fibroids before IVF
or in cases of recurrent miscarriage. It is complicated to
counsel women with intramural fibroids who desire to
conceive or who are undergoing infertility treatments be-
cause of the lack of a consensus on what should be done.
Furthermore, intramural fibroids comprise a dynamic
condition. While these patients try to conceive, the fi-
broids may change characteristics, such as sizes and dis-
tances from the endometrial cavity. These changes in the
fibroids may impact fertility and modify the indications
for surgery. Generally, myomectomy may be considered
for patients with large intramural fibroids (> 5 cm),
mainly, if embryo transfer failed or there were miscar-
riages, and if the patient accepts to wait the appropriate
time for myometrial healing before receiving infertility
treatments.
Authors’ Contributions
Drs. Ferraro, Barra, and Vellone conceptualized this
study. Dr. Ferraro was responsible for the methodology, and,
together with Dr. Barra, prepared the original draft of this
article. Drs. Giulio, Paudice, and Vellone reviewed and
edited it.
Authors Disclosure Statement
No financial conflicts of interest exist.
Funding Information
No funding was provided for this project.
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Address correspondence to:
Simone Ferrero, MD, PhD
Academic Unit of Obstetrics and Gynecology
Istituti di Ricovero e Cura a Carattere Scientifico
Ospedale Policlinico San Martino
Largo R. Benzi 1
16132 Genova
Italy
E-mail: simoneferrero@icloud.com