The Impact and Management of
Fibroids for Fertility
An Evidence-Based Approach
Xiaoxiao Catherine Guo, BS, James H. Segars, MD*
Uterine fibroids, or leiomyoma, are benign tumors of the uterus that may cause severe
pain, bleeding, and infertility.1Fibroids affect a woman’s quality of life, as well as her
fertility and obstetric outcomes. Fibroids affect approximately 35% to 77% of
reproductive-age women,2–4although the real prevalence is much higher because
many fibroids may be asymptomatic. Nearing age 50, this likelihood may increase
to 70% to 80% depending on the patient’s ethnicity.3Of particular note, Peddada
and colleagues5found that fibroid growth rates declined for white women older
Disclosure: The authors report no conflict of interest.
Reprint Requests: James H. Segars, MD; Xiaoxiao Catherine Guo, BS.
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health, 10 Center Drive,
Building 10 CRC 1-3140, MSC 1109, Bethesda, MD 20892-1109, USA
* Corresponding author.
E-mail address: email@example.com
? Leiomyoma ? Infertility ? Assisted reproductive technology (ART) ? Myomectomy
?Hysteroscopy ?Minimally invasive gynecologic surgeries
? Magnetic resonance–guided focused ultrasound (MRgFUS)
?Uterine artery embolization (UAE)
? Whenselectingatreatmentplan forsymptomatic uterinefibroids,thefibroidlocation,size,
and number will often dictate the proper intervention.
? Myomectomy is usually the best option for women desiring future fertility.
? Currently available medical therapies for uterine fibroids reduce symptoms,but are limited
and most are confined to short-term use.
? Initial fertility studies on magnetic resonance–guided focused ultrasound and uterine
artery embolization are encouraging, but randomized controlled trials need to be done.
At this time, uterine artery embolization is not recommended for women desiring to
? Additional options for treating symptomatic uterine fibroids, including nonsurgical and
preventative medical therapies, are still needed.
Obstet Gynecol Clin N Am 39 (2012) 521–533
0889-8545/12/$ – see front matter Published by Elsevier Inc.
than 35 years but did not decline for black women of the same age. Fibroids are
a public health concern and have been estimated to cost the US health care system
up to $34.4 billion per year.6
In this review, we examine the medical and surgical therapies that women and their
providers may choose to treat uterine fibroids, paying particular attention to preg-
nancy rates and obstetric outcomes. When selecting a treatment, individual patient
preferences should be taken into account, such as desire for future childbearing.
The fibroid location, size, and number are essential considerations.
Aside from traditional surgical therapies such as hysterectomy and myomectomy,
minimally invasive gynecologic surgeries, uterine artery embolization (UAE), and
magnetic resonance–guided focused ultrasound (MRgFUS) are increasing in popu-
larity. The preliminary data using these newer therapies are encouraging. However,
patients should be counseled that any uterus-sparing technique has the potential
for fibroid recurrence.
FIBROIDS AND INFERTILITY
Fibroids are present in 5% to 10% of infertile patients and may be the sole cause of
infertility in 1% to 2.4%.7,8Fibroids may cause infertility by obstructing the fallopian
tubes and impairing gamete transport. It is now clear that the critical factor may be
distortion of the endometrial cavity, causing abnormal endometrial receptivity,
hormonal milieu, and altered endometrial development9,10(see later). However, the
issue of whether fibroids can be the sole cause of infertility has been poorly under-
stood.7This is because of the lack of prospective, randomized, and controlled studies
separating out other infertility factors.8A randomized and prospective study evalu-
ating spontaneous conception in infertile women with and without fibroids was con-
ducted by Bulletti and colleagues11in 1999. The authors found a significant
discrepancy in pregnancy rate for infertile women (11% with fibroids vs 25% without
fibroids). Removing the fibroids increased the pregnancy rate from 25% to 42%.This
study supports fibroids influence infertility.
EFFECT OF FIBROIDS ON ASSISTED REPRODUCTIVE TECHNOLOGIES
The relationship between fibroids andinfertility has been elucidated through numerous
studies on patients who used assisted reproductive technologies (ART), which have
been summarized in several meta-analyses and systematic reviews.12–15Although
abnormal gamete transfer and blockage of fallopian tubes are circumvented by
ART, fibroids may also compromise fertility by altering the endometrial receptivity,9,10
thus negatively affecting embryo implantation and lowering the chances for
Fibroid location is of critical importance in ART outcomes.7Submucosal fibroids, in
particular, significantly reduce implantation and pregnancy rates of ART. Submucosal
fibroids that distort the uterine cavity have been found to carry a relative risk of 0.3 for
pregnancy and 0.28 for implantation after ART,12,13,16compared with infertile women
without fibroids. Other authors have also demonstrated reduced success following
ART with an odds ratio of 0.3 for conception and 0.3 for delivery in the presence of
submucosal fibroids.14The effect is not as pronounced for intramural fibroids with
an odds ratio of 0.62 for implantation rate and 0.7 for delivery rate per transfer cycle.15
Similarly, Somigliana and colleagues14determined an odds ratio of 0.8 for conception
and 0.7 for delivery with intramural fibroids. Subserosal fibroids have negligible impact
on fertility with ART.11,14
Guo & Segars
FIBROIDS AND PREGNANCY
The reported incidence of fibroids in pregnancy ranges from 0.1% to 10.7% of all
pregnancies.17–19A study by De Vivo and colleagues20reported that 71.4% of fibroids
grew during the first and second trimesters, whereas 66.6% grew between the second
and third trimesters. Fibroids during pregnancy are more likely to be encountered in
patients who are 35 years of age and older, nulliparous, or African American.14,18,21
Although most pregnancies with fibroids are uneventful, fibroids increase the risk of
During pregnancy, fibroids may grow quickly, causing intense pain. However,
fibroid regression after live birth has been demonstrated in 72% of women, with
a greater than 50% reduction in fibroid volume between early gestation and 3 to 6
months postpartum.22Women who had a miscarriage or used progestins after
delivery experienced less fibroid regression,22but this difference was not present
in women who delivered by cesarean, used other hormonal contraceptives, or
A patient with fibroids who is considering pregnancy should be evaluated with
a pelvic examination and an ultrasound to delineate the location and size of any
fibroid(s). For patients pursuing assisted reproduction, a preconception saline infusion
sonogram can be extremely helpful in such cases to identify submucosal fibroids.4,7
Alternatively, an office hysteroscopy can be used to assess the endometrial cavity.
Once a patient becomes pregnant, determining the fibroid location relative to the
placenta and cervical canal may be helpful in assessing the risk of placental
FIBROIDS AND OBSTETRIC OUTCOMES
Complications occur in approximately 10% to 40% of pregnancies in the presence of
fibroids.23,24Fibroids may contribute to miscarriage, cesarean section, premature
labor, malpresentation of the fetus, and postpartum hemorrhage (Table 1). Other
uncommoncomplications includepelvic pain causedby red or carneous degeneration
of the fibroid, low Apgar scores in the neonate, renal failure, fetal limb anomalies, and
hypercalcemia.25The risk of developing complications during pregnancy increases if
the fibroids are greater than 3 cm. However, women with fibroids larger than 10 cm
can achieve vaginal delivery approximately 70% of the time.18
Risk of obstetric outcomes in women with symptomatic uterine fibroids
Outcome Increased Risk with Fibroids
All values are odds ratios unless stated otherwise.
Data from Refs.13,24,54–56
Impact and Management of Fibroids for Fertility
Fibroids clearly increase the risk of pregnancy loss. Compared with women without
fibroids, women with fibroids in all locations have a relative risk of spontaneous abor-
tion of 1.678. Women with fibroids pursuing ART also have a significantly lower
ongoing pregnancy/live birth rate, with a relative risk of 0.697 compared with controls,
in part because of miscarriages. Additionally, the risk of pregnancy loss correlated
with fibroid location. Specifically, submucosal and intramural fibroids had notably
higher rates of spontaneous abortion and notably lower rates of live births. However,
subserosal fibroids had no significant impact.12Multiple fibroids may further increase
the miscarriage rate.13,26
Fibroids have also been associated with malpresentation of the fetus. An odds ratio
of 3.98 for breech presentation has been calculated for women with fibroids compared
with women without fibroids.17,23Fetal malpresentation may increase the probability
of a cesarean section, which subsequently increases the risk of maternal morbidity.
Last, fibroids may increase the risk of preterm labor. This is particularly true if the
fibroids are large, if there are multiple fibroids, or if placentation occurs next to or over-
lying a fibroid. Other reports concur that fibroids increase the risk of preterm labor but
do not agree on the increase in the risk of preterm birth. A 2009 meta-analysis by Olive
and Pritts12showed no significant disparity in preterm delivery rates among patients
with fibroids in all locations compared with controls.
Current medical treatment of fibroids includes progestins, oral contraceptives,
nonsteroidal anti-inflammatory drugs, tranexamic acid, and gonadotropin-releasing
hormone agonists (GnRHa). Progesterone receptor agonists, selective progesterone
receptor modulators, and aromatase inhibitors have also been investigated as alterna-
tives to surgery. Some of these medical therapies are limited by undesirable side
effects (Table 2). Progestins, nonsteroidal anti-inflammatory drugs, and oral contra-
ceptives s have been used off-label for temporary management of bleeding; however,
they are unlikely to affect fibroid volume. GnRHa reduced fibroid volume by 35% to
65% in 3 months27and induced amenorrhea but is typically used preoperatively to
postpone surgery in a severely anemic patient or possibly to reduce uterine volume
and to facilitate a vaginal approach to hysterectomy.28More recently, Parsanezhad
and colleagues29reported that letrozole at 2.5 mg/d reduced fibroid size by 45.6%
versus triptorelin, a GnRHa, which reduced fibroid size by only 33.2%. The antiproges-
tins mifepristone and ulipristal acetate also effectively induce amenorrhea and reduce
fibroid volume. Donnez and colleagues30,31recently published 2 studies of ulipristal
acetate as a treatment of fibroids. In one study, uterine bleeding was effectively
controlled in 91% and 92% of women taking a 5 mg and 10 mg daily dose of ulipristal
acetate, respectively, compared with 19% in women taking placebo.31In the second
study, Donnez and colleagues30daily oral doses of ulipristal acetate (at both 5 mg and
10 mg) had comparable clinical outcomes and reduction in fibroid volume compared
with once-monthly injections (3.75 mg) of the GnRHa leuprolide acetate. Further, this
reduction was sustained for 6 months after ulipristal acetate was stopped.30The
selective progesterone receptor modulator asoprisnil also causes a significant reduc-
tion in bleeding and size, and the effect seems to persist for 3 months.32,33It should be
noted, however, that some of these agents have been associated with altered endo-
metrial pathologic conditions. However, the long-term significance of the endometrial
changes is not clear at present.
An effective long-term medical therapy for uterine fibroids would reduce heavy
uterine bleeding and fibroid/uterine volume without excessive side effects. To date,
Guo & Segars
currently approved treatments reduce symptoms only temporarily, and although new
agents are in development, the ideal medical therapy has remained elusive.
There are different approaches to myomectomy: laparoscopically, abdominally (lapa-
rotomy), robotically, or hysteroscopically. Although myomectomies have traditionally
been performed by laparotomy, the first myomectomy by laparoscopy was performed
by Dr Kurt Semm in 1979. This approach eventually became mainstream in the early
1990s. Today, minimally invasive myomectomy approaches have become the
preferred approach by patients and providers alike.
Submucosal fibroids, in particular, lend themselves well to a hysteroscopic surgical
approach. Clinicians must determine the location, number, and percentage of the
fibroids that are located in the uterine cavity. The Wamsteker classification system,
used by the European Society of Gynecological Endoscopy, can be helpful in deter-
mining the probability of successful removal of submucosal fibroids by hysteroscopic
myomectomy.34Clinicians may also use the newer STEPW (size, topography, exten-
sion, penetration, wall) classification system proposed by Lasmar and colleagues in
2005.34Hysteroscopic resection of submucosal fibroids offers minimal complications
and rapid recovery times. Because there have been no reported cases of uterine
rupture with this technique,28patients may attempt a vaginal delivery after hystero-
Pregnancy Rates and Obstetric Outcomes after Myomectomy
Myomectomy is most often used for women who desire future fertility. Pregnancy
rates have reached 50% to 60% after both laparoscopy and abdominal myomectomy,
with good obstetric outcomes.35Myomectomy, however, does not eliminate symp-
toms permanently and is associated with surgical risks and complications (eg, loss
of blood, long procedure and hospital stay, postoperative morbidity). Postoperative
adhesions are of particular concern, because it is certainly possible that they may
negatively impact future fertility.
Success in myomectomy depends on the location of fibroids. Intramural and sub-
serosal fibroids are often resected using a laparoscopic or abdominal myomectomy.
After undergoing an abdominal myomectomy, the risk of uterine rupture in pregnancy
is low (w0.002%). Even though the incidence of uterine rupture is lower than that after
a previous cesarean (w0.1%), patients with transmural incisions after abdominal or
laparoscopic myomectomy generally undergo cesarean delivery.28
Myomectomy is of proven benefit. In a study by Casini and colleagues,36patients
who underwent myomectomy for resection of submucosal fibroids had higher clinical
pregnancy rates compared with patients with fibroids who did not undergo surgery
(43.3% for operated vs 27.2% for unoperated).36The likelihood of live births and spon-
taneous abortions was similar in both groups. Summarily, data from randomized and
controlled studies on the subject suggest that clinical pregnancy, live birth, and spon-
taneous abortion rates will normalize over time in women with submucosal fibroids
after myomectomy compared with infertile women without fibroids.
Myomectomy is also beneficial for infertile patients with intramural fibroids. Casini
and colleagues36found higher pregnancy rates in patients with intramural fibroids
who underwent myomectomy, as opposed to those who did not (56.5% vs 41%,
Impact and Management of Fibroids for Fertility
Summary of current medical treatment options for women with symptomatic uterine fibroids
Medications Decreased Size/Volume Decreased BleedingSide EffectsUse
ProgestinsNo Yes Induces uterine fibroid
Oral contraceptivesNo YesMinimalOff-label
NoYes, 36% decrease found in
Tranexamic acidNoYes Recently approved by Food and
Drug Administration, Can be
used for women with or without
GnRHaYes, 35%–65% reduction in
fibroid volume, mostly
occurring in the first 3 mo
Yes, in 97% of patients by
6 mo. However, menses
resumed in most patients
4–8 wk following
Controlled uterine bleeding in
89% of patients for 3.75 mg
monthly injection of
Estrogen deprivationOnly preoperatively
MifepristoneYes, 48.1% and 39.1%
reduction in fibroid
volume for 5 and 10 mg
Yes, induced amenorrhea in
60%–65% of patients27
Linked with endometrial
Long-term use is limited by
potential for endometrial
hyperplasia, 28% incidence59
Guo & Segars
(CDB 2914, aka ulipristal
Yes, 36% and 21% reduction
in fibroid volume for 10 and
20 mg dose of CDB-2914,
36% and 42% median
reduction in fibroid volume
for 5 and 10 mg dose of
ulipristal acetate, taken daily
for 3 mo. This reduction was
maintained for 6 mo in most
Yes, amenorrhea in 81% and
90% of patients for 5 and
10 mg dose of CDB-2914,
Amenorrhea in 73% and 82%,
controlled bleeding in 91%
and 92% of patients for
5 and 10 mg dose of ulipristal
acetate, respectively, taken
daily for 13 wk31
Linked with altered
In Europe, ulipristal acetate is
used to treat bleeding
Yes, 36% reduction in fibroid
volume for 25 mg dose of
Yes, suppressed uterine
bleeding in 28%, 64%, and
83% of patients for 5, 10,
and 25 mg dose of asoprisnil,
Suppressed bleeding in 91% of
patients for 25 mg dose of
Asoprisnil taken for 12 wk32
Linked with altered
Yes, 45.6% reduction in fibroid
NoLinked with ovarian
Data from Refs.27,29–32,57–60
Impact and Management of Fibroids for Fertility
respectively). As stated previously, subserosal fibroids are acknowledged as having
little impact on fertility.7
Effect of Myomectomy on ART Outcome
As discussed previously, evidence suggests that fibroid size before ART can cause
lower implantation rates. In patients with intramural fibroids greater than 50 mm, myo-
mectomy before IVF has been shown to positively impact pregnancy outcomes.37A
study by Bulletti and colleagues37in 2004 compared 84 women who chose to undergo
myomectomy before IVF with 84 women who started IVF but did not undergo surgery.
The women who did undergo surgery had a 25% rate of delivery and a clinical preg-
nancy rate of 33%, compared with 12% and 15% in the nonsurgical group.37This
study suggested that myomectomy before ART is likely to improve pregnancy
outcomes in infertile patients with submucosal fibroids and with intramural fibroids
greater than 5 cm.37For subserosal fibroids, myomectomy before ART does not affect
Myomectomy During Pregnancy
There is currently a lack of large, randomized, and controlled studies of the safety and
efficacy of myomectomies during pregnancy and cesarean sections. Thus, myomec-
tomy during pregnancy may be useful only in certain specific instances, such as early
in pregnancy and when fibroids are large, growing rapidly, and causing recurrent pain.
However, the risk of pregnancy complications including miscarriage or fetal loss is of
Recurrence and Reintervention after Myomectomy
Fibroid recurrence has been reported in 15% to 51% of cases up to 5 years after myo-
mectomy.38This large variability was probably the result of the ethnic diversity of the
study groups and of different criteria and methods used to diagnose recurrence. In the
past, the probability of a subsequent surgery was thought to be based on the patient’s
age during the first myomectomy but may actually be more affected by parity as the
cumulative probability of recurrence is decreased if a woman has children after
GnRHa Pretreatment Before Myomectomy
GnRHa treatment before a myomectomy has been proposed as a means to decrease
fibroid volume and, thus, enhance removal while reducing complications. Vercellini
and colleagues39showed that GnRHa pretreatment had negligible effects on blood
loss, postoperative morbidity, hospital stay, and operating time. Others27have
expressed concern that GnRHa pretreatment may increase the risk of recurrence.
MRgFUS for leiomyoma treatment was approved in 2004 by the Food and Drug
Administration. Initial results in symptom management are encouraging, and
outcomes may be enhanced by GnRHa pretreatment.38Rabinovici and colleagues40
reported 54 pregnancies in 51 women after MRgFUS, with a mean time to concep-
tion of 8 months after procedure with a 41% live birth rate. Of the women who
conceived, 28% had a spontaneous abortion and 64% delivered vaginally. Of the
women who delivered, there were 6.7% (1 of 15) preterm births, 2 cases of placenta
previa (9%), and 93% term births.40Although the preliminary results are reassuring,
Guo & Segars
women who become pregnant after MRgFUS should be carefully followed during
UAE (aka uterine fibroid embolization [UFE]) is a minimally invasive procedure that
involves cutting off the blood supply of the fibroids. UFE was introduced by Ravina
and colleagues41in 1995. In the past decade, UAE has become popular as a success-
ful alternative to surgery. Clinical outcomes with UAE are comparable to surgery.35
UAE offers low rates of serious complications42–44and rapid procedure and recovery
times. Early studies have shown that 80% to 95% of patients experienced improve-
ment in their symptoms.42Fibroids have also been reported to shrink by about 44%
in volume in 3 months.43As of August 2008, the American College of Obstetricians
and Gynecologists has even recognized UFE as having “level A evidence” to support
that it is safe and effective in appropriately selected women.45
Pregnancy Rates and Obstetric Outcomes after UAE
UAE is not recommended for women with fibroids who desire future fertility, in part
because of reported cases of transient and permanent amenorrhea. The reduction
in menstrual flow raises the concern for endometrial damage that may contribute to
abnormal placentation and/or reduced ovarian function or failure.46However, the inci-
dence of amenorrhea has been found to occur in less than 5% of patients28,44and is
clearly exacerbated by advanced age or perimenopausal status.
Goldberg and colleagues47suggested that pregnancies after UAE are at risk for
malpresentation, preterm birth, cesarean section, and postpartum hemorrhage
compared with the general population without fibroids. Homer and Sarodigan48found
that rates of miscarriage, cesarean section, and postpartum hemorrhage were
increased after UFE compared with control pregnancies with fibroids. Mara and
colleagues49used hysteroscopy to evaluate 127 patients at 3 to 9 months after
UAE (mean age 35.1 years) and found that 59.8% of the women had an abnormal
endometrium with tissue necrosis (40.9%), intracavitary myoma protrusion (35.4%),
endometrium “spots” (22.1%), intrauterine synechiae (10.2%), and “fistula” between
the uterine cavity and intramural fibroid (6.3%). Necrosis and/or hyalinization was
found in 35.4% of patients, even though 78% were asymptomatic.49This high rate
of intrauterine pathologies after UAE may help explain the reported increased risk of
in early pregnancy loss. Because UAE is still relatively new, long-term effects on
fertility and pregnancy outcomes have not yet been established, and more research
is needed with larger cohorts from multiple centers.
Recurrence and Reintervention after UAE
Two large randomized trials, the Randomised comparison of uterine artery embolisa-
tion (UAE) with surgical treatment in patients with symptomatic uterine fibroids
(REST)50and Uterine artery embolization vs hysterectomy in the treatment of symp-
tomatic uterine fibroids (EMMY)51trials, addressed the safety of UAE. The REST trial
was composed of patients who had undergone myomectomy, hysterectomy, and
UAE in the United Kingdom. Patients who had undergone surgery and UAE had similar
improvements in symptoms after 5 years, but reintervention was more likely after UAE
with a fibroid recurrence rate of 32%.50The EMMY trial, conducted in the Netherlands,
compared UAE and hysterectomy, concluding that symptoms improved at similar
rates for both procedures. A reintervention rate of 28% after 5 years was noted for
patients who had undergone an UAE.51
Impact and Management of Fibroids for Fertility
UAE VERSUS MYOMECTOMY
Myomectomy seems to have a higher pregnancy and delivery rate than UAE or UFE. A
randomized trial of 121 women conducted by Mara and colleagues52compared UFE
to myomectomy. Two years after their procedures, 78% of the myomectomy group
and 50% of the UFE group became pregnant.52The delivery rate was 48% and
19% and the abortion rate was 23% and 64%, for the myomectomy and UAE group,
respectively.52Further data with longer follow-up time are needed to expound on
these findings. However, Mara and colleagues52concluded that myomectomy seems
to have better reproductive outcomes, at least in the first 2 years. Goldberg and
Pereira35concurred that pregnancy after UFE likely yields higher rates of preterm
delivery and malpresentation (odds ratio of 6.2 and 4.3, respectively) compared with
The spontaneous abortion rate found in Mara and colleagues52study was higher
than that reported by the 2005 Ontario multicenter prospective trial (16.7%),46the
2005 retrospective trial of Carpenter and Walker (27%),53and the 2006 controlled
retrospective multicenter trial of Goldberg and Pereira (24% after UAE and 15% after
laparoscopic myomectomy).35However, all of these studies point toward the possi-
bility that pregnant women after UAE are more likely to miscarry compared with preg-
nant women after myomectomy.
It should be noted that 4 women in the Mara and colleagues52cohort experienced
reduced ovarian function. One patient had 6 weeks of amenorrhea but a normal
ovarian function (follicle-stimulating hormone 5 6.4 IU/L) 6 months after UAE. She
subsequently became pregnant. Three women had a transient ovarian dysfunction
or failure with a follicle-stimulating hormone elevation (from <10 IU/L before UAE to
15.0, 30.4, and 48.9 IU/L) accompanied by 2 months of amenorrhea in 1 patient
with no response to progesterone.
UAE VERSUS MRGFUS
and cesarean section rate was lower than that of UAE (93% vs 71%–82%, 36% vs
50%–73%, respectively). The authors40also noted an increased incidence of low birth
weight infants and stillbirths in women who had undergone an UAE. These obstetric
complications have not been reported after MRgFUS. The time to conception, miscar-
riage rate, and placenta previa rate were comparable between MRgFUS and UAE.
Available treatments for uterine fibroids include medical therapies, surgery, and newer
options such as UAE and MRgFUS. The proper treatment of each individual patient
will depend on the patient’s age and desire to retain her uterus and/or future fertility.
Current evidence supports that myomectomy is still the better choice for women who
desire to have a child. Treatment selection will also be dictated by the location, size,
and number of fibroid(s). For select women, fibroids size, previous surgery or operative
risk, UFE or UAE may be the best approach.
Clinicians must balance the potential for symptom relief with associated complica-
tions of the procedure. Decisions are best founded on evidence-based efficacy of
available treatment options for uterine fibroids, keeping in mind the goal of optimizing
pregnancy rates and obstetric outcomes in women who desire future fertility.
Designing individualized management plans will ensure optimal outcomes and
maximal patient satisfaction.
Guo & Segars
This research was supported, in part, by the Intramural Research Program in Repro-
ductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health. The authors would
like to thank Alan DeCherney, MD, for his mentorship and guidance and the National
Institutes of Health, NICHD, PRAE, and IRTA program for their support.
1. Walker C, Stewart E. Uterine fibroids: the elephant in the room. Science 2005;308:
2. Cramer S, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990;
3. Day Baird D, Dunson D, Hill M, et al. High cumulative incidence of uterine leio-
myoma in black and white women: ultrasound evidence. Am J Obstet Gynecol
4. Ezzati M, Norian J, Segars J. Management of uterine fibroids in the patient
pursuing assisted reproductive technologies. Womens Health (Lond Engl)
5. Peddada S, Laughlin S, Miner K, et al. Growth of uterine leiomyomata among
premenopausal black and white women. Proc Natl Acad Sci U S A 2008;105:
6. Cardozo E, Clark A, Banks N, et al. The estimated annual cost of uterine leiomyo-
mata in the United States. Am J Obstet Gynecol 2012;206:211.e1–9.
7. Cook H, Ezzati M, Segars J, et al. The impact of uterine leiomyomas on reproduc-
tive outcomes. Minerva Ginecol 2010;62:225–36.
8. Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for
a debate? Hum Reprod 2002;17:1424–30.
9. Rackow B, Taylor H. Submucosal uterine leiomyomas have a global effect on
molecular determinants of endometrial receptivity. Fertil Steril 2010;93:2027–34.
10. Sinclair D, Mastroyannis A, Taylor H. Leiomyoma simultaneously impair endome-
trial BMP-2-mediated decidualization and anticoagulant expression through
secretion of TFG-b3. J Clin Endocrinol Metab 2011;96:412–21.
11. Bulletti C, De Ziegler D, Polli V, et al. The role of leiomyomas in infertility. J Am
Assoc Gynecol Laparosc 1999;6:441–5.
12. Pritts E, Parker W, Olive D. Fibroids and infertility: an updated systematic review
of the evidence. Fertil Steril 2009;91:1215–23.
13. Olive D, Pritts E. Fibroids and reproduction. Semin Reprod Med 2010;28:218–27.
14. Somigliana E, Vercellini P, Daguati R, et al. Fibroids and female reproduction:
a critical analysis of the evidence. Hum Reprod Update 2007;13:465–76.
15. Benecke C, Kruger T, Siebert T, et al. Effect of fibroids on fertility in patients
undergoing assisted reproduction. A structured literature review. Gynecol Obstet
16. Pritts E. Fibroids and infertility: a systematic review of the evidence. Obstet
Gynecol Surv 2001;56:483–91.
17. Coronado G, Marshall L, Schwartz S. Complications in pregnancy, labor, and
delivery with uterine leiomyomas: a population-based study. Obstet Gynecol
18. Qidwai G, Caughey A, Jacoby A. Obstetric outcomes in women with sonograph-
ically identified uterine leiomyomata. Obstet Gynecol 2006;107:376–82.
Impact and Management of Fibroids for Fertility
19. Laughlin S, Baird D, Savitz D, et al. Prevalence of uterine leiomyomas in the first
trimester of pregnancy: an ultrasound-screening study. Obstet Gynecol 2009;
20. De Vivo A, Mancuso A, Giacobbe A, et al. Uterine myomas during pregnancy:
a longitudinal sonographic study. Ultrasound Obstet Gynecol 2011;37:361–5.
21. Stout M, Odibo A, Graseck A, et al. Leiomyomas at routine second trimester ultra-
sound examination and adverse obstetric outcomes. Obstet Gynecol 2010;116:
22. Laughlin S, Hartmann K, Baird D. Postpartum factors and natural fibroid regres-
sion. Am J Obstet Gynecol 2011;204:496.
23. Ouyang DW, Economy KE, Norwitz ER. Obstetric complications of fibroids.
Obstet Gynecol Clin North Am 2006;33:153–69.
24. Exacousto `s C, Rosati P. Ultrasound diagnosis of uterine myomas and complica-
tions in pregnancy. Obstet Gynecol 1993;82:97–101.
gynecology in practice. Oxford (United Kingdom): Wiley-Blackwell; in press.
26. Lee H, Norwitz E, Shaw J. Contemporary management of fibroids in pregnancy.
Rev Obstet Gynecol 2010;3:20–38.
27. Olive D, Lindheim S, Pritts E. Non-surgical management of leiomyoma: impact on
fertility. Curr Opin Obstet Gynecol 2004;16:239–43.
28. Stewart E. Uterine fibroids. Lancet 2001;357:293–8.
29. Parsanezhad M, Azmoon M, Alborzi S, et al. A randomized, controlled clinical trial
comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-
releasing hormone agonist (triptorelin) on uterine leiomyoma volume and
hormonal status. Fertil Steril 2010;93:192–8.
30. Donnez J, Tomaszewski J, Vazquez F, et al. Ulipristal acetate versus leuprolide
acetate for uterine fibroids. N Engl J Med 2012;366:421–32.
31. Donnez J, Tatarchuk T, Bouchard P, et al. Ulipristal acetate versus placebo for
fibroid treatment before surgery. N Engl J Med 2012;366:409–20.
32. Wilkens J, Chwalisz K, Han C, et al. Effects of the selective progesterone receptor
modulator asoprisnil on uterine artery blood flow, ovarian activity, and clinical
symptoms in patients with uterine leiomyomata scheduled for hysterectomy.
J Clin Endocrinol Metab 2008;93:4664–71.
33. Williams A, Critchley H, Osei J, et al. The effects of the selective progesterone
receptor modulator asoprisnil on the morphology of uterine tissues after 3 month
treatment in patients with symptomatic uterine leiomyomata. Hum Reprod 2007;
34. Lasmar R, Xinmei Z, Indman P, et al. Feasibility of a new classification of submu-
cous myomas: a multicenter study. Fertil Steril 2011;95:2773–7.
35. Goldberg J, Pereira L. Pregnancy outcomes following treatment for fibroids:
uterine fibroid embolization versus laparoscopic myomectomy. Curr Opin Obstet
36. Casini M, Rossi F, Agostini R, et al. Effects of the position of fibroids on fertility.
Gynecol Endocrinol 2006;22:106–9.
37. Bulletti C, DE Ziegler D, Levi Setti P, et al. Myomas, pregnancy outcome, and
in vitro fertilization. Ann N Y Acad Sci 2004;1034:84–92.
38. Al Hilli M, Stewart E. Magnetic resonance-guided focused ultrasound surgery.
Semin Reprod Med 2010;28:242–9.
39. Vercellini P, Trespidi L, Zaina B, et al. Gonadotropin-releasing hormone agonist
treatment before abdominal myomectomy: a controlled trial. Fertil Steril 2003;
Guo & Segars
40. Rabinovici J, David M, Fukunishi H, et al. Pregnancy outcome after magnetic Download full-text
resonance-guided focused ultrasound surgery (MRgFUS) for conservative treat-
ment of uterine fibroids. Fertil Steril 2010;93(1):199–209.
41. Ravina J, Herbreteau C, Ciracu-Vigneron N, et al. Arterial embolization to treat
uterine myomata. Lancet 1995;346:671–2.
42. Freed M, Spies J. Uterine artery embolization for fibroids: a review of current
outcomes. Semin Reprod Med 2010;28:235–41.
43. Spies J, Ascher S, Roth A, et al. Uterine artery embolization for leiomyomata.
Obstet Gynecol 2001;98:29–34.
44. Spies J, Roth A, Gonsalves S, et al. Ovarian function after uterine artery emboli-
zation for leiomyomata: assessment with use of serum follicle stimulating
hormone assay. J Vasc Interv Radiol 2001;12:437–42.
45. American College of Obstetricians and Gynecologists. ACOG practice bulletin:
alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol
46. Pron G, Mocarski E, Bennett J, et al. Pregnancy after uterine artery embolization
for leiomyomata: the Ontario multicenter trial. Obstet Gynecol 2005;105:67–76.
47. Goldberg J, Pereira L, Berghella V. Pregnancy after uterine artery embolization.
Obstet Gynecol 2002;100(5):869–72.
48. Homer H, Sarodigan E. Uterine artery embolization for fibroids is associated with
an increased risk of miscarriage. Fertil Steril 2010;92:324–30.
49. Mara M, Horak P, Kubinova K, et al. Hysteroscopy after uterine fibroid emboliza-
tion: evaluation of intrauterine findings in 127 patients. J Obstet Gynaecol Res
50. Moss J, Cooper K, Khaund A, et al. Randomised comparison of uterine artery em-
bolisation (UAE) with surgical treatment in patients with symptomatic uterine
fibroids (REST trial): 5-year results. BJOG 2011;118:936–44.
51. van der Kooij S, Hehenkamp W, Volkers N, et al. Uterine artery embolization vs
hysterectomy in the treatment of symptomatic uterine fibroids: 5-year outcome
from the randomized EMMY trial. Am J Obstet Gynecol 2010;203:105.e1–105.e13.
52. Mara M, Maskova J, Fucikova Z, et al. Midterm clinical and first reproductive
results of a randomized controlled trial comparing uterine fibroid embolization
and myomectomy. Cardiovasc Intervent Radiol 2008;31:73–85.
53. Carpenter T, Walker W. Pregnancy following uterine artery embolization for symp-
tomatic fibroids: a series of 26 completed pregnancies. BJOG 2005;11:321–5.
54. Klatsky P, Tran N, Caughey A, et al. Fibroids and reproductive outcomes:
a systematic literature review from conception to delivery. Am J Obstet Gynecol
55. Vergani P, Locatelli A, Ghidini A, et al. Large uterine leiomyomas and risk of
cesarean delivery. Obstet Gynecol 2007;109:410–4.
56. Rice J, Kay H, Mahony B. The clinical significance of uterine leiomyomas in preg-
nancy. Am J Obstet Gynecol 1989;160:1212–6.
57. Parker W. Uterine myomas: management. Fertil Steril 2007;88:255–71.
58. EsteveJ,AcostaR,Pe ´rezY,etal.Treatmentofuterinemyomawith5or10mgmife-
pristone during 6 months, post-treatment evolution over 12 months: double-blind
randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 2012;161:202–8.
59. Levens E, Potlog-Nahari C, Armstrong A, et al. CDB-2914 for uterine leiomyomata
treatment: a randomized controlled trial. Obstet Gynecol 2008;111:1129–36.
60. Chwalisz K, Larsen L, Mattia-Goldberg C, et al. A randomized, controlled trial of
asoprisnil, a novel selective progesterone receptor modulator, in women with
uterine leiomyomata. Fertil Steril 2007;87:1399–412.
Impact and Management of Fibroids for Fertility