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doi:10.1111/jog.

13437
doi:10.1111/jog.13437 J. Obstet. Gynaecol. Res. Vol. 43, No. 12:J. 1789–1804,
Obstet. Gynaecol. Res. 2017
December

Myoma and myomectomy: Poor evidence concern in


pregnancy

Giusi Natalia Milazzo , Angelica Catalano, Valentina Badia, Maddalena Mallozzi and
Donatella Caserta
Department of Medical and Surgical Sciences and Translational Medicine, Sant’Andrea Hospital, University of Rome “Sapienza”, Rome,
Italy

Abstract
Aim: Summarize the results of the many, but often underpowered, studies on pregnancy complicated by myoma
or myomectomy.
Methods: Survey of the electronic PubMed database for the last two decades was conducted. We selected re-
views, meta-analyses, case series, case reports, clinical studies only with statistical analysis, and guidelines from
scientific societies.
Results: Delaying childbearing leads to an increased incidence of pregnancy complicated by fibroids or previous
myomectomy. Approximately 10–30% of pregnant women with myomas develop complications during gesta-
tion, at delivery and in puerperium. Submucosal, retroplacental, large and multiple myomas have a greater risk
of complications. Cervical myomas, although rare, need careful management. The location and size of the fibroids
should be assessed from the first trimester. Despite the increased risk of cesarean section, fibroids are not a contra-
indication to labor, unless they obstruct the birth canal or other obstetric conditions coexist. Myomectomy during
pregnancy, in selected cases, is feasible and safe. Myomectomy cannot be considered a prophylactic measure prior
to conception, but has to be individualized. Uterine rupture after myomectomy generally occurs in the third tri-
mester or during labor and some associated risk factors have been identified. There is no consensus on the optimal
interval between myomectomy and conception.
Conclusions: Pregnancy in patients with fibroids or previous myomectomy should be considered as high risk,
requiring a maternal–fetal medicine specialist. To date available literature is inconsistent on evidence-based man-
agement. Further research is needed for definitive recommendations.
Key words: complication, fibroid, myoma, myomectomy, outcome, pregnancy.

Introduction experience any symptoms, whereas 10–30% develop


complications during gestation, at delivery and in the
The incidence of fibroids during pregnancy is likely to puerperium.1,2
increase in the coming years, in association with delay The most important factors in determining morbidity
in childbearing. The prevalence is approximately 2%, in pregnancy include fibroid number, size, location, and
ranging from 0.1% to 12.5%, and differs with ethnicity relationship to placenta implantation.3 Most studies have
(18% in African–American women, 8% in white been underpowered, retrospective or not properly con-
women, and 10% in Hispanic women). In older trolled for the confounding variables. Very few
women undergoing ovum donor recipient in vitro population-based studies have been identified in the lit-
fertilization (IVF) the incidence rises (25%). Most erature: only two meta-analyses have been conducted
pregnant women with uterine myomas do not on risks associated with myoma in pregnancy, and there

Received: April 18 2017.


Accepted: May 28 2017.
Correspondence: Professor Donatella Caserta, Department of Medical and Surgical Sciences and Translational Medicine, Sant’Andrea Hos-
pital, University of Rome “Sapienza”, via di grotta rossa 1035-1037, Rome, Italy. Email: donatella.caserta@uniroma1.it

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has been no randomized controlled trial on the subject. asymptomatic women with fibroids.6 Preconception
Only one systematic review in 2008 calculated the cumu- myomectomy seems to reduce uterine contractility, re-
lative obstetric outcomes.4 In some cases myomectomy store normal anatomy and stop local inflammation.7–9
during pregnancy is necessary: and despite its related In contrast, it may provoke endometrial damage and
risks, no guidelines have as yet been postulated. As the pelvic adhesions, responsible for unfavorable obstetric
number of women undergoing myomectomy has in- outcomes. The published literature notes that the benefit
creased in the recent years, first for treatment of infertility, of myomectomy in terms of reproductive outcome de-
a relevant number of women with previous myomec- pends on the location of the fibroids (involvement of
tomy will present to the obstetric care unit and the physi- the uterine cavity), both in terms of spontaneous
cian should counsel the patient about the risks and pregnancy as well as IVF outcomes.10 It should be
complications.5 tailored to the individual patient clinical characteristics
A search of the electronic PubMed database for the last (Table 1).10–13
two decades was conducted using the MeSH terms
“myoma/fibroid” AND “pregnancy complication”,
“pregnancy outcome”, “pregnancy ultrasound”,
Effects of Pregnancy on Myomas
“growth pregnancy”, “delivery”, “cesarean”, It is widely thought that myomas grow rapidly during
“miscarriage/abortion”, “placental abruption”, “fetal pregnancy under the influence of hormone stimulation
growth restriction”, “fetal anomalies”, “fetal and increased blood flow. Some authors have reported,
malpresentation”, “post-partum hemorrhage”, “preterm however, that they frequently remained unchanged or
labor/delivery”, “premature rupture of membranes”, even decreased in size.14 The previous studies may be bi-
“dystocia”, “obstructed labor”, “pain pregnancy”, “twin ased due to methodological factors with regard to data
pregnancy”, “puerperium”, “NIPT”, “prenatal screen- collection (retrospective analysis, different gestational
ing”, and “amniocentesis”; then we searched on “myo- age at enrollment, and ultrasound [US] equipment
mectomy” AND “pregnancy”, “fertility”, “uterine used).15 More recent studies reported a non-linear in-
rupture”, “pregnancy termination”, “placenta accreta”, crease in size, above all in the first half of pregnancy. In
“cesarean”, “preterm labor/delivery”, “post-partum myomas, however, the growth trend in pregnancy is dif-
hemorrhage/blood loss”. We selected reviews, meta- ferent to the trend for estrogen and progesterone concen-
analyses, case series, case reports, clinical studies only tration, the best-known growth factors for fibroids.
with statistical analysis, and guidelines from scientific According to the current evidence, the rapid exponential
societies. increase in serum human chorionic gonadotropin (hCG)
in the first weeks of pregnancy until 12 weeks and the
Impact of Myomas on Infertility particular kinetics of its receptor may explain the similar
(Effectiveness of Myomectomy) rapid growth trend of fibroids. This is supported by
in vitro studies.16 The mean increase in fibroid volume
There are poor data in the literature on the recommenda- during pregnancy is 12%, and very few fibroids increase
tion for elective preconception myomectomy in by >25%.17 Strobelt et al. found that larger fibroids

Table 1 Indications for preconception myomectomy


Patients with unexplained Pre-IVF or pre-natural
Infertile patients10 infertility11 conception in infertile patients12,13
Submucous Suggested (myomectomy improves Suggested Suggested FIGO L0–L2 of any size
myomas PR, but not OPR, LBR, MR)
Intramural Controversial (not sufficient evidence Discussed (suggested in In some cases FIGO L3–L5 > 50 mm
myomas to recommend myomectomy even patients undergoing IVF
if the presence of myomas reduces or cases of unexplained
fertility) infertility with no other
options of treatment)
Subserosal Not recommended Not recommended In some cases FIGO L6–L7 only for
myomas improving symptoms or to prevent
pregnancy complications
FIGO, International Federation of Gynecology and Obstetrics; IVF, in vitro fertilization; LBR, live birth rate; MR, miscarriage rate; OPR, ongoing
pregnancy rate; PR, pregnancy rate.

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(>5 cm in diameter) are more likely to grow.10 Contrast- pregnancy, through mechanical distortion of the endo-
ing evidence exists among the clinical variables (body metrial cavity, impairment of endometrial vasculariza-
mass index [BMI], age, parity), influencing volumetric tion, and endometrial inflammation.23 The spontaneous
change in myomas.16,19 Controlled ovarian hyperstimu- abortion rate is the same in the case of IVF as for sponta-
lation for IVF does not seem to affect myoma growth it- neous conception.24 Preconceptional removal is recom-
self, but does only if pregnancy occurs.15 To date it is mended in cases of unexplained infertility or recurrent
impossible to predict the growth of fibroids accurately pregnancy loss.10–12
because fibroids respond differently to pregnancy in dif- Retroplacental fibroids are associated with a higher in-
ferent individuals. cidence of miscarriage, intrauterine growth restriction
(IUGR), intrauterine fetal demise (IUFD), preterm labor,
Ultrasound during pregnancy placental abruption, and post-partum hemorrhage
Until the advent of US the diagnosis of fibroids was (PPH).23
made clinically, burdened by the low detection rate for Large myomas (mostly defined as >5 cm) are associ-
myomas < 5 cm (12.5%).18,20 Deveer et al. suggested that ated with an increased risk of premature delivery and
the first trimester (targeted for the sixth week of gesta- blood loss at delivery. A crucial issue is whether or not
tion) represents the ideal timing for measuring and iden- to myomectomy should be performed on large asymp-
tifying leiomyomas, because the growth of the fetus and tomatic myomas. Myomectomy does not improve the
the increase in uterine size can impede visualization later obstetric or delivery outcomes, but removing large fi-
in pregnancy.2After precise determination of number, broids distorting the uterine cavity improves pregnancy
size and location of myomas during the first trimester, rates and decreases miscarriage rates.25 Shavell et al.
monthly US controls should be performed, because my- stated that it is premature to make specific recommenda-
oma growth may modify the related obstetric risk. Fur- tions regarding the value of myomectomy prior to con-
thermore, an uncommon rapid growth must be ception.21 They recommend to counsel patients about
investigated, in order to exclude malignancy. In the case the increased likelihood of the unfavorable obstetric out-
of suspicion, flow Doppler analysis may help in the deci- comes and to perform frequent controls during
sion making for myomectomy, given that a sharp drop in pregnancy.21
resistance index seems to be related to tumor necrosis.21 Cervical myomas in pregnancy are rare (<1% of all
During pregnancy it is sometimes difficult to differenti- myomas in pregnancy). The literature on their manage-
ate fibroids from physiologic thickening of the ment is poor and consists only of case reports and one
myometrium on US, especially in the case of small fi- retrospective study. Nonetheless, the problems caused
broids (<5 cm). Repeat scanning after 30 min and color by cervical leiomyomas during pregnancy may be signif-
Doppler at lower velocity settings are suggested. icant: pressure effects on the bladder or urethra
Myometrial thickening due to contraction is likely to dis- (increased micturition frequency, urinary retention due
appear at the next check. Moreover, in cases of myoma to pressure on the bladder neck, to overflow inconti-
the image will show the splaying of the vessels around nence if the problem remains untreated), infection
the mass, while uterine contraction will be recognized and/or degeneration, and complications during deliv-
as vascular flow throughout the thickening.22 ery (hemorrhage, malpresentation, dystocia, labor
obstruction, infection, and even hysterectomy). There is
no association with preterm birth or fetal growth restric-
Obstetric Complications of Myomas tion. The management of the different type of cervical
During Pregnancy myoma is given in Table 2.26,27
Subserosal myomas do not worsen pregnancy out-
Because of the bias in the earlier studies, any pregnancy comes.2–4
complication that occurred in the presence of a fibroid
was often attributed to the fibroid itself. The major Miscarriage
complications, however, appear to be related to the The hypothetical mechanisms causing miscarriage are:
location of the myoma, and whether it is in contact with placental implantation over a myoma (leading to subop-
the placenta. timal blood supply and placental insufficiency), degen-
Submucous fibroids have the strongest association eration of leiomyomata during pregnancy (causing
with lower rate of ongoing pregnancy. They may ad- release of prostaglandins) and deformation of the uterine
versely affect implantation, placentation, and ongoing cavity (responsible for decreased distensibility of the

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Table 2 Management of cervical fibroids


SUPRA-VAGINAL FIBROID CERVICAL LIPS FIBROID PEDUNCULATED FIBROID
Clinical • Centrally lying in the pelvis • Recurrent vaginal bleeding • Vaginal bleeding and lower
features abdominal pain (due to the
attempt of the uterus to
expel the fibroid)
• Assess the base implant (MRI
may help in the location)
• in the cervical canal
• in the uterine cavity with
protrusion through the
cervix
Possible • When there is a significant • Risk of pPROM • Serious symptoms➔ removal
consequences growth➔displacement of during pregnancy
the lower segment high up
• pPROM
• Chorionamniotitis
• Preterm delivery
Mode of • CS: prefer vertical uterine • CS (Rarely vaginal delivery) • Vaginal delivery
Delivery incision
Myomectomy At time of delivery: debated At time of delivery At time of delivery
• Pros of myomectomy➔ • Recommended➔via abdominal • Vaginal myomectomy in
reduce the risk of atony and route or vaginal post-partum
infection • conservative management is
• Cons of myomectomy➔ available (possible post-partum During pregnancy
localization next to cervical involution) and next easier
vessels (high risk of profuse surgery • The surgical technique
hemorrage) depend on

The risk of hysterectomy is • Location of the base


independent if (vaginal route is not
myomectomy is performed advisable when the base
or not (larger myoma are is inaccessible)
more at risk). • Thickness of the base/
peduncule:
thin➔twisting of the fi-
broid
thick➔enuclation

CS, cesarean section; pPROM, preterm premature rupture of membranes.

uterus with advancing gestation). Any fibroid location is and US-guided curettage would reduce the rate of
associated with an increased risk of miscarriage of 1.7.11 complications.
Abortion, however, usually occurs during early/mid tri-
mester when implantation occurs over a submucous fi-
broid. Intramural and subserosal fibroids <3 cm are Placental abruption
often considered not clinically significant, except in the The published results are conflicting.30–37 A recent meta-
case of multiple intramural myomas. Large fibroids analysis showed a significant association with placental
(>5 cm) are more likely to interfere with fertility.28 An- abruption (2.63; 95%CI: 1.38–3.88), after correcting for
other aspect to take into account is the technical diffi- maternal age, maternal weight gain, smoking, previous
culty of the uterine curettage following abortion in a preterm birth, and preterm premature rupture of
fibromatous uterus, because the cavity may be distorted membranes (pPROM).38 The increased risk would come
and the possibility of uterine wall lesion or retention of from interference or distortion of the normal perfusion
material is increased. Furthermore, uterine curettage is of the placental site. The impairment of fetoplacental
reported to be a causal factor of pyomyoma.29 For these unit flow seems to be affected in cases of retro-
reasons antibiotic treatment should be contemplated, placental submucous myomas with great fibroid volume

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(>200 cm3)33 and in the case of intramural myoma with is not considered an indication for sonographic cervical
growth during pregnancy.21 length measurement during pregnancy.54

IUGR/small for gestational age Placenta previa


4
Fibroids may have a small effect on fetal growth. Large Data are conflicting.25,34–37 Placenta previa seems to be
(>200-mL volume) submucosal and retroplacental fi- related to the presence of large fibroids.30,51
broids are likely to interfere with placentation and may
Adherent placenta
clinically cause IUGR.17,33 Recent evidence indicates an
increased risk of small for gestational age (SGA) only When the placenta overlies any uterine abnormality, in-
with retroplacental leiomyomas > 4 cm.39 In women cluding fibroids, a careful search for invasive placenta-
with large submucosal or retroplacental fibroid, regular tion is warranted. Adherent placenta is to be expected
monitoring for fetal growth during pregnancy should in cases of submucosal fibroid.55 US can visualize pla-
be undertaken and a maternal–fetal medicine consulta- centa overlying an anterior fibroid, whereas magnetic
tion is advisable if IUGR is noted.40 resonance imaging (MRI) is more suitable for evaluating
posterior fibroids, above all in advanced pregnancy, and
Intrauterine fetal demise helps when US is insufficient.56 When placental invasion
abnormalities are suspected, the family should be in-
Data are scarce.30,31,34 Lai found that IUFD was particu-
formed, and the birth should be in a tertiary center with
larly significant before 32 weeks’ gestation.37
preoperative preparations carried out in a planned
manner.
Fetal compression syndrome
Large uterine leiomyomas (approx. 10 cm) may induce Post-partum hemorrhage
restriction of the uterine cavity, causing fetal deformities The risk of PPH is twofold higher than in the general
from long-term compressive force. The anatomic anoma- population.3 Decreased uterine contractility and unco-
lies described in the literature are limb reduction, caudal ordinated contractions may lead to inefficient
dysplasia, head deformation, and congenital torticollis.42 myometrial retraction in the third stage of labor. The
Moreover the space limitation in the uterus may limit the risk of PPH is higher in cesarean delivery.23 Difficulties
movements of the fetus, especially when it occurs early in comparing the results of various studies arise from
in gestation: this makes the joints stiff and may lead to the non-uniform definitions of PPH used. On US, mul-
arthrogryposis. Also the respiratory movements may tiple myomas was the only parameter independently
be compromised, leading to hypoplastic lungs.43A case associated with excessive blood loss at delivery.57 Also
of fetal “entrapment” is described, secondary to com- the increasing size48 and the location of fibroids in the
partmentalization of the fetus in the uterine cavity by a lower part49 increase the risk of PPH. Retroplacental
large submucousmyoma.44 Pregnant patients with large submucous myomas increase not only the risk of PPH
myomas should have thorough fetal anatomical scans to but also that of retained and adherent placenta.58 Rarely
exclude fetal compression syndrome. myomas may obstruct the passage of lochia and induce
uterine atony for hematometra (large myomas
Preterm birth and pPROM obstructing the internal os or pedunculated fibroids
There seems to be a small increase in preterm labor and protruding through the cervix).59 It is advisable to orga-
preterm birth.25,30–32,34,36,39,45–48 Not all studies nize a care plan for PPH prophylaxis in women with
agree.10,33,35,49–51 Myomas may distort the shape of the fibroids.23
uterine cavity; as pregnancy advances, myometrium
with fibroids is overstretched and this mechanism can Malpresentation
initiate labor and thus result in an increased rate of pre- A recent meta-analysis stated that uterine myomas
term births.52 A decrease in oxytocinase activity in the increase the risk of malpresentation at term,60 but not
gravid fibroid uterus could increase the concentration all the articles included defined size and location of
of oxytocin, predisposing to premature contractions.53 myomas, therefore the authors declared that this
Large uterine fibroids are significantly associated with lack of information may have partially biased their
pPROM25,37 and with delivery at an earlier gestational results. Large and multiple fibroids distorting the uterine
age.25,31,37 Others found an association with multiple in- cavity have been consistently associated with fetal
tramural myomas.37,46,48 The presence of uterine fibroids malpresentation.30,31,37,51,61

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Dysfunctional labor Performance of CS


There is a lack of knowledge and basic research on the ef- For the high risk of PPH, at least 9.5–10 mg/dL hemoglo-
fect of fibroid on labor. Fibroids may physically impede bin is recommended before CS. Preoperative devices
the propagation of contraction waves throughout the should be considered on a case-by-case basis (placement
uterus; furthermore they lack prostaglandin receptors, of bilateral iliac artery balloon catheters, use of a cell
essential for physiological uterine peristalsis.23,54 The saver, and availability of blood products in the operating
uterus with fibroid(s), however, is no less responsive to room). The usual practice is to keep away from the fi-
the use of oxytocics.23 The majority of patients have a broid and choose the best accessible incision line at least
successful vaginal delivery, except in the case of cervical 2 cm from the fibroid margin. If possible, a lower seg-
or anterior isthmic fibroid. ment CS is preferred. In cases of myoma involving the
lower segment many surgeons prefer the classic CS in-
stead of low transverse CS (but this procedure carries a
Obstructed labor risk of increased blood loss), others prefer to perform a
Large previa myomas may block the passage required myomectomy at the time of CS, before fetus delivery.
for vaginal delivery. Until the advent of US the diagno- The operation is technically challenging with difficult in-
sis of obstructed labor for huge previa myoma was done traoperative hemostasis and is associated with a higher
clinically: when it was impossible to displace the my- incidence of postoperative complications.23,54 A sum-
oma upwards toward the fetal head an obstructed labor mary of the data about obstetric complications discussed
was diagnosed, providing an indication for cesarean above are presented in Table 3.
section (CS).62 Nowadays US is fundamental for estab-
lishing the modality of delivery before labor onset: the
vaginal delivery cannot be carried out if myoma is
Pain: Fibroid torsion and degeneration
located between the fetal head and the internal os, inter- Focal abdominal pain is a frequent complaint during
fering with both cervical dilatation and fetal head pregnancy (Fig. 1). Pain related to fibroids is often seen
descent.23 in women with large fibroids (>5 cm) or posterior
fibroids.2 Approximately 5–21% will require hospitaliza-
tion during pregnancy for pain control: this phenome-
Cesarean section non is usually correlated with increasing fibroid size.48
The risk of CS at term is more than doubled.60 Pain may result from torsion or partial obstruction of
Leiomyoma may theoretically influence the route of the vessels supplying a pedunculated fibroid. Torsion is
birth via complications that occur before the onset of la- more likely to occur in the first trimester and after deliv-
bor (placenta previa, malpresentation, myoma previa) ery, when there is enough space in the abdominal pelvic
or after the onset of labor (dysfunctional labor). But even cavity to permit fibroid twisting.54 Another cause of pain
after correcting for malpresentation, myoma previa and is red degeneration, occurring in 10% of pregnancies. It is
placenta previa, the presence of leiomyoma remains sig- typical of pregnancy and consists of infarction-specific
nificantly associated with increased risk for CS.30 This histological changes. Usually, this “syndrome” is more
strong association may be biased by previous studies frequent during the first and the beginning of the second
based on codes charted retrospectively at patient dis- trimester of pregnancy when the growth of myomas can
charge; in this view the presence of a fibroid has to be be more rapid. Pain may result from the necrotic infarc-
read as an adjunctive diagnosis but it would not be itself tion (due to the tissue anoxia consequent to rapid
the indication for CS.4 Michels et al. found that larger size growth), the change in blood supply of the growing
or greater number of myomas increase the risk for CS,59 uterus and the release of prostaglandins from cellular
but not all authors agreed with this finding,48,49,51 prob- damage.52 Clinically, fibroid red degeneration is charac-
ably because of the difficulty in comparing effects across terized by focal abdominal pain of acute onset, mild fe-
studies.63 Although the presence of a large myoma is not ver, nausea and vomiting, localized tenderness over the
per se an indication for CS before labor, in clinical prac- fibroid, rebound tenderness, and leukocytosis, even if
tice it has possibly lowered the threshold to proceed with the clinical presentation is not so acute.2 Differential di-
the abdominal route of delivery when other obstetric agnosis must be considered (Fig. 1). Clinical examination
complications are present.51 Large fibroids or multiple fi- and appropriate laboratory tests supported by US and
broids are not an immediate contraindication to labor if MRI can help establish the diagnosis. On US, painful my-
women are eligible for vaginal delivery.49 oma >200 cm3 presenting a change in the echogenicity

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Table 3 Obstetric outcomes and related fibroid features

Piazze
Rice Davis Hasan Exacoustos Vergani Garnica Roberts Coronado Benson Sheiner Qidawai Vergani Pritts
1989†27 1990†41 1991¶57 1993†29 1994†31 1995¶12 1999†46 2000†30 2001†24 2004†28 2006†32 2007†47 2009‡18

© 2017 Japan
Miscarriage/ /+ /+R / /+ +M/ + SM,
threatened
miscarriage

Japan Society
Societyof
Cesarean section + +L>5, + + + + + +L>5
P
Preterm birth/ / +L>5 +/ /+ / / +/ +/
labor
+L>5,M/ /

ofObstetrics
pPROM +
Malpresentation +L>3– +L>6 + + +L>5

Obstetricsand
5
Placenta previa + +L>5
Placental +L>5, +L>7,SM + +
abruption R
IUFD +R
IUGR /LBW or / / / / /+ /

andGynecology
SGA

Gynecology
NS NS NS
PPH/EBL +/ +/ §§ / / / ¶¶ +/ ‡‡+/
†Case–control; ‡meta-analysis; §prospective cohort; ¶retrospective observational; ††>500 mL if vaginal delivery, >1000 mL if cesarean section; ‡‡>1000 mL; §§>500 mL; ¶¶>1000 mL if
vaginal delivery, >1500 mL if cesarean section. +, associated; , not associated; empty space, variable not analyzed. EBL, excessive blood loss; IM, intramural myoma; IUFD, intrauterine
fetal death; IUGR, intrauterine growth restriction; L > n, large myoma (n, measured in cm); LBW, low birthweight; M, multiple myomas; NS, not specified; P, myoma previa; post, posterior
myoma; PPH, post-partum hemorrhage; pPROM, preterm premature rupture of membranes; R, retroplacental myoma; SGA, small for gestational age; SM, submucosal myoma.
Myoma
Myomaand
andmyomectomy

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with the appearance of internal cystic areas can suggest

2016†45
Martin red degeneration and infarction.17 Low indices on 3-D
Doppler are associated with the ischemic processes

/+L
/

/
+L
within the tumor.64 MRI should be considered in such
situations to confirm the diagnosis and facilitate fibroid
2016¶35

mapping before surgery. Some authors recommend its


Knight

/+R>4
use in the differential diagnosis between cystic degen-
eration and ovarian malignancy.65 The management is
illustrated in Figure 1.66 It should be remembered that
the necrotic areas are a perfect medium for anaerobic
Ciavattini
2015†33

+L>5,M/

infection, which may be severe and resistant to ther-


apy, therefore it would be suitable to monitor the pa-
+M

+M

/
tient with blood exams in order to initiate antibiotic
+

therapy.54
2014¶44

Rare complications of fibroids in pregnancy are de-


‡‡+P,L/
Lam

scribed in Table 4.67–72


+M/
+P

Puerperium
Michels
2014§59

Most uterine fibroids either stop growing or decrease in


+L>3

size after birth, and only 10% will show an increase in


volume. The mechanical and cellular mechanisms re-
lated to birth and uterine involution may play a role in
2013†43
Conti

fibroid regression during puerperium.73 For this reason


/NS+

most studies agree on the protective effect of parity on fi-


/+

+/
+

broids.74 Sometimes in puerperium, myomas can en-


large, outgrowing their blood supply, and may
2012†37
Lai

degenerate. Red degeneration may be more common


+/

due to a diminished blood supply to the fibroid after de-


+
/

livery, and can lead to serious complications such as ne-


Shavell

†† /+L>5

crosis and secondary infection, thrombosis and


2012†21

+L>5,M,

embolism.75
+L>5/

SM

Twin pregnancies
Table 3 Obstetric outcomes and related fibroid features

There are little data on how fibroids influence obstetric


Deveer
2012¶2

outcomes in twin pregnancies, because of the exclusion


+post/
+SM

of multiple gestations from most studies.76,77 Recent


studies failed to demonstrate any significant associa-
tion, probably because the narrowing of intrauterine
2010†26

+M,L>5
+L>5, P

space related to fibroids is less significant than the re-


Stout

+L>5

+L>5

duced intrauterine space in twin pregnancies. Addi-


+/

+/
+

tionally, frequent prenatal US could have helped to


reduce the occurrence of some adverse obstetric out-
2009†42
Chen

comes; planned earlier deliveries in twins may mitigate


+IM/

adverse effects attributable to fibroids detected in sin-


/+

gleton cohorts; additionally, the high rate of CS in twin


pregnancies could be a factor in the similar incidence
Andreani
2009¶53

of adverse obstetric outcomes. Screening strategies al-


+L>5,M

ready in place for women with twin pregnancies do


/+M

not need to be altered based on the presence or ab-


sence of fibroids.

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Myoma andmyomectomy
myomectomy in pregnancy

Figure 1 Management of pelvic–abdominal pain in fibroid-complicated pregnancy. NSAID, non-steroidal anti-inflammatory


drug.

Fetal US pregnancy in women with uterine fibroids. It was con-


An emerging problem related to the performance of US cluded that more etiopathogenic studies are needed, al-
in a fibromatous uterus is the interference of fibroids in though their findings may help the physician to better
the carrying out of optimal fetal US, such as measure- interpret the false positive results and counsel the pa-
ment of nuchal translucency, evaluation of fetal biome- tients about their significance, despite the unquestion-
try, and study of the fetal anatomy, thereby reducing able need to proceed to diagnostic tests in cases of
the reliability of the exam.78 The patient should be in- positive biochemistry screening.
formed about such limiting factors.
Non-invasive prenatal testing
Biochemistry screening for fetal chromosomal Non-invasive prenatal testing (NIPT) using maternal
abnormalities blood can be confounded by maternal conditions that
Uterine leiomyomas, uterine scar (after uterine surgery) lead to structural variants/copy number variations in
and pathological placental location are associated with the genome, as in cases of chromosomal instabilities
higher hCG concentration. Based on this assumption, found in maternal neoplasms. These conditions may
in a recent study the presence of uterine leiomyomas produce abnormal and non-reportable NIPT result, re-
was found to increase the number of false-positive re- quiring an in-depth analysis with diagnostic tests. In a
sults from Bi-test and Triple test.79 The reason for the recent study a uterine leiomyoma was found to be the
hCG increase seems to be linked to an impaired source of extra genetic material in maternal plasma that
maternal–placental circulation due to trophoblast im- skewed the NIPT result. Physicians may encounter this
plantation in the uterus with leiomyomas, suggested phenomenon when counseling the patient about prena-
by the observation of decreased impedance in uterine– tal screening and should advise the laboratory about
placental circulation on US color Doppler in early the patient’s clinical history.80

© 2017 Japan
Japan Society
Societyof
ofObstetrics
Obstetricsand
andGynecology
Gynecology 1797
9
10
Table 4 Rare complications of fibroids in pregnancy

1798
Consequences of delayed
Physiopathology Signs and symptoms Diagnosis Treatment treatment

Pyomyoma Suppurate inflammation Triad: Pain, CT limitated in pregnancy Antibiotics intravenous (first line) Peritonitis
G. N. Milazzo
Milazzo et

of necrotic degenerated Sepsis, myoma. MRI and US inconclusive Surgery (if imaging inconclusive Renal cortical necrosis
fibroid Both in pregnancy in case of aseptic necrosis or resistance to medical therapies) Deep vein thrombosis
et al.
al.

and puerperium Surgical option depending on GA: Endocarditis


-Hysterectomy after CS (best choice) Pancreatitis
-Myomectomy in early pregnancies Septic shock
(poor obstetrical outcomes) Death
-CT guided drainage in post-partum
(case report)
Uterine axial Torsion of pregnant Pain, OE: twisted close cervical canal Surgical option depending on GA: Venous obstruction➔
torsion uterus >45° along Non-specific CTG: Hypertonia, fetal distress -early GA: derotation + increased pressure
its major axis abdominal US findings: change position myomectomy in placental
symptoms, of placental and fibroid versus -near term: derotation+ CS or CS + cotyledons➔
Shock previous scans. derotation (attention to avoid abruption
Conclusive diagnosis with MRI: injuries because of subverted
X shaped upper vagina anatomy)
Uterine istmic fibroid induces Severe pain, OE: fundal height <GA; cervix displaced Early GA: Uterine dystocia➔
incarceration uterine fundus Miscarriages, behind the pubic symphysis; fetal h -Maneuvers to reduce uterine rupture
backward rotation Acute urine ead in the Douglas. incarceration
into the Douglas retention, -Pessary Irreversible uterine
pouch IUGR/IUFD, US: bladder displaced anteriorly; -Myomectomy ischemia
pPROM, +/- hydronephrosis; cervix not -Termination of
Preterm labor visualized by TVS; fundal placental pregnancy Miscarriage
implantation mistaken for placenta
previa Near term: Bladder dysfunction
-CS (attention to

©©2017
MRI conclusive diagnosis avoid bladder and Rectal gangrene
cervical injuries)
Fibroid rupture Hemoperitoneum (H): Pain Anamnestic datum of a large Myomectomy Hemorrhagic shock➔

2017Japan
Rupture of superficial subserosal myoma One case report: suture of the tears death
veins of large Rapid anemia
subserousmyoma US/MRI:hemoperitoneum (H)

JapanSociety
Non-specific or myoma enlargement (IH)

Societyof
Intra myoma hemorrhage abdominal
(IH): hemorrhagic necrosis symptoms
in pedunculated subserous
myoma shock

ofObstetrics
Precipitating factors:
trauma, torsion, lifting

Obstetrics and
heavy weights, violent
coitus, uterine
manipulation
CT:computed tomography; MRI: magnetic resonance imaging; US: ultrasound; OE: obstetrical examination; CTG: cardiotocography; GA: gestational age; TVS: transvaginal sonography; CS:
cesarean section; IUGR: intrauterine growth restriction; IUFD: intrauterine fetal demise; pPROM: preterm premature rupture of membranes

and Gynecology
Myomaand
Myoma andmyomectomy
myomectomy in pregnancy

Amniocentesis of the pregnant uterus, can be utilized with either the


The risk of miscarriage, pPROM or preterm birth in open technique or Verres needle. Induction of pneumo-
women with fibroids undergoing amniocentesis is not peritoneum can be safely performed, adjusting the ac-
increased compared with the general population, espe- cess site according to fundal height. CO2 insufflation at
cially if antibiotic prophylaxis is used. The increased rate 10–15 mmHg can be safely used. To ensure hemostasis,
of fetal loss in patients with myoma is to attribute only to bipolar electricity is the best choice to minimize the
the fibroids themselves, and amniocentesis does not in- myometrial damage and any possible injury to the fetus.
crease this risk.81–84 During morcellation care should be taken to avoid dam-
age to the uterus or to the surrounding tissues. The preg-
nant patient must be placed in the left lateral position
Myomectomy in pregnancy during surgery. Fetal heart rate monitoring should be
Surgeons usually hesitate to perform myomectomy in performed immediately before and after the procedure.
pregnancy because of the increased uterine blood flow
and volume during gestation, which raise the risk of
hemorrhagic complications and increase the likelihood Effects of Preconceptional Myomectomy
of hysterectomy, while the uterine manipulation can pre- on Pregnancy
dispose toward adverse pregnancy outcomes: miscar-
riage (18–35%), infection, preterm birth, uterine The incidence of fibroids is higher in women aged
dehiscence. These risks may be increased in the case of >35 years and this, added to the delay in childbearing,
removal of submucous, posteriorly located, or multiple causes an increase in pregnancies complicated by a
intramural myoma.85–88 In some cases the surgical re- previous myomectomy.
moval of myoma is the only choice to resolve severe clin-
ical situations.87 The reported incidence of complications Uterine rupture
after conservative treatment ranges from 3 to 38%, and One of the most life-threating complications during
untreated patients with uterine myomas seem to have pregnancy is the uterine rupture (UR). UR may lead to
a worse pregnancy outcome than surgically treated pa- hemorrhage, shock, hysterectomy and even maternal
tients.87 The most common indications for myomectomy and fetal mortality. The hypothetical risk of UR during
during pregnancy are acute pelvic pain not responsive to pregnancy is due to the presence of scar tissue; therefore
medical therapy >72 h, rapid growth potentially hiding any previous surgical interventions on the uterus are
malignancy, the bulk of the mass compressing pelvic or- considered a risk factor for UR. This risk appears similar
gans, and clinical observations of threat to the pregnancy after both myomectomy and CS.93 The true incidence of
(fetal compression syndrome, oligoamnios, IUGR, bleed- UR after myomectomy is difficult to assess: 1–3.7% of
ing, anomalies of the placentation site).85–89 It was previ- pregnancies has been reported in some studies, while
ously thought that in the first trimester the primary in others it was estimated at 0.2% after abdominal myo-
option should be the interruption of pregnancy followed mectomy (AM) and 0.26% after laparoscopy (LSM).94–97
by subsequent myomectomy; today there is evidence The scar after LSM is thinner than after AM, but recent
that myomectomy could be performed during every tri- studies found no difference between the two
mester. Although laparotomic myomectomy has been approaches, concluding that LSM is safe if performed
reported safe since the end of the 19th century, a recent by skilled surgeons.98,99 UR is unpredictable, for this rea-
review stated that laparoscopic myomectomy must be son it is important to recognize quickly non-specific
considered the first choice for abdominal and pelvic sur- signs and symptoms, in every pregnant woman with a
gery during pregnancy at any gestational age because it previous myomectomy. Most cases of UR occur in the
provides better intra-abdominal visualization, a mini- third trimester or during labor, when intrauterine pres-
mally invasive approach and earlier mobilization after sure is more elevated.100 In a review of case series and re-
surgery (fundamental to prevent thromboembolism).90 ports, a high recurrence of UR was noted in women who
To our knowledge, from 1994 to date, 11 cases of laparo- had undergone IVF, most of whom had twin pregnan-
scopic myomectomy during pregnancy have been re- cies. The uterine scars cause a reduction in elasticity
ported, which were uneventful to term (except in two and tensile strength in a focal site of the myometrium,
cases); in four cases vaginal delivery was carried due to the substitution of the muscle tissue with fibroid
out.91,92 The abdominal access modality, particularly tissue. The repair process after myomectomy is funda-
troubling for the increased risk of damage due to the size mental to preserve uterine integrity and depends on

© 2017 Japan
Japan Society
Societyof
ofObstetrics
Obstetricsand
andGynecology
Gynecology 1799
11
Milazzo et
G. N. Milazzo et al.
al.

the general status of the patient, enucleation technique, Therefore myomectomy causes the formation of scar that
use of electrocoagulation, formation of hematoma and damages the endometrial layer, causing possible subse-
type of suture.101 The opening of the uterine cavity, quent abnormal placentation with invasion of the
electrocoagulation and single-layer suture are risk fac- myometrium in the resection site.114–116 In the literature,
tors for UR: electrocoagulation leads to the development there are not many cases of accretism after myomec-
of a thin scar while a single-layer suture increases the risk tomy.52,93,117 Although the incidence is low, early diagno-
of rupture fourfold compared with double-layer sutur- sis is indispensable. If there is a strong suggestion of
ing.102 Nevertheless, the full-thickness suture, avoiding accretism, health-care providers should refer the patient
the formation of hematoma, is the real determinant risk to a tertiary care center.
factor, more than the double layer suture.103 Other risk
factors are extent of tissue destruction, development of Preterm delivery
infection or hematoma, BMI and the individual charac- Given the currently available evidence, pregnancy after
teristics related to the production of growth factors.95 myomectomy carries a risk of preterm delivery.91,118–120
The literature suggests the use of contraception after sur- The risk of preterm delivery after myomectomy does
gery, to allow for adequate wound healing. The estab- not seem to be associated with the surgical technique
lishment of an adequate interval period is problematic: (LM vs AM).118 One study noted a rate of 35% for pre-
some studies suggested a period between 2 and term delivery,91 while another found a rate of 6.3%.119
12 weeks, others, 12 months; while others concluded that There is a lack of data on the analysis of other indepen-
there is no safe interval.96,103–106 The challenge is how to dent risk factors that play a role in the incidence of pre-
identify women at higher risk: a possible strategy is to term delivery: advanced maternal age, obesity, fertility
perform second-look laparoscopy to assess the thickness treatment, multiple pregnancy and so on, and that can
and quality of hysterotomy, or intraoperative US, which obviously influence the mode and the time of delivery.
could evaluate the presence of hematoma.101 Fertile Available data suggest that scheduled CS at 36–39 weeks
women who undergo myomectomy are at risk of UR, optimizes maternal and fetal outcomes.
therefore they should be completely counselled and care-
fully followed up. Blood loss during delivery
The presence of uterine scars creates an area of substitu-
UR during second trimester pregnancy termination tion of the muscle tissue with a fibroid tissue that causes
The number of women seeking a second trimester abor- reduced capacity for contraction during and after deliv-
tion has been increased due to the widespread availabil- ery, and indeed, significant blood loss at delivery in
ity of prenatal diagnostic techniques. Medical abortion in pregnant women with previous myomectomy has been
women with a history of CS and myomectomy is rarely reported.91,118,120 The incidence of hemorrhage does not
attempted because of the more severe complications in depend on the surgical technique (LSM vs AM).118
this group.107 Data in the literature are poor.108,109 There
is an increase in UR in pregnancies terminated in the Cesarean delivery
mid-trimester by the induction of labor, above all when Most women with a previous myomectomy were more
oxytocin is used with prostaglandin.110 Larger random- likely to require CS to minimize the risk of UR. The risk
ized trials should be performed to identify the optimal appears to be low after both AM and LSM, and similar
therapy for patients with scarred uterus. For all these to the risk after previous CS. One study noted a rate of
reasons, it would be advisable to perform prenatal 74.5% for CS, for which the indications for elective CS
screening tests to facilitate pregnancy interruption dur- were patient age, uterine scar, infertility length, and pa-
ing the first trimester if needed. tient and practitioner concerns.121 Despite poor data on
the risk of UR after hysteroscopic myomectomy,122,123
Abnormal placentation an increased incidence of CS (35.6%) is recorded after
A previous CS or any other conditions of myometrial hysteroscopy myomectomy, although the CS rate seems
damage represent a risk of placenta accreta.111–113 The not to be affected by the number and the characteristics
substitution of the muscle tissue with collagen repair of removed myomas (G0, G1, G2).124,125 The reported
tissue (resectoscopic myomectomy and abdominal or rate of CS (22%) after uterine artery embolization
laparoscopic myomectomy, endometrial defect, (UAE) is associated with the high rate of
submucous myoma, thermal ablation and transarterial malpresentation because, although UAE decreases the
embolization) carries a great risk of placenta accreta. size of fibroids, it does not eliminate myoma.120

1800
12 ©©2017
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JapanSociety
Societyof
ofObstetrics
Obstetrics and
and Gynecology
Myomaand
Myoma andmyomectomy
myomectomy in pregnancy

According to the literature, however, CS is advisable 7. Benaglia L, Cardellicchio L, Filippi F et al. The rapid growth of
when >50% of the myometrium is involved during fibroids during early pregnancy. PLoS One 2014; 9: e85933.
8. Ciavattini A, Delli Carpini G, Clemente N et al. Growth trend
myomectomy; when a multiple myomectomy is per- of small uterine fibroids and human chorionic gonadotropin
formed; and when myomectomy has created a large de- serum levels in early pregnancy: An observational study. Fertil
fect in the active segment of the uterus.126 Careful Steril 2016; 105: 1255–1260.
management of labor is a prerequisite to ensure low risk 9. Rosati P, Exacoustos C, Mancuso S. Longitudinal evaluation
of maternal complications and good perinatal outcome. of uterine myoma growth during pregnancy. A sonographic
study. J Ultrasound Med 1992; 11: 511.
Pregnant women with previous myomectomy could be 10. Strobelt N, Ghidini A, Cavallone M, Pensabene I, Ceruti P,
managed similarly to those with previous CS with trial Vergani P. Natural history of uterine leiomyomas in preg-
of labor. nancy. J Ultrasound Med 1994; 13: 399–401.
In conclusion, pregnancy in patients with fibroids 11. De Vivo A, Mancuso A, Giacobbe L et al. Uterine myomas dur-
ing pregnancy: A longitudinal sonographic study. Ultrasound
should be considered as high risk, not only because of
Obstet Gynecol 2011; 37: 361–365.
the adverse outcomes due to fibroid (s) but also because 12. Piazze Garnica J, Gallo G, Marzano PF et al. Clinical and ultra-
of the other clinical associated factors, such as advanced sonographic implications of uterine leiomyomatosis in preg-
maternal age, obesity, pregnancy obtained by assisted re- nancy. Clin Exp Obstet Gynecol 1995; 22: 293–297.
productive techniques, and uterine scar. Patients with fi- 13. Gojnic M, Pervulov M, Petkovic S, Papic M, Jeremic K, Mostic
broids should be counseled by a senior clinician and T. Indication of myomectomy during pregnancy from Doppler
ultrasonography. Clin Exp Obstet Gynecol 2004; 31: 197–198.
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ing from the literature in the management of myomas Color Doppler ultrasonography for distinguishing myomas
or prior myomectomy with respect to obstetric care is from uterine contractions in pregnancy. J Reprod Med 2001;
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counsel gynecologists, because conflicting results from 15. Bronshtein M, Zimmer EZ, Miselevich I, Sabo E, Ohel G,
Löwenstein L. The possible impact of a myomatous uterus
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Disclosure 91: 1215e23.
19. Carranza-Mamane B, Havelock J, Hemmings R et al. The man-
The authors declare no conflict of interest. agement of uterine fibroids in women with otherwise unex-
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ofObstetrics
Obstetrics and
and Gynecology
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myomectomy in pregnancy

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