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This chapter should be cited as follows:
Parazzini F, Gerli S, et al, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.415733

The Continuous Textbook of Women’s Medicine SeriesObstetrics Module

Volume 6

Pregnancy complaints and complications: clinical presentations

Volume Editor: Professor Gian Carlo Di Renzo, University of Perugia, Italy

Chapter

Fibroids and Pregnancy

First published: August 2021

AUTHORS

Fabio Parazzini
Department of Clinical Sciences and Community Health University of Milan, Milan, Italy
Sandro Gerli
Department of Surgical and Biochemical Sciences, Center of Perinatal and Reproductive Medicine, University of Perugia, Perugia, Italy
Stefano Bianchi
Department of Clinical Sciences and Community Health University of Milan, Milan, Italy
Francesca Chiaffarino
Department of Woman, Newborn and Child, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Alessandro Favilli
Department of Obstetrics and Gynecology, AOUI Verona, Verona, Italy

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INTRODUCTION

Uterine fibroids are common among women of fertile age, affecting 50–60% of women by the age of 50 years.1

Considering pregnant women, the reported prevalence of myoma ranges from 3 to 12%.2,3 As in the general population, among pregnant women fibroids are more common in black women and are associated with advancing maternal age, and thus the incidence of myoma in pregnant women increases with the age at pregnancy.4,5

Although in most cases fibroids produce no symptoms and do not require treatment, their presence in pregnancy may be a cause of worry for both patient and gynecologist, and are also a potential cause of more severe complaints; it has been estimated that 10–40% of women with fibroids during pregnancy experience complications associated with myoma.5 Myoma in pregnancy can cause pain and discomfort due to torsion or degeneration. Furthermore, several studies and clinical experience have suggested that, in particular, larger intramural myomas may increase the frequency of spontaneous abortion, fetal malpresentation, placenta previa, preterm birth, and cesarean section, and increase the risk of peripartum hemorrhage.

In this paper we review the association between fibroids and pregnancy outcome. Furthermore, we consider the evidence regarding the safety of myomectomy during pregnancy. We also briefly consider the role of treatment of fibroids before pregnancy in improving pregnancy outcome.

EFFECT OF PREGNANCY ON FIBROIDS

Most textbooks generally indicate that fibroid size increases during pregnancy.

This suggestion is traditionally supported by the hypothesis that the increasing levels of serum estrogens in pregnancy cause the growth of fibroids.

However, this hypothesis is not totally confirmed by clinical considerations: for example, myomas significantly increase in size during early pregnancy when estrogen and progesterone are still low, and decrease in the third trimester when hormone levels are higher.6

Another hypothesis links fibroid growth with the rapid raise in serum human chorionic gonadotropin in early pregnancy and the particular kinetic of its receptor.6

The true effect of pregnancy on fibroids is, however, controversial, some studies showing an increase in size and others not.7,8,9

Vitagliano et al. recently conducted a systematic review on uterine size modification during pregnancy and concluded that: Concerning the first trimester of pregnancy, all authors reported a significant growth of uterine fibroids. Contradictory evidence was found about uterine fibroid modifications during the second and third trimesters, mainly supporting a slowdown during mid pregnancy and a subsequent size reduction during late pregnancy. Concerning the overall modifications during pregnancy and puerperium, poor evidence quality suggests that uterine fibroids do not modify their volume/slightly enlarge during pregnancy and subsequently reduce in size during puerperium.10

Fibroids of the cervix seem to be at the highest risk of growth during pregnancy11 when compared to those in other locations. It should be also considered that cervical myomas may migrate upwards during pregnancy, due to development of the lower uterine segment.12

SYMPTOMS OF FIBROIDS IN PREGNANCY

Pain and bleeding early in pregnancy are the most common fibroid-related symptoms. In a large series of pregnant women with fibroids the most common symptom was pain, followed by both bleeding and pain, and then bleeding only.13

Increase in size may cause compression and displacement of surrounding organs and consequent urinary and gastroenteric symptoms. Not only large tumors, but also small fibroids and increasing numbers of myomas, are associated with pain.13

Torsion of pedunculated fibroids may occasionally occur, causing acute abdominal pain, necrosis, and inflammatory peritoneal reaction. This is a rare condition, and surgery is inevitable.

EFFECTS OF FIBROIDS ON PREGNANCY

In 2008 a review on the effect of myomas on pregnancy outcome was published14 giving an estimation of the frequency of possible outcomes.

Since the publication of that review, other general or systematic reviews focused on specific pregnancy outcomes have been published. The following section is based mainly on the evidence reported in these reviews.

Miscarriage

In 2008 Klatsky et al.14 reported an increased risk of miscarriage in women with uterine fibroids versus those without. Likewise any location of fibroids was associated with increased risk of miscarriage in a meta-analysis conducted by Pritts et al.15 This analysis, however, included women who underwent assisted reproductive technology (ART). Similar results were reported in our previous paper.16

In 2017, Sundermann et al. reviewed studies analyzing the risk of spontaneous abortion among pregnant women of typical reproductive potential with and without uterine leiomyoma: no increase was reported in the risk of spontaneous abortion among those with leiomyoma compared to those without (11.5% compared with 8.0%; risk ratio [RR]: 1.16, 95% confidence interval [CI]: 0.80–1.52). The authors suggested that: “Failure of prior studies to adjust for confounders may have led to the common clinical belief that leiomyomas are a risk factor for spontaneous abortion”.17

Although in general the presence of fibroids appears not to increase the risk of miscarriage, it should be considered that their effect may differ according to size and location. Submucosal and small myomas (<3 cm) increase the risk of spontaneous miscarriage slightly, whereas larger subserosal or intramural myomas do not increase the risk of pregnancy loss.18

Continuing this theme, a meta-analysis was published in 2011 on the role of intramural fibroids in reproductive outcomes after ART.19 The authors of this meta-analysis considered ten studies reporting the effects of intramural fibroids on assisted conception treatment. A combined analysis of the included studies, after taking into account possible confounding factors, showed no evidence of a significant effect of intramural fibroids on the rate of miscarriage (OR: 1.61, 95% CI: 0.61–4.20).

Fetal Malpresentation

Fibroids may alter the uterine cavity causing fetal malpresentation – mainly breech presentation. Klatsky et al.14 reported a cumulative frequency of malpresentation of 13%, i.e., about 2.5 times higher than in the general population. In 2018, Jenabi and Khazaei conducted a systematic review on this issue20 and confirmed this estimation of the risk.

Placenta Previa

Klatsky et al.14 showed an increased risk of around twofold of placenta previa in women with uterine fibroids. Janabi and Fereidooni21 reviewed the data from case–control and cohort studies and found that, based on OR estimates in women with uterine leiomyoma, the adjusted risk of placenta previa was 2.2 (95% CI: 1.5–2.9).

Preterm Birth

Preterm birth is, with miscarriage, the most commonly reported negative outcome of pregnancy among women with fibroids. A recent meta-analysis considered the relation between uterine fibroids, as determined by ultrasound, and risk of preterm birth. Eighteen studies were included, comprising 276,172 pregnancies in which obstetric ultrasound assessment was performed for the presence/absence of fibroids. Women with fibroids were older (mean difference = 2.40 years, 95% CI: 0.94–3.85) and were at higher risk of preterm birth before 37 weeks (RR: 1.43, 95% CI: 1.27–1.60), 34 weeks (RR: 1.79, 95% CI: 1.32–2.42), 32 weeks (RR: 1.94, 95% CI: 1.33–2.85), and 28 weeks (RR: 2.17, 95% CI: 1.48–3.17) as compared to those without fibroids (P <0.01).22 The risk was similar for late and very late and preterm birth.

No association between fibroids and preterm birth in twin pregnancies emerged in a study by Kim et al.23 The authors partly explained this lack of association with the fact that twin pregnancies are surveyed more frequently by growth ultrasound and antenatal testing, and thus the risks for adverse outcomes seen in singleton cohorts with fibroids may be avoided in twin gestations.

Placental Abruption

Jenabi and Zagami analyzed the association between uterine fibroids and risk of placental abruption based on OR estimates obtained from case–control and cohort studies; they found a significant association (2.63; 95% CI: 1.38–3.88).24

A similar estimation was also reported in a systematic review conducted by Pérez-Roncero et al.22 The risk appears to be related to fibroid location.5

Cesarean Section

Several studies have shown that uterine fibroids increase the risk of cesarean delivery.14,20

The risk is higher in women with fibroids in comparison with those without the condition.

Part of this association is explained by the increased frequency of conditions such as breech presentation in women with uterine fibroids.2

Postpartum Hemorrhage

Few studies showing conflicting results, have been published on the relation between fibroids and postpartum hemorrhage risk.14,25,26

Pérez-Roncelo et al. analyzed this topic in a systematic review on the effect of fibroids on pregnancy outcome.22 They identified eight studies: the pooled OR of postpartum hemorrhage (1.4) was in women with uterine fibroids in comparison with those without;, this finding was not statistically significant.

SYNTHESIS OF THE EFFECT OF FIBROIDS ON PREGNANCY OUTCOME

Published data suggest that the presence of fibroids is associated with an increased risk of around two- to threefold of fetal malpresentation, placenta previa, preterm birth, placental abruption, and cesarean delivery. Less clear is the association with miscarriage and postpartum hemorrhage.

On the basis of published findings, it is also reasonable to conclude that size and number of fibroids are both associated with increased risk of poor pregnancy outcome. Regarding the site of fibroids, large intramural fibroids may increase the risk.

TREATMENT OF FIBROIDS IN PREGNANCY

Surgical treatment of fibroids is uncommon in pregnancy, particularly during the first trimester. Although conservative management is considered the gold standard, in some cases surgery must be performed.

Table 1 shows the main indications for surgical treatment of myoma (myomectomy) during pregnancy.

1

Indications for myomectomy in pregnancy.

Torsion of a pedunculated myoma

Necrosis of fibroid and consequent inflammatory peritoneal reaction

Pedunculated myoma causing complete axial torsion of the pregnant uterus

Spontaneous rupture of a degenerated fibroid

Recurrent or severe pain that did not respond to conservative management after the first trimester

Rapid growth of myoma

Large fibroids located in the lower uterine segment or causing deformation of the site of placentation

Large fibroid causing compression phenomena with intestinal obstruction or sub-obstruction

Major concerns relate to uncontrollable bleeding, uterine atony, hysterectomy, pregnancy injury and/or pregnancy loss, and formation of postoperative uterine–intestinal adhesions.

Similar risks have generally been considered in cases of cesarean myomectomy. However, several cases have been reported in the literature of myomectomy in pregnancy with favorable results, and also in one case of large fibroids.

Basso et al. reviewed the literature on the issue,27 reporting on 197 women who underwent myomectomy during pregnancy. The procedure was successful in 184 of these women, while in the remaining 13 a miscarriage or fetal demise occurred following myomectomy. Maternal outcomes were favorable after myomectomy, with only two episodes of hemoperitoneum, one uterine abscess, and only one woman requiring perioperative blood transfusion.

The absolute contraindications to myomectomy during pregnancy are listed in Table 2.

2

Absolute contraindications to myomectomy.

Uterine atony

Intramural nodules growing and expanding toward the uterine cavity or displacing large vessels

In the paper of Basso et al., the most common surgical approach was laparotomy.27 However, the laparoscopic approach should be considered; in this approach, the main concern is the Veress needle technique, due to the risk of damage to the uterus or other intra-abdominal organs as fundal height increases (Table 3).

3

Recommendations for myomectomy in pregnancy.

Open technique and the site of entry selected according to fundal height

Patient should be placed in left lateral recumbency

Pneumoperitoneum should not exceed 10–15 mmHg

Monopolar energy should never be used

Bipolar energy should be applied only if strictly necessary

Uterine mobilization should be avoided

Finally, myomectomy during cesarean section can be considered only in selected patients if unavoidable, to facilitate safe delivery of the fetus or closure of the uterine breach.

Pedunculated subserosal fibroids can also be safely dealt with during cesarean birth without increased risk of hemorrhage.

ROLE OF TREATMENT OF FIBROIDS BEFORE PREGNANCY TO IMPROVE PREGNANCY OUTCOME

Several observational studies have analyzed the effects of myomectomy before pregnancy on obstetric outcome. Unfortunately few randomized trials have investigated this topic.

In general, non-controlled studies have suggested a decrease in miscarriage rate following myomectomy. The rate of miscarriage after myomectomy was generally compared with that reported before surgery. The reported reduction in miscarriage rate ranges from 60 to 20% after hysteroscopic treatment of submucous fibroids, and from 45 to 25% after laparoscopic myomectomy. In particular, patients with submucosal myoma are known to benefit significantly more from myomectomy, with a greater impact on fertility and pregnancy outcome, although no sound data support this clinical judgment.

Metwally et al.19 conducted a systematic review of randomized controlled trials examining the effect of myomectomy compared to no intervention on fertility outcomes in infertile women. This analysis included four randomized controlled trials and 442 women.

The authors concluded that: “There is limited evidence to determine the role of myomectomy for infertility in women with fibroids as only one trial compared myomectomy with no myomectomy.”

With regard to the type of treatment used, the same review concluded that: “If the decision is made to have a myomectomy, the current evidence does not indicate a superior method (laparoscopy, laparotomy or different electrosurgical systems) to improve rates of live birth, preterm delivery, clinical pregnancy, ongoing pregnancy, miscarriage, or cesarean section."

In clinical practice, hysteroscopic myomectomy is the most common procedure for treatment of submucosal myoma. Transabdominal myomectomy (TAM), at laparotomy or laparoscopy, is indicated for intramural and subserosal myoma.

The potential complications  of these surgical procedures are listed in Table 4.

4

Potential complications of surgical procedures.


Potential complications

Hysteroscopic surgery

Intrauterine adhesions (more frequent in the case of large myomas or with postoperative endometritis)

TAM: laparotomy or laparoscopy

Postoperative adhesions

Uterine rupture during pregnancy

Following TAM at laparotomy or laparoscopy, most clinicians prefer cesarean section for patients with a transmural incision alongside the opening of the endometrial cavity. Other techniques, such as robot-assisted myomectomy, magnetic resonance-guided focused ultrasound, or artery embolization, are also currently available. However, the data on pregnancy outcome after these modalities of myomectomy are very limited. Likewise, little information is available on the risk of uterine rupture during pregnancy or delivery.

PRACTICE RECOMMENDATIONS

  • Submucous fibroids have a negative impact on pregnancy outcome.
  • The role of intramural fibroids is unclear.
  • Multiple or large fibroids are likely to have a negative impact on pregnancy outcome.
  • The treatment of uterine fibroids may improve pregnancy outcome but the real impact, particularly in quantitative terms, is unclear.
  • The main indications for myomectomy during pregnancy are: fibroid necrosis and consequent inflammatory peritoneal reaction; rapid growth of myoma; large fibroids located in the lower uterine segment or causing deformation of the placentation site; large fibroid causing compression phenomena with intestinal obstruction or sub-obstruction.
  • The comparative efficacy of different treatment modalities before and during pregnancy has not been studied.

CONFLICTS OF INTEREST

The authors of this chapter declare that they have no interests that conflict with the contents of the chapter.

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Conti N, Tosti C, Pinzauti S, et al. Uterine fibroids affect pregnancy outcome in women over 30 years old: role of other risk factors. J Matern Fetal Neonatal Med 2013;26(6):584–7.

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Zhao R, Wang X, Zou L, et al. Adverse obstetric outcomes in pregnant women with uterine fibroids in China: a multicenter survey involving 112,403 deliveries. PLoS One 2017;12:e0187821.

27

Basso A, Catalano MR, Loverro G, et al. Uterine fibroid torsion during pregnancy: a case of laparotomic myomectomy at 18 weeks' gestation with systematic review of the literature. Case Rep Obstet Gynecol 2017;2017:4970802. doi: 10.1155/2017/4970802).

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