Myomas are observed in about 3–12% of pregnant women. Uterine fibroids may affect the outcome of pregnancy. The presence of myomas – in particular of myomas that distort the uterine cavity and larger intramural myomas – has been associated with infertility. In the case of pregnancy, it has been linked to an increased risk of spontaneous abortion, fetal malpresentation, placenta previa, preterm birth, cesarean section, and peripartum hemorrhage. Although fibroids may negatively affect pregnancy outcome, the impact of their treatment, particularly in quantitative terms, is unclear. Hysteroscopic myomectomy is the treatment of choice for submucous fibroids. The comparative efficacy of laparoscopic, laparotomic, or new modalities of treatment of intramural fibroids is not known. Up to date the choice and modalities of treatment of submucous fibroids should not be based on sound evidence but on clinical concerns and the skill of each center.
Highlights
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Fibroids increase the risk of several obstetric diseases/conditions twice as high as that in the general population.
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Submucous fibroids have the greatest negative impact on pregnancy outcome whereas the role of intramural or subserous fibroids is less clear.
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The treatment of uterine fibroids may improve pregnancy outcome, although the real impact, particularly in quantitative terms, is unclear.
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Hysteroscopic myomectomy is the treatment of choice for submucous fibroids. The comparative efficacy of laparoscopic, laparotomic, or new modalities of treatment is not known.
Introduction
Uterine fibroids are a common condition : in particular, myomas are reported in about 3–12% of pregnant women . In addition to causing pain, uterine fibroids may also affect the outcome of pregnancy. The presence of myomas – in particular of myomas that distort the uterine cavity and larger intramural myomas – has been associated with infertility; in the case of pregnancy, this has been linked to an increased risk of spontaneous abortion, fetal malpresentation, placenta previa, preterm birth, cesarean section, and peripartum hemorrhage .
Myomectomy is the standard of care for treating symptomatic fibroids in women who wish to bear more children. However, presently, other techniques such as artery embolization, robot-assisted myomectomy, or magnetic resonance imaging (MRI)-guided focused ultrasound surgery (MRgFUS) are available. However, the different efficacy profiles of different techniques on the pregnancy outcome are still a matter of debate .
In this paper, we review the association between fibroids and pregnancy outcome, as well as the role of fibroid treatment in improving the pregnancy outcome.
In 2008, a review on the effect of myomas on pregnancy outcome was published along with a pool estimate of the frequency of outcomes. Metwally et al. published a Cochrane Database systematic review on the effect of treatment of fibroids on pregnancy outcome .
With the aim of updating these reviews/meta-analyses, we searched the electronic databases MEDLINE and EMBASE (from 2009 to present day), using the Medical Subject Heading (MeSH) term “uterine fibroids” combined with “pregnancy.” The results of the retrieved studies and the relevant reviews recently published were considered for this paper.
Fibroids and pregnancy outcome
The presence of fibroids has been associated with an increased risk of several obstetric diseases/conditions.
Miscarriage
In 2008, Klatsky et al. reported an increased risk of miscarriages in women with uterine fibroids compared to women without fibroids. Similarly, in a meta-analysis, Pritts et al. found any location of a fibroid to be associated with an increased risk of miscarriages of 1.7 (95% confidence interval (CI) 1.4–2.1). This analysis included women who underwent assisted reproductive technology (ART).
The studies published after the Klatsky review, which have also analyzed the association between uterine fibroids and miscarriage risk, are shown in Table 1 . All of these studies substantially confirmed the results reported by Klatsky et al. , confirming an overall twofold increased risk of miscarriage in women with (submucous/intramural) fibroids.
| Author, year | Type of study | Country | No. of women with fibroids | Miscarriage rate/1100 pregnancies | Malpresentation | Placenta previa | Preterm birth |
|---|---|---|---|---|---|---|---|
| Klatsky et al., 2008 | Systematic review | Several countries | Intramural 15.3–22.4°% Submucous 46.7% | women with fibroids 13.0% (466/3585), control 4.5% (5864/130,932), P = 0.001 OR: 2.9 (2.6–3.2) | 16% | ||
| Chen et al., 2009 | Analysis of population-based database | China | 5627 | preterm births (10.98 with fibroids vs. 7.78% without fibroids, P < 0.001) | |||
| Stout et al., 2010 | Retrospective cohort study | USA | 2058 | Breech presentation (5.3% compared with 3.1%, adjusted odds ratio (OR) 1.5, 95% confidence interval (CI) 1.3–1.9), | 1.4% compared with 0.5%, adjusted OR 2.2, 95% CI 1.5–3.2 | preterm birth <37 weeks 15.1% (compared with 10.5%, adjusted OR 1.5, 95% CI 1.3–1.8), and <34 weeks (3.9% compared with 2.8%, adjusted OR 1.4, 95% CI 1.0–1.8), | |
| Shavel et al., 2012 | Retrospective cohort study | USA | 95 | Compared to women with no fibroids or small fibroids (≤5 cm), women with large fibroids (>5 cm) delivered at a significantly earlier gestational age (38.6 vs. 38.4 vs. 36.5 weeks). | |||
| Lai et al., 2012 | Retrospective cohort study | USA | 401 | the presence of leiomyomata was associated with statistically significant increased risks of preterm delivery at <34 weeks (adjusted odds ratio (AOR) 1.7, 95% confidence interval (CI) 1.1–2.6), <32 weeks (AOR 1.9, 95% CI 1.2–3.2), and <28 weeks (AOR 2.0, 95% CI 1.1–3.8)) | |||
| Navid et al., 2012 | Prospective study | Pakistan | 80 | 10% | 12.5% | 2.5% | 10% |
| Stout et al., 2013 | Retrospective cohort study | USA | 59 twin pregnancies | Twin pregnancies with fibroids were no more likely to have preterm delivery <34 weeks (25.0% vs. 24.0%, aOR 1.0, 95%CI 0.5–1.9) than twin pregnancies without fibroids. | |||
| Borja de Mozota et al., 2014 | Retrospective study | Guadalupe | 66 pregnancies | 25.8% miscarriage. | |||
| Ciavattini et al., 2015 | Retrospective cohort study | Italy | 214 | Compared to women with no fibroids, women with multiple fibroids: breech presentation (11.8% vs. 2.7%, P = 0.04). | Compared to women with no fibroids, women with multiple fibroids had a significantly higher rate of preterm birth (29.4% vs. 5%, P < 0.001 Women with large fibroids:16.7% |
Fetal malpresentation
Fetal malpresentation, primarily breech presentation, has also been found to be increased among women with fibroids.
Klatsky et al. reported a cumulative frequency of malpresentation of 13%., that is, about 2.5 times higher than in the general population.
We identified three further studies that reported the frequency of breech presentation among women with fibroids. The reported frequency in two of these studies was largely consistent with the Klatsky estimate , whereas that in the third study was substantially lower, but higher than that in the control group .
Placenta previa
We identified two studies on the association between fibroids and the frequency of placenta previa. Consistent with the results of Klatsky et al. both studies reported an approximately twofold increased risk.
Preterm birth
In addition to miscarriage, preterm birth is the most commonly reported negative outcome of pregnancy among women with fibroids.
Klatsky et al. reported a frequency of preterm delivery of 16% among women with fibroids. In 2009, using a 3-year nationwide population-based database, Chen et al. examined the risk of adverse pregnancy outcomes including preterm gestation in pregnant women with uterine leiomyomas. A total of 5627 mothers with uterine leiomyoma and 28,135 unaffected mothers were included for analysis. After adjusting for mother and infant characteristics and monthly family income, women with uterine leiomyomas were found to have a significantly higher percentage of preterm births (11% vs. 7.8%, P < 0.001) than unaffected mothers were. Log-binominal regression models showed that the adjusted risk ratio (ARR) of preterm births for mothers with uterine leiomyoma was 1.32 (95% CI 1.19–1.46), compared with unaffected mothers . Similar results were reported by Lai et al. In a small series, Navid reported a frequency of preterm birth of 10% .
Shavel et al. showed that compared to women with no fibroids or small fibroids (≤5 cm), women with large fibroids (>5 cm) delivered at a significantly earlier gestational age (38.6 vs. 38.4 vs. 36.5 weeks).
Stout et al. reported no association between fibroids and preterm birth. The authors partly attributed this finding to the greater frequency of growth ultrasounds and antenatal testing used for twin pregnancies; thus, the risks of adverse outcomes seen in singleton cohorts with fibroids may be avoided in twin gestations.
Conti et al. conducted a multicentric, observational, and retrospective study including women with uterine fibroids. Patients with uterine fibroids showed a significantly greater incidence of preterm birth ( P < 0.0001).
Finally, Ciavattini et al. reported an increased risk of preterm birth among women with multiple or large fibroids.
Placental abruption
Placental abruption has been associated with uterine fibroids as well as their location .
Klatsky et al. estimated the frequency of placental abruption to be 3.0%. In a large study, Stout et al. reported an increased risk of placental abruption (1.4% vs. 0.7%, adjusted odds ratio (AdjOR) 2.1, 95% CI 1.4–3.0) . Navid et al. reported a frequency of placental abruption of 7.5% (6/80), although this estimate was based on very small numbers. However, Stout et al. and Navid et al. did not describe the site of the placenta and fibroids.
Cesarean section
In the Klatsky review , 48.8% of women with fibroids and 13.3% of those without fibroids were delivered by cesarean section. We identified three studies that focused on this issue. In a large retrospective study, Stout et al. found that women with leiomyomas were more likely to require cesarean deliveries, even after excluding diagnoses such as placenta previa and breech presentation (33.1% vs. 24.2 1%, AdjOR 1.2 (1.1–1.3)). To determine whether women with leiomyomas detected using uniform ultrasound methods are at an increased risk of cesarean birth, without any indication, women were enrolled in the prospective cohort “Right from the Start Study.” Leiomyomas were counted, categorized, and measured during the first-trimester ultrasounds. Women with leiomyomas showed a 27% increase in the risk of cesarean birth (RR, 1.27; CI, 1.17–1.37) compared to women without leiomyomas. The association was weaker after adjusting for maternal body mass index and age (ARR, 1.11; CI, 1.02–1.20). The adjusted risk was elevated for women with a single leiomyoma of ≥3-cm diameter (ARR, 1.22; CI, 1.14–1.32) and women with the largest total leiomyoma volumes (ARR, 1.59; CI, 1.44–1.76) .
Similar results were reported in a retrospective study conducted in Italy, which showed that women with fibroids had a significantly higher rate of cesarean section than those without fibroids, although the risk was limited to women with multiple fibroids .
Postpartum hemorrhage
Klatsky et al. reported a frequency of postpartum hemorrhage of 2.5% among women with fibroids and 1.4% among those without fibroids.
Conti et al. conducted a multicentric, observational, and retrospective study including women with uterine fibroids, who showed significantly more postpartum bleeding.
We did not identify any other paper reporting on the frequency of postpartum hemorrhage.
On summarizing the results on the association between myomas and pregnancy outcome, the presence of fibroids was found to increase the risk of several obstetric diseases/conditions. Some discrepancies in the risk estimate were noted for the studies. These may be partly attributed to the lack of control groups, residual confounding, and biases inherent in study designs . However, for almost all of the considered conditions, most of the studies show a twofold higher risk than that in the general population.
Fibroids and pregnancy outcome
The presence of fibroids has been associated with an increased risk of several obstetric diseases/conditions.
Miscarriage
In 2008, Klatsky et al. reported an increased risk of miscarriages in women with uterine fibroids compared to women without fibroids. Similarly, in a meta-analysis, Pritts et al. found any location of a fibroid to be associated with an increased risk of miscarriages of 1.7 (95% confidence interval (CI) 1.4–2.1). This analysis included women who underwent assisted reproductive technology (ART).
The studies published after the Klatsky review, which have also analyzed the association between uterine fibroids and miscarriage risk, are shown in Table 1 . All of these studies substantially confirmed the results reported by Klatsky et al. , confirming an overall twofold increased risk of miscarriage in women with (submucous/intramural) fibroids.
| Author, year | Type of study | Country | No. of women with fibroids | Miscarriage rate/1100 pregnancies | Malpresentation | Placenta previa | Preterm birth |
|---|---|---|---|---|---|---|---|
| Klatsky et al., 2008 | Systematic review | Several countries | Intramural 15.3–22.4°% Submucous 46.7% | women with fibroids 13.0% (466/3585), control 4.5% (5864/130,932), P = 0.001 OR: 2.9 (2.6–3.2) | 16% | ||
| Chen et al., 2009 | Analysis of population-based database | China | 5627 | preterm births (10.98 with fibroids vs. 7.78% without fibroids, P < 0.001) | |||
| Stout et al., 2010 | Retrospective cohort study | USA | 2058 | Breech presentation (5.3% compared with 3.1%, adjusted odds ratio (OR) 1.5, 95% confidence interval (CI) 1.3–1.9), | 1.4% compared with 0.5%, adjusted OR 2.2, 95% CI 1.5–3.2 | preterm birth <37 weeks 15.1% (compared with 10.5%, adjusted OR 1.5, 95% CI 1.3–1.8), and <34 weeks (3.9% compared with 2.8%, adjusted OR 1.4, 95% CI 1.0–1.8), | |
| Shavel et al., 2012 | Retrospective cohort study | USA | 95 | Compared to women with no fibroids or small fibroids (≤5 cm), women with large fibroids (>5 cm) delivered at a significantly earlier gestational age (38.6 vs. 38.4 vs. 36.5 weeks). | |||
| Lai et al., 2012 | Retrospective cohort study | USA | 401 | the presence of leiomyomata was associated with statistically significant increased risks of preterm delivery at <34 weeks (adjusted odds ratio (AOR) 1.7, 95% confidence interval (CI) 1.1–2.6), <32 weeks (AOR 1.9, 95% CI 1.2–3.2), and <28 weeks (AOR 2.0, 95% CI 1.1–3.8)) | |||
| Navid et al., 2012 | Prospective study | Pakistan | 80 | 10% | 12.5% | 2.5% | 10% |
| Stout et al., 2013 | Retrospective cohort study | USA | 59 twin pregnancies | Twin pregnancies with fibroids were no more likely to have preterm delivery <34 weeks (25.0% vs. 24.0%, aOR 1.0, 95%CI 0.5–1.9) than twin pregnancies without fibroids. | |||
| Borja de Mozota et al., 2014 | Retrospective study | Guadalupe | 66 pregnancies | 25.8% miscarriage. | |||
| Ciavattini et al., 2015 | Retrospective cohort study | Italy | 214 | Compared to women with no fibroids, women with multiple fibroids: breech presentation (11.8% vs. 2.7%, P = 0.04). | Compared to women with no fibroids, women with multiple fibroids had a significantly higher rate of preterm birth (29.4% vs. 5%, P < 0.001 Women with large fibroids:16.7% |
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