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OBSTETRICS

Congenital uterine anomalies and

adverse pregnancy outcomes
Meiling Hua, MD; Anthony O. Odibo, MD, MSCE; Ryan E. Longman, MD; George A. Macones, MD, MSCE;
Kimberly A. Roehl, MPH; Alison G. Cahill, MD, MSCI
OBJECTIVE: We sought to estimate whether the presence of a maternal

uterine anomaly is associated with adverse pregnancy outcomes.

STUDY DESIGN: This retrospective cohort study included singleton
pregnancies undergoing routine anatomic survey from 1990 through
2008 at a major tertiary care medical center. Pregnancies with a diagnosis of uterine anomaly (uterine septum, unicornuate uterus, bicornuate uterus, uterine didelphys) were compared to those with normal
anatomy. Primary outcomes of interest were spontaneous preterm birth
(PTB), breech presentation, and cesarean delivery.
RESULTS: The presence of an anomaly was associated with PTB 34

weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI],

4.8 11.4; P .01), PTB 37 weeks (aOR, 5.9, 95% CI, 4.3 8.1;
P .01), primary nonbreech cesarean delivery (aOR, 2.6; 95% CI,
1.7 4.0; P .01), preterm premature rupture of membranes (aOR,
3.2; 95% CI, 1.8 5.6; P .01), and breech presentation (aOR, 8.6;
95% CI, 6.212.0; P .01).
CONCLUSION: Women with a uterine anomaly are at risk for PTB, high-

lighting an at-risk population that needs additional study for possible interventions for PTB prevention.
Key words: adverse pregnancy outcomes, bicornuate, didelphys,
mllerian anomalies, preterm birth, septum, unicornuate

Cite this article as: Hua M, Odibo AO, Longman RE, et al. Congenital uterine anomalies and adverse pregnancy outcomes. Am J Obstet Gynecol 2011;205:558.e1-5.

he prevalence of mllerian anomalies is often derived from a primary

infertility cohort, but the true prevalence
among the general population is difficult
to estimate.1 The most common mllerian anomalies include uterine septum,
unicornuate uterus, bicornuate uterus,
and uterine didelphys. Although it has
been established that congenital uterine
anomalies lead to infertility and recurrent first-trimester pregnancy loss,2,3 the
relationship between uterine anomalies
and adverse pregnancy outcomes in the

The authors report no conflict of interest.

third trimester is less well studied. Some

who have found an association between
uterine anomalies and preterm birth
(PTB) theorize that diminished muscle
mass, particularly in a unicornuate uterus,
plays an important role in the mechanism
of preterm delivery.4 The existing data
linking the presence of uterine anomalies
to outcomes such as PTB, preterm premature rupture of membranes (PPROM),
breech presentation, and cesarean section
are mostly derived from small case-control
studies or case reports.1,2,4,5-7
We aimed to improve upon the existing published data regarding congenital
uterine anomalies and adverse pregnancy outcomes. We hypothesized that
the presence of a uterine anomaly at routine ultrasound is associated with PTB,
preterm rupture of membranes, and cesarean delivery.

Presented at the 31st annual meeting of the

Society for Maternal-Fetal Medicine, San
Francisco, CA, Feb. 7-12, 2011.

M ATERIALS AND M ETHODS

From the Department of Obstetrics and

Gynecology, Washington University in St.
Louis School of Medicine, St. Louis, MO.
Received Feb. 22, 2011; revised June 4, 2011;
accepted July 13, 2011.

Reprints: Meiling Hua, MD, Department of

Obstetrics and Gynecology, Washington
University School of Medicine, 4911 Barnes
Jewish Hospital Plaza, Campus Box 8064, St.
Louis, MO 63110. huam@wudosis.wustl.edu.
0002-9378/$36.00
2011 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2011.07.022

558.e1

We performed a retrospective cohort

study to estimate the relationship between congenital uterine anomalies and
adverse pregnancy outcomes. Our cohort was comprised of all consecutive
singleton pregnancies undergoing routine
anatomic survey from 1990 through 2008
at our tertiary care center. The study was

American Journal of Obstetrics & Gynecology DECEMBER 2011

conducted using the institutional perinatal

database. Before study initiation, approval
by our institutional human studies review
board was obtained.
Women participating in the study had
their demographic information, history,
and pregnancy outcomes entered into a
prenatal database. Since creation of the
prenatal database in 1988, all of the patients seen in the prenatal diagnosis
center have been followed by dedicated
pregnancy outcome coordinators. To
achieve complete follow-up information on pregnancy outcome, each patient was given a standardized form at
the first visit to be completed after delivery, which detailed pregnancy outcome.
The database included follow-up sheet
also included details about pregnancy
complications, delivery indications, and
neonatal outcomes, including chromosomal and structural abnormalities. If
the form was not returned within 4
weeks of expected date of delivery, the
patient received a telephone call from an
outcome coordinator. If the patient
could not be reached after delivery, the
referring physician was then contacted.
For patients delivering within network,
outcome information was extracted
from the electronic medical record. Ges-

Obstetrics

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TABLE 1

Maternal and pregnancy characteristics of patients with a

congenital uterine anomaly compared to those without

Characteristic

Abnormal uterine
morphology
(n 203)

Normal uterine
morphology
(n 66,753)

Mean maternal age, y

29.3 0.4

30.1 0.02

Median age, y (IQR)

30 (10)

30 (9)

P value
.02

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

Mean gravidity

2.4 1.5

2.7 1.6

Median gravidity (IQR)

2 (2)

2 (2)

Mean parity

0.7 0.9

1.0 1.2

.06

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

.01

..............................................................................................................................................................................................................................................

Median parity (IQR)

0 (1)

1 (2)

..............................................................................................................................................................................................................................................

Mean maternal BMI

23.7 7.8

25.0 9.4

Median maternal BMI (IQR)

23.8 (6.4)

24.7 (7.7)

Gestational age at examination, wk

18.9 1.7

19.2 1.7

Prior preterm birth

.03

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

.01

..............................................................................................................................................................................................................................................

11.3%

6.0%

.01

Chronic hypertension

1.0%

2.4%

.18

Prior stillbirth

5.4%

2.3%

.01

Preeclampsia

11.5%

8.0%

.07

Gestational diabetes

5.0%

5.1%

.9

African American race

7.4%

23.1%

.01

Maternal renal disease

3.0%

0.6%

.01

..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

BMI, body mass index; IQR, interquartile range.

Hua. Pregnancy complications associated with mllerian anomalies. Am J Obstet Gynecol 2011.

tational age was determined by the first

day of the womans last menstrual period
(LMP). If the LMP-estimated due date
was consistent (5 days in the first trimester, 14 days in the second trimester, and 21 days in the third trimester)
with the due date obtained from growth
measurements at the first ultrasound
then the due date was not changed. If the
due dates by LMP and first ultrasound
were not consistent, then the ultrasound-obtained due date was used to define gestational age. Maternal demographics, obstetric history, indications for the
ultrasound visit, findings from the ultrasound examination or any testing performed, and outcome of the pregnancy
were all collected and stored in the database. Patients with incomplete follow-up
data were excluded from this study.
Evaluation of maternal uterine anatomy was performed as part of every routine anatomic survey. We defined the
primary exposure as the presence of
a uterine anomaly diagnosed prior to
pregnancy or identified at that survey.

We compared the incidence of adverse

pregnancy outcomes in our 2 study populations: those with a congenital uterine
anomaly vs those with normal uterine
anatomy. Our primary outcomes were
spontaneous PTB (both 34 weeks and
37 weeks), PPROM (defined as rupture
of membranes 37 weeks), breech presentation, and cesarean delivery. Intrauterine
growth restriction (IUGR) was defined as
10th percentile for gestational age.8
The incidence of mllerian anomalies
in our study population was estimated.
Descriptive statistics were used to describe and compared the baseline characteristics of the 2 study groups. To compare baseline features between groups,
Student t test was used for continuous
variables, 2 for categorical variables, or
Fisher exact test for rare categorical variables. Univariable analysis was used to estimate the relative risk (RR) of each outcome of interest (PTB, PPROM, breech,
and cesarean delivery). We performed
stratified analyses to identify potentially
confounding factors. Logistic regression

Research

analyses were used to better estimate the

relationship between uterine anomalies
and our defined outcomes while adjusting
for potentially confounding effects. Factors identified by the stratified analyses, as
well as those with biological plausibility or
historically reported to be associated with
the outcomes of interest, were considered
in the logistic regression analysis. Year of
examination was considered categorically
in increments of 4 years, to account for the
long duration of the study period. Backward selection was used to reduce the
number of variables in the model by assessing the magnitude of change in the effect
size of the other covariates. Differences in
the explanatory models were tested using
the likelihood ratio test or Wald test.9 All
variables that were statistically significant
were included in the final models. A subgroup analysis of risk of PTB before both
34 and 37 weeks in women with a uterine
anomaly compared to women with normal anatomy by parity (nulliparas vs multiparas) was performed. Descriptive analysis was used to estimate the incidence of
various types of uterine anomalies within
the primary exposure group and subgroup
analysis to estimate the association between specific mllerian anomalies and
risk of spontaneous PTB was also performed. All statistical analyses were performed using software (STATA 10.0, special edition; StataCorp, College Station,
TX).

R ESULTS
Of 72,373 singleton pregnancies, 66,956
(93%) had complete pregnancy outcome
information and were used in this analysis.
A total of 203 (0.3%) pregnancies complicated by maternal uterine anomaly were
identified at anatomic survey.
When comparing women with a uterine anomaly to those with normal uterine
anatomy, the groups were statistically similar with respect to mean maternal age and
gravidity. The incidence of preeclampsia
and gestational diabetes was also statistically similar between the 2 groups. However, there were some differences. Women
with a uterine anomaly were more likely
to have a history of PTB or stillbirth.
Women with normal uterine anatomy

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FIGURE

Incidence of preterm birth <37 weeks by uterine anomaly subtype

Prevalence of uterine anomalies and subtypes, within cohort (dark gray). Incidence of spontaneous
preterm birth 37 weeks in patients with uterine anomalies in cohort, and by subtype (light gray).
Hua. Pregnancy complications associated with mllerian anomalies. Am J Obstet Gynecol 2011.

were more likely to have higher parity

and to be African American (Table 1).
Within our exposure population, bicornuate uterus represented 50% of
the uterine anomalies, while unicornuate uterus was the least common.
While women with uterine didelphys
accounted for only 13% of the uterine
anomalies, they had a higher proportion of
PTB 34 weeks and 37 weeks than any
other subgroup (Figure).
The presence of a uterine anomaly was
associated with a 7-fold increased risk

in PTB 34 weeks (adjusted odds ratio

[aOR], 7.4; 95% confidence interval
[CI], 4.8 11.4; P .01) and a nearly
6-fold increased risk in PTB 37 weeks
(aOR, 5.9; 95% CI, 4.3 8.1; P .01)
compared to those pregnancies in women
with normal uterine anatomy after excluding those with a history of PTB, and adjusting for prior African American race, and
preeclampsia. Uterine anomalies were
associated with a 3-fold increased risk of
PPROM (RR, 3.0; 95% CI, 1.8 5.0) after
adjusting for preeclampsia and African

American race (aOR, 3.2; 95% CI, 1.8

5.6; P .01) when compared with normal uterine anatomy (Table 2). Examination year did not influence the results
and therefore did not remain in the
models. The presence of a uterine anomaly also confers an increased risk of
breech presentation (aOR, 8.6; 95% CI,
6.212.0; P .01) and primary cesarean
delivery of a nonbreech fetus (aOR, 2.6;
95% CI, 1.7 4.0; P .01). Increased
rates of placenta previa (odds ratio, 5.8;
95% CI, 2.215.3; P .01) and placental
abruption (aOR, 3.1; 95% CI, 1.1 8.3; P
.01) were also seen (Table 3). Primiparous patients with a uterine anomaly,
compared to multiparas, were shown to
have a higher magnitude of risk of PTB
before both 34 and 37 weeks (Table 4).
Finally, to better estimate the relationship between the presence of a uterine
anomaly and stillbirth, we excluded all
pregnancies in women with a history of
stillbirth. There were 3 cases of antepartum stillbirth in the uterine anomaly
group and 668 in the normal uterine
morphology group (1.6% vs 1.0%; RR,
1.5; 95% CI, 0.55.0; P .40).

C OMMENT
We found that the presence of a maternal
uterine anomaly detected at the time of
anatomic survey is associated with an increased risk of PTB, PPROM, breech
presentation, and cesarean section. We
also found an increased risk for placenta

TABLE 2

Outcomes of interest: congenital uterine anomalies vs normal uterine morphology

Outcomes of interest

Incidence in abnormal
morphology group
(n 203)

Incidence in normal
morphology group
(n 66,753)

P value

Unadjusted RR
(95% CI)

aOR (95% CI)

P value

Preterm birth

.......................................................................................................................................................................................................................................................................................................................................................................
b

34 wk

14.5%

2.6%

.01

4.9 (3.56.8)

7.4 (4.811.4)

.01

37 wk

39.7%

10.4%

.01

3.5 (2.94.1)

5.9 (4.38.1)

.01

PPROM

7.0%

2.3%

.01

3.0 (1.85.0)

3.2 (1.85.6)

.01

.......................................................................................................................................................................................................................................................................................................................................................................
c
.......................................................................................................................................................................................................................................................................................................................................................................
d
.......................................................................................................................................................................................................................................................................................................................................................................
e

Breech presentation

23.6%

3.0%

.01

7.9 (6.110.1)

8.6 (6.212.0)

.01

Cesarean delivery

34.7%

16.2%

.01

2.1 (1.62.8)

2.6 (1.74.0)

.01

.......................................................................................................................................................................................................................................................................................................................................................................
a
f
................................................................................................................................................................................................................................................................................................................................................................................

aOR, adjusted odds ratio; CI, confidence interval; PPROM, preterm premature rupture of membranes; RR, relative risk.
a

Primary nonbreech cesarean section, excluding previa; b Adjusted for preeclampsia, African American race, and excluding history of preterm birth; c Adjusted for preeclampsia, African American race,
history of maternal renal disease, chronic hypertension, gestational diabetes, history of stillbirth, and excluding history of preterm birth; d Adjusted for preeclampsia, African American race; e Adjusted
for parity, African American race; f Adjusted for history of preterm birth, chronic hypertension, history of stillbirth, preeclampsia, gestational diabetes.

Hua. Pregnancy complications associated with mllerian anomalies. Am J Obstet Gynecol 2011.

558.e3

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Research

TABLE 3

Secondary outcomes of interest: congenital uterine anomalies vs normal uterine morphology

Outcomes of interest
Placenta previa

Incidence in abnormal
morphology group
(n 203)
2.8%

Incidence in normal
morphology group
(n 66,753)

P value

Unadjusted RR
(95% CI)

aOR (95% CI)

P value

0.5%

.01

5.8 (2.215.3)

................................................................................................................................................................................................................................................................................................................................................................................
c

IUGR

12.8%

8.4%

.02

1.5 (1.12.2)

2.0 (1.33.1)

.01

IUFD

1.6%

1.0%

.4

1.6 (0.55.0)

Placental abruption

2.0%

0.6%

.02

3.1 (1.28.2)

3.1 (1.18.3)

.01

................................................................................................................................................................................................................................................................................................................................................................................
b
................................................................................................................................................................................................................................................................................................................................................................................
d
................................................................................................................................................................................................................................................................................................................................................................................

aOR, adjusted odds ratio; CI, confidence interval; IUFD, intrauterine fetal demise; IUGR, intrauterine growth restriction; RR, relative risk.
a

Excluding prior cesarean section; b Excluding history of stillbirth; c Adjusted for chronic hypertension, African American race, preeclampsia; d Adjusted for preeclampsia.

Hua. Pregnancy complications associated with mllerian anomalies. Am J Obstet Gynecol 2011.

previa, placental abruption, and IUGR

in women with a uterine anomaly. These
findings support much of what has been
previously described by small, published
reports.1,2,5-7
A prospective cohort study by Acien10
compared 176 patients with known uterine malformations to 28 women with
other genital and/or urinary anomalies
but a normal uterus. The study confirmed higher rates of preterm delivery
and breech presentation in the uterine
anomaly group. However, the central
conclusions that can be drawn from this
study are limited due to its observational
nature and the inability to adjust for confounding factors, such as history of PTB.
Additionally, only 53% of the pregnancies in women with uterine malformations ended with a child surviving 7
days, suggesting that many of the PTBs
occurred before or near viability. This

makes it difficult to draw meaningful

conclusions from this study regarding
the risk of PTB in the viability period.
Woelfer et al7 performed a prospective
cohort study in which women considered to be at low risk for uterine anomalies
provided their obstetrical histories prior to
being screened for uterine anomalies via
transvaginal ultrasound. They reported a
higher incidence of preterm labor in their
arcuate uterus cohort than the normal
uterine anatomy group (12.5% vs 6.2%,
P .01). Their study did not comment on
the incidence of preterm delivery, nor did
it find an increased incidence of PPROM.
The interpretation of their study results
may be limited, due to analytical limitations with no adjustment for possible confounding factors, as well as examination of
surrogate rather than desired outcomes.
With respect to IUGR, our study
found an increased risk of growth re-

striction even after adjusting for confounding factors. Some have hypothesized that abnormal uterine blood flow
and decreased muscle mass may be the
culprits behind growth restriction related to uterine anomalies.11 A review by
Reichman et al2 of 20 studies examining
the impact of a unicornuate uterus on
pregnancy outcomes likewise found an
association between uterine anomalies
and growth restriction. Based on the current American Congress of Obstetrics
and Gynecology guidelines for management of IUGR,12 it would be reasonable
to consider serial growth ultrasound examinations in pregnancies complicated
by maternal mllerian anomalies to
screen for IUGR.
When examining the various types of
uterine anomalies, our most common
finding was bicornuate uterus; the second most common was septate uterus.

TABLE 4

Unadjusted and adjusted risk estimates for preterm birth before 34 and 37
weeks in the nulliparous cohort compared to the multiparous cohort
Variable

Incidence in abnormal
morphology group, %

Incidence in normal
morphology group, %

P value

Unadjusted RR
(95% CI)

aOR (95% CI)

P value

Preterm birth 34 weeks

.......................................................................................................................................................................................................................................................................................................................................................................
a

Nulliparas (n 104)

18.3

3.5

.01

5.3 (3.58.0)

7.3 (4.412.3)

.01

Multiparas (n 98)

10.2

2.6

.01

3.9 (2.17.0)

5.1 (2.69.8)

.01

.......................................................................................................................................................................................................................................................................................................................................................................
b
................................................................................................................................................................................................................................................................................................................................................................................

Preterm birth 37 weeks

.......................................................................................................................................................................................................................................................................................................................................................................
c

Nulliparas (n 104)

49.0

12.5

.01

3.9 3.24.8

7.0 (4.710.5)

.01

Multiparas (n 98)

30.6

11.0

.01

2.8 (2.13.8)

3.2 (2.05.1)

.01

.......................................................................................................................................................................................................................................................................................................................................................................
d
................................................................................................................................................................................................................................................................................................................................................................................

aOR, adjusted odds ratio; CI, confidence interval; IUFD, intrauterine fetal demise; IUGR, intrauterine growth restriction; RR, relative risk.
a

Adjusted for preeclampsia and African American race; b Adjusted for preeclampsia, African American race, and excluding history of preterm birth; c Adjusted for preeclampsia, African American race,
history of maternal renal disease, chronic hypertension, gestational diabetes; d Adjusted for preeclampsia, African American race, history of maternal renal disease, chronic hypertension, gestational
diabetes, history of stillbirth, and excluding history of preterm birth.

Hua. Pregnancy complications associated with mllerian anomalies. Am J Obstet Gynecol 2011.

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This distribution reflects that which Nahum13 reported among fertile women.
Although other texts have cited septate
uterus as the most common anomaly in
the general population, our study population is of women who present at anatomic survey in the midtrimester, which
reflects the risk of early pregnancy loss
published for women with a uterine
septum.14
We attempted to estimate the risk of
intrauterine fetal demise (IUFD) in the
uterine anomaly population. However,
given the low incidence of cases (n 3)
of IUFD in the uterine anomaly population, we were underpowered to report
reliably on the risk estimate of IUFD and
uterine anomaly.
Our study offered several strengths.
Our large sample size allowed us to study
a relatively rare diagnosis and its association with rare but clinically important
outcomes. Additionally, the comprehensive database allowed us to access complete pregnancy follow-up information
that was obtained in a prospective manner, as well as data on patient demographics and history. This allowed us to
estimate the relationship between uterine
anomalies and multiple outcomes of interest, while adjusting for known confounders. However, our study was not without
weaknesses. One potential weakness was
that we used ultrasound diagnosis of uterine anomaly at midtrimester screening
rather than the gold standard of magnetic resonance imaging.14,15 However, we would argue that the most
likely consequence of this was that uterine anomalies were likely underdiagnosed in our control population, and
this misclassification bias would bias our
results toward the null hypothesis. A second weakness, inherent to retrospective

558.e5

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cohort studies, is the potential for missing data. While our database was complete with respect to potentially confounding variables, we were lacking
follow-up information on 7.0% of our
patients. However, sensitivity analyses
revealed that the patients with missing
outcome data who were excluded from
this study were not significantly different
from those included with respect to
baseline and exposure data, making this
potential source of selection bias less
likely (data not shown, but available on
request). Lastly, while our cohort is, to
our knowledge, the largest used to study
congenital uterine anomalies and pregnancy outcomes, we were still limited in
our ability to refine the relationship estimates between specific subtypes of uterine anomalies and adverse pregnancy
outcomes due to the rare occurrence of
those outcomes in our cohort.
In conclusion, our study found a significant increase in the risk of PTB,
breech, cesarean delivery, and IUGR in
pregnancies complicated by a uterine
anomaly detected at routine ultrasound
compared to those with normal uterine
morphology. These findings can be used to
counsel women whose pregnancies are
complicated by a mllerian anomaly, and
to help guide appropriate antenatal surveillance. Specifically, it seems reasonable
to screen these pregnancies for the development of IUGR with serial ultrasound assessments of estimated fetal weight. Although there are limited data regarding
PTB prevention in this particular cohort,
we have identified an at-risk population
that deserves future study.
f
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