Uterine Synechiae and Pregnancy
Complications
Methodius G. Tuuli, MD, MPH, Anthony Shanks, MD, Lisa Bernhard, MD,
Anthony O. Odibo, MD, MSCE, George A. Macones, MD, MSCE, and Alison Cahill,
OBJECTIVE: Uterine synechiae have generally been con-
sidered benign findings in pregnancy. We used a large
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perinatal database to test the hypothesis that uterine
synechiae are associated with pregnancy complications.
METHODS: We performed a retrospective cohort study of
women with singleton pregnancies presenting for routine
ultrasonographic examinations at 17–22 weeks from 1990 –
2009. Pregnancies with multiple fetuses, amniotic bands,
and congenital uterine anomalies were excluded. We com-
pared pregnancy outcomes between women with and
without uterine synechiae. Multivariable logistic regression
was used to adjust for confounders.
RESULTS: Of 65,518 pregnancies meeting inclusion cri-
teria, 296 (0.45%) were diagnosed with uterine synechiae.
Women with uterine synechiae were significantly more
likely to have placental abruption (2.1% compared with
0.6%, adjusted odds ratio [OR] 3.25, 95% confidence
interval [CI] 1.43–7.36), preterm premature rupture of
membranes (PROM) (5.5% compared with 2.3%, ad-
justed OR 2.51, 95% CI 1.51– 4.18), and cesarean delivery
for malpresentation (5.1% compared with 3.0%, adjusted
OR 1.75, 95% CI 1.04 –2.95). The risks of placenta previa,
fetal growth restriction, stillbirth, and preterm delivery
were not significantly different.
From the Department of Obstetrics and Gynecology, Washington University
School of Medicine in St. Louis,, St. Louis, Missouri.
The contents of this publication are solely the responsibility of the authors and do
not necessarily represent the official view of the National Institutes of Health or
Robert Wood Johnson Foundation.
Corresponding author: Methodius G. Tuuli, MD, MPH, Department of Obstetrics and
Gynecology, Washington University School of Medicine, Campus Box 8064, 4566
Scott Avenue, St Louis, MO 63110; e-mail: tuulim@wudosis.wustl.edu.
Financial Disclosure
Dr. Tuuli is supported by a Women’s Reproductive Health Research Career
Development grant from the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (National Institutes of Health/National
Institute of Child Health and Human Development 1K12HD063086-01). Dr.
Cahill is a Robert Wood Johnson Faculty Physician Scholar, which partially
supports this work. The other authors did not report any potential conflicts of
interest.
© 2012 by The American College of Obstetricians and Gynecologists. Published
by Lippincott Williams & Wilkins.
ISSN: 0029-7844/12
810 VOL. 119, NO. 4, APRIL 2012
MD, MSCI
CONCLUSION: Uterine synechiae are associated with
significant increase in the risk of preterm PROM, placen-
tal abruption, and cesarean delivery for malpresentation.
The notion of uterine synechiae as benign findings in
pregnancy should be re-evaluated.
(Obstet Gynecol 2012;119:810–4)
DOI: 10.1097/AOG.0b013e31824be28a
LEVEL OF EVIDENCE: II
U terine synechiae are intrauterine adhesions
around which chorioamniotic membranes wrap
during pregnancy to produce amniotic sheets or
shelves.1,2 They have a characteristically wide base
along the uterine wall and associate with fetal mem-
branes that consist of two layers of amnion and two
layers of chorion.3 First described by Asherman in
1950, uterine synechiae are seen in 0.14 – 0.60% of
pregnancies and have generally been considered in-
cidental, benign findings.4 – 8 Although their exact
etiology is unknown, they are believed to be related to
intrauterine instrumentation or infection. Early stud-
ies suggested a benign course of uterine synechiae in
pregnancy but were limited to case reports, case
series, and small cohort studies.1,2,7
Recent studies have suggested a link between
uterine synechiae and adverse pregnancy outcomes
including earlier gestational age at delivery, cesarean
delivery for malpresentation, and intrauterine fetal
death.6,9 However, the small sample sizes of these
studies precluded detailed analysis to control for
confounders or necessitated the use of composite
outcome measures.6,9
The objective of this study was to use a large
perinatal database to test the hypothesis that uterine
synechiae are associated with pregnancy complications.
MATERIALS AND METHODS
We conducted a retrospective cohort study of all
viable, singleton pregnancies undergoing routine ul-
trasonographic anatomic survey between 17 and 22
OBSTETRICS & GYNECOLOGY

weeks of gestation from 1990 –2009 at Washington
University in St Louis Medical Center. The Depart-
ment of Obstetrics and Gynecology created a com-
prehensive perinatal database in 1990 that is com-
piled and maintained by dedicated data management
staff. Pregnancy and delivery information for all
patients who undergo ultrasonographic evaluation at
our medical center is entered into the database.
Delivery information for patients referred to our
center is obtained from the patients, their medical
records, and referring physicians using a standardized
pregnancy outcome record form.
Pregnancies were dated by the women’s last
menstrual periods and confirmed with first- or sec-
ond-trimester ultrasonography using standard criteria.
At the time of anatomic survey, the intrauterine cavity
is routinely surveyed for abnormalities.10 All ultra-
sonograms were performed by Registry of Diagnostic
Medical Sonographers-certified ultrasonographers
credentialed in obstetrics and gynecology. Final diag-
nostic interpretations were made by experienced
sonologists and maternal-fetal medicine attending
physicians. Uterine synechiae were identified as thick
bands associated with fetal membranes stretching across
the uterus without involvement of any fetal structure
(Fig., 1A and B). Presence of uterine synechiae of any
size and location was included in this analysis.
All women with complete follow-up data were
eligible for this study. We excluded pregnancies with
multiple fetuses and congenital uterine anomalies. We
also specifically excluded pregnancies with amniotic
bands, which are disrupted amniotic membranes as-
sociated with fetal deformity.11 All women in the
database who met inclusion criteria were included
and no a priori sample size calculation was per-
formed. The presence or absence of uterine synechiae
defined the two groups. We compared pregnancy
complications (preterm premature rupture of mem-
branes (PROM), placental abruption, intrauterine
growth restriction, stillbirth, preterm birth, placenta
previa, and cesarean delivery for malpresentation)
VOL. 119, NO. 4, APRIL 2012
Fig. 1. Uterine synechiae are seen
in the lower aspect of the uterus at
22 weeks of gestation (thin ar-
rows). The fetal limb (fat arrow) in
A and head (fat arrow) in B are
uninvolved.
Tuuli. Uterine Synechiae and
Pregnancy. Obstet Gynecol 2012.
between women with and without uterine synechiae.
Placental abruption was defined clinically by the attend-
ing physician at the time of delivery. Fetal growth
restriction was defined as birth weight less than the tenth
percentile on the Alexander growth standard.12 Still-
birth was defined as fetal death after 20 weeks of
gestation. Preterm PROM was defined as rupture of
membranes before 37 weeks of gestation and preterm
delivery was defined as birth before 37 or 34 weeks of
gestation.
We compared baseline characteristics of preg-
nancies with and without uterine synechiae. Contin-
uous variables were compared using the Student’s t
test, whereas categorical variables were compared
using the ␹2 or Fisher’s exact test as appropriate. We
calculated rates and unadjusted odds ratios (ORs)
with 95% confidence intervals (CIs) for each preg-
nancy complication. Multivariable logistic regression
was used to calculate adjusted ORs. Candidate vari-
ables for the logistic regression models were selected
on the basis of biologic plausibility, risk factors that
have been identified in the literature for the various
outcomes, and results of univariable and stratified
analyses. Backward elimination was used to reduce
the number of variables in each model. Differences
between hierarchical explanatory models were as-
sessed using the likelihood ratio test or Wald test.
Model fit for each final model was assessed with the
Hosmer-Lemeshow goodness-of-fit test.13 All tests
were two-tailed with P⬍.05 considered significant. All
statistical analyses were completed using STATA 11
software. The study was approved by our institutional
human studies review board.
RESULTS
Of 65,518 pregnancies meeting inclusion criteria, 296
(0.45%) were diagnosed with uterine synechiae (Fig.
2). The mean gestational age at diagnosis was similar
in the two groups. Women with uterine synechiae had
a lower body mass index on average and were
significantly more likely to be white, smoke cigarettes,
Tuuli et al Uterine Synechiae and Pregnancy 811
 Routine anatomy surveys at 17–22
weeks of gestation, 1990–2008
N=76,320

No obstetric outcome data

n=8,425

Pregnancies with obstetric outcome data

n=67,895

Excluded: n=2,377
Multiple gestations: 2,194
Other uterine anomalies: 183

Singleton pregnancies with outcome

data and no other uterine anomalies
n=65,518

Fig. 2. Flow of study participants.

Uterine synechiae No uterine synechiae
Tuuli. Uterine Synechiae and
n=296; 0.45% n=65,222; 99.55% Pregnancy. Obstet Gynecol 2012.

and have a history of spontaneous or induced abor- more likely to have preterm PROM (5.5% compared
tion (Table 1). with 2.3%, adjusted OR 2.51, 95% CI 1.51– 4.18) when
Women with uterine synechiae were significantly compared with women without uterine synechiae. They
more likely to experience pregnancy complications. were also nearly twofold more likely to have cesarean
They were more than threefold more likely to have delivery for malpresentation (5.1% compared with 3.0%,
placental abruption (2.1% compared with 0.6%, adjusted adjusted OR 1.75, 95% CI 1.04 –2.95]) (Table 2). In
OR 3.25, 95% CI 1.43–7.36) and more than twofold contrast, rates of placenta previa, fetal growth restriction,
stillbirth, and preterm delivery before 37 or 34 weeks of
gestation were not significantly different in women with
Table 1. Characteristics of Study Participants
and without uterine synechiae.
Uterine No Uterine To estimate whether improvement in ultrasono-
Synechiae Synechiae graphic technology has had a significant influence on
Variable (nⴝ296) (nⴝ65,222) P
the detection of uterine synechiae and their associa-
Maternal age (y) 30.1 ⫾ 6.3 30.1 ⫾ 6.1 .843 tion with pregnancy complications, we calculated the
Maternal body mass 23.1 ⫾ 5.2 25.3 ⫾ 6.3 ⬍.001 incidence of uterine synechiae and their association
2
index (kg/m )
Gestational age at 19.4 ⫾ 1.8 19.4 ⫾ 1.6 .436
with pregnancy complications among women evalu-
diagnosis (wk) ated before (1990 –2000) and after (2001–2009) 2001.
Race The incidence of uterine synechiae was higher among
White 212 (71.6) 40,360 (61.9) ⬍.001 women who underwent ultrasonographic evaluation
African American 35 (11.8) 14,595 (22.4) in the earlier time period compared with those eval-
Other 49 (16.6) 10,267 (15.7)
uated in the later period (0.52% compared with
Primiparous 100 (33.8) 25,132 (38.5) .094
Smoking 59 (19.3) 7,172 (11.0) ⬍.001 0.38%, P⫽.005). Risks for placental abruption, pre-
Alcohol use 62 (21.2) 12,729 (18.7) .284 term PROM, and cesarean delivery for malpresenta-
Obstetric history tion were similar in the two time periods (Table 3).
Prior spontaneous 99 (33.5) 16,919 (25.9) .003
abortion
Prior therapeutic 65 (22.0) 11,238 (17.2) .032 DISCUSSION
abortion We found that uterine synechiae are associated with a
Prior cesarean 58 (19.6) 19,680 (16.4) .140
threefold increased risk of placental abruption and a
delivery
Chronic hypertension 2 (0.7) 1,580 (2.4) .054 twofold increased risk of preterm PROM and cesar-
Pregestational diabetes 2 (0.7) 1,221 (1.9) .190 ean delivery for malpresentation. In contrast, we did
Data are mean⫾standard deviation or n (%) unless otherwise not find increased risks of placenta previa, fetal
specified. growth restriction, stillbirth, or preterm delivery.

812 Tuuli et al Uterine Synechiae and Pregnancy OBSTETRICS & GYNECOLOGY

Table 2. Association Between Uterine Synechiae and Adverse Perinatal Outcomes
Uterine No Uterine Unadjusted Odds Adjusted Odds
Outcome Synechiae (nⴝ296) Synechiae (nⴝ65,222) Ratio (95% CI) Ratio (95% CI)

Placenta and fetal membranes–related

complications
Preterm PROM 16 (5.5) 1,483 (2.3) 2.44 (1.47–4.05) 2.51 (1.51–4.18)*
Placenta previa 4 (1.4) 341 (0.5) 2.59 (0.96–6.99) —
Placental abruption 6 (2.1) 408 (0.6) 3.27 (1.45–7.38) 3.25 (1.43–7.36)†
Abnormal fetal presentation
Cesarean delivery for malpresentation 15 (5.1) 1,936 (3.0) 1.75 (1.04–2.94) 1.75 (1.04–2.95)‡
Fetal complications
Fetal growth restriction 29 (9.8) 7,625 (11.7) 0.82 (0.54–1.21) 0.80 (0.54–1.18)§
Stillbirth 3 (1.0) 636 (1.0) — —
Preterm delivery
Before 37 wk 48 (13.3) 7,298 (11.5) 1.18 (0.83–1.67) 0.66 (0.27–1.69)㛳
Before 34 wk 11 (3.9) 1,845 (2.9) 1.34 (0.73–2.45) 1.50 0.86–2.62)¶
CI, confidence interval; PROM, premature rupture of membranes; —, adjusted analysis was not performed as a result of sparse
numbers in two-by-two tables.
Data are n (%) unless otherwise specified.
* Adjusted for maternal race, parity, and smoking (goodness-of-fit, P⫽.34).
†
Adjusted for chronic hypertension, maternal body mass index, and smoking (goodness-of-fit, P⫽.58).
‡
Adjusted for myoma and amniotic fluid abnormalities (goodness-of-fit, P⫽.99).
§
Adjusted for maternal race, diabetes, chronic hypertension, body mass index, and smoking (goodness-of-fit, P⫽.06).
㛳
Adjusted for race, prior spontaneous preterm birth, and smoking (goodness-of-fit, P⫽.89).
¶
Adjusted for race and smoking (goodness-of-fit, P⫽.13).

Our findings contradict those of several small prior
studies that suggested no association between uterine
synechiae and pregnancy complications.1,2,7 This is
likely attributable to the reduced statistical power asso-
ciated with the small sample sizes of those studies. On
the other hand, our findings are consistent with those of
Nelson and Grobman who recently reported increased
risk of a composite obstetric morbidity.9 Notably, the
increased risk of the composite outcome in that study
was largely driven by higher rates of preterm PROM
Table 3. Effect of Year of Diagnosis on
Association Between Uterine Synechiae
and Perinatal Outcomes
1990–2000 2001–2009
Outcome (nⴝ38,514) (nⴝ37,806)
Preterm premature 2.87 (1.46–5.65) 2.46 (1.14–5.31)
rupture of
membranes*
Placental abruption† 3.35 (1.23–9.10) 3.16 (0.77–12.92)
Cesarean delivery for 1.74 (0.89–3.41) 1.74 (0.76–3.97)
breech presentation‡
Intrauterine growth 1.06 (0.64–1.77) 0.69 (0.37–1.29)
restriction§
Data are adjusted odds ratio (95% confidence interval).
* Adjusted for maternal race, parity, and smoking.
†
Adjusted for chronic hypertension, maternal body mass index,
and smoking.
‡
Adjusted for myoma and amniotic fluid abnormalities.
§
Adjusted for maternal race, diabetes, chronic hypertension,
maternal body mass index, and smoking.
and placental abruption. They also found an increased
risk of cesarean delivery. Our analysis improves on that
study by assessing individual pregnancy complications
and more adequately adjusting for confounders.
This is a large study dedicated to evaluating the
association between uterine synechiae and pregnancy
complications. The comprehensive database and large
sample size allowed us to assess relatively infrequent
pregnancy complications. Importantly, it permitted ad-
justment for multiple confounders. Despite these
strengths, there are limitations that should be considered
when interpreting our results. The retrospective nature
of our study makes it vulnerable to inaccuracies in data
collection, selection bias, and confounding. However,
our database has been well-validated in several studies
and inaccuracies were found to be infrequent.14–19
Nearly 11% of the potential participants in the database
lacked outcome data and could not be included in this
study. This has the potential to introduce selection bias.
However, analysis of the baseline characteristics of those
patients showed that they were similar to patients with
outcome data, suggesting that any effect on our results is
likely small. Although we controlled for multiple con-
founders, there is the potential for residual confounding.
Although all examinations were performed by Registry
of Diagnostic Medical Sonographers-certified ultra-
sonographers and final diagnostic interpretations were
made by experienced sonologists and maternal-fetal
medicine attending physicians, there is the potential for

VOL. 119, NO. 4, APRIL 2012 Tuuli et al Uterine Synechiae and Pregnancy 813
misclassification. If pregnancies with uterine synechiae
were missed and they are included in the nonexposed
group for this analysis, it would tend to bias our results
toward the null hypothesis of no difference rather than
produce spurious associations. It is also reassuring that
the incidence of uterine synechiae in our cohort (0.45%)
is remarkably similar to those of prior studies.4 – 8
We did not have information on the orientation of
the uterine synechiae and their relation to the placenta.
Therefore, we were unable to assess the effect of these
characteristics, which may be possibly related to the risk
of pregnancy complications.5 Another important consid-
eration for a study of this nature that spans a long period
of time is whether improving ultrasonographic technol-
ogy significantly influenced the detection of uterine
synechiae. In sensitivity analysis comparing the inci-
dence of uterine synechiae and the association with
pregnancy complications among women evaluated be-
fore and after 2001, a higher rate of uterine synechiae
was noted in the earlier time period with no differences
in the risks of pregnancy complications.
Despite the significant association we found be-
tween uterine synechiae and adverse pregnancy com-
plications, a study of this nature cannot establish a causal
relationship. It is possible that uterine synechiae may be
simply markers of underlying factors that cause preg-
nancy complications. However, a causal link between
uterine synechiae and placental abruption, PROM, and
malpresentation is biologically plausible. Placental im-
plantation near the poorly vascularized synechiae may
predispose to placental abruption and the wrapping of
fetal membranes around synechiae may lead to prema-
ture rupture as the uterus enlarges. The presence of
synechiae, especially when large, may distort the uterine
cavity, resulting in malpresentation and the need for
cesarean delivery.3,20
In conclusion, this large cohort study showed a
twofold to threefold increased risk of pregnancy com-
plications, including placental abruption, PROM, and
cesarean delivery malpresentation when uterine syn-
echiae are noted at routine second-trimester ultra-
sonography. This challenges the notion of uterine
synechiae as benign incidental findings in pregnancy.
Although there are currently no proven interventions
to prevent these complications, our results are useful
for counseling women diagnosed with uterine syn-
echiae. The finding of uterine synechiae should also
trigger increased vigilance on the part of patients and
their physicians. Further research will help determine
if there is indeed a causal relationship between uterine
synechiae and pregnancy complications and whether
adhesiolysis before pregnancy in women known to
have uterine synechiae is beneficial.
814 Tuuli et al Uterine Synechiae and Pregnancy
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