Original Research ajog.

org

GYNECOLOGY
Cesarean scar defect: a prospective study on risk
factors
Riitta M. Antila-Långsjö, MD; Johanna U. Mäenpää, MD, PhD; Heini S. Huhtala, MSc; Eija I. Tomás, MD, PhD;
Synnöve M. Staff, MD, PhD

BACKGROUND: Cesarean scar defect (isthmocele) is a known isthmocele was 45.6%. Independent risk factors for isthmocele
complication after cesarean delivery. It has become more common due to development were a history of gestational diabetes (odds ratio, 1.73;
a rising cesarean delivery rate. Isthmocele has been associated with 95% confidence interval, 1.02e2.92; P ¼ .042), previous cesarean
various gynecological and obstetric problems such as uterine rupture, delivery (odds ratio, 3.14; 95% confidence interval, 1.90e5.17; P <
cesarean scar pregnancy, and bleeding disorders. .001), and advanced maternal body mass index (odds ratio, 1.06; 95%
OBJECTIVE: We sought to prospectively investigate factors associated confidence interval, 1.01e1.11; P ¼ .012). Every additional unit of
with the risk for isthmocele assessed by sonohysterography. body mass index increased the risk of isthmocele by 6%. In the
STUDY DESIGN: A prospective observational cohort study was con- subgroup of emergency cesarean delivery, longer duration of active
ducted in 401 nonpregnant women who were recruited within 3 days of labor increased the risk for isthmocele (odds ratio, 1.06; 95% confi-
cesarean delivery. Women were evaluated with sonohysterography 6 dence interval, 1.01e1.11; P ¼ .032). There was no statistically
months after cesarean delivery to detect a possible isthmocele. The ul- significant difference in prevalence between the groups of elective and
trasonographer was blinded to any clinical information. The main outcome emergency cesarean delivery (P ¼ .898).
measure was the presence of isthmocele. Type of surgery (elective vs CONCLUSION: Based on sonohysterographic examination, maternal
emergency), maternal background variables, and factors related to body mass index, gestational diabetes, and previous cesarean deliveries
pregnancy, labor, and postoperative recovery were analyzed in relation to are associated with an increased risk for incomplete healing of the uterine
isthmocele. A logistic regression model was used to assess independent incision.
risk factors from univariate analysis.
RESULTS: In all, 371 women were examined with sonohysterog- Key words: cesarean delivery, cesarean scar defect, isthmocele,
raphy resulting in a follow-up rate of 92.5%. The prevalence of sonohysterography, ultrasonography

Introduction ectopic cesarean scar pregnancy are fairly to be a major potential risk factor for
Cesarean delivery (CD) is potentially a rare complications of cesarean scar isthmocele. Additionally, advanced stage
life-saving procedure if performed for defect yet with potentially catastrophic of labor and uterine retroflexion have
the right indications.1 The World Health consequences.5,6 However, post- been associated with isthmocele.13,15
Organization has stated that CD rates at menstrual spotting, dysmenorrhea, dys- However, prospective studies on this
up to 10e15% at the population level are pareunia, or chronic pelvic pain are subject are scarce and quite heteroge-
associated with decreases in maternal, frequently described in relation to ce- neous. Most of them include a small
neonatal, and infant mortality. Above sarean scar defect.7e11 Additionally, ce- sample size or are performed in selected
this level, the increasing rate of CD is no sarean scar defect may increase the risk populations of symptomatic women. To
longer associated with reduced mortal- for complications in gynecological pro- develop preventive strategies for
ity.2 However, rates up to 50% have been cedures such as intrauterine device reducing the risk for isthmocele and thus
reported, which consequently can lead to placement, evacuation, and embryo overcoming possible adverse outcomes,
a growing number of complications.3,4 transfer.11,12 it is essential to identify related risk fac-
One of these complications, cesarean Therefore, in the past several years, tors. The aim of this study was to
scar defect, has been shown to be asso- numerous studies have been published investigate factors that increase the risk
ciated with various gynecological and concerning the scar defect (also called of isthmocele in a large prospectively
obstetric problems. Uterine rupture and “isthmocele” or “niche”). The isthmo- collected and unselected population.
cele represents an inadequate healing of
the myometrium at the site of cesarean Materials and Methods
Cite this article as: Antila-Långsjö RM, Mäenpää JU, incision. Its prevalence varies substan- This prospective observational cohort
Huhtala HS, et al. Cesarean scar defect: a prospective tially, between 6.9e69%, depending on study was designed to assess the preva-
study on risk factors. Am J Obstet Gynecol
the study population and the method- lence, risk factors, and clinical outcome
2018;219:458.e1-8.
ology used.7,13 Appropriate diagnosis of of cesarean scar defect. The results of risk
0002-9378/$36.00 isthmocele is made with contrast- factor analysis are reported here, while
ª 2018 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2018.09.004 enhanced ultrasonography.14 A history the clinical outcome will be published
of multiple CDs is generally considered after a sufficient follow-up of the

458.e1 American Journal of Obstetrics & Gynecology NOVEMBER 2018

ajog.org GYNECOLOGY Original Research

AJOG at a Glance FIGURE 1

Schematic presentation of
Why was this study conducted? isthmocele measurements
The rate of cesarean deliveries is increasing. We evaluated the risk factors related
to isthmocele in a large prospective cohort study.

Key findings
Gestational diabetes, obesity, and multiple cesarean deliveries increase the risk of
isthmocele.

What does this add to what is known?

The identification of obesity and gestational diabetes as risk factors for isthmocele
is a novel finding. Thus, the results reported here are significant because there has
been a dramatic increase worldwide in the prevalence of obesity and diabetes in
women of childbearing age.

participants. The study was carried out and SHG procedures were performed by In longitudinal plane: a, depth and b, width of
at Tampere University Hospital, Tam- the first author, who was blinded to the isthmocele; thickness of c, adjacent and d, re-
pere, Finland. The date of the trial clinical information. Women were sidual myometrium. In transverse plane: e,
registration (ClincalTrials.gov identifier: examined in the lithotomy position with length of isthmocele.
NCT02717312, ID: R15104) of this an empty bladder. The uterus was Antila-Långsjö et al. Risk factors for postcesarean isthmocele.
study was March 9, 2016. The study examined in a standardized way, with Am J Obstet Gynecol 2018.

protocol was approved by the institu- TVUS performed first.16 Isthmocele was
tional review board of Tampere Univer- defined as an anechoic defect in the Paris, France) was inserted into the
sity Hospital, Finland (ETL code anterior wall of the lower uterine uterus, and sterile saline was flushed
R15104). segment, communicating with the until the site of cesarean scar was visu-
Women who delivered by CD at endometrial cavity. If an isthmocele was alized. The same measurements as
Tampere University Hospital from detected, the depth and width of the mentioned above were performed. The
January 2016 through January 2017 were isthmocele, the residual myometrial volume of flushed saline was measured.
asked to participate. They were recruited thickness (RMT) overlying the isthmo-
either before the CD in the case of elec- cele, and the adjacent myometrial Statistical analyses
tive surgery or within 3 days after the thickness fundal to the isthmocele were This prospective study was designed to
operation in the case of emergency CD. measured in the midsagittal plane. The investigate the prevalence, risk factors,
All participants provided written length of the isthmocele was measured in and clinical outcome of isthmocele. The
informed consent before enrollment. the transverse plane (Figure 1).8 The primary outcome measure of the entire
Exclusion criteria included a known uterine position was classified as ante- study was the prevalence of isthmocele.
uterine anomaly, lack of common lan- verted or retroverted. For the diagnosis The study was designed to assess the effect
guage, and age <18 years. Clinical in- of isthmocele, we used a predetermined of isthmocele on the incidence of
formation concerning pregnancy, definition of a defect at least 2.0 mm bleeding disorders (ie, postmenstrual
operation technique, and recovery time deep.10 In case >1 defect was found, the spotting defined as 2 days of brownish
were obtained from the electronic med- largest one was measured. To assess a low discharge at the end of menstruation with
ical database. Six months after the CD, RMT, we used the cut-off point of 3.0 total bleeding days of 7 or noncyclic
participants were invited to the gyneco- mm because it is regarded as the mini- bleeding not related to menstruation).
logic outpatient clinic for ultrasound mum RMT for hysteroscopic treatment The detection of a 2-fold difference in the
(US) examination. Transvaginal ultra- for symptomatic patients.17 Women prevalence of bleeding disorder between
sonography (TVUS) and sonohysterog- without isthmocele were included in the the isthmocele and nonisthmocele
raphy (SHG) were performed using the group of RMT of 3.0 mm because it is groups was the aim of the analyses. The
WS80 Elite (Samsung Medison Co Ltd, presumable that without isthmocele, the sample size calculations were based on
Gangwon-do, Republic of Korea). myometrium thickness remains un- the following assumptions: the preva-
Women without contraception were changed. Moreover, isthmocele was lence of bleeding disorders among
examined during the follicular phase of considered large if the ratio between the women with isthmocele is 30%, and the
the menstrual cycle to avoid an eventual depth of the isthmocele and the adjacent prevalence of isthmocele was estimated to
early pregnancy. Otherwise, a random myometrial thickness was 0.50. be approximately 50% according to pre-
phase of the menstrual cycle was Immediately after the TVUS, SHG was vious data.9 To achieve 80% power with a
accepted. Women who were pregnant at performed. A small catheter (insemina- 2-sided alpha of 0.05, we needed to enroll
the time of US were excluded. All TVUS tion cannula standard; Laboratoire CCD, 266 women in the study. Considering the

NOVEMBER 2018 American Journal of Obstetrics & Gynecology 458.e2

Original Research GYNECOLOGY ajog.org

dropout rate, which we anticipated to be

FIGURE 2
up to 30%, we planned to recruit 400
Flow chart of study
women. This number was supposed to be
sufficient also for the present study on
risk factors, where the primary objective Inclusion criteria=Delivery by cesarean
was the association of elective vs emer- secƟon (CD)
gency CD with the risk of isthmocele Exlusion criteria=uterine anomaly, lack of
when the prevalence of elective CD cor- common language, g , age under 18
responded to 44% of the total number of
CDs at our hospital.
Data were analyzed using software Consent to parƟcipate (n=401)
(SPSS, Version 22.0; IBM Corp,
Armonk, NY). Associations between Consent within 3 days of CD or prior surgery
(elecƟve CD)
categorical variables and the formation Excluded (n=30):
of isthmocele were compared with c2 ·Refused to conƟnue the
study (26)
tests and between continuous variables
·Pregnancy (3)
and isthmocele with binary logistic ·Vulvodynia (1)
regression. A logistic regression model Follow up
was used for the multivariate analysis (n=371)
assessing the effect of statistically signif-
icant risk factors from univariate anal-
ysis. Two-tailed P values of <.05 were
considered statistically significant.
The isthmocele detected by SHG was Ultrasound assesment 6 months aŌer CD
defined as the outcome of interest in the (n=371)
statistical analyses because SHG is
considered as a method of choice when
evaluating isthmocele.8,18

Results Data analysis

In all, 401 women gave their informed
consent. Later, 26 women refused to
continue the study. Three women were
Antila-Långsjö et al. Risk factors for postcesarean isthmocele. Am J Obstet Gynecol 2018.
excluded because of detected pregnancy
at the time of examination, and 1 was
excluded because of severe vulvodynia, an emergency CD. This distribution were no differences regarding the rate of
which made it impossible to perform corresponds to the rate upon which the primary or emergency CD, age, gesta-
SHG. Finally, we examined 371 women statistical power calculations were based. tional diabetes (GDM), body mass index
successfully by both TVUS and SHG Of the emergency CDs, 12 (3.2%) were (BMI), or parity between women who
resulting in a follow-up rate of 92.5% emergent-crash (ie, requiring immediate participated in the present study and
(Figure 2). The examinations were per- intervention). The most common rea- those who also delivered by CD during
formed, on average, 6.7 months after the sons for elective CD were fear of child- the study period but did not participate
CDs (range 4.5e10.0 months). De- birth (32.9%), breech presentation in the study.
mographic background variables testing (22.6%), and previous CD (20.0%). For In all, 83 isthmocele cases were detec-
for their predictive ability are shown in emergency CD the most common rea- ted by TVUS and 169 by SHG. Thus, 86
Table 1. The mean age of all participants sons were prolonged labor (44.0%) and women had a normal TVUS in spite of an
was 32.5 years. The gestational age at CD fetal asphyxia (32.4%). Intrapartum or isthmocele diagnosed by SHG. The
varied from 24e42 weeks, with a mean postoperative infection was diagnosed in prevalence of isthmocele was 22.4% with
value of 39þ2 weeks. A total of 215 59 of 371 women (15.9%). Diagnosed TVUS and 45.6% with SHG. Most of the
(58%) participants had no previous de- infections included chorioamnionitis, isthmoceles were triangular in shape
liveries. In all, 58 (16%) women had at postpartum wound infections, and (91.8%), while the rest were round
least 1 previous vaginal delivery (range endometritis. The diagnostic criteria for (3.9%), oval (2.5%), and total defect
1e6 deliveries), while 117 (32%) had a chorioamnionitis included intrapartum (1.8%). The prevalence of isthmocele
history of CD (range 1e3 CDs). In all, fever and elevated infection parameters detected by SHG was defined as the
155 women (41.8%) underwent elective (C-reactive protein, leucocyte count) outcome of interest in the statistical an-
CD, and 216 women (58.2%) underwent with maternal or fetal tachycardia. There alyses (Figure 3). There was no significant

458.e3 American Journal of Obstetrics & Gynecology NOVEMBER 2018

ajog.org GYNECOLOGY Original Research

TABLE 1
Demographic background data and results of univariate logistic regression analysis
Without isthmocele, With isthmocele,
n ¼ 202 (54.4%) n ¼ 169 (45.6%) OR 95% CI P value
Maternal age, mean (SD), y 32.1 (5.6) 33.1 (4.9) 1.04 1.00e1.08 .074
Gestational age, mean (SD), wkþd 39þ2 (2.5) 39þ2 (2.2) 1 0.92e1.09 .947
Parity, mean (range) 0 (0e6) 1 (0e5) 1.54 1.22e1.93 .001
Prior vaginal delivery, n (%) 35 (17.3) 23 (13.6) 0.75 0.43e1.33 .327
Prior CD, n (%) 38 (18.8) 79 (46.7) 3.69 2.38e6.03 <.001
Indication for CD, n (%)
Elective 85 (42.1) 70 (41.4) .898
Emergency 117 (57.9) 99 (58.6) 1.03 0.68e1.56
Birthweight, mean (SD), ga 3532 (705) 3595 (610) 1.02 0.98e1.05 .375
Smoking during pregnancy, n (%) 9 (4.5) 6 (3.6) 0.79 0.28e2.26 .660
Gestational diabetes, n (%) 49 (24.3) 66 (39.1) 2.00 1.28e3.12 .002
Diabetes mellitus, n (%) 6 (3.0) 6 (3.6) 1.20 0.38e3.80 .753
BMI before pregnancy, mean (SD), kg/m2 25.1 (5.3) 27.1 (6.1) 1.07 1.03e1.11 .001
2
BMI at CD, mean (SD), kg/m 30.4 (5.3) 32.3 (5.9) 1.06 1.02e1.10 .002
Change in maternal weight, mean (SD), kg 14.3 (6.2) 13.4 (6.0) 0.98 0.94e1.01 .159
Uterine position at ultrasound, n (%)
Anteversion 149 (73.8) 108 (64.3) .049
Retroversion 53 (26.2) 60 (35.7) 1.56 1.00e2.44
Cervical dilatation at CD, n (%), cm
0 95 (47.0) 82 (48.5) .071
1e4 62 (30.7) 36 (21.3) 0.67 0.41e1.12 .125
5 45 (22.3) 51 (30.2) 1.31 0.80e2.16 .284
Intrapartum or postoperative infection, n (%) 26 (12.9) 33 (19.5) 1.64 0.94e2.88 .083
Experience of operator, n (%)
Resident 133 (65.8) 110 (65.1) .879
Specialist 69 (34.2) 59 (34.9) 1.03 0.67e1.59
Induction of labor, n (%)b 59 (29.2) 38 (22.5) 0.63 0.37e1.10 .103
Multiple pregnancy, n (%) 12 (5.9) 8 (4.7) 0.79 0.31e1.97 .609
Preeclampsia, n (%) 15 (7.4) 8 (4.7) 0.62 0.26e1.50 .288
Antenatal corticosteroid, n (%) 16 (7.9) 10 (5.9) 0.73 0.32e1.66 .453
Duration of labor, mean (SD), hb 13.9 (6.7) 16.2 (7.6) 1.05 1.00e1.10 .039
b
Oxytocin augmentation during labor, n (%) 70 (59.8) 68 (68.7) 1.00 0.99e1.01 .530
b
Unsuccessful vacuum delivery prior to CD, n (%) 8 (6.8) 5 (5.1) 0.73 0.23e2.29 .584
b
Station of presenting part, n (%)
At or above pelvic inlet 105 (48.8) 85 (39.5) .494
Below pelvic inlet 12 (5.6) 13 (6.0) 1.34 0.58e3.09
BMI, body mass index; CD, cesarean delivery; CI, confidence interval; OR, odds ratio.
a
Twin pregnancies excluded; b in subgroup of emergency CD.
Antila-Långsjö et al. Risk factors for postcesarean isthmocele. Am J Obstet Gynecol 2018.

NOVEMBER 2018 American Journal of Obstetrics & Gynecology 458.e4

Original Research GYNECOLOGY ajog.org

FIGURE 3
Sonohysterographic image of isthmocele (*)

The asterisk points to the triangular-shaped isthmocele.

Antila-Långsjö et al. Risk factors for postcesarean isthmocele. Am J Obstet Gynecol 2018.

difference in the presence of isthmocele closure (single- vs double-layer sutures) multivariate analysis. Additionally,
between the groups of elective and could not be analyzed because in all but 1 maternal age was included in the multi-
emergency CD (P ¼ .898). Prior vaginal woman, the uterine incision was closed in variate analysis. Because BMI at CD is
deliveries did not influence on the risk of double layer with continuous unlocked dependent on BMI before pregnancy, we
isthmocele (P ¼.327), but a history of CD sutures using polyglactin (Vicryl, Ethi- decided to enter BMI at the time of CD
increased significantly the risk for isth- con, Johnson and Johnson Ltd., India), in the multivariate analysis. The results
mocele formation (P < .001). Women which represents the standard way of of the multivariate logistic regression
without previous CD had a 35% chance uterine wound closure at our hospital. analysis are shown in Table 2. Indepen-
of having isthmocele, while after 1, 2, or 3 The remaining 1 woman had single-layer, dent risk factors for isthmocele were
CDs the risk was 63%, 76%, and 88%, continuous unlocked sutures. In a sub- previous CDs, maternal BMI, and GDM
respectively. Similarly, parity increased group of women with emergency CD, the (odds ratio [OR], 3.14; 95% confidence
the risk of isthmocele (P < .001). duration of active labor (ie, number of interval [CI], 1.90e5.17; P < .001; OR,
Women with isthmocele had higher hours with regular contractions) was 1.06; 95% CI, 1.01e1.11; P ¼ .012; and
BMIs both before pregnancy and at the longer in women who developed isth- OR, 1.73; 95% CI, 1.02e2.92; P ¼ .042,
time of CD than women without isth- mocele, with a mean duration of 16.3 vs respectively).
mocele (P ¼ .001 and P ¼ .002, respec- 13.9 hours (P ¼ .039). Previous CD (P ¼ We also performed the multivariate
tively). Every additional unit of BMI .001), maternal age (P ¼ .032), peripartal analysis of the subcohort of patients
raised the risk by 6%. However, the ab- infections (P ¼ .035), and GDM (P ¼ undergoing an emergency CD (n ¼ 216).
solute change in maternal weight during .046) were also associated with the Factors showing statistically significant
pregnancy was not associated with the development of isthmocele. Cervical associations with isthmocele in the uni-
risk of isthmocele. Women with GDM dilatation or station of the presenting fetal variate analysis were entered into the
were more likely to have isthmocele (P ¼ part, induction of labor, multiple preg- multivariate analysis (ie, previous CD,
.002). However, type 1 diabetes did not nancy, and unsuccessful vacuum delivery parity, maternal age, peripartal in-
increase the risk. A retroverted position of prior to CD did not influence the risk of fections, duration of labor, and GDM).
the uterus at US examination was asso- developing isthmocele. The independent risk factor for isth-
ciated with an increased risk for isthmo- We entered the significant risk factors mocele in this subgroup was the dura-
cele (P ¼ .049). The method of wound from the univariate analysis into the tion of labor (OR, 1.06; 95% CI,

458.e5 American Journal of Obstetrics & Gynecology NOVEMBER 2018

ajog.org GYNECOLOGY Original Research

participants a few months after CD,

TABLE 2
which may cause selection bias since
Results of multivariate logistic regression analysis in study cohort (N [ 371)
symptomatic women may be more
Parameter Odds ratio 95% CI P value willing to participate. We found 2 pre-
Maternal age, y 1.00 0.95e1.04 .846 vious studies that recruited participants
close to CD.10,20 However, in those
Parity 0.90 0.64e1.27 .558 studies, the US examination was per-
Previous CD 3.14 1.90e5.17 <.001 formed as early as 6e12 weeks after CD.
Gestational diabetes 1.73 1.02e2.92 .042 We decided to perform the examinations
6 months after CD because it has been
BMI at CD 1.06 1.01e1.11 .012
suggested that the cesarean wound-
Uterine position at ultrasound 1.60 0.98e2.60 .058 healing process will take at least 6
BMI, body mass index; CD, cesarean delivery; CI, confidence interval. months. On the other hand, we wanted
Antila-Långsjö et al. Risk factors for postcesarean isthmocele. Am J Obstet Gynecol 2018.
to minimize the risk of a new pregnancy
at the time of US, which would have
prevented the performance of SHG.
1.01e1.11; P ¼ .032). The results of the advanced cervical opening raise the risk However, it is possible that the healing
multivariate logistic regression in this for low RMT values. process will continue >6 months. Thus,
subcohort are shown in Table 3. The strength of our study is that it doing the measurements at a later time
RMT was measured in 282 women. A represents, to our knowledge, the largest point might have revealed different re-
total of 73 (19.7%) of participants had study performed to date in which isth- sults, which has to be taken into account
RMT <3.0 mm. Risk factors for reduced mocele was evaluated with contrast- when interpreting the results.
RMT (<3.0 mm) were peripartal infec- enhanced sonography in relation to the It is a limitation of our study that 370
tion (P ¼ .008) and advanced cervical defined risk factors. As far as we know, out of 371 women received a double-
dilatation (P ¼ .045). Parity and the only 1 previous study included a larger layer closure of the uterine incision.
number of previous CDs were associated sample size in the assessment of isth- Therefore, we could not study the in-
with large isthmocele defects (P ¼ .033 mocele risk factors.19 However, they fluence of closure technique on the risk
and P ¼ .002, respectively). used only unenhanced TVUS to di- of isthmocele. Another limitation of our
agnose isthmocele. Currently, contrast- study is that RMT was measured only if
Comment enhanced ultrasonography is consid- there was any visible indentation at the
In this prospective observational cohort ered to be the gold standard in isthmo- site of the CD scar. Therefore, in 89
study, we show that advanced maternal cele diagnostics.8 (24.0%) women, RMT remained un-
BMI, a history of GDM, and CD are in- Another strength of our study is the measured. However, in that group,
dependent risk factors for isthmocele prospective observational cohort study almost all women had no history of CD
development, regardless of the type of design, in which participants were (n ¼ 78/89; 88%). Low RMT values have
CD. In the subgroup of emergency CD, recruited as early as within 3 days of CD, been associated with the number of
longer duration of active labor appears to thus avoiding possible selection bias. previous CDs, and a strong association
increase the risk for isthmocele. We also Only few previous prospective studies between low RMT values and the pres-
report here that peripartal infections and have been published, mainly recruiting ence of isthmocele has been shown.19
Therefore, we found it reasonable to
include women without isthmocele in
TABLE 3 the group with RMT 3.0 when we
Results of multivariate analysis in subcohort of emergency cesarean assessed the risk factors for low RMT.
delivery (N [ 216) Our results concerning the impact of
obesity and GDM are novel. Maternal
Parameter Odds ratio 95% CI P value BMI and diabetes have not been regarded
Maternal age, y 1.02 0.95e1.09 .670 as risk factors for isthmocele in previous
Parity 1.28 0.65e2.51 .472 trials.13,21,22 This may be due to a relatively
small sample size in these studies; thus, the
Previous CD 2.64 0.90e7.73 .076
number of women was too small for sig-
Gestational diabetes 1.81 0.86e3.79 .118 nificant associations. Additionally, the di-
Intrapartum or postoperative infection 2.05 0.95e4.42 .068 agnostics and treatment of GDM may vary
Duration of labor, h 1.06 1.01e1.11 .032 in different countries. In Finland, there is a
population-wide maternity health care
CD, cesarean delivery; CI, confidence interval.
Antila-Långsjö et al. Risk factors for postcesarean isthmocele. Am J Obstet Gynecol 2018. system and clear indications for glucose
tolerance testing during pregnancy,

NOVEMBER 2018 American Journal of Obstetrics & Gynecology 458.e6

Original Research GYNECOLOGY ajog.org

ensuring that almost all cases of GDM cervical dilatation raises the risk for large 5. Vikhareva Osser O, Valentin L. Clinical
become diagnosed. Obesity has been isthmocele, which was defined by RMT importance of appearance of cesarean hyster-
otomy scar at transvaginal ultrasonography in
associated with impaired cutaneous 2.5 mm. In contrast to our results, they nonpregnant women. Obstet Gynecol
wound healing in general and total wound also found that the station of the pre- 2011;117:525–32.
failure after surgical procedures.23 senting fetal part at CD was associated 6. Pędraszewski P, Wlazlak E, Panek W,
Consistently, diabetes mellitus has a with the risk for large isthmocele. This Surkont G. Cesarean scar pregnancyea new
negative effect on wound healing by difference may have arisen because our challenge for obstetricians. J Ultrason 2018;18:
56–62.
various mechanisms.23,24 We think that it study included only a few women with 7. Wang CB, Chiu WWC, Lee CY, Sun YL,
is reasonable to presume that obesity and presenting fetal part below the pelvic Lin YH, Tseng CJ. Cesarean scar defect: cor-
diabetes affect also the healing of uterine inlet. Moreover, the estimate of the relation between cesarean section number,
incision and the negative effect may be height of the presenting part is quite defect size, clinical symptoms and uterine posi-
true for GDM as well. Both obesity and subjective and thus sensitive to mistakes tion. Ultrasound Obstet Gynecol 2009;34:85–9.
8. Bij de Vaate AJM, van der Voet LF, Naji O,
diabetes have various systemic conse- and hardly repeatable. et al. Prevalence, potential risk factors for
quences. Chronic, low-grade inflamma- The development of isthmocele seems development and symptoms related to the
tion, insulin resistance, and hyperglycemia to depend on various patient-related and presence of uterine niches following cesarean
are some of the factors associated with pregnancy-related, as well as operative, section: systematic review. Ultrasound Obstet
impaired wound healing related to these factors. We have shown here for the first Gynecol 2014;43:372–82.
9. Bij de Vaate AJM, Brolmann HAM, van der
conditions.24,25 time that both maternal obesity and Voet LF, van der Slikke JW, Veersema S,
A relationship between multiple CDs GDM raise the risk for isthmocele. These Huirne JAF. Ultrasound evaluation of the cesar-
and isthmocele has been reported pre- findings are important since obesity and ean scar: relation between a niche and post-
viously.7,15,26,27 A preexisting CD scar GDM are conditions that could be menstrual spotting. Ultrasound Obstet Gynecol
has been shown to negatively influence affected by early management and in- 2011;37:93–9.
10. van der Voet LF, Bij de Vaate AM,
the healing of a new cesarean uterine terventions. In the future, this associa- Veersema S, Brolmann HAM, Huirne JAF. Long-
incision. The results from our study tion may become even more important term complications of cesarean section. The
support these data. The risk for isth- because there has been a dramatic in- niche in the scar: a prospective cohort study on
mocele increased considerably with the crease worldwide in the prevalence of niche prevalence and its relation to abnormal
number of previously performed CDs. obesity and GDM in women of child- uterine bleeding. BJOG 2014;121:236–44.
11. Tower AM, Frishman GN. Cesarean scar
The proposed pathophysiology is that bearing age.28 We want to emphasize defects: an underrecognized cause of abnormal
repeated trauma to the isthmic wall that our results reflect the quantitative uterine bleeding and other gynecologic compli-
disrupts the normal healing process. healing of the uterine scar. The clinical cations. J Minim Invasive Gynecol 2013;20:
Additionally, vascular perfusion may be outcome of isthmocele will be ascer- 562–72.
reduced in the scar tissue.7,15 tained only in the course of follow-up of 12. Patounakis G, Ozcan MC, Chason RJ, et al.
Impact of a prior cesarean delivery on embryo
In the subcohort of women who our prospective study cohort. Never- transfer: a prospective study. Fertil Steril
attempted a trial of labor, the duration of theless, more prospective high-quality 2016;106:311–6.
active labor increased the risk for isth- studies are needed to ascertain the clin- 13. Vikhareva Osser O, Valentin L. Risk factors
mocele. As far as we know, there are no ical significance of isthmocele to facili- for incomplete healing of the uterine incision after
previous studies in which a subgroup of tate the definition of clinical guidelines cesarean section. BJOG 2010;117:1119–26.
14. Osser OV, Jokubkiene L, Valentin L. High
emergency CD is evaluated for the risk for the possible prevention and man- prevalence of defects in cesarean section scars
factors. In univariate analysis, the results agement of isthmocele. n at transvaginal ultrasound examination. Ultra-
obtained from the subgroup analysis sound Obstet Gynecol 2009;34:90–7.
were similar compared to the whole References 15. Ofili-Yebovi D, Ben-Nagi J, Sawyer E, et al.
cohort with respect to parity, GDM, and 1. Betran AP, Torloni MR, Zhang JJ, et al. WHO Deficient lower-segment cesarean section
statement on cesarean section rates. BJOG scars: prevalence and risk factors. Ultrasound
obesity. In multivariate analysis, only the Obstet Gynecol 2008;31:72–7.
2016;123:667–70.
duration of labor remained as a signifi- 2. Betran AP, Torloni MR, Zhang J, et al. What is 16. Naji O, Abdallah Y, Bij De Vaate AJ, et al.
cant risk factor for isthmocele. This may the optimal rate of cesarean section at popula- Standardized approach for imaging and
be attributable to smaller sample size in tion level? A systematic review of ecologic measuring cesarean section scars using ultra-
the subgroup analysis. It is possible that studies. Reprod Health 2015;12:57. sonography. Ultrasound Obstet Gynecol
3. Betrán AP, Ye J, Moller A-B, Zhang J, 2012;39:252–9.
in active labor the healing circumstances
Gülmezoglu AM, Torloni MR. The increasing 17. Vervoort A, van der Voet LF, Hehenkamp W,
are unique because the lower uterine trend in cesarean section rates: global, regional et al. Hysteroscopic resection of a uterine ce-
segment is more stretched, which may and national estimates: 1990-2014. PLoS One sarean scar defect (niche) in women with post-
specifically affect the healing properties 2016;11:e0148343. menstrual spotting: a randomized controlled
of myometrium. 4. Souza JP, Gülmezoglu A, Lumbiganon P, trial. BJOG 2018;125:326–34.
et al. Cesarean section without medical in- 18. Antila-Långsjö R, Mäenpää JU,
We found that advanced cervical
dications is associated with an increased risk of Huhtala H, Tomás E, Staff S. Comparison of
dilatation raises the risk for low RMT adverse short-term maternal outcomes: the transvaginal ultrasound and saline contrast
values. This finding is in agreement with 2004-2008 WHO global survey on maternal and sonohysterography in evaluation of cesarean
previous data.13 Osser et al14 found that perinatal health. BMC Med 2010;8:71. scar defect. A prospective cohort study.

458.e7 American Journal of Obstetrics & Gynecology NOVEMBER 2018

ajog.org GYNECOLOGY Original Research

Acta Obstet Gynecol Scand 2018;97: prognostic factors for niche development in diabetes: a clinical update. World J Diabetes
1130–6. the uterine cesarean section scar. Eur J 2015;6:1065–72.
19. Pomorski M, Fuchs T, Rosner- Obstet Gynecol Reprod Biol 2017;213:
Tenerowicz A, Zimmer M. Standardized ul- 31–2.
trasonographic approach for the assessment 23. Guo S, Dipietro LA. Factors affecting wound Author and article information
of risk factors of incomplete healing of the healing. J Dent Res 2010;89:219–29. From the Department of Obstetrics and Gynecology
cesarean section scar in the uterus. Eur J 24. Baltzis D, Eleftheriadou I, Veves A. Patho- (Drs Antila-Långsjö, Mäenpää, and Staff), Tampere
Obstet Gynecol Reprod Biol 2016;205: genesis and treatment of impaired wound heal- University Hospital (Dr Tomás); and Faculty of Medicine
141–5. ing in diabetes mellitus: new insights. Adv Ther and Life Sciences (Dr Mäenpää), Faculty of Social
20. Yazicioglu HF, Sevket O, Ekin M, Ozyurt O, 2014;31:817–36. Sciences (Mrs Huhtala), and BioMediTech (Dr Staff),
Aygun M. Incomplete healing of the uterine 25. Pantham P, Aye ILMH, Powell TL. Inflam- University of Tampere, Tampere, Finland.
incision after cesarean section: is it preventable mation in maternal obesity and gestational dia- Received May 25, 2018; revised Aug. 15, 2018;
by intraoperative digital dilatation of the internal betes mellitus. Placenta 2015;36:709–15. accepted Sept. 10, 2018.
cervical ostium? Gynecol Obstet Invest 26. Chen Y, Han P, Wang Y-J, Li Y-X. Risk This study was supported by competitive research
2012;74:131–5. factors for incomplete healing of the uterine funding of Pirkanmaa Hospital District, grant number
21. Hayakawa H, Itakura A, Mitsui T, et al. incision after cesarean section. Arch Gynecol 9U036 (J.U.M.) and University of Tampere (R.M.A-L.).
Methods for myometrium closure and other Obstet 2017;296:355–61. The funding sources had no involvement in the study
factors impacting effects on cesarean section 27. Armstrong V, Hansen WF, Van Voorhis BJ, design; in the collection, analysis, and interpretation of
scars of the uterine segment detected by the Syrop CH. Detection of cesarean scars by data; in the writing of the report; or in the decision to
ultrasonography. Acta Obstet Gynecol Scand transvaginal ultrasound. Obstet Gynecol submit the article for publication.
2006;85:429–34. 2003;101:61–5. The authors report no conflict of interest.
22. Voet LLFV, Vaate AMJB, Heymans MW, 28. Kampmann U, Madsen LR, Skajaa GO, Corresponding author: Riitta M. Antila-Långsjö, MD.
Brölmann HAM, Veersema S, Huirne JAF. Iversen DS, Moeller N, Ovesen P. Gestational riitta.antila-langsjo@pshp.fi

NOVEMBER 2018 American Journal of Obstetrics & Gynecology 458.e8