Research www. AJOG.

org

OBSTETRICS
The diagnosis, treatment, and follow-up
of cesarean scar pregnancy
Ilan E. Timor-Tritsch, MD; Ana Monteagudo, MD; Rosalba Santos, RDMS;
Tanya Tsymbal, RDMS; Grace Pineda, RDMS; Alan A. Arslan, MD

OBJECTIVE: The diagnosis and treatment of cesarean scar pregnancy
(CSP) is challenging. The objective of this study was to evaluate the di-
agnostic method, treatments, and long-term follow-up of CSP.
STUDY DESIGN: This is a retrospective case series of 26 patients be-
tween 6-14 postmenstrual weeks suspected to have CSP who were re-
ferred for diagnosis and treatment. The diagnosis was confirmed with
transvaginal ultrasound. In 19 of the 26 patients the gestational sac was
injected with 50 mg of methotrexate: 25 mg into the area of the embryo/
fetus and 25 mg into the placental area; and an additional 25 mg was
administered intramuscularly. Serial serum human chorionic gonado-
tropin determinations were obtained. Gestational sac volumes and vas-
cularization were assessed by 3-dimensional ultrasound and used to
monitor resolution of the injected site and outcome.
RESULTS: The 19 treated pregnancies were followed for 24-177 days.
No complications were observed. After the treatment, typically, there
was an initial increase in the human chorionic gonadotropin serum con-
centrations as well as in the volume of the gestational sac and their vas-
cularization. After a variable time period mentioned elsewhere the val-
ues decreased, as expected.
CONCLUSION: Combined intramuscular and intragestational metho-
trexate injection treatment was successful in treating these CSP.
Key words: accreta, cesarean section, cesarean section scar
pregnancy, ectopic pregnancy, methotrexate, minimally invasive
procedure, placenta, pregnancy, punctures, ultrasound

Cite this article as: Timor-Tritsch IE, Monteagudo A, Santos R, et al. The diagnosis, treatment, and follow-up of cesarean scar pregnancy. Am J Obstet Gynecol
2012;207:44.e1-13.

S ince 1996, the cesarean delivery

(CD) rate in the United States has
increased by approximately 40%, and in
2007, the rate was 31.8%.1 This is largely
attributed to a rise in primary CD (from
From the Department of Obstetrics and
Gynecology, NYU School of Medicine, New
York, NY.
Received December 16, 2011; revised March
16, 2012; accepted April 9, 2012.
The authors report no conflict of interest.
Reprints: Ilan E. Timor-Tritsch, MD,
Department of Obstetrics and Gynecology,
NYU School of Medicine, 550 First Ave., NBV-
9N1, New York, NY 10016.
Ilan.timor@nyumc.org.
0002-9378/free
© 2012 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2012.04.018
For Editors’ Commentary, see
Contents
See related article, page 14
Click Supplementary Content under
VIDEO the title of this article in the
online Table of Contents
12.6-20.6%) and a decline in vaginal de-
liveries after CD (28-9.2%).1,2 The rate
of repeat CD is now about 91%.2 The
trend toward an increasing rate of CD
has been reported in other countries.3,4
A previous CD increases the risk for a
pathologically adherent placenta (ac-
creta, increta, and percreta) and the
magnitude of risk increases with each ad-
ditional CD. Similar risks were reported
for cesarean scar pregnancy (CSP).3,5-11
A particular complication of a preg-
nancy after CD is the implantation of the
gestational sac in the hysterotomy scar,
known as a “cesarean scar pregnancy”
(CSP).10 This condition is referred to us-
ing several terms including “cesarean ec-
topic pregnancy” or simply “cesarean
scar ectopic.”3,12-30 Some other terms in-
clude the word “ectopic.” The term “ce-
sarean delivery scar pregnancy” has also
been used.31,32 Since the majority of re-
ports use “cesarean scar pregnancy,”
(CSP)10,11,32-57 we will use this term in
the article. CSP are not ectopic gestations
by definition (even though no official
definition for them has been agreed
upon) since the bulk of the gestation in-
cluding the placenta are in the niche or in
the scar facing the uterine cavity and are
part of it.
The incidence of CSP has been esti-
mated to range from 1/1800 –1/2500 of
all CD performed.3,42,43,58 The diagnosis
is often difficult, and a false-negative
diagnosis may result in major compli-
cations, including a hysterectomy. The
diagnosis is based on finding a gesta-
tional sac at the site of the previous CD
in the presence of an empty uterine
cavity and cervix, as well as a thin myo-
metrium adjacent to the bladder. Dif-
ferent diagnostic, radiological imaging
methods, and management options have
been proposed. However, the optimal
management remains to be determined. If
the patient presents with a uterine rupture
or major bleeding, surgery is unavoidable.
Management of diagnosed but stable pa-
tients represent a challenge (the reader is
referred to a recent review for details).4 In
this article, we describe the use of intrages-
tational sac injection of methotrexate
(MTX) as a simple and effective office-
based treatment. The follow-up of the pa-
tients is described.

44.e1 American Journal of Obstetrics & Gynecology JULY 2012

www.AJOG.org
M ATERIALS AND M ETHODS
This is a retrospective case series of 26
patients between 6-14 weeks postmen-
strual age referred to NYU Langone
Medical Center over a period of 3 years
(2009 through 2011 and evaluated in
2011) with diagnosed or suspected CSP.
The diagnosis, treatment, and follow-up
of all patients were performed in the ul-
trasound facility without anesthesia.
Twenty-two of the 26 patients had de-
monstrable fetal heart activity at the time
of ultrasound examination in our insti-
tution. One patient was referred after she
had undergone elective termination of a
7-week pregnancy. However, we subse-
quently diagnosed that the pregnancy
had not been located within the uterine
cavity and was located in the hysterot-
omy scar. One patient was referred be-
cause of an arteriovenous (A-V) malfor-
mation in the scar of a CD. Two patients
presented with CSP with embryos/fe-
tuses without heart activity. Two pa-
tients were referred for a second opinion.
Twelve women had been treated with
various doses (25-50 mg) of intramuscu-
lar MTX prior to referral to our institu-
tion. Since MTX was not effective in
causing cessation of fetal heart activity in
these patients they were referred for ad-
ditional treatment.
In the presence of a positive pregnancy
test, a CSP was diagnosed by transvaginal
ultrasound using the following criteria:
1. Visualization of an empty uterine
cavity as well as an empty endocervi-
cal canal (Figure 1, A and B).
2. Detection of the placenta and/or a
gestational sac embedded in the hys-
terotomy scar (Figure 1, C).
3. In early gestations (ⱕ8 weeks), a tri-
angular gestational sac that fills the
niche of the scar (Figure 1, D); at ⱖ8
postmenstrual weeks this shape may
become rounded or even oval.
4. A thin (1-3 mm) or absent myome-
trial layer between the gestational sac
and the bladder (Figure 1, C).
5. A closed and empty cervical canal.
6. The presence of embryonic/fetal pole
and/or yolk sac with or without heart
activity.
7. The presence of a prominent and at
times rich vascular pattern at or in the
area of a CD scar in the presence of a
positive pregnancy test (Figure 1,
E-G).
All these criteria had to be present to
diagnose CSP. Some of the above criteria
were derived from the literature (items 1,
4, and 5)59,60 or generated and modified
by our group (items 2, 3, 6, and 7).
Sonographic diagnosis and a baseline
serum human chorionic gonadotropin
(hCG) concentration were determined.
In addition, 3-dimensional (3D) ultra-
sound data sets using a 4- to 8-MHz
transvaginal probe (Voluson 730; Gen-
eral Electric Medical Systems, Milwau-
kee, WI) were obtained. Volume of the
chorionic sac site and power Doppler
was used serially after the injection of
MTX and compared to baseline infor-
mation obtained before the local injec-
tion of MTX. Power Doppler settings
were 0.9 kHz pulse repetition frequency
and 200 MHz filter (standardized for all
examinations). Chorionic sac volume
and vascularization were analyzed of-
fline using a software system (4DView;
General Electric Medical Systems). The
placenta/gestational sac complex vol-
ume (mL) was calculated using the man-
ual segmentation procedure (Virtual Or-
gan Computer-aided Analysis [VOCAL]
4DView; General Electric Medical Sys-
tems) (Figure 2, A). The outer boundar-
ies of the segmentation, or in other
words the perimeter of the gestational
sac, were followed to define the sac size.
This area/volume also included the vas-
cular “ring.” Six rotational steps (60 de-
grees apart) were used to define sac vol-
ume. The sensitivity for defining the
vascularization index (VI) was men-
tioned above. The VI was calculated us-
ing the same software (Figure 2, B). The
VI is the number of color flow– contain-
ing voxels divided by the total number of
voxels contained within the volume ex-
pressed as a percent value (Figure 2, C).
The mean VI for patients undergoing
hysterectomies was compared to those
who were not treated by hysterectomy.
Sonographic examinations were re-
peated for 3 weeks at weekly intervals at
first, and subsequently, bimonthly, until
the site of the sac was barely visible and
the VI declined (usually ⬍3%). We also
required that the area of the gestational
JULY 2012 American Journal of Obstetrics & Gynecology
Obstetrics Research
sac site did not show any more color
Doppler signals with a pulse repetition
frequency as low as 0.3 kHz.
Patients were counseled about the
risks of the condition and management
alternatives, including potential benefits
and risks (known and unknown). The
need to adhere to a follow-up period was
specified. Patients signed a written in-
formed consent for treatment.
If interventional treatment was rec-
ommended as an option, this consisted
of a real-time, transvaginal ultrasound-
guided puncture and MTX injection into
the chorionic sac. An automated, spring-
loaded device (Labotect Co, Göttingen,
Germany) was attached to the transvag-
inal transducer (SL400; Siemens, Erlan-
gen, Germany). The procedure repre-
sented a slight modification of the
puncture injection approach previously
reported by the authors.61-64 We used
a 20-gauge needle. Under ultrasound
guidance, the area of the embryonic/fetal
heart was identified for the placement of
the tip of the needle.
After confirming the placement of the
needle, 25 mg of MTX in 1 mL of solu-
tion was injected slowly. The intragesta-
tional sac dose administered was 25 mg,
and an additional 25 mg was injected
outside the gestational sac as the needle
was withdrawn, preferably the placental
site if that area was in the needle tract.
The patient underwent another sono-
graphic examination 60-90 minutes after
the procedure to confirm cessation of fe-
tal heart activity and to identify local
bleeding. The patient also received an
additional intramuscular injection of 25
mg MTX (for a total, combined dose of
75 mg) before discharge from our unit.
Patients were asked to return in 24-48
hours for a follow-up scan. As for the
number of CD before the CSP, of the 26
patients, 15 had 1, 9 had 2, and 2 had
3 CD.
One patient had 2 chorionic sacs (twin
gestation) in the scar, but only 1 gesta-
tional sac had detectable embryonic
heart activity (an intragestational sac in-
jection was performed in the sac with
cardiac activity) since the other sac did
not contain viable embryo. One patient
had 3 consecutive CSP. All 3 were treated
44.e2
Research Obstetrics www.AJOG.org

FIGURE 1
Transvaginal sonographic criteria for diagnosis of cesarean scar pregnancy
A B

C D

F G

A, Empty uterine cavity with gestational sac (arrow) between cavity and cervix (Cx). B, Power Doppler of blood vessels surrounding gestational sac. C,
Gestational sac embedded in scar. Thin (1-3 mm) or lack of myometrium (arrow) between sac and bladder. D, Triangular shape of sac (on sagittal plane)
assuming shape of niche. E-G, Prominent, richly vascular area in site of previous cesarean delivery scar highlighted by power Doppler in patient presenting
with bleeding and positive serum human chorionic gonadotropin test. Arrows point to vascular malformation.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.

44.e3 American Journal of Obstetrics & Gynecology JULY 2012

www.AJOG.org Obstetrics Research

FIGURE 2
Evaluation of volume and vascular supply of cesarean scar pregnancy

Evaluation used 3-dimensional (3D) transvaginal ultrasound with Virtual Organ Computer-aided Analysis (VOCAL) software (General Electric Medical
Systems, Milwaukee, WI). A, 3D segmentation of sac perimeter drawn around outer boundaries of color ring resulting in sac volume. B, 3D angiographic
rendering of vascularization around gestational sac. C, 3D angiographic measurement of vascularization index representing percent blood flow containing
units (voxels) over outlined grayscale units.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.

according to the same protocol and
counted as 3 separate cases.
The protocol for follow-up included
evaluation of the outcome: (1) a weekly
serum hCG determination for 3 consec-
utive weeks, and 1 determination bi-
monthly until this hormone was unde-
tectable; and (2) determination of the
gestational sac volume and the area vas-
cularization at the above intervals using
the previously described techniques. Pa-
tients were asked not to have vaginal
intercourse until the resolution of the
CSP. This was judged by sonographic
examination.
Analysis of the data was as follows: val-
ues of the serum hCG, sac volume, and
VI were tabulated for each patient enter-
ing them into an Excel spreadsheet (Mi-
crosoft, Redmond, WA) on the day they
were obtained. These values were used to
generate graphic representation, as a
function of the days following treatment.
R ESULTS
Clinical details of the patients are sum-
marized in Table 1. Of the 26 patients, 2
of them (patients 4 and 15 in Table 1)
were referred to us for a second opinion.
They each had 1 prior CD and presented
at 9 and 14 weeks, respectively. After the
diagnosis of CSP (Figure 3) and counsel-
ing, both patients opted to continue their
pregnancies (after being informed of the
risk of a possible placenta accreta). Both
patients had uterine rupture with pro-
fuse bleeding at 15 and 17 weeks, respec-
tively, requiring massive blood transfu-
sions and hysterectomies.
Patient 10 in Table 1 was scheduled to
have intragestational sac MTX injection
of a CSP at 6 weeks and 1 day, but slightly
bled prior to the scheduled procedure.
The patient was treated by tamponade
with a 5-mL balloon catheter inserted
into the cervix and inflated until bleed-
ing ceased. The next morning, there was
absence of detectable fetal heart rate, and
no additional treatment was given. Six
weeks later, involution of the scar site
was noted.
On the day of referral, 2 patients (pa-
tients 23 and 24 in Table 1) had detect-
able embryonic/fetal cardiac activity and

JULY 2012 American Journal of Obstetrics & Gynecology 44.e4

Research Obstetrics www.AJOG.org

TABLE 1
Cesarean scar pregnancies with and without
intragestational MTX injections
Pretreatment Days to resolution
Patient GA, wks hCG, mIU/mL Sac volume, mL VI, % hCG Sac volume VI Treatment Observations
With MTX
................................................................................................................................................................................................................................................................................................................................................................................
1 7 2/7 46,300 14.1 7.3 88 133 133 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
2 10 3/7 101,000 119.9 25.5 63 150 150 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
3 6 1/7 37,200 10.6 34.6 125 125 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
5 7 0/7 2640 6.6 24.5 68 57 57 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
6 8 1/7 100,010 44.9 27.5 64 177 177 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
7 7 3/7 7600 8.3 37.1 95 140 140 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
8 8 2/7 2950 21.1 6.4 63 93 93 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
11 7 0/7 43,341 11.4 12.2 35 44 44 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
12 6 1/7 13,076 3.6 23.1 98 133 133 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
13 6 6/7 1976 28.7 24.1 89 110 110 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
14 6 2/7 8518 2.9 4.5 60 60 60 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
16 8 0/7 2717 14.3 9.3 24 76 72 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
17 6 2/7 5469 4.1 7.9 33 109 109 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
18 6 2/7 4673 17.0 43.0 63 22 63 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
19 6 4/7 2870 1.3 4.7 61 62 48 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
20 6 1/7 1340 2.1 6.1 63 63 63 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
21 7 2/7 2100 3.1 16.4 41 41 41 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
22 7 6/7 12,657 1.7 15.2 54 61 61 L⫹S MTX
.......................................................................................................................................................................................................................................................................................................................................................................
25 5 6/7 8550 3.2 3.9 26 26 26 L⫹S MTX Clots from cavity
aspirated on d 26
................................................................................................................................................................................................................................................................................................................................................................................
Without MTX
.......................................................................................................................................................................................................................................................................................................................................................................
4 9 1/7 Unavailable 59.9 39.7 — — — Declined Bled at 15 wk, TAH
.......................................................................................................................................................................................................................................................................................................................................................................
9 7 6/7 55 53.6 71 — — — UA embolization A-V malformation; TAH
(Table 2)
.......................................................................................................................................................................................................................................................................................................................................................................
10 6 0/7 59 2.6 7.8 39 39 39 Bleed: balloon catheter Resolved
.......................................................................................................................................................................................................................................................................................................................................................................
15 14 0/7 Unavailable 35.0 48.5 — — — Declined Rupture at 18 wk, TAH
.......................................................................................................................................................................................................................................................................................................................................................................
23 6 0/7 6081 3.1 4.1 58 65 65 No FHR Resolved
.......................................................................................................................................................................................................................................................................................................................................................................
24 6 4/7 8868 4.0 4.0 42 42 42 No FHR Resolved
.......................................................................................................................................................................................................................................................................................................................................................................
26 Unavailable 0 — 65.0 — — — Embolization A-V malformation
................................................................................................................................................................................................................................................................................................................................................................................
A-V, arteriovenous; FHR, fetal heart rate; GA, gestational age; hCG, human chorionic gonadotropin; L, local; MTX, methotrexate; S, systemic; TAH, total abdominal hysterectomy; UA, uterine artery;
VI, vascularization index.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.

were scheduled for treatment, but the lowed up according to the protocol de- tion of pregnancy at 7 weeks of gestation
following day (when the procedure was scribed above. at another institution (the pathology re-
scheduled), fetal cardiac activity had Patient 9 in Table 1 had a complex port described the presence of chorionic
ceased. No treatment was administered. clinical course. This 33-year-old patient villi). The patient had 2 previous CD and
Patient 23 received intramuscular MTX had 6 pregnancies, 4 deliveries, and 1 2 normal vaginal deliveries at term. At
prior to referral, while for patient 24, the abortion, and presented to the emer- presentation, the serum hCG was 55
fetal cardiac activity ceased without MTX gency room with vaginal bleeding 67 mIU/mL, and sonographic examination
administration. These patients were fol- days after an attempted elective termina- at our center revealed an empty uterine

44.e5 American Journal of Obstetrics & Gynecology JULY 2012

www.AJOG.org Obstetrics Research

FIGURE 3
Two untreated CSPs with subsequent uterine rupture and hysterectomy
A B

A, 3-Dimensional power Doppler angiogram at 9 weeks of patient 4 in Table 1. B, 2-Dimensional color Doppler ultrasound image at 14 postmenstrual
weeks of patient 15 in Table 1.
CSP, cesarean scar pregnancy cases.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.

cavity, a clearly imaged hysterotomy scar
niche (Figure 4, A), and a richly vascu-
larized anterior uterine wall (which was
double in thickness compared to the
posterior wall) (Figure 4, B). We consid-
ered that the images were consistent with
the diagnosis of placenta accreta or per-
creta that was left untouched during the
termination procedure. The pregnancy
was in close proximity to the hysterot-
omy scar. We managed this condition by
administering intramuscular MTX (80
mg) on day 81 after her initial dilatation
and curettage (D&C) on the first day un-
der our care. This injection was admin-
istered with the suspicion that the pa-
tient may have had residual gestational
trophoblastic disease. On follow-up the
hCG serum concentration became non-
detectable 2 weeks (on the 100th day)
from the time of the initial surgical inter-
vention. The VI and placental volume
showed a decrease in magnitude on the
105th day. However, the patient devel-
oped severe vaginal bleeding. A hysterec-
tomy and uterine artery embolization
were offered, but declined by the patient.
A repeat sonographic examination dem-
onstrated an increase in the VI. The ultra-
sound image was suspicious for the pres-
ence of an A-V malformation (Video Clips
1 and 2). Vaginal bleeding persisted, and
on the 155th day bilateral uterine artery
embolization was performed. Vaginal
bleeding decreased, but there was persis-
tence of the prominent vessel in the lower
anterior uterine wall (Figure 4, C). The
peak systolic velocity within the vascular
structure was 45.3 cm/s, consistent with an
A-V vascular malformation (Figure 4, D).
Five days later, the patient underwent a
hysterectomy with an uneventful recovery.
The sequence of events is illustrated in
Table 2.
Patient 26 in Table 1 was referred to us
for vaginal bleeding and a positive preg-
nancy test. On transvaginal ultrasound
an A-V malformation was seen at the site
of her previous CD scar (Figure 1, E-G).
This patient did not have any surgical in-
tervention for this pregnancy and was
promptly treated by emergency uterine
artery embolization to stop the bleeding.
Two other patients had no demonstrable
embryonic/fetal cardiac activity on the
day of their scheduled MTX injection
thus were not treated at all.
In only 1 patient (patient 3 in Table 1)
was the CSP the result of in vitro fertil-
ization and transfer of 2 embryos. Nine-
teen patients (6-9 weeks of gestation)
underwent successful local injection of
50 mg of MTX and all showed evidence
of embryonic/fetal cardiac activity. One
patient had 3 prior CD. Typically, pa-
tients had prolonged, intermittent vagi-
nal spotting for 2-3 weeks following the
procedure. During the follow-up period,
most women resumed menses before
resolution of the gestational sac volume
and vascularization. No side effects were
seen related to the MTX treatments.
Of interest, 1 patient with 2 previous CD
underwent intragestational sac MTX in-
jection of 50 mg at 7 postmenstrual weeks
for a CSP, and subsequently returned 10
weeks later with a second CSP at 6 post-
menstrual weeks. She underwent again in-
tragestational sac MTX injection. It is
noteworthy that the first CSP was a dicho-
rionic twin gestation with 1 empty sac
(blighted ovum?), and an additional gesta-
tional sac containing an embryo. This
same patient returned again, 4 months af-
ter her second CSP similarly treated with a
third CSP at 5 postmenstrual weeks and 6
days. She was treated again as per our de-
scribed protocol with good outcome.
A small number of clots from the uter-
ine cavity were aspirated on day 26 in

JULY 2012 American Journal of Obstetrics & Gynecology 44.e6

Research Obstetrics
patient 25 after continuous spotting was
reported.
The following observations were noted
regarding the hCG serum concentrations,
the gestational sac volume, and the VI:
1. Serum hCG: in 13 of the 19 injected
cases after an initial plateau or a small
temporary increase in the serum hCG
concentrations, the values decreased
slowly and became nondetectable
(cutoff was ⬍3 mIU/L) 41-100 days
following MTX injection (Figure 5).
2. Gestational sac volume: in 12 of the
cases the gestational sac volume in-
creased or plateaued after MTX injec-
tion, and this was followed by a slow
decrease in volumes (Figure 6). How-
ever, the area of involution was visible
even ⬎5 months’ posttreatment.
3. VI: in 14 of the cases after an initial in-
crease or brief plateau in the VI, a slow
but steady decline was observed to what
was considered to be minimal values
(⬍3%). Color Doppler did not demon-
strate vascularization 30-140 days from
the MTX injection (Figure 7).
The interquartile ranges for the serum
hCG concentrations, the sac volumes,
and VI are presented in Table 3.
C OMMENT
Principal findings of this study
First, an early diagnosis of CSP is possi-
ble using the criteria proposed in this ar-
ticle. Second, treatment is possible using
a combination of systemic and intrages-
tational sac injection with MTX. Third,
the local injection of MTX into the ges-
tational sac is simple to perform under
ultrasound guidance using a needle
guide, and in this report, was done trans-
vaginally. Lastly, the natural history of
hCG serum concentrations, gestational
sac volume, and the VI after systemic and
local MTX treatment is described. An in-
crease in both serum hCG and gesta-
tional sac volume was consistently ob-
served immediately after treatment, and
was followed by a progressive decline un-
til hCG became nondetectable and the
gestational sac involuted. The optimal
management of CSP continues to repre-
sent a challenge.4
44.e7 American Journal of Obstetrics & Gynecology JULY 2012
www.AJOG.org
FIGURE 4
Placenta percreta in case no. 9 from Table 1
B
A
C
D
A, Sagittal section of uterus. Anatomy is outlined by dotted lines and annotations indicate placental
location, cesarean section (C/S) niche, empty uterine cavity, and cervical canal. B, 3-Dimensional
power Doppler image of vascularization. C, After 140-144 days large dilated blood vessel is seen.
Inlay represents color flow of vessel. D, Peak systolic velocity of 45.3 cm/s was measured in vessel.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.
The clinical challenge of a cesarean a uterine rupture–in both, emergency
section pregnancy surgery or uterine artery embolization
This pregnancy complication can pres- by interventional radiology are re-
ent broadly in 2 ways: (1) as an acute quired36,65-68; and (2) at sonography in a
emergency in which the patient has patient with a history of CD, who under-
bleeding, or an acute abdomen due to goes an ultrasound examination.
TABLE 2
Clinical and laboratory data of patient 9 from Table 1
Events Date Days post D&C Volume, mL VI, % hCG, mIU/mL MTX, mg
1 10/17/09 0 Unavailable Unavailable Unavailable —
..............................................................................................................................................................................................................................................
2 01/04/10 81 48 66 16 100
..............................................................................................................................................................................................................................................
3 02/03/10 100 53.6 71 ⬍2 —
..............................................................................................................................................................................................................................................
4 02/05/10 102 60 42 ⬍2 —
..............................................................................................................................................................................................................................................
5 02/08/10 105 25 15.1 ⬍2 —
..............................................................................................................................................................................................................................................
6 02/24/10 121 34.4 52.6 Bleeding
..............................................................................................................................................................................................................................................
7 03/15/10 140 35 76.7 — —
..............................................................................................................................................................................................................................................
8 03/19/10 144 Bleeds again
..............................................................................................................................................................................................................................................
9 03/26/10 155 Embolization
..............................................................................................................................................................................................................................................
10 04/02/10 160 Hysterectomy
..............................................................................................................................................................................................................................................
D&C, dilatation and curettage; hCG, human chorionic gonadotropin; MTX, methotrexate; VI, vascularization index.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.
www.AJOG.org
FIGURE 5
Graph of serum hCG as function of days post injection
After initial increase most levels dropped to undetectable levels by day 40-60.
hCG, human chorionic gonadotropin.
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.
The optimal treatment of the patient
in the first trimester of pregnancy with a
sonographic diagnosis of suspected CSP
remains uncertain. The list of proposed
treatment modalities is long and in-
volves among other one main treatment
alone or its combination with other
treatment modalities:
FIGURE 6
Graph of gestational sac volumes as a function of days post injection
Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.
a. Curettage4,10,11,13-15,22,24,25,31,32,36,37,39,43,
45,48,49,53,68-83
b. Hysteroscopy12,17,24,54,55,84-86
c. Systemic MTX alone10,14,17,18,21,26-28,32,
33,35,40,41,47,50,52,56,69,76,87-98
d. Laparotomy21,51,77,84,86,99-102
e. Uterine artery embolization34,38,44,56,57,
86,93,96,103,104
JULY 2012 American Journal of Obstetrics & Gynecology
Obstetrics Research
In general, these procedures can be
performed by obstetricians and gynecol-
ogists with expertise in ultrasound. Some
procedures require involvement of the
radiology department.
Diagnosis of CSP
A recent literature search4 identified 751
cases of CSP. Of interest is that 13.6%
(107/751) had been misdiagnosed as cer-
vical pregnancies, spontaneous abor-
tions in progress (on its way to expul-
sion), or low intrauterine pregnancies.
Given the potential serious complica-
tions of a CSP, reliable diagnostic criteria
are required for the differential diag-
nosis. The primary scanning route used
was transvaginal using frequencies of
5-12 MHz. Transabdominal probes may
also be used. However, due to the lower
resolution ability of transabdominal
probes, fine details of placental implan-
tation site, definition of embryonic/fetal
as well as extraembryonic structures are
seen better using the transvaginal ultra-
sound probes. Another reason for using
transvaginal probes was that the viewing
point and viewing angle of the probe was
identical both at the diagnosis as well as
at the time of the injection. The diagnos-
tic criteria used in this study included
were mentioned in the “Materials and
Methods” section.
While the presence of embryonic/fetal
cardiac activity facilitates the diagnosis
of CSP, its absence does not exclude the
diagnosis, since in many cases there may
be cessation of cardiac activity, and this
does not eliminate the complications de-
rived from CSP. Another consideration
is that patients may have been previously
treated with intramuscular MTX and
come to the attention of the ultrasound
unit after fetal demise has already oc-
curred. Since the exact time and amounts
as well as, in certain cases, the intervals be-
tween multiple administrations were un-
reliable and inaccurate, we can only say
that these data could not be analyzed in a
meaningful way. The precise sensitivity,
specificity, and predictive values of these
criteria would need to be tested prospec-
tively. However, we have proposed these
criteria after considerable experience in
our unit and welcome evaluation of their
clinical utility.
44.e8
Research Obstetrics www.AJOG.org

Treatment of an early
FIGURE 7
diagnosis of CSP
VI as function of time after intragestational
Treatment of CSP carried a significant
sac injection of methotrexate
complication rate. Of the 751 cases, 331
(44.1%) ended up with complications.
As a result, 36 hysterectomies, 40 lapa-
rotomies, and 21 uterine artery emboliza-
tions were performed as emergency mea-
sures to treat complications. Treatments,
such as systemic MTX, D&C, and uterine
artery embolization carried the highest
number of complications (62.1%, 61.9%,
and 46.9%, respectively).4
Mean vascularity indices for the 3 pa-
tients undergoing hysterectomy in our
series was 63.1% while for the 16 patients
without hysterectomy the mean VI was
17.8% (P ⬍ .05). The lowest complica-
tion rates were achieved by using local
intragestational injection of MTX or ka-
lium chloride as well as hysteroscopy
VI increased after injection and steadily dropped thereafter.
(9.6% and 18.4%, respectively).4 In
VI, vascularization index.
treating our patients with local intrages- Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.
tational MTX injection we applied the
lessons learned from reviewing the entire
available literature on CSP. In all but one not fully effective leading to hysterec- vaginal ultrasound probe.61-64 The tech-
of the referred patients intramuscular tomy.4 It is important to mention that nique we used is not the only one to be
MTX injections by the primary provid- the patient who presented with heavy used for such a treatment. The fact is, al-
ers failed to stop the heart activity. All of bleeding to our emergency department most all manufacturers enable a needle
our injected cases were successfully (patient 26 in Table 1) was promptly di- guide to be attached to their transvaginal
treated (ie, the heartbeats were stopped) agnosed with an A-V malformation probe. They also feature an electronic on-
and yielded the expected results (ie, no within the CD and in this case the pa- screen needle path with depth markings.
complications were noted). CSP compli- thologies were successfully treated by Given the above, the technique of trans-
cation can present in 2 ways: (1) as an emergency embolization of the uterine vaginal (or for that matter, transabdomi-
acute emergency in which the patient is artery. nal) ultrasound-guided puncture and in-
bleeding, or has an acute abdomen due to Since real-time transvaginal (or transab- jection is widely available. Oocyte retrieval
uterine rupture–in both, emergency sur- dominal) ultrasound-guided intragesta- relies on similar needle insertion tech-
gery or uterine artery embolization by in- tional sac injections can be performed in niques for years.106,107 A considerable ad-
terventional radiology are required; and an outpatient office setting, no anesthesia vantage of ultrasound-guided intragesta-
(2) at sonography in a patient with a his- is required. None of our 19 patients had tional sac injection is that it can be
tory of CD, who undergoes ultrasound anesthesia. To perform the intragesta- performed as an office procedure. This is
examination. tional sac injection we used an automated, in contrast to most surgical treatment ap-
Our expectations of the treatment spring-loaded device mated to the trans- proaches, which are performed under an-
were based upon our previously re-
ported results of injecting various ecto- TABLE 3
pic pregnancies61-64 as well as the first in- Mean, SE, and interquartile range for serum hCG,
tragestational sac injection cases by volume of gestational sac, and VI
Godin et al.105 In the advanced case (pa-
tient 9 in Table 2) where D&C was used, Measure Mean SE 25-75% range
not only did the procedure fail to provide hCG, mIU/mL 4334.6 1114.1 9.0–4677.0
..............................................................................................................................................................................................................................................
the expected and final treatment, but it Volume, mL 18.1 3.1 2.4–24.6
..............................................................................................................................................................................................................................................
may have led to the development of an VI 18.9 2.1 7.0–26.4
A-V malformation. In the same case, as ..............................................................................................................................................................................................................................................
hCG, human chorionic gonadotropin; VI, vascularization index.
in some cases reported in the literature, Timor-Tritsch. Diagnosis and treatment of cesarean scar pregnancy. Am J Obstet Gynecol 2012.
embolization of the uterine artery was

44.e9 American Journal of Obstetrics & Gynecology JULY 2012

www.AJOG.org
esthesia, therefore, one has to also consider
this as an additional source of risk, mini-
mal as it may be. All our locally injected
cases provided adequate final treatment
with no resulting complications.
We have to address the issue of treat-
ment with MTX by the referring site
prior to our intervention. To our knowl-
edge, patients were injected with low
doses of MTX (25-50 mg) and were re-
ferred to our care 7-10 days later when
the serum hCG levels failed to drop and
the heart activity was still present. We
suggest that waiting in excess of 3-4 days
for the trophoblast to cease its function
and result in declining hCG production
causing the heart activity to stop endan-
gers the patient. During this period of
waiting for results, the gestation is grow-
ing and its vascularization is increasing,
presenting a more challenging manage-
ment problem. Our approach treating
pregnancies by injecting MTX is that this
should be done as early as possible for the
aforementioned reasons.
Follow-up and resolution
As to the resolution of the CSP after its
local treatment, it should be clear that
this is a long process measured in many
weeks or months. The mean time of res-
olution of the 22 patients who did not
have hysterectomy or embolization was
88.6 days (range, 26 –177). The literature
acknowledges this as well as the initial
increase of the serum hCG, the sac vol-
ume, and its vascularity before their
slow resolution.10,18,32,48,52,89,96,108-110
The reasons for the initial increase of the
serum hCG are unclear. More impor-
tantly, in the case reports many of the
secondary treatments (laparoscopy, hys-
teroscopy, laparotomy, and emboliza-
tion) were not triggered by bleeding, but
by the observation of the posttreatment
increase in serum hCG, as well as the size
and blood supply of the treated site.
Follow-up after intragestational
and intramuscular local MTX
injection of CSP
Ourapproachhasincluded3parameters:(1)
serial serum hCG determinations; (2) vol-
ume of the gestational sac; and (3) the degree
of vascularization. The rationale for selecting
this combination is that hCG is a marker of
trophoblast viability. Serum concentrations
of hCG are used to follow up patients with
ectopic pregnancies treated with MTX, and
also, gestational trophoblastic disease. The
finding of a nondetectable hCG concentra-
tion in serum is widely accepted as evidence
that no trophoblast is viable. This is a reason-
able indication that treatment of MTX injec-
tionoftheintragestationalsacwassuccessful.
However, we (and others) have observed
complications of ectopic pregnancy in pa-
tients with a nondetectable hCG.111 Such
complications often result from the detach-
mentofthegestationalsacfromthematernal
tissues.111 For this reason, we incorporated
the other 2 sonographic parameters: volume
estimation of the gestational sac and the de-
gree of vascularization. The expectation
would be that successful treatment would re-
sultinareductioninthesizeofthegestational
sac and decrease of the VI.
A fact is worth mentioning: the mean VI
in the 3 patients treated by hysterectomy
was higher than the 23 patients who did
not have their uteri removed (68.1% vs
17.8%). This may imply that a high VI at
presentation may be a predictor of compli-
cations. Even though patient 26 with an
A-V malformation did not undergo surgi-
cal treatment her VI was high (65%) and
she had uterine artery embolization.
An interesting observation of our
study is that, after the treatment regimen
was instituted, hCG concentrations ini-
tially increased, the volume of the gesta-
tional sac went up, and the VI also rose.
Similar observations have been made by
others.10,32,48,52,89,96,108-110 One possible
explanation for this is that, after MTX
administration, trophoblast cells un-
dergo necrosis. Stored hCG within tro-
phoblast cells may be released into the
circulation, and hence, the apparent in-
crease in hCG serum concentration. Ne-
crosis of trophoblasts may lead to a local
peritrophoblastic inflammatory reac-
tion: this may explain the transient in-
crease in volume observed with 3D ultra-
sound and the increase in VI. After the
initial inflammatory reaction subsides
and the CSP is in the process of resolu-
tion, volume and VI decrease. It is note-
worthy that the mass may persist in some
patients for months– clinicians should
be aware of this particular observation,
and if such a transient increase is ob-
JULY 2012 American Journal of Obstetrics & Gynecology
Obstetrics Research
served, we recommend expectant man-
agement, which has been successful in
the cases presented in this series.
We have used 3D ultrasound to
monitor the effect of treatment on
CSP. The rationale for this is that the
VOCAL software allows calculation of
the volume of the mass, and that the VI
is an index of the degree of vasculariza-
tion based upon power angiography
with 3D ultrasound. Whether these
modalities are superior to 2-dimen-
sional ultrasound and simple color and
power Doppler remains to be deter-
mined. A comparison of the 2 was not
the purpose of this study. Subjective
observation and follow-up of vessel
density in the injected area should
guide those who do not use the 3D ul-
trasound angiographic techniques.
Conclusion
CSP represents a diagnostic and thera-
peutic challenge. Its frequency is increas-
ing as more CD are performed. We have
used a set of diagnostic criteria as well as
a management and follow-up program
for the minimally invasive treatment of
this complication of pregnancy. The
combination of systemic and intragesta-
tional sac administration of MTX is rel-
atively simple, can be performed as an
office procedure, and has been highly
successful in the treatment of CSP in this
case series. Recent articles suggest that
transvaginal ultrasound can be used
to examine the first-trimester uterine
scar112 and the likelihood of placenta ac-
creta in the first trimester.113 f
REFERENCES
1. Hamilton BE, Martin JA, Ventura SJ. Births:
preliminary data for 2007. Natl Vital Stat Rep
2009;57:12.
2. Menacker F, Hamilton BE. Recent trends in
cesarean delivery in the United States. NCHS
Data Brief 2010:18.
3. Rotas MA, Haberman S, Levgur M. Cesarean
scar ectopic pregnancies: etiology, diagnosis,
and management. Obstet Gynecol 2006;107:
1373-81.
4. Timor-Tritsch IE, Monteagudo A. Unforeseen
consequences of the increasing rate of cesar-
ean deliveries: early placenta accreta and ce-
sarean section scar pregnancy; a review. Am J
Obstet Gynecol 2012 Mar 10 [Epub ahead of
print].
5. American College of Obstetricians and Gyne-
cologists Committee on Obstetric Practice.
44.e10
Research Obstetrics
ACOG committee opinion no. 266, January
2002: placenta accreta. Obstet Gynecol 2002;
99:169-70.
6. Clark SL, Koonings PP, Phelan JP. Placenta
previa/accreta and prior cesarean section. Ob-
stet Gynecol 1985;66:89-92.
7. Miller DA, Chollet JA, Goodwin TM. Clinical
risk factors for placenta previa-placenta ac-
creta. Am J Obstet Gynecol 1997;177:210-4.
8. Silver RM, Landon MB, Rouse DJ, et al. Ma-
ternal morbidity associated with multiple repeat
cesarean deliveries. Obstet Gynecol 2006;
107:1226-32.
9. Wu S, Kocherginsky M, Hibbard JU. Abnor-
mal placentation: twenty-year analysis. Am J
Obstet Gynecol 2005;192:1458-61.
10. Seow KM, Huang LW, Lin YH, Lin MY, Tsai
YL, Hwang JL. Cesarean scar pregnancy: is-
sues in management. Ultrasound Obstet Gyne-
col 2004;23:247-53.
11. Shi H, Fang A-H, Chen Q-F. Clinical analysis
of 45 cases of cesarean scar pregnancy. J Re-
prod Contraception 2008;19:101-6.
12. Annappa M, Tripathi L, Mahendran M. Ce-
sarean section scar ectopic pregnancy pre-
senting as a fibroid. J Obstet Gynaecol 2009;
29:774.
13. Arruda Mde S, de Camargo Junior HS. Ce-
sarean scar ectopic pregnancy: a case report
[in Portuguese]. Rev Bras Ginecol Obstet 2008;
30:518-23.
14. Ayoubi JM, Fanchin R, Meddoun M, Fer-
nandez H, Pons JC. Conservative treatment of
complicated cesarean scar pregnancy. Acta
Obstet Gynecol Scand 2001;80:469-70.
15. Ben Nagi J, Ofili-Yebovi D, Sawyer E, Aplin
J, Jurkovic D. Successful treatment of a recur-
rent cesarean scar ectopic pregnancy by surgi-
cal repair of the uterine defect. Ultrasound Ob-
stet Gynecol 2006;28:855-6.
16. Bignardi T, Condous G. Transrectal ultra-
sound-guided surgical evacuation of cesarean
scar ectopic pregnancy. Ultrasound Obstet Gy-
necol 2010;35:481-5.
17. Deans R, Abbott J. Hysteroscopic manage-
ment of cesarean scar ectopic pregnancy. Fertil
Steril 2010;93:1735-40.
18. Deb S, Clewes J, Hewer C, Raine-Fenning
N. The management of cesarean scar ectopic
pregnancy following treatment with methotrex-
ate–a clinical challenge. Ultrasound Obstet Gy-
necol 2007;30:889-92.
19. Fabunmi L, Perks N. Cesarean section scar
ectopic pregnancy following postcoital contra-
ception. J Fam Plann Reprod Health Care
2002;28:155-6.
20. Fylstra DL, Pound-Chang T, Miller MG,
Cooper A, Miller KM. Ectopic pregnancy within
a cesarean delivery scar: a case report. Am J
Obstet Gynecol 2002;187:302-4.
21. Holland MG, Bienstock JL. Recurrent ecto-
pic pregnancy in a cesarean scar. Obstet Gy-
necol 2008;111:541-5.
22. Jurkovic D, Ben-Nagi J, Ofilli-Yebovi D,
Sawyer E, Helmy S, Yazbek J. Efficacy of Shi-
rodkar cervical suture in securing hemostasis
following surgical evacuation of cesarean scar
44.e11 American Journal of Obstetrics & Gynecology JULY 2012
ectopic pregnancy. Ultrasound Obstet Gynecol
2007;30:95-100.
23. Korkontzelos I, Tsirkas P, Antoniou N, Sou-
liotis D, Kosmas I. Successful term pregnancy
after treatment of a cesarean scar ectopic ges-
tation by endoscopic technique and conserva-
tive therapy. Fertil Steril 2008;90:2010e13-5.
24. Kucera E, Krepelka P, Krofta L, Feyereisl J.
Cesarean scar ectopic pregnancy [in Czech].
Ceska Gynekol 2007;72:207-13.
25. Kung FT, Huang TL, Chen CW, Cheng YF.
Image in reproductive medicine: cesarean scar
ectopic pregnancy. Fertil Steril 2006;85:
1508-9.
26. McKenna DA, Poder L, Goldman M, Gold-
stein RB. Role of sonography in the recognition,
assessment, and treatment of cesarean scar
ectopic pregnancies. J Ultrasound Med 2008;
27:779-83.
27. Ozkan S, Caliskan E, Ozeren S, Corakci A,
Cakiroglu Y, Coskun E. Three-dimensional ul-
trasonographic diagnosis and hysteroscopic
management of a viable cesarean scar ectopic
pregnancy. J Obstet Gynaecol Res 2007;33:
873-7.
28. Persadie RJ, Fortier A, Stopps RG. Ectopic
pregnancy in a cesarean scar: a case report. J
Obstet Gynaecol Can 2005;27:1102-6.
29. Tulpin L, Morel O, Malartic C, Barranger E.
Conservative management of a cesarean scar
ectopic pregnancy: a case report. Cases J
2009;2:7794.
30. Wang YL, Su TH, Chen HS. Operative lap-
aroscopy for unruptured ectopic pregnancy in a
cesarean scar. BJOG 2006;113:1035-8.
31. Little EA, Moussavian B, Horrow MM. Ce-
sarean delivery scar ectopic pregnancy. Ultra-
sound Q 2010;26:107-9.
32. Wang JH, Xu KH, Lin J, Xu JY, Wu RJ.
Methotrexate therapy for cesarean section scar
pregnancy with and without suction curettage.
Fertil Steril 2009;92:1208-13.
33. Ayas S, Akoz I, Karateke A, Bozoklu O. Suc-
cessful medical treatment of cesarean scar
pregnancy: a case report. Clin Exp Obstet Gy-
necol 2007;34:195-6.
34. Chou MM, Hwang JI, Tseng JJ, Huang YF,
Ho ES. Cesarean scar pregnancy: quantitative
assessment of uterine neovascularization with
3-dimensional color power Doppler imaging
and successful treatment with uterine artery
embolization. Am J Obstet Gynecol 2004;190:
866-8.
35. Dieh AP, Greenlandm H, Abdel-Aty M, Mar-
tindale EA. Re: El-Matary A, Akinlade R, Jolaoso
A. 2007. Cesarean scar pregnancy with expect-
ant management to full term. Journal of Obstet-
rics and Gynaecology 27:624-625. J Obstet
Gynaecol 2008;28:663-4.
36. Einenkel J, Stumpp P, Kosling S, Horn LC,
Hockel M. A misdiagnosed case of cesarean
scar pregnancy. Arch Gynecol Obstet 2005;
271:178-81.
37. Ficicioglu C, Attar R, Yildirim G, Cetinkaya
N. Fertility preserving surgical management of
methotrexate-resistant cesarean scar preg-
www.AJOG.org
nancy. Taiwan J Obstet Gynecol 2010;49:
211-3.
38. Ghezzi F, Lagana D, Franchi M, Fugazzola
C, Bolis P. Conservative treatment by chemo-
therapy and uterine arteries embolization of a
cesarean scar pregnancy. Eur J Obstet Gynecol
Reprod Biol 2002;103:88-91.
39. Goynumer G, Gokcen C, Senturk B, Turk-
geldi E. Treatment of a viable cesarean scar
pregnancy with transvaginal methotrexate and
potassium chloride injection. Arch Gynecol Ob-
stet 2009;280:869-72.
40. Hasegawa J, Ichizuka K, Matsuoka R, Ot-
suki K, Sekizawa A, Okai T. Limitations of con-
servative treatment for repeat cesarean scar
pregnancy. Ultrasound Obstet Gynecol 2005;
25:310-1.
41. Hwu YM, Hsu CY, Yang HY. Conservative
treatment of cesarean scar pregnancy with
transvaginal needle aspiration of the embryo.
BJOG 2005;112:841-2.
42. Jurkovic D, Hillaby K, Woelfer B, Lawrence
A, Salim R, Elson CJ. Cesarean scar preg-
nancy. Ultrasound Obstet Gynecol 2003;21:
310.
43. Jurkovic D, Hillaby K, Woelfer B, Lawrence
A, Salim R, Elson CJ. First-trimester diagnosis
and management of pregnancies implanted
into the lower uterine segment cesarean section
scar. Ultrasound Obstet Gynecol 2003;21:
220-7.
44. Li SP, Wang W, Tang XL, Wang Y. Cesar-
ean scar pregnancy: a case report. Chin Med J
(Engl) 2004;117:316-7.
45. Liang F, He J. Methotrexate-based bilateral
uterine arterial chemoembolization for treat-
ment of cesarean scar pregnancy. Acta Obstet
Gynecol Scand 2010;89:1592-4.
46. Litwicka K, Greco E, Prefumo F, et al. Suc-
cessful management of a triplet heterotopic ce-
sarean scar pregnancy after in vitro fertilization-
embryo transfer. Fertil Steril 2011;95:291e1-3.
47. Muraji M, Mabuchi S, Hisamoto K, et al.
Cesarean scar pregnancies successfully
treated with methotrexate. Acta Obstet Gyne-
col Scand 2009;88:720-3.
48. Seow KM, Hwang JL, Tsai YL, Huang LW,
Lin YH, Hsieh BC. Subsequent pregnancy out-
come after conservative treatment of a previous
cesarean scar pregnancy. Acta Obstet Gynecol
Scand 2004;83:1167-72.
49. Sharma S, Imoh-Ita F. Surgical manage-
ment of cesarean scar pregnancy. J Obstet
Gynaecol 2005;25:525-6.
50. Shufaro Y, Nadjari M. Implantation of a
gestational sac in a cesarean section scar.
Fertil Steril 2001;75:1217.
51. Smith A, Ash A, Maxwell D. Sonographic
diagnosis of cesarean scar pregnancy at 16
weeks. J Clin Ultrasound 2007;35:212-5.
52. Tan G, Chong YS, Biswas A. Cesarean scar
pregnancy: a diagnosis to consider carefully in
patients with risk factors. Ann Acad Med Singa-
pore 2005;34:216-9.
53. Wang CB, Tseng CJ. Primary evacuation
therapy for cesarean scar pregnancy: three new
www.AJOG.org
cases and review. Ultrasound Obstet Gynecol
2006;27:222-6.
54. Wang CJ, Chao AS, Yuen LT, Wang CW,
Soong YK, Lee CL. Endoscopic management
of cesarean scar pregnancy. Fertil Steril
2006;85:494e1-4.
55. Wang CJ, Tsai F, Chen C, Chao A. Hyster-
oscopic management of heterotopic cesarean
scar pregnancy. Fertil Steril 2010;94:
1529e15-8.
56. Yan CM. A report of four cases of cesarean
scar pregnancy in a period of 12 months. Hong
Kong Med J 2007;13:141-3.
57. Yang XY, Yu H, Li KM, Chu YX, Zheng A.
Uterine artery embolization combined with local
methotrexate for treatment of cesarean scar
pregnancy. BJOG 2010;117:990-6.
58. March of Dimes. Printable articles. Available
at: www.marchofdimes.com/printableArticles/
csection_indepth.html. Accessed July 1, 2008.
59. Seow KM, Hwang JL, Tsai YL. Ultrasound
diagnosis of a pregnancy in a cesarean section
scar. Ultrasound Obstet Gynecol 2001;18:
547-9.
60. Vial Y, Petignat P, Hohlfeld P. Pregnancy in
a cesarean scar. Ultrasound Obstet Gynecol
2000;16:592-3.
61. Monteagudo A, Minior VK, Stephenson C,
Monda S, Timor-Tritsch IE. Non-surgical man-
agement of live ectopic pregnancy with ultra-
sound-guided local injection: a case series. Ul-
trasound Obstet Gynecol 2005;25:282-8.
62. Monteagudo A, Tarricone NJ, Timor-Tritsch
IE, Lerner JP. Successful transvaginal ultra-
sound-guided puncture and injection of a cer-
vical pregnancy in a patient with simultaneous
intrauterine pregnancy and a history of a previ-
ous cervical pregnancy. Ultrasound Obstet Gy-
necol 1996;8:381-6.
63. Timor-Tritsch IE, Monteagudo A, Mandev-
ille EO, Peisner DB, Anaya GP, Pirrone EC. Suc-
cessful management of viable cervical preg-
nancy by local injection of methotrexate guided
by transvaginal ultrasonography. Am J Obstet
Gynecol 1994;170:737-9.
64. Timor-Tritsch IE, Peisner DB, Monteagudo
A. Puncture procedures utilizing transvaginal ul-
trasonic guidance. Ultrasound Obstet Gynecol
1991;1:144-50.
65. Chang CY, Wu MT, Shih JC, Lee CN. Pres-
ervation of uterine integrity via transarterial em-
bolization under postoperative massive vaginal
bleeding due to cesarean scar pregnancy. Tai-
wan J Obstet Gynecol 2006;45:183-7.
66. Dabulis SA, McGuirk TD. An unusual case
of hemoperitoneum: uterine rupture at 9 weeks
gestational age. J Emerg Med 2007;33:285-7.
67. de Vaate AJ, Brolmann HA, van der Slikke
JW, Wouters MG, Schats R, Huirne JA. Thera-
peutic options of cesarean scar pregnancy:
case series and literature review. J Clin Ultra-
sound 2010;38:75-84.
68. Tanyi JL, Coleman NM, Johnston ND, Ay-
ensu-Coker L, Rajkovic A. Placenta percreta at
7th week of pregnancy in a woman with previ-
ous cesarean section. J Obstet Gynaecol
2008;28:338-40.
69. Arslan M, Pata O, Dilek TU, Aktas A, Aban
M, Dilek S. Treatment of viable cesarean scar
ectopic pregnancy with suction curettage. Int J
Gynaecol Obstet 2005;89:163-6.
70. Chen CH, Wang PH, Liu WM. Successful
treatment of cesarean scar pregnancy using
laparoscopically assisted local injection of eto-
poside with transvaginal ultrasound guidance.
Fertil Steril 2009;92:1747e9-11.
71. Damarey I, Durant-Reville M, Robert Y, Le-
roy JL. Diagnosis of an ectopic pregnancy on a
cesarean scar [in French]. J Radiol 1999;80:
44-6.
72. Harden MA, Walters MD, Valente PT. Post-
abortal hemorrhage due to placenta increta: a
case report. Obstet Gynecol 1990;75:523-6.
73. Huang KH, Lee CL, Wang CJ, Soong YK,
Lee KF. Pregnancy in a previous cesarean sec-
tion scar: case report. Changgeng Yi Xue Za Zhi
1998;21:323-7.
74. Liang HS, Jeng CJ, Sheen TC, Lee FK,
Yang YC, Tzeng CR. First-trimester uterine rup-
ture from a placenta percreta: a case report. J
Reprod Med 2003;48:474-8.
75. Lichtenberg ES, Frederiksen MC. Cesarean
scar dehiscence as a cause of hemorrhage after
second-trimester abortion by dilation and evac-
uation. Contraception 2004;70:61-4.
76. Michener C, Dickinson JE. Cesarean scar
ectopic pregnancy: a single center case series.
Aust N Z J Obstet Gynaecol 2009;49:451-5.
77. Moschos E, Sreenarasimhaiah S, Twickler
DM. First-trimester diagnosis of cesarean scar
ectopic pregnancy. J Clin Ultrasound 2008;36:
504-11.
78. Neiger R, Weldon K, Means N. Intramural
pregnancy in a cesarean section scar: a case
report. J Reprod Med 1998;43:999-1001.
79. Nonaka M, Toyoki H, Imai A. Cesarean sec-
tion scar pregnancy may be the cause of seri-
ous hemorrhage after first-trimester abortion by
dilatation and curettage. Int J Gynaecol Obstet
2006;95:50-1.
80. Reyftmann L, Vernhet H, Boulot P. Man-
agement of massive uterine bleeding in a cesar-
ean scar pregnancy. Int J Gynaecol Obstet
2005;89:154-5.
81. Rygh AB, Greve OJ, Fjetland L, Berland JM,
Eggebo TM. Arteriovenous malformation as a
consequence of a scar pregnancy. Acta Obstet
Gynecol Scand 2009;88:853-5.
82. Wu CF, Hsu CY, Chen CP. Ectopic molar
pregnancy in a cesarean scar. Taiwan J Obstet
Gynecol 2006;45:343-5.
83. Yang MJ, Jeng MH. Combination of tran-
sarterial embolization of uterine arteries and
conservative surgical treatment for pregnancy
in a cesarean section scar: a report of 3 cases.
J Reprod Med 2003;48:213-6.
84. Chueh HY, Cheng PJ, Wang CW, Shaw
SW, Lee CL, Soong YK. Ectopic twin preg-
nancy in cesarean scar after in vitro fertilization/
embryo transfer: case report. Fertil Steril
2008;90:2009e19-21.
85. Fernandez H. Isthmic pregnancy located in
a previous cesarean section scar treated with
methotrexate: a case report. Gynecol Obstet
JULY 2012 American Journal of Obstetrics & Gynecology
Obstetrics Research
Fertil 2005;33:772-775 [in French]. Gynecol
Obstet Fertil 2006;34:181.
86. Yang Q, Piao S, Wang G, Wang Y, Liu C.
Hysteroscopic surgery of ectopic pregnancy in
the cesarean section scar. J Minim Invasive Gy-
necol 2009;16:432-6.
87. Chao A, Wang TH, Wang CJ, Lee CL, Chao
AS. Hysteroscopic management of cesarean
scar pregnancy after unsuccessful methotrex-
ate treatment. J Minim Invasive Gynecol
2005;12:374-6.
88. Graesslin O, Dedecker F Jr, Quereux C, Ga-
briel R. Conservative treatment of ectopic preg-
nancy in a cesarean scar. Obstet Gynecol
2005;105:869-71.
89. Haimov-Kochman R, Sciaky-Tamir Y, Yanai
N, Yagel S. Conservative management of two
ectopic pregnancies implanted in previous uter-
ine scars. Ultrasound Obstet Gynecol 2002;
19:616-9.
90. Iyibozkurt AC, Topuz S, Gungor F, Kalelio-
glu IH, Cigerli E, Akhan SE. Conservative treat-
ment of an early ectopic pregnancy in a cesar-
ean scar with systemic methotrexate– case
report. Clin Exp Obstet Gynecol 2008;35:73-5.
91. Lam PM, Lo KW. Multiple-dose methotrex-
ate for pregnancy in a cesarean section scar: a
case report. J Reprod Med 2002;47:332-4.
92. Lam PM, Lo KW, Lau TK. Unsuccessful
medical treatment of cesarean scar ectopic
pregnancy with systemic methotrexate: a re-
port of two cases. Acta Obstet Gynecol Scand
2004;83:108-11.
93. Marchiole P, Gorlero F, de Caro G, Podesta
M, Valenzano M. Intramural pregnancy embed-
ded in a previous cesarean section scar treated
conservatively. Ultrasound Obstet Gynecol
2004;23:307-9.
94. Paillocher N, Biquard F, Paris L, Catala L,
Descamps P. Isthmic pregnancy located in a
previous cesarean section scar treated with
methotrexate: a case report [in French]. Gyne-
col Obstet Fertil 2005;33:772-5.
95. Ravhon A, Ben-Chetrit A, Rabinowitz R,
Neuman M, Beller U. Successful methotrexate
treatment of a viable pregnancy within a thin
uterine scar. Br J Obstet Gynaecol 1997;104:
628-9.
96. Sadeghi H, Rutherford T, Rackow BW, et al.
Cesarean scar ectopic pregnancy: case series
and review of the literature. Am J Perinatol
2010;27:111-20.
97. Wang YL, Su TH, Chen HS. Laparoscopic
management of an ectopic pregnancy in a
lower segment cesarean section scar: a review
and case report. J Minim Invasive Gynecol
2005;12:73-9.
98. Chuang J, Seow KM, Cheng WC, Tsai YL,
Hwang JL. Conservative treatment of ectopic
pregnancy in a cesarean section scar. BJOG
2003;110:869-70.
99. Al-Nazer A, Omar L, Wahba M, Abbas T,
Abdulkarim M. Ectopic intramural pregnancy
developing at the site of a cesarean section
scar: a case report. Cases J 2009;2:9404.
100. Passaro R, Battagliese A, Paolillo F. Ecto-
pic pregnancy on previous cesarean section
44.e12
Research Obstetrics
scar: case report. Minerva Ginecol 2005;57:
207-12.
101. Rempen A. An ectopic pregnancy embed-
ded in the myometrium of a previous cesarean
section scar. Acta Obstet Gynecol Scand
1997;76:492.
102. Yalinkaya A, Yalinkaya O, Olmez G, Yayla
M. Ectopic pregnancy in a previous cesarean
section scar: a case report. Internet J Gynecol
Obstet 2004;3:1.
103. Hois EL, Hibbeln JF, Alonzo MJ, Chen ME,
Freimanis MG. Ectopic pregnancy in a cesarean
section scar treated with intramuscular metho-
trexate and bilateral uterine artery embolization.
J Clin Ultrasound 2008;36:123-7.
104. Kiley J, Shulman LP. Cesarean scar ecto-
pic pregnancy in a patient with multiple prior
cesarean sections: a case report. J Reprod
Med 2009;54:251-4.
44.e13 American Journal of Obstetrics & Gynecology JULY 2012
105. Godin PA, Bassil S, Donnez J. An ectopic
pregnancy developing in a previous cesarean
section scar. Fertil Steril 1997;67:398-400.
106. Feichtinger W. Transvaginal oocyte re-
trieval. In: Chervenak FA, Isaacson GC, Camp-
bel S, eds. Ultrasound obstetrics and gynecol-
ogy. London: Little, Brown, and Co; 1993:
1397-406.
107. Feichtinger W, Putz M, Kemeter P. Four
years of experience with ultrasound-guided fol-
licle aspiration. Ann N Y Acad Sci 1988;
541:138-42.
108. Donnez J, Godin PA, Bassil S. Successful
methotrexate treatment of a viable pregnancy
within a thin uterine scar. Br J Obstet Gynaecol
1997;104:1216-7.
109. Hassan I, Lower A, Overton C. Ectopic preg-
nancy within a cesarean section scar. Ultrasound
Obstet Gynecol 2007;29:475-6.
www.AJOG.org
110. Lee JH, Kim SH, Cho SH, Kim SR. Lapa-
roscopic surgery of ectopic gestational sac
implanted in the cesarean section scar. Surg
Laparosc Endosc Percutan Tech 2008;18:
479-82.
111. Kadar N, Romero R. Observations on the
log human chorionic gonadotropin-time rela-
tionship in early pregnancy and its practical im-
plications. Am J Obstet Gynecol 1987;157:
73-8.
112. Stirnemann JJ, Chalouhi GE, Forner S, et
al. First-trimester uterine scar assessment by
transvaginal ultrasound. Am J Obstet Gynecol
2011;205:551e1-6.
113. Stirnemann JJ, Mousty E, Chalouhi G, Sa-
lomon LJ, Bernard JP, Ville Y. Screening for
placenta accreta at 11-14 weeks of gestation.
Am J Obstet Gynecol 2011;205:547e1-6.