a case series of caesarean section scar ectopic pregnancies

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LOST IN A SCAR:

A CASE SERIES OF CAESAREAN SECTION SCAR PREGANCIES

Aubrey Y. Señeris, RMT, MD

ABSTRACT

Implantation of an embryo inside a previous caesarean scar is considered to be the

rarest form of ectopic pregnancy and is a life-threatening condition. With the increasing

numbers of caesarean section being performed globally, and the widespread use of

transvaginal ultrasound with color flow Doppler imaging, more and more cases are

diagnosed and reported. A delay in the diagnosis and management of this life-threatening

condition may end in complications, primarily uterine rupture and hemorrhage with

considerable potential maternal morbidity. Diagnosis of a caesarean scar ectopic

pregnancy requires a high index of clinical suspicion, as up to half of patients may be

asymptomatic. Management plan should be on a case to case basis. Available statistics

suggest that termination of pregnancy is the treatment of choice in the first trimester soon

after the diagnosis. Expectant treatment has a poor prognosis because of risk of rupture.

Healthcare professionals should be familiar with the possibility of untoward sequelae and

how a modern work-up can help in guiding conservative options, thus reducing morbidity

and preserving fertility.

Keywords: pregnancy in scar, caesarean scar pregnancy, placenta accreta,

uterine rupture, scar ectopic pregnancy, magnetic resonance imaging, transvaginal

ultrasound, color Doppler imaging, uterine artery embolization

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INTRODUCTION

An ectopic pregnancy is the implantation of blastocyst anywhere else but the

endometrial lining of the uterine cavity. Based on the 10-year population-based study of

Callen, (2000) and Bouyer, et al, (2003), 95% of ectopic pregnancies are implanted in the

various segments of the fallopian tubes.1 The remaining 5% implant in the ovary,

peritoneal cavity, within the cervix, or within the previous caesarean scar. (Figure 1)

A caesarean scar pregnancy is considered to be the rarest form of ectopic

pregnancy.2 The first case was reported in the English medical literature by Larsen and

Solomon in 1978.3 At present, it is being reported more frequently, and the incidence is

now higher than that of cervical ectopic pregnancies.4 As abdominal delivery rates

increase, there has also been a substantial increase in published cases of caesarean scar

pregnancies in the medical literature since its first writing. The upsurge of the reported

caesarean scar pregnancies may also be attributed to the enhanced detection of this

condition through the routine use of transvaginal ultrasound during the first prenatal

visit.5 A delay in the diagnosis and management of this potentially fatal condition may

bring about complications such as rupture and haemorrhage, hence, early detection of the

caesarean scar pregnancy is crucial in avoiding maternal morbidity and mortality. A high

index of suspicion from patient history and physical examination combined with imaging

studies is necessary to arrive at the diagnosis. The improvement of technology in the use

of transvaginal ultrasound with Doppler flow imaging studies enable early detection and

thus aids in the prompt interventions and prevents potential complications. Various

treatment options are available and should be modified to sustain the needs of each

individual case.

Four cases of caesarean scar pregnancies will be discussed. All four were

managed by total abdominal hysterectomy.

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CASE DESCRIPTION

Case #1

A case of a 40-year old, Gravida 2 Para 1 (1001), from Cavite, at approximately

11 weeks age of gestation, consulted due to vaginal bleeding last March, 2013. Pregnancy

test was positive. Her first pregnancy was carried to term and delivered by caesarean

section for non-reassuring fetal status at a local hospital last 2006. She had one-month

history of vaginal bleeding soaking 3 pads per day without any associated abdominal pain

and other symptoms. Her vital signs were stable with essentially normal systemic

findings. Pelvic examination revealed normal external genitalia, smooth, nulliparous

vagina, cervix is 3x3 cm, smooth, slightly deviated posteriorly to the right, soft and

closed, corpus was enlarged to 10 to 12 weeks size, no adnexal masses or tenderness,

fornices formed, bilateral parametria were smooth and pliable. A transvaginal ultrasound

showed a heterogenous mass within the endometrial cavity at the lower uterine segment

measuring 5.5 x 6.9 x 5.7cm with cystic spaces within and seems to extend to almost full

thickness of the anterior myometrium at the area of the previous caesarean section scar.

(Figure 2-A) Color flow mapping of the mass shows moderate peripheral vascularity

Doppler interrogation showed intermediate resistance indices (PI=0.81, RI=0.56). (Figure

2-B). The impression was endomyometrial mass consider caesarean section scar

pregnancy vs gestational trophoblastic neoplasia. But because the preoperative Beta-HCG

level was only 311 mIU/mL, a gestational trophoblastic neoplasia was not highly

considered. Hence, the patient underwent exploratory laparotomy, total abdominal

hysterectomy. Intraoperatively, there were no ascites, no gross abnormalities on adjacent

organs, no palpable lymph nodes. The lower uterine segment measured 14 x 6.5 x 4 cm

(Figure 3-A). On cut section, within the lower uterine segment is a gestational sac-like

tissue which measured 2 x 2 cm in diameter with placental-like tissues (Figure 3-B). The

estimated blood loss was 900mL. The patient had an uneventful recovery post-op and

was discharged stable.

Case # 2

A 36-year old Gravida 3 Para 2 (2002), at 12 weeks and 6 days age of gestation

who came in for routine prenatal consult last April 2013 after a three-month history of

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amenorrhea with a positive pregnancy test. She had an unremarkable past medical and

family medical history. Her first two pregnancies were carried to term via abdominal

delivery. There was no history of vaginal spotting and hypogastric pain. However, during

routine transvaginal ultrasound, the gestational sac with an embryo was noted to be

implanted at the anterior myometrium at the lower uterine segment at the level of the

caesarean section scar. There was no cardiac activity noted. The overlying myometrium

was noted to be 0.15 cm thick. The impression was caesarean section scar pregnancy.

The patient underwent an elective total abdominal hysterectomy under regional

anesthesia and had an unremarkable post-operative course.

Case # 3

A 41-year old Gravida 4 Para 2 (2012) at her 7 weeks and 6 days age of gestation

consulted last July 2014 due to vaginal spotting. Her past medical history, family history

and personal and social history were unremarkable. Her first two pregnancies were

carried to term via caesarean section, the first was due to a non-reassuring fetal status and

the second was for repeat, last 2001 and 2004. She had an amenorrhea of approximately 2

months and pregnancy test was positive. However, she had 10 days history of vaginal

spotting soaking two panty liners per day which prompted consult at a local clinic where

ultrasound was done and revealed a gestational sac implanted at the lower uterine

segment. Patient was hence referred at a tertiary hospital. Upon consult, she had stable

vital signs with normal systemic findings. Pelvic examination revealed normal external

genitalia, smooth, nulliparous vagina, cervix is 3x3 cm, smooth, soft and closed, corpus

enlarged to 8 to 10 weeks size, no adnexal masses or tenderness, fornices formed,

bilateral parametria were smooth. Transvaginal scan revealed a heterogenous mass

occupying the anterior lower uterine segment measuring 4.0 x 3.5 x 2.6 cm with an

anechoic cyst structure within the gestational sac. (Figure 4-A) The anechoic cystic

structure is surrounded by dilated vessels with involvement of the full thickness of the

myometrium. (Figure 4-B) There was no embryonic pole or yolk sac seen. The overlying

uterine serosa is intact and seems to be adherent to the right posterior bladder wall. There

is no normal intervening myometrium between the mass and the posterior bladder wall.

The sonographic finding was suggestive of caesarean scar pregnancy. Diagnostic

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cystoscopy, exploratory laparotomy, adhesiolysis, total hysterectomy was done under

epidural anesthesia. On diagnostic cystourethroscopy, the urethral mucosa was smooth

and pink. The urethrovesical junction was intact. The trigone was smooth and pale.

Bilateral ureteral orifices are patent with good efflux of urine. There were no

hypervascularities, no prominent vessels seen. The rest of the bladder mucosa was

grossly normal (Figures 5-A to 5-D). There were no defects seen. Intraoperatively, the

lower uterine segment up to the isthmic area of the uterus was densely adherent to the

posterior bladder wall. On adhesiolysis, the lower uterine segment was thinned out on the

central portion. There was inadvertent tearing of the serosa during manipulation showing

a 3.5 x 2 x 1 cm cystic, unilocular mass, attached to the surrounding myometrium. The

mass, which seems to be the gestational sac, contained clear serous fluid within. There

was no fetus noted (Figure 6-A to 6-C). The patient tolerated the procedure well and was

discharged in stable condition.

Case # 4

A 35-year old Gravida 4 Para 3(2102) on 8 th week and 2 days age of gestation

came for consult last due to a 10-day history of vaginal spotting. This was associated

with 1 day history of hypogastric pain characterized as crampy with VAS score of 3/10.

Her first pregnancy was an abdominal delivery done at a local hospital in Mindoro at 6

months age of gestation for placenta previa, the baby expired within an hour after

delivery. Her subsequent pregnancies were delivered to term by repeat caesarean section

done at a local hospital in Mindoro. On physical examination, she has stable vital signs

with normal systemic findings. On internal examination, she has normal external

genitalia, nulliparous vagina, cervix is dilated by blood clots, corpus was enlarged to 8-10

weeks size. Transvaginal ultrasound was done showing a gestational sac within the

anterior isthmic area measuring 3.6 x1.8 x 2.1 cm with a mean sac diameter equivalent to

7 weeks and 4 days age of gestation. Within the gestational sac is a single live embryo

with a crown-rump length equivalent to 8 weeks and 1 day age of gestation. The yolk sac

measures 0.5cm. The CS scar is widened measuring 2.6cm and occupied by the growing

gestational sac. There is no overlying myometrium but the serosa is intact. No

hemorrhagic areas were noted. The overlying bladder and endopelvic fascia is intact. It

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was signed out as anterior isthmic mass consider CS scar pregnancy with CS scar

dehiscence (Figure 7-A and 7-B). The patient was then scheduled for total hysterectomy.

Her post-operative course was unremarkable and was discharged after three hospital

days.

DISCUSSION

Incidence

According to some authors CSP is the rarest form of ectopic pregnancy but its

incidence is not yet well established.9 The occurrence of caesarean scar pregnancy has

been estimated to range from 1/1800 to 1/2500 of all caesarean deliveries done.4, 6-8 A

case series9 done last 2004 estimated an incidence of 1:2226 of all pregnancies, with a

rate of 0.15% in women with a previous caesarean section and a rate of 6.1% of all

ectopic pregnancies in women who had at least one caesarean delivery. In a literature

review of 232 articles from 1995 to 2011, Dr. Timor-Tritsch found 751 reports of

caesarean scar pregnancies. Among them, the diagnosis was originally missed in as many

as 107 cases, or 13.6%.10

The time interval between the last caesarean section and the caesarean scar

pregnancy was 6 months to 12 years.9 Caesarean scar pregnancy has been described in

spontaneously conceived pregnancy as well as after in vitro fertilization (IVF) and

embryo transfer.9 An even rare case of in vitro fertilization-associated heterotopic

caesarean scar pregnancy, has also been described, both with twins11 and triplets.12 There

were no particular predilection for maternal age or parity reported for maternal.

The age of gestation at diagnosis ranged from 5 weeks to 12 and 4/7 weeks (mean

7.5 ± 2.5 weeks). Very few cases were reported to progress beyond first trimester6, 13 since

almost all are terminated during this period probably due to the significant risk of uterine

rupture resulting to haemorrhage if pregnancy in a caesarean section scar were to

continue to the second or third trimesters. A pregnancy that protrudes through the scar

can implant on other abdominal organs and continue to grow as a secondary abdominal

pregnancy. 14, 15 Conversely, if the pregnancy continues within the uterus, the risk of

placenta accreta is increased up to three- to five-fold.16, 17

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Figure 8 shows the number of publications containing cases, case series, and

reviews for the last 20 years.10 The numbers steadily increased toward the year 2010. This

apparent increase is likely multifactorial and related to increasing numbers of caesarean

deliveries, 4, 9 increased use of transvaginal sonography, and a heightened awareness of

this diagnosis.4,6 The growing number of articles promotes the fact that caesarean scar

pregnancy is becoming another diagnostic and obstetrical condition which needs an

urgent application of a standardized treatment protocol.

Risk Factors and Pathophysiology

Theories have been suggested to explain the occurrence of caesarean scar

pregnancy. Damage to the decidua basalis during uterine surgery can stay in the

endometrium in the form of tiny dehiscent tracts or minute wedge defects (Figure 9-A

and 9-B). The most acceptable mechanism is that the blastocyst inserts into the

myometrial wall through these tiny dehiscent tracts which may have been formed through

a trauma from a previous caesarean or any other uterine surgeries such as curettage,

myomectomy, metroplasty, hysteroscopy 18 or even following manual removal of the

placenta2, such that there is invasion of the myometrium through that minute tract

between the caesarean section scar and the endometrial canal.15, 19 Studies that were

conducted to evaluate the biochemical behaviour of the scarring process in previous

caesarean scar tissues found an altered biochemical process in the lower uterine segment

where the scar was present.32, 34 One of the studies33 found that there was a reduction of

pan-transforming growth factor-beta 31 in the scarred lower uterine segment. The

transforming growth factor-beta is known to influence collagen type I production. A

reduction of connective tissue growth factor was also noted, as well as a slight increase in

vascular and endothelial growth factor and tumor necrosis factor. These altered

biochemical process in the caesarean scar, given that the scar is already a thin tissue layer

made weaker by the invading trophoblast may partly explain some of the first trimester

and early second trimester uterine ruptures. Another theory is that production of local

injury to the endometrium such as after curettage may induce an inflammatory response

that prompted implantation. In a review done by Rosen35 last 2008, an in vitro work

demonstrated the role of a low oxygen tension that appears to be an important

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prerequisite for the invading cytotrophoblast to proliferate and regulate placental growth36

The scar tissue into which the placenta implants may provide that exact environment of

low oxygen tension stimulating the cytotrophoblast to deeply invade the scarred area.37

Contradictory to this theory, a different view done by Kliman38 showed that a trophoblast

has a stronger propensity for attaching to exposed extracellular matrix than endometrial

epithelial cells.38 This may explain why blastocysts have a preference to exposed scar

tissue, which is stripped of epithelial cells. This theory may explain the statement that the

higher the rate of previous caesarean deliveries, the higher the risk of caesarean scar

pregnancy.

There are two subtypes of caesarean scar pregnancies described in the literature.22

The first is an implantation on the prior caesarean scar with progression towards the

uterine cavity. The second is a deep implantation into the caesarean scar defect growing

towards the bladder and abdominal cavity. The first type of caesarean scar pregnancy

may progress to a viable birth but with the risk of a life-threatening bleeding. The second

type, on the other hand, is more prone to rupture if allowed to progress to a later

gestational age.

It is unclear if the risk of caesarean scar pregnancy is directly associated to the

number of previous caesarean sections done. In cases 1 and 3, the index patients only had

one previous caesarean section, with the latter having a previous history of curettage. The

second and fourth case, on the other hand, had two previous caesarean sections done.

Some authors have reported that between 50 and 72% of caesarean section pregnancies

occur after two or more prior caesarean sections.7, 23 Other literature believe that multiple

caesarean sections is a strong risk factor for caesarean scar pregnancies because of the

increased scar surface area,7 however, others debate against such a correlation. 24, 25 A

larger systematic review done in 2006 found that 52% cases followed only one previous

caesarean section, 36% after two and 12% after three or more previous caesarean

sections.4 There is inadequate data that suggests that there is an association with the

indication of the caesarean delivery and the risk of caesarean scar pregnancies, but

malpresentation (breech) has been documented as the most common indication for

caesarean section. There were no correlation found between the particular order of

previous caesarean sections and subsequent pregnancies.4 The time interval between the

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previous caesarean section may possibly contribute to the scar implantation. A caesarean

scar pregnancy that occurs within a few months after a caesarean section may suggest

that an incomplete healing of the caesarean sections scar lead to implantation to the

minute tract. 14 However, this theory may not explain the caesarean scar pregnancy that

has been reported as late as twelve years after a prior caesarean section.20 The surgical

technique for uterine closure might have a role in causation of caesarean scar pregnancy,

however, there is no current literature available to support this statement. Seow et al., also

suggested a possible correlation between caesarean scar pregnancies and the use of

intrauterine device, as well as a previous history of pelvic inflammatory disease. 9

Placenta Accreta vs CS Scar Pregnancy

Implantation of a pregnancy within the scar of a previous caesarean section is

different from that of an intrauterine pregnancy with placenta accreta.15 In placenta

accreta, the pregnancy is within the uterine cavity and is characterized by the absence of

decidua basalis, with varying degrees of invasion of the myometrium by trophoblastic

tissue. By definition, if the placenta attaches abnormally and penetrates to various depths

into the underlying myometrium, the term pathologically or morbidly adherent placenta,

is used. The degree of myometrial penetration defines the descriptive terminology used

such as accreta, percreta and increta. Accreta is identified when the villi penetrate

through the decidua basalis up to the level of the myometrium. If the villi penetrate into

the depths of the myometrium, the term increta is used by the pathologist. If it invades the

entire thickness of the myometrium, peritoneum or the bladder wall, the term percreta is

used. However, due to the challenge to provide an accurate diagnosis of the degree of

invasion, the term placenta accreta is used to refer to these of adherent placenta.10

Caesarean scar pregnancy, on the other hand is separate from the endometrial cavity since

the gestational sac is completely surrounded by myometrium and the fibrous tissue of the

scar. A caesarean scar pregnancy is more aggressive in nature than placenta accreta

because of its early invasion of the myometrium.20 The histopathological findings of the

specimen after a total hysterectomy proposed that the villi are not only penetrating the

myometrium but are attached with or implanted in it.21 A caesarean section scar

pregnancy is considered as an iatrogenic entity. The pathophysiology of placental

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implantation in placenta accreta and caesarean scar pregnancy appears to be similar.

However, there is one exception, a placenta accreta may occur in an unscarred uterus, as

compared to a caesarean scar pregnancy which refers only to implantation of the

gestational sac in the scar of the previous cesarean section.

Clinical Presentation

Patients with caesarean scar pregnancy may present with symptoms similar to

those of other forms of ectopic pregnancy. It may present as early as 5 to 6 weeks 9 to as

late as 16 weeks.26 The index cases were diagnosed at 7 to 12 weeks age of gestation. In

39% of cases, the early presenting symptom is usually a painless vaginal bleeding as the

presentation of the index cases. 16% of women with spotting had an associated mild to

moderate abdominal pain while 9% complain only of abdominal pain.4 Because of the

early onset in pregnancy of vaginal spotting or low abdominal pain, this condition could

be misdiagnosed as a case of spontaneous abortion.27 37% of cases are asyptomatic and

were only incidental findings during transvaginal scan as with the second index case.4

Physical examination in stable women is mostly unremarkable. The abdomen may be

tender on palpation if it is in the process of uterine rupture. Hemodynamic instability and

severe abdominal pain strongly indicates uterine rupture.

Diagnosis

A prompt and accurate diagnosis is crucial since the clinical diagnosis of an early

caesarean scar pregnancy can be difficult and may sometimes be delayed until the uterus

ruptures and the patient experiences severe bleeding. 9, 23, 28, 29 Among the diagnostics of

caesarean scar pregnancy, the most important is based on sonographic and Doppler

imaging findings.30

Ultrasound

Majority of caesarean scar pregnancies have been diagnosed using transvaginal

ultrasound and it is considered as the first-line diagnostic tool for caesarean scar

pregnancies. It has a sensitivity of 86.4% (95% CI 0.763–0.9050).4 There are criteria that

assist in distinguishing this type of pregnancy from other types of ectopic pregnancies

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such as cervicoisthmic implantation, cervical pregnancy and spontaneous abortion in

progress. 14, 19 These are:15, 19 (1) an empty uterine cavity and an empty cervical canal,

without contact with the sac (Figure 10-A), (2) presence of placenta or gestation sac

embedded in the caesarean section scar (Figure 10-B), (3) in early gestations (<8 weeks),

a triangular gestational sac that fills the niche of the scar (Figure 12-A); at >8

postmenstrual weeks this shape may become rounded or even oval. (4) absence of or a

defect in the myometrial tissue between the bladder and the sac (Figure 10-C), (5)

presence of embryonic/fetal pole and/or yolk sac with or without heart activity, (6)

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 12-C), (7) no adnexal mass or free fluid

in the pouch of Douglas, unless the caesarean scar pregnancy has ruptured.

Jurkovic et al.7 have described a finding of negative ‘sliding organ sign’ which is

defined as the inability to displace the gestational sac from its position at the level of the

internal os by using gentle pressure applied by the transabdominal probe and transfundal

manual pressure. Maymon et al.,25 on the other hand, believed that this approach might

provoke unnecessary vaginal bleeding and rupture and recommended an approach to

reduce the risk of a false diagnosis23, 25 He recommended a transvaginal scan to be done to

obtain the fine details of the gestation sac and its relation to the scar followed by an

abdominal scan with a full bladder. The abdominal scan will provide a panoramic view of

the uterus and an accurate measurement of the distance between the gestation sac and the

bladder. This combined approach should confirm the diagnosis and provide additional

information on the thickness of the myometrium between the bladder and the gestational

sac. In 67% of cases, the thickness of the myometrium between the gestation sac and the

bladder has been shown to be less than 5mm.28 There may be a discontinuity in the lower

anterior wall of the uterus, with a bulging pregnancy sac protruding through the gap

(Figure 11)39 indicating a pre-rupture state.

Doppler Studies

Further diagnostic information can be acquired by color flow Doppler which can

demonstrate a prominent circular peritrophoblastic flow around the gestation sac (Figure

12-C).9,19,22 This finding can help determine location of the placenta in relation to the scar

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and proximity to the bladder.7 Another advantage of the Doppler flow studies is the

differentiation between a viable and a non-viable intrauterine pregnancy.7 The

significance of knowing the viability will influence the choice of treatment. In a non-

viable intrauterine gestation, the gestational sac appears avascular which indicates that it

has detached from the implantation site. A viable caesarean scar pregnancy, on the other

hand, appears well-perfused on Doppler studies.7 With Doppler studies, more information

on the flow pattern of the peritrophoblastic vasculature can be obtained. The flow

velocity around the gestational mass located in the scar is of low impedance (pulsatility

index <1) and of high velocity (peak velocity .20 cm/s).7 Others 28 have reported a

resistance index (RI) of the blood flow as being <0.5 and a peak value ratio of systolic-to-

diastolic (S/D) blood flow as being <3.

Three-Dimensional Ultrasound

Others authors40, 41 have used the new 3-dimensional (3D) ultrasound and 3D

Power Doppler. According to their experience, using the combination of the multiplanar

views and 3D-rendered images permits more accurate diagnosis in the same situation.

Chou et al.29 have described a more sophisticated new 3-D colour Doppler imaging

technique to monitor the quantification of changes of uterine neovascularisation

characteristics before and after successful treatment of CSP. This was termed 3-D-virtual

organ computer-aided analysis (VOCAL) (Figure 13). They claim that this is a superior

technique to display the caesarean scar pregnancy sac volume as well as to reveal a more

detailed spatial vascular architecture pattern than the conventional color Doppler image.

Magnetic Resonance Imaging (MRI)

MRI is excellent in assessment of the pelvic structures because of improved

differentiation of soft tissue, spatial resolution and the possibility of a multiplanar

imaging.39 Some authors 19, 25, 28, 39, 42, 43 have used magnetic resonance imaging (MRI)

alongside with vaginal sonography as an additional diagnostic modality (Figure 14). The

sagittal and transverse T1- and T2-weighted MRI sequences can distinctly show the

gestational sac embedded in the anterior lower uterus. But the transverse sequence is

clearly seen only when the sac is embedded in the outer surface of the cervical canal.28 It

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can also measure the volume of the lesion and therefore help assess the success of

treatment with local methotrexate.39 Some limitationsof MRI include its long acquisition

time, cost and availability. Several authors 25, 28, 44 do not recommend this because they

found that sonography combined with Doppler flow imaging are very reliable tools for

diagnosing such cases. MRI then may be reserved for cases where transvaginal

ultrasound and color flow Doppler findings are inconclusive.

Diagnostic Hysteroscopy And Laparoscopy

Hysteroscopy allows distension of the cervix and the uterine cavity with relatively

little trauma. It also allows direct visualization of a normal and empty uterine cavity and

the placental tissues as well.45 Laparoscopy has also been used for diagnosis of CSP.45-47

The uterus is usually small or large depending on the gestation age. The pathology is

seen as a mound with a ‘salmon red’ ecchymotic appearance, distending the uterine

serosa from the previous caesarean section scar behind the bladder48 (Figure 15). Other

authors have used hysteroscopy and laparoscopy for simultaneously visualizing and/or

treating these pregnancies.20, 49

Histology

Specimen sent for histopathologic diagnosis showed interstitial trophoblasts

within the fibromuscular tissue of the old caesarean section scar.39, 40, 50 The placental

attachment in the lower segment may lack both decidua basalis and the myometrium is

usually thinned-out merging with the fibrous scar of the previous caesarean section such

that it merely consist of connective tissue.13 These microscopic features combined with

the absence of surrounding endocervical glands confirms a caesarean scar pregnancy and

rules out a cervical pregnancy.40Immunostaining with beta human chorionic

gonadotrophin (bhCG) and desmin confirm the presence of trophoblast cells within

smooth myometrial muscle fibres (Figure 16).25

Differential diagnosis

The major differential diagnoses to consider are spontaneous abortion in progress,

cervical ectopic pregnancy, and gestational trophoblastic neoplasia.51 In spontaneous

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abortion in progress, the transvaginal ultrasound shows a gestational sac in the cervical

canal and on colour flow Doppler, the sac appears avascular. This indicates that the sac

has been detached from its implantation site. The caesarean scar pregnancy, in contrast, is

well-perfused in its site.52 There is also a decreasing serum b-hCG level noted. In a

cervical ectopic pregnancy, there would be a layer of healthy myometrium visible

between the bladder and the gestation sac.14 The symptom of vaginal bleeding in cervical

pregnancy is more profuse than that of the caesarean scar pregnancy. To further establish

the diagnosis of cervical pregnancy, a transabdominal ultrasound should be performed

with a well-distended bladder. It should show an empty uterus with an endometrial stripe

with the gestation sac present dominantly within the cervix. It gives an hour-glass shape

to the uterus with a distended cervical canal.40 A caesarean scar pregnancy can sometimes

be misdiagnosed as a trophoblastic tumor if the ultrasound scan indicates no evidence of

pregnancy within the uterus but reveals a highly vascularised mixed mass infiltrating the

myometrium and the presence of a high serum b-hCG level.28 Diagnosis of a CSP is

relatively easy early in pregnancy, but as the pregnancy progresses, the distinction

between CSP, cervical pregnancy and a lowly implanted intrauterine pregnancy becomes

more difficult.6

Treatment

Due to the few individual cases reported in the literature, there was no agreement

on which is the most effective mode of treatment which will lead to the least or no

complications. A large variety of treatment approaches and their different combinations

reported in relatively small case series left the community of obstetricians and

gynecologists relatively unsure as to the best approach for treatment. Based on the

review of literature by Timor-Tritsch, et al.,10 they realized that gynecologic surgeons

tended to do curettage, laparoscopy, and hysteroscopy as their preferred first-line

approach. Some obstetricians on the other hand, preferred injecting the chorionic sac and

relied on the help of interventional radiology. Our index cases, on the other hand, were

all managed by abdominal hysterectomy to remove the pathology. Mostly, termination of

pregnancy in the first trimester is strongly recommended, as there is a high risk of

subsequent uterine rupture, massive bleeding and life-threatening complications. This is

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because at this gestation, the embryo is softer and fragile with less vascular placental bed,

with the depth of placental implantation and risk of invasion of the bladder are considered

less than those later in pregnancy. The objectives of the treatment should be to terminate

pregnancy prior to rupture, to remove the gestation sac and to retain patient’s future

fertility as much as possible. Gestational age and viability, evidence of myometrial

deficiency and clinical presentation should also be considered in determining the mode of

treatment.

Medical Management with Methotrexate

Methotrexate (MTX) has been used as the standard medical treatment for ectopic

pregnancies thus it can also be used in caesarean scar pregnancies. This has been the

recommended as appropriate for hemodynamically stable woman without any symptoms

of abdominal pain which is suggestive of an unruptured state. Another eligible criteria

used by some authors are the following: Beta-hCG of <5000mIU/mL, <8 weeks age of

gestation, myometrial thickness of <2mm between the caesarean scar pregnancy and

bladder. 25, 53

It has been shown that it has the same response as with the dosage used in ectopic

pregnancies which is 50 mg/m2. Surgery should also be advised to the patient if the

medical maanagment fails. This regimen needs multiple doses because of its short half

life. For these reason, some authors54 prefer direct intrasac injection of methotrexate into

the sac to achieve a high concentration locally and thus discontinues the pregnancy more

rapidly.

Ultrasound-Guided Local Injection

The use of intrasac injection with methotrexate, potassium chloride, hyperosmolar

glucose and crystalline trichosantin has also been reported with success.54 It can be done

by transabdominal or via transvaginal route. Transabdominal route requires a longer

needle, used with caution not to penetrate the bladder wall, and does not require any

anaesthesia. The transvaginal approach allows for a shorter distance to the gestation sac

with minimal risk of bladder injury. But the procedure may require general anaesthesia.

There was no agreement on the use of prophylactic antibiotics during the procedure.

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Combined medical treatment

Combined medical treatment in various regimens has been described by many

authors. Examples are the following: local injection of 8 mEq potassium chloride (2

mEq/ml) followed by 60mg of MTX injected into the gestation sac54, direct injection of 3

ml of 50% glucose plus oral MTX (2.5mg three times a day for 5 days)48, multi-dose

systemic MTX (1mg/kg) with alternate day folinic acid rescue50 failed systemicMTX

followed by successful local MTX.

Medical Treatment Combined With Surgical Sac Aspiration

Medical management has been combined with surgical aspiration of the sac in

some cases. These are the sequences of combination that have been described in the

literature: local potassium chloride/TVS-guided sac aspiration/local MTX injection

/intramuscular MTX injection, systemic MTX / TVS-guided sac aspiration, sac aspiration

(transvaginal or transabdominal) / local MTX injection, sac aspiration under ultrasound

guidance / systemic MTX, systemic MTX/sac aspiration by vaginal route/local MTX.10

In some cases, a salvage treatment, e.g. hysteroscopic or laparoscopic resection of the CS

pregnancy under direct vision, has been indicated. This mode of treatment avoids

unnecessary laparotomy and preserve the woman’s fertility, but it requires time and

patience. It may take 4 to16 weeks for B-hCG to drop to normal.46 Therefore, it is

essential to have a close follow up with serial B-hCG monitoring. The recommended

schedule of monitoring B-hCG is to do daily monitoring during the hospital stay and

weekly thereafter until a level of <5 mIU/mL. This should also be accompanied by a

repeat transvaginal ultrasound. It is hard to predict when the CS mass completely resolves

after a conservative treatment.46, it has been found to take several months to a year. A

possible explanation is that the scarce venous flow within the fibrous scar tissue making

resorption difficult. Another explanation may be related to the proliferation of collagen

fibers or fibrous tissue in the isthmic portion of the uterus in response to myometrial

injury induced by placental villi invasion.9

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Uterine curettage

A review of the literature by Arslan et al.55 shows that uterine curettage was either

unsuccessful or caused complications in eight out of nine women, requiring surgical

treatment, and in a case series of eight, Wang et al.47 had four secondary referrals after

failed curettage, thus indicating a failure rate of 70% (12/17). The gestation sac of a CSP

is not actually within the uterine cavity, and the chorionic villi implant into the caesarean

section scar of the lower segment. Therefore, not only the trophoblastic tissue is

unreachable by the curette but also such attempts can potentially rupture the uterine scar

leading to severe haemorrhage and cause more harm. An immediate laparotomy or

laparoscopy may be prompted if profuse bleeding happened during the procedure with

the absence of chorionic villi in the specimen obtained by curettage. Blind uterine

curettage as a primary treatment for CS scar pregnancies is therefore unsatisfactory and

should be discouraged. In patients having completion curettage for abortion with known

previous caesarean section, bleeding after an uncomplicqted procedure should raise the

suspicion for CSP. Various haemostatic measures have been used successfully as an

adjunct to conservative treatment of viable CSPs for the prevention and control of

profuse bleeding, examples are local injection of vasopressin, intrauterine balloon

tamponade by Foley catheter (30–90 ml of balloon capacity for 12–24 hours), Shirodkar

suture, prior selective bilateral uterine artery embolization and bilateral uterine artery

liagtion.10

Hysteroscopic Evacuation

In 2005, Wang et al.47 reported the first successful treatment of CSP by operative

hysteroscopy and suction curettage. At 4-week follow up, serum b-hCG level became

normal, with restoration of normal echotexture of the uterus on ultrasound scan. Clinical

follow up at 3 months did not reveal any complication. The authors have since reported

hysteroscopic management of six more cases with success in all of them, with no

complication and no blood transfusion.46 They concluded that this procedure offers an

important alterative treatment for CSP, with a short operative time (mean 36.7 ± 20.8

minutes), less blood loss (mean 50.0 ± 0.0 ml), short postoperative stay (mean 1.1 ± 0.9

days) and a rapid return of the pregnancy test to negative (<4 weeks, mean 22 days).

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Most importantly, the fertility is conserved after the surgery. Chao et al.56 have described

a successful hysteroscopic management of a CSP after failed curettage and MTX

treatment. The success rate of this modality (8/8 = 100%) is promising but the total

number of cases managed is small, and it is too early to know whether operative

hysteroscopy can be performed in presence of heavy bleeding or with unstable vital signs.

Laparoscopic removal

A laparoscopic approach is usually done when the CSP growa towards the

abdominal cavity and bladder while hysteroscopic approach is chosen when the CSP

grows inwards the uterine cavity. The first reported successful laparoscopic resection of

CS scar pregnanacies have been reported by Lee et al.49 Laparoscopic findings must

support the features of a CSP. The CSP mass is incised and the pregnancy tissue removed

in an endobag. Bleeding can be minimized by local injection of vasopressin, bipolar

cauterization, and the uterine defect suturing. Laparoscopy is safe and less time

consuming with mean of 113.8 ± 32.0 minutes, and range of 75–120 minutes,47 blood loss

is limited (mean 200.0 ± 108.0 ml, range 50–200 ml). Another advantage is a faster

recovery resulting to minimal hospital stay (mean 3.0 ± 0.0 days).46 However, this mode

of treatment is only suitable if the woman is stable and appropriate facilities are available.

Some cases are eventually converted to laparotomy due to difficulty in achieving

haemostasis or uncontrolled bleeding.

Primary Open Surgical Treatment

Laparotomy is done when uterine rupture is suspected. Some authors consider this

as the best mode of treatment2,22 because the excision of the old scar not only avoids

leaving residual trophoblasts in situ but also removes the microtubular tracts and thus

reduces the risk of recurrence. 40 However, this creates a larger surgical wound, longer

hospital stay and longer recovery time, with a possible higher risk of a future placenta

praevia accreta.2 Hysterectomy was done in cases where the patient had completed family

size and had no plans of future pregnancies. In a review done until August 2002,

hysterectomy was performed in 7 out of 19 cases.2 From then, six more hysterectomies

have been reported in the literature either as a primary procedure or because other

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treatment modalities failed. This shows that CSP is a potentially serious condition despite

advances in many of the diagnostic techniques and therapeutic measures.

Expectant Treatment

This option may be considered in woman who do not wish to terminaqte the

pregnancy and has sonographic evidence of the gestational sac growing towards the

uterine cavity. 22However, It must be emphasized, that the minimum thickness of the

myometrium anterior to the scar pregnancy sac to warrant safety of a continuing

pregnancy is unknown. Some authors question the prudence and safety of continuing a

CSP.25,47 If expectant treatment is proposed, a detailed care plan must be documented with

the risks and benefits of pregnancy. Appropriate counselling and clear explanation of the

serious consequences of continuation of pregnancy must be clearly explained to the

patient. An elective delivery by caesarean section around 28–30 weeks with antenatal

corticosteroid administered 24–48 hours before delivery would appear to be a reasonable

arrangement. Even as an elective procedure, massive haemorrhage may occur at

caesarean delivery, with the risk of hysterectomy. In women having expectant treatment,

emergency operative delivery must be instituted without delay in the event of any

features indicating uterine rupture. Expectant treatment failed in two of the three women

in a series of 18 cases reported by Jurkovic et al.,7 one woman requiring MTX and the

other an emergency hysterectomy. These results indicate that expectant treatment of

viable CSPs either fails or carries a significant risk of rupture requiring laparotomy and

hysterectomy.

SUMMARY

Four cases of caesarean scar pregnancies diagnosed by transvaginal sonography

have been managed by total hysterectomy. A missed diagnosis, lack of evidence-based

treatment modality and serious complications of having a caesarean scar pregnancy are

one of the reasons for the difficulty in managing such cases. The cases are often

misdiagnosed as low intrauterine pregnancy, cervical pregnancy or an abortion in

progress. The transvaginal ultrasound is considered the best diagnostic tool for this kind

of ectopic pregnancy. And an early recognition will lead to better outcome if the

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intervention is also done early. It is clear from the review of the literature that there is no

consensus regarding the modalities of treatment of caesarean scar pregnancies. But due to

the increasing trends of caesarean scar pregnancies reported, it may be the time to

standardize the treatment approach to these cases. Early recognition of these cases should

start with patient education such that before discharge of patients who had a caesarean

section, they should be advised of the importance of early visit to obstetricians for

transvaginal ultrasound.

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APPENDIX

Figure1. Sites of implantation of 1800 ectopic pregnancies from a 10-year population based study (Data from Callen, 2000, Bouyer and colleagues, 2003).1

Figure 2. Transvaginal scan of index patient case #1 showing: A. Antero-posterior view of the uterus. Within the endometrial cavity at the lower uterine segment is a heterogenous mass 6x7x6 cm with cystic spaces within which seems to extend to almost full thickness of the anterior myometrium at the area of previous caesarean section scar. B. Color flow mapping showed moderate peripheral vascularity with intermediate resistance indices (PI = 0.81, RI=O.56)

A

B

B

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Figure3. Gross specimen of the uterus of index patient case#1 showing: A. The lower

uterine segment was enlarged measuring 14 x 7.5 x 5 cm. B. Cut section of the posterior

portion of the uterus, showing gestational sac-like tissue attached anteriorly measuring

2x2 cm with placental-like tissues.

A

B

Fundus

A

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Figure 4. Transvaginal ultrasound picture of index patient case #3 showing: A. Antero-

posterior view of the uterus with a heterogenous mass occupying the anterior lower

uterine segment measuring 4.0 x 3.5 x 2.6 cm with an anechoic cyst structure within the

gestational sac. B. The anechoic cystic structure is surrounded by dilated vessels with

involvement of the full thickness of the myometrium.

A

B

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\

Figure 5. On diagnostic cystourethroscopy of index patient case #3: A. The urethrovesical

junction was intact. B. The trigone was smooth and pale. C and D. Right and left ureteral

orifice are patent with good efflux of urine.

A B

C D

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Figure 6. Intraoperative pictures of index patient case #3 showing: A. the lower uterine

segment up to the isthmic area of the uterus was densely adherent to the posterior bladder

wall. B. On adhesiolysis, the lower uterine segment was thinned out on the central

portion with an inadvertent tearing of the serosa during manipulation showing a 3.5 x 2 x

1 cm cystic, unilocular mass, attached to the surrounding myometrium. C. The mass,

which seems to be the gestational sac, contained clear serous fluid within.

A B

C

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Figure 7. Transvaginal scan of index patient case #4 showing: A. A single gestational sac

within the anterior isthmic area measuring 3.6x1.8x2.1cm, with mean sac diameter of 2.5

equivalent to 7 weeks and 4 days age of gestation. Within the gestational sac is a single

live embryo with a crown-rump length of 1.8cm equivalent to 8 weeks and 1 day age of

gestation. The yolk sac is 0.5 cm. B. The CS scar is widened measuring 2.6cm and is

occupied by the growing gestational sac.

A

B

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Figure 8. Number of early placenta accreta and cesarean scar pregnancy articles based on

their year of publication.10

Figure 9. Sonographic image of a niche (arrow) at the site of the caesarean scar: A. one

previous caesarean delivery and B. Two previous caesarean deliveries.10

Figure 10. Transvaginal sonographic criteria for diagnosing caesarean scar pregnancy

showing: A. Empty uterine cavity with gestational sac (arrow) between cavity and cervix

(Cx), B. Gestational sac embedded in scar with lack of myometrium (arrow) between the

sac and bladder.

A B

A B

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Figure 11. Ultrasound image of a sagittal section of uterus showing protrusion of the

gestation sac with fetus anteriorly through the scar, with empty uterine cavity at fundus.39

Figure 12. A midline sagittal image showing: A. Triangular shape of sac assuming shape

of niche. B. Prominent, richly vascular area in site of previous cesarean scar highlighted

by power Doppler in patient presenting with bleeding and positive pregnancy test.

Arrows point to vascular malformation.10 C. Prominent peritrophoblastic flow

demonstrated around the gestational mass.

A B

C

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Figure 13. 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.

Figure 14. Magnetic resonance image shows implantation of a gestational sac in a

caesarean section scar. 42 (Bl = bladder; Cx= cervix; Gs= gestation sac; Ut= uterus; V=

vagina)

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Figure 15. Under laparoscopy, an ‘ecchymotic’ lesion visible bulging from the uterine

wall at the previous caesarean scar area (arrow).20

Figure 16. Histology showing a cluster of trophoblast cells present in between

myometrial muscle bundles. 25

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a case series of caesarean section scar ectopic pregnancies

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