Case Report - III

CERVICAL PREGNANCY

Zulkarnain Tambunan
Adviser:
Dr. dr. Binarwan Halim, M.Ked (OG),
Sp.OG(K)

DEPARTMENT OF OBSTETRICS AND

GYNAECOLOGY
FACULTY OF MEDICINE
UNIVERSITAS SUMATERA UTARA/

HAJI ADAM MALIK GENERAL

HOSPITAL
MEDAN
2015
CHAPTER I
INTRODUCTION
Ectopic pregnancy, an important cause of maternal morbidity and
mortality, is estimated to occur in approximately 1-2% pregnancies worldwide.
Atypical ectopic pregnancies, such as those in the cervix, ovary, abdomen,
cesarean section scar and interstitial portion of the fallopian tube, are rare and
make up less than 10% of all ectopic pregnancies. 1
Cervical ectopic pregnancy is extremely rare and it was first described in
1817 and termed in 1860. It can be life threatening if not diagnosed and treated
early during the course of pregnancy as the endocervix is eroded by trophoblast
and the pregnancy proceeds to develop in the fibrous cervical wall. The higher
the trophoblast is implanted in the cervical cana, the greater is its capacity to
grow and cause bleeding. Its incidence accounts for less than 1% of all ectopic
pregnancies.2,3,4,24 Its etiology is still unclear. However, there are reports of
association with chromosomal abnormalities as well as prior history of
procedures that damage the endometrial lining such as cesarean section,
intrauterine device, and in vitro fertilization. 2
Increasing trend of cesarean sections and using other invasive methods
such as intrauterine device and in vitro fertilization seems to contribute to a
higher prevalence of cervical pregnancies nowadays.2 In spite of comparatively
high occurrence of ectopic pregnancy, early detection can be difficult. The
prevalence among pregnant patients presenting to an emergency department
(ED) in United States with first-trimester bleeding, pain or both, is 6-16%.5
The common presentation of cervical pregnancy is painless vaginal
bleeding after a period of amenorrhea, sometimes associated with cervical
enlargement and softening.6,7,8

There are two main treatment options for cervical pregnancy when fertility is
desired: surgical and pharmacological or conservative. In most reported cases
of cervical pregnancy, treatments from more than one category are used.
However, standard treatment protocol still has not been established yet 2,14
CHAPTER II
LITERATURE REVIEW
2.1. Definition
Cervical pregnancy is defined as a pregnancy that implants in the cervical
canal below the internal os and within the cervical mucosa. 6,16
2.2. Incidence
Nowadays, incidence of cervical pregnancy represents less than 1% of all
ectopic pregnancies, with a reported incidence varying from 1:1000 to 1:95000
pregnancies, with the highest figures reported from Japan, which also has a
high incidence of antecedent curettage. 15,17,19,20 Its etiology is still unknown, but
many risk factors have been suggested: presence of intraurine contraceptive
device, previous induced abortion, previous surgical termination of pregnancy,
endometrial ablation, Ashermans syndrome, uterine curettage, endometritis,
anatomic anomalies (eg: uterine fibroids, intrauterine synchiae), leiomyoma,
prior in utero exposure to diethylstilbesterol, previous Caesarean section, and in
vitro fertilization (IVF) treatment with embryo transfer may play a role.

6,7,8,15,18

Previous history of uterine curettage and pregnancies achieved through in vitro

fertilization constitute the major risk factors for cervical ectopic pregnancy.8 Few
studies evaluated the effect of cervical ectopic pregnancies in the reproductive
future. However, predisposing factors to cervical ectopic pregnancy are
themselves associated with other obstetric complications.15
2.3. Clinical Manifestation
The common presentation of cervical pregnancy is painless vaginal
bleeding after a period of amenorrhea, sometimes associated with cervical
enlargement and softening.6,7,8 Paalman and Mc Elin have described the most
accepted clinical definition of cervical pregnancy: (1) Uterine bleeding after

amenorrhea, without cramping pain, (2) Disproportionally enlarged cervix, (3)

Products of conception entirely confined within the endocervix and (4) A snug
internal os and partially open external os.19
2.4. Diagnosis
Diagnosis and treatment of cervical ectopic pregnancy has changed
dramatically in the last two decades. Before 1980, the diagnosis commonly was
made at the time of spontaneous abortion or reach the second trimester or
when dilatation and curettage for presumed incomplete abortion, which were
associated with life-threatening hemorrhage frequently requiring hysterectomy.
Nowadays, cervical ectopic pregnancy is commonly diagnosed on a first
trimester ultrasound examination.16,17,26
It is important to distinguish among cervical pregnancy, cervical abortion
and uterine scar pregnancy.3 Studies have found that the historical features,
physical examination, and laboratory parameters are of limited values in
identifying patients with minimal symptomatology who are at risk for an ectopic
pregnancy. However, -hCG was found to be an essential tool in evaluating
potential ectopic pregnancy in these patients.5
Since most pregnant patients will have a -hCG <1500 at some point in
their pregnancy, the researchers quantified the increased risk of ectopic
pregnancy in patients with -hCG <1500 mIU/ml by comparing -hCG
distribution of symptomatic women with ectopic pregnancy, abnormal
intrauterine pregnancy, and normal intrauterine pregnancy. A below- threshold
-hCG levels <1500mIU/ml doubled the pretest odds of ectopic pregnancy and
was extremely useful at separating all abnormal pregnancies from normal
intrauterine pregnancies. A protocol of quantitative hCG levels <1500 mIU/ml,
combined with transvaginal ultrasound, has been proposed in diagnosing
ectopic pregnancy with 100% sensitivity and 99.9% specificity.5
The combined approach incorporating Transvaginal ultrasonography
(TVUSG) and Doppler ultrasonography is the gold standard for diagnosis, and
MRI can be performed to confirm the location of pregnancy.6,22 Usually,
speculum examination may reveal an open external cervical os with a fleshy
mass protruding (Fig 2.1).7,16

Figure 2.1. Speculum appearance of cervical pregnancy presenting as a

mass at the external cervical os16
Ultrasonographic diagnosis of this abnormal pregnancy was first described
by Raskin (1978). Since then technical improvements in ultrasound have been
crucial to an early diagnosis in either weakly or non-symptomatic women in the
first trimester, thus allowing conservative management. 15
The ultrasound diagnosis of a cervical pregnancy requires visualization of
an intracervical ectopic gestational sac or trophobastic mass below a closed
internal os. If internal os cannot be visualized, the sac should be below the
uterine artery insertion or vesico-uterine fold. Recognizing its sonographic
appearance is the first step for a correct management, because it may be
mistaken for an intrauterine pregnancy, an incomplete abortion or even a
endocervical cyst.15
Raskin suggested that the diagnosis by ultrasound examination of cervical
pregnancy required 4 criteria: enlargement of the cervix, uterine enlargement,
diffuse amorphous intrauterine echoes, and absence of an intrauterine
pregnancy. Timor-Tritsch et al refined the criteria insisting the placenta and

entire chorionic sac containing the pregnancy be below the internal cervical os
and the cervical canal must be dilated and barrel shaped. It may be necessary
to exclude the diagnosis of a spontaneous abortion in progress by noting the
presence of embryonic cardiac activity and/or doppler ultrasound indicating
vascular attachment to confirm a living pregnancy.16,29 With transvaginal
ultrasound, especially with 3 dimensional rendering, these implantations are
easily identified (Fig 2.2) and can, thus, be treated with conservative fertilitysparing options. Traditionally, when 2 dimensional ultrasound had been
nondiagnostic, magnetic resonance imaging was required to establish the true
diagnosis of a cervical implantation. However, the rendered coronal plane view,
established with 3 dimensional ultrasound volume acquisition, clearly delineates
the relationship of the uterus, cervical canal, and the pregnancy. The closed
internal cervical os and the pregnancy within the cervical canal can be easily
visualized.16

Figure 2.2. Three dimension ultrasound images of a cervical pregnancy at

12 weeks gestation

Below the internal os, the gestational sac usually is situated completely
within the cervix, below the uterine corpus level. A classic sign on ultrasound is
a hyperechogenic trophoblastic ring surrounding the implantation site. Thus,
gestation sacs specific location in the cervix, trophoblastic invasion of the
cervix, and the identification of the uterine corpus and endometrium are
essential in diagnosing cervical pregnancy (Fig 2.3- 2.8).9

Figure 2.3. Ultrasonography of a cervical twin pregnancy; sagittal view of the

uterus showing thick endometrium and two gestational sacs in the cervix below
the internal os.9

Figure 2.4. Ultrasonography of a cervical twin pregnancy.9

Figure 2.5. Ultrasonography of a cervical twin pregnancy; demonstrating a yolk

sac in the larger gestational sac.9

Figure 2.6. Ultrasonographic diagnose of cervical twin pregnancy with the

second sac a blighted ovum.9

Figure 2.7. A gestational sac with small embryonic pole with a fetal
heartbeat of 122 bpm located in the cervix below the scar of the previous
cesarean section (vertical arrow). Cervix was closed, enlarged, and tender
(horizontal arrow). Estimated gestational age based on last menstrual period
was 6 weeks and 6 days.2
Without ultrasonographic evidence of trophoblastic invasion of the cervix,
no diagnose can be confirmed. A gestational sac situated in the cervix could
merely be the cervical stage of abortion before dilatation of the external os. 9 To
further identify a cervical stage of abortion rather than a cervical pregnancy, the
sliding sign can be ascertained by ultrasound. If the gestational sac slides with
gentle pressure on the cervix with ultrasound probe, a cervical abortion is often
indicated.7,9
Occasionally, fetal implantation is situated at the isthmico cervical
junction. In these patients, it is difficult to differentiate between a cervical
pregnancy and a cervico isthmic pregnancy. In such cases, ultrasonography
should be used to identify intracervical placentation if an intact part of the
cervical canal exists between the gestational sac and the uterine endometrium. 9

Figure 2.8. Transabdominal ultrasound section of a 32-year- old woman

presented with mild pain abdomen and slight bleeding per vaginum for 5 days,
showing the typical hour- glass configuration of the uterus that measures
8.98cm with a ballooned- out cervical canal containing a gestational sac
measuring 4.7cmx 4.1cm3
Although the advent of sonography has made the diagnosis more
accurate, it is still a problem in developing countries. Clinically it is often
mistaken for inevitable or missed abortion. Sonologist may be mistaken as
incomplete or missed abortion in lower uterine cavity.17,29
Magnetic resonance imaging (MRI) was used to confirm the diagnose of
cervical pregnancy and to rule out uterine scar pregnancy. The findings on MRI
included a typical hour-glass configuration of the uterus with thickened
endometrium, a ballooned-out cervix containing the gestational sac with fetal
pole and closed internal os (Fig 2.9 - 2.10).3

Figure 2.9. T2- weighted sagittal section of the pelvis showing a gestational sac
with fetal pole in the cervix (arrow) and hour glass configuration of the uterus 3

Figure 2.10. Sagittal T2- weighted MR image shows a heterogenous highsignal intensity mass that occupies the cervical anterior wall.10

Color Doppler allows the placentas location, the extent of trophoblastic

invasion, and the flow of blood to be documented. 9 Doppler helps distinguish a
cervical pregnancy from a displaced intrauterine pregnancy.7
More recently, with the advent of sensitive diagnostic methods, the use of
conservative and fertility-sparing methods for the management of cervical
pregnancy has been described. Data regarding the use of hysteroscopy in
cervical pregnancy are limited, but there are case reports that describe this
method.23 Hysteroscopy is a rapidly advancing field of gynecologic practice that
enables direct visualization of the cervical canal and uterine cavity (Fig 2.11).
Moreover, it is most of the time a well-tolerated procedure, thus avoiding
general anaesthesia and decreasing the costs. 24

Figure 2.11. Transcervical hysteroscopic view of a cervical pregnancy.14

Figure 2.12. Cervical pregnancy within the right cervical canal using
hysteroscopy.23
Once the correct diagnosis is achieved, the treatment option must be
decided. An early diagnosis allows the adoption of conservative methods which
reduce potential morbidity and mortality associated with surgical interventions
and allows fertility preservation.15
2.5. Treatment
Because of the rarity of this condition, there has been no consensus on
the

preferred

treatment

for

cervical

pregnancy,

and

no

standard

recommendations have been available.16,21

There are two main treatment options for cervical pregnancy when
fertility is desired: surgical and pharmacological (conservative). 20 The basic
problem with the conservative approaches is the risk of life-threatening bleeding
episodes; therefore, various techniques has been used to control bleeding after
the procedure, such as placing a Foley catheter as a tampon into the cervical
canal, local prostaglandin injection into cervix, or placing hemostasis sutures to
cervix. However, these techniques may fail; in these circumstances bleeding
can be stopped via surgical ligation of cervical branches of uterine artery,

hysteroscopic endocervical resection during transient occlusion of iliac arteries

with balloon inflation, selective uterine artery embolization, or hysterectomy. 22,28
Cervical pregnancy management is dependent on the patients
gestational age, the stability of the patient, the patients interest in retaining
future fertility, and the resources and expertise of the practice treating the
patient. Regardless, the management must address the serious danger of
uncontrollable hemorrhage.2 Because of the relatively large gestational sac and
the highly vascular nature of the cervical tissue, treatment of cervical pregnancy
was often associated with massive hemorrhage. 23 Managing this danger
includes

several

options:

curettage

and

local

prostaglandin

injection,

hysteroscopic resection, angiographic uterine artery embolization (UAE), uterine

artery ligation and cervicotomy, intracervical injections of vasoconstrictive
agents, and Shirodkar- type cervical cerclage. 2
Early diagnosis is mandatory to avoid a more advancing gestation into
the second trimester, whose such cases may not be so simply evacuated and
may require hysterectomy with or without pelvic embolization. When treating all
cervical ectopic pregnancies, anticipation of significant bleeding and a
management plan to prevent and/or control hemorrhage can help avoid
hysterectomy. All patients should have blood products available and should
understand the potential need for hysterectomy.16
In 13 consecutive first trimester cervical pregnancies, from 1995-2014,
Fylstra demonstrates that a specialized suction curettage technique was 100%
successful in terminating 1st trimester cervical pregnancy. Curettage for the
treatment of cervical pregnancy has also been previously reported by other
authors. They suggested that 1st trimester cervical pregnancies, even
heterotopic cervical pregnancies, can be easily reached with curettage, can be
safely and successfully treated with suction curettage and postcurettage balloon
tamponade. The technique begins with circumferential infiltration of the cervical
stroma around the cervical pregnancy with a hemostatic vasoconstricting agent,
such as 20 mL of dilute vasopressin (20 units diluted within 50 mL of injectable
normal saline) to a depth reachable with a 1 1/2 inch, 21 gauge needle (Fig
2.13). This is followed by the placement of an untied cervical suture high around

the cervical portio, using a McDonald cerclage technique (Fig 2.14). This stitch
is left in place ready to tie, if necessary, to temporarily occlude the descending
cervical branches of the uterine arteries should bleeding occur during the
procedure. Then, without cervical canal dilation (the canal is already open
containing the pregnancy) an appropriately sized suction curettage (diameter in
millimeters equal to the gestational age in weeks), attached to suction, is
rotated and slowly passed through the cervical canal and into the endometrial
cavity (Fig 2.15). Immediately postcurettage a cervical canal balloon, such as a
30 mL balloon foley catheter, is placed against the cervical canal placental bed
and inflated to permit a tamponade effect within the cervical canal (Fig 2.16).
The balloon must be inflated within the cervical canal and not within the
endometrial cavity. The balloon tamponade is left in place for approximately 24
hours, then slowly deflated, in anticipation of no cervical bleeding. Should such
bleeding occur the balloon is reinflated for later removal. Pain control may be
needed because of balloon catheter postprocedure cervical canal distention,
however this has been unnecessary. A key point with this suction evacuation is
to not attempt cervical dilation before initiation of the passage of an
appropriately sized suction canula. The cervical canal is already dilated by the
cervical implantation, and further dilation can lead to immediate and profuse
cervical bleeding. Sharp curettage is to be avoided. During the treatment of
these 13 women, no procedure lasted more than 15 minutes, and no immediate
intraoperative nor delayed postoperative bleeding occurred. The cerclage
suture was never tied but remained in place until after the curettage, ready to be
tied should immediate intraoperative bleeding occur. The cerclage suture was
removed followed the curettage and placement of the balloon tamponade.
Despite not encountering intraoperative bleeding, the balloon tamponade was
used in all cases with the anticipation that as the effect of the hemostatic
cervical infiltration weaned, bleeding from the cervical placental bed would
occur.16

Figure 2.13 Infiltration of the cervical stroma with dilute vasopressin around the
cervical pregnancy

Figure 2.14 Placement of cerclage-type suture high on the cervical portio

Figure 2.15 Initiation of suction curettage without cervical dilation

Figure 2.16. Foley catheter balloon tamponade of the cervical implantation site
after curettage
Classically the treatment of cervical ectopic pregnancies includes
surgical intervention. Hysterectomy is considered the mainstay therapy. This
modality leads to loss of reproductive capability and is associated with
significant morbidity and potential mortality.8 Clinical indications for surgery are
abdominal pain that is severe and persistent beyond 12h, orthostatic
hypotension or decreasing hematocrit values. 11 Jacob, et al. reported an ectopic
cervical pregnancy which presented in such an atypical fashion (as a missed
abortion) that diagnosis was only made at surgical evacuation during which the
sudden

severe

hemorrhage

could

only be

controlled

by emergency

hysterectomy. Inspite of various advances, surgical interventions like total

abdominal hysterectomy may be required to arrest life-threating hemorrhage,
especially in women who do not desire future fertility.27 As an alternative to
hysterectomy, interventional radiology personnel experienced in arteriography
and embolization of the pelvic vessels may control hemorrhage, requiring that
the treatment of cervical pregnancy be done within a facility with such
expertise.16 More recently, attempts have been made to treat cervical ectopics in
a more conservative manner. Nonsurgical treatment usually consists of a
combination of medical and interventional measures.

Timor-Tritsch et al successfully terminated 5 living cervical pregnancies

with transvaginal ultrasound-guided local intrasac injections of methotrexate.
Jeng et al, likewise, terminated 38 cervical ectopic pregnancies with ultrasoundguided methotrexate injection, with a mean time to resolution of 49 days.
Uterine artery embolization alone, or followed by curettage, has terminated
cervical pregnancies without significant hemorrhage, preserving the uterus.
Parente et al reported 5 cases in 1983, 4 of which required hysterectomy, and

the fifth was successfully treated with curettage and vaginal packing. Vela and
Tulandi reported in 2007, 12 cases treated over 20 years, 4 of which required
hysterectomy for significant bleeding, independent of gestational age, and the
remaining 8 were treated with a variety of methotrexate, uterine artery
embolization, and curettage with ligation of the descending branches of the
uterine arteries. Monteagudo et al successfully terminated a heterotopic cervical
pregnancy with an intrasac injection of potassium chloride, leaving the
intrauterine pregnancy intact. A heterotopic ectopic cervical pregnancy has been
also successfully terminated with ultrasound-guided suction curettage,
leaving the intrauterine pregnancy undisturbed 16
In 1992, Roussis et al. described the first case in which hysteroscopy
was used to visualize a cervical pregnancy and guide removal by suction
curettage after sonography revealed incomplete resolution despite multiple
doses of systemic methotrexate. Four years later, Ash and Farrell published the
first case using operative hysteroscopy, without prior chemotherapy, to
completely resect a viable cervical pregnancy. Jozwiak et al. in their 2003 report
demonstrated a successful live birth in a subsequent pregnancy after
hysteroscopic removal of a cervical pregnancy. In this case, it is also
demonstrated that hysteroscopic resection is a potentially safe and effective
option for fertility-sparing management after failure of more traditional measures
such as IM methotrexate. Operative hysteroscopy allows direct visualization of
a cervical pregnancy, thereby enabling the surgeon to resect the ectopic
pregnancy and simultaneously ablate bleeding vessels if necessary. In 2006,
Matteo et al. also used hysteroscopy to successfully resect a cervical
pregnancy and in this case, after two cycles of methotrexate treatment, found
that hemostasis could be achieved via direct hysteroscopic coagulation of
bleeding vessels. In both cases, operative time was approximately 35 minutes,
there was minimal bleeding, and there was rapid resolution of the bhCG postresection. In 2004, Kung et al. performed laparoscopy-assisted uterine artery
ligation in conjunction with hysteroscopic endocervical resection of a cervical
ectopic pregnancy in 6 patients, eliminating the need for adjuvant chemotherapy
prior to hysteroscopy. Normal menstruation resumed in a mean period of 2

months, and 1 patient achieved spontaneous pregnancy 14 months

postoperatively.23

Figure 2.17. No residual tissues remain after surgical treatment using

hysteroscopic guidance.14

Figure 2.18. Empty uterine cavity after resection of cervical pregnancy using
hysteroscopic guidance.23

Generally, treatment choices for cervical pregnancy may be divided into

five categories:

1. Tamponade has been used mostly after other techniques (e.g.,

curettage). Cervical tamponade was performed with a Foley catheter,
placed gently past the external os, followed by inflation of the bulb
with 30 mL normal saline and it has proven to be more effective in
achieving haemostasis than packing.3,29
2. reduction of blood supply. This may be undertaken by cervical
cerclage, vaginal ligation of cervical arteries, uterine artery ligation,
internal iliac artery ligation and angiographic embolization of the
cervical, uterine atau internal iliac arteries. This is usually done in
preparation for surgical therapy like curettage, or along with
chemotherapy, as a conservative treatment modality aimed at
preserving future fertility. Embolization is primarily used as a rescue
therapy when profuse bleeding follows other conservative methods
like chemotherapy.3
Artery embolization by resorbable particles reduces arterial circulation
by occluding the vessels for 2- 6 weeks. This procedure has many
complications, including pelvic infection, pelvic pain, ischemia of
tissues, and complications from angiography. However, it is now the
method of choice when treatment with methotrexate is too late or
fails. Pelvic artery embolization reduces the risks inherent to the
surgical procedure, avoids massive bleeding during or after the
curettage, and reduces time of hospitalization. Ben Farhat et al
(2010) found that uterine artery embolization combined with
chemotherapeutic agents is effective in the treatment of cervical
pregnancy and has the advantage of preserving the womens
fertility.10 Angiographic arterial embolization may also result in the
radiation of the viable intrauterine pregnancy, and influence on
endometrial receptivity, which could decrease future fertility.21
Recently, there were reports on the use of arterial embolization before
or after dilatation and curettage for succesful treatment of cervical
pregnancy, although some authors suggest arterial embolization only
if significant bleeding occurs (Fig 2.19 - 2.20).25

Figure 2.19. Arteriogram of the left uterine artery before embolization showing a
hypertrophied and tortuous uterine artery. The vascularity is seen at the lower
uterine segment and cervix.10

Figure 2.20. Arteriogram of the left uterine artery after embolization. Only
collateral vascularization is seen.10
3. excision of trophoblastic tissue. Curettage and hysterectomy are the
classic methods for surgical excision of trophoblast tissue. Curettage
is the age-old fertility preserving method, but risks hemorrhage.

Therefore, it has been used in conjunction with mechanical methods

like cervical artery ligation and tamponade. Primary hysterectomy
may still be the preferred modality of treatment in intractable
hemorrhage, second trimester or third trimester diagnose of cervical
pregnancy and possibly to avoid emergency surgery and blood
transfusion in a woman not desirous of fertility. In a review, 100% of
cervical pregnancy beyond 12 weeks gestation ultimately required
hysterectomy.3
4. intra-amniotic feticide. Ultrasound- guided intra- amniotic instillation of
potassium chloride and/ or methotrexate has been used as
conservative approach for the management of cervical pregnancy.3
Verma and Goharkhay (2009) used 2mL (2mEq/mL) KCl solution
which was injected fetal intracardiac while guided by ultrasound. Fetal
intracardiac KCl injection combined with systemic methotrexate
administration is a viable option in the vast majority of patients. 8 Intraamniotic injection in combination with systemic methotrexate appears
to increase the chance of successful treatment.18
5. systemic chemotherapy. Unlike tubal ectopic pregnancy, cervical
pregnancy has no established criteria for methotrexate treatment. 6
The most commonly used agent is methotrexate, used in single dose
or multiple doses, with or without folinic acid.3
Methorexate is a folic acid antagonist. It works by inhibiting the
synthesis of purines and pyrimides and therefore interfering with DNA
synthesis. Methotrexate affects rapidly dividing cells and halts
mitosis. In ectopic gestations, it prevents the proliferation of the
cytotrophoblasts. This results in decreased trophoblast - hCG
production, which causes decreased secretion of progesterone by the
corpus luteum.11
This systemic chemotherapy with methotrexate is given in either
single dose regimens (50mg/m 2) or in multiple dose regimens
(1mg/kg on days 1,3 , 5 and 7) intramuscularly.6,9 If a patient is on a
multiple dose regimen, on days 2, 4, 6 and 8 folinic acid rescue
(leucovorin

0.1mg/kg)

should

methotrexates side effects.9,11

also

be

given

to

ameliorate

In the multidose protocol, up to four doses of methotrexate are given

until -hCG decreases 15% in 2 days consecutively. -hCG level
must be followed up per week until its level is less than 15 IU/L. A
second course of methotrexate may be given after 1 week if -hCG
levels increase or plateau.11
A single dose protocol was developed subsequently. It was noted in
prior studies that giving a single- dose of methotrexate might enhance
patient compliance without decreasing effectiveness. Therefore, the
protocol came to be known as the single- dose methotrexate protocol.
In this protocol, methotrexate is given at a dose of 50mg/m 2 on day 1.
A second dose is given on day 7 if -hCG values do not decrease by
at least 15% between days 4 and 7. -hCG levels are followed
weekly until they are undetectable (see table 2.1). 11
In a meta-analysis by Kung et al, methotrexate administration was
found to be 91% effective in the treatment of cervical ectopic
pregnancy. Hung et al also found the similar results in another metaanalysis.18
Table 2.1. Methotrexate protocols.11

The ectopic gestation may actually increase in size after methotrexate

treatment, which may be due to hematoma formation. Prior to giving
methotrexate, a complete blood count, liver function tests and creatinine
should be checked. In a patient with a history of pulmonary disease, a
chest x-ray should be obtained owing to the risk of interstisial
pneumonitis with methotrexate therapy.11
Absolute

contraindications

to

methotrexate

therapy

are

hemodynamically unstable patient, a patient who is breastfeeding, has

immunodeficiency, liver disease or alcoholisms, active pulmonary
disease, peptic ulcer disease and hematologic, renal or liver dysfunction.
Relative contraindications are an ectopic gestation 3.5cm in size or
greater and the presense of fetal heart activity.11
High-dose methotrexate has been associated with bone marrow
suppression, hepatotoxicity, stomatitis, pulmonary fibrosis, reversible
alopecia, photosensitivity and febrile morbidity. The most common side
effect is mild elevations of liver transaminases. Patients receiving
methotrexate should stop prenatal vitamins or folic acid supplements. 3,11
During treatment with methotrexate, -hCG levels may actually rise or
plateau between days 1 and 4 before they start to decrease. This is
thought to be due to the syncytiotrophoblasts that continue to produce hCG after methotrexate treatment. Another phenomenon seen during
treatment with methotrexate is transient abdominal pain, which can occur
3-7 days after the start of therapy and can last for 4-12 h. 11
Beyond the clinical signs of treatment failure, other signs indicating
possible methotrexate failure include an increase or plateaus -hCG,
which occurs after the first week of treatment.11
Given the lower success rate of the single- dose methotrexate protocol, a
two dose methotrexate protocol was developed in the hope of having a
more effective regimen that was not too burdensome. In this protocol, the
first dose of methotrexate is given on day 1 and a second dose is given

on day 4. A third dose is given on day 7 only if the -hCG level did not
decrease by 15% between day 4 and day 7.11
The success rate of methotrexate treatment in cervical pregnancy was
reported as high as 81.3%. Methotrexate combined with such methods
has a success rate of almost 90%.11
In most reported cases of cervical pregnancy, treatments from more than
one category are used.2 Treatment with methotrexate chemotherapy of patients
with either viable or nonviable cervical pregnancies at <12 weeks gestation
carries a high success rate (>91%) for preserving uterus.2,3
Generally, for clinically stable patients with a cervical pregnancy of less
than 9 weeks gestational age and without fetal cardiac activity, systemic
chemotherapy with methotrexate alone is the first line of treatment. 3,6,9
Gestational period more than 9 weeks with the presence of cardiac activity
demonstrated on ultrasound in a clinically stable patient may require addition of
intra- amniotic potassium chloride in addition to systemic methotrexate. 3
Transvaginal ultrasound-guided intra-amniotic injection of methotrexate can be
successfully used for cervical pregnancy treatment, but the risk of systemic
adverse effects, such as thrombocytopenia, leukopenia, elevated serum liver
enzymes, and especially the teratogenic effect, should be taken into
consideration.21 Second or third trimester diagnose may warrant hysterectomy.
In a hemorrhaging patient, the treatment options are tamponade with Foley
balloon, large vessel ligation or angiographic embolization with hysterectomy
reserved for intractable bleeding.3
If the methotrexate is unsuccessful, then UAE minimizes the risk of
hemorrhage of cervical pregnancy. Curretage was then performed to ensure the
eradiation of the pregnancy.9 UAE in conjuction with other methods, such as
dilation and curettage, has been widely used as a highly effective technique for
treating cervical pregnancy. Combination of the two methods is necessary
because if the cervical pregnancy is not evacuated soon after UAE, some
gestational tissue may remain and result in bleeding. Numerous studies on UAE
in treating obstetric hemorrhage and fibroids have demonstrated its safety and

efficacy. It is associated with low morbidity rates and complication rates are
similar to or less than those associated with surgery. Complications associated
with UAE, however, such as pelvic infection and premature ovarian failure, have
also been reported.24 For patients who are no longer interested in fertility, a
hysterectomy is an option if they are diagnosed with an actively bleeding
cervical pregnancy.9
Based on Sijanovic et al (2013), in cases of cervical pregnancies that do
not respond well to methotrexate treatment, the first aids are area cervical
evacuation/ dilatation and curettage, with or without balloon tamponade. Case
report by Sijanovic et al (2013) showed that viable ectopic pregnancy could
successfully be resolved with combination of local conservative methotrexate
therapy and local surgical therapy- primarily hysteroscopic resection of products
of conception, even in cases when conservative therapy fails. 12

Figure 2.11. Algorithm of Cervical Ectopic Pregnancy.13

The conception rate after the successful treatment of cervical pregnancy
has generally been low and the patient should be counseled about the risk of

future ectopic pregnancies, second trimester pregnancy losses, and the

potential need of subsequent prophylactic cervical cerclage. 19

CHAPTER III
CONCLUSION
Cervical ectopic pregnancy is extremely rare that can be life threatening
if not diagnosed and treated early during the course of pregnancy. Its incidence
accounts for less than 1% of all ectopic pregnancies. Increasing trend of
cesarean sections and using other invasive methods such as intrauterine device
and in vitro fertilization seems to contribute to a higher prevalence of cervical
pregnancies nowadays. Diagnosis is usually made by ultrasound, MRI and
hysteroscopy can be performed to confirm the location of pregnancy. Usually,
speculum examination may reveal an open external cervical os with a fleshy
mass protruding.
Classically the treatment of cervical ectopic pregnancies includes
surgical intervention. Clinical indications for surgery are abdominal pain that is
severe and persistent beyond 12h, orthostatic hypotension or decreasing
hematocrit values. More recently, attempts have been made to treat cervical
ectopics in a more conservative manner.
In most reported cases of cervical pregnancy, treatments from more than
one category are used. Generally, for clinically stable patients with a cervical

pregnancy of less than 9 weeks gestational age and without fetal cardiac
activity, systemic chemotherapy with methotrexate alone is the first line of
treatment. Gestational period more than 9 weeks with the presence of cardiac
activity demonstrated on ultrasound in a clinically stable patient may require
addition

of intra-amniotic

potassium chloride

in

addition

to

systemic

methotrexate. Second or third trimester diagnose may warrant hysterectomy. In

a hemorrhaging patient, the treatment options are tamponade with Foley
balloon, large vessel ligation or angiographic embolization with hysterectomy
reserved for intractable bleeding. If the methotrexate is unsuccessful, then UAE
minimizes the risk of hemorrhage of cervical pregnancy. Curretage was then
performed to ensure the eradiation of the pregnancy. For patients who are no
longer interested in fertility, a hysterectomy is an option if they are diagnosed
with an actively bleeding cervical pregnancy.
REFERENCES
1. Orazulike, N.C., Konje, J.C. 2013. Diagnose and Management of Ectopic
Pregnancy. Womens Health 9 (4): 373-85.
2. Mohebbi, M. R., Rosenkrans, K. A., Luebbert, E. E., Hunt, T. T., Jung, M.
J. 2011. Ectopic Pregnancy in the Cervix: A Case Report. Hindawi
Publishing Corporation Volume 2011, Article ID 858241, 2 pages. doi:
10.1155/2011/858241.
3. Singh, S. 2013. Diagnose and Management of Cervical Ectopic
Pregnancy. J Hum Reprod Sci

6 (4): 273-6. Available

from:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963313/#ref6. [Accessed
on 1th June 2015].
4. Tehrani, H.G., Movahedi, M., Hashemi, L., Ghasemi, M. 2015. Cervical
Ectopic Pregnancy. Clinical Medicine Journal Vol 1 No 2, pp. 60-2.
5. Downey, L.V.A., Zun, L.S. 2011. Indicators of Potential for Rupture for
Ectopics Seen in the Emergency Department. Journal of Emergencies,
Trauma, and Shock I 4: 3 I Jul- Sep. DOI:10.4103/0974-2700.83867.
6. Weibel, H.S., Alserri, A., Reinhold, C., Tulandi, T. 2012. Multidose
Methotrexate Treatment of Cervical Pregnancy. J Obstet Gynaecol Can
34(4): 359- 62.

7. Institute of Obstetricians and Gynaecologists, Royal College of

Physicians of Ireland and Directorate of Clinical Strategy and
Programmes, Health Service Executive. 2014. Clinical Practice Guideline
The Diagnose and Management of Ectopic Pregnancy. Guideline no33.
8. Verma, U., Goharkhay, N. Conservative Management of Cervical Ectopic
Pregnancy. 2009. Fertil Steril 91: 671-4.
9. Rizk, B., Holliday, C. P., Owens, S., Abuzeid, M. 2013. Cervical and
Cesarean Scar Ectopic Pregnancies: Diagnose and Management. Middle
East Fertility Society Journal 18: 67-73.
10. Ben Farhat, L., Ben Salah, Y., Askri, A., Dali, N., Hendaoui, L. 2010.
Conservative Treatment of A Cervical Twin Pregnancy with Uterine Artery
Embolization. Diagn Interv Radiol 16: 248-50.
11. Kulp, J.L., Barnhart, K.T. 2008. Ectopic Pregnancy: Diagnose and
Management. Womens Health 4 (1): 79- 87.
12. Sijanovic, S., Vidosavljevic, D., Topolovec, Z., Milostic-Srb, A., Mrcela, M.
2014. Management of Cervical Ectopic Pregnancy after Unsuccessful
Methotrexate Treatment. Iran J Reprod Med Vol12. No 4. pp 285-8.
13. Hrestiana, D., Cheng, A.B., Panebianco, N. L., Dean, A. J. 2014. Case
Report: Pitfalls in Cervical Ectopic Pregnancy Diagnose by Emergency
Physicians using Bedside Ultrasonography. American Journal of
Emergency Medicine 32: 397.e1- 397.e3.
14. Kim, J.S., Nam, K.H., Kim, T.H., Lee, H.H. and Lee, K.H. 2008.
Hysteroscopic Management of Cervical Pregnancy with Intrauterine
Irrigation with H2O2. The Journal of Minimally Invasive Gynecology,
15(5): 627-30.
15. Correia, L., Simoes, M., Luz, R., Silva, A. and Barros, C. 2014. Cervical
ectopic pregnancy: Ultrasound diagnosis and conservative management.
Acta Obstet Ginecol Port, 8(1): 84-7.
16. Fylstra, D.L. 2014. Cervical pregnancy: 13 cases treated with suction
curettage and balloon tamponade. Am J Obstet Gynecol, 210:581.e1-5.
17. Saha, E. and Paul, A.K. 2011. Cervical ectopic pregnancy mimicking
missed abortion. Bang Med J (Khulna), 44: 28-30.
18. Palshetkar, N., Pai, H. and Bansal, B. 2009. Cervical Ectopic Pregnancy.
South Asian Federation of Obstetrics and Gynecology, 1(1):40-1.

19. Pandher, D.K. and Shehgal, A. 2009. D Diagnosis and management of

cervical ectopic pregnancy report of three cases. Nepal Med Coll, 11(1):
64-5.
20. Yitzhak, M., Orvieto, R., Nitke, S., Neuman-Levin, M., Ben-Rafael, Z. and
Schoenfeld, A. 1999. Cervical pregnancy a conservative stepwise
approach. Human Reproduction, 14(3):847-9.
21. Kim, J.W., Park, H.M., Lee, W.S. and Yoon, T.K. 2012. What is the best
treatment of heterotopic cervical pregnancies for a successful pregnancy
outcome?. Clin Exp Reprod Med, 39(4):187-92.
22. Genc, M., Genc, B., Kurt, S. and Solak, A. 2014. A Case of Cervical
Ectopic Pregnancy: Management and Review of the Literature. American
Journal of Medical Case Reports, 1(1): 9-15.
23. Kofinas, J.D., Purisch, S.E., Brandt, J.S. and Montes, M. 2012.
Hysteroscopic Removal of Cervical Ectopic Pregnancy Following Failed
Intramuscular/Intra-Sac Methotrexate: A Case Report. Journal Of
Gynecologic Surgery, 28(5): 369-71.
24. Scutiero, G., Nappi, L., Matteo, M., Balzano, S., Macarini, L. and Greco
P. 2013. Cervical pregnancy treated by uterine artery embolisation
combined with office hysteroscopy. European Journal of Obstetrics &
Gynecology and Reproductive Biology, 166:104-6.
25. Sejekan, P., Vaclavinkova, V., Leven, H., and Krolikowski, A. 2000.
Unilateral uterine artery embolization and systemic methotrexate therapy
in cervical pregnancy. Medical Sciences, 2: 557.
26. Ferrara, L., Belogolovkin, V., Gandhi, M., Litton, C., Jacobs, A.,
Saltzman, D. and Rebarber, A. 2007. Successful Management of a
Consecutive

Cervical

Pregnancy

by

Sonographically

Guided

Transvaginal Local Injection. J Ultrasound Med, 26:959-65.

27. Gupta, V., Acharya, R., Bansal, N., Nanda, A., Tandon, A. and Rani, A.
2010. Cervical ectopic pregnancy: Case reports and management
modalities. South Asian Federation of Obstetrics and Gynecology,
2(1):77-9.
28. Hirakawa, M., Tajima, T., Yoshimitsu, K., Irie, H., Ishigami, K., Yahata, H.,
Wake, N. and Honda, H. 2009. Uterine Artery Embolization Along With
the Administration of Methotrexate for Cervical Ectopic Pregnancy:
Technical and Clinical Outcomes. AJR, 192:1601-7.

29. Lele, P., Tangri, M.K. and Bal, H. 2015. Cervical Pregnancy: A Dilemma

for Diagnosis and Management. International Journal of Biomedical and

Advance Research, 6(05): 454-6.