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Best Practice & Research Clinical Obstetrics and Gynaecology 23 (2009) 529538

Contents lists available at ScienceDirect

Best Practice & Research Clinical


Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

10

Treating non-tubal ectopic pregnancy


Maya Chetty, MBBS, Specialist Trainee Obstetrics and Gynaecology a,
Janine Elson, MD, MRCOG, Consultant Gynaecologist b, *
a

Obstetrics and Gynaecology ST2, Simpsons Centre for Reproductive Health, Royal Infirmary of Edinburgh,
51 Little France Crescent, Old Dalkeith Rd, Edinburgh, EH16 4SA, UK
b
Leicester Fertility Centre University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, LE1 5WW, UK

Keywords:
ectopic pregnancy
cervical pregnancy
caesarean scar
ovarian
interstitial
cornual
abdominal
laparoscopy
expectant management
uterine artery embolisation
methotrexate

The purpose of this review is to examine the current state of


knowledge regarding the treatment of non-tubal ectopic
pregnancies.
This review looks at the management of cervical, caesarean scar,
ovarian, interstitial, cornual and abdominal pregnancies. Traditionally these pregnancies have been diagnosed late and managed
by open surgery. Earlier diagnosis has led to the use of minimal
access techniques, medical and conservative management for all
types of non-tubal pregnancies.
Increased awareness and the experience of specialised centres
have led to an improved understanding of the best way to manage
non-tubal ectopic pregnancies and the development of new
techniques.
! 2009 Elsevier Ltd. All rights reserved.

Non-tubal ectopic pregnancies have been traditionally diagnosed late and have been associated
with significant morbidity and mortality. Advances in ultrasound technology and the development of
specialised early pregnancy assessment units over recent years have led to an increase in the early
diagnosis of non-tubal ectopic pregnancies. This means that management of these rare ectopic pregnancies has now progressed from open surgical management to the use of minimal access techniques
and the exploration of medical and conservative treatments either alone or as adjuvant therapies.
Increased diagnosis and centralisation of management in centres of excellence has meant that
a sufficient number of cases have been dealt with to begin to develop robust diagnostic and
management criteria.

* Corresponding author. Tel: 44 116 258 6426.


E-mail address: Janine.elson@uhl-tr.nhs.uk (J. Elson).
1521-6934/$ see front matter ! 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bpobgyn.2008.12.011

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M. Chetty, J. Elson / Best Practice & Research Clinical Obstetrics and Gynaecology 23 (2009) 529538

Cervical pregnancy
Cervical pregnancies are rare, accounting for less than 1% of all ectopic gestations. They result from
the passage of a blastocyst through the uterine cavity and its subsequent implantation and growth
within the mucosa that lines the endocervical canal, and have an estimated incidence of one in 2500 to
one in 18,000 pregnancies.13 The aetiology of cervical pregnancy is unknown, although it is likely to
result from a combination of factors including local cervical pathology. Predisposing factors include
previous instrumentation of the endocervical canal, anatomic anomalies (myomas, synechiae), intrauterine device (IUD) use, in vitro fertilisation (IVF), and diethylstilbestrol exposure, although these are
not strong associations.
Presenting symptoms generally include vaginal bleeding which is usually painless but may be
coupled with abdominal pain and urinary problems, particularly in more advanced pregnancies.4
Examination findings at admission vary, but include an enlarged, globular or distended cervix, which is
often associated with dilatation of the external os.35
A cervical pregnancy before 1979 was almost always associated with hysterectomy for uncontrollable vaginal bleeding, and therefore made women sterile.6 The diagnosis was primarily made by
histological analysis of the hysterectomised uterus. Preoperative diagnosis was rarely possible. Raskin
published the first ultrasound report of cervical pregnancy in 1978.7 Since then, transvaginal ultrasonography has become the main diagnostic tool, allowing the diagnosis to be made accurately and
earlier in the course of the pregnancy. This has opened the door to more conservative approaches that
attempt to limit morbidity and preserve fertility. The majority of patients with a cervical pregnancy are
women with low parity, thus preservation of reproductive function is a priority.3
When sonographic examination identifies a gestational sac located in the cervix, the diagnostic
possibilities include a cervical ectopic pregnancy and intrauterine pregnancies with a low implantation
site (isthmico-cervical pregnancy) or in the process of spontaneous expulsion. Sonographic criteria
have been defined to differentiate between these types of pregnancy.8
Cervical pregnancy can present as (1) a haemorrhagic mass, (2) a gestational sac, or (3) with the
presence of a fetus (with or without cardiac activity). There are defined sonographic criteria (Table 1).
Following diagnosis, conservative medical and/or surgical management have become the standard
first-line approach to treatment of women who desire preservation of fertility, although hysterectomy
is still recommended for second and third trimester cervical pregnancy and for uncontrolled bleeding.3
As with tubal ectopic pregnancies, early, accurate diagnosis is the key factor in conservative
management of cervical pregnancies. Gestation < 12 weeks, absence of fetal cardiac activity and lower
serum hCG levels are associated with more successful conservative management.9,10
A range of conservative (uterus preserving) treatment options have been suggested and may be
broadly categorised as: tamponade, reduction of blood supply, excision of trophoblastic tissue, intraamniotic fetocide and systemic chemotherapy.5 Most reports of successful conservative therapy
involve the use of a combination of methods.
Among the first approaches used was dilatation and curettage, with uterine artery ligation or
embolisation, or cervical balloon tamponade to prevent blood loss.2 These procedures had a high
failure rate (hysterectomy required in 22% of patients)11 and their role is now limited mainly to patients
with life-threatening bleeding.
Local injection of the ectopic pregnancy with potassium chloride or methotrexate became
the favoured technique in the late 1990s. The success rates were high (close to 100%) and systemic

Table 1
Sonographic criteria for cervical pregnancy.
Anatomical structure

Sonographic appearance

Uterus
Cervix
Gestational sac
Sliding sign
Doppler blood flow

Empty
Barrel shaped
Below uterine arteries
Absent
Around sac

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side-effects and complication rates low.2 A transvaginal approach under ultrasound guidance was used
to inject the agent into the gestational sac. This technique has also been used in a number of cases of
heterotopic pregnancy with coexistent intrauterine and cervical ectopic pregnancies. The cervical
pregnancies were successfully treated and the intrauterine pregnancies preserved with subsequent
delivery of viable infants.12,13
The folic acid antagonist methotrexate is the most widely used systemic chemotherapy in the
treatment of cervical ectopic pregnancy. It has long been considered to be an acceptable conservative
treatment for tubal ectopic pregnancy in single and multiple dose protocols14,15 and the efficacy of its
use in cervical ectopic pregnancy has been examined by Kung et al. (1999). This meta-analysis of 62
cases of cervical ectopic pregnancy estimated the efficacy of systemic methotrexate administration in
the treatment of cervical ectopic pregnancy to be approximately 91%. There was, however, no standard
protocol of methotrexate used and successful cases required surgical debulking, or local injection with
methotrexate in addition to systemic therapy. Gestational age > 9 weeks, hCG levels > 10,000 mIU/ml,
crown-rump length >10 mm, and fetal cardiac activity have been shown to be associated with a higher
risk of primary failure of treatment of cervical ectopic pregnancy with systemic methotrexate16 and
again combination therapy with intra-amniotic injection seemed to increase the chance of successful
treatment in this meta-analysis. There is no evidence to suggest that treatment with systemic methotrexate is detrimental to subsequent reproductive performance or obstetric outcome8, though there
remains no clear recommendation about the optimal dosage or route of administration for its use in the
treatment of cervical ectopic pregnancy.11
A number of adjunctive methods to control haemorrhage in the treatment of cervical ectopic
pregnancy have been described; these include uterine artery ligation and uterine artery embolisation.17
Case series report success with these methods in combination with intracervical or systemic methotrexate18, but the number of cases reported are small and associated complications include infection,
uterine infarction, sciatic nerve injury, and necrosis of the bladder or rectum.10,18
Early diagnosis and treating patients with conservative methods results in decreased morbidity and
mortality associated with cervical pregnancy, and, very importantly, preserves the uterus and subsequent fertility. Although many different methods have been advocated, the optimal approach to the
treatment of cervical ectopic pregnancy is largely unknown. Case reports of conservative treatment
using a combination of modalities show a number of strategies which appear to be safe and effective.
Ovarian ectopic pregnancy
Ovarian pregnancy is a rare form of ectopic gestation with estimates of frequency ranging from 1 in
2100 to 1 in 7000 pregnancies19, or 3% of all ectopic pregnancies.20 Risk factors include previous pelvic
inflammatory disease, IUD use, endometriosis, and assisted reproductive technologies.2125
Diagnosis of ovarian ectopic pregnancies can be difficult. In 1878 Spiegelberg described criteria for
the pathologic diagnosis of ovarian pregnancy: (1) Tube entirely normal, (2) Gestational sac anatomically located in the ovary, (3) Ovary and gestational sac connected to the uterine ovarian ligament, and
(4) Placental tissue mixed with ovarian cortex.26 Today, diagnosis is more usually made by ultrasound,
ovarian pregnancies usually appearing on or within the ovary as a cyst with a wide echogenic outside
ring (Fig. 1). A yolk sac or embryo is less commonly seen and the appearance of the sac contents tends
to lag in comparison to gestational age.21 Ovarian pregnancies are often mistaken for corpus luteal
cysts. Three-dimensional ultrasound imaging and intra-operative ultrasound have been used to
distinguish between the two23,24, although Doppler ultrasonography has not been shown to be
useful.21 Thick-walled ovarian cysts in the patient with an empty uterus and a serum bhCG level above
the discriminatory zone should be investigated with particular care.22 Presenting symptoms are most
commonly abdominal pain and light vaginal bleeding21 and diagnostic laparoscopy is often required to
make the diagnosis of an ovarian pregnancy which is later confirmed by histological examination of the
specimen.27 Intraoperatively, ovarian ectopic pregnancies often resemble haemorrhagic cysts.
In the past, patients with an ovarian pregnancy usually presented after rupture of the gestational
sac with massive intraperitoneal haemorrhage. These patients usually underwent laparotomy with
oophorectomy or ovarian wedge resection. The widespread use of transvaginal ultrasonography and
serial measurements of serum bhCG allows for earlier detection of an ovarian pregnancy, prior to

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Fig. 1. Ultrasound showing ovarian ectopic, and corpus luteum in same ovary.

rupture. This can permit laparoscopic surgery and removal of the ectopic pregnancy with conservation
of healthy ovarian tissue. This is especially important if future fertility is desired. Case series have
described many cases of successful treatment of ovarian ectopic pregnancies with conservative ovarian
surgery23,28 and successful subsequent pregnancy.22,28 Oophorectomy should therefore be reserved for
cases of advanced gestation.23
Medical management with systemic methotrexate has been used successfully.29 This may not be
feasible in many cases as laparoscopy is often the key in making the diagnosis. There may, however, be
a place for medical management of carefully selected cases of ovarian ectopic pregnancy but selection
criteria are not defined. Methotrexate may also be useful in the treatment of persistent trophoblastic
tissue after laparoscopy.23
Caesarean scar ectopic pregnancy
Caesarean section scar pregnancy is one of the rarest forms of ectopic pregnancy. It has only
relatively recently been described and there are only a small number of case reports in the literature
that describe the first-trimester diagnosis and management of pregnancies implanted into Caesarean
section scars. The aetiology of Caesarean scar pregnancy is unclear although previous Caesarean
section, myomectomy, adenomyosis, IVF, previous dilatation and curettage, and manual removal of
placenta have been linked as risk factors.3032 These pregnancies are challenging to diagnose and carry
with them a high risk of bleeding and uterine rupture.33,34 Presentation can be with uterine rupture
and hypovolaemic shock but they may also present with painless vaginal bleeding.26 Ultrasound with
Doppler, hysteroscopy and MRI have been used to make the diagnosis, and differentiate Caesarean scar
from cervical ectopic pregnancies.26
The diagnosis of a Caesarean section scar pregnancy is based on the visualisation of trophoblast
located between the anterior uterine wall and the bladder. Jurkovic et al.35 set out the following
ultrasound diagnostic criteria: (1) empty uterine cavity; (2) gestational sac located anteriorly at the
level of the internal os covering the visible or presumed site of the previous lower uterine segment
Caesarean section scar (Fig. 2); (3) evidence of functional trophoblastic/placental circulation on
Doppler examination; (4) negative sliding organs sign. Discontinuity of the anterior uterine wall in the
sagittal plane has been proposed by Vial et al.36 to be associated with a high risk of uterine rupture.
With the limited experience of Caesarean section scar pregnancies in the first trimester, it is difficult
to conclude on the optimal management for individual cases. Expectant, medical and surgical
management have all been reported with varying levels of success. The mode of treatment in some

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Fig. 2. Ultrasound of gestational sac implanted at level of caesarean scar.

cases is dictated by the clinical presentation, with laparotomy and hysterectomy being the most
appropriate treatment for the patients who present with haemoperitoneum and hypovolaemic shock.
There are five reported cases of Caesarean section scar pregnancies managed expectantly in the
literature. Two of these required additional treatment with methotrexate33,35 and two had emergency
hysterectomies.35,37 Expectant management does not therefore seem to be an appropriate choice, with
the majority of cases reported requiring medical or surgical intervention. Expectant management of
viable Caesarean section scar pregnancies carries a significant risk of emergency hysterectomy,
particularly if the pregnancy progresses beyond the first trimester.
Medical management with local injection of methotrexate has been more successful, with success
rates of 7080% when used as the initial treatment option.35 This involves the direct injection of 25 mg
methotrexate into the pregnancy, performed transvaginally under ultrasound guidance. Local injections of potassium chloride have also been reported and were used by Jurkovic et al.35 prior to local
methotrexate where embryonic cardiac activity was detected. Methotrexate has also been used
systemically in combination with dilation and evacuation with success.31,38
Controversy exists as to the optimal surgical management of Caesarean scar pregnancies. In their
report of 18 cases of Caesarean scar pregnancies, Jurkovic et al.35 used suction curettage under ultrasound guidance followed by tamponade with a Foley balloon in cases complicated by heavy intraoperative bleeding. They achieved similar success rates using this simpler approach with quicker
postoperative recovery and so recommend this transcervical approach over laparoscopy or laparotomy.
Uterine artery embolisation has also been described as an adjunctive therapy to reduce haemorrhage.38,39 Most recently, use of a Shirodkar suture inserted pre-evacuation has been advocated. In
a case series of 28 women, 79% needed the suture to be tied to minimise blood loss with only 2 then
needing blood transfusion.40
Interstitial pregnancy
Around 2.5% of ectopic pregnancies are interstitial pregnancies.20 The diagnosis of an interstitial
pregnancy is made by visualisation of the interstitial line adjoining the gestational sac and the lateral
aspect of the uterine cavity and continuation of the myometrial mantle around the ectopic sac (Fig. 3).41
Expectant, medical and surgical management have all been reported. Traditionally, interstitial
pregnancies have been managed by hysterectomy or cornual resection at laparotomy.42 From the
1990s onwards laparoscopic management of interstitial pregnancies became the surgical management
of choice, with both cornual resection and salpingotomy being described initially.43 More recently,
further endoscopic approaches have been reported.44 Vasopressin injection followed by excision of the

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Fig. 3. Ultrasound of interstitial pregnancy.

pregnancy and endoloop closure may be useful in very early pregnancies. Alternatively,
laparoscopic haemostatic suturing techniques have been described to reduce haemorrhage in larger
pregnancies.45
Conservative management is a safe option for most interstitial pregnancies, with the likely success
of this approach being determined by the initial level of serum hCG.46 The options for conservative
management include local or systemic methotrexate or expectant management. In a series of 42
women, initial serum HCG levels of less than 9000 IU/l were associated with 100% success of conservative management. There are few reports of expectant management in the literature.46 It is most
suitable for women with low or falling hCG levels in whom the addition of methotrexate may not
improve the outcome. Medical management involves the use of methotrexate either given systemically
or by local injections. The largest case study of 17 women treated using a single dose systemic injection
of methotrexate 50 mg/m2 reported a 94% success rate.47 They reported no complications from the use
of systemic methotrexate but other studies have reported up to 40% of women suffering from side
effects.46 Local injection of interstitial pregnancy involves aspiration of the exocoelomic fluid, injection
of 25 mg of methotrexate with 0.20.4 mEq of potassium chloride administered transvaginally under
ultrasound guidance. This is reported as having a 91% success rate, with the advantages of fewer side
effects and the ability to perform embryocide at the same time. Its disadvantage is that it is a technically more challenging method. There have been several case reports of successful selective uterine
artery embolisation used in conjunction with methotrexate in order to reduce haemorrhage.48,49
However, there are concerns about the safety and complications of future pregnancies after this
technique.

Cornual pregnancy
A true cornual pregnancy is one in the rudimentary horn of a unicornuate uterus. Cornual pregnancies are the rarest form of ectopic pregnancy at 0.27%.50 The term is often used interchangeably in
the medical literature with interstitial pregnancy51,52 but the two are distinct entities. The following
criteria have been suggested to diagnose cornual pregnancy on ultrasound examination41: (1) a single
interstitial portion of Fallopian tube in the main uterine body; (2) a gestational sac, mobile and separate
from the uterus, surrounded by myometrium; (3) a vascular pedicle adjoining the gestational sac to the
unicornuate uterus.

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Conservative, laparoscopic and open surgical methods of management have all been described.
There is a case report of successful conservative management of a missed miscarriage within the
rudimentary horn, although the woman represented with a further corneal pregnancy.53There are
several other reported cases of methotrexate and potassium chloride injection prior to later laparoscopic rudimentary horn excision.54 Excision of the rudimentary horn is therefore the best approach.
Laparoscopic excision is safe but attention needs to be paid to the possibility of urinary tract anomalies
which may be associated with unicornuate uteri. The technique involves excision of the fibrous band
that attaches the rudimentary horn to the unicornuate uterus with removal of the rudimentary horn
through the suprapubic port.55 Advanced cases in the second and third trimester where the risk of
rupture is high require an open approach to excision at laparotomy.56

Abdominal pregnancy
Abdominal pregnancy is the rarest form of ectopic pregnancy at 1.3%.20 It is described as primary
or secondary where a tubal pregnancy aborts through the fimbrial end and implants in the peritoneal cavity. The following ultrasound criteria have been suggested by Gerli et al.57 as being
diagnostic: (1) absence of an intrauterine gestation sac, (2) absence of both an evident dilated tube
and a complex adnexal mass, (3) a gestational cavity surrounded by loops of bowel and separated by
peritoneum, (4) a wide mobility similar to fluctuation of the sac particularly evident with pressure
of the transvaginal probe toward the posterior cul-de-sac. The traditional management involves
a laparotomy with removal of the fetus with or without placental tissue.58 Recently, there have been
several reports of laparoscopic management. Shaw et al.59 describe a case series of 11 abdominal
pregnancies in which half were managed by laparotomy and half laparoscopically. Laparoscopic
management was associated with a shorter operative time and reduced blood loss. One of the
problems associated with the removal of abdominal pregnancies after the first trimester is the risk
of uncontrolled bleeding from the placental bed. Adjuvant treatment with methotrexate alongside
selective arterial embolisation has been suggested to control this.60 There are also case reports of
early abdominal pregnancies being treated successfully with systemic methotrexate and ultrasound
guided injection of potassium chloride, leading to resorption of the products of conception without
the need for further surgery.61

Summary
Ultrasound criteria now exist for all non-tubal ectopic pregnancies, facilitating early diagnosis and
giving the patient options for management, resulting in a decreased morbidity and mortality from
these rare ectopics. Despite this, patients may still present late in pregnancy and the diagnosis always
needs to be suspected in women admitted with a positive pregnancy test and haemorrhagic shock.
There are many different approaches to the management of cervical and caesarean scar pregnancies
using a combination of surgical and medical methods and the treatment is therefore best tailored on an
individual case basis taking into account the operators expertise. It seems reasonable therefore to treat
these pregnancies with a combination of local or systemic chemotherapy and/or surgical removal.
Adjunctive techniques for controlling haemorrhage (cervical cerclage, uterine artery embolisation)
should also be considered and a plan made for urgent attainment.
The initial hCG level is the determinant of the safest approach for interstitial pregnancies with
conservative and medical management being effective for those pregnancies with levels less than
9000 IU/l. For larger pregnancies, laparoscopic techniques with or without adjuvant therapies and
haemostatic measures may be appropriate.
Surgery remains the mainstay of treatment for ovarian, cornual and abdominal ectopic pregnancies
with minimal access techniques being continually advanced.
As early ultrasound diagnosis improves and early pregnancy centres develop larger case series of
these challenging pregnancies, further evidence and treatment criteria will emerge as to the safest way
to manage these potentially life threatening conditions.

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Practice points
" Medical management is appropriate in carefully selected patients with cervical, caesarean
scar and interstitial pregnancies.
" Surgical management of cervical and caesarean scar pregnancies must include an available
technique for controlling severe haemorrhage.
" Laparoscopic excision of the rudimentary horn is the appropriate management of cornual
pregnancies.
" Oophorectomy should be reserved for advanced cases of ovarian pregnancy.
" Primary abdominal pregnancies in the first trimester can be safely managed laparoscopically.

Research agenda
" Cervical cerclage vs. balloon tamponade for cervical and caesarean scar pregnancies
" Criteria for medical management of interstitial, cervical, caesarean scar and abdominal
pregnancies
" Fertility outcomes following use of uterine artery embolisation

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