Dr. Mamta Dagar is MD (Ob-Gyn), MRCOG, FICOG, FICMCH, trained in Gynae Laparoscopy from Kiel, Germany and Robotic Surgery at EEC, Paris. She is graduate and postgraduate of prestigious Institute Lady Hardinge Medical College. She is currently working as a Consultant in Institute of Obstetrics and Gynaecology at Sir Ganga Ram Hospital, Delhi and Associate Professor GRIPMER, with more than 20 year of clinical experience. She is the Course Convener for AICC-RCOGNZ Colposcopy Courses and Member Representative RCOG-NZ India. She is a keen academician with publications in various peer reviewed journals. She has been co-investigator in several research projects with DST, DBT and ICMR. Dr. Dagar is an active member of RCOG-NZ, teaching faculty for MRCOG courses and is Editor, IMS Delhi Chapter.
Methods:
Three cases of interstitial pregnancy were retrospectively
analyzed.
Result Successful laparoscopic cornuostomy and removal
of products of conception were performed in two cases,
while one case was successfully managed by local injection
with KCL and methotrexate followed by systemic
methotrexate.
Conclusion: Early diagnosis and timely management are
key to the management of interstitial and cornual ectopic
pregnancy. With expertise in ultrasound imaging and
advances in laparoscopic skills progressively, conservative medical and surgical measures are being used to treat
interstitial and cornual ectopic pregnancy successfully.
Keywords: Interstitial pregnancy Cornual pregnancy
Laparoscopic cornuostomy Methotrexate
Interstitial and cornual pregnancy is a rare and most dangerous
form of ectopic pregnancy, accounting for 2–4% of
all ectopic pregnancies [1]. Clinician often uses the term
cornual ectopic pregnancy interchangeably with interstitial
pregnancy. By definition, a cornual pregnancy refers to the
implantation and development of a gestational sac in one of
the upper and lateral portions of the uterus. Conversely, an
interstitial pregnancy is a gestational sac that implants
within the proximal, intramural portion of the fallopian
tube that is enveloped by the myometrium [2, 3]. The
interstitial portion is approximately 0.7 mm in width and
approximately 1–2 cm in length. The surrounding
myometrial tissue allows progression of the pregnancy into
the second trimester, but rupture at such an advanced
gestation may result in catastrophic hemorrhage with a
mortality of up to 2% [1].
Interstitial and cornual pregnancy remains the most
difficult type of ectopic pregnancy to diagnose due to low
sensitivity and specificity of symptoms and imaging. The
classic triad of ectopic pregnancy abdominal pain, amenorrhea
and vaginal bleeding occurs in\40% of patients.
The site of implantation in the intrauterine portion of fallopian
tube and invasion through the uterine wall makes
this pregnancy difficult to differentiate from an intrauterine
pregnancy on ultrasound. The ultrasonographic criteria
proposed for diagnosing this condition are: an empty
uterine cavity, a gestational sac located eccentrically
and[1 cm from the most lateral wall of the uterine cavity,
and a thin (\5 mm) myometrial layer surrounding the
gestational sac [4]. ‘‘Interstitial line sign’’ that extends from
the upper region of the uterine horn to border the intramural
portion of the fallopian tube has also been used [5].
Besides this, three-dimensional ultrasonography scans and
magnetic resonance imaging allow for accurate early
diagnosis of interstitial pregnancy if suspected on two-dimensional
ultrasonography scans [6, 7].
Traditionally, treatment of interstitial pregnancy has
been surgical and may include hysterectomy or cornual
resection by laparotomy or laparoscopy [1]. But increasingly,
more conservative approaches are being used such as
cornuostomy instead of cornual resection, as well as
laparoscopy in place of laparotomy. In the last few years,
the use of more conservative surgical alternatives, such as
cornuostomy rather than cornuectomy, is introduced to better preserve uterine integrity for future fertility. Many
cases of laparoscopic cornuostomy have been reported in
the literature so far [8, 9].
Although patients with serious signs and symptoms of
ectopic pregnancy (hypotension, severe abdominal pain or
heavy vaginal bleeding) are likely to receive immediate
surgical intervention, those with milder symptoms may be
considered for medical therapy (methotrexate).
We report here three cases of interstitial and cornual
ectopic pregnancy of which two were successfully managed
by laparoscopic cornuostomy, while one was managed
with local injection of KCl and methotrexate followed
by systematic methotrexate.
Case I
A 23-year-old woman, third gravida with previous two
vaginal deliveries, referred to our hospital at 7 ? 3-week
gestation as a suspected case of cornual ectopic pregnancy.
She had earlier bleeding at 5 ? 2-week gestation, and
pelvic USG done outside suggested left cornual ectopic
pregnancy and was given injection methotrexate 75 mg
intramuscularly. There was no history of tuberculosis (TB),
pelvic inflammatory disease (PID) or surgery. On admission,
she was hemodynamically stable. Abdominal examination
was normal. On per vaginum examination os was
closed with minimal bleeding and no cervical exitation
pain. Uterus was retroverted, para size with minimal left
fornix fullness. On admission, her b-hCG was 9169 IU/l
and USG pelvis suggested a heteroechoic well-defined
rounded area (3.5 9 3.3 cm) with peripheral thick echogenic
rim (trophoblast) and central cystic area 11.9 mm
corresponding to gestational age 6 weeks 1 day with tiny
yolk sac in the left-sided cornu of uterus, with surrounding
myometrium 3 mm (Fig. 1).
Medical managment was considered initially in view of hemodynamic stability after informed consent and serial S.b-hCG on day 0, 4 and 7 was 9169, 5410 and 5561 IU/l respectively. In view of failed medical management decision for surgical intervention was taken. She underwent laparoscopic left cornuostomy. The uterus was injected with diluted vasopressin (20 in 100 ml of normal saline) and uterine bulge was incised with scissors, and products of conception and gestational sac were removed followed by repair of incision with Vicryl no 1. Post-op period was uneventful. Histopathology report confirmed products of gestation (ectopic cornual gestation). Serial decline in bhCG noted till 6 weeks when it became\2 IU/l. Patient was advised contraception COCP at 6-week follow-up and counseled regarding the risk of ruptured uterus in the next pregnancy and elective cesarean in future pregnancy (Fig. 2).
Case II
A 39-year-old woman, gravida 4, para 1 previous LSCS with previous 2 miscarriages presented with amenorrhea 6 ? 3 weeks and no other complaints. She was hemodynamically stable. Per vaginum examination revealed bulky uterus with no fornicial mass or tenderness. Transvaginal ultrasound suggested heteroechoic mass 2.9 9 2.5 9 2.8 cm in right uterine cornu with increased vascularity and small cystic component of size 6 9 3 mm within gestational sac indicative of right cornual ectopic pregnancy. She was counseled and she opted for conservative surgical management. She underwent laparoscopic right cornuostomy after informed consent. The uterus was injected with diluted vasopressin (20 in 100 ml of normal saline) and uterine bulge was incised with scissors, and products of gestation were removed followed by repair of incision with Vicryl no 1. Histopathology report confirmed cornual ectopic pregnancy with products of gestation. She was followed with serial weekly S.b-hCG till it became< 2.0 IU/l, 4 weeks later (Fig. 3).
Case III
A 28-year-old woman second gravida with previous missed miscarriage presented at 9 ? 4-week gestation with pelvic USG suggestive of right-sided cornual ectopic pregnancy.
She was under strict follow-up since 7-week gestation as no
clear-cut diagnosis of cornual ectopic pregnancy was made
on ultrasound. On admission, she was hemodynamically
stable. Per abdominal examination was normal. On per
vaginal examination, uterus was retroverted, bulky, soft,
with no cervical motion tenderness and no adnexal mass was
felt. USG pelvis was suggestive of gestational sac of
8 ? 5 weeks with cardiac activity, CRL 20.7 mm, myometrium
thickness 3.6 mm suggestive of cornual ectopic
pregnancy. Her S.b-hCG was 51,569 IU/l. Management
options both medical and surgical were discussed. She opted
for medical management. She received transvaginal USGguided
intra-amniotic injection of KCl (4 ml) and intraplacental
injection of methotrexate (25 mg) after informed
consent. Disappearance of cardiac activity was noted on
USG. She received injection methotrexate 50 mg intramuscularly
after 24 h followed by injection folinic acid 5 mg
next day. She remained stable during hospital stay and was
discharged in stable condition after 5 days.
Follow-up was done with weekly serum beta hCG till it
became < 2 IU/l and pelvic USG. Subsequent decline in
serum beta hCG and reduction in size of ectopic gestational
sac were noted on USG (Fig. 4).
including medical management and laparoscopy [12]. In a
report by Tulandi and Al-Jaroudi [13], the management of
32 cases of interstitial pregnancy was discussed. Eight
women were treated with methotrexate either systemically
(n = 4), locally under ultrasonographic guidance (n = 2)
or under laparoscopic guidance (n = 2). Eleven patients
were treated by laparoscopy and 13 by laparotomy. Systemic
methotrexate treatment failed in three patients, and
they subsequently required surgery. Persistently elevated
serum b-hCG levels were found in one patient after
laparoscopic cornual excision, and she was successfully
treated with methotrexate. Subsequent pregnancy was
achieved in ten patients. No uterine rupture was encountered
during pregnancy or labor [13].
In a prospective observational study [14] at St George’s
Hospital Medical School in London, 17 out of 20 women
with cornual pregnancy were treated with single-dose
intramuscular methotrexate, which was administered on
day 0. A second dose of methotrexate was given if the
human chorionic gonadotrophin (hCG) levels had not fallen
by 15% between days 4 and 7. Sixteen (94%) were
treated successfully, including all four cases with presence
of fetal heart activity. A second methotrexate dose was
given to six women.
Where surgery can be avoided, systemic medical management
is a safe and considered to be effective treatment
for cornual pregnancy. In the event the interstitial pregnancy
is medium-sized (\5 cm), conservative management
with methotrexate is often used with caution [15].
Unfortunately, methotrexate treatment has been associated
with a 9–65% failure rate [16, 17].
Systemic administration of methotrexate is widely used
in nearly all forms of ectopic pregnancy in patients with
stable vital signs. However, transvaginal USG-guided local
methotrexate injection to the cornual gestational sac has
been presented as case reports and suggested to be a safe
and effective alternative to surgical and systemic
methotrexate therapy [18]. Especially in live ectopic gestations,
systemic methotrexate should not be the first-line
treatment due to high failure rates (30%), and surgery or
local methotrexate injection into the sac should be considered
[19]. In case 3, we presented the successful combined
use of systemic and transvaginal USG-guided local
KCl and methotrexate injection in the management of a
cornual pregnancy with a very high initial beta hCG level
and live ectopic.
In case 3, we combined both modalities, local and systemic
methotrexate administration along with local KCl
injection, which is one the few case reports of such an
approach. In the literature, successful treatment of cornual
pregnancy with just a single dose of methotrexate has been
reported [20, 21]. Medical treatment with a single
methotrexate injection has been recommended as an alternative to surgical treatment of cornual pregnancy.
However, it is associated with significantly increased risk
of failure, subsequent uterine rupture and emergency surgery
[21]. Cornual pregnancy with an initial beta hCG
value of\5000 IU/ml is usually treated successfully with
single-dose methotrexate, but when the value is
[5000 IU/ml, more than a single dose is usually required
and failure or complication is more likely [22]. However,
upper limit of beta hCG value at which medical treatment
with methotrexate will fail is not clear. For local administration
of methotrexate, various injected doses such as
12.5, 25 and 100 mg were given in the literature.
Regarding surgical treatment, main concerns are hemorrhage
and the need for adequate cornual reconstruction to
prevent uterine rupture in future subsequent pregnancy, which
necessitate advanced laparoscopic skills and technique
[23, 24]. Integrity of myometrium after conservative treatments
is unclear; patients must be counseled carefully about
the risk of uterine rupture in subsequent pregnancy. To prevent
this severe complication, normal uterine tissue must be
preserved, avoiding tissue damage by electrosurgery and by
minimal excision of cornual tissue [24, 25]. Suture closure of
the cornual defect remains the most appropriate method for
the achievement of hemostasis and may also minimize the
risk of uterine rupture in subsequent pregnancy [25, 26].
To minimize blood loss, different techniques such as
uterotonic vaginal misoprostol insertion and laparoscopic
injection of vasoconstrictors prior to surgery can be used.
Diluted intra-myometrial vasopressin injection is the most
well-known and preferable procedure [27, 28] obtaining a fast
whitening of the tissue and allowing a non-bleeding surgery
effectively. Other methods used by laparoscopists include
ligation of ascending branches of the uterine vessels, uterine
de-vascularization, apposition of fibrin glue or tourniquets
applied around the cornual mass or through the avascular area
of the broad ligament to minimize bleeding [26, 29]. These
methods require a high level of laparoscopic skills [29]. We
used diluted vasopressin injection to minimize bleeding.
Close antenatal follow-up of patient with history of cornual
ectopic pregnancy (CEP) is mandatory. The incidence of
recurrent CEP is unknown [30, 31]. Transvaginal ultrasound
should be performed 5–6 weeks after the last menstrual period
to ensure the correct implantation of the subsequent gestation
[31]. Typically, elective cesarean section should be planned to
reduce the risk of rupture in labor [25, 31].
Conflict of interest: The authors declare that they have no conflict of
interest.
Ethical Approval: This article does not contain any studies with
human participants or animals performed by any of the authors.
Informed Consent: For this type of study formal consent is not
required.
