Management of

Ectopic Pregnancy
Topic Review by :
Banavit Bhekasuta
Khansatit Thawornsawadi
Supervised by : Dr. Kamol Pataradool

Classification

Management
Expectant management
Medical management
Surgical management

Expectant Management
close observation
initial values <200 IU/L predict
successful spontaneous resolution in 88
to 96 percent of attempts
values >2000 IU/L the success rate was
only 7 percent.
risk of tubal rupture persists

Medical Management
predictors of success
1. Initial serum -hCG level
single best prognostic indicator of treatment success in
women given single-dose methotrexate
an initial serum value <5000 IU/L was associated with a
success rate of 92 percent, whereas an initial concentration
>15,000 IU/L had a success rate of 68 percent

2. pregnancy size
a 93-percent success rate with single-dose methotrexate
when the ectopic mass was <3.5 cm

3. Fetal cardiac activity

Identification of cardiac activity sonographic is a relative
contraindication to medical therapy

Methotrexate
folic acid antagonist : competitively
inhibits the binding of dihydrofolic
acid to the enzyme dihydrofolate
reductase
arrest of DNA, RNA, and protein
synthesis
can be given orally, intravenously, or
intramuscularly (IM) or can be
directly injected into the ectopic
pregnancy sac

 Methotrexate Contraindications
Sensitivity to MTX
Intrauterine pregnancy
Peptic ulcer disease
Tubal rupture
Hepatic, renal, or hematologic dysfunction
Active pulmonary disease
Breast feeding
Evidence of immunodeficiency

 Prior to methotrexate therapy

complete blood count, serum creatinine
and -hCG levels, liver function tests,
and blood type and Rh
Avoid

folic acid-containing supplements

NSAID
Alcohol
Sunlight
sexual activity

 Side effects
Stomatitis
Conjunctivitis
Transient liver dysfunction
Myelosuppression
Mucositis
Pulmonary damage
Anaphylactoid reactions

 Single-Dose Methotrexate
Multidose Methotrexate
Oral Methotrexate

 Single-dose therapy was more

commonly used because of
simplicity.
less expensive
less intensive posttherapy monitoring
not require leucovorin rescue

 Direct Injection into Ectopic Pregnancy

Methotrexate
local injection into the gestational sac u
sonographic or laparoscopic guidance
1 mg/kg of methotrexate injected

Hyperosmolar Glucose
direct injection of 50-percent glucose
94-percent successful in women with an unruptured
ectopic whose serum -hCG level was <2500 IU/L.
success was significantly better in sonographicrather than laparoscopic-guided injection

 Post therapy monitoring

screens for signs of persistent ectopic
pregnancy
recommend contraception for 3 to 6
months

Surgical Management
Laparoscopic vs. Laparotomy
Salpingotomy vs. Salpingostomy
Salpingo/gostomy vs. Salpingectomy

 Indication:
Hemodynamic instability
Impending or ongoing rupture of ectopic mass
Contraindications to methotrexate
Coexisting intrauterine pregnancy
Not able or willing to comply with medical
therapy post-treatment follow-up
Lack of timely access to a medical institution
for management of tubal rupture
Failed medical therapy

Laparoscopic vs. Laparotomy

Laparoscopic
higher persistent trophoblast rate
shorter operation time
less perioperative blood loss
shorter duration of hospital stay
shorter convalescence time
Cost effective
No different in number of subsequent
intrauterine pregnancies

Salpingotomy vs. Salpingostomy

C: Linear salpingostomy

Salpingotomy vs.
Salpingostomy
No evidence of a difference was
found

Salpingo/gostomy vs.
Salpingectomy

When to Choose
Salpingectomy?
Uncontrollable bleeding/ Shock (from
Rupture)
Recurrent ectopic pregnancy at the
same side
Severely damaged tube
No fertility needed

Salpingo/gostomy vs.
Salpingectomy
Fertility need
Healthy
contralateral
tube
Ectopic
pregnancy
Damage
contralateral
tube

Salpingo/gosto
my

Salpingectomy

No need

Salpingectomy

Fertility need

Salpingo/gosto
my

No need

Salpingectomy

JOURNAL CLUB

Introduction
1-2% of all pregnancies are ectopic
In early years, the standard
treatment was salpingectomy
In 1914, Beckwith Whitehouse
studying the histopathology of tubal
pregnancies, he showed that
salpingotomy was also a feasible
intervention

Introduction
In 1957, despite the fact that RCT had
not been done, salpingotomy was widely
adopted on the basis of a presumed
favourable outcome with respect to
future reproductive capacity
Later on, they recognised disadvantages
of salpingotomy :
repeat ectopic pregnancy in the same tube
persistent trophoblast, that need additional
treatment

METHODS

 Study design and participants

open-label, multicentre, randomised
controlled trial in university hospitals
and other teaching and non-teaching
hospitals in the Netherlands, Sweden,
the UK, and the USA

 Inclusion
Women were eligible for the trial if they had a
presumptive diagnosis of tubal pregnancy
transvaginal ultrasonography
serum human chorionic gonado tropin (hCG)

women with a tubal pregnancy amenable to either

treatment intervention and with a healthy
contralateral tube were enrolled.
At surgery, the presence of a tubal pregnancy had to
be confirmed.
If tubal rupture was present, women were still eligible for
the trial as long as the tubal rupture did not aff ect the
possibility of doing a salpingotomy.

 Exclusion
younger than 18 years
haemodynamically unstable
no desire for future pregnancy
pregnant after in-vitro fertilisation (IVF)
only have one tube, or with contralateral
tubal occlusion or a hydrosalpinx
documented at a previous hystero
salpingography or laparoscopy.

 Randomization & Masking

Randomized by central internet-based
program running a computer-generated
randomization sequence
Stratified by :
Hospital
Womans age (<35 or 35 years)
history of tubal disease (i.e. previous ectopic
pregnancy, tubal surgery, or PID)

Randomization sequence was not

accessible by the recruiters

 The study was open-label because the

nature of the intervention meant that
masking patients to the assigned
intervention was not possible (from
ethical point of view)
The researchers who collected data for
fertility outcomes were masked, but
those who analyzed the data were not

 Procedures
Salpingotomy
linear salpingotomy
epinephrine, terlipressin, ornipressin, or any
analogue, or the application of fibrin glue was
allowed

salpingectomy
all techniques were allowed
including clamping, cutting and suturing, and use of
bipolar forceps and scissors,bipolar cutting forceps,
vessel sealing instruments,ultrasonic devices, and
endoloop snares

 all women were informed about their study group

assignment and the intervention that they received after
surgery,
identify persistent trophoblast
serum hCG(expressed in IU/L)was measured postoperatively
until undetectable concentrations

assess fertility
contacted the participants by telephone, email, or postal mail
every 6 months for 36 months
questionnaire about the occurrence and outcome of subsequent
pregnancies until an ongoing pregnancy occurred.
Repeated attempts by telephone,email, or postal mail were
made when participants did not respond to the initial follow-up
contact

 Primary outcome
An ongoing pregnancy by natural conception
an intrauterine pregnancy visible on ultrasound at a
gestational age of 12 weeks or more with fetal cardiac
activity, or a pregnancy that resulted in a livebirth
calculated the time to the first ongoing pregnancy in
months, from the date of surgery to the first day of the last
menstrual period before the conception that led to the
ongoing pregnancy
If an ongoing pregnancy did not occur, follow-up ended at the last
date of contact, or at the moment when either IVF or reconstructive
tubal surgery was done
Natural conceptions that occurred after failed IVF treatment were
registered
not included as primary endpoint events in the initial analysis.

 Secondary outcomes
persistent trophoblast
rising or plateauing serum hCG concentrations
ostoperatively that necessitated systemic
methotrexate treatment or surgical intervention

first repeat ectopic pregnancy

any ectopic pregnancy or a persisting pregnancy
of unknown location for which surgery or medical
treatment with methotrexate was necessary

first ongoing pregnancy after ovulation

induction, intrauterine insemination, or IVF

 Statistical analysis
They assumed the cumulative proportion
of women with an ongoing pregnancy
after salpingectomy-to-salpingotomy
would be 40%-to-55%(15%) after 36
months, with a median time to ongoing
pregnancy of 14-to-10 years to be
clinically relevant enough to overcome
the potential disadvantages of persistent
trophoblast and repeat ectopic pregnancy

 Sample size needed to enroll 404

women for a power of 80% with a twosided significance of 0.05
Anticipated a 10% loss to follow-up, we
aimed to enroll 450
Primary outcome was analyzed by
intention to treat & per protocol
Secondary outcomes were expressed
as RRs with 95% CI

 Prespecified subgroup analyses for

maternal age, history of a previous
ectopic pregnancy, preoperative
serum hCG concentration, and size of
the ectopic pregnancy on U/S

RESULTS

 446 women were randomly assigned between Sept

24,2004, and Nov 29, 2011,
215 allocated to salpingotomy and 231 to salpingectomy.
Of the 215 women in the salpingotomy group, 164 (76%)
underwent the assigned intervention as planned, and the
remaining 51 women in
the group received salpingectomy.
43 women were converted to salpingectomy during the
initial surgery because of persistent tubal bleeding, three
had a salpingectomy at reintervention because of
suspected tubal bleeding, and five had a salpingectomy
because of persistent trophoblast.

Baseline characteristics were similar between

the study groups.

the frequencies of adverse events, such as

conversion to laparotomy or
salpingectomy,blood transfusions,and

 446 women who underwent random

assignment and were analysed
222 had an ongoing pregnancy by
natural conception
108 after salpingotomy and 114 after
salpingectomy.

 The cumulative ongoing pregnancy rate by

natural conception within a time horizon of 36
months
607% after salpingotomy
562% aftersalpingectomy
(fecundity rate ratio 106, 95% CI 081138; log-rank
p=0678; fi gure 2). Persistent

trophoblast occurred significantly more

frequently in the salpingotomy group than in the
salpingectomy group, but the numbers of repeat
ectopic pregnancies did not differ significantly

 The per-protocol analysis incorporated the 164

women who underwent a completed salpingotomy
and the 231 women who were assigned to and
received salpingectomy.
201 women in the per-protocol analysis had an
ongoing pregnancy by natural conception; 87 after
salpingotomy and 114 after salpingectomy.
The cumulative ongoing pregnancy rate by natural
conception was 623% after salpingotomy and 562%
after salpingectomy (fecundity rate ratio 110, 95%
CI
083146; log-rank p=0492).

 The prespecified subgroup analyses

showed no significant beneficial
effect of salpingotomy on the
cumulative rates of ongoing
pregnancy by natural conception in
any of the subgroups

 The results of all the analyses were similar when the

four women from the hospital that was unable to
provide data were included (data not shown).
Our meta-analysis, which included our own results and
data from another study,16 substantiated our finding
that cumulative rates of ongoing pregnancy by natural
conception were similar between salpingotomy and
salpingectomy
Meta-analysis for the outcome of persistent trophoblast
was not possible since only data from our study were
available. The risk of repeat ectopic pregnancy was not
significantly increased after salpingotomy