This document discusses heterotopic pregnancy, which is defined as a simultaneous pregnancy where one embryo implants in the uterus and another implants outside the uterus, usually in a fallopian tube. The incidence is about 1 in 30,000 for natural conceptions but higher with ART. Risk factors include ART, damage to the fallopian tubes, and prior tubal surgery. Diagnosis can be challenging as symptoms mimic other conditions, but ultrasound may reveal an adnexal mass or free fluid. Treatment depends on the location and stability of the patient, ranging from medical management to surgery. Outcomes include risk of miscarriage of the intrauterine pregnancy as well as maternal morbidity if not diagnosed and treated promptly.
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Heterotopoic pregnancy
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HETEROTOPIC PREGNANCY
CONTENTS
1. INTRODUCTION
2. DEFINITION
3. SITES
4. INCIDENCE
5. RISK FACTORS
6. CL MANIFESTATIONS
7. EVALUATION
8. DD
9. RISKS
10. TREATMENT
11. FOLLOW UP
12. OUTCOME
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INTRODUCTION
Hetero-’ meaning ‘other
topos’ meaning ‘place
A multiple pregnancy
one embryo viably implanted in the uterus &
other implanted elsewhere as an ectopic
First described by
Duverny in 1708
DEFINITION
Simultaneous pregnancies at two different
implantation sites.
Most commonly
1 pregnancy is implanted in the uterus& at least
1 other is implanted outside the uterus
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SITES
Most often
combination of IU & ectopic pregnancies, rather
than 2 ectopic pregnancies.
The majority (90%)
fallopian tube
10%
cervix
ovary
interstitial (cornual) tubal segment
abdomen
previous cesarean scar
Interstitial pregnancy” and “cornual pregnancy” are
used synonymously.
Cornual pregnancy pregnancy in
one horn of a bircornuated uterus or
one half of a septated or subseptated uterus.
bicornuate uterus predisposes the embryo to high implantation.
Intramural pregnancies occur when the embryo
implants in and is completely surrounded by
myometrium clearly removed from either the
uterine cavity or the interstitial portion of the tube.
The management can be complicated because of
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Interstitial pregnancy
implantation occurs in the interstitial part of the
fallopian tube that is embodied within the muscular
wall of the uterus.
It is not associated with uterine anomalies.
often progress without symptoms until a rupture
occurs later than other tubal pregnancies.
For practical reasons, all cases where the
gestational sac is partially or completely enveloped
by the myometrium should be classified as
interstitial pregnancies.
INCIDENCE:
Dependent upon
rates of ectopic pregnancy
dizygotic twinning.
Natural conception
1 in 30,000
pregnancies
ART:
1 in 100 pregnancies
Fresh Vs Frozen cycles
No significant
difference
(Xiao et al, 2018).
significantly higher
(0.56% Vs. 0.22%)
(Guan, Ma, 2017)
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RISK FACTORS
71% had at least one risk factor
10% had 3 or more
(Talbot et al, 2011).
1.ART:
The most important risk factor
±related to the high
proportion of patients with tubal disease
levels of E2& progesterone
numbers of
transferred embryos
±Other factors
volume & viscosity of transfer medium
technique of ET
[Clayton et al, 2007].
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2.Damage to fallopian tube:
history of PID
prior tubal surgery
endometriosis
cigarette smoking
[Barrenetxea et al, 2007].
CLINICAL MANIFESTATIONS
should be sort for in all pregnancies during early
scan, especially in those with
Risk factors for
multiple gestations
ectopic gestation
(Tal et al, 1996).
High index of suspicion in women with IUP
with or without symptoms of ectopic gestation
irrespective of the existence of risk factors
HP should not be eliminated once IUP is diagnosed.
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Symptoms & signs
closely mimics the symptoms of
threatened abortion &
ectopic pregnancy in other locations.
abdominal pain
adnexal mass
peritoneal irritation
enlarged uterus
[Onoh et al, 2018].
HP should be considered in a patient with
viable IUP
experiencing significant abdominal pain.
DIAGNOSTIC EVALUATION
1. βHCG levels
not useful
{primarily reflect IUP}
Only if high concentration with singleton IUP
(Stanley et al, 2018).
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2. Ultrasound
unreliable for the detection
only 66 % were diagnosed by US
[Talbot et al, 2011].
Suggestive signs:
1. Complex adnexal mass or
2. Fluid in the pelvis. (sign of tubal rupture)
3. Yolk sac or
fetal pole with cardiac activity
{Advanced ectopic gestations}
[Lyu et al, 2017].
Low suspicion of HP after visualizing IUP:
False labeling
1. Complex adnexal mass as a corpus luteum
cyst.
2. Free fluid in pelvis as ascites associated with
OHSS
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If there is suspicion of HP
1. Repeat US
2 w after the diagnosis of IUP
(Molinaro et al, 2019).
2. Routine TVS at day 27 after ET
(Bharadwaj et al, 2005).
3. Symptoms onset before or after day 27 are clues to
early diagnosis
3. Surgical evaluation
a key role in the diagnosis of HP.
In hemodynamic instability or
with severe pain or
surgical evaluation& treatment necessary
[Lyu et al, 2017].
In the stable patient
laparoscopy offers the advantage of
minimally invasive evaluation
limiting the impact to a coexistent IU fetus.
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HP should be considered in viable IUP with:
1. History of ART
2. Significant abdominal pain.
3. US:
1. free fluid in the pelvis or
2. adnexal mass
4. Rise in hCG after treatment
DIFFERENTIAL DIAGNOSIS
1. Uterine bleeding & pain early in pregnancy.
Threatened abortion
Ruptured corpus luteum
2. Abdominal pain early in pregnancy.
Appendicitis
Nephrolithiasis
UTI
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RISKS
Dangerous condition
Risks associated with an ectopic pregnancy.
Catastrophic outcomes if the diagnosis is delayed,
{The presence of a simultaneous IUP}
1. Significant maternal morbidity, including blood
transfusion
2. Hemorrhagic shock
3. Fetal loss
TREATMENT
Rules:
1. Tailored according to site of implantation
2. Utilize the least invasive therapy in order to
preserve IUP
can be preserved in many cases
has a favorable prognosis with 50–70 %
survival rate
[Barrenetxea et al, 2007].
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angular pregnancy
which is distinguished from cornual and interstitial
pregnancy anatomically by its position in relation to
the round ligament, should be taken into the
diagnostic considerations. Unlike the interstitial
and cornual pregnancies, angular pregnacies may
have a favorable outcome (4).
A. Tubal HP:
Hemodynamically unstable patient:
Surgery
Laparoscopy or laparotomy
For diagnosis & treatment
As early as possible to
prevent maternal & fetal harm
improve the survival of IUP
[Goldberg et al, 2006].
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Salpingectomy
standard surgical approach
should be the first line of TT in
hemodynamic instability or
tubal rupture
[Barrenetxea et al, 2007].
Laparoscopy
preferred operative approach
depends on
availability of necessary surgical equipment
skill of the surgeon
(Goldstein et al, 2006).
Laparotomy
large amounts of intra-abdominal bleeding or
hgic shock.
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Hemodynamically stable
Diagnostic laparoscopy
when clinical presentation&imaging are unclear.
Medical TT:
During
laparoscopy or
ultrasonography.
injection of a substance into
an intact heterotopic gestational sac or
fetus
Substances should have
high therapeutic effectiveness
low toxicity to the concurrent IUP
no lasting damage to the fallopian tube
[Tsakos et al, 2015].
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Methotrexate:
Systemic is contraindicated
{potential catastrophic effects on the viable IUP}.
Hyperosmolar glucose.
KCL injection
11 cases of HP
55% failed this therapy & required surgical
intervention
[Vikhareva et al, 2018].
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B. Cervical, cornual, or interstitial pregnancy
in order to reserve IUP
(Wu et al, 2018).
Embryo suction with or without local drug
injection would be more advisable compared
with surgery
1. Heterotopic cesarean scar pregnancy
Selective embryo reduction by aspiration
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2. Heterotopic cervical pregnancy
No guidelines for safe & effective treatment.
Lyu et al, 2017
1. KCL injection
complicated by delayed bleeding
2. cervical stay sutures
IUP progressed to term
Tsakos et al, 2015
1. Aspiration of the cervical pregnancy
2. Foley catheter placement
3. Cervical cerclage suturing.
Safest method
cervical pregnancy was removed
IUP was preserved: term delivery
(Dendas et al, 2017).
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3. Heterotopic Interstitial pregnancies
86 cases (Dendas et al, 2017)
80.2% occurred after IVF-ET.
History of salpingectomy is a major risk factor, present in
39.5% .
37.2% presented with cornual rupture.
Surgery: performed in 53.5% of cases.
Medical TT: in unruptured, early diagnosed (32.6%).
Watchful waiting: when interst pregn miscarried (5.8%)
LBR of IUP, when viable at presentation, was 70.0%
LBR of the interstitial pregnancy was only 4.7%
17 patients with interstial HP (Jiang et al, 2018)
58.5%: surgical treatment
7 laparoscopic corneal resection
3 laparotomy
3 cases simultaneously terminated IUP by suction
evacuation
23.5%: selective embryo reduction under TVS.
3 patients: Expectant management
13 women: delivered healthy babies
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4. Heterotopic cornual pregnancy
14 patients
(Xu et al, 2017).
laparoscopic cornuostomy or corneal repair.
No one was converted to laparotomy
Post-operation pregnancy was uneventful.
An effective TT even in ruptured ones.
Safe
well-trained laparoscopists
experienced support teams.
5. Heterotopic abdominal pregnancy
28 cases (Yoder et al, 2016)
History of ectopic pregnancy in 39 %.
History of tubal surgery in 50 %
32 % cases having had bilateral salpingectomy.
Transfer of 2 embryos or more (79 %)
Fresh ET(71 %)
Heterotopic abdominal pregnancy in 46 % of cases
54 % were abdominal ectopic pregnancies.
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6. Heterotopic triplets
Tubal ectopic pregnancy & a twin pregnancy, are
rare disorders
(Bataille et al, 2016).
6 cases
Early surgical intervention
key to successful treatment
allows good neonatal outcome.
FOLLOW UP
Ectopic portion of some HP can resolve
spontaneously without initiating any intervention.
No guidelines or diagnostic tests that demonstrate
which women appropriate for observation.
Serial assessment of
Serum β-hCG: not helpful
US: unclear whether or not is helpful
[Smisek et al, 2008].
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OUTCOME
1 in 3 coexistent IUP spontaneously abort
this rate is higher than that in singleton IUP
[Xiao et al, 2018].
64 patients (Na et al, 2018).
14.1% miscarried before 10 w after TT
G age at TT:
only independent risk factor for miscarriage
regardless of TT methods.
Miscarriage group: 5.97 ± 0.50 w
Non miscarriage group: 6.80 ± 1.04 w (P = .008).
Immediate TT after diagnosis: favorable prognosis
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CONCLUSIONS
HP is very rare in the general population.
Any risk factor for an ectopic pregnancy is a risk
factor for HP.
The incidence 1 in 100 pregnancies in ART
Diagnosis is difficult as IU pregnancy will lead many
clinicians to neglect S&S of a parallel pregnancy.
A condition sharing the same significant morbidity&
mortality as an ectopic pregnancy is thus masked&
consequently rendered extremely dangerous