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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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