Ectopic Pregnancy

Definition:
Ectopic pregnancy is one in which the blastocyst implants
anywhere other than the endometrial lining of the uterine
cavity
Ectopic pregnancy accounted for 10 % of all pregnancy-
related deaths
Incidence
Ectopic pregnancies occurred, at a rate of 16 ectopic
pregnancies per 1,000 reported pregnancies (1.6%)
More than 95 % ectopic pregnancy are tubal
Various sites and frequency of ectopic pregnancies.
 Ectopic Contd.

After an ectopic pregnancy, there is a 7- to 13-fold

increase in the risk of a subsequent ectopic pregnancy.
The chance that a subsequent pregnancy will be
intrauterine is 50% to 80%, and the chance that the
pregnancy will be tubal is 10% to 25%; the remaining
patients will be infertile.
Blighted ova occur more commonly in tubal conceptions
than in intrauterine conceptions, although there is no
increase in the incidence of chromosomal abnormalities
in ectopic pregnancies
 Ectopic Contd.

Ectopic pregnancy is increasing in the world.

The proposed reasons are
1. Increase in prevalence of sexually transmitted tubal infection and
damage.
2. Ascertainment through earlier diagnosis of some ectopic
pregnancies otherwise destined to resorb spontaneously.
3. Popularity of contraception that predisposes failures to be ectopic.
4. Use of tubal sterilization techniques that increase the likelihood of
ectopic pregnancy.
5. Use of assisted reproductive techniques.
6. Use of tubal surgery, including salpingostomy for tubal pregnancy
and tuboplasty for infertility.
 Risk Factors

An appreciation of risk factors for ectopic pregnancy leads to a

more timely diagnosis with improved maternal survival and
future reproductive potential.
Prior ectopic pregnancy, documented tubal pathology,
surgery to restore tubal patency, or tubal sterilization carry the
highest risks of obstruction and subsequent ectopic pregnancy
Risk factors for ectopic pregnancy can be divided into those that
confer
High
Moderate, or
Low/slight risk
 Risk factor for ectopic pregnancy
Risk factor Odds Ratio
High Risk
Tubal corrective surgery 21.0
Tubal sterilization 9.3
Previous ectopic pregnancy 8.3
In utero DES exposure 5.6
Intrauterine device 4.2–45
Documented tubal pathology 3.8–21
Moderate Risk
Infertility 2.5–21
Previous genital infection 2.5–3.7
Multiple partners 2.1
Slight Risk
Previous pelvic or abdominal surgery 0.93–3.8
Smoking 2.3–2.5
Douching 1.1–3.1
Intercourse before 18 years 1.6
Pathophysiology of Ectopic pregnancy

Histopathology
Lack of a submucosal layer within the fallopian tube
wall provides easy access for the fertilized ovum to
burrow through the epithelium and allow
implantation within the muscular wall.
As the rapidly proliferating trophoblast erodes the
subjacent muscularis layer, maternal blood pours into the
spaces within the trophoblast or the adjacent tissue.
The lack of resistance allows early penetration by
trophoblasts
The anatomic location of a tubal pregnancy may predict
the extent of damage.
 Clinical Manifestations

Symptoms
Triads occur in 50% of patients
o Amenorrhea
o vaginal bleeding
o Abdominal pain on the affected side,

Other pregnancy discomforts such as breast tenderness, nausea, and

urinary frequency may accompany more ominous findings.
Shoulder pain worsened by inspiration, which is caused by
phrenic nerve irritation from sub diaphragmatic blood, or
Vertigo and syncope from hemorrhagic hypovolemia.
Many women with a small unruptured ectopic pregnancy have
unremarkable clinical findings.
 Clinical Manifestations Contd.

Physical examination
Vital Signs normal or deranged
Abdominal and pelvic findings are notoriously scant in
many women before tubal rupture.
With rupture
o Pale
o Acutely sick
o Signs of fluid collection
o signs of acute abdomen.
o Cervical motion tenderness
o Adnexal mass
o Bulging cul-de-sac
 Clinical Manifestations Contd.

Acute Vs chronic ectopic pregnancy

There may be a difference between an "acute" and a
"chronic" ectopic pregnancy with regard to the risk of
tubal rupture.
Acute ectopic pregnancies are those with a high serum β -
HCG level at presentation and rapid growth.
These carry the highest risk of tubal rupture
compared with chronic ectopic pregnancies, which
demonstrate static serum β -HCG levels.
Theoretically, an acute ectopic pregnancy has healthy
growing trophoblastic cells that do not result in early
bleeding, and women thus present for care later.
 Clinical Manifestations Contd.
“Chronic” tubal pregnancy: has abnormal trophoblastic cells, which
die early, have lower serum β -HCG levels, and present with early
pregnancy bleeding that leads to earlier diagnosis.
Timing of tubal rupture is partially dependent on pregnancy location.
As a rule, tubes rupture earlier if implantation is in the isthmic or
ampullary portion.
Later rupture is seen if the ovum implants within the interstitial
portion.
Rupture is usually spontaneous, but can also be caused by trauma
such as that associated with bimanual pelvic examination or
coitus
 Differential diagnosis

Abortion Renal colic

GTD Adnexal cyst torsion
PID
Degenereting Myoma
TOA
Corpus luteum cyst
Appendicitis
Cystitis Mesenteric lymph
adenitis
 Diagnosis
Clinical: high index of suspicion
Laboratory tests:
Hct
Blood group & Rh
Urine HCG
Serum beta HCG
Serum progesterone
Ultrasound
Culdocentesis
Endometrial Sampling
Serum Markers : e.g. VEGF not used for every day clinical use
Diagnostic laparoscopy : Gold standard for diagnosis of
ectopic pregnancy
 Diagnosis Contd.

Serum β-HCG Measurements

β-HCG detected as early as 8 days after the LH surge.
In normal pregnancies, serum β -HCG levels rise in a log-linear
fashion until 60 or 80 days after the last menses, at which time
values plateau at about 100,000 IU/L.
Given an inter assay variability of 5 to 10 percent,
interpretation of serial values is more reliable when performed
by the same laboratory.
With a robust uterine pregnancy, serum β -HCG levels should
increase between 53 and 66 percent every 48 hours.
Inappropriately rising serum β -HCG levels only indicate a dying
pregnancy, not its location.
 Diagnosis Contd.

Serum progesterone
Done when serum β-HCG determinations & sonographic findings are
inconclusive
There is minimal variation in serum progesterone concentration
between 5 and 10 weeks' gestation, thus a single value is sufficient.
They found that results were most accurate when approached from the
viewpoint of healthy versus dying pregnancy.
With serum progesterone levels of <5 ng/mL, a dying pregnancy was
detected with near perfect specificity and with a sensitivity of 60
percent.
Conversely, values of >20 ng/mL had a sensitivity of 95 percent with
specificity around 40 percent to identify a healthy pregnancy.
Ultimately, serum progesterone can only be used to buttress a clinical
impression, but cannot differentiate between an ectopic and
uterine pregnancy.
 Diagnosis Contd.

Sonography
 Using TVS, a gestational sac is visible between 4.5 and 5 weeks,
the yolk sac appears between 5 and 6 weeks, and a fetal pole with
cardiac activity is first detected at 5.5 to 6 weeks
 When the last menstrual period is unknown, serumβ–HCG
testing is used to define expected sonographic findings.
 Each institution must define a β -HCG discriminatory value, that is,
the lower limit at which an examiner can reliably visualize
pregnancy.
 At most institutions, a concentration between 1,500 and 2,000 IU/L
represents this value.
 Accurate diagnosis by sonography is three times more likely if the
initial β-HCG level is above this value.
 Free peritoneal fluid suggests intra-abdominal bleeding
 Diagnosis Contd.

The absence of intra uterine pregnancy on TVU

with β-HCG levels above the discriminatory value
signifies an abnormal pregnancy either
Ectopic
Incomplete abortion, or
Resolving completed abortion
Conversely, sonographic findings obtained when β-
HCG values lie below the discriminatory value are
not diagnostic in nearly two-thirds of cases.
Repeat in 48 hrs
 Diagnosis Contd.

Ultrasound identifies
An intra cavitary fluid collection caused by sloughing of
the decidua can create a pseudogestational sac, or
pseudosac.
This one-layer sac is typically situated in the midline
of the uterine cavity, whereas a normal gestational sac is
eccentrically located.
Visualization of an extra uterine yolk sac or embryo
confirms a tubal pregnancy, although such findings are
present in only 15 - 30 % of cases .
Fluid collection (hemoperitonium )
Adnexal mass
Summary of Diagnostic Evaluation
Cont`d…
Cont`d…
 Diagnosis Contd.

Culdocentesis
With a 16- to 18-gauge spinal needle, the cul-de-sac may be entered
through the posterior vaginal fornix as upward traction is applied to the cervix
with a tenaculum.
Normal-appearing peritoneal fluid is designated as a negative test.
If fragments of an old clot or non clotting blood are found in the aspirate
when placed into a dry clean test tube, then hemoperitoneum is diagnosed.
Test is positive
If the aspirated blood clots after it is withdrawn, this may signify active
intraperitoneal bleeding or puncture of an adjacent vessel.
If fluid cannot be aspirated, the test can only be interpreted as unsatisfactory.
Finally, purulent fluid suggests a number of infection-related causes such as
salpingitis or appendicitis.
There also are a number of non gynecologic findings, for example, fat
necrosis from pancreatitis and feculent material from a perforated or
ruptured colon or an inadvertent puncture of the rectosigmoid colon.
 Diagnosis Contd.

Endometrial Sampling
There are a number of endometrial changes associated with
ectopic pregnancy that include decidual reactions found
in 42% of samples, secretory endometrium in 22 %, and
proliferative endometrium in 12 %.
 Management of ectopic pregnancy

1. Medical: Oral, parenteral or direct Injection into Ectopic

Pregnancy
Methotrexate
Prostaglandins
Mifepristone
Potassium chloride
Hyperosmolar glucose
2. Surgical
3. Expectant management
4. Anti D for Rh negative women
 Medical Management
Medical therapy is preferred by most, if feasible.
The best candidate for medical therapy is a woman who
is asymptomatic, motivated, & has resources to be
compliant with treatment surveillance.
Absolute contraindications for medical therapy
include
Ruptured ectopic pregnancy
Hemodynamic instability
Inability to remain compliant with post therapeutic
monitoring
Intrauterine pregnancy
Breast feeding, and
Clinically important hepatic/renal dysfunction
 Medical Management Contd.

Predictors of success in medical therapy include:

1. Initial serum β-HCG level:
Single best prognostic indicator of
treatment success in women given single-
dose methotrexate
Serum β-HCG level <5,000 IU/L success
rates of 92 %
2. Ectopic pregnancy size (<3.5cm)
3. Absent fetal cardiac activity: if cardiac activity is
seen in the ectopic pregnancy , success is low.
 Medical Management Contd.
Methotrexate
This is a folic acid antagonist that competitively inhibits the
binding of dihydrofolic acid to dihydrofolate reductase, which
in turn reduces the amount of the active intracellular metabolite,
folinic acid.
This leads to diminished nucleotide precursors and
limited DNA synthesis.
The most common side effects of methotrexate include
stomatitis, conjunctivitis, and transient liver
dysfunction, although myelosuppression, mucositis,
pulmonary damage, and anaphylactoid reactions have been
reported with only one dose of 50 to 100 mg
Although these side effects are seen in as many as a third of
women treated, they are usually self-limited.
 Medical Management Contd.

In some cases, leucovorin (folinic acid) is given following

treatment to blunt or reverse methotrexate side effects.
Such therapy is termed leucovorin rescue.
The single-dose and multi-dose methotrexate protocols
are associated with overall resolution rates for ectopic
pregnancy of about 90 %.
Failures included women with tubal rupture, massive
intra-abdominal hemorrhage, need for urgent surgery,
and blood transfusions.
Contraception for 3 to 6 months after successful
medical therapy with methotrexate, as this drug may
persist in human tissues for up to 8 months after a
single dose
Medical Treatment Protocols for Ectopic Pregnancy

Single Dose Two dose Multidose

Dosing One dose; repeat if necessary Days 0 and 4
Medication Dosage
Methotrexate 50 mg/m2 BSA (day 1) IM
Leucovorin N/A
Serum β-HCG level Days 0 (baseline), 4, and 7
Indication for
additional dose •If serum β-HCG level does
not decline by 15% from day 4
to day 7
•Less than 15% decline during
weekly surveillance
Up to 4 doses of both
drugs until serum β-HCG
declines by 15%
50 mg/m2 BSA IM 1 mg/kg, days 1, 3, 5, and
7
N/A 0.1 mg/kg days 2, 4, 6,
and 8
Days 0 (baseline),4, and 7 Days 0 (baseline), 1, 3, 5,
Days 11 and 14 if repeat and 7
dose is given
If serum β-HCG declines
•If serum β-HCG does not <15%, give additional
decline by 15% from day 4 dose; repeat serum β-
to day 7 HCG in 48 hours and
•If serum β-HCG does not compare with previous
decline by 15% from day 7 value; maximum four
to day 11 doses
•Maximum of four doses

Post therapy Weekly until serum -hCG Weekly until serum β- Weekly until serum β-
surveillance undetectable HCG undetectable HCG undetectable
 Medical Management Contd.
Direct Injection into Ectopic Pregnancy
1. Methotrexate
 In efforts to minimize systemic side effects of
methotrexate,
 Done under sonographic or laparoscopic guidance.
 Pharmacokinetic studies with 1 mg/kg of methotrexate
injected either into the sac or intramuscularly showed similar
success rates but fewer side effects with intra
gestational injection .
2. Hyperosmolar Glucose
 Direct injection of 50 % glucose into the ectopic mass using
laparoscopic guidance was 94 % successful in women with an
unruptured ectopic whose serumβ -HCG level was <2,500
IU/L.
 Surgical Management

Laparotomy or Laparoscopy
Salpingectomy
Salpingostomy (conservative surgery)
 Expectant Management

In select women, some choose close observation in the

event that there will be spontaneous resorption of an
ectopic pregnancy.
Intuitively, it is difficult to accurately predict which
woman will have an uncomplicated course with such
management.
Although an initial serum β-HCG concentration has been
shown to best predict outcome, the range varies widely.
Preferable to avoid expectant management because of
the prolonged surveillance and associated patient
anxiety.
 Persistent Ectopic Pregnancy
Incomplete removal of trophoblastic tissue and its continued growth
causes tubal rupture in 3 to 20 % of women who had
conservative surgery.
Perhaps ironically, persistent ectopic pregnancy is more likely with
very early pregnancies. Specifically, surgical management is more
difficult because pregnancies smaller than 2 cm are harder to
visualize and completely remove.
To obviate this, administered a prophylactic dose of 1 mg/m2
methotrexate postoperatively, which reduced the incidence of
persistent ectopic pregnancy as well as length of surveillance.
The optimal schedule to identify persistent ectopic pregnancy
after surgical therapy has not been determined.
Protocols describe serumβ -HCG level monitoring from every 3
days to every 2 weeks.
Currently, standard therapy for persistent ectopic pregnancy is
single-dose methotrexate with 50 mg/m2 BSA.
 Ovarian Pregnancy

Ectopic implantation of the fertilized egg in the ovary is rare.

Risk factors are similar to those for tubal pregnancies.
4 classic Spiegelberg anatomic and histologic criteria which are as
follows:
1. The fallopian tubes should be intact and separate from the ovary;

2. The gestation should appear in the usual ovarian pelvic location;

3. The gestation should be connected to the uterus by the ovarian

ligament; and
4. Ovarian tissue must be present in the histologic specimen of the
gestation sac walls
 Abdominal pregnancy

Studdiford's criteria used to diagnose primary

abdominal pregnancy are described as:
Studdiford criteria to diagnose primary
abdominal pregnancy:
1. Normal bilateral fallopian tubes and
ovaries;
2. Absence of uteroperitoneal fistula; or
3. Presence of a pregnancy related to the
peritoneal surface exclusively
 Cervical Pregnancy
Incidence of is reported to be between 1 in 8,600 to 12,400
pregnancies
The incidence appears to be rising because of assisted reproductive
technology, especially in vitro fertilization and embryo transfer
A risk factor unique to cervical pregnancy is a history of dilation and
curettage, seen in nearly 70 % of cases
Two diagnostic criteria are necessary for confirmation of cervical
pregnancy:
1. Presence of cervical glands opposite the placental attachment site, and
2. Portion of or the entire placenta must be located below either the
entrance of the uterine vessels or the peritoneal reflection on the anterior
and posterior uterine surface.
Early diagnosis of cervical pregnancy may obviate uncontrollable
hemorrhage and subsequent hysterectomy in these women.
Because of its rarity, experiences with medical therapy of cervical
pregnancy are limited.
 Heterotopic Pregnancy
A uterine pregnancy in conjunction with an extrauterine pregnancy is
termed heterotopic pregnancy.
Prior to ART, incidence was 1 in 30,000 pregnancies
Since ART, incidence is 1 in 3900
The rate of heterotopic pregnancies for ART patients is 1.5 in 1000
pregnancies.
When a tubal pregnancy coexists with a uterine pregnancy, potassium
chloride can be injected into the tubal pregnancy sac.
Methotrexate is contraindicated due to the detrimental effects on the
normal pregnancy.
Cases of craniofacial, skeletal, cardiopulmonary, and
gastrointestinal anomalies have been described even with limited
first-trimester methotrexate exposure
 Cesarean Delivery Scar Pregnancy
Implantation within the scar of a previous cesarean delivery
through a microscopic tract in the myometrium
represents a rare condition carrying serious maternal
morbidity and mortality from massive hemorrhage.
There are four sonographic criteria that must be met to secure
the diagnosis:
1. An empty uterine cavity,
2. An empty cervical canal,
3. Gestational sac in the anterior part of the uterine
isthmus, and
4. Absence of healthy myometrium between the bladder and
gestational sac.
Treatment is medical or surgical depending clinical condition
of patient
 Prevention
Ectopic pregnancy is difficult to prevent because risk
factors are poorly modified.
Tubal pathology carries one of the highest risks and pelvic
inflammatory disease plays a major role in tubal adhesions and
obstruction.
Because chlamydial infections constitute nearly half of
pelvic inflammatory disease cases, efforts have been directed
towards screening high-risk populations for asymptomatic
infections.
These include sexually active women under the age of 25 or
women who use non barrier forms of contraception.
Such screening programs in Sweden have demonstrated steady
declines in both chlamydial infections and ectopic pregnancy
rates, especially in women aged 20 to 24 years
 Reference

William gynacology 4th edition.

Medstar obgyn second edition.
STG 2021.