ECTOPIC

PREGNANCY
DEOMICAH D. SOLANO
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OBJECTIVES
Normal histology of the Fallopian tube
§ Pathophysiology of Ectopic Pregnancy
§ Pharmacology of Methotrexate

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NORMAL HISTOLOGY OF
FALLOPIAN TUBE
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Fallopian Tube

• Paired uterine tubes or fallopian tubes or

oviducts, extend outward from the superolateral
portion of the uterus and ends by curling around
the ovary.
• Salpingo- à “tube”
• Contained in the free edge of the superior
portion of the broad ligament
• Mesosalpinx, contains blood supply and nerves
• Connect the cornua of the uterine cavity and the
peritoneal cavity.
• Each fallopian tube are between 10-14 cm in
length

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Anatomic sections:
§ Interstitial or intramural segment
- most proximal, 1-2 cm in length, embodied within the uterine
muscular wall
- surrounded by myometrium

§ Isthmic segment
- begins as the tube exits the uterus
- narrow, 2-3 mm wide, 4 cm length
- has the most highly developed musculature.

§ Ampullary segment
- 5-8mm wide,4-6 cm in length, wider and more tortous in its course
- where fertilization normally occurs

§ Infundibulum
- funnel-shaped fimbriated distal extremity of the tube which opens into the
abdominal cavity. 5
3 main layers of the fallopian tube wall:
§ Mucosa
- lined by simple columnar epithelium
- lamina propria
- characterized by longitudinal folds (plicae)

§ Muscularis layer
- Inner circular and outer longitudinal layer of
smooth muscle

§ Serosa layer
- simple squamous epithelium

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3 different cell types of MUCOSA:
§ Columnar ciliated epithelial cells
- most prominent near the ovarian end of the tube
- compose 25% of the mucosal cells

§ Secretory cells
- columnar in shape
- compose 60% of the epithelial lining
- more prominent in the isthmic segment

§ Narrow peg cells

- found between secretory and ciliated cells, and are believed to be a morphologic
variant of secretory cells.

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PATHOPHYSIOLOGY OF
ECTOPIC PREGNANCY
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Ectopic pregnancy
§ occurs when the fertilized ovum/developing blastocyst implants at a site outside of the endometrial
cavity.
§ 1-2% of all pregnancies

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Factors contributing to the risk:

q Tubal pathology

q Contraception failure

q Hormonal alterations

q Previous abortions
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Tubal pathology leading to ectopic risk

Disruption of normal anatomy from:

§ Infection

- Salpingitis - major factor contributing to the risk of ectopic pregnancy

- One episode can be followed by a subsequent ectopic pregnancy in up to 9%
- Risk of ectopic pregnancy after acute salpingitis ↑ both with number of episodes of
infection and with increasing age of the women at the time of infection

- Chlamydia – odd ratio after two and after three or more episodes are 2.1% and 4.5%
respectively
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§ Surgery
- prior tubal surgery: sterilization procedures or for fertility restoration
- incidence after salpingoplasty or salpingostomy: 15-25%
- Prior ectopic pregnancy – five-fold increased risk for having a subsequent ectopic
pregnancy

§ Congenital anomalies
- secondary to in utero diethylstilbestrol (DES) exposure (4-5%)
- likely due to abnormal tubal morphology and impaired function of the fimbriae

§ Inflammatory disease
- Endometriosis – 2x the risk for ectopic pregnancy

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Contraception failure

§ Investigators have reported that if pregnancy occurred after tubal sterilization by

laparoscopic fulguration, the ectopic pregnancy rate was as high as 50%

§ It has been hypothesize that with the extensive tissue destruction caused by
electrocoagulation, a uteroperitoneal fistula develops that allows sperm to pass into
the distal segment of the oviduct and fertilize the egg

§ Copper T380 IUD or progestin-only oral contraceptives - 5%

§ Progestogen-releasing IUDs - 23%.

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Hormonal alterations

§ If increased levels of exogenous or endogenous estrogens are present shortly after the
time of ovulation, the incidence of ectopic pregnancy is increased.

§ Investigators reported that the ectopic pregnancy rate is about 1.5% for conceptions
that occur after ovulation has been induced with clomiphene citrate.

§ Ectopic rate in pregnancies occurring after ovulation with human menopausal

gonadotropins (HMG) has been reported to range between 3% and 4%.

§ Increased levels of estrogen, as well as of progesterone, interfere with tubal motility and
increase the chance of ectopic pregnancy.

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Previous abortions

§ Although some studies have suggested that a prior induced abortion increases the risk of
ectopic pregnancy, there is probably no major association of increased risk.

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 Implantation of the morula on the mucosa of the endosalpinx

Trophoblast invades the lamina propria and then the muscularis of the tube and grow mainly
Between the lumen of the tube and its peritoneal covering

Growth occurs both parallel to the long axis of the tube and circumferentially around it

Trophoblast invades vessels

Retroperitoneal tubal hemorrhage

Hemoperitoneum

Maximal growth à inadequate blood supply à necrosis à RUPTURE

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 1
TUBAL PREGNANCY
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TUBAL PREGNANCY

▰ Nearly 95% of ectopic pregnancies are implanted in the various segments of the fallopian tube:
• Ampulla 70% - most frequent site
• Isthmic 12%
• Fimbrial 11%
• Interstitial tubal pregnancies 2% - severe morbidity
• Nontubal ectopic pregnancies 5%
- Ovary
- Peritoneal cavity
- Cervix
- Prior cesarean scar 18
OUTCOMES

§ Ectopic pregnancies may rupture and cause hemorrhage:

- As a rule, if the affected fallopian tube ruptures in the first few weeks of pregnancy (approx.8
weeks or less), the ectopic pregnancy is most likely located in the isthmic portion, whereas
the ampulla is slightly more distensible.

- If the fertilized ovum implants within the interstitial portion, rupture usually occurs at a later
AOG (approx. 10-14 weeks AOG)

§ Tubal abortion
- Ectopic pregnancy may abort out the distal fallopian tube (usually happens in fimbrial and
ampullary pregnancies) → hemorrhage may cease and symptoms eventually disappear

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§ Acute ectopic pregnancy
- High serum b-hCG level
- Rapid growth
- Higher risk of tubal rupture

§ Chronic ectopic pregnancy

- Negative or low serum b-hCG
- Ruptures late
- Form a complex pelvic mass

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CLINICAL MANIFESTATIONS
§ Classic triad:
- Delayed menstruation
- Abdominal pain
- Vaginal bleeding / spotting – 60-80%

§ Tubal rupture
- Lower abdominal and pelvic pain – severe, sharp, stabbing, or tearing PLUS
tenderness on abdominal palpation
§ Symptoms of diaphragmatic irritation – pain the neck or shoulder, especially on
inspiration, may develop in women with massive hemoperitoneum
§ On internal exam:
(+) cervical motion or wriggling tenderness
(+) tender, boggy mass felt on one side of the uterus
(+) fullness in the culdesac
(+) uterus slightly enlarged – due to hormonal stimulation 21
● In addition to bleeding, women with ectopic
tubal pregnancy may pass a decidual
cast, which is the entire sloughed
endometrium that takes the form of the
endometrial cavity.

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DIAGNOSIS
Beta-human chorionic gonadotropin (ß-hCG)

§ Discriminatory ß-hCG levels (Discriminatory zone) – minimum levels of ß-hCG above which failure to
visualize an intrauterine pregnancy (IUP) indicates that the pregnancy either is not alive or is ectopic.

§ An empty uterus with a serum ß-hCG concentration >1,500 mIU / mL (Discriminatory zone) was 100%
accurate in excluding a live uterine pregnancy.

§ Some institutions set their discriminatory threshold higher at >2,000 mIU / mL ß-hCG.

§ If the initial ß-hCG levels exceeds the set discriminatory level and no evidence for uterine pregnancy is
seen in TVS, then the diagnosis is narrowed to failed uterine pregnancy, complete abortion, or an
ectopic pregnancy.

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ß-hCG

§ Serum and urine pregnancy tests that use enzyme-linked immunosorbent assays (ELISAs) for ß-hCG
are sensitive to levels of 10-20 mIU / mL and are positive in >99% of ectopic pregnancies.

§ For cases where pregnancy test is positive, but TVS could not detect any intrauterine or extrauterine
pregnancy → Pregnancy of Unknown Location (PUL) is used until additional clinical information
allows determination of pregnancy location.

§ For PULs
- serial ß-hCG level assays are done to identify patterns that indicate either a growing or failing
intrauterine pregnancy.
- If ß-hCG level doubles every 48 hrs → VIABLE INTRAUTERINE PREGNANCY
- if failing intrauterine pregnancy, ß-hCG level declines (rates of decline expected approx. 21-
35%)

§ In pregnancies without these expected rise or falls in ß-hCG levels → Repeat ß-hCG level evaluation

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Serum Progesterone

• Serum progesterone value exceeding 25 ng/mL excludes ectopic pregnancy

• <5 ng/mL suggest either a nonliving uterine pregnancy or an ectopic pregnancy

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Transvaginal Ultrasound (TVS)
In Ectopic pregnancy, TVS can detect:
§ Absence of intrauterine gestational sac/fetal pole
§ Complex adnexal mass or extrauterine GS with “ring of fire” pattern
- placental blood flow within the periphery of the complex adnexal mass
§ Trilaminar endometrial pattern
§ Pesudosac – fluid collection between the endometrial layers and conforms to the cavity shape
§ Decidual cyst – anechoic area lying within the endometrium but remote from the canal and often at
the endometrial-myometrial border
§ Hemoperitoneum – for ruptured ectopic pregnancy (as low as 50 mL can be seen in the cul-de-sac
using TVS)
* For significant hemorrhage, fluid is seen to fill Morisson pouch near the liver. (Free fluid in this
pouch typically is not seen until accumulated blood reaches 400-700 mL)
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Culdocentesis

§ A long 1 8-gauge needle is inserted through the posterior

vaginal fornix into the retrouterine culde-sac.

§ A failure to aspirate fluid is interpreted only as

unsatisfactory entry into the culde-sac and does not
exclude ectopic pregnancy.

§ Fluid containing fragments of old clots or bloody fluid that

does not clot suggests hemoperitoneum.

§ If the blood sample clots, it may have been obtained

from an adjacent blood vessel or from a briskly bleeding
ectopic pregnancy.

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Laparoscopy
§ Direct visualization of the fallopian tubes and pelvis by laparoscopy offers a
reliable diagnosis in most cases of suspected ectopic pregnancy.

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PHARMACOLOGY OF
METHOTREXATE
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METHOTREXATE (MTX)

§ Antimetabolite, folic acid antagonist, binds to dihydrofolate reductase, blocking the reduction of
dihydrofolate to terahydrofolate.
§ Purine and pyrimidine synthesis is halted, which leads to arrested DNA, RNA, and protein
synthesis
§ Ectopic tubal pregnancy resolution rates approximate 90 percent with its use

Patients eligible for medical management:

§ Low initial serum ß-hCG level – single best prognostic indicator of successful treatment.
§ Small ectopic pregnancy size - <3.5 cm
§ Absent fetal cardiac activity

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Toxicities:

§ Toxic to the bone marrow , gastrointestinal mucosa, respiratory epithelium, and

hepatocytes
- Leucovorin, which is folinic acid and has activity equivalent to folic acid
§ It is directly toxic to hepatocytes and is renally excreted.
§ Potent teratogen
§ Methotrexate embryopathy is notable for craniofacial and skeletal abnormalities
and fetal-growth restriction

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SURGICAL MANAGEMENT

§ Laparoscopy - is the preferred surgical treatment for ectopic pregnancy unless a woman is
hemodynamically unstable

§ Before surgery, future fertility desires are discussed.

§ In women desiring permanent sterilization, the unaffected tube can be ligated or removed
concurrently with salpingectomy for the affected fallopian tube.

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CONSERVATIVE

§ Salpingostomy
- incision made over the fallopian tube to evacuate the ectopic pregnancy, without
suturing it close (heal by secondary intention).

§ Salpingotomy
- incision made over the fallopian tube to evacuate the ectopic pregnancy, and
suturing it close after evacuation.

§ Preferred for small unruptured ectopic pregnancies (<2cm)

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RADICAL SURGERY

§ Salpingectomy
- permanent removal of the fallopian tube

§ Preferred for large and/or ruptured ectopic pregnancies.

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 2
NON-TUBAL ECTOPIC
PREGNANCY
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INTERSTITIAL ECTOPIC PREGNANCY

§ Implants within the proximal tubal segment that lies within the
muscular uterine wall

§ Risk factors are similar to tubal ectopic pregnancy, although

previous ipsilateral salpingectomy is a specific risk factor
§ Undiagnosed interstitial pregnancies usually rupture following
8 to 16 weeks of amenorrhea, which is later than for more
distal tubal ectopic pregnancies.
- This is due to greater distensibility of the myometrium
covering the interstitial fallopian tube segment.
§ Because of the proximity of these pregnancies to the uterine
and ovarian arteries, there is a risk of severe hemorrhage.

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ABDOMINAL ECTOPIC PREGNANCY

§ An implantation in the peritoneal cavity exclusive of tubal, ovarian,

or intraligamentous implantations.

§ Are thought to follow early tubal rupture or abortion with

reimplantation.
§ Clinically, abnormal fetal positions may be palpated, or the cervix
is displaced.

§ Other clues include:

- Oligohydramnios is common but nonspecific.
- A fetus seen separate from the uterus or eccentrically
positioned within the pelvis
- Lack of myometrium between the fetus and the maternal
anterior abdominal wall or bladder
- Extrauterine placental tissue
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OVARIAN ECTOPIC PREGNANCY

§ Ectopic implantation of the fertilized egg in the ovary.

Four clinical criteria (Spiegelberg):

1. The tube and fimbria must be intact and separate from the
ovary
2. The gestational sac must occupy the normal position of
the ovary
3. The sac must be connected to the uterus by the ovarian
ligament
4. Ovarian tissue should be demonstrable in the walls of the
sac

§ Risk factors are similar to those for tubal pregnancies, but

ART or IUD failure seems to be disproportionately
associated
§ Presenting complaints and findings mirror those for tubal
ectopic pregnancy. 39
CERVICAL ECTOPIC PREGNANCY

§ Defined by cervical glands noted histologically opposite the

placental attachment site and by all or part of the placenta found
below the entrance of the uterine vessels or below the peritoneal
reflection on the anterior uterus.

§ In a typical case, the endocervix is eroded by trophoblast, and

the pregnancy develops in the fibrous cervical wall.

§ Predisposing risks: ART and prior uterine curettage.

§ Painless vaginal bleeding is reported by 90% of women with a

cervical pregnancy - a third of these have massive hemorrhage

§ As pregnancy progresses, a distended, thin-walled cervix with a

partially dilated external os may be evident

§ Above the cervical mass, a slightly enlarged uterine fundus can

be felt. 40
CS SCAR PREGNANCY

§ Implantation within the myometrium of a prior cesarean delivery scar.

§ Pathogenesis of cesarean scar pregnancy (CSP) has been likened to that for
placenta accreta and carries similar risk for serious hemorrhage.

§ It is unknown if the incidence increases with multiple cesarean deliveries or if it is

affected by either one- or two-layer uterine incision closure during cesarean.

§ Women with CSP usually present early, and pain and bleeding are common.
However, up to 40% of women are asymptomatic.

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THANK YOU!
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