Pathophysiology

Tubal Ectopic Pregnancy

Because most ectopic pregnancies initially implant in a fallopian tube, the

pathophysiology will focus on tubal ectopic pregnancies. The blastocyst burrows into
the epithelium of the tubal wall, tapping blood vessels, by the same process as normal
implantation into the uterine endometrium. However, the environment of the tube is
quite different because of the following factors:

1. There is a decreased resistance to the invading trophoblastic tissue by the

fallopian tube.

2. There is a decreased muscle mass lining the fallopian tubes; therefore their
dispensability

3. The blood pressure is much higher in the tubal arteries than in the uterine
arteries is greatly limited.

4. There is limited decidual reaction; therefore human chorionic gonadotropin

(hCG) is decreased and the signs and symptoms of pregnancy are limited.

It is because of these characteristic factors the termination of a tubal pregnancy

occurs gestationally early by an abortion, spontaneous regression, or rupture,
depending on the gestational age and the location of the implantation. If the embryo
dies early in gestation, spontaneous regression often occurs. If spontaneous regression
fails to occur, then usually an ampullar or fimbriated tubal pregnancy ends in an
abortion and an isthmic or interstitial pregnancy ends in a rupture

A tubal abortion primarily occurs because of separation of all or part of the

placenta. This separation is caused by the pressure exerted by the tapped blood vessels
or tubal contractions.

With complete separation, The products of conception are expelled into the
abdominal cavity by way of the fimbriated end of the fallopian tube

With an incomplete separation, bleeding continues until complete separation takes

place, and the blood flows into the abdominal cavity collecting in the rectouterine cul-
de-sac of Douglas.

Tubal rupture results from the uninterrupted invasion of the trophoblastic tissue or
tearing of the extremely stretched tissue. In either case the products of conception are
completely or incompletely expelled into the abdominal cavity or between the folds of
the broad ligaments by way of the torn tube.

The duration of the tubal pregnancy depends on the location of the implanted
embryo or fetus and the distensibility of that part of the fallopian tube. For instance, if
the implantation is located in the narrow isthmic portion of the tube, it will rupture
very early, within 6 to 8 weeks; the distensible interstitial portion may be able to
retain the pregnancy up to 14 weeks of gestation.
Abdominal Ectopic Pregnancy

An abdominal pregnancy almost always results from an implantation secondary to

a tubal rupture or abortion through the fimbriated end of the fallopian tube. In these
cases the placental continues to grow following attachment to some abdominal
structure, usually the surface of the uterus, broad ligaments, or ovaries. However, it
can be any abdominal structure including the liver, spleen, or intestines. Because the
invading trophoblastic tissue is not held in check, it can erode major blood vessels at
any because they are not cushioned by the myometrium.

Cervical Ectopic Pregnancy

In very rare cases the fertilized ovum bypasses the uterine endometrium and
implants itself in the cervical mucus. Painless bleeding begins shortly after
implantation, and surgical termination is usually required before the fourteenth week
of gestation.

Signs and Symptoms

Before Rupture

♦ Abdominal Pain

Abdominal pain occurs close to 100% of the time. It is usually first manifested by
a dull pain caused by tubal stretching following by a sharp colicky tubal pain caused
by further tubal stretching and stimulated contractions. It is diffuse and is bilateral or
unilateral.

♦ Amenorrhea

A history of a late period for approximately 2 weeks or a higher than usual or

irregular period is reported by 75 % to 90 % of the patients

♦ Abnormal Vaginal Bleeding

Mild to intermittent dark red or brown vaginal discharge occurs in 50 % to *0 % of

the cases related to uterine decidual shedding secondary to decreased hormones.

♦ Absence of Common Signs of pregnancy

Absence of common signs of pregnancy is secondary to decreased pregnancy

hormones and occurs 75 % of the time.

♦ Abdominal Tenderness

Abdominal Tenderness occurs in approximately 95 % of the cases.

♦ Palpable Pelvic Mass

 Referred Shoulder Pain approximately 50 % of the cases. It may be in the opposite
abdominal quadrant from the ectopic growth related to a corpus luteum cyst.

Rupture

Exacerbation of the pain occurs during rupture in an ectopic pregnancy.

After Rupture

♦ Faintness / Dizziness

Faintness and dizziness occur in the presence of significant bleeding

Generalized, Unilateral, or Deep Lower Quadrant Acute

♦ Abdominal Pain

Pain is caused by blood irritating the peritoneum

♦ Referred Shoulder Pain

Referred shoulder pain

is related to diaphragmatic irritation from blood in the peritoneal cavity

♦ Signs of Shock

Shock is related to the severity of the bleeding into the abdomen.

Maternal Effects

⇒ Ectopic pregnancies account for approximately 10% of all maternal deaths.

⇒ They are the fourth leading cause of maternal mortality, but they are the
number one cause of maternal mortality in the first trimester of pregnancy.

⇒ Hemorrhage is the cause of death in 85 % to 89 % of the cases and occurs more

frequently with an interstitial or abdominal ectopic pregnancy.

⇒ The greater risk of mortality related to an ectopic pregnancy is associated with

an abdominal ectopic growth, which has a 7.7 times greater risk when
compared to other types of ectopic pregnancies.

Sites of an ectopic pregnancy are

⇒1the fallopian tube,

⇒2ovary,
 ⇒3cervix,

⇒4or abdominal cavity

The majority of ectopic pregnancies (95%) are located in the fallopian tube, with
1% located on an ovary, less than 1 % on the cervix, and 3% to 4% in the abdominal
cavity,

Of all tubal pregnancies, more than half are located in the ampulla, or largest
portion of the tube. The next most common site in the isthmus, or the narrow part of
the tube that connects the interstitial to the ampullar portion. Three percent are located
in the interstitial or muscular portion of the tube adjacent to the uterine cavity. Rarely
does the ectopic pregnancy locate in the fimbria or terminal end of the tube. The
outcome and gestational length of the ectopic pregnancy will be influenced by its
location in the fallopian tube.

Incidence

The incidence of ectopic pregnancy is approximately 1 out of every 60

pregnancies, or 2% with the number increasing each year worldwide . Women over
35 years old, nonwhites, or those who have a history of infertility are at a greater risk
of experiencing an of ectopic pregnancy.

Etiology

♦1 Previous Tubal Infections

Previous pelvic infections caused by certain sexually transmitted diseases, such as

chlamydia and gonorrhea, postpartum endometritis and postabortal uterine infections
can predispose to a tubal infection. A tubal infection can cause damage to the mucosal
surface of the fallopian tube, causing intraluminal adhesions that interfere with the
transportation of the fertilized ovum to the uterine cavity.

♦2 Previous Tubal or Pelvic Surgery

During surgery, if blood is allowed to enter the fallopian tubes, tubal adhesions can
result from the irritation of the mucosal surface. Salpingectomy, for previous ectopic
pregnancy or for treatment of an inflammatory process, and salpingoplasty, for
infertility are the surgeries that most frequently cause tubal adhesions. Occasionally
irritation results from an appendectomy.

♦3 Hormonal Factors

Altered estrogen/progesterone levels or inappropriate levels of prostaglandines can

interfere with normal tubal motility of the fertilized ovum.

♦4 Contraceptive Failure
 Ectopic pregnancies occur with the use of an intrauterine device (IUD) in
approximately 2 per 1000 users each year. The cause is unknown but may be related
to altered tubal motility or a tubal infection. There is increased risk for an ectopic
pregnancy with the progestin-only oral contraceptive because of the decreased
motility - induced effect of progesterone.

♦5 Stimulation of Ovulation

There is a 3% increased incidence of an ectopic pregnancy associated with

ovulation -stimulating drugs such as human menopausal gonadotropin and
clomiphene citrate. These drugs alter the estrogen/progesterone level, which can
affect tubal motility.

♦6 Infertility Treatment

There is an increased risk of an ectopic pregnancy with in vitro fertilization (IVF)

or gamete intrafallopian transfer (GIFT) since underlying tubal damage is frequently
one of the causative factors predisposing one to this type of infertility treatment.

♦7 Environmental Effect

Maternal cigarette smoking at the time of conception was found in a case-

controlled study, to be associated with an increased risk of an ectopic pregnancy.

♦8 Transmigration of Ovum

Migration of the ovum from one ovary to the opposite fallopian tube can occur by
an extrauterine or intrauterine route. This can cause a potential delay in transportation
of the fertilized ovum to the uterus. Then trophoblastic tissue is present on the
blastocyst before it reaches the uterine cavity, and therefore the trophoblastic tissue
implants itself on the wall of the fallopian tube.

♦9 Endometriosis

The presence of endometrial tissue located outside the uterine cavity increases the
receptivity of the fertilized ovum to an ectopic implantation.

Normal Physiology

The fallopian tube is very muscular and narrow and contains very few ciliated cells
at the interstitial area. In the ampullar area the fallopian tube becomes less muscular,
the luminal size increases, and the ciliated cells are more abundant.

The fimbriated end of the fallopian tube has the unique function of moving the
ovum and sperm in opposite directions almost simultaneously by peristaltic (muscular
contraction) and ciliated activity. This tubal activity is initiated by two or more
adjacent pacemakers in the ampullar and isthmic areas of the fallopian tube by
sending out myoelectrical activity is in either direction. The net directional movement
in the fallopian tubes will vary during the menstrual cycle. During menstruation the
net directional force is toward the uterus starting from the ampullar area to prevent
menstrual blood reflux into the tube. This is stimulated primarily by estrogen induced
prostglandins. Just before ovulation, the directional force from the ampullar area is
inward in order to pick the released ovum from the ovary and moved it into the
ampullar area of the fallopian tube. At the same time the directional force from the
uterine area is just the opposite in order to facilitate sperm motility toward the ovum.
This is influenced by estrogen primarily. After fertilization the directional force varies
in the ampullar area, which delays ovum transport. Approximately 5 days after
ovulation, the net directional force from the middle of the ampullar area is inward
through the isthmus in order to transport the ovum to the uterus. This is influenced by
increasing progesterone and prostaglandin E2 (PGE). Approximately 7 days after
ovulation, the myoelectrical activity become variable again, moving in both directions
from each of the pacemakers.

The fertilized ovum should reach the uterine cavity in 6 to 7 days, just about the
time the trophoblast cells begin to secrete the proteolytic enzyme and start to develop
the threadlike projections called chorionic villi that initiate the implantation process.

The uterus is normally prepared by estrogen and progesterone to accept the

fertilized ovum, now called a blastocyst. As the chorionic villi invade the
endometrium, the villi are held in check by a fibrinoid zone. The uterus is also
supplied with an increased blood supply capable of nourishing the products of
conception.

Risk Factors for Ectopic Pregnancy

Strong evidence for association

Pelvic inflammatory disease
Previous ectopic pregnancy
Endometriosis
Previous tubal surgery
Previous pelvic surgery
Infertility and infertility treatments
Uterotubal anomalies
History of in utero exposure to diethylstilbestrol
Cigarette smoking

Weaker evidence for association

Multiple sexual partners
Early age at first intercourse
Vaginal douching