Ectopic pregnancy

Chapter 27. Ectopic pregnancy

May 1. 1997 1st year resident S.H OH M.D.

I. General considerations

A. Etiology

1.Mechanical factors

Salpingitis
- agglutination of the arborescent folds of the tubal mucosa with narrows of
  the lumen or formation of blind pockets
- reduced ciliation
Peritubal adhesions
- kinking of the tube and narrowing of the lumen
Development abnormalities of the tube : diverticula accessory ostia, hypoplasia
Previous ectopic pregnancy : the increased risk likely is due to previous salpingitis
Previous operations on the tube
Multiple previous induced abortions : likely due to small increases in the incidence
of salpingitis
Tumors that distort the tube
Previous cesarean section

2. Functional factors

External migration of the ovum
Menstrual reflux
Altered tubal motility
- increased incidence of ectopic pregnancies has been reported with use of
  progesterone-only oral contraceptives
- with use of intrauterine devices
- after use of postovulatory high-dose estrogens to prevent pregnancy
- after ovulation induction
- increased in woman with luteal phase defects
Cigarette smoking at the time of conception

3. Increased receptivity of tubal mucosa to fertilized ovum

4. Assisted reproduction

Tubal pregnancy : increased following ovulation induction, gamate intrafallopian
transfer, and in vitro fertilization and ovum transfer - with concurrent tubal disease
Heterotypic tubal pregnancy : increased after IVF, ET, and ovulation induction
Abdominal pregnancy : increased after gamate intrafallopian transfer , in vitro
fertilization and ovum transfer
Cervical pregnancy
Ovarian pregnancy

B. Epidemiology

In 1992, almost 2 percent of all pregnancies were ectopic , and ectopic pregnancy-
related deaths accounted for 10 percent of all pregnancy-related deaths
At Parkland hospital the incidence of ectopic pregnancy has more than doubled
in the past decade

* Causes for increased rates of ectopic pregnancy

Increased prevalence of sexually transmitted tubal infections
Popularity of contraception that prevents intrauterine but not extrauterine
pregnancies
Unsuccessful tubal sterilizations
Assisted reproductive techniques
Previous pelvic surgery including salpingotomy for previous tubal pregnancy and
tuboplasty
Exposure to DES in utero
Better and earlier diagnostic technique

C. Mortality

The dramatic decrease in deaths from ectopic pregnancies is probably due to
improved diagnosis and management
85% of women died from hemorrhage
Infection in 5 percent and anesthesia complications in 2 percent

D. Anatomical considerations

Any portion of the oviduct
The ampulla is the most frequent site of implantation and the isthmus the next
most common
Zygote implantation

. promptly burrows

. invades and erodes the subjacent muscularis (lacks a submucosa)

. maternal blood vessels are opened
Uterine changes
- Arias-stella reaction : Epithelial cells are enlarged and their nuclei are
  hypertrophic, hyperchromatic, lobular, and irregularly shaped. A loss of polarity,
  abnormal nuclei tend to occupy the luminal portion of the cells. Cytoplasm may be
  vacuolated and foamy, occasional mitoses are found
- External bleeding : uterine in origin, with degeneration and sloughing of the
  uterine decidua

II. Natural history of tubal pregnancy

A. Tubal abortion

Common in ampullary tubal pregnancy, rupture of the tube is the usual outcome
with isthmic pregnancy
Complete : all of the products of conception may be extruded through the fimbriated
end into the peritoneal cavity->hemorrhage may cease and symptoms eventually
disappear
Products of conception remain in the oviduct, and blood slowly trickles from the
tubal fimbria into the peritoneal cavity and typically pools in the rectouterine
cul-de-sac
Hematosalpinx, placental polyp

B. Tubal rupture

In the first few weeks, isthmic portion of the tube in most cases rupture occurs
spontaneously
Abdominal pregnancy : in such cases, a portion of the placenta remains attached to
the tubal wall and the periphery grows beyond the tube and implants on
surrounding structures
Broad ligament pregnancy : when the original implantation of the zygote is toward
the mesosalpinx, the contents of the gestational sac may be extruded into a space
formed between the folds of the broad ligament.

C. Interstitial pregnancy

Implantation of the fertilized ovum within the segment of tube that penetrates the
uterine wall results in an interstitial or cornual pregnancy
3% of all tubal gestations
Rupture occurs later, between the end of the 8th and 16th gestational weeks
Fatal because the implantation site is located between the ovarian and uterine
arteries
Because of the large uterine defect , hysterectomy is commonly necessary

D. Multifetal ectopic pregnancy

* Heterotypic ectopic pregnancy by a coexisting intrauterine gestation

Assisted reproduction
With persistent or rising chorionic gonadotropin levels after dilation and
curettage for an induced or spontaneous abortion
When the uterine fundus is larger than menstrual dates
With more than one corpus luteum
With absence of vaginal bleeding in the presence of signs and symptoms of
an ectopic pregnancy
When there is ultrasound evidence of uterine and extrauterine pregnancy

* Multifetal tubal pregnancy

III. Clinical and laboratory features of tubal pregnancy

A. Symptoms and signs

1. Pain

Pelvic and abdominal pain (95%)
Gastrointestinal symptoms (80%) and dizziness or light-headedness (58%)
500ml of blood introduced into the peritoneal cavity most often caused abdominal
tenderness, moderate intestinal distention and especially pain in the top of the
shoulder and the side of the neck from diaphragmatic irritation

2. Amenorrhea

Character of the last menstrual period be elicited in detail with respect to time of
onset , duration, and amount of bleeding , and it is advisable to ask whether it
impressed her as abnormal in any way

3. Vaginal spotting or bleeding

Scanty dark brown although profuse vaginal bleeding is suggestive of an incomplete
abortion rather than an ectopic gestation such bleeding can occur with tubal
gestations

4. Abdominal and pelvic pain

Motion of the cervix is demonstrable in over three fourths of women however, such
tenderness may be absent prior to rupture

5. Uterine changes

Because of placental hormones , in about one fourth of cases, the uterus grows
during the first 3 months of a tubal gestation

6. Blood pressure and pulse

In a healthy young woman with an extrauterine pregnancy, blood pressure will fall
and pulse rise only if bleeding continues and hypovolemia becomes significant

7. Hypovolemia

8. Temperature

After acute hemorrhage, normal or even low

9. Pelvic mass

About 20 percent

10. Pelvic hematocele

Absorbed
Form an abscess
Most commonly, however, the hematocele causes continued discomfort and the
physician is finally consulted weeks or even months after the original rupture

B. Laboratory tests

Hemoglobin and hematocrit : for the first few hours after an acute hemorrhage , a
decrease in hemoglobin or hematocrit level is a more valuable index of blood loss
than is the initial reading
Leukocyte count : varies
Pregnancy tests : in virtually all cases of ectopic gestation, chorionic gonadotropin
will be detected in serum, but usually at markedly reduced concentrations compared
with normal pregnancy
- Urinary pregnancy tests
  
  . Latex agglutination inhibition (50-60%)
  
  . Tube-type tests (80-85%)
  
  . ELISA (90-96%)
- Serum chorionic gonadotropin assays
  
  - Radioimmunoassay : in combination with sonography have been developed to
  establish the diagnosis of an extrauterine pregnancy
  
  - Chorionic gonadotropin in peritoneal fluid
Serum progesterone

*In order to establish a diagnosis of normal pregnancy (Yeko and associated)

. ectopic pregnancy : less than 15ng/ml

. live pregnancy : 20ng/ml or higher

. serum progesterone less than 5ng/ml only identifies a nonviable pregnancy

C. Sonography

1. Abdominal sonography

2. Vaginal sonography

A more sensitive and specific technique to diagnose ectopic pregnancy than is
abdominal ultrasound in earlier and more specific diagnoses of intrauterine
pregnancy

* Diagnostic criteria

Identification of a 1 to 3 mm or larger gestational sac, eccentrically placed
in the uterus, and surrounded by a decidual-chorionic reaction

* Accurate clinical diagnosis

An intrauterine pregnancy is identified as described
An empty uterus and an ectopic pregnancy are seen based upon the
demonstration of an adnexal mass separate from two clearly identified ovaries
The study may be nondiagnostic, that is neither adnexal mass or intrauterine
pregnancy sac is identified

* Either repeat serial ultrasound studies or serial sonography along with serial
quantitative β-hCG measurements. In doubtful cases, either laparoscopy or
laparotomy may be necessary

3. Quantitative serum β-hCG plus sonography

Hemodynamically stable : serial quantitative serum β-hCG values and abdominal
or vaginal sonograms

* Kadar and associates

ⓐAbove 6000mIU/ml and an intrauterine gestational sac is seen using abdominal
sonography (1000-2000mIU/ml : vaginal sonography)
ⓑ ⓐ + there is an empty uterine cavity, an ectopic pregnancy is very likely
ⓒ Less 6000mIU/ml : a definite intrauterine ring of pregnancy is visualized then
spontaneous abortion is likely now or very soon
ⓓ ⓒ + empty uterus : suspected ectopic pregnancy

Another plan : concluded that a failure to maintain this rate of increased β-hCG
production, along with an empty uterus, was suggestive evidence for an ectopic
pregnancy.
Table 27-5

* Cacciatore and associates

The uterus was empty
An adnexal mass clearly separate from the ovaries was present
The β-hCG level was greater than 1000mIU/L : sensitivity of 97%, specificity of
99%

4. Culdocentesis

The cervix is pulled toward the symphysis with a tenaculum and a long 16-18
gauge needle is inserted through the posterior vaginal fornix into the cul de sac.
Fragments of old clots, or bloody fluid that does not clot

5. Curettage

Stovall and colleagues : recommend curettage in suspected cases of incomplete
abortion versus ectopic pregnancy when serum progesterone is less than 5ng/ml,
β-hCG levels are rising abnormally (less than 2000mIU/ml) and an intrauterine
pregnancy is not seen using transvaginal sonography

6. Laparoscopy

* Advantages

Definitive diagnosis
A concurrent route to remove the ectopic mass using operative laparoscopy
A direct route to inject chemotherapeutic agents into the ectopic mass

7. Laparotomy

IV. Treatment and prognosis of tubal pregnancy

A. Surgical management

1. Salpingostomy

Less than 2cm in length, in the distal one third of the fallopian tube, unruptured
ectopic pregnancy
The incision is left unsutured
Associated with a higher subsequent pregnancy rate than salpingectomy

2. Salpingotomy

Irrigated with lactated Finger solution (not isotonic saline)
One-layer closure with 7-0 interrupted vicryl sutures
Through an operative laparoscope, preferred surgical method for unruptured tubal
pregnancies exceeding 2cm in length

3. Salpingectomy

An operative laparoscope, both ruptured and unruptured ectopic pregnancies
to excise a wedge no more than the outer third of the interstitial portion
of the tube
Even with cornual resection a subsequent interstitial pregnancy may not be
prevented

4. Segmental resection and anastomosis

Unruptured pregnancy, isthmic portion , salpingotomy or salpingostomy would
likely cause scarring and subsequent narrowing of this small lumen
Interrupted 7-0vicryl sutures

5. Fimbrial evacuation

Milking or suctioning the ectopic mass
Not recommended - an ectopic recurrence rate twice that of salpingotomy

6. Persistent trophoblast

Serum β-hCG levels be determined 2weeks postoperatively to compare with
the original value --> persistent or increasing values, the choice of reexploration
or chemotherapy with methotrexate.

B. Medical management

* Methotrexate

1. Patient selection

Hemodynamically stable with a normal hemogram and normal liver and
renal function
Fails in 5 to 10 percent of cases
Failure of medical therapy means elective surgery or if tubal rupture occurs
emergency surgery
If treated as an outpatient, rapid transportation must be available
Signs and symptoms of tubal rupture such as vaginal bleeding, abnormal and
pleuritic pain, weakness, dizziness, or syncope must be reported promptly
Sexual intercourse is prohibited until after serum β-hCG is undetectable
No alcohol can be consumed
Multivitamins with folic acid should not be taken

2. Monitoring methotrexate toxicity

Serum hepatic enzyme levels or plasma creatinine-increase --> stop
Evidence of bone marrow suppression --> stop
Dermatitis, stomatitis, gastritis, or pleuritis --> stop

3. Monitoring efficacy of therapy

After therapy the hormone usually disappears from plasma between 14
and 21 days
β-hCG : 1. 2. 5. 10 and 15 and every 5 days
Vaginal sonography : 5, 10, 15 and every 5 days
Failure is judged when there is no decline in β-hCG level, persistence of
the ectopic mass, or any intraperitoneal bleeding

4. Systemic therapy

* Stovall and associates

1) 34 of 36 women

Alternating days of intramuscular MTX(1.0mg/kg) followed the next day
by intramuscular citrovorum(0.1mg/kg)
Continued until there was a decline in β-hCG levels of 15%
Daily measurements ,β-hCG, CBC, serum aspartate aminotransferase after the
last drug dose, serum β-hCG was measured 2 to 3 times weekly until it was
less than 10mIU/ml

2) 16 of 17 women

Outpatient MTX for asymptomatic ectopic pregnancy is effective
Tubal rupture can occur as late as 23 days after starting therapy
Fetal cardiac activity is a relative contraindication for chemotherapy
Chemotherapy is contraindicated in symptomatic women
Chemotherapy offers no immediate advantages over laparoscopic surgery

5. Tubal patency and fertility

Both tubal anatomy and function were restored and return of menses was
not delayed
61% intrauterine pregnancies and only 8% have had another ectopic pregnancy

6. Salpingocentesis therapy

MTX injection was likely to be unsuccessful if the initial hCG was more than
2000mIU/ml or the ectopic mass was larger than 2cm

* Other medical therapy

PGF2, E2 analogue : not been widely used, cardiac arrhythmias, transient
hypertension, pulmonary edema, atrioventricular block, expected nausea, vomiting,
and diarrhea

V. Abdominal pregnancy

A. Frequency

1 in 25000 births (Parkland)

B. Etiology

Early rupture or abortion of a tubal pregnancy into the peritoneal cavity -->

neighboring serosa, oviduct, the posterior aspect of the broad ligament and uterus
Gamate intrafallopian transfer, invitro fertilization and ovum transfer and induced
abortion ->increased
Endometriosis, tuberculosis, intrauterine devices

C. Diagnosis

Symptoms : nausea, vomiting, flatulence, constipation, diarrhea, and abdominal pain
Physical finding : abdominal massage over the pregnancy does not stimulate the
mass to contract as it almost always does with advanced intrauterine pregnancy.
Laboratory findings.
- Unexplained transient anemia
- The presence of an otherwise unexplained increase in serum alpha-fetoprotein
  value as such always suggests the possibility of an abdominal pregnancy
- Oxytocin stimulation
- Sonography : suggestive
- MRI : confirm

D. Treatment

* Management of the placenta

In general, the infant should be delivered , the cord severed close to the placenta
and the abdomen closed monitored using ultrasound and a variety of placental
hormones.
Selective embolization of bleeding sites

E. Maternal prognosis

With appropriate preoperative planning maternal mortality has been reduced from
approximately 20% to less than 5% in the last 20years

VI. Ovarian pregnancy

* In 1878, Spiegeberg

The tube on the affected side must be intact
The fetal sac must occupy the position of the ovary
The ovary must be connected to the uterus by the ovarian ligament
Definite ovarian tissue must be found in the sac wall

VII. Cervical pregnancy

1 in 18,000 pregnancies

A. Clinical presentation and diagnosis

1. Symptoms

Usually, painless bleeding appearing shortly after nidation is the first sign
A distended thin-walled cervix with the external os partially dilated may be evident
Above the cervical mass , a slightly enlarged uterine fundus may be palpated

2. Diagnosis

High degree of suspicion and confirmed with either vaginal or abdominal
sonography
Paalman and McElin (1959)
- Uterine bleeding without cramping after a period of amenorrhea
- Softened cervix disproportionately enlarged to a size equal to or larger than the
  corpus
- Complete confinement and firm attachment of the products of conception to the
  endocervix
- A snug internal cervical os
Pathological criteria
- Cervical gonads must be present opposite placental attachment
- Attachment of placenta to cervix must be intimate
- The placenta must be below the entrance of uterine vessels or below the
  peritoneal reflection on the anteroposterior uterine surfaces
- Fetal elements must not be present in the uterine corpus

B. Surgical management

Cerclage, foley catheter, uterine artery embolization : preventing hemorrhage

C. Medical management

MTX has been used successfully to treat cervical pregnancy
Pregnancies greater than 6 weeks generally require induction of fetal death or
high-dose and prolonged MTX therapy