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
  • Unsuccessful tubal sterilizations
  • Assisted reproductive techniques
  • Previous pelvic surgery including salpingotomy for previous tubal pregnancy and
  • 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

  • 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

  • Hematosalpinx, placental polyp

B. Tubal rupture

  • In the first few weeks, isthmic portion of the tube in most cases rupture occurs

  • 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

  • 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

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

  1. 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

  2. Leukocyte count : varies

  3. 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

  4. 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

* 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

  • 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

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

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
  • 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

  1. The tube on the affected side must be intact

  2. The fetal sac must occupy the position of the ovary

  3. The ovary must be connected to the uterus by the ovarian ligament

  4. 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
  • 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
    • Complete confinement and firm attachment of the products of conception to the
    • 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