Case 43. Ectopic Pregnancy

 A 19-year-old G2P0 Ab1 woman at 7 weeks’ gestation by last menstrual period

(LMP) complains of vaginal spotting. She denies the passage of tissue per

vagina, any trauma, or recent intercourse. Her past medical history is significant for a pelvic infection approximately 3 years ago. She had used an oral

contraceptive agent 1 year previously. Her appetite is normal. On examination, her blood pressure (BP) is 100/60 mm Hg, heart rate (HR) is 90 beats per

minute (bpm), and temperature is afebrile. The abdomen is nontender with

normoactive bowel sounds. On pelvic examination, the external genitalia are

normal. The cervix is closed and nontender. The uterus is 4 weeks’ size, and no

adnexal tenderness is noted. The quantitative beta-human chorionic gonadotropin (β-hCG) is 2300 mIU/mL (Third International Standard). A transvaginal

sonogram reveals an empty uterus and no adnexal masses.

» What is your next step?

» What is the most likely diagnosis?

CASE 43

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ANSWERS TO CASE 43:

Ectopic Pregnancy

Summary: A 19-year-old G2Ab1 woman at 7 weeks’ gestation by LMP has vaginal

spotting. Her history is significant for a prior pelvic infection. H er BP is 100/ 60

mm H g, H R is 90 bpm, and her abdomen is nontender. Pelvic examination shows

a closed and nontender cervix, a uterus of 4 weeks’ size, and no adnexal tenderness. The quantitative β-hCG is 2300 mIU/ mL (Third International Standard). A

transvaginal sonogram reveals an empty uterus and no adnexal masses.

 Next step: Laparoscopy.

 Most likely diagnosis: Ectopic pregnancy.

ANALYSIS

Objectives

1. Understand that any woman with amenorrhea and vaginal spotting or lower

abdominal pain should have a pregnancy test to evaluate the possibility of

ectopic pregnancy.

2. Understand the role of the hCG level and the threshold for transvaginal sonogram.

3. Know that the lack of clinical or ultrasound signs of ectopic pregnancy does

not exclude the disease.

Considerations

The woman is at 7 weeks’ gestation by last menstrual period and presents with

vaginal spotting. Any woman with amenorrhea and vaginal spotting should have a

pregnancy test. The physical examination is normal. Notably, the uterus is slightly

enlarged at 4 weeks’ gestational size. The enlarged uterus does not exclude the diagnosis of an ectopic pregnancy, due to the human chorionic gonadotropin effect on

the uterus. The lack of adnexal mass or tenderness on physical examination likewise does not rule out an ectopic pregnancy. The hCG level and transvaginal ultrasound are key tests in the assessment of an extrauterine pregnancy. The ultrasound

is primarily used to assess for the presence or absence of an intrauterine pregnancy

(IUP), because a confirmed IUP would decrease the likelihood of an ectopic pregnancy significantly (risk 1:10,000 of both an intrauterine and ectopic pregnancy,

that is, heterotopic pregnancy). Also, the presence of free fluid in the peritoneal

cavity, or a complex adnexal mass, would make an extrauterine pregnancy more

likely. This woman’s hCG level of 2300 mIU/ mL is greater than the threshold of

1500 to 2000 mIU/ mL (transvaginal sonography); thus, the patient has a high

likelihood of an ectopic pregnancy. Although the risk of an extrauterine pregnancy

is high, it is not 100%. Therefore, laparoscopy is indicated, and not methotrexate,

since the latter would destroy any intrauterine gestation.

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APPROACH TO:

Possible Ectopic Pregnancy

DEFINITIONS

ECTOPIC PREGNANCY: A gestation that exists outside of the normal endometrial implantation sites.

HUMAN CHORIONIC GONADOTROPIN: A glycoprotein produced by syncytiotrophoblasts, which is assayed in the standard pregnancy test.

THRESHOLD HCG LEVEL: The serum level of hCG where a pregnancy should

be seen on ultrasound examination. When the hCG exceeds the threshold and no

pregnancy is seen on ultrasound, there is a high likelihood of an ectopic pregnancy.

LAPAROSCOPY: Surgical technique to visualize the peritoneal cavity through a

rigid telescopic instrument, known as a laparoscope.

CLINICAL APPROACH

See also Case 42 (Spontaneous Abortion).

The vast majority of ectopic pregnancies involve the fallopian tube (97%), but

the cervix, or cornua (the portion of the tube that traverses the uterine muscle),

abdominal cavity, and ovary have also been affected. In the United States, 2% of

pregnancies are extrauterine. H emorrhage from ectopic gestation is the most common reason for maternal mortality in the first 20 weeks of pregnancy. Risk factors

for ectopic pregnancy are summarized in Table 43– 1.

A woman with an ectopic pregnancy typically complains of abdominal pain,

amenorrhea of 4 to 6 weeks’ duration, and irregular vaginal spotting. In the case

of a ruptured ectopic, the pain becomes acutely worse, and may lead to syncope.

Shoulder pain can be a prominent complaint due to the blood irritating the diaphragm. An ectopic pregnancy can lead to tachycardia, hypotension, or orthostasis.

Abdominal or adnexal tenderness is common. An adnexal mass is only palpable half

the time; hence, the absence of a detectable mass does not exclude an ectopic pregnancy. The uterus may be normal in size, or slightly enlarged. A hemoperitoneum

can be confirmed by the aspiration of nonclotting blood with a spinal needle piercing the posterior vaginal fornix into the cul-de-sac (culdocentesis).

Table 43–1 • RISK FACTORS FOR ECTOPIC PREGNANCY

Salpingitis, particularly with Chlamydia trachomatis

Tubal adhesive disease

Infertility

Progesterone-secreting IUD

Tubal surgery

Prior ectopic pregnancy

Ovulation induction

Congenital abnormalities of the tube

Assisted reproductive technology

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The diagnosis of an ectopic pregnancy can be a clinical challenge. The differential diagnosis is noted in Table 43– 2.

The usual strategy in ruling out an ectopic pregnancy is to try to prove whether

an intrauterine pregnancy (IUP) exists. Because the likelihood of a coexisting intrauterine and extrauterine (heterotopic) gestation is so low, in the range of 1 in 10 000,

if a definite IUP is demonstrated, the risk of ectopic pregnancy becomes very low.

Transvaginal sonography is more sensitive than trans-abdominal sonography, and

can detect pregnancies as early as 5.5 to 6 weeks’ gestational age. Hence, the demonstration of a definite IUP by crown-rump length or yolk sac is reassuring. The

“identification of a gestational sac” is sometimes misleading since an ectopic pregnancy can be associated with an irregularly shaped fluid collection in the midline

of the uterine cavity, a so-called “pseudogestational sac.” A normal gestational sac

would be eccentrically located and have a decidual sign, which is an echogenic rim

around the gestational sac that is absent in a pseudogestational sac. Other sonographic findings of an extrauterine gestation include an embryo seen outside the

uterus, or a large amount of intra-abdominal free fluid, usually indicating blood.

Often, the quantitative human chorionic gonadotropin level is used in conjunction with transvaginal sonography. When the hCG level equals or exceeds 1500 to

2000 mIU/ mL, an intrauterine gestational sac is usually seen on transvaginal ultrasound; in fact, when the hCG level meets or exceeds this threshold and no gestational

sac is seen, the patient has a high likelihood of an ectopic pregnancy. (If there is a high

suspicion of multiple gestation, where hCG levels can be higher than singletons at any

comparable gestational age, this threshold may not apply.) Laparoscopy is usually

performed in this situation. When the hCG level is less than the threshold, and

the patient does not have severe abdominal pain, hypotension, or adnexal tenderness and/ or mass, then a repeat hCG level in 48 hours is permissible. A rise in the

hCG of at least 53% above the initial level is good evidence of a normal pregnancy;

in contrast, a lack of an appropriate rise of the hCG is indicative of an abnormal

pregnancy, although the abnormal change does not identify whether the pregnancy

is in the uterus or the tube. Some practitioners will use a progesterone level instead

of serial hCG levels to assess the health of the pregnancy. A progesterone level of

greater than 25 ng/ mL almost always correlates with a normal intrauterine pregnancy, whereas a level of < 5 ng/ mL almost always correlates with an abnormal

pregnancy.

Treatment of an ectopic pregnancy may be surgical or medical. Salpingectomy

(removal of the affected tube) is usually performed for those gestations too large

Table 43–2 • DIFFERENTIAL DIAGNOSIS OF ECTOPIC PREGNANCY

Acute salpingitis

Abortion

Ruptured corpus luteum

Acute appendicitis

Dysfunctional uterine bleeding

Adnexal torsion

Degenerating leiomyomata

Endometriosis

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for conservative therapy, when rupture has occurred, or for those women who do

not want future fertility. For a woman who wants to preserve her fertility and has

an unruptured tubal pregnancy, a salpingostomy can be performed (Figure 43– 1).

An incision is carried out along the long axis of the tube, and the pregnancy tissue is removed. The incision on the tube is not re-approximated because suturing

may lead to stricture formation. Conservative treatment of the tube is associated

with a 10% to 15% chance of persistent ectopic pregnancy. Serial hCG levels are,

therefore, required with conservative surgical therapy to identify this condition.

Methotrexate, a folic acid antagonist, is the principal form of medical therapy.

It is usually given as a one-time, low-dose, intramuscular injection, reserved for

ectopic pregnancies less than 3.5 cm in diameter, without fetal cardiac activity, and

hCG levels < 5000 mIU/ mL. Methotrexate is highly successful, leading to resolution of properly chosen ectopic pregnancies in 85% to 90% of cases. Occasionally,

a second dose is required because the hCG level does not fall. Between 3 and 7

days following therapy, a patient may complain of abdominal pain, which is usually

Figure 43–1. Salpingostomy. Needle-point cautery is used to incise over the ectopic pregnancy (A).

The pregnancy tissue is extracted (B) and heals without closure of the incision (C).

A

B

C

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due to tubal abortion and, less commonly, rupture. Most women may be observed;

however, hypotension, worsening or persistent pain, or a falling hematocrit may

indicate tubal rupture and necessitate surgery. About 10% of women treated with

medical therapy will require surgical intervention.

Rare types of ectopic gestations such as cervical, ovarian, abdominal, or cornual

(moved to above) pregnancies usually require surgical therapy.

CASE CORRELATION

 See also Case 13 (Abdominal Pain in Pregnancy), Case 41 (Threatened and

Completed Abortion). A patient who presents with threatened abortion may

have a normal IUP, an abnormal IUP (miscarriage), or an ectopic pregnancy.

COMPREHENSION QUESTIONS

43.1 A 22-year-old woman at 8 weeks’ gestation has vaginal spotting. H er physical

examination reveals no adnexal masses. The hCG level is 400 mIU/ mL and

the transvaginal ultrasound shows no pregnancy in the uterus and no adnexal

masses. Which of the following is the next best step?

A. Laparoscopy

B. Methotrexate

C. Repeat the hCG level in 48 hours

D. Dilatation and curettage

43.2 A 26-year-old G2P1 woman at 7 weeks’ gestation was seen 1 week ago with

crampy lower abdominal pain and vaginal spotting. H er hCG level was 1000

mIU/ mL at that time. Today, the woman does not have abdominal pain or

passage of tissue per vagina. Her repeat hCG level is 1100 mIU/ mL. A transvaginal ultrasound examination today shows no clear pregnancy in the uterus

and no adnexal masses. Which of the following can be concluded based on

the information presented?

A. The woman has a spontaneous abortion and needs a dilation and

curettage.

B. The woman has an ectopic pregnancy.

C. No clear conclusion can be drawn from this information, and the hCG

needs to be repeated in 48 hours.

D. The woman has a nonviable pregnancy, but its location is unclear.

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43.3 A 17-year-old woman with lower abdominal pain and spotting comes into

the emergency room. She is noted to have an hCG level of 1000 mIU/ mL and

a progesterone level of 26 ng/ mL. Which of the following is the most likely

diagnosis?

A. This is most likely a normal intrauterine pregnancy.

B. This is most likely an ectopic pregnancy.

C. This is most likely a nonviable intrauterine pregnancy.

D. No clear conclusion can be drawn from this information.

43.4 Which of the following statements describe the primary utility of the transvaginal ultrasound in the assessment of an ectopic pregnancy?

A. Assessment of an intrauterine pregnancy

B. Assessment of adnexal masses

C. Assessment of fluid in the peritoneal cavity

D. Color Doppler flow in the adnexal region

43.5 A 29-year-old woman complains of syncope. She is 6 weeks’ pregnant and on

examination has diffuse significant lower abdominal tenderness. The pelvic

examination is difficult to accomplish due to guarding. H er hCG level is 400

mIU/ mL and the transvaginal ultrasound shows no pregnancy in the uterus

and no adnexal masses. Which of the following is the next best step?

A. Follow-up hCG level in 48 hours

B. Institution of methotrexate

C. Observation in the hospital

D. Surgical therapy

ANSWERS

43.1 C. When the hCG is below the threshold in an asymptomatic patient, the hCG

level may be repeated in 48 hours to assess for viability. If the hCG level

had been above the threshold in this patient, the chances that an extrauterine pregnancy exists would be even more likely (close to 100%), laparoscopy

would be indicated to confirm suspicion. Since there is still a chance that this

is a viable pregnancy, methotrexate should not be used since it could destroy

any intrauterine gestation. Dilation and curettage would also destroy any

viable intrauterine pregnancy, and would not be a good option for treatment

of an ectopic pregnancy since they exist outside the uterus.

43.2 D. A plateau in hCG over 48 hours means it is a nonviable pregnancy; this

finding does not identify the location of the pregnancy. Levels of hCG that

plateau in the first 8 weeks of pregnancy indicate an abnormal pregnancy,

which may be either a miscarriage or an ectopic pregnancy. It is unlikely that

this patient had an incomplete or a completed abortion, given that she does

not recall any passage of tissues.

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43.3 A. A progesterone level greater than 25 ng/ mL reflects a normal IUP. This

patient’s hCG level is below the threshold of being visible on ultrasound,

so it is a very early pregnancy. Spotting and lower abdominal pain can be a

normal occurrence in pregnancy, especially very early in the first trimester.

Some patients have symptoms of lower abdominal pain, similar to menstrual

cramps, and vaginal spotting during the first few weeks of pregnancy when

the embryo implants into the wall of the uterus.

43.4 A. The best use of ultrasound for assessment of an ectopic pregnancy is to

diagnose an IUP, as an IUP and coexisting ectopic pregnancy is very rare.

Color Doppler flow in the adnexal region is typically used when there is suspicion of ovarian torsion and concern that the ovarian vessels are constricted

and unable to perfuse the ovaries. Assessment of adnexal masses using transvaginal ultrasound is not very specific. A hemoperitoneum can be confirmed

by culdocentesis, but not typically a transvaginal ultrasound (one could argue

that with current ultrasound technology, clotted blood appears different

from simple fluid and hemoperitoneum that is clotted can be diagnosed by

ultrasound, especially if in pouch of Douglas).

43.5 D. Surgery is indicated. Although this woman has an hCG level lower than

the threshold, she has an acute abdomen and this is most likely due to a

ruptured ectopic pregnancy. If not addressed, the patient may exsanguinate.

Methotrexate requires several days to weeks to act, and is appropriate in an

asymptomatic patient with an ectopic pregnancy less than 3.5 cm in size.

CLINICAL PEARLS

» Levels of hCG that plateau in the first 8 weeks of pregnancy indicate an

abnormal pregnancy, which may either be a miscarriage or an ectopic

pregnancy.

» The classic triad of ectopic pregnancy is amenorrhea, vaginal spotting,

and abdominal pain.

» When the quantitative hCG exceeds 1500 to 2000 mIU/mL and the transvaginal sonogram does not show an intrauterine gestational sac, then

the risk of ectopic pregnancy is high.

REFERENCES

American College of Obstetricians and Gynecologists. Medical management of ectopic pregnancy.

ACOG Practice Bulletin 94. Washington, DC; 2008. (Reaffirmed 2014.)

Lobo RA. Ectopic pregnancy. In: Lentz GM, Lobo RA, Gersenson DM, Katz VL, eds. Comprehensive

Gynecology. 6th ed. Philadelphia, PA: Elsevier-Mosby; 2012:361-382.

Shamonki M, Nelson AL, Gambone JC. Ectopic pregnancy. In: H acker NF, Gambone JC, H obel CJ, eds.

Essentials of Obstetrics and Gynecology. 6th ed. Philadelphia, PA: Saunders; 2015:290-297.