Ectopic Pregnancy Case File
Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD
CASE 43
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.
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ANSWER 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. Her BP is 100/ 60 mm Hg, HR 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
- 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.
- Understand the role of the hCG level and the threshold for transvaginal sonogram.
- 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.
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. Hemorrhage 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).
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 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).
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).
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 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.
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CASE CORRELATION
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COMPREHENSION QUESTIONS
43.1 A 22-year-old woman at 8 weeks’ gestation has vaginal spotting. Her 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. LaparoscopyB. MethotrexateC. Repeat the hCG level in 48 hoursD. 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. Her 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.
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 pregnancyB. Assessment of adnexal massesC. Assessment of fluid in the peritoneal cavityD. 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. Her 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 hoursB. Institution of methotrexateC. Observation in the hospitalD. 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.
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
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» 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, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 6th ed. Philadelphia, PA: Saunders; 2015:290-297.
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