Emergency Medicine Ectopic Pregnancy Case File
Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS
Case 26
A 26-year-old woman presents to the emergency department (ED) with a 6-hour history of worsening abdominal pain. She states the pain initially was a dull pain near her umbilicus but has since moved to her lower right side. She rates the pain as 8 on a scale of 10 and crampy in nature. The patient states that she noted some vaginal spotting this morning, but denies any passage of clots or tissue. The patient ate breakfast that morning, but states she has not eaten since because she feels nauseous. She denies any fever or chills or any change in her bowel habits. Upon further questioning, the patient states her last menstrual period was 2 months ago, but her periods are irregular. She also states that she was told that she had a vaginal infection a year ago but does not recall having been treated for the illness. On physical examination, her blood pressure is 120/76 mm Hg, heart rate is 105 beats per minute, and she is afebrile. In general, she is in mild distress. The abdomen reveals tenderness to palpation in her right lower quadrant that is greater than that in the left lower quadrant. The examination reveals some minimal voluntary guarding, but no rebound tenderness is appreciated. On pelvic examination, the uterus appears mildly enlarged without cervical motion tenderness. There are no masses or tenderness in the adnexal region. Her complete blood count (CBC) reveals a mildly elevated white blood cell count with a left shift. A beta–human chorionic gonadotropin (β-hCG) was 4658 mIU/mL. A transvaginal sonogram reveals an empty uterus but no adnexal masses or free fluid is noted.
⯈ What is the most likely diagnosis?
⯈ What is the next step?
⯈ What is the initial treatment?
ANSWER TO CASE 26:
Ectopic Pregnancy
Summary: A 26-year-old woman complains of severe abdominal pain, nausea, and vaginal spotting. She has a positive pregnancy test, a quantitative β-hCG level of 4658 mIU/mL, and a transvaginal sonogram showing no intrauterine pregnancy.
- Most likely diagnosis: Ectopic pregnancy.
- Next step: Diagnostic versus operative laparoscopy.
- Initial treatment: Establish an IV line and stabilize the patient in preparation for surgery.
ANALYSIS
Objectives
- Understand the diagnosis and workup of ectopic pregnancy.
- Know the different sonographic appearances of ectopic pregnancy.
- Know the common differential diagnoses for lower abdominal pain and be able to consult the appropriate specialties based on the physical examination.
Considerations
This patient presents to the emergency department with complaints of vaginal bleeding, abdominal pain, and a positive pregnancy examination. Her quantitative hCG level is above the threshold of 1200 to 1500 mIU/mL, and no intrauterine pregnancy is seen on transvaginal sonography; thus, her risk for an ectopic pregnancy approaches 85%. Other diagnoses should be considered, such as threatened abortion, incomplete abortion, pelvic inflammatory disease, or appendicitis. Ectopic pregnancy is defined as a pregnancy that develops after implantation of the blastocyst anywhere other than in the lining of the uterine cavity.
Approach To:
Ectopic Pregnancy
DEFINITIONS
ECTOPIC PREGNANCY: Pregnancy that develops after implantation anywhere other than the lining of the uterus.
RUPTURED ECTOPIC PREGNANCY: Ectopic pregnancy that has eroded through the tissue in which it has implanted, producing hemorrhage from exposed vessels.
SALPINGECTOMY: Surgical excision and removal of the oviduct and ectopic pregnancy.
SALPINGOSTOMY: Surgical excision of the ectopic pregnancy with preservation of the tube. The tube remains opened to heal by secondary intention.
CLINICAL APPROACH
Ectopic pregnancy is defined as a pregnancy outside the lining of the uterus, most commonly occurring in the oviduct, but it may also be found in the abdomen, ovary, or cervix. The incidence of the ectopic pregnancy has increased in the United States for three reasons: (1) the increased incidence of salpingitis caused by increased infection with Chlamydia trachomatis or other sexually transmitted diseases, (2) improved diagnostic techniques, and (3) the increase in assisted reproductive technology pregnancies. Other risk factors include prior tubal surgery, previous ectopic pregnancy, use of exogenous progesterone, and a history of infertility agents. The most common presenting symptoms are abdominal pain, absence of menses, and irregular vaginal bleeding. Other symptoms found on physical examination may include a palpable adnexal tenderness, uterine enlargement, tachycardia, hypotension, syncope, peritoneal signs, and fever.
Approximately half of the episodes of ectopic pregnancy are linked to previous salpingitis, although these episodes may be asymptomatic. Prior infections are likely to lead to anatomic tubal pathology that prevents the normal passage of an embryo into the uterus. In the remaining incidences of ectopic pregnancy, an identifying factor cannot be determined and may be linked to a physiologic disorder. Increased levels of estrogen and progesterone interfere with tubal motility and increase the chance of ectopic pregnancy.
Approximately 97% of ectopic pregnancies occur in the oviduct, specifically in the ampullary region. The remainder of ectopic pregnancies implant in the abdomen, cervix, or ovary. Pathogenesis of ectopic pregnancy begins as the embryo invades the lumen of the tube and its peritoneal covering. As the embryo continues to grow, surrounding vessels may bleed into the peritoneal cavity, resulting in a hemoperitoneum. The stretching of the tube results in abdominal pain until necrosis ensues and results in rupture of the ectopic pregnancy.
The differential diagnosis of ectopic pregnancy includes many other gynecologic and surgical illnesses. Most common are salpingitis, threatened or incomplete abortion, ruptured corpus luteum, adnexal torsion, and appendicitis. The diagnosis of ectopic pregnancy must be considered in any woman of reproductive age with abnormal vaginal bleeding and abdominal pain.
Diagnosis of ectopic pregnancy may be aided with the use of transvaginal ultrasound. Visualization of the pelvic organs may reveal the absence of an intrauterine pregnancy, the presence of a complex adnexal mass, or the presence of an embryo in the adnexa. It is important to note that with higher resolution ultrasound, the hCG discriminatory zone is closer to 1200 to 1500 mIU/mL than the traditionally quoted figure of 1500 to 2000 mIU/mL, in which an intrauterine pregnancy is almost always seen on transvaginal sonography. Lack of visualization of an intrauterine gestational sac on transvaginal sonography confers up to an 85% risk of an ectopic pregnancy. At times, sonography can visualize an ectopic pregnancy even with hCG levels lower than this threshold; the level of hCG does not reliably correlate with the size of the ectopic pregnancy. When hCG levels are lower than the above threshold, the ED physician should rely on the clinical impression to diagnose an ectopic pregnancy.
In a reliable and asymptomatic patient whose initial hCG level is below the threshold, a repeat hCG level can be obtained in 48 hours. The hCG should increase by at least 66% over 48 hours; lack of normal rise strongly implies an abnormal pregnancy, although the test does not indicate the location of the pregnancy (ectopic or miscarriage). A definitive diagnosis of ectopic pregnancy can most always be made by direct visualization of the pelvic organs using laparoscopy if the diagnosis remains uncertain.
More pregnancies are associated with in vitro fertilization, which carries a higher risk of ectopic pregnancy, and multiple gestation. Notably, in women who have IVF pregnancies, a proven intrauterine pregnancy may not rule out ectopic pregnancy, since these patients can have heterotopic pregnancies (concomitant intrauterine and ectopic pregnancies).
Treatment options include both medical and surgical therapy. Medical treatment consists of using intramuscular methotrexate, a folinic acid antagonist that interferes with deoxyribonucleic acid (DNA) synthesis, repair, and cellular replication. Actively dividing tissue, such as fetal cell growth is susceptible to methotrexate and may be used for treatment of ectopic pregnancy under specific conditions (Figure 26–1). Methotrexate is found to be more successful if the hCG is less than 5000 mIU/mL, if the fetus is smaller than 3.5 cm, and if there is no detectable fetal cardiac activity. It is important to note that each individual patient may present with different complaints and different levels of hCG, and at times medical management involves multiple doses of methotrexate.
Potential problems associated with medical management of ectopic pregnancy include drug side effects and treatment failure. Some patients treated with methotrexate will develop acute abdominal pain due to the process of “tubal abortion.” In these individuals, pelvic sonography is useful- if the vital signs are stable, and the ultrasound does not show much intra-abdominal fluid, the patient may be observed in the hospital to assess for resolution of the pain. However, those
patients who have hypotension or evidence of intra-abdominal bleeding should go to the operating room.
If medical therapy fails, surgical intervention is necessary. Surgical management commonly consists of laparoscopy and/or laparotomy. A few common surgical techniques used for treatment of ectopic pregnancy include salpingotomy, salpingostomy, and partial salpingectomy. These techniques can be used to treat the majority of unruptured ectopic pregnancy, whereas exploratory laparotomy may be used in cases of ruptured ectopic pregnancy.
COMPREHENSION QUESTIONS
26.1 A 22-year-old woman complains of lower abdominal pain and vaginal spotting. Which of the following tests is the first priority?
A. Pelvic ultrasound
B. KUB (kidneys, ureters, bladder) radiograph
C. hCG level
D. Chlamydia antigen test of the cervix
26.2 A 22-year-old woman underwent methotrexate treatment for an ectopic pregnancy 1 week ago and complains of lower abdominal cramping. She denies vaginal bleeding, dizziness, or vomiting. On examination, her blood pressure is 120/80 mm Hg and her heart rate is 80 beats per minute. The abdomen reveals mild tenderness. Which of the following is the best management?
A. Observation
B. Surgical management of the ectopic pregnancy
C. Administration of folinic acid
D. Transfusion of 2 units of red blood cells
26.3 A 42-year-old woman complains of an acute onset of significant abdominal pain of 6 hours duration. She states that she underwent in vitro fertilization and is currently 8 weeks pregnant. Her blood pressure is 90/60 mm Hg and her heart rate is 110 beats per minute. Her quantitative hCG level is 22,800 mIU/mL. Transvaginal sonography reveals a singleton intrauterine gestation with cardiac activity, and a moderate amount of free fluid in the cul de sac. Which of the following is the most likely diagnosis?
A. Heterotopic pregnancy
B. Ruptured corpus luteum
C. Cirrhosis with ascites
D. Urinary tract infection
26.4 A 33-year-old woman complains of vaginal bleeding and abdominal cramping. She passed some blood clots. Her last menstrual period was 6 weeks previously. On examination her cervical os is open to 1 cm. Her quantitative hCG level is 2000 mIU/mL. Which of the following is the most likely diagnosis?
A. Ectopic pregnancy
B. Incomplete abortion
C. Completed abortion
D. Incompetent cervix
26.5 A 28-year-old woman complains of lower abdominal cramping pain for about 3 hours, and passed what was described as “liver-like” tissue, after which her pain resolved. In the ED, her blood pressure is 120/70 mm Hg and heart rate is 80 beats per minute. Her uterus is firm and the cervix is closed. The hCG level is 2000 mIU/mL. Transvaginal sonography reveals no intrauterine pregnancy. Which of the following is the next step?
A. Laparoscopy
B. Methotrexate therapy
C. Progesterone level
D. Repeat hCG level in 48 hours
ANSWERS
26.1 C. In general, any woman in the childbearing age group with abdominal pain or abnormal vaginal bleeding should have a pregnancy test. If pregnant, then ectopic pregnancy should be ruled out.
26.2 A. A large number of women who undergo methotrexate treatment of ectopic pregnancy will have some abdominal discomfort. As long as there are no signs of rupture such as hypotension, severe pain, or free fluid on ultrasound, expectant management may be practiced.
26.3 A. In vitro fertilization with embryo transfer produces a rate of coexisting intrauterine pregnancy and ectopic pregnancy of up to 3% (markedly higher than the spontaneous rate of 1:10,000). Thus, a woman who has undergone in vitro fertilization who presents with abdominal fluid and hypotension must be suspected as having an ectopic pregnancy, even when an intrauterine pregnancy has been visualized on sonography.
26.4 B. The presence of uterine cramping, vaginal bleeding, passage of tissue, and an open cervical os in a pregnant woman is consistent with an incomplete abortion. Uterine curettage would be the therapy.
26.5 D. This patient likely has a completed abortion with the resolution of symptoms following passage of tissue and now with a small uterus and closed cervical os. Nevertheless, there is still a possibility of ectopic pregnancy and perhaps the “tissue” passed was only blood clot. The tissue should be sent for pathologic analysis. Also, a repeat hCG level should be performed to ensure that all tissue has passed. The hCG level should fall by about 50% in 48 hours if all tissue has passed. A plateau in the hCG level may indicate incomplete abortion or ectopic pregnancy. Dilation and curettage would generally be performed, and if chorionic villi found the diagnosis is miscarriage; absence of chorionic villi establishes the diagnosis of ectopic pregnancy which may be treated by surgery or methotrexate.
CLINICAL PEARLS
⯈ In any woman of childbearing age, consider pregnancy. If the pregnancy test is positive, consider an ectopic pregnancy.
⯈ Consider pregnancy even when a woman has had a tubal ligation or is using contraception.
⯈ When the serum quantitative hCG level is above 1500 to 2000 mIU/mL and transvaginal ultrasound does not reveal an intrauterine pregnancy, the risk of ectopic pregnancy is high.
⯈ Surgery, not methotrexate, is the best treatment for the patient who is hemodynamically unstable or with significant abdominal pain.
⯈ Laparoscopy remains the gold standard for ectopic pregnancy.
References
Cunningham FG, Leveno KJ, Bloom SL, et al. Ectopic pregnancy. In: Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY, eds. Williams Obstetrics. 23rd ed. New York, NY: McGraw- Hill; 2010: Chapter 10.
Hoover KW, Tao G, Kent KC. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. ACOG. March 2010;115(3):495-502.
Silva C, Sammel MD, Zhou L, et al. Human chorionic gonadotropin profile for women with ectopic pregnancy. ACOG. March 2006;107(3):605-610.
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