by Dan O’Brien
An ectopic pregnancy occurs when a fertilized egg implants somewhere other than the main cavity of the uterus. The true incidence worldwide is uncertain; however, in the United States, the incidence ranges from 2.7 to 6 deaths per 10,000 live births. Approximately 1%-2% of pregnancies in the United States are ectopic and ectopic pregnancy accounts for 3%-4% of pregnancy-related deaths. Ectopic pregnancy remains the leading cause of maternal death in the first trimester of pregnancy and is the second leading cause of maternal mortality. Early diagnosis and appropriate management may prevent serious adverse outcomes and potentially improve subsequent fertility.
A 24-year-old woman presents to the emergency department with the complaint of lower abdominal pain and vaginal spotting. She has never been pregnant. Her last normal menstrual period was two months ago. She had light spotting last month and states that her period this month is late.
Her history is notable for one episode of lower abdominal pain two years ago thought to be the pelvic inflammatory disease that responded to a two-week course of oral antibiotics. She has no medical allergies and is not on any medications. Review of systems and family history are unremarkable. Her social history is significant in that she is in a monogamous relationship and is not using birth control.
Her general appearance is that of a well-developed female with a temperature of 37ºC, a blood pressure of 110/70 mm Hg and a pulse of 90 bpm. An examination of her abdomen reveals normal bowel sounds, no masses, distension, organomegaly or rebound tenderness. She is mildly tender to palpation in the left lower quadrant. Pelvic exam reveals left adnexal tenderness without palpable masses. The rectal exam is normal with hemoccult negative stool.
Pertinent lab values: urine dip pregnancy testing is positive, quantitative serum B-hCG is 2000 mIU/mL, hemoglobin 13 gr/dL, hematocrit 40%. She is Rh-positive. A transvaginal ultrasound performed by the emergency physician during the pelvic exam fails to demonstrate an intrauterine pregnancy. There is a small amount of fluid in the rectouterine cul-de-sac. 2 cm ectopic pregnancy was identified.
Two large-bore IV’s were started, the patient was crossmatched for blood and OB-GYN was consulted. Treatment options were discussed.
Critical Bedside Actions and General Approach
Given the consequences of missing an ectopic pregnancy, all women of childbearing years with abdominal or pelvic pain with or without vaginal bleeding must have ectopic pregnancy excluded. Once the diagnosis is entertained, the first step is to determine whether the patient is hemodynamically stable. Most ectopic pregnancies are stable on presentation. Alternatively, any woman of childbearing years with abdominal or pelvic complaints and unstable vitals should be considered to have a ruptured ectopic pregnancy.
An essential step is to determine if the patient is pregnant. The easiest method is to determine the presence of the ß subunit of human chorionic gonadotropin (ß-hCG) in the urine or serum. Qualitative urines tests can be easily performed at the bedside. Urine testing is positive when ß-hCG is greater than 20 mIU/mL in the urine. Although dilute urine may reduce sensitivity, at this level of detection, the false negative rate will be less than one percent. Quantitative serum testing should be obtained as well since the serum ß-hCG level may assist subsequent disposition.
It is important to determine the Rh factor status of the mother. An ectopic pregnancy can sensitize an Rh factor negative mother to Rh-positive fetal blood. Obtaining a type and screen on a stable patient is the most efficient method. A baseline complete blood count is warranted.
Other causes of abdominal or pelvic pain with vaginal bleeding in the first twenty weeks of pregnancy include abortion, implantation bleeding, and gestational trophoblastic disease. Abdominal or pelvic pain causes without bleeding may include gallbladder disease, appendicitis, and hyperemesis. Urinalysis, electrolytes, and liver function studies should be considered.
Abdominal or pelvic pain is a common complaint in the emergency department with an extensive differential. All patients who are in childbearing age should be suspected and investigated for appendicitis, endometriosis, ovarian cyst, ovarian torsion, pelvic inflammatory disease, renal colic, and urinary tract infection. In the pregnant patients, however, intrauterine pregnancy, implantation bleeding, threatened abortion, inevitable abortion, corpus luteal cyst, molar pregnancy, and ectopic pregnancy possibilities should be evaluated.
History and Physical Exam Hints
“A 24-year-old woman presents to the emergency department with the complaint of lower abdominal pain and vaginal spotting. She has never been pregnant. Her last normal menstrual period was two months ago. She had light spotting last month and states that her period this month is late.”
From the emergency physician perspective, the differential diagnosis of a woman with a positive pregnancy test and abdominal or pelvic complaint is broad and will require, in almost all instances in the first trimester, an abdominal and pelvic exam.
Although abdominal pain is reported in 90% of ectopic pregnancies, vaginal bleeding in more than half and menstrual irregularities in up to 70%, none of these symptoms narrow the diagnosis enough to include or exclude the diagnosis of ectopic pregnancy reliably. The classic triad of abdominal pain, vaginal bleeding and amenorrhea is not specific for ectopic pregnancy and, in fact, occurs more frequently with other more common complaints such as spontaneous abortion. Therefore, ectopic pregnancy should be considered in any women of childbearing age who presents with an abdominal or pelvic complaint.
“An examination of her abdomen reveals normal bowel sounds, no masses, distension, organomegaly or rebound tenderness. She is mildly tender to palpation in the left lower quadrant. Pelvic exam reveals left adnexal tenderness without palpable masses. The rectal exam is normal with hemoccult negative stool.”
Unfortunately, the physical exam may not be helpful in distinguishing the ectopic pregnancy from other causes of abdominal or pelvic symptoms. In cases of ruptured ectopic pregnancy, a patient may present in shock, with peritoneal signs on the abdominal and pelvic exam. Vital signs are likely normal. The abdominal exam may be nonspecific, the pelvic exam may reveal normal or minor cervical motion tenderness. The uterus may be normal size, and there may be minimal bleeding in the vaginal vault. In fact, patients with unruptured ectopic pregnancies may present identically as a healthy pregnancy.
Emergency and Diagnostic Tests and Interpretations
“Pertinent lab values: urine dip pregnancy testing is positive, quantitative serum B-hCG is 2000 mIU/mL, hemoglobin 13 gr/dL, hematocrit 40%. She is Rh-positive.”
The patient is pregnant. The primary goal at this point is to determine if an intrauterine pregnancy (IUP) is present. From the emergency physician perspective, an intrauterine pregnancy proven by transabdominal or transvaginal sonography may safely rule out an ectopic pregnancy. She is Rh positive and therefore not at risk for alloimmunization.
Advances in ultrasound imaging and the capability of emergency physicians to perform transabdominal and transvaginal imaging have enhanced patient safety and improved clinical accuracy. There is no definitive guideline regarding sequencing the transabdominal and transvaginal study. In a stable patient, it is reasonable to perform the transvaginal ultrasound exam with the vaginal exam. The exams complement the other. If there is no IUP identified, it is reasonable to search for free fluid in the abdomen. If the vaginal exam is delayed or the patient is judged low risk, a transabdominal exam to identify an IUP may suffice.
Figure 1 Intrauterine pregnancy. Transvaginal image. Normal early pregnancy. Note yolk sac (red) and intrauterine gestational sac (yellow)
UP had been considered to exclude ectopic pregnancy. The incidence of heterotopic pregnancy may be as low as 1 in 30,000 pregnancies. However, it is as high as 1 in 100 in pregnants who have undergone in vitro fertilization or have taken ovulation-inducing drugs.
“Transvaginal ultrasound performed by the emergency physician during the pelvic exam fails to demonstrate an intrauterine pregnancy. There is a small amount of fluid in the rectouterine cul-de-sac. 2 cm ectopic pregnancy was identified.”
Figure 2 Transvaginal ultrasound of embryo in the adnexa next to the empty uterus
Figure 3 Evidence of living embryo on M-mode. M-mode pictorially describes temporal changes at a given depth on one axis while measuring time in the second axis. The fluttering noted is cardiac activity.
Figure 4 A small amount of free fluid is noted in the cul-de-sac (red). Don’t confuse endometrial reaction typical of pregnancy (yellow) for a gestational sac. An ectopic pregnancy (green) is noted in the adnexa.
Video 1 Ectopic Pregnancy – Transvaginal Ultrasound
Figure 5 A pseudo-gestational sac (red), is a collection of intrauterine fluid and may be confused with a true gestational sac. A true gestational sac is normally embedded in the endometrium rather than in the uterine cavity, contains a yolk sac typically seen at 5.5 weeks and has a characteristic double ring or double decidual sign at 4-6.5 weeks.
Laparoscopy should be considered in patients with suspected ectopic pregnancy and nondiagnostic vaginal ultrasound. It is both diagnostic and therapeutic.
Culdocentesis involves extracting fluid from the rectouterine pouch posterior to the vagina through a needle. It has been supplanted by the ß-hCG and ultrasound but may be useful when ultrasound is not available.
Emergency Treatment Options
“Two large-bore IV’s were started, the patient was cross-matched for blood and OB-GYN was consulted. Treatment options were discussed.”
Ectopic pregnancy requires consultation with OB-GYN. If the patient is unstable; resuscitation, urgent consultation, and laparoscopic or open surgery are indicated. In this instance, IV access was established, the patient was typed and cross-matched for blood. The OB-GYN surgeon elected laparoscopic surgery. Ectopic pregnancy was confirmed in the left fallopian tube which was successfully removed.
If the patient is stable and the ectopic is early (ß-hCG levels < 3000 mIU/mL) the consulting OB-GYN physician may consider medical management with methotrexate. The surgeon, not the emergency physician, should decide the treatment.
The Discriminatory Zone
If the urine ß-hCG is positive, but the transvaginal ultrasound does not demonstrate an IUP, the emergency physician should consider a concept known as the “discriminatory zone.” The discriminatory zone is the level of serum ß-hCG above which an examiner should be able to see an IUP. With transvaginal ultrasound, an IUP should be seen with a ß-hCG level above 1500 mIU/mL and with transabdominal above 6000 mIU/mL. If the serum ß-hCG is above 1500 mIU/mL and transvaginal sonography does not identify an IUP, consultation with OB-GYN is essential. These patients should be presumed to have an ectopic pregnancy. Additional diagnostic techniques may include laparoscopy or dilation and curettage.
If the serum ß-hCG is below 1500 mIU/mL, the patient is at low risk, and with the concurrence with OB-GYN consultant, the patient may be discharged with follow-up in two days for reexamination and repeat ß-hCG levels.
ß-hCG levels rise rapidly during the first ten weeks of pregnancy then plateau. Although pathologic pregnancies often have lower ß-hCG levels than normal pregnancies, there is significant overlap, and absolute levels are not helpful in distinguishing a normal from abnormal pregnancy. A general advisory rule is that ß-hCG levels double every 48 hours in a normal pregnancy. However, even here there is significant variation and some controversy. In stable patients, serial measurements and repeated sonography may be used to raise or lower suspicion of an occult ectopic pregnancy.
The ß-hCG level representing the discriminatory zone is dependent on the technique and capabilities of the examiner and equipment. The discriminatory zone should not be used to determine viability or treatment plan associated with an IUP.
Documented ectopic pregnancies have presented with a ß-hCG level below test resolution. Therefore do not forgo transvaginal ultrasound investigation in any pregnant patient with a serum ß-hCG below 1500 mIU/mL.
If an ectopic is diagnosed in an unstable patient, that patient will require resuscitation, urgent consultation, and surgical intervention.
If an unruptured ectopic is diagnosed in a stable patient, the consulting OB-GYN surgeon may consider surgical or medical intervention based on the characteristics of the ectopic, patient risk factors and stability. Many of the patients managed medically may be discharged with close follow up and strict return instructions. Patients treated with methotrexate who return may represent a unique challenge as the pain associated with methotrexate-induced tubal abortion may not be readily distinguishable from a ruptured ectopic.
A consulting OB-GYN should evaluate a pregnant patient with a ß-hCG above the discriminatory zone but without evidence of IUP. Laparoscopic surgery is often diagnostic and, in the case of an ectopic pregnancy, is often therapeutic.
A pregnant patient with a ß-hCG below the discriminatory zone and without evidence of IUP may be discharged with the concurrence of the consulting OB-GYN surgeon for close outpatient follow up and serial exams. A portion of these patients will subsequently be diagnosed as an IUP, an ectopic pregnancy, or a threatened, incomplete or completed miscarriage.
References and Further Reading
- CDC. Pregnancy-related mortality surveillance—United States, 1991– 1999. MMWR 2003;52
- Saraiya M, Berg CJ, Shulman H, et al. Estimates of the annual number of clinically recognized pregnancies in the United States, 1981–1991. Am J Epidemiol 1999;149:1025–9
- Berg CJ, Callaghan WM, Syverson C, et al. Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol 2010;116:1302–9
- Creanga AA, Shapiro-Mendoza CK, Bish CL, et al. Trends in ectopic pregnancy mortality in the United States 1980–2007. Obstet Gynecol 2011;117:837–43
- CDC. Surveillance for ectopic pregnancy- United States, 1970-1989. MMWR 1193;42(SS-6)
- Montagnana M, Trenti T, Aloe R, et al. Human chorionic gonadotropin in pregnancy diagnostics. Clinica Chimica Acta 2011;412:1515-1520
- Heaton HA; Ectopic Pregnancies and Emergencies in the First 20 Weeks of Pregnancy;Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, chapter 98, 8th ed. McGraw Hill, 2016. Tintinalli, Stapczynski, Ma, Cline, Meckler, Yealy (Eds.)
- Dart RG, Kaplan B, Varaklis. Predictive value of history and physical exam in patients with suspected ectopic pregnancy. Ann Emerg Med 1999 Mar;33(3):283-90
- American College of Emergency Physicians: Clinical policy: critical issues in the initial evaluation and management of patients presenting to the emergency department in early pregnancy. Ann Emerg Med 60: 381, 2012
- Emergency Ultrasound Guidelines. Annals of Emergency Medicine 53(4): 550-570
- Clayton HB, Schieve LA, Peterson HB, et al: Ectopic pregnancy risk with assisted reproductive technology procedures. Obstet Gynecol 107: 595, 2006
- Grynberg M, Teyssedre J, Andre C, et al. Rupture of ectopic pregnancy with negative serum beta-hCG leafing to hemorrhagic shock. Obstet Gynecol. 2009 Feb;113(2 Pt 2):537-9