Ectopic Pregnancy
Virginia Mensah
Melissa Yates
An ectopic pregnancy (EP) occurs when a fertilized ovum implants outside of the uterine cavity.
EPIDEMIOLOGY OF ECTOPIC PREGNANCY
Two percent of all first-trimester pregnancies and 6% of all pregnancy-related deaths
EP is the leading cause of death in the first trimester.
At least one third of pregnancies that occur after tubal sterilization procedures are EPs.
Women who use an intrauterine device (IUD) have an overall decreased risk of both intrauterine and extrauterine pregnancies. However, when pregnancy does occur, risk of EP is higher than in women not using an IUD.
In assisted reproductive technology (ART), the incidence of EP is approximately 3% to 5%. These pregnancies tend to be recognized at an earlier stage due to close monitoring in these patients.
Ninety-seven percent of ectopic pregnancies are implanted within the fallopian tube, although implantation can occur within the abdomen, cervix, ovary, or uterine cornua. Other rare locations for implantation include previous hysterotomy scars and the rudimentary horn of a uterus. EPs also occur following hysterectomy.
Risk factors for EP include pelvic inflammatory disease, previous tubal surgery, infertility, current or previous use of an IUD, two or more pregnancy termination procedures, diethylstilbestrol exposure, age >40 years, smoking, greater than three previous spontaneous abortions, and assisted reproduction.
Risk factors for recurrent EP include previous EP (even if previous EP was treated by salpingectomy), previous spontaneous miscarriage (with likelihood increasing with each miscarriage), and a history of pelvic surgery. No significant increase exists in women with a history of pelvic infections when these patients are compared to those with a primary presentation of EP.
Etiology of EPs is often multifactorial, and an estimated 40% to 50% of EPs have an unknown etiology.
DIAGNOSIS OF ECTOPIC PREGNANCY
Clinical Presentation
The Classic triad (present in less than 50% of patients) is amenorrhea followed by abnormal vaginal bleeding and abdominal or pelvic pain.
Pain is present in 95% of patients with rupturing EP. It is usually located in the lower quadrants but can be anywhere within the abdomen. Cervical motion tenderness (CMT) is present in 75% of patients with ruptured EP.
Vaginal spotting is present in 60% to 80% of patients and is usually scant, dark brown bleeding, either intermittent or continuous.
EP may present as a surgical emergency, and timely diagnosis is essential (Fig. 29-1).
 Figure 29-1. Evaluation of the stable patient with suspected EP. Hormonal parameters can vary depending on the assay technique and reference standard used. The discriminatory threshold for sonographic detection of an intrauterine gestational sac is established by each institution. (Reused with permission from Damario MA, Rock JA. Ectopic pregnancy. In Rock JA, Jones HW III, eds. TeLinde’s Operative Gynecology, 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2003:516.) |
Differential Diagnosis
Salpingitis presents with similar signs and symptoms as EP, but negative pregnancy test results, and an elevated white blood cell (WBC) and temperature.
Threatened abortion: In this condition, bleeding is usually heavier, pain is localized to the lower mid abdomen, and CMT is generally absent.
Appendicitis: Persistent right lower quadrant pain, with fever and gastrointestinal (GI) symptoms, suggests appendicitis. CMT, if present, is usually less severe than with EP. Pregnancy test results are negative, and amenorrhea or abnormal vaginal bleeding is usually absent.
Ovarian torsion: Pain is initially intermittent and later becomes constant as vascular supply is compromised. Findings may include an elevated WBC and a palpable adnexal mass, but pregnancy test results are negative.
Other conditions in the differential should include normal intrauterine pregnancy, heterotopic pregnancy (especially in the case of ART), ruptured ovarian cyst, bleeding corpus luteum, endometriosis, diverticulitis, and dysfunctional uterine bleeding. Gastroenteritis, urinary tract infection, or renal calculus early in pregnancy may also mimic an EP.
Physical Examination
Ruptured unstable EP is a surgical emergency. If unstable, patients may have signs of hypovolemic shock, including tachycardia, hypotension, and confusion. Abdominal exam may reveal peritonitis, including guarding, rigidity, or rebound tenderness. Up to 15% of women complain of shoulder pain, secondary to diaphragmatic irritation from hemoperitoneum.
Hemodynamically stable EP: Tenderness in patients with EP may be generalized (45%), located bilaterally in the lower quadrants (25%), or located unilaterally in a lower quadrant (30%). Rebound tenderness may or may not be present. CMT, resulting from peritoneal irritation, is usually present but is not specific for EP. A palpable adnexal mass or mass in the cul-de-sac is reported in approximately 40% of cases; absence of a palpable mass does not rule out EP.
Laboratory Evaluation
If EP is diagnosed before rupture, a laboratory diagnosis may be made and conservative treatment offered.
Quantitative Gonadotropin Levels
Quantitative beta-human chorionic gonadotropin (β-hCG): The titer climbs in a linear fashion from 2 to 4 weeks after ovulation in normal pregnancy, frequently doubling every 48 to 72 hours until it reaches 10,000 mIU/mL.
Minimum rise in β-hCG for a viable intrauterine pregnancy (IUP) is typically 53% in 48 hours. Thus, β-hCG that increases less than 50% in 48 hours is almost always associated with an abnormal pregnancy. Serial serum hCG values that increase or decrease more slowly than expected when compared to viable IUPs or spontaneous abortions, respectively, are suggestive of EP; however, the entire clinical picture must be considered.
Levels of β-hCG are more likely to plateau (<15% change) with an EP than with a spontaneous abortion.
A β-hCG level of <1,500 mIU/mL accompanied by pain and vaginal bleeding increases the likelihood of an EP by 2.5 times.
Patients with a single β-hCG of 2,000 mIU/mL and no identifiable gestational sac on transvaginal ultrasound (TVUS) should have a repeat β-hCG in 12 to 24 hours. A rapidly falling β-hCG can indicate a completed spontaneous abortion. However, careful consideration of last menstrual period and the possibility of a multifetal gestation should be considered.
Seventeen percent of patients with EP will have normal β-hCG doubling time (greater than 53% rise in 48 hours).
Hemoglobin and Hematocrit
Baseline blood counts should be obtained. Serial measurements are useful if the diagnosis of ruptured EP is uncertain. An acute drop in hemoglobin or hematocrit over the first few hours of observation is more revealing than the initial reading. After acute hemorrhage, initial readings may be at first unchanged or only slightly decreased; a subsequent decline represents restoration of depleted blood volume by hemodilution.
Metabolic Panel
Baseline creatinine and liver transaminases should be obtained in preparation for methotrexate (MTX) treatment for EP. Any signs of renal, hepatic, or hematologic dysfunction are a contraindication to MTX treatment.
Progesterone
A normal IUP should be associated with a serum progesterone value of 20 ng/mL or greater. A value of <5 ng/mL indicates a nonviable pregnancy.
Of limited use in diagnosing EP, as many patients with EP will have serum progesterone levels between 10 and 20 ng/mL. A progesterone level may be used to predict viability of a pregnancy of unknown location but is insufficient for EP diagnosis.
Diagnosis by Imaging: Transvaginal Ultrasound
Most common sites of EP: ampullary (70%), isthmic (12%), fimbrial (11.1%), ovarian (3.2%), interstitial and cornual (2.4%), abdominal (1.3%), and cervical (0.15%).
The discriminatory zone is the lowest β-hCG level in which ultrasound should detect evidence of an IUP. Depending on the institution, this β-hCG level ranges from 1,500 to 2,000 mIU/mL for detection via TVUS.
When the β-hCG level is below 2,000, ultrasound diagnosis of EP should be based on visualization of an adnexal mass rather than absence of intrauterine gestational sac.
Heterotopic pregnancy (combined intrauterine and extrauterine pregnancy) is rare, although less so among women conceiving through in vitro fertilization (IVF). Serial hCG concentrations are not interpretable in the presence of both a viable IUP and EP. On ultrasound examination, the diagnosis is suggested by visualization of both an ectopic and an IUP or the presence of echogenic fluid in the cul-de-sac in the presence of an IUP. Surgery (e.g., salpingostomy or salpingectomy) is the standard treatment of heterotopic pregnancy with a tubal component because the IUP is a contraindication to medical therapy.
Sensitivity of TVUS in the diagnosis of EP ranges from 70% to 90%. Despite relative accuracy in detection of EPs, there remain some cases where results of TVUS are inconclusive regarding location of pregnancy in the setting of a positive pregnancy test. These are deemed pregnancy of unknown location (PUL). An EP is eventually diagnosed in 7% to 20% of women with PUL. It is important to note that PUL is a classification scheme and not a final diagnosis.
PUL is a term provided by a classification scheme which was designed to “improve objective comparison of research outcomes in the diagnosis of EP and to reduce clinical heterogeneity.” Using this scheme, there are five classifications depending on sonographic findings: definite EP, probable EP, PUL, probable IUP, and definite IUP.
For women with PUL, final outcome is classified as visualized EP, visualized IUP, spontaneously resolved PUL, and persisting PUL. In the category of persisting
PUL, further final outcomes are classified as nonvisualized EP, treated persistent PUL, resolved persistent PUL, or histologic IUP.
Radiologic signs of EP include an empty uterus, cystic or solid adnexal masses, dilated and thick-walled fallopian tubes, free echogenic fluid in pelvis, hematosalpinx, extrauterine gestational sac that contains a yolk sac (with or without an embryo), and increased blood flow to the adnexa which contains the EP (using Doppler technology).
Pseudosac: Ten percent of ectopic pregnancies have a pseudosac in the uterus that lacks the “double decidual” sign of an IUP. A pseudosac tends to be oval in shape with irregular margins in contrast to the smooth margins of an IUP. It also tends to appear centrally in the intrauterine cavity.
An EP greater than 2 cm in size can be visualized with TVUS.
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