Ectopic Pregnancy

Author: Josie L. Tenore
Date: Feb 15, 2000

Ectopic pregnancy occurs at a rate of 19.7 cases per 1,000 pregnancies in North America and is a leading cause of maternal mortality in the first trimester. Greater awareness of risk factors and improved technology (biochemical markers and ultrasonography) allow ectopic pregnancy to be identified before the development of life-threatening events. The evaluation may include a combination of determination of urine and serum human chorionic gonadotropin (hCG) levels, serum progesterone levels, ultrasonography, culdocentesis and laparoscopy. Key to the diagnosis is determination of the presence or absence of an intrauterine gestational sac correlated with quantitative serum beta- subunit hCG (s-hCG) levels. An ectopic pregnancy should be suspected if transvaginal ultrasonography shows no intrauterine gestational sac when the s-hCG level is higher than 1,500 mlU per mL (1,500 IU per L). If the s-hCG level plateaus or fails to double in 48 hours and the ultrasound examination fails to identify an intrauterine gestational sac, uterine curettage may determine the presence or absence of chorionic villi. Although past treatment consisted of an open laparotomy and salpingectomy, current laparoscopic techniques for unruptured ectopic pregnancy emphasize tubal preservation. Other treatment options include the use of methotrexate therapy for small, unruptured ectopic pregnancies in hemodynamically stable patients. Expectant management may have a role when s-hCG levels are low and declining. (Am Fam Physician 2000;61:1080-8.)

Ectopic pregnancy is any pregnancy in which the fertilized ovum implants outside the intrauterine cavity. More than 95 percent of ectopic pregnancies occur in the fallopian tubes.1 Another 2.5 percent occur in the cornua of the uterus, and the remainder are found in the ovary, cervix or abdominal cavity.1 Because none of these anatomic sites can accommodate placental attachment or a growing embryo, the potential for rupture and hemorrhage always exists. A ruptured ectopic pregnancy is a true medical emergency. It is the leading cause of maternal mortality in the first trimester and accounts for 10 to 15 percent of all maternal deaths.2-4

Modern advances in ultrasound technology and the determination of serum beta-subunit human chorionic gonadotropin (b-hCG) levels have made it easier to diagnose ectopic pregnancy. Nonetheless, the diagnosis remains a challenge.


The number of ectopic pregnancies has increased dramatically in the past few decades. Based on hospital discharge data, the incidence of ectopic pregnancy has risen from 4.5 cases per 1,000 pregnancies in 19705,6 to 19.7 cases per 1,000 pregnancies in 1992.2 The rise can be attributed partly to increases in certain risk factors but mostly to improved diagnostics. Some ectopic pregnancies detected today, for instance, would have spontaneously resolved without detection or intervention in the past. Ectopic pregnancy is more often detected in women over 35 years of age and in non-white ethnic groups.1

The case-fatality rate has declined from 35.5 maternal deaths per 10,000 ectopic pregnancies in 1970 to only 3.8 maternal deaths per 10,000 ectopic pregnancies in 1989.6 Even though overall survival has increased, the risk of death associated with ectopic pregnancy remains higher among black and other non-white minority women.

Risk Factors

Several factors increase the risk of ectopic pregnancy (Table 1). These risk factors share a common mechanism of action-namely, interference with fallopian tube function. Normally, an egg is fertilized in the fallopian tube and then travels down the tube to the implantation site. Any mechanism that interferes with the normal function of the fallopian tube during this process increases the risk of ectopic pregnancy. The mechanism can be anatomic (e.g., scarring that blocks transport of the egg) or functional (e.g., impaired tubal mobility).

In the general population, pelvic inflammatory disease is the most common risk factor for ectopic pregnancy. Organisms that preferentially attack the fallopian tubes include Neisseria gonorrhoeae, Chlamydia trachomatis and mixed aerobes and anaerobes. Unlike mixed aerobes and anaerobes, N. gonorrhoeae and C. trachomatis can produce silent infections. In women with these infections, even early treatment does not necessarily prevent tubal damage.7

Intrauterine devices (IUDs) used for contraception do not increase the risk of ectopic pregnancy, and no evidence suggests that currently available IUDs cause pelvic inflammatory disease. One explanation for the mistaken association of IUDs with ectopic pregnancy may be that when an IUD is present, ectopic pregnancy occurs more often than intrauterine pregnancy.1,8 Simply because IUDs are more effective in preventing intrauterine pregnancy than ectopic pregnancy, implantation is more likely to occur in an ectopic location.

Previous ectopic pregnancy becomes a more significant risk factor with each successive occurrence. With one previous ectopic pregnancy treated by linear salpingostomy, the recurrence rate ranges from 15 to 20 percent, depending on the integrity of the contralateral tube.1,9 Two previous ectopic pregnancies increase the risk of recurrence to 32 percent, although an intervening intrauterine pregnancy lowers this rate.1,10

Endometriosis, tubal surgery and pelvic surgery result in pelvic and tubal adhesions and abnormal tubal function. The fallopian tubes may also be affected by other, less clearly understood causes of infertility, as well as many of the hormones that are administered to aid ovulation and improve fertility.10

In utero exposure to diethylstilbestrol (DES) is associated with uterotubal anomalies ranging from gross structural abnormalities such as a double uterus to more subtle microscopic abnormalities resulting in tubal dysfunction.1,10,11 Any uterotubal anomalies, with or without DES exposure, increase the risk of ectopic pregnancy.

Cigarette smoking has an independent and dose-related effect on the risk of ectopic pregnancy. Cigarette smoking is known to affect ciliary action in the nasopharynx and respiratory tract. A similar effect may occur within the fallopian tubes.3,12

Multiple sexual partners, early age at first intercourse and vaginal douching are often considered risk factors for ectopic pregnancy. The mechanism of action for these risk factors is indirect, in that they are markers for the development of sexually transmitted disease, ascending infection, or both.3,10

Clinical Findings

Recent technologic improvements have made it possible to diagnose ectopic pregnancy earlier. This has altered the clinical presentation from that of a life-threatening surgical emergency to a less severe constellation of signs and symptoms.

Historically, the hallmark of ectopic pregnancy has been abdominal pain with spotting, usually occurring six to eight weeks after the last normal menstrual period. This remains the most common presentation of tubal pregnancy in symptomatic patients. Other presentations depend on the location of the ectopic pregnancy. Less commonly, ectopic pregnancy presents with pain radiating to the shoulder, vaginal bleeding, syncope and/or hypovolemic shock.

Physical findings include a normal or slightly enlarged uterus, pelvic pain with movement of the cervix and a palpable adnexal mass. Findings such as hypotension and marked abdominal tenderness with guarding and rebound tenderness suggest a leaking or ruptured ectopic pregnancy. Case reports indicate that viable abdominal ectopic pregnancies may be discovered at cesarean section, albeit rarely.13

Diagnostic Evaluation

Between 40 and 50 percent of ectopic pregnancies are misdiagnosed at the initial visit to an emergency department.4,14 Failure to identify risk factors is cited as a common and significant reason for misdiagnosis.4 A proper history and physical examination remain the foundation for initiating an appropriate work-up that will result in the accurate and timely diagnosis of an ectopic pregnancy.

Identification of risk factors can raise the index of suspicion and lend significance to otherwise minor physical findings. For example, subtle changes in vital signs, such as mild tachycardia or lower than usual blood pressure, should prompt further investigation. Scoring systems have been proposed to facilitate earlier diagnosis of ectopic pregnancy by indicating the level of risk as a function of weighted risk factors.15

Biochemical Markers

After a careful history and physical examination, ancillary studies may include a urine pregnancy test and determination of the serum progesterone level and serum quantitative b-hCG levels. Other chemical markers, such as creatine kinase16,17 and fetal fibronectin levels,18 have been investigated and rejected because of inadequate diagnostic sensitivity.

JOSIE L. TENORE, M.D., S.M., is a full-time faculty member and lecturer with the Department of Family Medicine at Northwestern University Medical School, Chicago. A portion of her work is done at the Glenbrook Family Care Center, the site of the family practice residency program for Northwestern University. She received her medical training at the University of Toronto Faculty of Medicine, Ontario, and earned a master of science degree in maternal and child health at Harvard School of Public Health, Boston. Dr. Tenore is board certified in family medicine in Canada and the United States.

Address correspondence to Josie L. Tenore, M.D., S.M., Glenbrook Family Care Center, 2050 Pfingsten Rd., Suite 200, Glenview, IL 60025. Reprints are not available from the author.

Table 1Risk Factors for Ectopic PregnancyStrong evidence for associationPelvic inflammatory diseasePrevious ectopic pregnancyEndometriosisPrevious tubal surgeryPrevious pelvic surgeryInfertility and infertility treatmentsUterotubal anomaliesHistory of in utero exposure to diethylstilbestrolCigarette smokingWeaker evidence for associationMultiple sexual partnersEarly age at first intercourseVaginal douchingTable 2Criteria for the Use of Methotrexate (Rheumatrex)in Patients with Ectopic PregnancyAbsolute requirementsHemodynamic stabilityUltrasound findings consistent with an ectopic pregnancyWillingness on the part of the patient to adhere to close follow-upNo contraindications to methotrexate therapyRelative requirementsUnruptured ectopic mass less than 3.5 cm in greatest dimensionNo fetal cardiac motion detectedBeta-subunit human chorionic gonadotropinlevel that does not exceed 5,000 mIU per L (5,000 IU per L)Adapted with permission from ACOG practice bulletin no. 3. Medicalmanagement of tubal pregnancy. Clinical management guidelines forobstetrician-gynecologists. Washington, D.C.: American College ofObstetricians and Gynecologists, 1998.

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