ectopic pregnancy

Ectopic pregnancy. Implantation of a fertilized ovum outside the endometrial cavity defines this condition. This potential life-threatening implantation occurs in approximately 1.5% to 2.0% of pregnancies and remains the most common cause of non-traumatic maternal death in the first trimester.33 It accounts for 6% of pregnancy-related deaths in the United States overall.34

Risk factors include pelvic inflammatory disease, previous tubal surgery, prior ectopic pregnancy, infertility, diethylstilbestrol (DES) exposure, smoking, age over 35 years, intrauterine device use, and many lifetime sex partners.33,35,36 Nevertheless, almost half of all cases of ectopic pregnancy occur in women without risk factors.37

The presence of both an ectopic pregnancy and an intrauterine pregnancy is known as a heterotopic pregnancy. In women undergoing in vitro fertilization, the risk of heterotopic pregnancy increases from 1 per 4000 to 1 per 100.33

Most ectopic pregnancies occur in the fallopian tube. Eighty percent occur in the ampulla of the fallopian tube, 12% in the isthmic segment, 5% in the fimbria, and 2% in the corneal/interstitial region. Ectopic pregnancies occurring in nontubal sites are rare, with 1.4% in the abdomen and 0.2% in the ovary and cervix.36

Classically, ectopic pregnancy presents with the triad of vaginal bleeding, abdominal bleeding, and amenorrhea. Other signs and symptoms include tachycardia and hypotension secondary to rupture and hemorrhage, and shoulder pain secondary to diaphragmatic irritation caused by hemoperitoneum. It is imperative to remember that the patient may not report having missed her period.

Pelvic examination may reveal cervical motion tenderness and an adnexal mass; however, the physical examination has never been proven to be useful in ruling out ectopic pregnancy. In fact, almost 50% of patients who were found to have an ectopic pregnancy in one review had benign physical findings on first presentation.37

The most important laboratory test in a woman of childbearing age with pelvic pain is urine qualitative beta-hCG measurement. A positive test correlates with a serum beta-hCG level of approximately 10 to 50 mIU/mL, and 90% of pregnancies can be diagnosed on the first day of the missed menstrual period.38 False-negative results occur when the beta-hCG level is less than 50 mIU/mL, usually as a result of dilute urine or testing too soon after ovulation. Under these conditions, the urine pregnancy test would miss only 1 in 2000 ectopic pregnancies, most of which would be too small to be dangerous.

Serum beta-hCG can be measured qualitatively or quantitatively, and the test can detect a beta-hCG level as low as 3 mIU/mL. There is minimal difference in sensitivity compared to urine testing; however, serum beta-hCG measurement is helpful in highly suspicious cases with a negative urine test. The most useful aspect of the quantitative test is that it is helpful in interpreting ultrasound results and in following patient progress.

Classically, it has been taught that the serum beta-hCG level doubles every 48 hours in early viable pregnancies. Studies have shown that the hCG concentration rises by at least 66% every 48 hours during the first 40 days of pregnancy in 85% of viable intrauterine pregnancies.39 More recently, it has been shown that a rise of 53% every 2 days can be seen in potentially viable pregnancies.40 While the beta-hCG level can vary among viable pregnancies, 71% of ectopic pregnancies have serial serum hCG values that increase more slowly than expected with a viable intrauterine pregnancy or decrease more slowly than expected with a miscarriage.33

ultrasound, pregnancy

The discriminatory beta-hCG zone is defined as the serum hCG level above which a gestational sac should be visualized by ultrasound examination if an intrauterine pregnancy is present.39 The gestational sac is the first structure of a pregnancy that can be visualized via ultrasound (at about 4.5 to 5 weeks). It is visible on transvaginal ultrasonography when the quantitative beta-hCG level is above 1500 mIU/mL, while on transabdominal ultrasonography it is visible with levels above 6500 mIU/mL. Ultrasound findings and their corresponding beta-hCG levels in a viable intrauterine pregnancy are listed in Table 2.

During the evaluation for a possible ectopic pregnancy, a quantitative beta-hCG measurement and a transvaginal ultrasound scan should be obtained. There is no need to wait for the quantitative beta-hCG results before obtaining the ultrasound scan. In symptomatic patients, it is possible to diagnose up to one-third of ectopic pregnancies even with a beta-hCG level of less than 1000 mIU/mL.41

double decidual ring

Beta-hCG above the discriminatory zone (higher than 1500 mIU/mL). The finding of a gestational sac on an ultrasound scan is suggestive but not completely diagnostic of an intrauterine pregnancy. This is because the gestational sac can be confused with a pseudogestational sac, which is an endometrial fluid collection often associated with an ectopic pregnancy.36 The pseudogestational sac is seen in 10% to 20% of ectopic pregnancies (Figure 4).42

The double decidual ring, two echogenic rings around the gestational sac, is seen slightly later in pregnancy (Figure 5). In the radiology literature, it is considered highly reliable for the diagnosis of an intrauterine gestational sac and is pathognomonic for an early intrauterine pregnancy.43,44 Visualization of the double decidual ring helps differentiate the gestational sac from a pseudogestational sac. However, the double decidual ring has only a short window in which to be visualized and is not consistently seen.43,44 Furthermore, the double decidual ring can be difficult for clinicians who are not expert radiologists to identify correctly, leading to the incorrect diagnosis of an intrauterine pregnancy.42 Therefore, definitive evidence of an intrauterine pregnancy includes visualization of a yolk sac within the gestational sac, visualization of a fetal pole, or cardiac activity. This will exclude an ectopic pregnancy unless a heterotopic pregnancy is suspected.

Definite evidence of an ectopic pregnancy includes visualization of an extrauterine sac containing a yolk sac, fetal pole, or cardiac activity. This, however, is seen in only 16% to 32% of ectopic pregnancies. Other findings that raise concern for an ectopic pregnancy include an empty uterus with tubal ring, complex adnexal mass, or moderate to large free fluid. All these scenarios mandate consultation with an obstetrician-gynecologist.42

double decidual ring

Approximately 10% to 20% of patients who are evaluated for ectopic pregnancy will have a non-diagnostic scan. These patients include those with an empty uterus without any evidence of an extrauterine pregnancy. This scenario is indicative of an ectopic pregnancy or a nonviable pregnancy. However, it is possible that multiple gestations are present, causing an inability to visualize the gestation sac despite a beta-hCG level higher than 1500 mIU/mL.45 It is also possible that the gestation sac or ectopic pregnancy was not visualized because of suboptimal pelvic ultrasound imaging. These patients must have close follow-up with a repeated ultrasound scan, beta-hCG measurement, and clinical examination within 48 hours. Because of the concern for possible rupture of an unidentified ectopic pregnancy, this plan should be made in conjunction with an obstetrician-gynecologist.

Beta-hCG below the discriminatory zone (less than 1500 mIU/mL). While it is possible to detect a gestational sac or findings that raise concern for an ectopic pregnancy in a patient with a beta-hCG level lower than 1500 mIU/mL, such patients often have normal pelvic ultrasound scans. The differential in this situation includes ectopic pregnancy, early intrauterine pregnancy, and nonviable pregnancy. These patients should be followed every 48 to 72 hours with repeated beta-hCG testing. When the level is lower than 1500 mIU/mL, an ultrasound scan should be performed to evaluate for a gestation sac. An abnormally rising or falling beta-hCG level suggests an abnormal pregnancy or failed pregnancy, respectively.39

Some obstetrician-gynecologists employ progesterone tests to help differentiate normal from abnormal pregnancies. Very low values (less than 5 ng/mL) are predictive of abnormal pregnancy in 97% to 100% of patients. High values (greater than 25 ng/mL) are predictive of normal pregnancy in 97% of patients. Unfortunately, intermediate values are not helpful in evaluation.

Treatment. Surgery (most often laparoscopic) is indicated for hemodynamically unstable patients, patients who fail medical therapy, or for those patients who are not candidates for medical therapy.

Methotrexate, a folate antagonist, can be used for medical treatment of ectopic pregnancies. It may be used in stable and reliable patients with an empty uterus, an ectopic mass smaller than 3.5 to 4 cm, no fetal cardiac activity on ultrasound, and a beta-hCG level of less than 5000 mIU/mL. A beta-hCG level higher than 5000 mIU/mL portends a significant increase in treatment failure, and such patients may benefit from a multi-dose regimen.33,46 If the patient is stable and the ectopic pregnancy appears to be resolving, serial examinations and observation may be elected.