Clinical Review

Heterotopic pregnancy: an emerging diagnostic challenge

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Due in part to rising rates of in vitro fertilization, heterotopic pregnancy isn’t nearly as rare a condition as it was in times past. Here, the authors detail protocols for diagnosing and treating this challenging disorder.



  • The prevalence of heterotopic pregnancy has increased, due in part to in vitro fertilization techniques that transfer multiple embryos into the uterus.
  • An interstitial eccyesis can be distinguished from an angular pregnancy by the anatomical relationships of the round and ovarian ligaments to the fallopian tube.
  • Sonographic signs of interstitial heterotopic pregnancy include an eccentrically located echogenic mass surrounded by a thin myometrial rim, an interstitial line sign, and a myometrial bridge separating a suspected eccyesis from an intrauterine pregnancy.
  • The choice of surgical or medical treatment of heterotopic pregnancy depends upon the hemodynamic status of the patient and the expertise of the physician.
  • Physicians must closely observe during labor the hemodynamic status of women treated for interstitial or cornual heterotopic pregnancy, since the risk of uterine rupture is unknown.

Heterotopic pregnancy is a condition on the rise. In 1948, just 1 in 30,000 gravidas presented with this disorder, in which uterine and extrauterine gestations exist concomitantly.1 Today that rate is 1 in 3,800.2 And for women undergoing in vitro fertilization (IVF), the number is a startling 1 in 100.3

Why such a dramatic shift? In the general population of women, the increase may be due in part to a rise in pelvic inflammatory disease (PID),4 but other risk factors—including history of eccyesis, previous pelvic surgery, and congenital or acquired abnormalities of the uterine cavity—also may be contribute to the condition.3,5 But for IVF patients, the rise is largely attributable to the transfer of multiple embryos into the uterus.2,6 In fact, when more than 5 embryos are implanted, the risk of heterotopic pregnancy increases to 1 in 45.

When these rising incidence rates are coupled with the ever-increasing number of fertility treatments, it becomes clear that now it’s more important than ever that clinicians be able to readily recognize and treat this often-elusive condition.


Heterotopic pregnancy is extremely difficult to diagnose. More than 50% of these pregnancies are identified by sonography or laparoscopy 2 weeks or more after the initial visualization of the intrauterine pregnancy,6 though approximately 85% go undiagnosed before the rupture of the eccyesis.

Typically, in women with suspected ectopic pregnancy, serial serum quantitative beta (ß) human chorionic gonadotropin (hCG) tests are combined with transvaginal ultrasonography (TVUS) to determine whether the pregnancy is intrauterine or extrauterine in nature. In distinguishing between ectopic and heterotopic pregnancies, however, serum ß-hCG determinations have not been particularly helpful, since each of the 2 pregnancies contribute to the total amount of circulating ß-hCG.5 In addition, up to 23% of heterotopic pregnancies have hCG levels comparable to singleton intrauterine pregnancies.5

Treatment of an eccyesis must consider the viability of the intrauterine pregnancy.

The assumption that detecting an intrauterine gestational sac by TVUS excludes eccyesis is based on the 50-year-old estimate of the prevalence of heterotopic pregnancy (1 in 30,000). In fact, TVUS has been quite useful in the early detection of heterotopic pregnancy. The sonographic finding of 1 gestational sac in the uterine cavity with another in the adnexum is diagnostic of this condition.

Approximately 90% of eccyesis accompanying intrauterine pregnancy occur in the fallopian tube, usually within its ampulla (FIGURE 1). It is perhaps easier to diagnose an ampullary pregnancy than an interstitial pregnancy, because there is a greater index of suspicion with a tube in place. However, an ampullary pregnancy also may be missed unless a heartbeat is detected in the adnexum.

Unfortunately, for women with heterotopic pregnancy who have undergone salpingectomy and whose eccyesis resides in the interstitial or cornual remnants of the fallopian tube—a condition that occurs in 4% of heterotopic pregnancies7—an ultrasonic mass adjacent to the uterus is unlikely to raise suspicion of an eccyesis. This is because the adjacent intrauterine gestational sac mimics a singleton intrauterine pregnancy. (Few eccyesis occur in the ovary, cervix, or abdomen.6) But failure to diagnose an interstitial or cornual heterotopic pregnancy increases a woman’s risk of intraabdominal hemorrhage, as rupture of the thickened, vascular muscularis surrounding the eccyesis is delayed for up to 16 gestational weeks.

The sonographic signs suggestive of an interstitial eccyesis include a chorionic sac, or echogenic mass, located approximately 1 cm lateral to the uterine cavity and surrounded by a thin myometrial rim (less than 5 mm). In addition, an interstitial line sign—defined as an echogenic line extending through the cornual region and into the middle of the interstitial mass—is 92% sensitive and nearly 100% specific for diagnosing an interstitial pregnancy.6,8 Color Doppler sonography may detect a “ring of fire” from high-velocity or low-impedance blood flow surrounding an eccyesis (separate from a corpus luteum). A resistance index of less than 0.40 for such a mass (outside the ovary) is suspicious of an extrauterine pregnancy.9 Plus, an 8% difference in the resistance index between tubal arteries is 86% sensitive and 96% specific for eccyesis.10 In addition to these findings, a TVUS showing a bridge of myometrium separating a suspected eccyesis from an intrauterine pregnancy strongly suggests a heterotopic pregnancy.6,11

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