The incidence of ectopic pregnancies has steadily increased from 4.5/1,000 in 1970 to 20/1,000 in 1992(NCHS, 1992). While this increase is for the most part real, earlier diagnosis also plays a role by identifying ectopic pregnancies that would have spontaneously resolved. Quantitiative B-hCG levels and transvaginal sonography have been responsible for a shifting in the presentation of ectopic pregnancies from a medical emergency to a more benign condition. Prior to 1978 only 28% (Kim, 1987) of ectopics were diagnosed prior to rupture; this figure had changed to 85% by 1988 (Senterman, 1988). Despite these improvements ectopic pregnancies still account for 9% of all maternal deaths in the United States (NCHS, 1992). The maternal mortality associated with an ectopic pregnancy is ten times greater than that associated with childbirth (Filly, 1987).
The risk factors associated with an ectopic pregnancy are generally self-evident. A history of a prior ectopic pregnancy increases a patient's risk to 12%-18% (Stabile, 1990). Women undergoing invitro fertilization have a 3% to 4% incidence of ectopic pregnancy (Nazari, 1993; Stabile, 1990). The rate of heterotopic pregnancies approaches 1% after assisted reproduction (Frates, 1995)
(Figure 1). Other risk factors are listed in Table 1.
Risk Factors for Ectopic Pregnancy
Intra-uterine contraceptive device
Multiple sex partners
Pelvic inflammatory disease
Location of Ectopic Pregnancies
Approximately 80% of ectopic pregnancies occur in the ampullary portion of the fallopian tube; 10% are in the isthmus; 5% are fimbrial in location and 2-4% are cornual. Ovarian, cervical and abdominal pregnancies are rare (Breen, 1970).
Historically, pelvic pain was the most common symptom of an ectopic pregnancy. Initially, the pain may be localized to the side of the ectopic. After rupture, the pain becomes more diffuse. With the earlier diagnosis of ectopic pregnancies, a skipped menstrual cycle or early first trimester spotting may be a patient's only initial complaint. The classic triad of vaginal bleeding, adnexal tenderness, and an adnexal mass is present in less than 30% of ectopic pregnancies (Kim, 1987).
Quantitative B-hCG Levels
Serum B-hCG can be detected by 6 days after conception (Daya, 1987). While the B-hCG of ectopic pregnancies are generally lower than for normal pregnancies, there is significant overlap. The B-hCG level of unruptured (1190mIU/ml) and ruptured (4160 mIU/ml) ectopic pregnancies are significantly different (Ackerman, 1982). Ectopic pregnancies with very low B-hCG levels are unlikely to rupture and may spontaneously resolve (Hay, 1989). However, in cases when gestational age is uncertain, a chronic ectopic pregnancy should be considered. Recurrent small episodes of bleeding result in a gradual disintegration of the tubal wall; a pelvic mass eventually forms. Since the trophoblastic tissue may have died, the B-hCG level may be low to absent (Abramov, 1997).
There is a direct correlation between gestational sac size and the exponential rise in B-hCG during the first 5 weeks of pregnancy. Hence, by comparing ultrasound findings with B-hCG levels, the concept of a "discriminatory zone" was developed. With transvaginal sonography a gestational sac is usually visualized at a serum B-hCG level between 1000 and 2000 mIU/ml. However, technical factors (multiple gestation, leiomyomas, subchorionic hemorrhage) and biologic variability in singleton gestations may result in a normal intrauterine gestational sac not being detected until a greater B-hCG level is obtained. In general, the 95% confidence interval for the detection of a normal intrauterine gestational sac is 3000 mIU/ml (Kadar, 1994; Shapiro, 1992).
A normal intrauterine gestational sac is embedded below the mid-line endometrial stripe. The hormonal changes associated with a pregnancy results in an endometrial fluid collection (pseudo-sac) in 8% of ectopic pregnancies (Hill, 1990) (Figure 2). A low-level echo pattern may be observed in a pseudogestational sac, particularly in a patient with a high B-hCG level (Thorsen, 1990).
The presence of an embryo with cardiac activity outside of the uterus is diagnostic of an ectopic pregnancy (Figure 3). In the past this presentation of an ectopic pregnancy occurred between 8% -26% of the time (Timor-Tritsch, 1989; Atri, 1992). Today an "echogenic ring" (Figure 4) has been reported more commonly; occurring in 40% to 70% of ectopic pregnancies (Atri 1992; Fleischer, 1990). Because of there approximation, it is sometimes difficult to distinguish between an ectopic "echogenic ring" adjacent to an ovary and a corpus luteum. The transvaginal transducer can be used to determine if the "echogenic ring" moves with or is independent of, the ovary.
Once an ectopic pregnancy has ruptured, a complex adnexal mass of mixed echogenicity (Figure 5) may be imaged. Particulate cul-de-sac fluid indicates associated intraperitoneal hemorrhage (Nyberg, 1991).
Because of the surrounding myometrium, cornual ectopics can grow to a large size before becoming symptomatic. Since a cornual pregnancy is not located within the endometrial cavity, transvaginal sonography will reveal an "interstitial line" that extends from the uterine cavity to the cornual gestational sac (Figure 6) (Frates, 1995).
In order to diagnose a cervical pregnancy, the embryo/fetus must not be within the uterine cavity and the placenta must be attached to the cervix (Figure 7). The differential diagnosis would include an imminent miscarriage. The presence of cardiac activity in a cervically located gestational sac would confirm the diagnosis. When cardiac activity is not present, a follow-up scan in 24 hours would exclude a diagnosis of an imminent miscarriage. Cervical ectopics occur more frequently after invitro fertilization (Parente 1983; Ginsburg, 1994).
Ovarian pregnancies result from either ovum fertilization within the ovary (primary) or the implantation of a tubal abortion on an ovary (secondary). The sonographic appearance of an ovarian pregnancy can vary from an "echogenic ring" fixed to the ovary to a complex adnexal mass that involves the ovary. It may, therefore, be difficult to distinguish a hemorrhagic ovarian cyst from an ovarian pregnancy (Malinger, 1988). Since the fallopian tube is not affected, an ovarian pregnancy is not a risk factor for a repeat ectopic pregnancy.
An abdominal pregnancy occurs when a tubal abortion implants on a peritoneal cavity and continues to grow. While anhydramnios is common, it is not an invariable finding with abdominal pregnancies. Additional sonographic signs include a failure to visualize the uterine wall around a pregnancy; an abnormal fetal lie; and an empty uterus with an adjacent fetus. A pregnancy in one horn of a bicornuate or didelphysis uterus may mimic an abdominal pregnancy (Ombelet, 1988; Stanley 1986).
Vascular flow around an ectopic pregnancy is directly related to the amount of viable trophobastic tissue present. In the classic case there is a "ring of fire" surrounding the ectopic (Figure 8). A corpus luteum may have a similar sonographic appearance. There is more flow surrounding an established ectopic pregnancy. However, in these cases the "echogenic ring" would be most apparent on standard two-dimensional sonography. In 1 of 65 cases color Doppler identified an ectopic pregnancy that was not identified with gray scale (Pellerito, 1992). While color Doppler has been a useful adjunct, it has not changed the diagnostic accuracy achieved with the combination of B-hCG levels and transvaginal sonography (Tekay, 1992; Bourne, 1991).
The traditional management for ectopic pregnancies has been surgical, i.e. salpingectomy or linear salpingostomy. With the latter approach, residual chorionic villi may remain. The prevalence of a persistent ectopic pregnancy is 2%-5% with linear salpingostomy at laparotomy in contrast to 3% - 20% at laparoscopy (Seifer, 1993). Prophylactic methotrexate within 24 hours of salpingostomy significantly reduces the incidence of persistent ectopic pregnancy (Graczykowski, 1997).
Medical management of ectopic pregnancies consists of the systemic administration of methotrexate (50 mg/m2 of body surface area, IM). A falling B-hCG level of > 15% between days 4 and 7 after treatment is considered successful therapy; B-hCG levels are then followed weekly until they are not detectable. When the B-hCG level fails to fall 15% , either initially or when the subsequent weekly follow-up levels are obtained, a repeat dose of methotrexate is given. Successful treatment of ectopic pregnancies with methotrexate has been reported in 85.7% to 94.2% of selected cases (Brumsted, 1996). All of the reports have not been this successful. In a systematic review of single-dose intramuscular methotrexate for ectopic pregnancy, Parker et al (1998) reported a pooled success rate of 71%. Serious complications, including 1 maternal death, have occurred after methotrexate therapy for ectopic pregnancy. When methotrexate is successful, post treatment hysterosalpingograms have demonstrated tubal patency on the side of the ectopic in 82.3% of patients (Stoval, 1993).
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