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Ectopic pregnancy refers to the implantation of a fertilised ovum outside of the uterine cavity.
The overall incidence has increased over the last few decades and is currently thought to affect 1-2% of pregnancies. The risk is as high as 18% for first-trimester pregnancies with bleeding 15.
in vitro fertilisation
prior ectopic pregnancy
tubal injury or surgery, including tubal ligation
previous placenta previa 16
maternal age (advanced maternal age increases the risk of ectopic pregnancy)19
history of subfertility 20
The classic presentation is abdominal pain and bleeding. In practice, the symptoms are not necessarily severe - often there may be only mild pelvic pain and spotting in early pregnancy (5-9 weeks of amenorrhea 5). Nonetheless, monitoring of hemodynamic status is crucial, as hemorrhage can be life-threatening.
In the vast majority of cases, the ectopic implantation site is within a fallopian tube.
tubal ectopic: 93-97%
ovarian ectopic: ovarian pregnancy; 0.5-1%
cervical ectopic: cervical pregnancy; rare <1%
abdominal ectopic: rare ~1.4%
Serum beta HCG levels tend to increase at a slower rate. Whereas a normal doubling rate in early pregnancy is approximately 48 hours, an increase of 50% or less in 48 hours is strongly suggestive of a non-viable (either intra- or extrauterine) pregnancy 11. Rarely the urinary and/or serum b-HCG will be negative despite an ectopic pregnancy 13.
Serum progesterone levels are generally lower in a non-viable (including ectopic) pregnancy 6; progesterone of 5 ng/mL or less is strongly associated with pregnancy failure, whereas in a viable pregnancy, progesterone is usually 20 ng/mL or more 5. Clearly, there is a significant grey zone. Furthermore, serum progesterone levels may take days to process. Progesterone is therefore not included in standard protocols for managing the suspected ectopic pregnancy.
The most reliable sign of ectopic pregnancy is the visualization of an extra-uterine gestation, but this is not seen in 15-35% of ectopic pregnancies 3.
The ultrasound exam should be performed both transabdominal and transvaginally. The transabdominal component provides a wider overview of the abdomen, whereas a transvaginal scan is important for diagnostic sensitivity.
Positive sonographic findings include:
an empty uterine cavity or no evidence of an intrauterine pregnancy
an exception to this is a rare heterotopic pregnancy
current evidence suggests that one should not initiate treatment for ectopic pregnancy in a haemodynamically stable woman on the basis of a single hCG value 11
thick echogenic endometrium
tube and ovary
simple adnexal cyst: 10% chance of an ectopic
complex extra-adnexal cyst/mass: 95% chance of a tubal ectopic (if no intrauterine pregnancy)
an intra-adnexal cyst/mass is more likely to be a corpus luteum
solid hyperechoic mass is possible but non-specific
95% chance of a tubal ectopic if seen
described in 49% of ectopics and in 68% of unruptured ectopics
ring of fire sign: can be seen on color Doppler in a tubal ectopic, but can also be seen in a corpus luteum
an absence of color Doppler flow does not exclude an ectopic
live extrauterine pregnancy (i.e. extra-uterine fetal cardiac activity): 100% specific, but only seen in a minority of cases
the presence of free intraperitoneal fluid in the context of a positive beta HCG and the empty uterus is
~70% specific for an ectopic pregnancy 4
~63% sensitive for ectopic pregnancy 4
not specific for ruptured ectopic (seen in 37% of intact tubal ectopics)
free fluid in the hepatorenal recess
live pregnancy: 100% specific, but only seen in a minority of cases
In patients receiving in vitro fertilisation (IVF), it is important not to be completely reassured by the presence of a live intrauterine pregnancy 8, as there is a possibility of a coexisting ectopic pregnancy in ~1-3:100 17 (i.e. heterotopic pregnancy). In patients not receiving IVF, the risk of heterotopic pregnancy is minuscule (1:30,000).
Treatment and prognosis
Management depends on the location of the ectopic pregnancy and the patient's hemodynamic status. In general, the options are:
methotrexate (a folate antagonist) either administered systemically or by direct ultrasound-guided injection
relative contraindications to methotrexate include 12:
mass >3.5 cm
fetal cardiac activity
bHCG >6000-15,000 mIU/mL
the gestational mass can paradoxically increase in size following methotrexate on subsequent scanning and does not necessarily imply failure of methotrexate therapy 3
potassium chloride (via ultrasound-guided direct injection only)
conservative or expectant management is being recognized as an option for those ectopics where rupture has not occurred (i.e. no hemoperitoneum) and fetal demise has already taken place
Complications somewhat depend on the type of ectopic. General complications for a typical (tubal) ectopic pregnancy include:
tubal rupture: 15-20%
lithopedion: may result with larger ectopic pregnancies which have been left in situ
The differential diagnosis of abdominal pain in a pregnant patient is broad. An ectopic pregnancy must be excluded by ultrasound. Other common diagnoses in this setting include:
exophytic corpus luteum of pregnancy
incidental adnexal mass
The scenario of clinically suspected ectopic pregnancy that is not confirmed on ultrasound, is referred to as a pregnancy of unknown location, with the alternative possibilities being of very early pregnancy or a completed miscarriage.