Ectopic pregnancy refers to the implantation of a fertilised ovum outside of the uterine cavity.
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Epidemiology
The overall incidence has increased over the last few decades and is thought to affect 1-2% of pregnancies. The risk is as high as 18% for first-trimester pregnancies with bleeding 15.
Risk factors
in vitro fertilisation
prior ectopic pregnancy
tubal injury or surgery, including tubal ligation
endometrial injury
previous placenta praevia 16
smoking 17
maternal age (advanced maternal age increases the risk of ectopic pregnancy)19
history of subfertility 20
Clinical presentation
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 amenorrhoea 5). Nonetheless, monitoring of haemodynamic status is crucial, as haemorrhage can be life-threatening.
Pathology
Location
In the vast majority of cases, the ectopic implantation site is within a fallopian tube.
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tubal ectopic: 93-97%
ampullary ectopic: most common ~70% of tubal ectopics and ~65% of all ectopics
isthmal ectopic: ~12% of tubal ectopics and ~11% of all ectopics
fimbrial ectopic: ~11% of tubal ectopics and ~10% of all ectopics
interstitial ectopic/cornual ectopic: 3-4%; also essentially a type of tubal ectopic
ovarian ectopic: ovarian pregnancy; 0.5-1%
cervical ectopic: cervical pregnancy; rare <1%
scar ectopic: site of previous caesarean section scar; rare
abdominal ectopic: rare ~1.4%
Markers
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.
Radiographic features
It is useful to know a quantitative beta HCG prior to scanning as this will guide what you expect to see. At levels <2000 IU, a normal early pregnancy may not be visible.
The most reliable sign of ectopic pregnancy is the visualisation of an extra-uterine gestation, but this is not seen in 15-35% of ectopic pregnancies 3.
Ultrasound
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:
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uterus
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an empty uterine cavity or no evidence of an intrauterine pregnancy
an exception to this is a rare heterotopic pregnancy
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pseudogestational sac or decidual cyst: may be seen in 10-20% of ectopic pregnancies
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
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tube and ovary
simple adnexal cyst: 10% chance of an ectopic
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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
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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 colour Doppler in a tubal ectopic, but can also be seen in a corpus luteum
an absence of colour 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
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peritoneal cavity
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free pelvic fluid or haemoperitoneum in the pouch of Douglas
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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)
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free fluid in the hepatorenal recess
interrogation of the right upper quadrant for free fluid reduces time to diagnosis 21
free fluid in Morison's pouch in the context of an ectopic pregnancy is highly suggestive that operative management will be necessary 20
live pregnancy: 100% specific, but only seen in a minority of cases
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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 haemodynamic status. In general, the options are:
surgical: (in the case of tubal ectopics with open or laparoscopic salpingectomy or salpingotomy)
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medical
methotrexate (a folate antagonist) either administered systemically or by direct ultrasound-guided injection
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relative contraindications to methotrexate include 12:
rupture
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 recognised as an option for those ectopics where rupture has not occurred (i.e. no haemoperitoneum) and fetal demise has already taken place
Complications
Complications somewhat depend on the type of ectopic. General complications for a typical (tubal) ectopic pregnancy include:
tubal rupture: 15-20%
lithopaedion: may result with larger ectopic pregnancies which have been left in situ
Differential diagnosis
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
intrauterine pregnancy
incidental adnexal mass
appendicitis (negative beta-hCG)
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.
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