see also:

• gynaecology
• EMRAPTV Episode 49: Ectopic Pregnancy June 2008 lecture
• RCOG guidelines Mx of ectopic (pdf)

• ectopic pregnancy is said to occur in ~2% of all pregnancies with a rising incidence
• it accounts for 9% of all pregnancy related deaths in the USA
• although the diagnosis of ectopic pregnancy has become more reliable and at earlier gestation with improving ultrasound technology, diagnosis is still often delayed or missed, usually because it has not been considered in the differential of the patient with acute abdominal pain in the ED or dizziness, or because of language barriers or socio-cultural issues.
• delayed diagnosis may lead to death, which is particularly a risk when access to appropriate medical care is not available such as in rural areas.
• it is critical to have a high index of suspicion and consider performing a serum HCG on all women of child bearing age who present with abdominal pain, shoulder tip pain or dizziness.
• furthermore, an ultrasound finding of intrauterine pregnancy does not fully exclude an associated ectopic pregnancy (such concurrent pregnancies are called heterotopic pregnancies) which occur in ~1:10,000 but much more commonly in those at risk of multiple pregnancies such as those undergoing IVF or ovulation induction.
• patients with an empty uterus on ultrasound and positive HCG should be closely monitored and followed up with serial HCG's.

• anything that hampers the migration of the embryo to the endometrial cavity will predispose to ectopic pregnancy
• PH pelvic inflammatory disease (PID)
  • one episode increases risk by 400% and thus risk is ~13%
  • successive episodes of PID increases risk of tubal damage and thus ectopic to 35% after 2 episodes, and 75% after 3 episodes
• PH ectopic pregnancy or tubal surgery
  • increases risk of subsequent ectopic by 7 to 13-fold which gives a 10-25% probability
• smoking - impairs cilia within the Fallopian tubes
  • 1.6 to 3.5 times risk compared with non-smokers
• tubal ligation
  • if pregnancy occurs, in 35-50% cases it will be an ectopic
• IUCD - although not a risk factor, by decreasing the intrauterine pregnancy rate, if a pregnancy does occur, there is high chance it will be an ectopic pregnancy.
• ovulation induction with clomiphene or gonadotrophin Rx
  • increases risk 4-fold
• increasing age
  • 35-44 yr old women have a 3 to 4 fold risk compared to 15-24 yr old women
• salpingitis isthmica nodosum
  • defined as the microscopic presence of tubal epithelium in the myosalpinx or beneath the tubal serosa.
  • these pockets of epithelium protrude through the tube, similar to small diverticula and are found in 50% of patients with ectopic pregnancy.
• PH ruptured appendicitis
• endometriosis
• progesterone Rx

• >80% occur in the ampullary section of the Fallopian tube
• 12% occur in the isthmic section of the Fallopian tube
• 5% occur in the fimbria of the Fallopian tube
• 2% occur in the cornual and interstitial region of the Fallopian tube
• 1.4% are abdominal
• 0.2% are ovarian
• 0.2% are cervical

• 50% present with classic triad of lower abdominal pain, generally mild PV bleeding following a period of amenorrhoea.
• 20% are said to present with ruptured ectopic with haemodynamic compromise
  • some of these patients only had prior dizziness as a main symptom
  • some will have shoulder tip pain due to intra-abdominal bleeding irritating the diaphragm, particularly when lying down
  • don't be deceived by normal pulse rates - many have excessive vagal tone due to the pain - the presence of white lips should signal imminent death to you though!
• most will have lateral lower abdominal or adnexal tenderness at presentation

• the diagnosis should be high on your differential in any patient with lower abdominal pain with a positive pregnancy test who does not appear to have an intra-uterine pregnancy or who has had IVF or ovulation induction Rx.

• TV USS may show:
  • an adnexal mass,
  • an ectopic pregnancy with fetal heart beat,
  • free fluid in the Pouch of Douglas (FFPOD)
  • an empty uterus
  • a uterus containing a pseudosac
  • and in the case of an heterotopic pregnancy, a normal intrauterine pregnancy and thus NOT helpful.

• almost always will be positive and usually less than 10,000 IU/L but no single HCG level is diagnostic of ectopic.
• an ectopic may rupture even if:
  • HCG is only 35
  • HCG is doubling every 48hrs for a week (usually indicative of a live i/uterine pregnancy)
• a normal pregnancy in the 1st trimester should double every 48hrs, a rise to less than 166% of the 1st sample suggests a failed intrauterine pregnancy or an ectopic
• some patients will have falling HCG levels suggesting a tubal miscarriage, but these still need to be followed closely with serial HCGs as some can have a delayed rise in HCG and then rupture.
• each US service should have a cut-off HCG value (the “discriminatory zone” which for most centers doing TV scans is in the range 1000-1500IU/L) for which all intrauterine pregnancies with HCG above that level should be visible on USS. Thus if not visible, this is highly suspicious of ectopic pregnancy assuming no obvious POC has been passed.
• more details at emedicine

• move patient into a resuscitation cubicle
• place at least one large bore iv line
• take bloods for FBE, cross match, U&E, HCG
• start fluid resuscitation
  • avoid excessive crystalloid if there is a ruptured ectopic
• contact O&G reg and anaesthetic reg ASAP as Rx is early surgical Rx

• don't forget to Mx Rh Status
• contact O&G reg who will decide on medical vs surgical Mx
• the gynae reg should physically review the patient before a decision to discharge home is made - a phone consult is generally not adequate to provide clinical risk mitigation

• since the 1990's, methotrexate Rx has been used as a non-surgical Rx of ectopic pregnancy but requires close follow up as some may still rupture.
• see also emedicine

• haemodynamic compromise
• ruptured ectopic (eg. FFPOD)
• HCG > 5,000 IU/L
  • succesful Rx is inversely related to initial HCG value, thus failure increases substantially for initial HCG values > 5,000IU/L
• ectopic size on USS > 3.5cm diameter
• fetal cardiac activity on USS
• likely poor patient compliance with follow up
• HS to methotrexate
• breastfeeding
• immunodeficiency
• alcoholism or alcoholic or other liver disease or abnormal LFT's
• blood dyscrasias, leukopenia, thrombocytopenia, anaemia, other haematologic disorders
• active pulmonary disease, PU, renal impairment

• baseline FBE, HCG, U&E, LFT
• im methotrexate dose:
  • usually 50mg/sq.m where surface area in sq.m = sq.root(height in cm x weight in kg / 3600 )
• methotrexate administration requires protective gown, gloves, mask and safety glasses
• im injection is given via the “z track” method and then firm pressure applied for a few minutes and patient advised NOT to rub the site
• counsel patient:
  • when to return if suspect rupture (risk is ~5%)
  • drink at least 3L fluid/day
  • avoidance of alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), sexual intercourse
  • avoid pregnancy for 3 months after single dose, and for 6 months after multiple doses
  • avoid IUCD use
  • avoid excessive sunlight exposure
• O&G reg to order methotrexate with usual cytotoxic agent precautions and signed consent
• serial HCG's:
  • on day 4 and 7 then every week until becomes zero
  • a transient rise by day 3 is common and not a cause for alarm
  • a decline in HCG of at least 15% from day 4 to 7 indicates succesful Rx
• failure of medical Rx is indicated by either:
  • failure of HCG levels to decrease adequately by 15% from days 4-7 postinjection
  • severe pain or clinical rupture (NB. most patients experience some transient mild increase in pain on day 2-3 lasting 24-48hrs without evidence of haemodynamically instability which is NOT regarded as Rx failure or rupture)