Ectopic Pregnancy: Clinical Manifestations and Diagnosis

1/17/2016
Ectopicpregnancy:Clinicalmanifestationsanddiagnosis
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Author
TogasTulandi,MD,MHCM
SectionEditor
RobertLBarbieri,MD
DeputyEditor
SandyJFalk,MD,FACOG
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Dec2015.|Thistopiclastupdated:Sep02,2015.
INTRODUCTIONAnectopicpregnancyisanextrauterinepregnancy.Almostallectopicpregnanciesoccurin
thefallopiantube(98percent)[1],butotherpossiblesitesinclude:cervical,interstitial(alsoreferredtoascornual
apregnancylocatedintheproximalsegmentofthefallopiantubethatisembeddedwithinthemuscularwallofthe
uterus),hysterotomyscar,intramural,ovarian,orabdominal.Inaddition,inrarecases,amultiplegestationmaybe
heterotopic(includebothauterineandextrauterinepregnancy).
Thediagnosisofectopicpregnancyisbaseduponacombinationofmeasurementoftheserumquantitativehuman
chorionicgonadotropin(hCG)andfindingsontransvaginalultrasonography(TVUS).
Theclinicalmanifestationsanddiagnosisofectopicpregnancywillbereviewedhere.Thistopicwillfocusmainly
onthediagnosisoftubalpregnancy.Thesurgicaltreatmentofectopicpregnancyisreviewedelsewhere.Related
topicsregardingectopicpregnancyarediscussedindetailseparately,including:
Epidemiology,riskfactors,andpathology(see"Ectopicpregnancy:Incidence,riskfactors,andpathology")
Managementwithmethotrexate(see"Ectopicpregnancy:Choosingatreatmentandmethotrexatetherapy")
Surgicaltreatment(see"Ectopicpregnancy:Surgicaltreatment")
Expectantmanagement(see"Ectopicpregnancy:Expectantmanagement")
Diagnosisandmanagementofuncommonsites(see"Abdominalpregnancy,cesareanscarpregnancy,and
heterotopicpregnancy")
CLINICALPRESENTATIONThemostcommonclinicalpresentationofectopicpregnancyisfirsttrimester
vaginalbleedingand/orabdominalpain[2].Ectopicpregnancymayalsobeasymptomatic.
Normalpregnancydiscomforts(eg,breasttenderness,frequenturination,nausea)aresometimespresentin
additiontothesymptomsspecificallyassociatedwithectopicpregnancy.Theremaybealowerlikelihoodofearly
pregnancysymptoms,becauseprogesterone,estradiol,andhumanchorionicgonadotropin(hCG)maybelowerin
ectopicpregnancythaninnormalpregnancy[35].
Inaretrospectivestudyof2026pregnantwomenwhopresentedtotheemergencydepartmentwithfirsttrimester
vaginalbleedingandabdominalpain,376(18percent)werediagnosedwithectopicpregnancy.Ofthese376
women,76percenthadvaginalbleedingand66percenthadabdominalpain[6].Inapopulationbasedregistryof
ectopicpregnancyfromFrance,theincidenceofrupturewas18percent[7].
Clinicalmanifestationsofectopicpregnancytypicallyappearsixtoeightweeksafterthelastnormalmenstrual
period,butcanoccurlater,especiallyifthepregnancyisinanextrauterinesiteotherthanthefallopiantube.
Anectopicpregnancymaybeunrupturedorrupturedatthetimeofpresentationtomedicalcare.Tubalrupture(or
ruptureofotherstructuresinwhichanectopicpregnancyisimplanted)canresultinlifethreateninghemorrhage.
Anysymptomssuggestiveofruptureshouldbenoted.Theseincludesevereorpersistentabdominalpainor
symptomssuggestiveofongoingbloodloss(eg,feelingfaintorlossofconsciousness).
Basedupontheconcernabouttheriskofruptureatthetimeorafterpresentation,cliniciansshouldconsider
ectopicpregnancyasadiagnosisinanywomanofreproductiveagewithvaginalbleedingand/orabdominalpain
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whohasthefollowingcharacteristics:(1)pregnant,butdoesnothaveaconfirmedintrauterinepregnancy(IUP)(2)
pregnancystatusuncertain,particularlyifamenorrheaof>4weeksprecededthecurrentvaginalbleeding(3)in
rarecases,awomanwhopresentswithhemodynamicinstabilityandanacuteabdomenthatisnotexplainedby
anotherdiagnosis.
VaginalbleedingTheamountandtimingofvaginalbleedingvaryandthereisnobleedingpatternthatis
pathognomonicforectopicpregnancy.Bleedingmayrangefromscantbrownstainingtohemorrhage.Bleedingis
typicallyintermittent,butmayoccurasasingleepisodeorcontinuously.
Thevaginalbleedingassociatedwithectopicpregnancyistypicallyprecededbyamenorrhea.However,some
womenmaymisinterpretbleedingasnormalmenses,andmaynotrealizetheyarepregnantpriortodeveloping
symptomsassociatedwithectopicpregnancy.Thisisparticularlytrueinwomenwhohaveirregularmensesor
whodonotkeeptrackofmenstrualcycles.
Bleedingoccursinmanyotherconditionsinearlypregnancy.(See'Differentialdiagnosis'below.)
AbdominalpainThepainassociatedwithectopicpregnancyisusuallylocatedinthepelvicarea.Itmaybe
diffuseorlocalizedtooneside.Incasesinwhichthereisintraperitonealbloodthatreachestheupperabdomenor
inrarecasesofabdominalpregnancy,thepainmaybeinthemiddleorupperabdomen.Ifthereissufficient
intraabdominalbleedingtoreachthediaphragm,theremaybereferredpainthatisfeltintheshoulder.Blood
poolingintheposteriorculdesac(pouchofDouglas)maycauseanurgetodefecate.
Thetiming,character,andseverityofabdominalpainvary,andthereisnopainpatternthatispathognomonicfor
ectopicpregnancy.Theonsetofthepainmaybeabruptorslow,andthepainmaybecontinuousorintermittent.
Thepainmaybedullorsharpitisgenerallynotcrampy.Thepainmaybemildorsevere.Tubalrupturemaybe
associatedwithanabruptonsetofseverepain,butrupturemayalsopresentwithmildorintermittentpain.
DIAGNOSTICEVALUATION
OverviewThemaingoalsandstepsoftheevaluationofawomanwithasuspectedectopicpregnancyare:
Confirmthatthepatientispregnant(see'Humanchorionicgonadotropin'below).
Determinewhetherthepregnancyisintrauterineorectopic(inrarecases,thepregnancyisheterotopic).
Determinethesiteoftheectopicpregnancy.
Determinewhetherthestructureinwhichthepregnancyisimplanted(mostcommonly,thefallopiantube)
hasrupturedandwhetherthepatientishemodynamicallystable.Failuretodiagnoseectopicpregnancy
beforetubalrupturelimitsthetreatmentoptionsandincreasesmaternalmorbidityandmortality.
Performadditionaltestingtoguidefurthermanagement(eg,bloodtypeandantibodyscreen,pretreatment
testingformethotrexatetherapy).
HistoryAmenstrualhistoryshouldbetakenandtheestimatedgestationalageshouldbecalculated.(See
"Prenatalassessmentofgestationalageandestimateddateofdelivery".)
Thehistoryshouldfocusonthepresenceandcharacteristicsofvaginalbleedingandabdominalpain.(See
'Clinicalpresentation'above.)
Riskfactorsforectopicpregnancyshouldbeelicited,includingpriorectopicpregnancy,currentuseofan
intrauterinedevice,priortuballigation,andinvitrofertilization(IVF)(table1).However,over50percentofwomen
areasymptomaticbeforetubalruptureanddonothaveanidentifiableriskfactorforectopicpregnancy[8].A
populationbasedFrenchstudyidentifiedfourfactorsthatincreasedtheriskofrupturewhenanectopicpregnancy
wassuspected:(1)neverhavingusedcontraception,(2)historyoftubaldamageandinfertility,(3)inductionof
ovulation,and(4)highlevelofhumanchorionicgonadotropin(hCG,atleast10,000IU/L)[7].Theoverallrateof
tubalruptureinthisserieswas18percent.(See"Ectopicpregnancy:Incidence,riskfactors,andpathology",
sectionon'Riskfactors'.)
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Themedicalandsurgicalhistoryshouldbereviewed,sincethismayimpacttreatment.Thefocusshouldbeon
obstetrichistoryandpelvicorabdominalsurgicalhistoryandmedicalcomorbiditiesthatarepotential
contraindicationsforsurgeryormethotrexatetherapy(eg,renalorhepaticdisease).(See"Ectopicpregnancy:
Choosingatreatmentandmethotrexatetherapy",sectionon'Contraindications'.)
PhysicalexaminationVitalsignsshouldbemeasuredandhemodynamicstabilityassessed.Inyoung,healthy
patientswithbloodloss,assessingthevitalsignsshouldincludeanevaluationforposturalchange.However,vital
signs,includingposturalchanges,maybenormalearlyinthecourseofsignificantbleedingduetocompensatory
mechanisms[9].Womenwithhemodynamicinstabilityandsuspectedectopicpregnancyrequireemergency
surgery.(See"Initialmanagementoftraumainadults",sectionon'Circulation'.)
Theabdominalexaminationisoftenunremarkableormayreveallowerabdominaltenderness.Ifrupturewith
significantbleedinghasoccurred,theabdomenmaybedistendedanddiffuseorlocalizedtendernesstopalpation
and/orreboundtendernessmaybefoundonexamination.
Acompletepelvicexaminationshouldbeperformed.Thespeculumexaminationisusedtoconfirmthattheuterus
isthesourceofbleeding(ratherthanacervicalorvaginallesion)andtoassessthevolumeofbleedingbynoting
thequantityofbloodinthevaginaandpresenceorabsenceofactivebleedingfromthecervix.
Abimanualpelvicexaminationisperformedtheexaminationisoftenunremarkableinawomanwithasmall,
unrupturedectopicpregnancy.Palpationoftheadnexashouldbeperformedwithonlyasmalldegreeofpressure,
sinceexcessivepressuremayruptureanectopicpregnancy.Findingsonexaminationmayincludecervical
motion,adnexal,and/orabdominaltenderness.Anadnexalmassisnotedinsomewomen.
Theuterusmaybesomewhatenlarged,butwilllikelybesmallerthanappropriateforgestationalage.Uterine
enlargementinwomenwithectopicpregnancymaybeduetoendocrinechangesofpregnancy,rarecasesof
heterotopicpregnancy,orincidentaluterinepathology(mostcommonly,uterinefibroids).
DiagnostictestingThetestsusedtodiagnoseanectopicpregnancyareacombinationofserumquantitative
hCGlevelandtransvaginalultrasound(TVUS)(algorithm1andtable2).
TransvaginalultrasoundTVUSisthemostusefulimagingtestfordeterminingthelocationofapregnancy.
TVUSshouldbeperformedaspartoftheinitialevaluationandmayneedtoberepeated,dependinguponthehCG
levelorasuspicionofrupture.Theultrasoundshouldbeperformedbyaclinicianwithexpertiseingynecologic
ultrasoundandwiththeevaluationofectopicpregnancy,wheneverpossible.
TVUSalone(withoutmeasurementofhCG)canexcludeordiagnoseanectopicpregnancyonlyifoneofthe
followingfindingsispresent:
Findingsdiagnosticofanintrauterinepregnancy(IUP,gestationalsacwithayolksacorembryo).
Findingsdiagnosticofapregnancyatanectopicsite(gestationalsacwithayolksacorembryo).
Ineithercase,agestationalsacaloneisnotsufficientfordiagnosis.Insomeectopicgestations,apseudosacis
formedthatmayappeartobeagestationalsac(see"Ultrasonographyofpregnancyofunknownlocation",section
on'Pseudosac').Cardiacactivitymayormaynotbepresent.
Inthegreatmajorityofcases,eithertwofindingsaboveexcludesordiagnosesanectopicgestation.Therare
exceptionsareheterotopicpregnanciesandmisdiagnosesofanIUP(ie,interstitialpregnancyorrudimentaryhorn
pregnancy).Inareviewof568casesofrudimentaryuterinehornpregnanciesfrom1900to1999,arupturerateof
50percentwasfoundwith80percentoccurringbeforethethirdtrimester[10].(See'Heterotopicpregnancy'below
and'Interstitialpregnancy'below.)
TVUScanalsodetectfindingsthataresuggestive,butnotdiagnostic,ofectopicpregnancy.Anadnexalmassis
themostcommonultrasoundfindinginectopicpregnancyandispresentin89percentormoreofcases[1113].
IfTVUSisnondiagnostic,itmaybebecausethegestationistooearlytobevisualizedonultrasound.Ifso,serial
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measurementsoftheserumhCGconcentrationshouldbetakenuntilthehCGdiscriminatoryzoneisreached[14].
(See'Clinicalprotocol'below.)
Theultrasoundexaminationisalsousedtoevaluatewhetherruptureofthetubeorotherstructurehasoccurred.A
findingofechogenicfluid(consistentwithblood)inthepelvicculdesacand/orabdomenisconsistentwith
rupture.However,asmallamountoffluidispresentinmanywomenandasmallamountofbloodmaybepresent
inotherconditions(eg,spontaneousabortion).Arupturedovariancystisanotherconditionthatiscommonin
pregnantwomenandmayresultinasmallorlargeamountofblood.Ruptureisindicatedbyultrasoundfindingsof
freefluid(blood)intheabdominalcavity.
UltrasoundevaluationforectopicpregnancyversusIUPisdiscussedindetailseparately.(See"Ultrasonography
ofpregnancyofunknownlocation".)
Eitherultrasoundorotherabdominalimagingmodalitiesareusedforevaluationintherarecasesofabdominal
pregnancy.(See"Abdominalpregnancy,cesareanscarpregnancy,andheterotopicpregnancy",sectionon
'Diagnosticevaluation'.)
HumanchorionicgonadotropinMeasurementofhCGisperformedinitiallytodiagnosepregnancyand
thenfollowedtoassessforectopicpregnancy.Forfollowup,hCGismeasuredserially(every48to72hours)to
determinewhethertheincreaseisconsistentwithanabnormalpregnancy.AsinglehCGmeasurementalone
cannotconfirmthediagnosisofectopicornormalpregnancy.
TheinitialtesttodiagnosepregnancymaybeeitheraurineorserumhCG.Onceapregnancyisconfirmed,if
ectopicpregnancyissuspected,theserumhCGisthenrepeatedserially(typicallyeverytwodays)toassess
whethertheincreaseinconcentrationisconsistentwithanabnormalpregnancy.Insomecases,thediagnosisof
ectopicpregnancycanbemadeafterasinglemeasurementofhCGincombinationwithtransvaginalultrasound,if
thehCGisabovethediscriminatoryzoneandtransvaginalultrasoundshowsnoevidenceofanintrauterine
pregnancyandthepresenceoffindingsthatsuggestanectopicpregnancy.(See'Transvaginalultrasound'above.)
Inpregnantwomen,hCGcanbedetectedinserumandurineasearlyaseightdaysaftertheluteinizinghormone
surge(approximately21to22daysafterthefirstdayofthelastmenstrualperiodinwomenwith28daycycles).
ThehCGconcentrationinanormalIUPrisesinacurvilinearfashionuntilabout41daysofgestation,afterwhichit
risesmoreslowlyuntilapproximately10weeks,andthendeclinesuntilreachingaplateauinthesecondandthird
trimesters[15].ItisnotpossibletodeterminewhetherapregnancyisnormalfromasinglehCGlevelbecause
thereisawiderangeofnormallevelsateachweekofpregnancy[16].(See"Clinicalmanifestationsanddiagnosis
ofearlypregnancy",sectionon'Serumpregnancytest'and"Humanchorionicgonadotropin:Testinginpregnancy
andgestationaltrophoblasticdiseaseandcausesoflowpersistentlevels",sectionon'Pregnancy'.)
StudiesinviableIUPshavereportedthefollowingchangesinserumhCG[17,18]:
Themeandoublingtimeforthehormonerangesfrom1.4to2.1daysinearlypregnancy.
In85percentofviableIUPs,thehCGconcentrationrisesbyatleast66percentevery48hoursduringthe
first40daysofpregnancyonly15percentofviablepregnancieshavearateofriselessthanthisthreshold.
Theslowestrecordedriseover48hoursassociatedwithaviableIUPwas53percent.
AserumhCGthatdoesnotriseappropriatelyisconsistentwithanabnormalpregnancy.ThehCGconcentration
risesatamuchslowerrateinmost,butnotall,ectopicandnonviableIUPs[18,19].Inoneseries,asanexample,
only21percentofectopicpregnancieswereassociatedwithhCGlevelsthatfollowedtheminimumdoublingtime
ofaviableIUP(definedinthisseriesas53percentincreaseovertwodays)[18].
AdecreasinghCGconcentrationismostconsistentwithafailedpregnancy(eg,arrestedpregnancy,anembryonic
pregnancy,tubalabortion,spontaneouslyresolvingectopicpregnancy,completeorincompleteabortion).
ThehCGresultvariesacrossdifferentassaysandlaboratories.Theintraassayandinterassayvariabilitiesdepend
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onthetypeofassay.Inonestudy,theintraassayandinterassaycoefficientofvariationwere4.87and
6.25percent,respectively[20].Thus,interpretationofserialhCGconcentrationsismorereliablewhentheassays
areperformedinthesamelaboratory.Inaddition,thepossibilityoffalselypositiveornegativehCGtestresults
shouldbeconsidered[21,22].(See"Humanchorionicgonadotropin:Testinginpregnancyandgestational
trophoblasticdiseaseandcausesoflowpersistentlevels",sectionon'Falsenegativetest(hookeffect)'and
"Humanchorionicgonadotropin:Testinginpregnancyandgestationaltrophoblasticdiseaseandcausesoflow
persistentlevels",sectionon'Falsepositivetestor"phantomhCG"'.)
DiscriminatoryzoneThediscriminatoryzoneistheserumhCGlevelabovewhichagestationalsac
shouldbevisualizedbyTVUSifanIUPispresent.
Inmostinstitutions,thediscriminatoryzoneisaserumhCGlevelof1500or2000IU/LwithTVUS.Thereported
sensitivityandspecificityofhCGof>1500IU/Lare15.2and93.4percent,andforanhCGlevelof>2000IU/L,
theyare10.9and95.2percent,respectively[23].Thelevelishigherfortransabdominalultrasound(approximately
6500IU/L),butTVUSisthestandardmodalityusedtoevaluateectopicpregnancy.
Settingthediscriminatoryzoneat2000IU/Linsteadof1500IU/Lminimizestheriskofinterferingwithaviable
IUP,ifpresent,butincreasestheriskofdelayingdiagnosisofanectopicpregnancy.
However,thecorrectleveltouseforthediscriminatoryzoneiscontroversial.Theuseof1500or2000IU/Lasthe
discriminatoryzoneisbaseduponobservationsthatanintrauterinegestationalsaccouldbedetectedbyTVUSin
patientswithserumhCGconcentrationsaslowas800IU/Landwasusuallyidentifiedbyexpert
ultrasonographersatconcentrationsabove1500to2000IU/L[24].Inonerepresentativestudy,185of188(98
percent)IUPsinwomenwithhCGabove1500IU/Lwerevisualized[25].Itisimportanttonotethatthereisa
variationinthelevelofhCGacrosspregnanciesforeachgestationalageandthediscriminatorylevelsarenot
alwaysreliable.Accordingly,beforedecidingonmethotrexatetreatment,onehastobesurethatthereisno
possibilityofaviableintrauterinepregnancy.
Anothercauseforvariationofthediscriminatoryzoneisthatitisdependentupontheskilloftheultrasonographer,
thequalityoftheultrasoundequipment,thepresenceofphysicalfactors(eg,fibroids,multiplegestation),andthe
laboratorycharacteristicsofthehCGassayused.
ClinicalprotocolTheclinicalprotocolfortheevaluationforanectopicpregnancyincludesassessment
withserumhCGandTVUS:
HCGbelowthediscriminatoryzoneAserumhCGconcentration<1500or2000IU/L(oranothervalue,
thediscriminatoryzonefortheinstitutionshouldbeused)shouldbefollowedbyrepeatedmeasurementof
quantitativehCGtofollowtherateofrise.Asnotedabove,foraviableIUP,themeanhCGdoublingtimeis
1.4to2.1daysandslowestrecordedriseover48hoursassociatedwithaviableIUPwas53percent.Also,
thesamelaboratoryshouldbeusedforserialmeasurements.(See'Humanchorionicgonadotropin'above.)
ThemostcommonprotocolistomeasurethehCGeverytwodays.Inourpractice,wefindthat
measurementevery72hoursismorepracticalthanevery48hours,andallowing72hoursfordoublinghelps
toavoidmisclassifyingthoseviablepregnancieswithslowerthanaveragedoublingtimes.Thus,theprotocol
isasfollows:
hCGisrisingnormally(increasingbyatleast53percentin48hoursORdoublingin72hours)The
patientshouldbeevaluatedwithTVUSwhenthehCGreachesthediscriminatoryzone.Atthattime,an
IUPorectopicpregnancycanbediagnosedbyTVUS.
hCGisrising,butNOTnormallyThelackofanormalriseinhCGacrossthreemeasurements(the
initialserumquantitativehCGandtwoadditionalserialmeasurements)isconsistentwithanabnormal
pregnancy(anectopicgestationorIUPthatwillultimatelyabort).ThehCGlevelmayberisingslowly
ormayplateauatorveryclosetothepreviouslevel.Thecliniciancanbereasonablycertainthata
normalIUPisnotpresent.Thenumberofserialmeasurementstousetomakethediagnosishasnot
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beenwellstudied.Somedatasuggestthatuseofthreeserialmeasurementsismoreeffectivethantwo
measurements[26].
InpatientswithanabnormalriseinhCG,theTVUSshouldberepeated.Iftherearefindingsthat
confirmanIUP,anectopicpregnancyisexcludedandthepatientshouldbemanagedasafailed
pregnancy.Ifanadnexalmassconsistentwithanectopicpregnancyisvisualized,thenmedicalor
surgicaltreatmentisadministeredforapresumedectopicpregnancy.Ifanadnexalmassisnot
visualized,somecliniciansadministermethotrexateandothersperformcurettagetoexcludeanIUP
andtherebyavoidmedicaltherapyofnonviableIUP[27].(See'Curettage'below.)
hCGisdecreasingAdecreasinghCGismostconsistentwithafailedpregnancy(eg,spontaneous
abortion,tubalabortion,spontaneouslyresolvingectopicpregnancy).Tofollowupwiththesepatients,
weeklyhCGconcentrationsshouldbemeasureduntiltheresultisundetectable.
Patientswhoarebeingfollowedforsuspectedectopicpregnancyshouldbecounseledabouttheriskofrupture
andshouldbeadvisedtocallifsymptomsassociatedwithruptureoccur.Theseincludethenewonsetofora
significantworseningofabdominalpain,vaginalhemorrhage,orfeelingfaint.Inaddition,womenwithasuspected
ectopicpregnancyshouldbecounseledaboutpossibleoutcomesoftheevaluation,includingviableIUPortheend
ofapregnancywithtreatmentforectopicpregnancy.
hCGabovethediscriminatoryzoneForwomenwithaquantitativeserumhCGabovethediscriminatory
zone,theresultsofTVUSguidemanagement.IfTVUSdoesnotrevealanIUPandshowsacomplex
adnexalmass,anextrauterinepregnancyisalmostcertain.Treatmentofectopicpregnancyshouldbe
instituted.
Thediagnosisofectopicpregnancyislesscertainifnocomplexadnexalmasscanbevisualized,since
thereisvariabilityinthelevelofexpertiseamongultrasonographers.Furthermore,aserumhCG>1500IU/L
withoutvisualizationofintrauterineorextrauterinepathologymayrepresentamultiplegestation,sincethere
isnoprovendiscriminatorylevelformultiplegestations.Forthesereasons,ournextstepinthisclinical
scenarioistorepeattheTVUSexaminationandhCGconcentrationtwodayslater.IfanIUPisstillnot
observedonTVUS,thenthepregnancyisabnormal.
AncillarydiagnostictestsAdditionaldiagnostictestshavebeenusedinwomenwithsuspectedectopic
pregnancy.Exceptinselectedcases,suchtestsdonotprovideadditionalclinicallyusefulinformation.
ProgesteroneSerumprogesteroneconcentrationsarehigherinviableIUPsthaninectopicpregnancies
andIUPsthataredestinedtoabort[28].Ametaanalysisof26cohortstudiesincluding9436womeninthefirst
trimesterofpregnancyevaluateduseofasinglemeasurementofserumprogesteroneforthediagnosisofa
nonviablepregnancy[29].Forwomenwithbleedingorpainandaninconclusivepelvicultrasound,aprogesterone
<3.2to6ng/mL(10.2to19.1nmol/L)hadasensitivityof75percentandaspecificityof98percent.Forwomen
withbleedingorpainalone,aprogesterone<10ng/mL(31.8nmol/L)hadasensitivityof67percentanda
specificityof96percent.
Thepredictivevalueofalowserumprogesteroneforidentifyingnonviablepregnanciesvarieswiththepatient
population.Thesensitivityandspecificityofalowserumprogesteroneconcentrationforpredictinganonviable
pregnancyinspontaneouslypregnantpatientsaredifferentfromthoseininfertilepatientswhohaveundergone
controlledovarianhyperstimulationforIVForintrauterineinsemination[30].
Inourexperience,progesteronemeasurementsmerelyconfirmdiagnosticimpressionsalreadyobtainedbyhCG
measurementsandtransvaginalsonography.Wedonotroutinelymeasureserumprogesterone.However,
measurementofserumprogesteronemaybeusefulinapatientwithabdominalpainandbleedingandwhohasa
serumhCGlevelbelowthatexpectedforhergestationalage.Itshouldbenoted,however,thatthedefinitionofa
lowprogesteroneisunclear.
CurettageTheintrauterinelocationofapregnancyisdiagnosedwithcertaintyiftrophoblastictissueis
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obtainedbyuterinecurettage.Obviously,theuseofcurettageasadiagnostictoolislimitedbythepotentialfor
disruptionofaviablepregnancy.Moreover,falsenegativescanoccur:chorionicvilliarenotdetectedby
histopathologyin20percentofcurettagespecimensfromelectiveterminationofpregnancy[31].Pipelle
endometrialbiopsyisevenlesssensitivethancurettagefordetectionofvillisensitivitiesreportedintwosmall
serieswere30and60percent[32,33].Ifcurettageisperformed,serumhCGlevelscanbefollowedpostcurettage
ifhistopathologydoesnotconfirmtheclinicalimpression.WhenanIUPhasbeenevacuated,hCGlevelsshould
dropbyatleast15percentthedayafterevacuation[27].
SomeexpertshaverecommendedperformingcurettageonlyonwomenwithbothahCGconcentrationbelowthe
discriminatoryzoneandalowdoublingrate[34,35].Approximately30percentofthesepatientshaveanonviable
intrauterinegestationandtheremainderhaveanectopicpregnancy[35,36].Knowingtheresultsofcurettage
avoidsunnecessarymethotrexatetreatmentofthe30percentofpatientswithoutectopicpregnancy.
Adecisionanalysiscomparingthecost/complicationratesinpatientswhoundergodiagnosticcurettagebefore
administrationofmethotrexatewiththosewhodonothaveacurettageconcludedtherewasnosignificantbenefit
ofoneapproachovertheother[36].However,theauthors'preferencewastoperformcurettageinthesepatients
tobemorecertainofthediagnosis,andfeltthisinformationwasusefulprognostically(eg,riskofrecurrence)and
forfuturedecisionmaking.Incontrast,weandothersbelieveitismorepracticalandlessinvasivetocontinue
observationoradministeronedoseofmethotrexatethantoperformcurettage[37,38].Thesideeffectsofonedose
ofmethotrexatearenegligible.Inaddition,curettagecarriesariskofintrauterineadhesionformation.(See"Ectopic
pregnancy:Choosingatreatmentandmethotrexatetherapy"and"Intrauterineadhesions".)
OthertestsRarely,laparoscopyisusedtoconfirmthediagnosisifhCGandultrasoundresultsare
ambiguous.Anectopicpregnancydetectedatlaparoscopyshouldbetreatedimmediatelybysurgery.Inthis
situation,amedicalapproachconfersadditionalriskandhasnoprovenbenefit.
Historically,culdocentesiswasusedtodetectbloodintheposteriorculdesachowever,thisfindingcanbeeasily
demonstratedwithtransvaginalultrasound.Bloodintheposteriorculdesacmaybefrombleedingfroman
unrupturedorrupturedtubalpregnancy,butitmayalsobetheresultofarupturedovariancyst.Therefore,a
culdocentesispositiveforbloodisnondiagnostic.(See"Culdocentesis".)
AdditionaltestingAdditionaltestingisperformedtoevaluatethepatientshemodynamicstatus,Rh(D)type.If
methotrexatetreatmentisapossibility,pretreatmentlaboratorytestsshouldbedrawn.
CompletebloodcountWomenwithsuspectedectopicpregnancyshouldbeevaluatedforanemiawitha
hemoglobinand/orhematocrit.
Inseverecases,ifheavybleedingissuspected,measurementofplateletsorcoagulationtestsmayalsobe
indicated.(See"Massivebloodtransfusion",sectionon'Alterationsinhemostasis'.)
Ifectopicpregnancyisdiagnosedandtreatmentwithmethotrexateisconsidered,acompletebloodcountispartof
thepretreatmentlaboratoryevaluation.
BloodtypeandscreenARh(D)typingandantibodyscreenshouldbedrawnifnotpreviouslyperformed
duringthecurrentpregnancy.WomenwithbleedinginpregnancywhoareRh(D)negativeshouldbegivenantiD
immuneglobulin.(See"PreventionofRh(D)alloimmunization".)
Ifsignificantbleedingissuspected,asampleshouldbesenttothebloodbankforcrossmatchingforpotential
transfusion.
PretreatmentlaboratorytestsForwomentreatedwithmethotrexate,pretreatmenttestingtypicallyincludes
acompletebloodcountandrenalandliverfunctiontests.(See"Ectopicpregnancy:Choosingatreatmentand
methotrexatetherapy",sectionon'Pretreatmenttesting'.)
DIAGNOSISThediagnosisofectopicpregnancyisaclinicaldiagnosismadebaseduponserialserumhuman
chorionicgonadotropin(hCG)testingandtransvaginalultrasound(TVUS).(See'Transvaginalultrasound'above
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and'Humanchorionicgonadotropin'above.)
Histologicconfirmationofthediagnosisisnottypicallyrequired.Inselectedcases,uterinecurettageisperformed
toconfirmtheabsenceofanintrauterinepregnancy(IUP)priortomethotrexatetherapy.Ifanectopicpregnancyis
treatedsurgically,histologicconfirmationisobtainedfollowingtreatment.
DiagnosticcriteriaThediagnosticcriteriadependupontherelationshiptothehCGdiscriminatoryzone(serum
hCGlevelabovewhichagestationalsacshouldbevisualizedbyTVUSifanIUPispresent).ThehCGlevelof
thediscriminatoryzonevaries,butinmostinstitutionsitis1500to2000IU/L(see'Discriminatoryzone'aboveand
'Clinicalprotocol'above):
Belowthediscriminatoryzone
IftheserialhCGleveldoesnotriseappropriatelyacrossatleastthreemeasurements48to72hours
apartandthereisnoevidenceonTVUSthatconfirmsanIUP,thepregnancyisconsideredabnormal.
Apresumptivediagnosisofectopicpregnancycanbemadeandthepatientmaybetreated.Inselected
cases,uterinecurettageisperformedtoconfirmtheabsenceofanIUP(see'Curettage'above).
IftheserialserumhCGlevelisrisingappropriately,thepatientisfolloweduntilthehCGisabovethe
discriminatoryzone.
AbovethediscriminatoryzoneThediagnosisismadebasedupontheabsenceofTVUSfindingsthat
diagnoseanIUPORfindingsatanextrauterinesitethatconfirmanectopicpregnancy.Thepresenceofa
gestationalsacwithayolksacorembryoisdiagnosticofapregnancy.Thegestationalsacisanearly
findingandissuggestiveof,butdoesnotfullyconfirm,anIUP(see'Transvaginalultrasound'above).
Ultrasoundfindingssuggestiveofanectopicpregnancyinthefallopiantube,ovary,orothersitesfurthersupport
thediagnosis,butarenotdiagnosticontheirown(see'Transvaginalultrasound'above).
IntheabsenceofadefinitivesonogramconfirminganIUPorhistopathologicfindings,itissometimesimpossible
todifferentiatebetweenanectopicpregnancyandanearlyfailedintrauterinegestation.Thisisreferredtoasa
pregnancyofunknownlocationand8to40percentareultimatelydiagnosedasectopicpregnancies[23].
RupturedversusnonrupturedectopicpregnancyDiagnosisofruptureofthestructurewithinwhichthe
ectopicgestationisimplanted(usuallythefallopiantube)isaclinicaldiagnosis.Thetypicalfindingsofruptureare
abdominalpain,shoulderpainduetodiaphragmaticirritationbybloodintheperitonealcavity,andeventually,
hypotensionandshock.Abdominalexaminationfindingsincludetendernessandpossibleperitonealsigns.The
typicalfindingonTVUSisfreebloodintheperitonealcavity.However,thepresenceorabsenceofperitonealfree
fluidisnotareliableindicatorofwhetheranectopicpregnancyhasruptured.(See"Ultrasonographyofpregnancy
ofunknownlocation",sectionon'Peritonealfreefluid'.)
Forwomenwhoundergosurgery,thediagnosisofrupturecanbemadebydirectvisualization.
DIFFERENTIALDIAGNOSISTheclassicsymptomsofectopicpregnancyarevaginalbleedingandabdominal
pain.
Thedifferentialdiagnosisofbleedingorpainearlyinpregnancyalsoincludes[39]:
Physiologic(ie,believedtoberelatedtoimplantation)
Spontaneousabortion
Gestationaltrophoblasticdisease
Cervical,vaginal,oruterinepathology
Subchorionichematoma
Nonuterinesourcesofbleedingcanbeidentifiedbyphysicalexamination.Screeningforcervicalcancershould
alsobeperformed,asappropriate(table3).(See"Differentialdiagnosisofgenitaltractbleedinginwomen"and
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"Screeningforcervicalcancer".)
Evenifanothersourceofbleedingisidentified,allwomenwithfirsttrimesterbleedingshouldbeevaluatedby
transvaginalultrasonography.Whenthehumanchorionicgonadotropin(hCG)concentrationisunusuallyhighfor
thegestationalage,gestationaltrophoblasticdiseaseshouldbesuspected.Theevaluationoffirsttrimestervaginal
bleedingisoutlinedinthealgorithm(algorithm2)andisdiscussedseparately.(See"Overviewoftheetiologyand
evaluationofvaginalbleedinginpregnantwomen"and"Spontaneousabortion:Riskfactors,etiology,clinical
manifestations,anddiagnosticevaluation"and"Hydatidiformmole:Epidemiology,clinicalfeatures,and
diagnosis".)
Thedifferentialdiagnosisoflowerabdominalpaininwomenincludesurinarytractinfection,kidneystones,
diverticulitis,appendicitis,ovarianneoplasms,ovariancystrupture,ovariantorsion,endometriosis,endometritis,
leiomyomas,pelvicinflammatorydisease,andpregnancyrelatedconditions.(See"Diagnosticapproachto
abdominalpaininadults".)
SPECIALISSUES
MultiplegestationInwomenwithanintrauterinemultiplepregnancy,theserumhumanchorionicgonadotropin
(hCG)levelcouldbehigherthan1500mIU/mLandyetultrasoundexaminationwillnotrevealanintrauterine
pregnancy(IUP)[14].Levelsofover9000IU/Lhavebeendescribedforintrauterinetripletpregnanciesunobserved
bytransvaginalultrasound(TVUS)[40].
HeterotopicpregnancyTheinvestigationforectopicpregnancycanbeterminated,undermostcircumstances,
ifatransvaginalsonogramrevealsanIUP.Heterotopicpregnancy(combinedintrauterineandextrauterine
pregnancy)israre,exceptamongwomenconceivingthroughinvitrofertilization(IVF).Theextrauterinepregnancy
isusuallyinthefallopiantube,butcanbeatanotherlocation,suchasthecervix.(See"Abdominalpregnancy,
cesareanscarpregnancy,andheterotopicpregnancy".)
Earlydiagnosisofheterotopicpregnancyisdifficultbecauseoflackofsymptoms.Thus,ahighindexofsuspicion
forthisdiagnosisisimportant,especiallyinpatientswhohaveundergoneIVFandwhoexperienceabdominalpain
orvaginalbleeding.
SerialhCGconcentrationsarenotinterpretableinthepresenceofbothaviableintrauterineandectopicpregnancy.
Onultrasoundexamination,thediagnosisissuggestedbyvisualizationofbothanectopicpregnancyandIUPor
thepresenceofechogenicfluidintheposteriorculdesacinthepresenceofanIUP.Heterotopictubal
pregnancieshavebeenreportedaslateas16weeksofgestation,whileabdominalorrudimentaryhorn
pregnanciescancontinuetodeveloplateingestation[41,42].
Theultrasonographershouldcarefullyexaminenotonlytheuterus,butalsotheadnexaofwomenwhoconceive
followingIVF.WesuggestthatwomenwithaconfirmedIUPwhoareexperiencingabdominalpainorvaginal
bleedingundergoserialTVUSexaminationseveryweekuntilthepossibilityofaconcomitanttubalectopic
pregnancycanbeeliminated.
Thediagnosisandmanagementofheterotopicpregnancyarediscussedseparately.(See"Abdominalpregnancy,
cesareanscarpregnancy,andheterotopicpregnancy",sectionon'Heterotopicpregnancy'.)
UncommonsitesofectopicpregnancyThepossibilitythatanectopicpregnancymayoccurinanontubal
location,orevenbilaterally[43],shouldbeconsidered.Theseectopicpregnancysitesareuncommon,andinclude
cervical,hysterotomyscar,rudimentaryuterinehorn,interstitial,ovarian,andabdominalpregnancy.Regardlessof
thelocation,theendometriumoftenrespondstoovarianandplacentalproductionofpregnancyrelatedhormones,
sovaginalbleedingisacommonsymptom.
Cervicalpregnancyisestimatedtooccurin1/2500to1/18,000pregnanciesandaccountsfor1percentof
ectopicpregnancies[44].
Interstitialpregnancyaccountsforupto1to3percentofectopicpregnancies[45,46].
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Ovarianpregnancyoccursin1/2100to1/60,000pregnanciesandaccountsfor1to3percentofectopic
pregnancies[47].
Abdominalpregnancyaccountsforupto1.4percentofectopicpregnancies[48].Thesepregnanciescango
undetecteduntilanadvancedageandoftenresultinseverehemorrhage[49].Ratesofmaternalmortality
havebeenreportedashighas20percent[41,50].
Intramuralpregnancyreferstopregnancyimplantedwithinthemyometriumoftheuterus.Thistypeof
pregnancyisextremelyrarewithlessthan50reportedcasesintheliterature[51].
OvarianpregnancySonographicdiagnosisofanovarianpregnancyisdifficult.Ultrasoundevaluationfor
ovarianpregnancyisdiscussedindetailseparately.(See"Ultrasonographyofpregnancyofunknownlocation".)
Thediagnosisofovarianpregnancyistypicallymadeatthetimeofsurgery,butdifferentiationfromahemorrhagic
ovariancystorpregnancyinthedistalfallopiantubecanbedifficult.Ultrasoundmaysuggestthediagnosis
preoperatively[47].Stricthistopathologicalcriteriaareusedtodistinguishovarianpregnanciesfromthose
originatinginthefallopiantube.Theexactdiagnosisisnotclinicallyimportant,asthesepregnanciesareusually
treatedbysurgicalexcisionoftheinvolvedorgans.Methotrexatetreatmenthasbeensuccessfulincasereports
[52].(See"Ectopicpregnancy:Incidence,riskfactors,andpathology",sectionon'Ovarianpregnancy'.)
InterstitialpregnancyTheinterstitialportionofthefallopiantubeistheproximalsegmentthatisembedded
withinthemuscularwalloftheuterus.Apregnancyimplantedatthissiteiscalledaninterstitialpregnancy(figure
1)thetermcornualpregnancyisalsowidelyusedtodescribeapregnancyatthislocation.Originally,theterm
cornualpregnancyreferredonlytopregnanciesimplantedineitherthehornofabicornuateuterus,arudimentary
hornofaunicornuateuterus,orinonesideofaseptatedorpartiallyseptateduterus[46].
AninterstitialpregnancycanbedifficulttodistinguishonultrasoundfromanIUPthatiseccentricallypositioned.
Ultrasoundevaluationforinterstitialpregnancyisdiscussedindetailseparately.(See"Ultrasonographyof
pregnancyofunknownlocation".)
Grossly,aninterstitialpregnancyappearsasagestationalswellinglateraltotheinsertionoftheroundligament
(figure1)[46].Theuniqueanatomiclocationofaninterstitialpregnancyoftenleadstoadelayindiagnosis,
althoughanaveragedelayofonlyfourdaysincomparisonwithtubalpregnancieswasreportedinalargeseries
[53].
Interstitialpregnancypresentswithruptureinapproximately20to50percentofcases[5456].Aseriesofcases
ofinterstitialpregnancyreportedtoasurgicalregistryincluded14patientswithtubalrupture,allofwhichwere
before12weeks[54].Thisisincontrasttopreviousreportsthatruptureofinterstitialpregnancyoccurredlatein
pregnancy.Otherclinicalmanifestationsarethesameasforallectopicgestations(pelvicorabdominalpain,
vaginalbleeding)[53].
Althoughthematernalmortalityrateassociatedwithtubalpregnancyisdecreasing,therateforinterstitial
pregnanciesremainsat2to2.5percentbecauseofmisdiagnosisofthesegestationsasIUPs.
OthersitesDiagnosisandmanagementofcesareanscarandabdominalpregnancyarediscussedindetail
separately.(See"Abdominalpregnancy,cesareanscarpregnancy,andheterotopicpregnancy".)
ScreeningasymptomaticwomenRoutineprenatalcaredoesnotincludeserialmeasurementofserumhCG.
Theexceptionstothisarewomenathighriskofanectopicpregnancy,includingthosewithanIVFpregnancy,
pregnancyafterreconstructivesurgeryofthefallopiantube,orpriorhistoryofectopicpregnancy.Forwomenwho
aremonitoredinthisway,anectopicpregnancymaypresentwithanabnormalriseinhCG.Thenormalpatternof
theriseinserumhCGinearlypregnancyisdiscussedbelow.(See'Humanchorionicgonadotropin'above.)
Inourpractice,wemonitorwomenathighriskofectopicpregnancy(table1)withlaboratoryandimagingstudies.
Weusethesameprotocolasforthediagnosisofectopicpregnancy,andstartwiththefirstmissedmensesor
afterembryotransferforIVF.Thegoalistoestablishthediagnosisearlytoavoidrupture.(See"Ectopic
http://www.uptodate.com/contents/ectopicpregnancyclinicalmanifestationsanddiagnosis?topicKey=OBGYN%2F5487&elapsedTimeMs=4&source=searc
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pregnancy:Incidence,riskfactors,andpathology",sectionon'Riskfactors'and"Invitrofertilization",sectionon
'Monitoringforpregnancy'.)
NATURALHISTORYIfleftuntreated,anectopicpregnancyinthefallopiantubecanprogresstoatubal
abortionortubalrupture,oritmayregressspontaneously.
RuptureTubalruptureisusuallyassociatedwithprofoundhemorrhage,whichcanbefatalifsurgeryisnot
performedexpeditiouslytoremovetheectopicgestation.Salpingectomyisthemostcommonsurgical
approachwhenthetubehasruptured.Rupturedectopicpregnancyisthemajorcauseofpregnancyrelated
maternalmortalityinthefirsttrimester[57].Mostofthesedeathsoccurpriortohospitalizationorproximate
tothewoman'sarrivalintheemergencydepartment.
AbortionTubalabortionreferstoexpulsionoftheproductsofconceptionthroughthefimbria.Thiscanbe
followedbyresorptionofthetissueorbyreimplantationofthetrophoblastsintheabdominalcavity(ie,
abdominalpregnancy)orontheovary(ie,ovarianpregnancy).Tubalabortionmaybeaccompaniedbysevere
intraabdominalbleeding,necessitatingsurgicalintervention,orbyminimalbleeding,notrequiringfurther
treatment.
SpontaneousresolutionTheincidenceofspontaneousresolutionofanectopicpregnancyisunknown.In
oneolder(1955)seriesof119hospitalizedpatientswithtypicalectopicpregnancysymptoms,57weresafely
managedexpectantly,withoutsurgicalormedicalintervention(exceptopiates)[58].Itisdifficulttopredict
whichpatientswillexperienceuncomplicatedspontaneousresolution.Potentialcandidatesare
hemodynamicallystablewomenwithaninitialhCGconcentrationlessthan2000IU/Lthatisdeclining[59].
Gestationalproductsleftinthefallopiantubemayresorbcompletelyor,lesscommonly,maycausetubal
obstruction[60].Alternatively,atubalabortionmayoccur.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Ectopicpregnancy(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Ectopic(tubal)pregnancy(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Anectopicpregnancyisanextrauterinepregnancy.Almostallectopicpregnanciesoccurinthefallopiantube
(98percent),butotherpossiblesitesinclude:cervical,interstitial,hysterotomyscar,ovarian,orabdominal.In
rarecases,amultiplegestationmaybeheterotopic(includebothauterineandextrauterinepregnancy).(See
'Introduction'aboveand'Uncommonsitesofectopicpregnancy'above.)
Abdominalpainandvaginalbleedingarethemostcommonsymptomsofectopicpregnancy.Ectopic
pregnancyshouldbesuspectedinanywomenofreproductiveagewiththesesymptoms,especiallythose
whohaveriskfactors(table1).However,over50percentofwomenareasymptomaticbeforetubalrupture
anddonothaveanidentifiableriskfactorforectopicpregnancy.(See'Clinicalpresentation'above.)
Thekeycomponentsoftheevaluationofawomanwithsuspectedectopicgestationareatransvaginal
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ultrasound(TVUS)examinationandquantitativehumanchorionicgonadotropin(hCG)level.ThehCGis
measuredseriallyevery48to72hours.(See'Clinicalprotocol'above.)
Additionaltestingisperformedtoevaluateforanemia,forRh(D)bloodtyping,andforpretreatmentevaluation
forpotentialmethotrexatetherapy.(See'Additionaltesting'above.)
ThediagnosisofectopicpregnancyisaclinicaldiagnosismadebaseduponserialhCGtestingandTVUS.A
diagnosisofectopicpregnancycannotbemadebaseduponasinglehCGresult.Histologicconfirmationof
thediagnosisisnottypicallyrequired.(See'Transvaginalultrasound'aboveand'Humanchorionic
gonadotropin'aboveand'Diagnosis'above.)
ThediagnosticcriteriadependupontherelationshiptothehCGdiscriminatoryzone(serumhCGlevelabove
whichagestationalsacshouldbevisualizedbyTVUSifanintrauterinepregnancy[IUP]ispresent).The
hCGlevelofthediscriminatoryzonevaries,butinmostinstitutionsitis1500to2000IU/L.(See
'Discriminatoryzone'aboveand'Diagnosticcriteria'above.)
IftheserialhCGisrisingabnormally(doesnotincreasebyatleast53percentin48hoursORdoubling
in72hours)andisbelowthediscriminatoryzone,thediagnosisismadebaseduponthehCGpattern.
IfthehCGisabovethediscriminatoryzone,thediagnosisismadebaseduponultrasoundfindingsthat
confirmeitheranintrauterineorextrauterinepregnancy(gestationalsacwithayolksacorembryo).
Diagnosisofruptureofthestructurewithinwhichtheectopicgestationisimplanted(usuallythefallopian
tube)isaclinicaldiagnosismadeprimarilybaseduponafindingofechogenicfluid(consistentwithblood)in
thepelvicculdesacand/orabdomencombinedwiththepresenceofabdominalpainand/ortenderness.(See
'Rupturedversusnonrupturedectopicpregnancy'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
Topic5487Version25.0
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GRAPHICS
Riskfactorsforectopicpregnancy
Degreeofrisk
High
Moderate
Low
Riskfactors
Oddsratio
Previousectopicpregnancy
9.347
Previoustubalsurgery
6.011.5
Tuballigation
3.0139
Tubalpathology
3.525
InuteroDESexposure
2.413
CurrentIUDuse
1.145
Infertility
1.128
Previouscervicitis(gonorrhea,
chlamydia)
2.83.7
Historyofpelvicinflammatory
disease
2.13.0
Multiplesexualpartners
1.44.8
Smoking
2.33.9
Previouspelvic/abdominal
surgery
0.933.8
Vaginaldouching
1.13.1
Earlyageofintercourse(<18
years)
1.12.5
Forwomenundergoingassistedreproductivetechnology(ART)procedures,theriskofectopic
pregnancyvariesaccordingtothetypeofARTprocedure,thewoman'sreproductivehealth
characteristics,andestimatedembryoimplantationpotential. 1
WomenwhoundergoARTareatmuchhigherriskofheterotopicpregnancythanwomenwho
conceivenaturally(152/100,000versus3.3to6.4/100,000). 2
References:
1. ClaytonHB,SchieveLA,PetersonHB,etal.Ectopicpregnancyriskwithassistedreproductive
technologyprocedures.ObstetGynecol2006107:595.
2. ClaytonHB,SchieveLA,PetersonHB,etal.Acomparisonofheterotopicandintrauterineonly
pregnancyoutcomesafterassistedreproductivetechnologiesintheUnitedStatesfrom1999to
2002.FertilSteril200787:303.
Adaptedfrom:
1. AnkumWM,MolBWJ,VanDerVeenF,BossuytPMM.Riskfactorsforectopicpregnancy:ameta
analysis.FertilSteril199665:1093.
2. MurrayH,BaakdahH,BardellT,TulandiT.Diagnosisandtreatmentofectopicpregnancy.CMAJ
2005173:905.
3. BouyerJ,CosteJ,ShojaeiT,etal.Riskfactorsforectopicpregnancy:acomprehensiveanalysis
basedonalargecasecontrol,populationbasedstudyinFrance.AmJEpidemiol2003157:185.
Graphic82282Version5.0
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Testsforsuspectedectopicpregnancy
EP:ectopicpregnancyIUP:intrauterinepregnancyTVS:transvaginalultrasoundhCG:human
chorionicgonadotropin.
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Significanceoffeaturesassociatedwithectopicpregnancy
Features
SN(percent)
SP(percent)
Clinicalfeatures
Estimatedgestationalage<70days
95
27
Vaginalbleeding
69
26
Abdominalpain
97
15
Abdominaltenderness
85
50
Peritonealsigns
23
95
Cervicalmotiontenderness
33
91
Adnexaltenderness
69
62
Adnexalmass
96
100
89
Separatefromovary
93
99
Cardiacactivity
20
100
Yolksacorembryo
37
100
Tubalring/yolksacorembryo
65
99
Any
63
69
Echogenic
56
96
95
98
Transvaginalultrasound
Nointrauterinegestationalsac
Adnexalmass
FluidinpouchofDouglas
ColorflowDoppler
hCGcombinedwithtransvaginalultrasound
Emptyuterus
1000mIU/mL
4396
86100
1500mIU/mL
4099
8496
2000mIU/mL
3848
8098
1000mIU/mL
73
85
1500mIU/mL
4664
9296
2000mIU/mL
55
96
Adnexalmass*
Sn:sensitivitySp:specificityhCG:betahumanchorionicgonadotropin.
*MassorfluidinculdesacforhCG1500mIU/mLand2000mIU/mL.
Datafrom:Ramakrishnan,K,Scheid,DC.Ectopicpregnancy:Forgetthe"classicpresentation"ifyou
wanttocatchitsooner:Anewalgorithmtoimprovedetection.JournalofFamilyPractice200655:388.
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Causesofabnormalgenitaltractbleedinginwomen
Genitaltractdisorders
Uterus
Benigngrowths:
Trauma
Sexualintercourse
Sexualabuse
Endometrialhyperplasia
Foreignbodies(includingintrauterine
device)
Adenomyosis
Pelvictrauma(eg,motorvehicleaccident)
Leiomyomas(fibroids)
Straddleinjuries
Endometrialpolyps
Cancer:
Endometrialadenocarcinoma
Sarcoma
Infection:
Pelvicinflammatorydisease
Endometritis
Ovulatorydysfunction
Cervix
Benigngrowths:
Cervicalpolyps
Ectropion
Endometriosis
Cancer:
Invasivecarcinoma
Metastatic(uterus,choriocarcinoma)
Infection:
Cervicitis
Vulva
Benigngrowths:
Skintags
Sebaceouscysts
Condylomata
Angiokerataoma
Cancer
Vagina
Benigngrowths:
Gartnerductcysts
Polyps
Drugs
Contraception:
Hormonalcontraceptives
Intrauterinedevices
Postmenopausalhormonetherapy
Anticoagulants
Tamoxifen
Corticosteroids
Chemotherapy
Phenytoin
Antipsychoticdrugs
Antibiotics(eg,duetotoxicepidermal
necrolysisorStevensJohnsonsyndrome)
Systemicdisease
Diseasesinvolvingthevulva:
Crohn'sdisease
Behcet'ssyndrome
Pemphigoid
Pemphigus
Erosivelichenplanus
Lymphoma
Bleedingdisorders:
vonWillebranddisease
Thrombocytopeniaorplateletdysfunction
Acuteleukemia
Somecoagulationfactordeficiencies
Advancedliverdisease
Thyroiddisease
Adenosis(aberrantglandulartissue)
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Cancer
Polycysticovarysyndrome
Vaginitis/infection:
Chronicliverdisease
Bacterialvaginosis
Cushing'ssyndrome
Sexuallytransmitteddiseases
Hormonesecretingadrenalandovarian
tumors
Atrophicvaginitis
Uppergenitaltractdisease
Renaldisease
Fallopiantubecancer
Emotionalorphysicalstress
Ovariancancer
Smoking
Pelvicinflammatorydisease
Excessiveexercise
Pregnancycomplications
Diseasesnotaffectingthegenital
tract
Urethritis
Bladdercancer
Urinarytractinfection
Inflammatoryboweldisease
Hemorrhoids
Other
Endometriosis
Vasculartumorsandanomaliesinthe
genitaltract
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Algorithmvaginalbleeding
*Thisstepmaybeomittedinwomenwhoareknowntohaveanintrauterinepregnancy.
Proceeddirectlytoultrasoundexamination.
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Normalfemalereproductiveanatomy
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