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OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Hydatidiformmole:Management
Authors
RossSBerkowitz,MD
DonaldPeterGoldstein,MD
NeilSHorowitz,MD

SectionEditors
RobertLBarbieri,MD
BarbaraGoff,MD

DeputyEditors
SandyJFalk,MD,FACOG
SadhnaRVora,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jul2016.|Thistopiclastupdated:Dec11,2015.
INTRODUCTIONHydatidiformmole(HM)ispartofagroupofdiseasesclassifiedasgestationaltrophoblasticdisease
(GTD),whichoriginateintheplacentaandhavethepotentialtolocallyinvadetheuterusandmetastasize.The
pathogenesisofGTDisuniquebecausethematernaltumorarisesfromgestationalratherthanmaternaltissue[1].
HMismadeupoftwodistinctentities,completehydatidiformmoleandpartialhydatidiformmole.Thesedifferonthebasis
ofchromosomalpattern,grossandmicroscopichistopathology,andclinicalpresentationandoutcome[24].Molar
pregnancies,althoughbenign,areconsideredtobepremalignantbecausetheyhavethecapabilityofdevelopingintoa
malignancy.Malignantdiseaseisreferredtoasgestationaltrophoblasticneoplasia(GTN)thehistologicentitiesincluded
inthisgroupare:

Invasivemole
Choriocarcinoma
Placentalsitetrophoblastictumor
Epithelioidtrophoblastictumor

ThemanagementofHMwillbereviewedhere.ThepathologyofGTD,epidemiologyanddiagnosisofHM,andtopics
regardingGTNarediscussedseparately:
(See"Gestationaltrophoblasticdisease:Pathology".)
(See"Hydatidiformmole:Epidemiology,clinicalfeatures,anddiagnosis".)
(See"Gestationaltrophoblasticneoplasia:Epidemiology,clinicalfeatures,diagnosis,staging,andriskstratification",
sectionon'Differentialdiagnosis'.)
(See"Initialmanagementoflowriskgestationaltrophoblasticneoplasia".)
(See"Initialmanagementofhighriskgestationaltrophoblasticneoplasia".)
(See"Managementofresistantorrecurrentgestationaltrophoblasticneoplasia".)
MANAGEMENTSurgicaluterineevacuation(alsoreferredtoasdilationandevacuationordilationandcurettage)isthe
mainstayofmanagementforhydatidiformmole(HM),eithercompleteorpartialmole.Hysterectomyisanoptioninwomen
whohavecompletedchildbearing.
UterineevacuationSuctioncurettageisthepreferredtechniqueforuterineevacuation,regardlessofuterinesize[5].
ForwomenwithHM,wesuggestuterineevacuationwithsuctioncurettageratherthanmedicationonlymethods.Useof
medicationonlymethodsforuterineevacuation(misoprostol,mifepristone,oxytocin)iscontroversial,andfewstudies
haveevaluatedtheefficacyorsafetyofthisapproach[5].Concernhasbeenraisedthatinducinguterinecontractionswith
uterotonics(oxytocin,prostaglandins)willincreasetheriskoftrophoblasticembolizationtothelungsorofmetastatic
disease.Inaddition,obtainingaspecimenforpathologyevaluationiscrucialforconfirmingthediagnosisofHMand
identifyingcompleteversuspartialmole.Itismoredifficulttoobtainacompletespecimenwithmedicationonly
evacuation.
TheonlystudythatevaluatedmedicationonlyevacuationforHM(n=4257)reportedthatamongwomenwhounderwent
medicationonlyevacuation(mainlywithprostaglandins),20of77(26percent)subsequentlyrequireduterinecurettage,

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andsevenweretreatedwithchemotherapy(9percentcomparedwith4to6percentafteruterinecurettage)[6].Further
studyofthisissueisneeded.
Duringsuctionevacuation,wedonotuseprostaglandinsforcervicalripening,baseduponthestudycitedabove[6].
Startingatthetimeofanesthesiainduction,wedoadministeranoxytocininfusion(10unitsin1LRingerlactatesolution
at50drops/min)toincreasemyometrialtoneandfacilitatecontraction,andthusdecreasebloodloss.
Theprocedureforsuctionevacuationconsistsofmechanicaldilationofthecervix,followedbysuctionevacuationand
thencurettage.Thetechniqueisthesameasforspontaneousorinducedabortion.(See"Spontaneousabortion:
Management",sectionon'Surgicalevacuation'and"Surgicalterminationofpregnancy:Firsttrimester",sectionon
'Curettage'.)
Mechanicaldilationofthecervixshouldbeperformedgraduallytoaccommodateacannuladiameterappropriateforthe
uterinesize.Somecliniciansadvocatetheuseoflaminariainsertedonthepreviousdayinnulliparatofacilitatedilation.
Duringdilatation,briskbleedingmaybeencounteredduetopassageofcopiousamountsofbloodretainedinthe
endometrialcavity.Evacuationoftheuterinecontentsinarapid,yetinathoroughandsafefashion,reducesoverallblood
loss.Aftertheinitiationofsuctionevacuation,theuterusgenerallyshrinksrapidly,andbleedingiswellcontrolled.Ifthe
uterusislargerthan14weekssize,thesurgeonmayusefundalmassageviatheabdomentofacilitateuterinecontraction.
Whensuctionevacuationisthoughttobecomplete,agentlesharpcuretteshouldbeusedtoremoveanyresidual
chorionictissue.Somesurgeonsprefertouseintraoperativesonographytomonitortheproceduretodeterminewhen
evacuationiscomplete.Whereasconfirmationofthediagnosisofcompletemoleisusuallypossibleongrossinspectionof
thecurettings,theappearanceofpartialmoleisfrequentlynonspecific.Bleedingfromamolarevacuationmaybe
substantiallymorethanfromaspontaneous,missed,orincompleteabortion.Completemolartissuewillusuallyhave
markedlydilatedvillithatappearlikegrapeclusters.Thechangesinpartialmoleareusuallymoresubtle,andpartialmole
mayonlybesuspectedordiagnosedbaseduponthemicroscopicfindings.
PatientsathighriskforGTNPatientsatahighriskofgestationaltrophoblasticneoplasia(GTN)maybenefitfrom
hysterectomyorprophylacticchemotherapy.Highriskfeaturesarediscussedbelow.(See'Gestationaltrophoblastic
neoplasia'below.)
HysterectomyWesuggesthysterectomyforwomenwithHMwhoare40yearsandhavecompletedchildbearing.
GTNismorelikelyinthisagegroup.Comparedwithuterineevacuation,hysterectomyappearstodecrease,butnot
eliminate,theriskofGTN.(See'Gestationaltrophoblasticneoplasia'below.)
Thebenefitofhysterectomyinthisagegroupwasillustratedinaseriesof82womenaged40to49withcompletemole
GTNdevelopedin37of68(54percent)womentreatedwithdilationandevacuationaloneandinnoneofthesixpatients
treatedwithhysterectomyalone[7].Markedlyelevatedhumanchorionicgonadotropin(hCG)levels>175,000mIU/mL
appearedtoconstitutean"ultrahighrisk"groupforwhomprophylacticchemotherapyorhysterectomyshouldbe
especiallyconsidered.Eleven(85percent)ofthirteenpatientswithpreevacuationhCGlevels>175,000mIU/mL
developedGTN.Similarly,anotherstudythatincluded22womenaged50orolderwithcompletemolefoundthatGTN
developedin9of15patients(60percent)treatedwithdilationandevacuationaloneandinnoneofthesevenpatientswho
underwentprimaryhysterectomy[8].
Whencounselingpatientsabouttreatmentoptions,itisimportanttoinformthepatientthathysterectomyeliminateslocal
invasionandreducesthechanceofdevelopingpersistenttrophoblasticdisease,butitdoesnotpreventallcasesof
metastaticdiseaseduetooccultmetastases[9].Womentreatedwithhysterectomystillrequiremonitoring,including
serialhCGlevels[5].MetastaticGTNdevelopsin4percentofpatientsafteruterineevacuationofacompletehydatidiform
mole[1].(See'Followup'below.)
Attimeofhysterectomy,theovariesmaybepreservedsinceovarianmetastasesarerarelyencountered.Ifprominent
ovarianthecaluteincystsarepresent,theycanbeaspiratedtoreducethevolumeandpatientdiscomfort.Duetothe
highlyvascularnatureofthegraviduterus,supracervicalhysterectomyisfrequentlyperformedtoreducebloodlossand
avoidureteralinjury.
Hysterectomymayalsobeperformedfortheemergencymanagementofacutehemorrhageatthetimeofmolar
evacuation,althoughtheuseofuterinearteryembolizationhasbeenshowntobesuccessfulinmanagingthis
complication[10].
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ProphylacticchemotherapyAtourinstitution,weofferchemotherapyfollowingevacuationofacomplete
hydatidiformmoletohighriskwomen(see'Gestationaltrophoblasticneoplasia'below),butnottoothers.Italsomaybe
particularlyusefulinpatientswithhighriskcompletemolewhenhormonalfollowupiseitherunavailableorunreliable,as
maybethecasewithadolescentsorincertainresourcepoorregions,suchassomepartsofAsiaandAfrica[5].
Importantly,chemoprophylaxisdoesnotappeartoimpactfuturefertilitypotential[11,12].Bothmethotrexateand
actinomycinDhavebeenusedinthissetting,andtherearenodatatosuggestwhetheroneshouldbethepreferredagent.
Atourcenter,wegenerallyadministeractinomycinDtohighriskpatients.
Thispractice(otherwiseknownasprophylacticchemotherapyorchemoprophylaxis)issupportedbydatathatconsistently
showthatchemotherapycanreducetheriskofsubsequentprogressionorthediagnosisofGTNinthesepatients[1217].
Forwomenatlowrisk,wedonotproceedwithprophylacticchemotherapy,butratherinitiatefollowup.(See'Followup'
below.)
Theadministrationofprophylacticchemotherapyissupportedbya2012metaanalysisthatincludedthreerandomized
trials(n=613patients,alldiagnosedwithcompletemole)[13].Theuseofprophylacticchemotherapywasassociated
witha63percentreductionintheriskofGTN(relativerisk[RR]0.37,95%CI0.240.57).Despitethisfinding,issues
relatedtothemethodologicalqualityofthetrials,includingthesmallsizeofthestudypopulationsincluded,limitthewider
acceptanceofthisrecommendation.Inaddition,asnotedinthismetaanalysis,thebenefitofprophylacticchemotherapy
isnotentirelyclearbecauseotherdatasuggestthatpatientswhounderwentprophylacticchemotherapyandwere
subsequentlydiagnosedwithGTNexperiencedadelayinsubsequentdiagnosisandrequiredmorecoursestoachieve
remission[13].
AttheNewEnglandTrophoblasticCenter,wehavetreated93patientsinthisfashion,andonly10(11percent)developed
persistentdisease[12].Ofnote,noneofthesepatientshadmetastaticdiseaseatthetimepersistentdiseasewas
detected.Sixpatientsweretreatedwithmethotrexateforpersistenttumor,andofthese,fiverequiredonlyonecourseof
methotrexatetoattainremission.
Rh(D)immuneglobulinPatientswhoareRh(D)negativeshouldreceiveantiDimmuneglobulinatthetimeof
treatmentbecausetheRh(D)factorisexpressedontrophoblast.(See"PreventionofRh(D)alloimmunizationin
pregnancy".)
MANAGEMENTOFCOMPLICATIONS
HyperthyroidismMolarpregnancyassociatedhyperthyroidismwillresolvewithtreatmentofthegestational
trophoblasticdisease(GTD).SomepatientswillrequireantithyroidtherapyuntilGTDtreatmentiscomplete.Beta
adrenergicblockingagentsmayberequiredbeforetheinductionofanesthesiatopreventorrapidlyreversemanyofthe
metabolicandcardiovascularcomplicationsofathyroidstorm[18].
Thecriteriafortreatmentandapproachtotherapyarethesameasforotherhumanchorionicgonadotropin(hCG)mediated
hyperthyroidism.(See"Hyperthyroidismduringpregnancy:Treatment".)
OvarianthecaluteincystsThecaluteincystsusuallyregressslowlyovertwotofourmonthsfollowingevacuation
withdeclininghCGlevels.Iftheyaresymptomatic,theycanbeaspiratedtransabdominallyunderultrasoundguidance.
Thecaluteincystsmaycauseadnexaltorsionor,rarely,theyrupturespontaneously.Insuchcases,theycanbemanaged
laparoscopically[19].(See"Ovarianandfallopiantubetorsion"and"Evaluationandmanagementofrupturedovarian
cyst".)
PreeclampsiaPreeclampsiaassociatedwithcompletemolarpregnancyresolvespromptlyaftermolarevacuationand
usuallydoesnotrequiremedicalmanagement.
CardiopulmonarysymptomsInwomentreatedinthefirsttrimester,cardiopulmonarysymptomsarerare[20].After
uterineevacuationforcompletehydatidiformmoleinthesecondtrimester,approximately2percentofpatientsusedto
developcardiopulmonarysymptoms,includingchestpain,dyspnea,tachypnea,andtachycardia.Auscultationofthechest
usuallyrevealsdiffuserales,andthechestradiographoftendemonstratesbilateralpulmonaryinfiltrates.Thesignsand
symptomsusuallyresolvewithin72hoursafterevacuationwithcardiopulmonarysupport.
Respiratorydistressisusuallyattributedtotrophoblasticembolization,butcanalsobeduetothecardiopulmonary
complicationsofthyroidstorm,toxemia,andmassivefluidreplacement.Thepresenceofpulmonaryinfiltratescan
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sometimesbemisinterpretedasmetastases,forwhichchemotherapyisinappropriatelyadministered.Inmostcases,the
infiltrateswillresolveover48to72hoursasthehCGleveldecreases[21].
FOLLOWUPFollowupoftreatmentofhydatidiformmole(HM)consistsofmeasurementofserialserumhuman
chorionicgonadotropin(hCG)levels,untilanundetectablelevelisreachedandismaintainedforseveralmonths(algorithm
1).
Poorcompliancewithpostmolarsurveillanceandtreatmentprotocolsisassociatedwithpooreroutcomesdueto
advanceddisease.IntheUnitedStates,indigentwomentreatedaturban,publichospitalsarethegroupmostlikelytofail
tocomplywithstandardprotocolsforanumberofreasons,includingcost,transportationissues,andchildcare
requirements[22].Patienteducationiscrucialtohelppatientstounderstandandcomplywithsurveillanceprotocols.
SerialhCGAllpatientswithHMshouldbemonitoredwithserialserumhCGtestingvaluesafterevacuationtoevaluate
forpostmolargestationaltrophoblasticneoplasia(GTN).
SurveillanceprotocolGuidelinesfromtheAmericanCollegeofObstetriciansandGynecologistsadvisethe
followingprotocol[23]:
Everyweekuntilnondetectableforthreeweeks,then
EverymonthforsixmonthsIfthehCGremainsundetectableforsixmonths,thenthepatientmayresumetryingto
becomepregnant,ifshewishes.
ShorterdurationofmonitoringManypatientsfindthesixmonthperiodoffollowupdifficulttocomplete.
Womenmaywishtobeginattemptinganotherpregnancysooner,particularlythoseoverage35.Furthermore,weeklyor
monthlyhCGtestingisanxietyprovokingformanywomen,expensive,andinconvenient,makingnoncompliance
common.
AshorterperiodofhCGmonitoringappearstobesafe[2431].TheriskofGTNis<1percentafteranundetectablehCG
levelisattained,basedupondatafromseveralthousandwomenfrommultipleinstitutions,includingtheCharingCross
Hospital,UniversityofTexasSouthwestern,NewEnglandTrophoblasticDiseaseCenter(NETDC),andcentersin
Hungary,Australia,andtheNetherlands[2531].Thiswasillustratedinalargeseriesofwomenwithmolarpregnancy(n=
22,053)fromCharingCrossHospitalinEnglandamongwomeninwhomthehCGnormalized,only1in760developed
GTN[32].IfthehCGnormalizedwithin56daysafterevacuation,theriskofGTNwas1in1536comparedwith1in464
whenhCGnormalizedingreaterthan56days.ThemeantimetofirstraisedhCGlevelafternormalizationwas449and
462daysinthe<56and>56daygroups,respectively.DuetothelongintervaltothehCGriseafternormalization,itis
possiblethatsomeofthesecaseswerenewmolarconceptions.Similarly[25],inaseriesof1029patientswithcomplete
moletreatedwithevacuation,nopatientdevelopedGTNafterthehCGlevelbecameundetectableusinganassay
sensitiveto<5mIU/mL.
PatientswithpartialmolemaybeparticularlysuitableforshorteneddurationofhCGsurveillancebecauseoftheirlowrisk
ofpersistence[29].Asanexample[31],inaprospectivecohortstudy(n=2008)ofpatientsregisteredattheFrench
TrophoblasticDiseaseCentre,theriskofpostmolarGTNafterhCGnormalizationwas0.34percentaftercompletemole,0
percentafterpartialmole,and0.36percentafteramultiplepregnancywithcoexistingmole.Similarly,inastudyinvolving
284womenwithpartialmole,noneofthepatientsdevelopedGTNfollowingspontaneousdeclineandnormalizationofthe
hCGlevel[27].
Onthebasisofthesedata,itmaybereasonabletoabbreviatehCGfollowupforwomenwithbothcompletemoleand
partialmolewithoutappreciablyincreasingtheriskofdelayeddiagnosisofGTN.Itisthecurrentpolicyatourcenter,the
NETDC,toallowpatientsfollowingeitheracompleteorpartialmoletobecomepregnantafterachievingthreeconsecutive
weeklyfollowedbythreeconsecutivemonthlyundetectablehCGlevels.
ItispossibletoutilizehCGregressioncurvestopredictapatientsriskofdevelopingGTNaftermolarevacuation[3335].
Inonestudy,anhCGlevelof>199mIU/mLinthethirdthrougheighthweekfollowingpartialmoleevacuationwas
associatedwithatleasta35percentriskofGTN[36].Similarly,anotherstudyreportedthatwomenafteracompletemole
whosehCGlevelswere<200mIU/mLinthefourthweekafterevacuationor<100mIU/mLinthesixthweekafter
evacuationhadariskofpersistencebelow9percent.AnhCGlevel>2000mIU/mLinthefourthweekafterevacuation
wasassociatedwitha63.8percentriskofdevelopingpersistentdisease[26].
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DiagnosisofGTNFollowingevacuationofacompleteorpartialmolarpregnancy,ifhCGlevelsriseorremain
elevatedoverseveralweeks,thepatientisclassifiedashavingGTN.ThediagnosisofpostmolarGTNisbaseduponthe
followingInternationalFederationofGynecologyandObstetrics(FIGO)criteria[3739]:
hCGlevelsplateau(remainwithin10percentofthepreviousresult)acrossfourmeasurementsoverathreeweek
period(eg,days1,7,14,and21)
hCGlevelincreases>10percentacrossthreevaluesoveratwoweekduration(eg,measurementsondays1,7,and
14,increaseis>10percentfromday1today14)
PersistenceofdetectableserumhCGformorethansixmonthsaftermolarevacuation
ThereareinternationallyacceptedcriteriatomakethediagnosisofGTNforwomenwhohadapriormolarpregnancy.
However,FIGOalsoacceptsthediagnosisofGTNbasedonahistologicdiagnosisofchoriocarcinomaorinvasivemole
(eg,madebyexaminationofuterinecurettings)and/ortheidentificationofclinicalorradiologicalevidenceofmetastases.
TheevaluationanddiagnosisofGTNisdiscussedindetailseparately.(See"Gestationaltrophoblasticneoplasia:
Epidemiology,clinicalfeatures,diagnosis,staging,andriskstratification",sectionon'Diagnosticevaluation'and
"Gestationaltrophoblasticneoplasia:Epidemiology,clinicalfeatures,diagnosis,staging,andriskstratification",sectionon
'Diagnosis'.)
PersistentlowhCG(quiescentGTN)Onrareoccasionsfollowingmolarevacuation,thehCGlevelwillfailto
normalizeandremainelevatedatlowlevels(<200mIU/mL).Onecauseofpersistent(presentforatleastthreemonths)
lowlevelhCGisquiescentGTN,alsoreferredtoasinactiveGTN.
QuiescentGTNisapersistentlylowlevelofhCGintheabsenceofanyclinicalorradiologicalevidenceofGTN.While
quiescentGTNmostcommonlyoccursafteracompletemole,itmaydevelopafterpartialmole,invasivemole,or
choriocarcinoma.Thisconditionisthoughttobeduetothepresenceofasmallfocusofhighlydifferentiated,noninvasive
syncytiotrophoblastcellsthatproducesmallstableamountsofhCGandusuallydonotprogresstoinvasivediseaseas
longascytotrophoblastorintermediatecellsareabsent[40].
QuiescentGTNischaracterizedbythefollowing:(1)fociofdiseasearenotreadilyidentifiableclinically,and(2)hCGlevel
isunresponsivetotherapy,presumablybecausethegrowthcycleofthesecellsislongandcomparabletonormalcells.
PatientswithquiescentGTNshouldnotbetreatedwithchemotherapy,butclosefollowupisindicatedbecause6to10
percentwilleventuallydevelopactiveGTN,requiringtreatment[4143].
AlthoughFIGOguidelinesrecommendtreatmentinpatientswithpersistenthCGlevelssixmonthsaftermolarpregnancy,
agroupfromCharingCrossHospitalreportedon76patientsfromacohortof13,960withHMswhohadpersistently
elevatedbutdeclininghCGlevelssixmonthsafterevacuation.Inthisstudy,66(87percent)patientsweretreated
expectantly,andonly13percentrequiredchemotherapytreatment[44].
ThemeasurementofhyperglycosylatedhCG(hCGH)hasbeenproposedforsurveillanceinpatientswithquiescentGTN
[42,45].hCGHisaglycoproteinproducedbycytotrophoblastcellsandisassociatedwithtrophoblastinvasion,growthof
cytotrophoblastcells,andoverallpromotionofplacentalimplantation.Itisthoughttobeapromoterofchoriocarcinoma
growthandtumorigenesis,andisthemainformofhCGproducedinactiveGTN.
ThepresenceoflowlevelsofhCGHindicatesthepresenceofquiescentGTN.IncreasinglevelsofhCGHindicatethe
developmentofactiveGTNthatrequirestreatment[40,41].
PatientswithquiescentGTNshouldbemonitoredwithmonthlyhCGtestingandadvisedtoavoidpregnancy[46].Active
GTNshouldbediagnosed,andtreatedappropriately,ifhCGHrisestogreaterthan20percentoftotalhCGoriftotalhCG
hastwodoublings[45,47,48].(See"Initialmanagementoflowriskgestationaltrophoblasticneoplasia".)
ThereareseveralotheretiologiesofapersistentlowlevelhCG,includingpituitaryglandhCGproductionparticularlyin
perimenopausalwomen.ThedifferentialdiagnosisofpersistentlowhCGisdiscussedindetailseparately.(See"Human
chorionicgonadotropin:Testinginpregnancyandgestationaltrophoblasticdiseaseandcausesoflowpersistentlevels",
sectionon'CausesandevaluationofpersistentlowlevelsofhCG'.)
ContraceptionWomenwithmolarpregnancymustbeadvisedtousereliablecontraceptionduringtheentireintervalof
hCGmonitoring.AnewpregnancyduringthisperiodwouldmakeitdifficultorimpossibletointerprethCGresultsand
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wouldcomplicatemanagement.Optionsincludehormonalcontraceptionorbarriermethods.Depotmedroxyprogesteroneis
anoptionforwomenwhohavedifficultycomplyingwithcontraceptiveuse[22].Anintrauterinedeviceshouldnotbeused
beforethehCGnormalizesbecauseoftheriskofuterineperforationduetosubinvolutionoftheuterusorinvasivemole.
Historically,womenwereadvisedtouseonlybarriercontraceptionbaseduponaconcernthathormonalcontraceptives
mayincreasetheriskofGTN[49].Somedatasuggestthatthisincreasedriskwasassociatedwithestrogendosesof50
mcgorhigherinolderoralcontraceptives[50].However,thesafetyofpostmolaruseoforalcontraceptiveshasbeen
demonstratedinthreereports,includingtworandomizedtrials[5153].ThelargestwasaGynecologicOncologyGroup
randomizedtrial(n=266)thatassignedpatientstooralcontraceptivesorbarriercontraceptionafterevacuationofanHM
[52].Nosignificantdifferenceintherateofpostmolartrophoblasticdiseasewasfoundbetweenthegroupsinfact,the
oralcontraceptivegrouphadalowerrate(23versus33percent).Themediantimetospontaneousregressionintheoral
contraceptivesgroupwasnineweeks,whereasthemediantimetoregressioninthebarriergroupwas10weeks.Twice
asmanypatientsinthebarriergroupbecamepregnantintheimmediatefollowupperiod.Inaddition,asystematicreview
ofsevenstudiesincluding1533womenreportedthatallbutonestudyfoundnoincreasedriskofGTNwithpostmolaruse
oforalcontraceptives[54].
OUTCOME
GestationaltrophoblasticneoplasiaHydatidiformmole(HM)iswellrecognizedtohaveariskofdevelopinginvasive
disease,referredtoasgestationaltrophoblasticneoplasia(GTN).
ThereportedincidenceofGTNaftereachtypeofmolarpregnancyis[9,5558]:
Completemole(15to20percent)
Partialmole(1to5percent)
ThewiderangeofthereportedincidenceofpostmolarGTNresultsfromdifferencesindiagnosticcriteriaandthesizeof
thepopulationstudied.Amongwomenwithmolarpregnancy,theriskfactorsfordevelopingGTNinclude:(1)complete
molewithsignsoftrophoblasticproliferation(uterinesizegreaterthangestationalage,serumhumanchorionic
gonadotropin[hCG]levels>100,000mIU/mL)(2)ovarianthecaluteincysts>6cmindiameterand(3)age>35to40
years.
Theincreasedriskincompletemolewithsignsofmarkedtrophoblasticproliferationwasillustratedbydatafromour
center,theNewEnglandTrophoblasticDiseaseCenter(NETDC),from858womenwithcompletemole[5].Thepresence
versusabsenceoftrophoblasticproliferativesigns(uterinesizegreaterthangestationalage,serumhCGlevels>100,000
mIU/mL,andovarianthecaluteincysts>6cmindiameter)wasassociatedwithsignificantlyhigherratesofuterine
invasion(31.0versus3.4percent)andmetastases(8.8versus0.6percent).Sincecompletemolesarecurrentlyusually
diagnosedinthefirsttrimester,theclassicalsignsoflatemolarpregnancyarenotcommonlyencountered.Despiteearly
diagnosis,however,theincidenceofpostmolarGTNisunchanged.Firsttrimestercompletemolesstillfrequentlypresent
withhighhCGvalues,andhighhCGvaluesinfirsttrimestercompletemolesarestillassociatedwiththedevelopmentof
GTN.
Olderpatientswithcompletemolearealsoatincreasedriskofdevelopingapostmolartumor.Studieshavefoundthat33
to60percentofwomenoverage40withcompletemoledeveloppersistentdisease[7,59,60].Otherstudieshavereported
that53to56percentofwomenover50withcompletemolesdevelopedpostmolartumor[8,61].
Completemolesaremorecommonlyaneuploidinolderwomen,andaneuploidymaybeariskfactorforGTN[62].One
studyreportedthat10of13(77percent)aneuploidcompletemolesdevelopedpersistenttumor[63].
Incontrasttopatientswithadvancedage,adolescents(<age20)donotappeartohaveahigherriskofdeveloping
postmolardisease.Asanexample,onestudyoftheclinicalpresentationandoutcomein220adolescentpatientswith
completemolenotedasignificantlydecreasedriskofdevelopingGTN[64].
Forpartialmole,noriskfactorsfordevelopingGTNhavebeenidentified[65].Afterpartialmole,persistenttumoris
generallynonmetastatic[5].Asanexample,11studiesincluding7579patientswithpartialmoleshowthatonly76(1.0
percent)womendevelopedpersistenttumorandonlynine(0.1percent)hadmetastases[2,3,6573].
Patientswithrepeatmolarpregnancyareatanincreasedriskofdevelopingpersistenttumor.Onestudyreporteda
threefoldincreasedriskofpostmolartumorinpatientswitharepeatmolarpregnancy[74].Among39patientswithtwo
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molarpregnanciesmanagedattheNETDCfrom1965to2013,persistenttumordevelopedfollowingthefirstmolein4of
20(20percent)completemolesandfollowingthesecondmole,in8of20(40percent)completemoles,andin2of17
(11.7percent)partialmoles[75].
SubsequentpregnancyIngeneral,patientswithbothcompletemoleandpartialmolecananticipatenormalfuture
reproductiveoutcomes.
AttheNETDCbetween1965and2013,obstetricoutcomesincluded[75]:
Patientswithcompletemolehad1388subsequentpregnancies:949(68.4percent)termlivebirths,103(7.4percent)
prematuredeliveries,seven(0.5percent)stillbirths,256(18.4percent)spontaneousabortions,and11(0.8percent)
ectopicpregnancies.Majorandminorcongenitalanomaliesweredetectedin40(3.8percent)infants.
Patientswithpartialmolehad357subsequentpregnancies:260(72.8percent)termlivebirths,eight(2.2percent)
prematuredeliveries,one(0.3percent)stillbirth,64(17.9percent)spontaneousabortions,andtwo(0.6percent)
ectopicpregnancies.Majorandminorcongenitalanomalieswerediagnosedinonlyfour(1.5percent)infants.
Theseratesaresimilartootherinstitutions[76,77].
RepeatmolarpregnancyWomenwithapriorHMareatincreasedriskofdevelopingsubsequentHMcompared
withthegeneralpopulation[78].
EstimatesoftheriskofsubsequentHMare:
Afteronemolarpregnancy(1to1.9percent)[76,77,79]
Aftertwomolarpregnancies(15to17.5percent)[75,76]
Asingleinstitutionseriesreportedthatamong2578womenwithcompletemole,thesubsequentpregnancywasmolarin
27(1.9percent),including22(81percent)completemolesandfive(19percent)partialmoles[77].Among2627patients
withapartialmole,thesubsequentpregnancywasmolarin25(1.7percent),including17(68percent)partialmolesand
eight(32percent)completemoles.Theoverallriskofmolarpregnancywas1.8percent,whichrepresenteda20fold
increasecomparedwiththegeneralpopulation.Among27caseswithrepeatcompletemole,threehadlatermolar
pregnancies,indicatingarecurrencerateaftertwopreviouscompletemolesof11percent.
AttheNETDCbetween1965and2013,followingtwomolarpregnancies,25patientshad40subsequentpregnancies:
seven(17.5percent)molarpregnancies(sixcomplete,onepartial),25(62.5percent)termlivebirths,oneintrauterinefetal
demise(2.5percent),threespontaneousabortions(7.5percent),threeinducedabortions(7.5percent),andoneectopic
pregnancy(2.5percent)[75].
ObstetricmanagementDuetotheriskofrecurrentHM,inourpractice,weadvisepatientswithapriorHMtohave
afirsttrimesterultrasoundtoconfirmnormalgestationaldevelopmentinsubsequentpregnancies.Additionally,we
measureaserumhCGatsixweeksafterthecompletionofanytypeoffuturepregnancy(eg,termdelivery,spontaneous
abortion,inducedabortion)toexcludechoriocarcinoma.Afterpretermortermdeliveriesinpatientswithpriormolar
pregnancyorGTN,theplacentashouldbecarefullyexaminedandsenttopathologyifanyabnormalitiesarepresent.
Additionally,allproductsofconceptionfrommiscarriagesorabortionsshouldbeexaminedpathologically.
SUMMARYANDRECOMMENDATIONS
Hydatidiformmole(HM)ispartofagroupofdiseasesclassifiedasgestationaltrophoblasticdisease(GTD),which
originateintheplacentaandhavethepotentialtolocallyinvadetheuterusandmetastasize.(See'Introduction'
above.)
UterineevacuationisthemainstayoftreatmentforHM.ForwomenwithHM,wesuggestuterineevacuationwith
suctioncurettageratherthanmedicationonlymethods(Grade2C).(See'Uterineevacuation'above.)
ForwomenwithHMwhoareage40yearsandhavecompletedchildbearing,wesuggesthysterectomyratherthan
uterineevacuation(Grade2C).(See'Hysterectomy'above.)
FollowupoftreatmentofHMconsistsofmeasurementofserialweeklyserumquantitativehumanchorionic
gonadotropin(hCG),untilanundetectablelevelisreached(algorithm1).(See'Surveillanceprotocol'above.)
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Followingevacuationofacompleteorpartialmolarpregnancy,ifhCGlevelsriseorremainelevatedoverseveral
weeks,thepatientisclassifiedashavinggestationaltrophoblasticneoplasia(GTN).Thediagnosisofpostmolar
GTNisbasedupontheInternationalFederationofGynecologyandObstetrics(FIGO)criteria.(See'Diagnosisof
GTN'above.)
WomenwithmolarpregnancymustbeadvisedtousereliablecontraceptionduringtheentireintervalofhCG
monitoring.AnewpregnancyduringthisperiodwouldmakeitdifficultorimpossibletointerprethCGresultsand
wouldcomplicatemanagement.Optionsincludehormonalcontraceptionorbarriermethods.(See'Contraception'
above.)
EstimatesoftheriskofrecurrentHMare:afteronemolarpregnancy(1to1.9percent),andaftertwomolar
pregnancies(15to17.5percent).(See'Repeatmolarpregnancy'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic3194Version14.0

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GRAPHICS
Molarpregnancymanagementalgorithm

*Betahumanchorionicgonadotropin.
Patientsshouldusecontraceptionuntilfollowupiscomplete.
AdecreasinghCGisdefinedasalevelthatdecreases>10percentcomparedwiththeprevious
result,andcontinuestomeetthiscriterionacrossfourvaluesduringathreeweekperiod.
AnincreasinghCGisdefinedasalevelthatincreases>10percentcomparedwiththeprevious
result,andcontinuestomeetthiscriterionacrossthreevaluesduringatwoweekperiod.
AnunchangedhCGisdefinedasalevelthatremainswith+/10percentcomparedwiththe
previousresult,andcontinuestomeetthiscriterionacrossfourvaluesduringathreeweekperiod.
AfterachievingoneundetectablehCGvalue(<5mIU/mL),theriskofdevelopinggestational
trophoblasticneoplasiais<1percent.AmericanCollegeofObstetricianandGynecologyguidelines
advisethatafterthehCGisundetectable,tocontinuetomeasurehCGmonthlyforsixmonths.
BasedontheextremelylowriskofariseinhCGafteritbecomesundetectable,inourpractice,we
continuemonthlyhCGfollowupforthreemonthsandthenfollowupiscomplete.
Graphic105721Version1.0

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ContributorDisclosures
RossSBerkowitz,MDNothingtodisclose.DonaldPeterGoldstein,MDNothingtodisclose.NeilSHorowitz,MD
Nothingtodisclose.RobertLBarbieri,MDNothingtodisclose.BarbaraGoff,MDConsultant/AdvisoryBoards:Roche
Diagnostics[Biomarkersforovariancancer(HE4)].Employment(Spouse):Lilly[Generaloncology(Gemcitabine,
pemetrexed)].SandyJFalk,MD,FACOGNothingtodisclose.SadhnaRVora,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedby
vettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.
AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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