Post on 30-Aug-2018
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Recurrent Pregnancy Loss What can we do?
Pradnya Pisal London Gynaecology
Recurrent Pregnancy Loss | www.london-gynaecology.com
Recurrent Pregnancy Loss | www.london-gynaecology.com
Recurrent Pregnancy Loss | www.london-gynaecology.com
Recurrent Pregnancy Loss | www.london-gynaecology.com
Recurrent Pregnancy Loss
03/06/16
Recurrent Pregnancy Loss | www.london-gynaecology.com Recurrent Pregnancy Loss | www.london-gynaecology.com
Defn:RecurrentPregnancyLoss(RPL)
• Classical:3ormoreconsecu>vepregnancylossesbefore20weeksgesta>on,1-2%
• 5% couples experience 2/> consecutive losses
• Riskoffurtherpregnancylossissimilarfor2and3consecu>velosses,43.7%,44.6%
• Inves>ga>onmaybeappropriateaNer2pregnancylosses,especiallyinolderwomenandifkeentobeinves>gated
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RecurrentPregnancyloss
• Possiblecauses
• Inves>ga>on
• Management
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Causes
• Age• Previouspregnancyloss• Uterinefactors
• Anomalies• Fibroids• Polyps• Adhesions• Cervicalinsufficiency• Defec>veendometrialrecep>vity
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Causes
• Immunologicalfactors• An>phospholipidsyndrome• Otherimmunologicalfactors
• Endocrinefactors• Diabetesmellitus• PCOS• Thyroidan>bodiesanddisease• Hyperprolac>naemia• Lutealphasedefects
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Causes
• Chromosomalabnormality• Gene>cdisorders• Thrombophilia • Infec>on• Decreasedovarianreserve• Personalhabits• Malefactor• Environmentalchemicalsandstress
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Age
12-19yrs 13% 20-24yrs: 11% 25-29yrs: 12% 30-34yrs: 15% 35-39yrs: 25% 40-44yrs: 51% >/=45yrs: 93%
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Chromosomalabnormality
%Abnormal Gesta/onalage
60 12
45 16
12 20
6 24
-1 40
• Increaseswithadvancingmaternalage• Parentalabnormali>esin3-5%ofcoupleswithRPL• Balancedtransloca>onmostcommon
• Reciprocal(60%)orRobertsonian(40%)• 25-50%riskofpregnancyloss
• Trisomy,monosomyandtriploidy;85%losses
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Karyotyping
• Shouldbeperformedonproductsofconcep>on(POC)ofthe3rdandsubsequentconsecu>vemiscarriage(s)
• ParentalperipheralbloodkaryotypingofbothpartnersshouldbeperformedincoupleswithRPLwheretes>ngofPOCreportsanunbalancedstructuralchromosomalabnormality,orPOCarenotavailableforkaryotyping
• Ifthekaryotypeofthemiscarriedpregnancyisabnormal,thereisabe`erprognosisforthenextpregnancy
• RoleforPGDinIVFpregnancies
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An>phospholipidsyndrome(APS):Hughessyndrome
• Mostimportanttreatablecauseofrecurrentmiscarriage,2%innormal,15%withRPL.
• Associa>onbetweenan>phospholipidan>bodies–lupusan>coagulant,an>cardiolipinan>bodiesandan>-B2glycoprotein-Ian>bodies–andadversepregnancyoutcomeorvascularthrombosis.
• Test:on2ormoreoccasionsatleast12weeksapart
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APS:Adversepregnancyoutcomes
• Threeormoreconsecu>vemiscarriagesbefore10weeksofgesta>on
• OneormoremorphologicallynormalfetallossesaNerthe10thweekofgesta>on
• Oneormorepretermbirthsbeforethe34thweekofgesta>onowingtoplacentaldisease.
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APSan>bodies:ac>on
• Inhibi>onoftrophoblas>cfunc>onanddifferen>a>on• ac>va>onofcomplementpathwaysatthematernal–fetalinterfaceresul>nginalocalinflammatoryresponse
• inlaterpregnancy,thrombosisoftheuteroplacentalvasculature
• InvitrostudieshaveshownthattheeffectofAPSan>bodiesontrophoblastfunc>onandcomplementac>va>onisreversedbyheparin.
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Treatment
• Stronglyadvisewomentoplanpregnancy• Stopsmoking• Maintaingooddietandhealthyweight• Regularexercise• Aspirin• Clexane
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Cervicalincompetence
• Lookforhistory:LargeLLETZ,conebiopsy,transcervicalmyomectomy,later1stTMTOPorERPC,painless2ndTMlossorPPROM
• Currentlynosa>sfactoryobjec>vetestthatcaniden>fywomenwithcervicalweaknessinthenon-pregnantstate
• Inwomenwithsingletonpregnancy&one2ndTMmiscarriagea`ributabletocervicalfactors,anUSS-indicatedcerclage,ifcervicallengthof</=25mmisdetectedbyTVSbefore24wks
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Normalcervix Shortcervix
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Management:cervicalincompetence
• Serialcervicallengths• Progesteronesupport• Prophylac>ccervicalsuture
• Vaginal:• MacDonald’s• Shirodkar’s
• Abdominal• Laparoscopic• Open
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Uterineanomalies
• Prevalence&implica>onsingeneralisunknown• InRPL:between1.8%and37.6%• RPLmayberelatedtocervicalincompetence• Higherprevalencewith2ndTMlosscomparedwith1stTMmiscarriages,PTD• Termdeliveryrateofonly50%
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Uterineanomalies:Treatment
• Stronghistory• PelvicUSS,3DUSS,MRI• Hysteroscopicevalua>on+/-laparoscopy• Transcervicalresec>onofseptae• Hysteroscopicresec>onof:
• polyps• fibroids• adhesions
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Endocrinefactors:DM
• PoorlycontrolledDiabetesmellitushasbeenassociatedwithmiscarriage
• WomenwithdiabeteswhohavehighhaemoglobinA1clevelsinthe1stTMareatriskofmiscarriageandfetalmalforma>on
• Pre-pregnancycounseling:Improvediet,exercise,bloodglucosecontrol,5mgfolicacidpriortopregnancy
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Endocrinefactors:Thyroiddisease
• Thyroiddysfunc>on&An>-thyroidan>bodieshavebeenlinkedtorecurrentmiscarriage
• TSH:4-5mIU/LwasconsiderednormalbutrecentlyTSHvalueofover2.5mIU/Lareconsideredoutsidenormalrange
• Hencelookforandtreatsubclinicalhypothyroidism
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Polycys>covariansyndrome:PCOS
• Increasedriskofmiscarriagerecentlya`ributedtoinsulinresistance,hyperinsulinaemia,hyperandrogenaemiabutuncertaincause(?highLHlevels)
• Elevatedfreeandrogenindexappearstobeaprognos>cfactorforasubsequentmiscarriageinwomenwithrecurrentmiscarriage
• Treatment:Diet,Exercise,Meqormin,Progesteronesupport
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Immunefactors
• Noclearevidencetosupporthumanleucocytean>genincompa>bilitybetweencouples,theabsenceofmaternalleucocytotoxican>bodiesortheabsenceofmaternalblockingan>bodies
• Naturalkiller(NK)cellsarefoundinperipheralbloodandtheuterinemucosa
• NoclearevidencethatalteredperipheralbloodNKanduterineNKcellsarerelatedtorecurrentmiscarriage
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Infec>ons
• Bacterialvaginosisinthe1stTMisariskfactorfor2ndTMmiscarriageandPTD:oralclindamycinsignificantlyreducesrisk
• Noroleforrou>neTORCHinves>ga>ons• Noroleofan>bio>ctherapyinwomenwithaprevious2ndTMmiscarriage• Anysevereinfec>onthatleadstobacteraemiaorviraemiacancausesporadic
miscarriage• Syphilisinareasofhighprevalence
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Thrombophilias
• Associa>onbetweenthrombophiliaandlatepregnancylosshasbeenconsistently
strongerthanforearlypregnancyloss
• Womenwith2ndTMmiscarriageshouldbescreenedforinheritedthrombophilias
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Thrombophilias:Tests
• FactorVLeiden• Ac>vatedproteinCresistance• Prothrombingenemuta>on• ProteinCandpro>enSdeficiency• Methylenetetrahydrofolatemuta>on(MTHFR)• CarriersoffactorVLeidenorprothrombingenemuta>onhavedoubletheriskof
experiencingrecurrentmiscarriagecomparedwithwomenwithoutthesethrombophilicmuta>ons
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LutealPhaseDefect
• ControversialcauseofRPL• NoconvincingstudiesshowingLPDtreatment
improvespregnancyoutcome(LeeSeminReprodMed2000;18(4):433-40)
• 80%ofwomenwithlowmid-lutealprogesteroneproceedtoterm
• 20%offer>lewomenhaveabnormalendometrialbiopsies
• Progesteroneand/orovula>oninduc>onforLPD
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Malefactor
• Nosignificantdifferenceinsemenparameters• Nodifferenceinincidenceofan>-sperman>bodies• Asidefromcytogene>cabnormali>es,malefactorcontribu>ontoRPLunknown
(HillASRM2002Course6p.56)• Oligoasthenoteratospermia35-74%• Fer>ledonorsperm4-7%
• DNAFragmenta>onmayresultinearlyembryoloss(HumReprod.2006Nov;21(11):2876-81)
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EnvironmentalFactors
Confirmedassocia>on• Ionizingirradia>on• Organicsolvents• Alcohol• Mercury• Lead
(Gardella&HillSeminReprodMed2000;18(4):407-424)
Suspectedassocia>on• Caffeine(>300mg/d)
• Fever• Cigare`eSmoking
• Unknownassocia>on• Pes>cides
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Summary:tests
• FBC:Plateletcount• APLan>bodies• Thrombophiliascreen• FSH,LH,Day21progesterone,Prolac>n• Parentalkaryotypes• HVSandChlamydia• TFT,Thyroidan>bodies• TestsforPCOS,DMifindicated• USS• Hysteroscopy
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Summary
• Morethan50%ofcoupleswithRPLhavenoexplana>ondespiteextensiveevalua>on
• Roleofaspirin,progesteronesupplements
• 70%livebirthratesreportedincoupleswithunexplainedRPLwhoundertakeanuntreatedsubsequentpregnancy
• dependsonmaternalage&numberofpriorlosses
• Informa>veandsympathe>ccounselingappearstoplayanimportantrole
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Recurrent miscarriage package from London Gynaecology
• Ourrecurrentmiscarriagepackageaimstoquicklydiagnosereasonsformiscarriageinwomen• 30minuteconsulta>onwithaconsultantgynaecologist• Abdominalandpelvicexamina>on• Bloodtestsincluding• Fullbloodcount• Coagula>onprofile• An>thrombinIII• FactorVLeidengene• FactorIIProthrombingene• MTHFYgene• Ac>vatedproteinCresistance• Lupusan>coagulant• ProteinCandProteinS• An>cardioplipinan>bodies• Chromosomalanalysis • ComprehensivereporttoyouandyourGP• Directaccesstoconsultant24/7
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ThankYou London Gynaecology Limited The Portland Hospital 212, Great Portland Street London W1W 5QN Practice Manager: Viviana Amoretti M: 07971 200 832 T : 020 8367 8999 F : 020 8082 5667 contact@london-gynaecology.com www.london-gynaecology.com