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why life birth rate after ART declined?

prof aboubakr elnashar

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why life birth rate after ART declined?

  1. 1. WHYLIFEBIRTHRATE AFTERIVFDECLINED? Prof.AboubakrElnashar Benhauniversityhospital CONTENTS 1.IVFLBRworldwide 2.IVFLBRinEGYPT 3.CAUSES 1.AGESOFWOMENHAVEBEENRAPIDLY INCREASING 2.NEWLYINTRODUCEDADDITIONS 3.INDUSTRIALIZATIONANDCOMMODITIZATION OFIVF 4.CONCLUSIONS 5.RECOMMENDATION
  2. 2. LBRfollowingfreshautologousIVFcyclesfrom1995to2016. ▪Reachingpeakbetween2008and2010 ▪Declineby2016 1.LBR/startedIVF/ICSIcycle(CDC,2019) ▪Thedataarebasedonregistrydatafrom ▪Governmentsand/orspecialtysocieties,covering ▪USA ▪Canada ▪UK ▪Australia/NewZealand ▪LatinAmerica ▪Japan.
  3. 3. 2.IVFLBRinEgypt:ICMART InternationalCommitteeforMonitoringAssistedReproductive Technologiesworldreport RefYearAspirations PR/asp (%) DR/asp (%) Babies /aspfresh (%) Mansouretal, 2014 2006753637.728.940.4 Dyeretal,20162008103136.8NA42.7 2009782434.129.237.1 2010680336.225.734.2 Adamsonetal, 2018 2011533335.927.435.9 Mouzonetal, 2020 2012784835.017.928.0 3.CAUSES 1.AgesOfInfertileWomenInIVFCentersHave BeenRapidlyIncreasing(Gleicheretal.,2016) ▪15%postponedtheirdesireforpregnancyrequesting reproductivettafter40(CDC,2011) ▪Numberofwomen≥43yseekingIVFisincreasing ▪ICSIcycles≥40y ▪InEurope:25% ▪InEgypt:10%(Mansour&Abousetta2006). ▪Proportionofgoodprognosispatients:declining Poorprognosispatients:increasing.
  4. 4. Femaleage:proportionofadvancedagedpatientsofthetotal numberofwomenundergoingIVFandICSIcycleseachyear. Redcolumn:35–39years; Bluecolumn:40yearsormoreyear(Ferrarettietal,2017) 2.NewlyIntroducedAdditions I.Embryoselection 1.Extendedembryoculturetoblastocyst 2.Electivesingleembryotransfer 3.Timelapseimaging 4.PGS II.Mildovarianstimulations 1.‘Mini-IVF’ 2.Naturalcycle 3.IVFPatient-friendlyIVF III.Cycleinterruptions 1.All-freezecycleswithfrozen-thawedcycle 2.Embryobankingwithcombinedfrozen-thawed cycle
  5. 5. I.EmbryoSelection 1.BSC: ▪2/3offreshIVFcyclesutilizedBSC(CDC,2016). ▪Developedasanembryoselectionmethodin goodprognosispatients ▪Fornoobviousreasonsbecamearoutinefor almosteverybody. ▪NoimprovementincumulativePRor implantationratesinfirsttransfersinanypatient populationbutgoodprognosispatients(DeVoset al.,2016;Glujovskyetal.,2016) 2.eSET ▪uniformincreasesinAustralia/NewZealand,Japan, UK,Canada{Kushniretal.,2017): ▪eSET,vsdoubleET: ▪reducesCPR(McLernonetal.,2010). ▪compensatoryincreasesinIVFcyclesstarted (Kushniretal.,2017).
  6. 6. ▪ProponentsofeSET ▪lowerLBRaftereSETarecompensatedby ▪improvingoutcomes ▪increasingLBRof,frozen-thawed2ndcycles (Pandianetal.,2013;Weietal.,2019) ▪Thisargumentisincorrect: 1.Nopatientcaneverbeguaranteedanopportunity forasubsequentfrozen-thawedcycle 2.2ndcyclesincreasecost&lengthtoconception 3.Argumentisbasedoninappropriatepatient selection&therefore,atbest,onlyapplytogood prognosispatients.
  7. 7. ▪BSC&eSET: ▪80%offreshIVFcyclesinAustralia/NewZealand. Japan ▪reducetwinPR(Bissonnetteetal.,2011) ▪PRhaddropped ▪33.1%fewerIVFinfants(Gleicher,2011). ▪increasingcyclestarts(Kushniretal.,2017). 3.Timelapseimaging ▪Questionableclinicalutility(Harperetal.,2017). ▪InsufficientevidenceofdifferencesinLBR, miscarriage,stillbirthorCPRtochoosebetween TLS,withorwithoutembryoselectionsoftware,& conventionalincubation(CochraneSystRev.2019)
  8. 8. 4.PGS/PGT-A. ▪IneffectiveinimprovingIVFoutcomes{ASRMand SocietyforART2018). ▪Highfalse-positivityrate(Munnéetal.,2017;Victoretal.,2019). ▪largenumberofperfectlynormalembryosare nowroutinelydiscardedwhich,iftransferred:high percentagesofnormalbirths ▪Inpoorerprognosispatients,PGS/PGTAaffects IVFpregnancychancesnegatively. ▪Inunselectedpatientpopulations,PGS/PGT-A actuallyreducesLBR(Kushniretal.,2016). II.MildOvarianStimulation ▪:greatlyreducedeggnumbersincomparisonto standardovarianstimulations(Kushniretal.,2016,2017). ▪Afterawoman’sage,transferrableembryo numbersarethebestpredictorsofIVFsuccess (Gleicheretal.,2016).
  9. 9. ▪Katoprotocol’Japan ▪Mildovarianstimulation,BSC&eSET. ▪DeclineLBR ▪IncreasingIVFcyclestartstocompensatefor thelossoftwo-thirdsofherlivebirthsbetween 2004&2013(Kushniretal.,2017). III.IVFCycleInterruptions: ▪Embryobankinginpoorprognosispatients(who usuallyproducefewoocytes&embryos) ▪Sequentialfreeze-allcyclesofferclinical&/orfinancial benefitsbydelayingETorPGS/PGT-Auntilsufficient eggs/embryoshavebeenaccumulated. ▪LBRof10centerswithespeciallyhigh percentagesofembryobankingcycles:were belowthemedianofallotherremainingUS centers(Kushniretal.,2016,2017).
  10. 10. 3.Industrialization&CommoditizationOfIVF ▪Theinvestmentcommunityinthepast10–15years considered:practiceofIVF,asapotentialgrowth industry. ▪MegaIVFcenterswereestablished,theconceptofso- calledphysicianpracticemanagementcompanies. ▪Aggregationsoffertilitycentersintolargeprovider networksstartedinAustralia,Europe&USA ▪ConsolidationinAustralia/NewZealandmarket, whereonly3IVFcompaniescontrol80%ofIVFcycles (IBISWorld,2015). ▪Industrialization: Transitionfromaprivatepracticemodeltoan investor-drivenindustry ▪Commoditization ▪Primarycompetitiveimportanceofrevenueand incomeratherthanIVFoutcomes ▪Risingutilizationofadd-ons ▪Rapidworldwide‘industrialization:(Hafner,2018). ▪Risingutilizationofadd-ons(‘commoditization’) ▪IncreasedIVFcostswithReducedLBR:poorer patientsatisfaction(Kushniretal.,2017).
  11. 11. CONCLUSIONS 1.WorldwidedeclineinIVFLBR 2.Causes 1.Agesofwomenhavebeenrapidlyincreasing 2.Newlyintroducedadditions 3.Industrialization&commoditizationofIVF. RECOMMENDATIONS 1.MorecarefullyconsiderchangestoroutineIVF practicebeforeclinicalimplementation. 2.ProspectiveRCToftheeffectsofrecentadd-onson IVFcycleoutcomesinordertoconfirmorrefutethe observedassociations 3.Investigatetheeffectsof‘industrialization’and ‘commoditization’onIVFoutcomes,asbothare rapidlyacceleratinginmostregionsoftheworld
  12. 12. ❑YoucangetThislecture&455lecturesfrom: 1.MyscientificpageonFacebook: AboubakrElnasharLectures. https://www.facebook.com/groups/227744884 091351/ 2.Slidesharewebsite 3.elnashar53@hotmail.com ▪Alllecturesfrom: Myclinic,3AlthawraSt.Almansura AboubakrElnashar ▪As‘Forbes’reported(Helft,2016),serialentrepreneur MartinVarsavsky,witha$200millionbudget,launched ‘Prelude’,describedasa‘comprehensivefertilitycompany focusedonproactivefertilitycaretoimprovepeople’s chancesofhavinghealthybabieswhenthey’reready’ina four-stepprocess: 1.fertilitypreservationthroughfreezingofeggsandsperm atpeakfertility(ages20stoearly30s); 2.embryocreationinthelaboratorywhenclientsareready tostartafamily(inotherwords,whatisproposedisthe endofconceptionviaintercourse),and 3.eggsandspermareunfrozenandembryosarecreated; 4.geneticscreening,whereembryosaretestedfor chromosomalabnormalitiesandgeneticmutationsbefore transfer;andeSET. ▪Preludeis,thus,aremarkableaccumulationofrecentadd-
  13. 13. ▪Currentlyavailableoutcomedataonsocialoocyte cryopreservationare,indeed,stillconsideredinadequate (Hammarbergetal.,2017). ▪Yet,‘Prelude’hasbecomethelargestaccumulatorof fertilityclinicsintheUSAand,therefore,offersyetanother exampleofwhyrapid‘industrialization’and ‘commoditization’ofIVFmustbeviewedwithserious concern.

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