prof aboubakr elnashar

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. LBRfollowingfreshautologousIVFcyclesfrom1995to2016.
▪Reachingpeakbetween2008and2010
▪Declineby2016
1.LBR/startedIVF/ICSIcycle(CDC,2019)
▪Thedataarebasedonregistrydatafrom
▪Governmentsand/orspecialtysocieties,covering
▪USA
▪Canada
▪UK
▪Australia/NewZealand
▪LatinAmerica
▪Japan.

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. 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. 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. ▪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. ▪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. 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. ▪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. 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. 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. ❑YoucangetThislecture&455lecturesfrom:
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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. ▪Currentlyavailableoutcomedataonsocialoocyte
cryopreservationare,indeed,stillconsideredinadequate
(Hammarbergetal.,2017).
▪Yet,‘Prelude’hasbecomethelargestaccumulatorof
fertilityclinicsintheUSAand,therefore,offersyetanother
exampleofwhyrapid‘industrialization’and
‘commoditization’ofIVFmustbeviewedwithserious
concern.