GeneticRisksinIVFandICSI

JaneFleming,AssociateGeneticCounsellor,Brisbane

Infertilityisreportedtooccurinapproximately15%ofcouples,andchromosomalorgenetic causeshavebeenidentifiedinasubstantialnumberofthesepatients.Tocircumventthese fertilityproblemsmanycouplesundergofertilitytreatments,invitrofertilisation(IVF)or intracytoplasmicsperminjection(ICSI);however,therearereportsofadditionalgeneticrisks associatedwiththeseprocedures.Inthispresentation,anoutlineofgeneticrisksinIVFandICSI willbeexplored,includingrisksassociatedwithinfertility,transmissionofgeneticconditions, limitationsofgenetictestingorscreeningandtheimplicationsoftheARTprocedure. Bothmaleandfemalefactorinfertilityhavebeenassociatedwithanincreasedincidenceof aneuploidy,structuralchromosomerearrangements,ormonogenicconditionsinsubfertile patients.Forexample,inapproximately25%ofcasesofazoospermiaandsevere oligozoospermiainmales,infertilityisattributabletoasexchromosomeaneuploidy,Y chromosomemicrodeletion,orcongenitalbilateralabsenceofthevasdeferensoften associatedwithcysticfibrosistransmembranereceptorgenemutations.Infemales,sex chromosomeabnormalities(mostlymosaic),autosomalstructuralrearrangementsandsome geneticconditionscanalsoleadtosubfertility.Insomeofthesecasesofinfertilitythereisan additionalriskofverticaltransmissionofachromosomalorgeneticconditiontoARTconceived offspring. IVFandICSIarealsoperformedincaseswhereageneticconditionisknownwithinthefamily, forcoupleswithrecurrentpregnancylossorimplantationfailure,orindividualsusingdonor gametes.Preimplantationgeneticdiagnosis,preimplantationgeneticscreeningandprenatal diagnosisareoptionsforthosepatientsatriskoftransmittingageneticconditionor chromosomalabnormalitytotheiroffspring.Howevertheseproceduresalsohavebenefitsand limitations. Currently,itisestimatedthatoverthreemillionchildrenworldwidehavebeenconceivedusing ART.Overthistime,therehavebeenreportsofincreasedrisksofbirthdefects,aneuploidy, imprintingerrorsduetomaternalhypomethylation,andpossiblechildhoodcancersinoffspring conceivedthroughIVFandICSI.Althoughtheserisksappeartobelow,researchinthisareais continuingandcurrentlyitisunclearwhethertheserisksmightbeassociatedwiththecausesof parentalsubfertilityortheARTprocedure. Incaseswherefertilitytreatmentisbeingconsideredandthereisageneticriskforoffspring, regulatorybodiesrecommendthatcouplesorindividualsreceivegeneticcounselling,toprovide informationaboutthediagnosis,todiscussriskstooffspringandotherfamilymembers,to reviewreproductiveoptionsavailable,andanypsychosocialoremotionalneedsofthecouple. Therefore,theimplicationsofgeneticriskinIVFandICSIwillalsobeexploredfromagenetic counsellingperspective.