Ultrasound versus 'clinical touch' for catheter guidance during

57 Pages·2011·0.66 MB·English

Ultrasound versus ’clinical touch’ for catheter guidance during
embryo transfer in women (Review)
Brown J, Buckingham K, Abou-Setta AM, Buckett W
ThisisareprintofaCochranereview,preparedandmaintainedbyTheCochraneCollaborationandpublishedinTheCochraneLibrary
2010,Issue1
http://www.thecochranelibrary.com
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review)
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Figure5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure8. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure10. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Figure11. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis1.1.Comparison1Pregnancy,Outcome1Livebirth(perwomanrandomised). . . . . . . . . . . 37
Analysis1.2.Comparison1Pregnancy,Outcome2Ongoingpregnancies(perwomanrandomised). . . . . . . 37
Analysis1.3.Comparison1Pregnancy,Outcome3Clinicalpregnancies(perwomanrandomised). . . . . . . 38
Analysis2.1.Comparison2Adverseevents,Outcome1Multiplepregnancies(perwomanrandomised). . . . . . 39
Analysis2.2.Comparison2Adverseevents,Outcome2Ectopicpregnancy(perwomanrandomised). . . . . . 40
Analysis2.3.Comparison2Adverseevents,Outcome3Spontaneousmiscarriage(perwomanrandomised). . . . 41
Analysis2.4.Comparison2Adverseevents,Outcome4Bloodoncatheter. . . . . . . . . . . . . . . . 42
Analysis2.5.Comparison2Adverseevents,Outcome5Notconsideredaneasytransfer. . . . . . . . . . . 43
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) i
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Ultrasound versus ’clinical touch’ for catheter guidance during
embryo transfer in women
JulieBrown1,KarenBuckingham2,AhmedMAbou-Setta3,WilliamBuckett4
1Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand. 2Auckland DHB, New Zealand, Auckland, New
Zealand.3UniversityofAlbertaEvidence-basedPracticeCentre(UA-EPC),AlbertaResearchCentreforHealthEvidence(ARCHE),
Edmonton, Canada. 4Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, McGill
University,Montreal,Canada
Contact address: Julie Brown, Obstetrics and Gynaecology, University of Auckland, FMHS, Auckland, New Zealand.
[email protected].
Editorialgroup:CochraneMenstrualDisordersandSubfertilityGroup.
Publicationstatusanddate:Edited(conclusionschanged),publishedinIssue1,2010.
Reviewcontentassessedasup-to-date: 8November2009.
Citation: Brown J, Buckingham K, Abou-Setta AM, Buckett W. Ultrasound versus ’clinical touch’ for catheter guidance
during embryo transfer in women. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD006107. DOI:
10.1002/14651858.CD006107.pub3.
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
ManywomenundergoinganAssistedReproductiveTechnology(ART)cyclewillnotachievealivebirth.Failureattheembryotransfer
stagemaybeduetolackofgoodqualityembryo/s,lackofuterinereceptivity,orthetransfertechniqueitself.Numerousmethods,
includingtheuseofultrasoundguidanceforpropercatheterplacementintheendometrialcavity,havebeensuggestedasamoreeffective
techniqueofembryotransfer.Thisreviewevaluatestheeffectivenessofultrasoundguidedembryotransfer(UGET)comparedwith
’clinicaltouch’(CTET)thetraditionalmethodofembryotransfer.
Objectives
Todeterminewhetherultrasoundguidanceinfluencestreatmentoutcomesinwomenundergoingembryotransfer(ET)duringassisted
reproductivetechnology(ART)cycles.
Searchstrategy
ElectronicdatabasesweresearchedinNovember2009.WesearchedtheCochraneMenstrualDisordersandSubfertilityGrouptrials
register (searched November 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2009),
MEDLINE(1970-2009),EMBASE(1985-2009),BIOExtracts(1980-2009).Relevantconferenceproceedingswerealsohandsearched
(ASRM,ESHREandFIGO).
Selectioncriteria
Onlyrandomisedcontrolledtrialswereincluded.
Datacollectionandanalysis
Tworeviewersindependentlyassessedeligibilityandqualityoftrialsandextracteddatafromthoseselected.
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 1
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Mainresults
Thisupdateidentified59potentialtrialsofwhich42wereexcluded.Dataforanalysiswasavailableinseventeenstudies.Onestudy
reportedlivebirthsandpersonalcommunicationresultedindatarelatingtothisoutcomebeingobtainedintwoadditionalstudies.There
isnoevidenceofasignificantdifferenceintheoutcomeoflivebirth(OR1.14(95%CI0.93to1.39;P=0.02)althoughheterogeneity
was high (64%) and the results should be interpreted with caution. Seven studies reportedon ongoing pregnancies. The ongoing
pregnanciesperwomanrandomisedassociatedwithUGET(441/1254) wassignificantly higherthanforclinicaltouch(350/1218)
OR1.38,95%CI1.16to1.64,P<0.0003). Nostatisticallysignificantdifferencesintheincidenceofadverseeventswereidentified
betweenthecomparisongroups.Theseeventsarerelativelyrareandsamplesizeslimittheabilitytodetectsuchdifferences.
Authors’conclusions
Thestudiesarelimitedbytheirqualitywithonlytwostudiesreportingdetailsofbothcomputerisedrandomisationtechniquesand
adequateallocationconcealment.Ultrasoundguidancedoesappeartoimprovethechancesoflive/ongoingandclinicalpregnancies
comparedwithclinicaltouchmethods.Thequalityoffuturestudiesshouldbeimprovedwithadequatereportingofrandomisation,
allocationconcealment,andpowercalculations.Theprimaryoutcomemeasureoffuturestudiesshouldbethereportingoflivebirths
perwomanrandomised.
PLAIN LANGUAGE SUMMARY
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen
Theinability toachievealivebirthforsomewomenundergoing fertilitytreatmentcanbeduetoanumberoffactorssuchaslack
ofgoodqualityembryo/s,problemswiththeuterus,orthetransfertechniqueitself.Thisreviewlooksatoneaspectofthetransfer
techniqueandwhetherultrasoundguidanceimprovespregnancyratescomparedwithclinicaljudgement.Althoughclinicalpregnancies
andongoingpregnancieswereincreasedfortheultrasoundguidedgroupcomparedwiththeclinicaltouchgroup;therewasnoevidence
ofadifferencebetweenultrasoundguidedembryotransferandclinicaltouchfortheoutcomeoflivebirth.Therisksofharmusing
ultrasound guided transfer, including miscarriage, ectopic pregnancies and multiple pregnancies, are no different to when clinical
judgementisused.
BACKGROUND
uremaybeduetolackofgoodqualityembryo/s,lackofuterine
receptivityorthetechniqueofembryotransferitself.
Descriptionofthecondition
Since the first pregnancy using in vitro fertilisation (IVF) was
Descriptionoftheintervention
achievednearly30yearsago(Steptoe1978)manyaspectsofthe
procedure,suchasovarianstimulation,oocyterecoveryandthein Embryos are usually replacedinto the uterine cavity, through a
vitrotechniquesoffertilizationandembryoculturehaveunder- transcervicaltransfercatheter,betweendays2to5ofdevelopment.
gonemajorrevision.Incontrast,thetechniqueofembryotransfer Traditionally,the“clinicaltouch”methodhasbeenusedtoguide
(ET)hasremainedlargelyunchanged.Today,approximately80% placement of the transfer catheter to within ~10 mm from the
of women undergoing IVF/ICSIwill reach theembryo transfer uterine fundus prior to injection of the embryos. This method
stagewithgoodqualityembryos.However,onlyasmallpropor- isessentially“blind”andreliesontheclinician’stactilesensesto
tionwillthengoontoachieveaclinicalpregnancyandfewerwill judgewhenthetransfercatheterisinthecorrectposition.Some
achievealivebirth.Thismakestheembryotransferphasethefinal clinicianstransfertheembryosatafixeddistancefromtheexternal
andleastsuccessfulstepinART.Indeed,itisestimatedthatupto os(~6cm),howeverthismaynottakeintoaccount variationin
85%ofreplacedembryosfailtoimplant,despitetheselectionof cervicallengthoruterinesize,orposition(retroverted).
apparentlynormalembryosfortransfer(Sallam2002).Thisfail- Assessmentofthetransfercatheterpositionisoftenunreliableus-
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 2
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ingthe“clinicaltouch”method.ThiswasdemonstratedbyWool- is in some cases, moving the catheter to improve identification
cottandStanger(Woolcott1997)whoutilisedtransvaginalultra- is required, a motion that is not needed in transfers performed
soundtoobservecatheterplacementinrelationtotheendome- by“clinicaltouch”.Thismanoeuvremaypotentiallydisruptthe
trial surface and uterine fundus during 121 embryo transfers. endometrium,thusreducingthebenefitsprovidedbyultrasound
Theynotedsub-optimalcatheterplacementinmorethanhalfof (Garcia-Velasco2002).Anotherdisadvantagetotheprocedureare
cases,withthecathetereitherindentingorembeddedintheen- thepossibleunknownsideeffectsofearlyultrasoundonthepre-
dometrium. implantationembryo.
Itisgenerallyacceptedthataneasy,atraumaticembryotransferis
essentialforsuccessfulimplantation(Matorras2002).Itispossible
thatminimizing endometrialtraumacoulddecreasemyometrial
Whyitisimportanttodothisreview
contractions, which could in turn enhance implantation. Most
clinicianstrytoavoidthecathetertipcomingintocontactwith Conflictingresultsintermsofpregnancyrateshavebeenreported
the uterine fundus during embryo transfer (Kovacs 1999), as it for studies comparing ultrasound guidance with the traditional
hasbeen suggested thatthis may stimulate uterine contractions clinical touchmethod.Asaresultof thelackofconcurrence in
(Lesny1998),whichmayinturnleadtoexpulsionoftheembryos. theliteratureitwasdecidedtoreviewtheevidencesystematically
Indeedithasbeennotedthathighfrequencyuterinecontractions toevaluatethismethodforsuccessfulembryotransfer.
visualisedbyultrasoundareassociatedwithalowerongoingclin-
icalpregnancyrate(Fanchin1998).
Thus,the“clinicaltouch”methodmaybechallengedasapotential
cause of cyclefailureasaresultof(1)initiation ofuterine con-
OBJECTIVES
tractilitythatmayleadtoimmediateordelayedexpulsionofthe
embryo/s,and(2)theinabilitytoaccuratelyidentifytheideallo-
Todeterminewhetherultrasoundguidanceinfluencestreatment
cationfordepositionofembryos,especiallyinpatientswithacute
outcomes in women undergoing Embryo Transfer (ET) during
utero-cervicalangulations,cervicalstenosisoranatomicaldistor-
assistedreproductivetechnology(ART)cycles.
tionofthecervicalcanalanduterus.
Numerousmethodstoimprovethetechniqueofembryotransfer
havebeenstudiedtotryandimprovepregnancyrates,including
changingthetypeofcatheterused,performingatrialor“mock” METHODS
transferbeforetheactualprocedure,removinganycervicalmucus
priortotransfer,avoidingtheuseofatenaculum,encouragingbed
restfollowingembryotransfer,comparingfullandemptybladder
Criteriaforconsideringstudiesforthisreview
aswellasperformingtheprocedureunderultrasoundguidance.
Howtheinterventionmightwork Typesofstudies
Allpublished,unpublishedandongoingprospectiverandomised
Theuseofultrasoundtoguideembryotransferwasfirstdiscussed
trialsthatreporteddata comparing outcomes of womenunder-
byStrickleretal(Strickler1985)whopostulatedthatthiswould
goingUltrasoundGuidedEmbryoTransfer(UGET)versusClin-
allowaccurateandatraumaticpositioningofthecathetertipnear
icalTouch EmbryoTransfer(CTET)throughthecervicalroute
the uterine fundus, along with visualization of the injection of
following in-vitro fertilisation (IVF), or intracytoplasmic sperm
thetransferfluidcontainingtheembryos.Byallowingidentifica-
injection (ICSI)including frozenembryotransferswereconsid-
tionofthecervicalcanalandendometrialcavity,ultrasoundcan
th
eredforinclusion.Quasi-randomised(samplingofeveryn en-
facilitate atraumatic penetration of the catheterinto the uterus,
tryfromalist)trialswereexcluded.Therewasnolimitationon
thereby minimizing endometrial trauma. Moreover, its use can
language.
confirmthatthecathetertipisbeyondtheinternalosofthecervix
and placementof the embryos is at the desired levelin the en-
dometrialcavity(Lorusso2005).Thiscanbeespeciallyhelpfulin
Typesofparticipants
womenwheretheuterineanatomymaybedistortedbyfibroidsor
septae(Hurley1991).Forthesereasons,ultrasound guidedem- The participants comprisedwomen with any formof infertility
bryotransfershavebeenratedas“easier”and“cleaner”byclini- undergoing embryo transfer via the cervical route (using either
cians(Prapas2001).Disadvantagesaretheneedforasecondop- fresh or cryopreserved embryos), after either IVF or ICSI and
erator,alongertimetoexecuteandtheinconvenience offilling randomisedtoeitherultrasound-guidedorclinicaltouchembryo
thepatient’sbladder(Martins2004).Anotherpossibledrawback transferthroughthecervicalroute.
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 3
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Typesofinterventions information for more detailson themake-up of the Specialised
Thestudieshadtocompare transcervical embryotransferusing Register.
ultrasoundguidancewithclinicaltouchmethods. (2) The Cochrane Central Register of Controlled trials (CEN-
Embryotransfersthatinvolveddonatedgametesorembryoswere TRAL;TheCochraneLibraryIssue3,2009)wasalsosearched
included.AstandardIVF/ICSIprocedureshouldhavebeencon- inallfieldsusingthefollowingsearchterms:embryotransfer,em-
ducted,usingstandardprotocolsforcontrolledovarianstimula- bryo transfer technique, embryo replacement, ultrasound guid-
tionandtranscervicalreplacementofembryos.Standardculture ance,sonography,echography,vaginalultrasound,trans-abdomi-
mediumandcathetersshouldhavebeenusedforcultureandtrans- nalultrasound,implantationrate,clinicalpregnancyrate.
ferofembryosrespectively. (3)MEDLINE(1966-2009)Appendix2,andEMBASE(1980-
2009) Appendix3weresearchedNovember2009usingthefol-
lowingsubjectheadings(MeSHterms)andkeywordsasasearch
Typesofoutcomemeasures string:
Primaryoutcomes Searchingotherresources
Theprimaryoutcomemeasuresforthissystematicreviewwerethe WesearchedTheNationalResearchRegister(NRR)(aregistration
livebirths/ongoingpregnanciesperwomanrandomised.Ongoing ofongoingandrecentlycompletedresearchprojectsfundedby,or
pregnancies weredefinedas thosecontinuing for atleasttwelve ofinterestto,theUnitedKingdom’sNationalHealthService);the
weeksafterembryotransfer. MedicalResearchCouncil’sClinicalTrialRegister;anddetailson
reviewsinprogresscollectedbytheNHSCentreforReviewsand
Dissemination,fortrialsthathaveanyofthefollowingkeywords:
Secondaryoutcomes embryotransfer,embryotransfertechnique,embryoreplacement,
Thesecondaryoutcomemeasureswere: ultrasoundguidance,ultrasound,implantationrate,clinicalpreg-
(1)Clinical pregnancies perwoman randomised(asdetermined nancyrate,implantation.
byheartbeatdetectedusingultrasound); Thecitationlistofrelevantpublications,reviewarticles,abstracts
(2)Multiplepregnancyrate-Multiplepregnancy(twins,tripletsor ofscientificmeetingsandincludedstudieswasalsohandsearched.
higherorderspecifiedifpossible)perclinicalpregnancy,confirmed Commercialentitiesandexpertsinthefieldwerecontacted,where
byultrasoundordelivery; identified,foridentificationoftrials.Searcheswerenotrestricted
(3)Multiplebirthrateperwomanrandomised; bylanguage.Authorswerecontactedwherenecessarytoprovide
(4)Miscarriagerate-Miscarriage(confirmedbyultrasoundand missingdataonlivebirthrates.
pregnancy test or histology) per woman randomised (including
partiallossofmultiplepregnancies);
(5) Ectopic pregnancy rate -Ectopic gestation per woman ran- Datacollectionandanalysis
domised;
(6) Fetal abnormalities as determined by fetal anatomy scan or
afterdeliveryperwomanrandomised;
Selectionofstudies
(7)Complicationrate-Adverseeffects/eventsassociatedwithem-
Thestudyselectionwasundertakenbytworeviewers(JBandKB),
bryotransferperwomanrandomised;
oneofwhomisaclinicalexpertinthefield(KB).Thetitlesand
(8)Easeoftransferasdeterminedbyclinician.
abstractsofthearticlesidentifiedinthesearchwerescreenedby
JB,whodiscardedstudieswhichwereclearlyineligiblebutaimed
tobeoverlyinclusiveratherthanrisklosingrelevantstudies.JB
Searchmethodsforidentificationofstudies
obtained thefulltextarticlesandmadecopiesforKB.Bothre-
viewersindependentlyassessedwhetherthestudiesmetinclusion
criteria.Furtherinformationwassoughtfromauthorswhereclar-
Electronicsearches
itywasrequired.
See:MenstrualDisordersandSubfertilityGroupmethodsusedin
reviews.
Dataextractionandmanagement
Thisreviewwasupdatedin2009.
(1)WeelectronicallysearchedtheMenstrualDisordersandSub- Astandardiseddataextractionformwasdevelopedandpilotedfor
fertilityGroup’s SpecialisedRegister of Trials (November 2009) consistencyandcompleteness.Trialswereanalysedforthequality
foranytrialsthathadthetermscontainedinAppendix1inthe criteriaandmethodologicaldetailsoutlinedbelow.Thisinforma-
title,abstractorkeywordsections.SeetheReviewGroup’smodule tion,whereavailable,ispresentedintheincludedstudiestableand
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 4
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
alsoinadditionaltables.Thestudiesaredescribedandprovidea been received. No correspondence has been received from any
contextfordiscussing thereliabilityofthestudiesandpotential others.ClarificationofrandomisationwasrequestedfromLi(Li
sourcesofbias.Wheredatawasincompleteormissing,theauthors 2005)althoughnoresponsehasbeenreceivedandBlake(Blake
contactedtheinvestigators ofindividual trialsbye-mail orpost 1998)cannotidentifythestudyrequestedasshewastheheadof
foradditionalinformation. theresearchdepartmentthatsubmittedthesummaryandcannot
identifytheoriginalauthorsofthestudywithintheinstitution.
Assessmentofriskofbiasinincludedstudies
Measuresoftreatmenteffect
Theriskofbiasinincludedstudieswasassessedindependentlyby
two researchersfor thefollowing factors(refertoriskof bias in Analysis
Characteristicsofincludedstudies). Statistical analysiswasperformedinaccordance with theguide-
(1)Methodofrandomisation: linesforstatisticalanalysisdevelopedbytheMenstrualandSub-
(a)Thirdpartyrandomisatione.g.bypharmacy,centralisedran- fertilityGroup.Theoutcomeoflivebirth/ongoingpregnancyand
domisationscheme,computerortelephonerandomisation; clinicalpregnancyisconsideredapositiveconsequenceoffertility
(b) True randomisation by trialist e.g. sequentially numbered treatmentthereforeahigherproportionofwomenwithaclinical
sealed,opaqueenvelopes,register,onsitecomputersystem; pregnancyorlivebirthisconsideredabenefit.Whereasoutcomes
(c)Methodnotstated. suchasmultiplepregnancyareanegativeconsequence,therefore
(2)Studydesign: highernumbersareconsideredtobedetrimental.Thisshouldbe
(a)Methodofallocation(random,quasi-random,unclear); takenintoaccountwhenviewingsummarygraphs.
(b)Methodofconcealment; Where possible the outcomes were pooled statistically. A fixed
(c)Blindingafterconcealment(patient,investigator,assessor); effect model of analysis was used. As the main outcomes were
(d)Multiorsinglecentredesign; dichotomousdatathePetooddsratiowasusedasthesummary
(e)Durationandtimingoftrial. statistic.Dataisreportedasoddsratiosandtranslatedintoabsolute
(3)Sizeofstudy: risksforexplanatorypurposes.Sensitivityanalysiswasconducted
(a)Numberofwomenrecruited; on ’quality of studies’ i.e. unsatisfactory allocation concealment
(b)Numberofwomenrandomised; andconferenceabstractswithincompleteinformation.
(c)Numberofwomenexcluded;
(d)Numberofwomenanalysed;
(e)Numberofwomenlosttofollowupanddetails.
Unitofanalysisissues
(4)Analysis:
Datawasonlyanalysedwheretheoutcomeperwomanrandomised
(a)Samplesizeandpowercalculationconducted;
could be calculated. In studies which reported on outcome per
(b)WhetherornotanalysedbyIntention-to-treat(ITT).
embryotransferverificationwassoughtfromtheprimaryauthor/
(5)Characteristicsofstudyparticipants:
s.
(a)WomenundergoingIVF/ICSI;
(b)Frozen/thawedorfreshembryosreplacementcycle.
(5.1)BaselineCharacteristicsofparticipants:
(a)Ageofwomen; Dealingwithmissingdata
(b)Durationofsubfertility;
Datawillbe presentedastheoutcome perwoman randomised.
(c)Aetiologyofsubfertility;
Wheresuchdata cannotbe collatedfromthepaper verification
(d)Numberofembryostransferred;
wassoughtfromtheprimaryauthor/s.
(e)Protocolsofovarianstimulation;
(f)Methodoftransfer.
Allassessmentsoftrialqualityanddataextractionwereindepen-
Assessmentofheterogeneity
dentlyperformedbytworeviewers(JB,KB)usingpredesigned
dataextractionforms.Anydiscrepancieswerereferredtoathird Heterogeneitybetweentheresultsofdifferentstudieswasexam-
reviewer(WBorAMAS).Additionalinformationontrialmethod- ined by inspecting the scatter in the data points and overlapin
ology or actual original data was sought fromprincipal authors theirconfidence intervalsandformallybyexamining theresults
of trials appearing tomeeteligibility criteria but where areas of of Chisquare andI2 statistic. Anypossible contribution of dif-
clarificationwererequiredwithregardstomethodologyordata. ferencesintrialdesigntoheterogeneityidentifiedinthismanner
Datahasbeenrequestedfromallauthorsofabstracts(BarHarva wasdeterminedusingtheI2statisticwhichisastatisticalmeasure
2003;Faure1998;Moraga-Sanchez2004;Weissman2003),are- usedtoquantifyheterogeneity,anI2valuegreaterthan50%may
sponse has been receivedfromBar-Harva although no data has beconsideredtorepresentsubstantialheterogeneity
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 5
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Assessmentofreportingbiases Resultsofthesearch
Thedataincludedinthisreviewincludespublishedandunpub- One hundred and four potential studies were identified in the
lisheddatawithbothpositiveandnegativefindings.Nopre-pub- originalsearchandanadditionalsixstudiesintheupdatein2009.
licationprotocolswereidentified.
Includedstudies
Nineteenpapers/conferenceabstractsinallwereidentifiedasran-
Datasynthesis
domisedtrialscomparingultrasoundguidancewithclinicaltouch.
Afixedeffectmodelwasusedformeta-analysis. Seventeen trials (Bar Harva 2003;Chen 2007 Coroleu 2000;
Coroleu 2002;Drakeley 2008;Eskander 2008 Garcia-Velasco
2002; Kosmas 2007; Li 2005; Marconi 2003; Martins 2004;
Matorras 2002; Moraga-Sanchez 2004;Tang 2001; Weissman
Subgroupanalysisandinvestigationofheterogeneity
2003; Wisanto 1989; Zakova 2008) were included in the final
Whereheterogeneitywasfoundtoexceed50%subgroupanalysis
analysis.ThestudybyFaure1998isawaitingfurtherinformation
wasperformedtotryandexplainthefindings.
fromauthorsregardingdatabeforeinclusion.Andtheauthorsof
Blake1998couldnotbeidentified.Allofthetrialsincludedinthe
reviewandfinalanalysiswereprospectiverandomisedcontrolled
Sensitivityanalysis trials.
Financial support/conflict of interest: Three of the studies (
Whereheterogeneitywasfoundtoexceed50%sensitivityanalysis
Drakeley2008;Li2005;Zakova2008)reportedreceivingfunding.
wasperformedtotryandexplainthefindingsintermsofquality
Noneofthefundingsourceswascommercial.
ofthestudies.
Baselinecharacteristicsofparticipants
Studiesemergedfromavarietyofcentresaroundtheworld:from
the UK (Drakeley 2008) Spain (Coroleu 2000; Coroleu 2002;
Garcia-Velasco2002;Matorras2002),China(Tang2001),Bel-
gium(Kosmas2007;Wisanto1989),Brazil(Martins2004),Israel
RESULTS
(BarHarva2003;Weissman2003),China(Li2005),Argentina
(Marconi 2003), Taiwan (Chen 2007); Saudi Arabia (Eskander
2008), the Czech Republic (Zakova 2008) and Mexico/USA
(Moraga-Sanchez2004).Allofthestudiesusedtransabdominalul-
Descriptionofstudies
trasound.Thethirteenstudiesincludedreportedon3622women
See:Characteristicsofincludedstudies;Characteristicsofexcluded undergoingembryotransfer.Allreportedonmaternalageexcept
studies;Characteristicsofstudiesawaitingclassification. Moraga-Sanchez2004.Table1
Allcoupleswereinfertileandparticipatinginsomeformoffer-
tility programme. Inclusion criteria reported in the studies was 2007; Coroleu 2000;Eskander 2008; Kosmas 2007; Li 2005;
forthewomentobeonanIVFembryotransferprogramme(Bar Marconi 2003; Martins 2004; Matorras 2002; Garcia-Velasco
Harva 2003; Coroleu 2000; Coroleu 2002; Li 2005; Marconi 2002; Wisanto 1989)included women who hadembryo trans-
2003;Weissman2003;Wisanto1989),undergoingIVFbutless ferrelatedtofreshIVF/ICSIcycles,onestudy(Tang2001)had
thanfortyyearsofage(Marconi2003;Matorras2002),tobere- 56.3%freshembryosintheultrasoundguidedgroupand54%in
cipientsofoocytedonation programmeandbeundergoing em- theclinicaltouchgroupandCoroleu2002usedfrozen/thawed
bryotransferofgoodqualityembryos(Garcia-Velasco2002),aged embryosinbothgroups.Drakeley,2008(Drakeley2008)included
28to41yearsundergoingIVF(includingICSI),undergoingICSI both fresh and frozen embryo transfers. Women with cryopre-
(Li2005;Martins2004),orundergoingICSIorIVFwithfrozen servedembryos,havingoocytedonationorundergoingICSIwere
thawedembryos.Marconi2003alsorequiredthatwomenhada excludedbyMatorras2002andthoserequiringgeneralanaesthe-
day3FSHlevel<12IU/ml.Womenwereunderfortyyearswith siaorrefusingtoparticipatewereexcludedbyTang2001.Node-
fresh embryos undergoing non-donor embryo transfer (Kosmas tailswereprovidedbyZakova2008.
2007) exclusions were cryopreserved embryos and women with The duration of infertility was reported in six studies (Coroleu
previous cervical excision for cervical dysplasia (CIN). No de- 2000; Li 2005; Matorras 2002; Tang 2001; Wisanto 1989;
tailsofinclusionorexclusioncriteriawereprovidedby(Drakeley Weissman2003)andprimarycausesofinfertilitywerementioned
2008;Moraga-Sanchez2004;Eskander2008;Zakova2008). infivestudies(Coroleu2002;Wisanto1989;Li2005;Matorras
Meanagewasdescribedinfifteenofthestudies.Tenstudies(Chen 2002;Tang2001).Theremainingstudiesprovidednodetails.
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 6
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ThirteenstudiesprovidedIVFprotocolinformation(Chen2007; Details regarding day of embryo transfer was not detailed by
Coroleu 2000; Coroleu 2002;Eskander 2008; Garcia-Velasco (Bar Harva 2003; Moraga-Sanchez 2004) and type of ultra-
2002; Kosmas 2007; Li 2005; Marconi 2003; Martins 2004; soundmachineusedfortheprocedureweredescribedby(Chen
Matorras 2002;Tang 2001; Wisanto 1989;Zakova 2008) and 2007; Coroleu 2000; Coroleu 2002;Drakeley 2008; Eskander
eleven described embryo transfer information (Chen 2007; 2008;Garcia-Velasco2002;Kosmas2007;Li2005;Martins2004;
Coroleu 2000; Coroleu 2002; Eskander 2008; Garcia-Velasco Matorras2002;Tang2001).
2002;Kosmas2007;Li2005;Martins2004;Matorras2002;Tang DetailsonrequirementoffullbladderweredetailedbyDrakeley
2001;Wisanto1989).Detailsontheembryomediawasdescribed 2008;Eskander2008;Garcia-Velasco2002;Tang2001;Coroleu
insixstudies(Coroleu2000,Coroleu2002;Li2005;Tang2001; 2002;Kosmas 2007; Matorras 2002 ; Weissman 2003; Wisanto
Garcia-Velasco2002;Wisanto1989).Allofthestudieswiththe 1989.BedrestpostprocedurewasdetailedbyGarcia-Velasco2002;
exceptionof(BarHarva2003;Moraga-Sanchez2004)included Kosmas2007;Li2005;Wisanto1989;Tang2001;Coroleu2002
detailsofthecathetertypeusedforembryotransfer.Thedistance ;Matorras2002.
fromthefunduswheretheembryoswereplacedwasnotdetailedby DetailsofthetransferprotocolandIVFprotocolcanbereferred
(BarHarva2003;Kosmas2007;Moraga-Sanchez2004;Marconi toinTable1.Detailsofdayoftransfer,whetherpatientswereon
2003;Weissman2003;Zakova2008)andonlyonestudyfailed bedrestornotandwhethertheyhadafullbladderornotaswell
torecordthenumberofembryostransferred(Zakova2008). as thetype of ultrasound machine used are detailedinTable 2.
Easeoftransferwasdetailedbytenstudies(Coroleu2000,Coroleu Detailsofthetransfer/replacementprocedurewherereportedare
2002;Drakeley 2008;Eskander 2008;Kosmas 2007; Matorras detailedinTable3.
2002;Tang2001;Weissman2003;Wisanto1989;Zakova2008).
Outcomesstudied
Livebirth Thesewerenotreportedinanystudy.
One study reported on the number of live births per women
randomised (Drakeley 2008). Data was later obtained on this Excludedstudies
outcomefrompersonalcommunicationwithtwooftheauthors
Forty-twostudiesofthe104 potentialstudieswererejectedim-
(Martins2004;Matorras2002).
mediatelybasedonthetitleorcontentoftheavailableabstract.
Ongoingpregnancies:
Theremainingpaperswereretrieved;afurtherfortystudieswere
Seven studies reported on ongoing pregnancies (Coroleu 2000;
rejected(seeCharacteristicsofexcludedstudies)becausemorede-
Eskander 2008; Garcia-Velasco 2002; Kosmas 2007; Marconi
tailedanalysisofthecontentfoundtheywerenotrandomisedcon-
2003;Tang2001;Weissman2003).
trolledtrialsorbecause theywerecomparing cathetertypesand
Clinicalpregnancyrate:
notultrasoundguidanceversusclinicaltouchmethodsofembryo
Allseventeenstudiesreportedclinicalpregnancyrate.
transferorbecausetheywereconferenceproceedingswhichhad
Adverseevents:
subsequently beenpublishedasfullpapers. Tenpaperswerere-
A variety of adverse events including miscarriage, spontaneous
viewsor’letterstotheeditor’whichdidnotcontainanyoriginal
abortion,multiplepregnanciesandbloodonthetransfercatheter
data.
were reported in twelve studies (Coroleu 2000; Coroleu 2002;
Drakeley 2008;Eskander 2008;Garcia-Velasco 2002; Kosmas
Riskofbiasinincludedstudies
2007;Martins2004;Matorras2002;Tang2001;Weissman2003;
Wisanto1989;Zakova2008). See’Characteristicsofincludedstudies’table,Figure1andFigure
Foetalabnormalities: 2.
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 7
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Figure1. Methodologicalqualitygraph:reviewauthors’judgementsabouteachmethodologicalquality
itempresentedaspercentagesacrossallincludedstudies.
Ultrasoundversus’clinicaltouch’forcatheterguidanceduringembryotransferinwomen(Review) 8
Copyright©2010TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.