Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities

57 Pages·2015·0.65 MB·English

Hysteroscopy for treating subfertility associated with
suspected major uterine cavity abnormalities (Review)
Bosteels J, Kasius J, Weyers S, Broekmans FJ, Mol BWJ, D’Hooghe TM
ThisisareprintofaCochranereview,preparedandmaintainedbyTheCochraneCollaborationandpublishedinTheCochraneLibrary
2015,Issue2
http://www.thecochranelibrary.com
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review)
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAINLANGUAGESUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARYOFFINDINGSFORTHEMAINCOMPARISON . . . . . . . . . . . . . . . . . . . 4
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Figure2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Figure3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Figure4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Figure5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Figure6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
ADDITIONALSUMMARYOFFINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . 22
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
AUTHORS’CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
CHARACTERISTICSOFSTUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
DATAANDANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
ADDITIONALTABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
WHAT’SNEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
CONTRIBUTIONSOFAUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
DECLARATIONSOFINTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
SOURCESOFSUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
DIFFERENCESBETWEENPROTOCOLANDREVIEW . . . . . . . . . . . . . . . . . . . . . 54
INDEXTERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) i
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
[InterventionReview]
Hysteroscopy for treating subfertility associated with
suspected major uterine cavity abnormalities
JanBosteels1,JennekeKasius2,StevenWeyers3,FrankJBroekmans2,BenWillemJMol4,ThomasMD’Hooghe5
1BelgianBranchoftheDutchCochraneCentre,Leuven,Belgium.2DepartmentofReproductiveMedicineandGynecology,University
Medical Center,Utrecht,Netherlands.3Obstetricsand Gynaecology, University Hospital Ghent, Ghent,Belgium. 4The Robinson
Institute,SchoolofPaediatricsandReproductiveHealth,TheUniversityofAdelaide,Adelaide,Australia.5LeuvenUniversityFertility
Centre,UniversityHospitalGasthuisberg,Gasthuisberg,Belgium
Contact address: Jan Bosteels, BelgianBranch of the Dutch Cochrane Centre, Kapucijnenvoer 33 blok J bus 7001, 3000 Leuven,
Leuven,[email protected].
Editorialgroup:CochraneGynaecologyandFertilityGroup.
Publicationstatusanddate:Newsearchforstudiesandcontentupdated(nochangetoconclusions),publishedinIssue2,2015.
Reviewcontentassessedasup-to-date: 8September2014.
Citation: BosteelsJ,KasiusJ,WeyersS,BroekmansFJ,MolBWJ,D’HoogheTM.Hysteroscopyfortreatingsubfertilityassociated
withsuspectedmajoruterinecavityabnormalities.CochraneDatabaseofSystematicReviews2015,Issue2.Art.No.:CD009461.DOI:
10.1002/14651858.CD009461.pub3.
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
ABSTRACT
Background
Observationalstudiessuggesthigherpregnancyratesafterthehysteroscopicremovalofendometrialpolyps,submucousfibroids,uterine
septumorintrauterineadhesions,whicharedetectablein10%to15%ofwomenseekingtreatmentforsubfertility.
Objectives
Toassesstheeffectsofthehysteroscopicremovalofendometrialpolyps,submucousfibroids,uterineseptumorintrauterineadhesions
suspectedonultrasound,hysterosalpingography,diagnostichysteroscopyoranycombinationofthesemethodsinwomenwithotherwise
unexplained subfertilityor prior tointrauterine insemination (IUI),invitrofertilisation (IVF)or intracytoplasmic sperminjection
(ICSI).
Searchmethods
WesearchedtheCochraneMenstrualDisordersandSubfertilitySpecialisedRegister(8September2014),theCochraneCentralRegister
ofControlledTrials(TheCochraneLibrary2014,Issue9),MEDLINE(1950to12October2014),EMBASE(inceptionto12October
2014),CINAHL(inceptionto11October2014)andotherelectronicsourcesoftrialsincludingtrialregisters,sourcesofunpublished
literature and referencelists. We handsearchedthe AmericanSociety for Reproductive Medicine (ASRM) conference abstracts and
proceedings(fromJanuary2013toOctober2014)andwecontactedexpertsinthefield.
Selectioncriteria
Randomisedcomparisonsbetweenoperativehysteroscopyversuscontrolinwomenwithotherwiseunexplainedsubfertilityorunder-
goingIUI,IVForICSIandsuspectedmajoruterinecavityabnormalitiesdiagnosedbyultrasonography,salineinfusion/gelinstillation
sonography,hysterosalpingography,diagnostichysteroscopyoranycombinationofthesemethods.Primaryoutcomeswerelivebirth
andhysteroscopycomplications.Secondaryoutcomeswerepregnancyandmiscarriage.
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) 1
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Datacollectionandanalysis
Tworeviewauthorsindependentlyassessedstudiesforinclusionandriskofbias,andextracteddata.Wecontactedstudyauthorsfor
additionalinformation.
Mainresults
We retrieved 12 randomised trials possibly addressing the research questions. Only two studies (309 women) met the inclusion
criteria.Neitherreportedtheprimaryoutcomesoflivebirthorprocedurerelatedcomplications.Inwomenwithotherwiseunexplained
subfertility and submucous fibroids there was no conclusive evidence of a difference between the intervention group treated with
hysteroscopicmyomectomyandthecontrolgrouphavingregularfertility-orientedintercourseduring12monthsfortheoutcomeof
clinicalpregnancy.Alargeclinicalbenefitwithhysteroscopicmyomectomycannotbeexcluded:if21%ofwomenwithfibroidsachieve
aclinicalpregnancy having timedintercourse only,theevidencesuggests that39% ofwomen(95% CI21%to58%)willachieve
asuccessfuloutcomefollowingthehysteroscopicremovalofthefibroids(oddsratio(OR)2.44,95%confidenceinterval(CI)0.97
to6.17,P=0.06,94women,verylowqualityevidence).Thereisnoevidenceofadifferencebetweenthecomparisongroupsforthe
outcomeofmiscarriage(OR0.58,95%CI0.12to2.85,P=0.50,30clinicalpregnanciesin94women,verylowqualityevidence).The
hysteroscopicremovalofpolypspriortoIUIcanincreasethechanceofaclinicalpregnancycomparedtosimplediagnostichysteroscopy
andpolypbiopsy:if28%ofwomenachieveaclinicalpregnancywithasimplediagnostichysteroscopy,theevidencesuggeststhat63%
ofwomen(95%CI50%to76%)willachieveaclinicalpregnancyafterthehysteroscopicremovaloftheendometrialpolyps(OR4.41,
95%CI2.45to7.96,P<0.00001,204women,moderatequalityevidence).
Authors’conclusions
Alargebenefitwiththehysteroscopicremovalofsubmucousfibroidsforimprovingthechanceofclinicalpregnancyinwomenwith
otherwiseunexplainedsubfertilitycannotbeexcluded.Thehysteroscopicremovalofendometrialpolypssuspectedonultrasoundin
womenpriortoIUImayincreasetheclinicalpregnancyrate.Morerandomisedstudiesareneededtosubstantiatetheeffectivenessof
thehysteroscopicremovalofsuspectedendometrialpolyps,submucousfibroids,uterineseptumorintrauterineadhesionsinwomen
withunexplainedsubfertilityorpriortoIUI,IVForICSI.
PLAIN LANGUAGE SUMMARY
Hysteroscopyfortreatingsuspectedabnormalitiesofthecavityofthewombinwomenhavingdifficultybecomingpregnant
Reviewquestion
Cochraneauthorsreviewedtheevidenceabouttheeffectofthehysteroscopictreatmentofsuspectedabnormalitiesofthecavityofthe
wombinwomenhavingdifficultybecomingpregnant.
Background
Human life startswhen a fertilisedegg has successfully implanted in the inner layer of the cavity of the womb. It is believedthat
abnormalitiesoriginatingfromthissite,suchaspolyps,fibroids,septaoradhesions,maydisturbthisimportantevent.Theremoval
oftheseabnormalitiesbydoingahysteroscopyusingaverysmalldiameterinspectingdevicemightthereforeincreasethechanceof
becomingpregnanteitherspontaneouslyorafterspecialisedfertilitytreatment,suchasinseminationorinvitrofertilisation.
Studycharacteristics
Wefoundonlytwostudiesin309women.Thefirststudycomparedtheremovaloffibroidsversusnoremovalin94womenwishingto
becomepregnantfromJanuary1998untilApril2005.Thesecondstudycomparedtheremovalofpolypsversussimplehysteroscopy
only in 215 women before insemination with husband’s sperm from January 2000 to February 2004. The evidence is current to
September2014.Nostudyreportedfundingsources.
Keyresults
Noneofthestudiesreportedlivebirth.
Thestudyontheremovaloffibroidsinwomenwithunexplainedinfertilitysuggestsdoesnotexcludeahigherchanceofconceiving
aftersurgerycomparedtoregularsexualintercoursefor12months.Howeveruncertaintyremainsbecausethenumberofwomen(94)
andthenumberofpregnancies(30)aretoosmallforanydifferencesbetweenbothcomparisongroupstoreachstatisticalsignificance.
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) 2
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
If21%ofwomenwithfibroidsachieveapregnancyhavingtimedintercourseonly,theevidencesuggeststhatbetween21%to58%of
womenwillachieveasuccessfuloutcomefollowingthehysteroscopicremovalofthefibroids.
Thesecondstudyonthehysteroscopicremovalofpolypssupportsabenefitwiththehysteroscopicremovalofpolyps.If28%ofwomen
become pregnantinthecontrolgroup, theevidencesuggests thatbetween50%to76% ofwomenwillbecome pregnant afterthe
removaloftheendometrialpolyps
Nostudyreporteddataonadverseprocedurerelatedevents.
Morestudiesareneededbeforehysteroscopycanbeproposedasafertility-enhancingprocedureinthegeneralpopulationofwomen
havingdifficultybecomingpregnant.
Qualityoftheevidence
Thequalityoftheevidenceonfibroidsisverylow:therewasonlyonepoorlyconductedstudylackingsufficientdata.
Thequalityoftheevidenceonpolypsismoderate:therewereissueswithselectivereportingofoutcomes.
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) 3
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
CoHy SUMMARY OF FINDINGS FOR THE MAIN COMPARISON [Explanation]
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chransubfe Intervention:hysteroscopicremovalofonesubmucousfibroid≤40mm
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inthecomparisongroupandtherelativeeffectoftheintervention(andits95%CI).
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chransubfe 1Aclinicalpregnancywasdefinedbythevisualisationofanembryowithcardiacactivityatsixtosevenweeks’gestationalage.
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BACKGROUND resorbed.Auterineseptumispresentin1%to3.6%ofwomen
withotherwiseunexplainedsubfertility(Saravelos2008).
Ultrasonography(US),preferablytransvaginally(TVS),isusedto
Descriptionofthecondition screenforpossibleendometriumoruterinecavityabnormalitiesin
thework-upofsubfertilewomen.Thisevaluationcanbeexpanded
Subfertility is “a disease of the reproductive system defined by
withhysterosalpingography(HSG),salineinfusion/gelinstillation
the failure to achieve a clinical pregnancy after 12 months or
sonography (SIS/GIS) and diagnostic hysteroscopy. Diagnostic
more of regular unprotected sexual intercourse” according to
hysteroscopy is generally considered as being the gold standard
theInternationalCommitteeforMonitoringAssistedReproduc-
procedurefortheassessmentoftheuterinecavitysinceitenables
tive Technology (ICMART) and the World Health Organiza-
directvisualisation;moreover,treatmentofintrauterinepathology
tion(WHO)revisedglossaryofassistedreproductivetechnology
canbedoneinthesamesetting(Bettocchi2004).Nevertheless,
(ART)(Zegers-Hochschild2009)(see:http://www.icmartivf.org/
evenforexperiencedgynaecologiststhehysteroscopicdiagnosisof
ivf-glossary.html).Itisestimatedthat72.4millionwomenaresub-
themajoruterinecavityabnormalitiesmaybeproblematic(Kasius
fertileandthat40.5millionofthesearecurrentlyseekingfertility
2011a).
treatment(Boivin2007).Unexplainedsubfertilityusuallyrefersto
adiagnosis(orlackofdiagnosis)madeincouplesinwhomallthe
standard investigations such as tests of ovulation, tubal patency
Descriptionoftheintervention
andsemenanalysisarenormal:itcanbefoundinasmanyas30%
to40%ofsubfertilecouples(Ray2012). Hysteroscopy is performed for the evaluation, or for the treat-
Theevaluationoftheuterinecavityseemsabasicstepinthein- mentoftheuterinecavity,tubalostiaandendocervicalcanalin
vestigationofallsubfertilewomensincetheuterinecavityandits womenwithuterinebleedingdisorders,Mülleriantractanoma-
inner layer,the endometrium, are assumed to be important for lies,retainedintrauterinecontraceptivesorotherforeignbodies,
theimplantationofthehumanembryo,calledablastocyst.Nev- retainedproductsofconception,desireforsterilisation,recurrent
ertheless,thecomplexmechanismsleadingtosuccessfulimplan- miscarriageandsubfertility.Iftheprocedureisintendedforevalu-
tationarestillpoorlyunderstood(Taylor2008).Despitethehuge atingtheuterinecavityonly,itiscalledadiagnostichysteroscopy.
investmentinresearchanddevelopmentsofthetechnologiesand Iftheobservedpathology requiresfurthertreatment,theproce-
biology involvedinmedicallyassistedreproduction(MAR), the dure is calledan operative hysteroscopy. In everyday practice, a
maximumimplantationrateperembryotransferredstillremains diagnostichysteroscopyconfirmingthepresenceofpathologywill
only30%(Andersen2008).Thedifferentphasesoftheimplanta- be followedby an operative hysteroscopy in a symptomatic pa-
tionprocessareestablishedbythecomplexinterchangebetween tient.
theblastocystandtheendometrium(Singh2011). Hysteroscopyallowsthedirectvisualisationoftheuterinecavity
Majoruterinecavityabnormalitiescanbefoundin10%to15% through a rigid, semi-rigid or flexible endoscope. The hystero-
ofwomenseekingtreatmentforsubfertility;theyusuallyconsist scope consists of arigid telescopewith aproximal eyepieceand
ofthepresenceofexcessivenormaluterinetissue(Wallach1972). a distal objective lens that may be angled at 0° to allow direct
Themostcommonacquireduterinecavityabnormalityisanen- viewingoroffsetatvariousanglestoprovideafore-obliqueview.
dometrial polyp. This benign, endometrial stalk-like mass pro- Advancesinfibreoptictechnologyhaveledtotheminiaturisation
trudesintotheuterinecavityandhasitsownvascularsupply.De- of the telescopeswithout compromising the image quality. The
pendingonthepopulationunderstudyandtheapplieddiagnostic total working diametersofmoderndiagnostic hysteroscopesare
test,endometrialpolypscanbefoundin1%to41%ofthesubfer- typically2.5to4.0mm.Operativehysteroscopyrequiresadequate
tilepopulation(Silberstein2006).Afibroidisanexcessivegrowth visualisation throughacontinuous fluidcirculationusinganin-
originatingfromthemuscularpartoftheuterinecavity.Fibroids andanoutflowchannel.Theouterdiametersofmodernoperative
arepresentin2.4%ofsubfertilewomenwithoutanyotherobvi- hysteroscopeshavebeenreducedtoadiameterbetween4.0and
ouscauseofsubfertility(Donnez2002).Asubmucousfibroidis 5.5mm.Thesheathsystemcontainsoneortwo1.6to2.0mm
locatedunderneaththeendometriumandisthoughttointerfere workingchannelsfortheinsertionofsmallgraspingorbiopsyfor-
withfertilitybydeformingtheuterinecavity.Intrauterineadhe- ceps,scissors,myomafixationinstruments,retractionloops,mor-
sionsarefibroustissuestringsconnectingpartsoftheuterinewall. cellators (surgical instruments used to divide and remove tissue
Theyarecommonlycausedbyinflammationoriatrogenictissue duringendoscopicsurgery)andaspirationcannulae,orunipolar
damage(meaninginvoluntarilycausedbyaphysician’sinterven- orbipolarelectrodiathermyinstruments.
tion, for example an aspiration curettage after miscarriage) and Mostdiagnosticandmanyoperativeprocedurescanbedoneinan
arepresentin0.3%to14%ofsubfertilewomen(Fatemi2010). officesettingusinglocalanaesthesiaandfluiddistension media,
Aseptateuterusisacongenitalmalformationinwhichthelongi- while more complex procedures are generally performed as day
tudinalbandseparatingtheleftandrightMüllerianducts,which surgery under general anaesthesia (Clark 2005). Operative hys-
formtheuterusinthehumanfemalefetus,hasnotbeenentirely teroscopicproceduresrequireacomplexinstrumentationset-up,
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) 6
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
special training of the surgeon and appropriate knowledge and shouldnotbeofferedhysteroscopyonitsownaspartoftheinitial
managementofcomplications(Campo1999). investigation unlessclinicallyindicatedbecause theeffectiveness
Althoughcomplicationsfromhysteroscopyarerare,theycanbe ofsurgicaltreatmentofuterineabnormalitiesonimprovingpreg-
potentiallylifethreatening.Amulticentrestudyincluding13,600 nancyrateshasnotbeenestablished”(NICE2004).Thereis,how-
diagnostic and operative hysteroscopicproceduresperformedin ever,atrendinreproductivemedicinethatisdevelopingtowards
82centresreportedacomplicationrateof0.28%.Diagnostichys- diagnosisandtreatmentofallmajoruterinecavityabnormalities
teroscopyhadasignificantlylowercomplicationratecomparedto prior to fertility treatment. This evolution can be explained by
operativehysteroscopy(0.13%versus0.95%).Themostcommon threereasons.Firstly,diagnostichysteroscopyisgenerallyaccepted
complicationofbothtypesofhysteroscopywasuterineperforation ineverydayclinicalpracticeasthe‘goldstandard’foridentifying
(0.13%fordiagnostic; 0.76%foroperativehysteroscopy).Fluid uterineabnormalitiesbecauseitallowsdirectvisualisationofthe
intravasationoccurredalmostexclusivelyinoperativeprocedures uterine cavity (Golan 1996). Secondly, since 2004 several ran-
(0.02%).Intrauterineadhesiolysiswasassociatedwiththehighest domisedcontrolledtrials(RCTs)havedemonstratedthetechni-
incidenceofcomplications(4.5%);alloftheotherprocedureshad calfeasibilityandthehighpatientsatisfactionrateinwomenun-
complicationratesoflessthan1%(Jansen2000). dergoingbothdiagnostic andoperativehysteroscopyforvarious
reasons including subfertility (Campo 2005; De Placido 2007;
Garbin2006;Guida2006;Kabli2008;Marsh2004;Sagiv2006;
Shankar2004;Sharma2005).Thirdly,inasubfertilepopulation
Howtheinterventionmightwork
screenedsystematicallybydiagnostichysteroscopy,theincidence
Itisassumedthatmajoruterinecavityabnormalitiesmayinterfere ofnewlydetectedintrauterinepathologymaybeashighas50%
with factorsthatregulate theblastocyst-endometrium interplay, (Campo1999;DePlacido2007).
forexamplehormonesandcytokines,precludingthepossibilityof This review aims to summarise and critically appraise the cur-
pregnancy.Manyhypotheseshavebeenformulatedinthelitera- rentevidence ontheeffectivenessof operative hysteroscopic in-
tureofhowendometrialpolyps(Shokeir2004;Silberstein2006; terventionsinsubfertilewomenwithmajoruterinecavityabnor-
Taylor2008;Yanaihara2008),submucousfibroids(Pritts2001; malities,bothinwomenwithunexplainedsubfertilityandthose
Somigliana2007;Taylor2008),intrauterineadhesions(Yu2008) boundtoundergoMAR.Sinceuterinecavityabnormalitiesmay
anduterineseptum(Fedele1996)arelikelytodisturbtheimplan- negativelyaffecttheuterineenvironment,andthereforethelike-
tationofthehumanembryo;nevertheless,theprecisemechanisms lihood of conceiving (Rogers 1986), it has been recommended
of action through which eachone of thesemajor uterine cavity thattheseabnormalitiesbediagnosedandtreatedbyhysteroscopy
abnormalitiesaffectsthisessentialreproductiveprocessarepoorly toimprovethecost-effectivenessinsubfertilewomenundergoing
understood.Thefetal-maternalconflicthypothesistriestoexplain MAR,whererecurrentimplantationfailureisinevitablyassociated
howasuccessfulpregnancymayestablishitselfdespitetheintrin- withahighereconomicburdentosociety.
sicgenomicinstabilityofhumanembryosthroughthespecialist Thestudyoftheassociationbetweensubfertilityandmajoruter-
functionsoftheendometrium,inparticularitscapacityforcyclic inecavityabnormalitiesmightincreaseourcurrentunderstanding
spontaneous decidualisation, sheddingandregeneration. Anex- ofthecomplexmechanismsofhumanembryoimplantation.This
cellentin-depthreviewlinkingbasicresearchofhumanimplanta- could lead to the development of cost-effective strategies in re-
tionwithclinicalpracticecanbefoundelsewhere(Lucas2013). productivemedicinewithbenefitsforboththeindividualwoman
For endometrial polyps, submucous fibroids, intrauterine adhe- sufferingfromsubfertilityassociatedwithmajoruterinecavityab-
sionsanduterineseptum,observationalstudieshaveshownaclear normalitiesaswellasforsociety,inabroaderperspective.
improvementinthespontaneouspregnancyrateafterthehystero-
scopicremovaloftheabnormality(Taylor2008).Thechancefor
pregnancyissignificantlylowerinsubfertilewomenwithsubmu-
cous fibroids compared toother causes of subfertility according OBJECTIVES
toasystematicreviewandmeta-analysisof11observationalstud-
Toassesstheeffectsofthehysteroscopicremovalofendometrial
ies(Pritts2001;Pritts2009).Threeobservational studiesfound
polyps,submucousfibroids,uterineseptumorintrauterineadhe-
amajor benefitforremovingauterineseptumbyhysteroscopic
sionssuspectedonultrasound,hysterosalpingography,diagnostic
metroplasty in subfertile women with a uterine septum (Mollo
hysteroscopyoranycombinationofthesemethodsinwomenwith
2009;Shokeir2011;Toma evi 2010).
otherwiseunexplainedsubfertilityorpriortointrauterineinsemi-
nation(IUI),invitrofertilisation(IVF)orintracytoplasmicsperm
injection(ICSI).
Whyitisimportanttodothisreview
ANationalInstitute forHealthandClinicalExcellence(NICE)
guidelineonfertilityassessmentandtreatmentstatesthat“women METHODS
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) 7
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.
Criteriaforconsideringstudiesforthisreview Typesofinterventions
Two types of randomised interventions were addressed; within
bothcomparisonsthesuspectedmajoruterinecavityabnormali-
Typesofstudies tieswerestratifiedintoendometrialpolyps,submucousfibroids,
uterineseptumandintrauterineadhesions.Forthesecondcom-
parisontherewasastratificationintoIUI,IVForICSI.
Inclusioncriteria • Randomisedcomparisonbetweenoperativehysteroscopy
versuscontrolinwomenwithotherwiseunexplainedsubfertility
• Onlytrialsthatwereeitherclearlyrandomisedorclaimed
andsuspectedmajoruterinecavityabnormalitiesdiagnosedby
toberandomisedanddidnothaveevidenceofinadequate
US,SIS,GIS,HSG,diagnostichysteroscopyoranycombination
sequencegenerationsuchasdateofbirthorhospitalnumber
ofthesemethods.
wereeligibleforinclusion.
• Randomisedcomparisonbetweenoperativehysteroscopy
• Clustertrialswereconsideredtobeeligibleifthe
versuscontrolinwomenundergoingIUI,IVForICSIwith
individuallyrandomisedwomenweretheunitofanalysis.
suspectedmajoruterinecavityabnormalitiesdiagnosedbyUS,
• Cross-overtrialswerealsoconsideredtobeeligiblefor
SIS,GIS,HSG,diagnostichysteroscopyoranycombinationof
completenessbutweplannedtouseonlypre-cross-overdatafor
thesemethods.
meta-analysis.
Typesofoutcomemeasures
Exclusioncriteria
• Quasi-randomisedtrials.
Primaryoutcomes
1.Effectiveness:livebirth,definedasadeliveryofalivefetusafter
Typesofparticipants 20completedweeksofgestationalagethatresultedinatleastone
livebabyborn.Thedeliveryofasingleton,twinormultiplepreg-
nancywascountedasonelivebirth(Zegers-Hochschild2009).
2. Adverse events: hysteroscopy complications, defined as any
Inclusioncriteria
complicationduetohysteroscopy.
• Womenofreproductiveagewithotherwiseunexplained
subfertilityandendometrialpolyps,submucousfibroids,septate
Secondaryoutcomes
uterusorintrauterineadhesionsdetectedbyUS,SIS,GIS,HSG,
diagnostichysteroscopyoranycombinationofthesemethods. 3.Pregnancy
Besidesunexplainedsubfertilityasthemainclinicalproblem, • Ongoingpregnancy,definedasapregnancysurpassingthe
othergynaecologicalcomplaints,suchaspainorbleeding,might firsttrimesteror12weeksofpregnancy.
ormightnotbepresent. • Clinicalpregnancywithfetalheartbeat,definedasa
• Womenofreproductiveagewithsubfertility,undergoing pregnancydiagnosedbyUSorclinicaldocumentationofatleast
IUI,IVForICSIwithendometrialpolyps,submucousfibroids, onefetuswithaheartbeat(Zegers-Hochschild2009).
septateuterusorintrauterineadhesionsdetectedbyUS,SIS, • Clinicalpregnancy,definedasapregnancydiagnosedbyUS
GIS,HSG,diagnostichysteroscopyoranycombinationofthese visualisationofoneormoregestationalsacsordefinitiveclinical
methods. signsofpregnancy(Zegers-Hochschild2009).
4.Adverseevents:miscarriage,definedasthespontaneouslossof
aclinicalpregnancybefore20completedweeksofgestation,orif
Exclusioncriteria
gestationalageisunknownafetuswithaweightof400gorless
• Womenofreproductiveagewithsubfertilityand (Zegers-Hochschild2009).
intrauterinecavityabnormalitiesotherthanendometrialpolyps, Weplannedtoreporttheminimallyimportantclinicaldifference
submucousfibroids,intrauterineadhesionsandseptateuterus, (MICD)fortheprimaryoutcomeoflivebirth.AMICDof5%for
e.g.subserousorintramuralfibroidswithoutcavitydeformation thelivebirthratewaspredefinedasbeingrelevantforthebenefits.
onhysteroscopy,acuteorchronicendometritis,adenomyosisor The imputation of thisvalue was based on data froma clinical
otherso-called’subtlefocal’lesions. decisionanalysisonscreeninghysteroscopypriortoIVF(Kasius
• Womenofreproductiveagewithendometrialpolyps, 2011b).
submucousfibroids,intrauterineadhesionsorseptateuterus We planned to include the main outcome measures ’live birth’,
withoutsubfertility. ’hysteroscopycomplications’and’miscarriage’ina’Summaryof
• Womenofreproductiveagewithrecurrentpregnancyloss. findings’ table. The ’Summary of findings’ table was generated
Hysteroscopyfortreatingsubfertilityassociatedwithsuspectedmajoruterinecavityabnormalities(Review) 8
Copyright©2015TheCochraneCollaboration.PublishedbyJohnWiley&Sons,Ltd.