Int J Gynecol Obstet 2017; 1–4 wileyonlinelibrary.com/journal/ijgo  | 1© 2017 International Federation of Gynecology and Obstetrics

DOI: 10.1002/ijgo.12181

F I G O S P E C I A L A R T I C L E

FIGO’s updated recommendations for misoprostol used alone in gynecology and obstetrics

Jessica L. Morris1,* | Beverly Winikoff2 | Rasha Dabash2 | Andrew Weeks3 |  Anibal Faundes4 | Kristina Gemzell-Danielsson5 | Nathalie Kapp6 | Laura Castleman6,7 |  Caron Kim8 | Pak Chung Ho9 | Gerard H.A. Visser10

1InternationalFederationofGynecologyandObstetrics,London,UK2GynuityHealthProjects,NewYork,NY,USA3DepartmentofWomen’sandChildren’sHealth,UniversityofLiverpool,Liverpool,UK4DepartmentofObstetricsandGynecology,UniversityofCampinas,SãoPaulo,Brazil5DepartmentofWomen’sandChildren’sHealth,KarolinskaInstitutet,Stockholm,Sweden6Ipas,ChapelHill,NC,USA7UniversityofMichigan,AnnArbor,MI,USA8Independentconsultant9TheUniversityofHongKong,HongKong,China10UniversityMedicalCenter,Utrecht,Netherlands

*CorrespondenceJessicaL.Morris,InternationalFederationofGynecologyandObstetrics,London,UK.Email:jessica@figo.org

1  | BACKGROUND

In 2012, the International Federation of Obstetrics andGynecology(FIGO)producedachartdetailingrecommendeddos-agesofmisoprostolwhenusedalone,foravarietyofgynecologicandobstetricindications.Inlightofnewevidence1–13andthroughexpertdeliberation,thischarthasnowbeenrevisedandexpanded(Fig.1).Someareaswereparticularlychallengingtodevelopgiventhe limited, low-quality, or inconsistent evidence. The presentcommentaryisintendedtoexplainsomeofthechangesanddeci-sionsmade.

2  | GENERAL CHANGES

Thelayoutisnowcategorizedverticallybygestationandhorizontallyby indication.Gestation is labelledandreferredtoasthenumberofweeksofgestation (<13weeks,13–26weeks, and>26weeks),withthefinal columnbeing forpostpartumuse.However, in the caseofincompleteabortionunder13weeks,andinevitableabortionbetween13–26weeks,womenshouldbetreatedonthebasisoftheiruterinesizeratherthanlastmenstrualperioddating.Recommendationshavebeenaddedforinevitableabortionandcervicalpreparationbetween

13 and 26weeks, and for termination of pregnancy at more than26weeks.

3  | NUMBER OF DOSES

Forlessthan13weeks’gestation,wedecidedtorecommendafixednumberofdoseswithoutspecifyingamaximum.Thisisbecausemanyearlypregnancyregimenswillbeusedonanoutpatientbasis,soitisusefulforhealthcareproviderstoknowinadvancehowmanydosestogivetheclient;thereisalsosufficientevidencetosupportafixednumberofdosesforuseinpregnanciesoflessthan13weeks’gesta-tion,aswellasevidencethatitissafetogivefurtherdosesiftheyarerequired.1–4,14

For13–26weeks’gestation,thenotionofamaximumnumberofdoseshasbeenextrapolatedfromclinicalresearchinwhichmaximumdosesarecommonlynotednotonthebasisofpatientsafetyissuesorefficacy,9butratherastangibleendpoints.Inclinicalpractice,however,they might not have great utility, and dosing should continue untilexpulsion,intheabsenceofrarecomplications.Suggestingthatprovid-ersshoulddiscontinuedosingcouldactuallyincreaserisks,particularlywhenprovidershavefewalternativesavailableifexpulsionhasnotyetoccurred.Someunpublishedstudiesandclinicalexperiencehaveshown

2  |     Mooris ET  AL

thatcompleteexpulsioncanbesafelyachievedbycontinuingtheregi-menupto72hours,withoutcompromisingthewoman’ssafety.9

4  | ROUTE OF ADMINISTRATION

Given recently published evidence,2–9 we have added alternativeroutes for taking misoprostol; in most cases, this has meant theadditionofthebuccalroute,inwhichthetabletsareplacedinthecheekfor30minutesafterwhichanyremnantsareswallowed.Thisroute has a similar pharmacokinetic profile to the vaginal route.Furtherongoingstudiesareindicatingthistobeapromisingrouteforother indicationson the chart, but these indicationshavenotbeen included because data on efficacy have not been reported.Future studies will continue to provide evidence on what mightbe a variety of effective regimens and routes of administration.Althoughthiscouldresultinseveralavailableoptionsforproviders,it will also enable women’s preferences to be taken into consid-eration.Women’spreferences canvary,with somepreferring thevaginalroute(ifinsertingthepillsthemselves)andsomepreferringnon-vaginalroutes.However,thevaginalrouteshouldbeavoidedwhenthereisbleedingand/orsignsofinfection.Thechartdoesnotinclude the rectal route.We recommend against using this routebecausethepharmacokineticprofileisnotassociatedwiththebestefficacy.

5  | MISOPROSTOL USE IN PREGNANCIES WITH PREVIOUS CESAREAN OR TRANSMURAL UTERINE SCAR

The use of misoprostol at 13–26weeks’ gestation in women withpreviouscesareanortransmuraluterinescarwasdebatedbecauseofconcernsaboutan increasedriskofuterinerupture.Forfetaldeath,aCochranemeta-analysis15reportedmixedfindings,concludingthatthedatawereinsufficienttoassesstheoccurrenceofuterinerupture.Afewstudieshavereportednoincreasedlikelihoodofrupture,16 but oftenwomenwithpriorcesareanoruterinesurgeryareexcludedfromstudiesorreviews,ortrialsareinsufficientlypoweredtodetectadif-ferenceinsafetyoutcomesasaresultoftherarityofmajoradverseevents.Thereissomeevidencethat,forterminationsinthisperiod,theriskofuterineruptureamongwomenwithapriorcesareandeliveryusingmisoprostolislessthan0.3%1,17;otherstudies9,18–20concludedthattherearenosignificantdifferencesinoutcomesforwomenwithpreviouscesarean(s).Wethereforeconcludedthatmisoprostolcanbeusedforwomenwithpreviouscesareanorothertransmuraluterinescarthroughout13–26weeks.

Thereisinsufficientevidenceavailabletorecommendaregimenofmisoprostolforuseatmorethan26weeks’gestationinwomenwho have had a previous cesarean or transmural uterine scar.Therefore,withoutevidencetosupportasaferegimen,wedonotprovide one, other than to recommend following local protocol inthesecases.

6  | MANAGEMENT OF PREGNANCY TERMINATION AND FETAL DEATH OVER 26 WEEKS’ GESTATION

Althoughthere issomeevidencetosupportadecreasingdosewithincreasinggestationalage,thereislittleevidencetosupporttheadvicegiven in some international and national clinical guidelines to uselowerdosesofmisoprostolincasesoffetaldeath.Irrespectiveoftheissueofrecommendationsfordifferentdoses,variousreviews15,20,21 haveconcludedthatthereisinsufficientevidenceoverallofsuperior-ity of onedoseor schedule ofmisoprostol over another for use inpregnancies at or over 13weeks’ gestation. In making recommen-dations,weacknowledged thatprovidersmightbekeen to identifylowestpossibledosesbecauseofreducedadverseeffects,21butthatitwasalsoimportanttoconsidersuccessratesandtimetodelivery:lowdoseshavebeenshowntobeassociatedwithalongerinduction-to-delivery interval and lower overall effectiveness,15,21 and evi-dencehassupportedthesafetyofthe“higher”dosesforwomen.7–9 Recommendationsinthechartwerecompiledwiththisinmind,whilealsoacknowledgingthatitispossiblethatarangeofdosagescouldbeeffectiveandsafe.

7  | RETAINED PLACENTA

Therehavebeentwostudiesoftheuseofmisoprostolforthetreat-mentofretainedplacentafollowinglivebirth,neitherofwhichshowany benefit over placebo.22We therefore do not recommendmis-oprostolforretainedplacentainlatepregnancy.

8  | SECONDARY PREVENTION OF POSTPARTUM HEMORRHAGE FOR COMMUNITY- BASED PROGRAMS

Secondaryprevention isacommunity-basedstrategy thathasbeenshown to be a comparable alternative to a universal prophylaxisapproachintwolargecommunitytrials(oneinpress).12Ratherthanmedicatingallwomenduringthethirdstageoflaborwithaprophy-lacticdose,aregimenof800μgsublingualmisoprostol(thesameasfor treatment) can be used to treat onlywomenwith higher-than-averagebleeding(e.g.approximately350mLormore).Althoughthereislimitedpublisheddata,itwasagreedthatsecondarypreventionofPPHisastrongalternativeapproachtouniversalprophylaxis,becauseit involves medicating far fewer women (5%–10% vs 100%), thuscausingfeweradverseeffectsandreducingcosts.

9  | CONCLUSION

The FIGO Misoprostol-only Recommended Regimens 2017 chart(Fig.1)istheresultofextensivecollaborationamonganinternational

     |  3Mooris ET  AL

FIGURE 1 TheFIGOmisoprostol-onlyrecommendedregimens2017chart.

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expert group. It has been endorsed by the FIGO Prevention ofUnsafe AbortionWorking Group and the FIGO SafeMotherhoodandNewbornHealthCommittee,andapprovedbytheFIGOOfficers.Available in other languages and formats fromhttp://figo.org, it ishopedthatitwillbeaswidelydistributedandusedasthepreviousversion.Although these recommendeddosageshavebeendecidedonthebasisofcurrentevidenceavailableandexpertopinion,newevidenceisregularlyemergingandthusthereisaneedtoreviewandrevisetheserecommendationsinthefuture.

Misoprostolisanimportantmedicineand,althoughitshouldnotbe used in preference over oxytocin for postpartum hemorrhage,or instead of mifepristone plusmisoprostol for pregnancy termina-tion, it couldbe theonlymedicineavailable insomecircumstances,which iswhyFIGObelievesthis “misoprostol-only”chart isneeded.Misoprostolmustcontinuetobehighlightedasanessentialmedicineand included in international documents, national guidelines, andessentialmedicines lists.Further,wemustworktoensuretheavail-abilityofhigh-qualitymisoprostol,andtheestablishmentofpolicyandprogramsthatsupportitsavailabilityanduse.

The recentWHOguidelinesonhealthworker roles inprovidingsafeabortioncare23outlineawidevarietyofhealthcareproviderswhocanmanagemedical abortion andpostabortion care in thefirst tri-mester,withauxiliarynurses,nurses,andmidwives listed,aswellaslayhealthworkersanddoctorsofcomplementarysystemsforsomesubtasks.Womencanalsofulfillsomeofthecomponentsofassess-mentandmanagementthemselvesoutsideofahealthcarefacility.ItisanticipatedthatthismisoprostolchartcanbeusedbyallhealthcareprovidersidentifiedintheWHOpublicationandthatbyimplementingboth,wewillcomeclosertoachievingoptimalcareforthewomenweaimtoserve.

AUTHOR CONTRIBUTIONS

Allauthorscontributedtothedevelopmentofthechartandthewrit-ingofthecommentary.

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