Tuberculosis of The Female Genital Tract - GLOWM

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TuberculosisoftheFemaleGenitalTract|GLOWM
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Thischaptershouldbecitedasfollows:
Varma,T,Glob.libr.women'smed.,
(ISSN:17562228)2008DOI10.3843/GLOWM.10034
Thischapterwaslastupdated:
October2008
TuberculosisoftheFemaleGenitalTract
ThankamR.Varma,MD
MedicalDirector,InstituteofReproductiveMedicineandWomen'sHealth,MadrasMedicalMission,Chennai,India
INTRODUCTION
INCIDENCE
PATHOGENESIS
PATHOLOGY
TUBERCULOSISOFTHEPELVIS
TUBERCULOSISOFTHEFALLOPIANTUBES
MICROSCOPICAPPEARANCE
TYPESOFTUBERCULOUSSALPINGITIS
MODEOFSPREADFROMTUBES
TUBERCULOSISOFTHEENDOMETRIUM
TUBERCULOSISOFTHEOVARY
PERIOOPHORITIS
OOPHORITIS
TUBERCULOSISOFTHECERVIX
TUBERCULOSISOFTHEVULVAANDVAGINA
TUBERCULOUSPERITONITIS
CLINICALFEATURES
SYMPTOMS
PHYSICALSIGNS
DIAGNOSIS
RADIOGRAPHY
ULTRASONOGRAPHY
CERVICALCYTOLOGY
ENDOSCOPY
RAPIDMOLECULARTECHNIQUES
POLYMERASECHAINREACTION
NUCLEICACIDAMPLIFICATIONTECHNIQUESFORTUBERCULOSIS
SEROLOGICDIAGNOSIS
DRUGSENSITIVITYTEST
DIFFERENTIALDIAGNOSIS
https://www.glowm.com/section_view/heading/Tuberculosis%20of%20the%20Female%20Genital%20Tract/item/34#20681
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COMPLICATIONOFGENITALTUBERCULOSIS
MANAGEMENT
TREATMENT
GENITALTUBERCULOSISANDPREGNANCY
PERINATALOUTCOMEOFPREGNANCYFOLLOWINGTREATMENTFORGENITALTUBERCULOSIS
ACKNOWLEDGMENT
REFERENCES
INTRODUCTION
Genitaltuberculosis(TB)infemalesisbynomeansuncommon,particularlyincommunitieswherepulmonaryor
otherformsofextragenitalTBarecommon.TBcanaffectanyorganinthebody,canexistwithoutanyclinical
manifestation,andcanrecur.
TBwasrecognizedasaclinicalentityasfarbackas1000BC.However,itwasnotuntil1744thatMorgagni,1
followingapostmortemexaminationofa20yearoldwomanwhodiedofTBandwhoseuterusandfallopian
tubeswerefoundtobefilledwithcaseousmaterial,describedthefirstcaseofgenitalTB.Thewordtuberculosis
wasfirstusedin1834,althoughKochdidnotdiscoverthetuberclebacilliuntil1882.
TBisconsideredthemostimportantcommunicablediseaseintheworld.Sincethebeginningofthe20th
century,theincidenceofTBingeneralandgenitalTBmoreparticularlyhasbeensteadilydecliningindeveloped
countries.However,TBremainsamajorhealthprobleminmanydevelopingcountries,andintheseareas,
genitalTBisresponsibleforasignificantproportionoffemalespresentingwithinfertility.2TBaffectsalmost
50%ofthepopulationinThirdWorldcountries.Anestimated30millionpersonshaveactiveTB,and710
millionpeopledieeachyearofTB.3, 4
AreviewoftheliteraturerevealsthatthehighestincidenceofTBisstillinIndia,followedbyScandinaviaand
Scotland.ItisestimatedthatalmostonehalfofthepopulationofIndiahasTBandthatonepersondiesevery
minutefromTB.ThetrueincidenceofgenitalTBisnotknowngiventhat,owingtoitssubtlepresentation,many
casesremainundiagnosed.Ithasbeenestimatedthatapproximately5%offemalespresentingtosubfertility
clinicsworldwidehavegenitalTB.5However,estimatesofincidencevarytremendouslybasedoncountryof
origin,fromlessthan1%intheUnitedStatesto19%inIndia.IntheUnitedStates,genitalTBisrarely
encountered,butthefrequencyvariesconsiderablywithgeographiclocationandtypeofpatientsseen.The
diseaseismoreprevalentamongimmigrants,patientsininnercitylivingconditions,andpersonnelandlong
termresidentsincertainchroniccareinstitutions,suchasnursinghomes,mentalinstitutions,andprisons.6, 7 , 8
ReportsfromScotlandandScandinaviasuggestahigherincidenceofgenitalTB.9
AccordingtotheCentersforDiseaseControlandPrevention,a5%annualdecreaseintheincidenceofTBhas
occurredsincethe1970s.However,theincreasesince1985maybeassociatedwithanincreaseinacquired
immunodeficiencysyndrome(AIDS)andassociatedtuberculosis.10InNewYorkCity,forexample,TBcases
increasedfrom1630to2223(36%increase)from1984to1986duringthesameperiod,reportedcasesforthe
entirenationincreasedfrom22,255to22,768cases(2%increase).
TripathyandTripathystatedthatgenitalTBismostlyasecondarymanifestationofprimaryTB,themost
commonprimarysitebeingthelungs.11Theyreportedthatthegenitaltractisvulnerabletothisdiseaseafter
puberty,andmostcasesoccurduringthechildbearingperiod.
FemalegenitalTBistypicallyunderstoodasadiseaseofyoungwomen,with80%to90%ofcasesdiagnosedin
patients2040yearsold,oftenduringworkupforinfertility.5MorerecentreportsfromSwedenandScotland
suggestatrendtowardpresentationinwomenintheir40sto50s.12, 13
INCIDENCE
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TheactualincidenceofgenitalTBcannotbedeterminedaccuratelyinanypopulationbecauseitisestimatedthat
atleast11%ofpatientsareasymptomaticandthediseaseisdiscoveredincidentally.8Incidencevariesgreatly
accordingtosocioeconomicandpublichealthconditionsitusuallyparallelstheincidenceofpulmonaryand
abdominalTB.
TheincidenceofgenitaltractTBis0.69%inAustralia,50.07%intheUnitedStates,10lessthan1%inFinland,14
4.2%inSaudiArabia,155.6%inScotland,16and19%inIndia.17
Estimatesofthefrequencyhavebeenmadeonthebasisofpostmortemexamination,operativespecimens,and
endometrialbiopsysamplestakenfrompatientswithinfertility.Autopsystudiesbydifferentauthorsrevealthat
412%ofwomenwhohavediedofpulmonaryTBalsohadevidenceofgenitalTB.18Inareviewpublishedin
1976,Schaeferestimatedthat510%ofinfertilefemalesworldwidehavegenitalTB,5althoughthisvariesfrom
lessthan1%intheUnitedStatestonearly1319%inIndia.19Falkandassociates,inareviewofnewlydiagnosed
casesin47Swedishhospitalsfrom1968to1977,foundanincidenceof2casesper10,000gynecologic
admissions.12
FrancisstatedthattheincidenceofgenitalTBvariesnotonlywiththeprevalenceofextragenitalTBinthe
communitybutalsowiththephysiciansinterestinsearchingforthedisease.20
Sivanesaratnamandcoworkersreportedthatoutofatotal39,204gynecologicadmissionsduringthestudy
period,only12patientshadgenitalTB,givinganincidenceof0.31per1000gynecologicadmissionsduringthe
17yearperiodfromMarch1968toFebruary1985attheUniversityHospital,KualaLumpur,whichactsasa
majorreferralcenterinMalaysia.21TheystatedthatactiveimmunizationofallthenewbornsinMalaysia
perhapsresultedinthedecreasedincidenceofTBfrom10per1000in1960to5.7per1000in1970,thus
explainingthelowincidenceofpelvicTBof0.31per1000gynecologicadmissions.22Othersreportanincidence
of0.20.5per1000.12, 13
InaseriesconductedinIndia,800womenwithpelvicinflammatorydiseasewereassessed6%of48caseswere
attributedtoTB.23TripathyandTripathystudiedpatientswithahistoryofinfertility,menstrualirregularity,
andlowerabdominalpainfromJuly1971toFebruary1983.11In165patients,endometrialTBwasdiagnosed
histopathologically,withapproximately13newcaseseachyear.
KhilnaniandcolleaguesreportedthatTBisoneofthemostcommondiseasesinIndia.24Incasesofinfertility,
theincidenceofgenitalTBis17.4%.InwomenwhodiedofpulmonaryTB,postmortemstudiesrevealedgenital
TBin8%.Carefulhistologicexaminationbyserialsectionoffallopiantubesresultedinanincreaseddiagnosisof
tubalTBfrom7.7%to20%inautopsyseries.
Insurgicallyremovedadnexa,thefrequencyofgenitalTB,asreportedintheexaminationofoperative
specimens,variesfrom2%to20%.Thecarewithwhichexcisedfallopiantubesareexaminedhistologicallyin
differentlaboratoriesisanimportantandvariablefactorindeterminingtheincidenceoftuberculoussalpingitis
orendometritis.
ExaminationbyNogalesOrtizandcoworkersofmorethan1400pathologicspecimenfrompatientswithfemale
genitalTBremovedatoperationrevealedthatthisdiseasehadgraduallydecreasedintheirlaboratoryfrom5.5%
intheyears1950to1966toabout0.27%in1977.25
InIbadan,Ojoandassociatesfoundthat3.5%ofpatientspresentingwithinfertilityhadgenitalTB.26Ojoand
UnuigbereportedthattheincidenceofgenitalTBwas1in300admissions.27 deVynckandcolleaguesstatedthat
theincidenceofgenitalTBwas7.98%(36of451)inthegroupofwomentheystudiedbetweenJune1986and
December1987.28
GiniandIkerionwureportedthattheincidenceofgenitalTBinEnugu,Nigeria,was0.2%.29Theystudied4700
specimensofpremenstrualendometrialcurettingsfrominfertilewomenattendingtheuniversityhospital,
Enugu.Theyfoundonly10casesoftuberculousendometritis.Theysuggestedthatmoredeliberateand
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meticulouseffortsshouldbemadetosearchforgenitalTBininfertilewomenindevelopingcountries.Theyalso
suggestedthatthelowerincidenceofTBfoundintheirseriesmightbetheresultoftheinadequatesearchfor
diseaseinthegenitaltract.TheincidenceofpulmonaryTBishighinNigeria,andthelowincidenceofgenitalTB
mayverywellbeduetoaninadequatesearchforthedisease.30, 31
MaranaandassociatesreportedthattheincidenceofgenitalTBisdecreasinginindustrializedcountries.32Of
their101patientswithinfertilityassociatedwithatubalproblem,only2hadprovenTBbybothendometrial
biopsyandculture,and34hadlaparoscopicfindingssuggestiveofTBMycobacteriumtuberculosisisolateswere
foundonlyintheurine.
In1960,theWorldHealthOrganizationExpertCommitteeonTuberculosisstatedthatTBisgenerally
consideredtobethemostimportantspecificcommunicablediseaseintheworldasawhole,anditscontrol
shouldreceivepriorityandemphasis.In1900,TBwasthesecondmajorcauseofdeathintheUnitedStates.
Today,TBisstilloneoftheworldsbiggesthealthproblems.TheincidenceofTBisdeclininginAmerica,butit
stillrepresentsamassiveeconomicburdentoindividualsandsociety,especiallyinthedevelopingworld.Muir
andBelseystatethatgenitalTBremainsamajorhealthproblemindevelopingcountries.2
PATHOGENESIS
GenitalTBisalmostalwayssecondarytoTBelsewhereinthebodyusuallypulmonaryandsometimesrenal,
gastrointestinal,bone,orjointoccasionallyitispartofageneralizedmiliarydiseaseprocess.Ifthebacilliare
noteradicated,thereisalifelongriskofreactivation,especiallyinconjunctionwithdiseasesordrugsthatcause
attenuationofTcellresponse(e.g.Hodgkinslymphoma,AIDS,steroids,stress,ormalnutrition).Themodeof
spreadisusuallyhematogenousorlymphaticandoccasionallyoccursbywayofdirectcontiguitywithan
intraabdominalorperitonealfocus.5, 33Thefocusinthelungoftenheals,andthelesionmayliedormantinthe
genitaltractforyears,onlytoreactivateatalatertime.
HematogenousSpread
Aftertuberclebacilliinvadethelung,inmostcasesthebacilliaredisseminatedbywayofthebloodstreamwithin
amatterofhoursanddepositedinvariousorgansofthebody.Thisbacillemiamaypersistfor6weeksorlonger,
ifthediseaseisnotrecognizedandtreatedpromptlywithantituberculousdrugs.Noorganortissueofthe
humanbodyisimmunefromtheattackofthetuberclebacillus,althoughtherearemarkeddifferencesinthe
frequencywithwhichdifferentorgansareinfected.Thesedifferencesareduetothedegreetowhichthevarious
organsaredirectlyexposedtobacilli,tomechanicalfactorsthatinfluencetheextenttowhichbacillibroughtby
wayofthebloodstreamwilllodgeineachorgan,andinparttotheabilityofthedifferenttissuestosupportthe
bacillithatlodgeinthem.
Tuberclebacillialsomayreachthebloodstreamandthusthegenitaltractfromextrapulmonaryandchronic
pulmonarylesions.Thefallopiantubeformsamostfavorablenidusfortuberclebacilli,withtheearliestlesion
foundinthemucosa.Thetendencyofthetuberclebacillustoaffectbilateralorgansresultsinbothtubesbeing
involvedinthetuberculousprocess.Thereisalmostuniforminitialpelvicinvolvementofthetubes,with
subsequentdisseminationtoothergenitalorgansandtheperitoneum.Tuberculousperitonitisiscommonlyseen
withgenitaltractinvolvementandmayalsobeassociatedwithruptureofacaseousabdominallymphnodeor,
lessfrequently,withspreadfromanintestinalfocus.34
LymphaticSpread
Alesscommonmodeofinfection,lymphaticspread,occurswhentheprimarylesionisintheabdominalcavity.In
somecountriesinwhichpeopledrinkrawmilk(unpasteurized),infectionwhichspreadsbywayofthealimentary
tractandcausedbythebovinetuberclebacillusisstillreported.Gavallerandcoworkersreportedthatinone
areaofHungary,33%ofcasesoffemalegenitalTBwereduetobovinebacillus,whichwasspreadtothefallopian
tubesbywayofthelymphatics.35
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DirectSpreadFromaNeighboringViscus
Directextensiontothegenitaltractorgansfromtuberculousabdominalviscera,suchasthebladder,rectum,
appendix,andintestines,hasbeendescribed.Someresearchersbelievethatthisspreadisalongtheperitoneal
surface.However,peritonealinvolvementcanalsobetheresultofspillageofinfectedmaterialfromthe
fallopiantubesthus,theprimaryprocessisnotalwaysclear.Italsomayoccurwhenadhesionsbindthebladder
orintestinetothefallopiantubesandperforationofatuberculousulcerresultsindirectspreadtothegenital
organs.
Oncethegenitaltractiscolonized,granulomatacontainingviabletuberclebacilliformwithinvariouspelvic
organs.Afterthedevelopmentoftubercularhypersensitivity,thesegenerallybecomeclinicallysilent,and
intervalsof110yearsorevenlongermaypassbeforeinfectioninthislocationisreactivatedorbecomes
clinicallymanifest,ifsymptomsoccuratall.Mostfociareofnofurthersignificanceclinically.Often,thereislittle
ornoremainingevidenceofinfectionattheprimarysiteoncegenitaltractdiseaseisestablished.36, 37 Thereis
someevidencethatwhenprimaryinfectionoccursclosetothetimeofmenarche,thereisanincreasedlikelihood
ofgenitaltractinvolvement.38
Mostpathologistsstatethatprimaryinfectionofthefemalegenitalorgansdoesnotoccur.Itisknownthat
tuberculousfocimayexistinthebodyandremainundetectedforalongtime.Theselesionsmayprecedethe
genitallesionsandhealwithoutleavingtracesdemonstrableonclinicalexamination.Thecriterianecessaryfora
diagnosisofprimarygenitalTBarethat(1)thegenitallesionsshouldbethefirsttuberculousinfectioninthe
bodyand(2)regionallymphnodesshoulddemonstratethesamestageoftuberculousdevelopmentasdothe
genitalorgans.Auerbachstatedthatnosuchcasehadeverbeendescribedintheliteraturehereviewed.39
Therearereportsofprimarycervicalandvulvardiseaseinwhichsexualpartnershavebeenthoughttobethe
sourceofinfection.ThistypeofdiseasemayalsooccurinawomanwhohasTBofanotherorganandwho
excretestuberclebacilliinherstool,urine,orsputum.Whentheseexcretionscomeintocontactwiththeexternal
genitalia,TBofthevulvaorvaginamayresult,particularlyiftheskinisabradedorbroken.Sutherlandfound
thatof128womenwithprovenTB,5(3.9%)oftheirhusbandshadactivegenitourinaryTBhowever,3ofthe5
wivesofthesemenalsohadevidenceofTBoutsidethegenitaltract.40Lattimerandcolleaguesreportedthe
presenceofM.tuberculosisinthesemenofmenwithgenitourinaryTBin1954.41
Thelesionsinthecervixandvaginaarerareandusuallypresentasisolated,chronic,ulcerativelesions.42The
infectiousagentinTBisusuallyM.tuberculosisoccasionallyMycobacteriumbovismaycausehumandisease,
includinggenitaltractinfection,especiallyinunderdevelopedcountrieslackingfacilitiesforpasteurizationof
milkandaneffectiveTBcontrolprogramforcattle.Themycobacteriaareobligateaerobeswithareplicating
cycleontheorderof1724hoursandarecharacterizedbytheiracidfaststaining.
PATHOLOGY
Whenthetuberclebacilliinfectasusceptiblehost,theinitialreactionisapolymorphonuclearinflammatory
exudate.Within48hours,thisisreplacedbymononuclearcells,whichbecometheprimesitesforintracellular
tuberclereplication.Ascellularimmunitydevelops,destructionoftuberclebacillitakesplaceandcaseation
necrosisoccurs.Laterreactivationofafocusofinfectionresultsinproliferativegranulomatouslesion,classically
withcentralcaseationnecrosissurroundedbyconcentriclayersofepithelialandgiantcells,withperipheral
lymphocytes,monocytes,andfibroblasts.37
TUBERCULOSISOFTHEPELVIS
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PelvicTBmayexistastuberculousadenitis,ofeitherthemesentericorthepelviclymphnodes,without
involvementofthegenitaltract.GeneralizedmiliaryperitonealTB,inwhichgrayishwhitetuberclesstudthe
abdomen,mayinvolvetheserosalsurfaceofbothabdominalandpelvicorganswithoutpenetratingtothe
mucosa.Suchsuperficiallesionsdonotusuallyimpairthereproductivefunctionofthepelvicorgans.Itshould
beemphasizedthatpelvicTBisnotthesamediseaseasgenitalTB.
TUBERCULOSISOFTHEFALLOPIANTUBES
VarioussourcesonthetopicofgenitalTBappeartoagreethatthefallopiantubesarelikelytheinitialsourceof
infection,becausebothtubesareinvolvedinnearly100%ofcases.5, 25, 43Thefallopiantubesconstitutethe
initialfocusofgenitalTBintheoverwhelmingmajorityofcases(Table1),andTBhasaccountedfor
approximately5%ofallcasesofsalpingitisinmanyareasoftheworld.44Inmorethan90%ofpatientswith
genitalTB,thetubesareinvolvedbilaterally.Althoughonlyonetubeappearsinfected,thereprobablyare
microscopiclesionsintheother.Intheearlystages,thetubesshowlittlechange,butasprogressionoccurs,the
diameterofthetubebecomeslarger.Usually,theampullaryregionshowstheearliestandmostextensive
changes,thefimbrialprocessesbecomegreatlyswollen,andtheostiaremainopenorclosed(Fig.1).Thegross
appearancevariesandisnondiagnosticthetubesmayappearnormaloronlyslightlyedematousbutaremuch
morelikelytopresentapictureconsistentwithchronicsalpingitisofanontubercularnature.
Table1.Frequencyoftuberculosisingenitalorgans
Organ
Frequency(%)
Fallopiantubes
90100
Endometrium
5060
Ovaries
2030
Cervix
515
Vulvaandvagina
(FromSchaeferG:Femalegenitaltuberculosis.ClinObstetGynecol19:23,1976)
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/001f.jpg)Fig.1.Anenlargedfallopiantube
isseenwithapoutingfimbrialendontherightsideofthephotograph.
TheisthmusandtheadjacentinterstitialportionofthetubemayremainfreeofTB.Astheprocesscontinues,the
tubesbecomesofter,andcaseationdevelopsintheinnerwall.Attimes,theperitonealsurfacesofthetubeswill
bestuddedwithtubercles,andthecrosssectionsmayshowthemtobefilledwithcaseousmaterial.25In2550%
ofcasesofgenitalTB,thetubesremainpatentwithrecognizableevertedfimbriae,eveniftheremainingtubeis
enlargedanddistended,thesocalledtobaccopouchappearance.37 , 44
Microscopically,granulomataandachronicinflammatoryinfiltratemayinvolvethefullthicknessofthetubal
wall,andcaseationnecrosisiscommoninadvancedstates.Sometubercleshaveacaseouscenter,which,asthey
progress,involvestheoverlyingmucousmembraneorcausespressureatrophy.Afterliquefaction,thecaseous
focipourtheirbacilliintothelumenandformanulceratthesite.Caseationorapyogenicmembranelinesthe
ulcerbeyondtheinnerzoneisanareaofvasculargranulationtissuecontainingepithelioidandgiantcells.
Adhesionoftheindividualfocimayoccur,resultinginlargecysticspacespseudofollicularsalpingitis.When
healingoccurs,thepictureisfurtherchanged,andcalciumdeposits,hyalinization,andincreasedfibroustissue
maybeseen.Themucosafrequentlyexhibitsahyperplastic,adenomatouspatternwithacomplexnetworkof
fusedpapillaethatmaybeconfusedwithadenocarcinoma(Fig.2)andhasbeenassociatedwithectopic
pregnancies.37 , 44Thereissomesuggestionthatthispatternmayactuallypredisposetothedevelopmentof
tubaladenocarcinoma,althoughtheevidenceisinsufficientforstatisticalassessment.45Tuberculoussalpingitis
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maycontainSchaumannbodies,whichareconchoidal,laminated,calcifiedstructuressurroundedbyforeign
bodygiantcells(Fig.3).Inchronictuberculoussalpingitis,unlessmultiplesectionsaretaken,thecharacteristic
lesionmaybemissed.
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/002f.jpg)Fig.2.Tuberculoussalpingitis.
Chronicsalpingitisduetotuberculosispresentsthecharacteristichistologicfeaturesofthetuberculous
granuloma:lymphocytes,epithelioidcellgranulomata,andgiantcellsofboththeLangerhansandtheforeign
bodytypeareseen.Tuberculousinfectionofthefallopiantubeoftenresultsinanadenomatous
proliferationoftheliningepithelium.Thisisseenontheleftofthisphotomicrographandmaygiveriseto
confusionwithadenocarcinoma.(100.)
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/003f.jpg)Fig.3.Tuberculoussalpingitis
maycontainSchaumannbodies,whicharemorecharacteristicofsarcoidosisthantuberculosis.Theseare
conchoidal,laminated,calcifiedstructures,usuallysurroundedbyforeignbodygiantcells.(100.).
TYPESOFTUBERCULOUSSALPINGITIS
Exudative
Intheexudativetype,thetubemaybesignificantlyenlarged.Althoughalargepyosalpinxmayform,thesetubes
showfewadhesionsandusuallyarereasonablymobileifsurgeryisneeded.Frequently,theorganscontaina
largeamountofcaseousmaterialpluspurulentexudatefromsecondaryinfection.Thisisarelativelyacutephase
oftheprocess.
ProductiveAdhesive
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Intheproductiveadhesiveform,whichisfoundmostfrequentlyatlaparoscopyorlaparotomy,thetubesare
studdedwithtuberclesandaredenselyadherenttothesurroundingorgans.Thetuberclesareseenmostlynear
theattachmentofthetubetothemesosalpinx.Thetubewallisthickenedandnodular,andthefimbriaeandtube
areslightlyswollen.Eventually,whentheprocessstartshealing,itresultsincalcificationandfibrosis.
MODEOFSPREADFROMTUBES
Aftertheinitialinvolvementofthetubes,thetuberculousinfectionspreadstotheuterusandovariesbydirect
extension.Extensiontotheuterusisalongtheendometriumandrarelyintothemyometrium.Direct
hematogenousspreadtotheuterusaspartofageneralizedhematogenousTBhasrarelybeenreported.
Theovariesmaybeinvolvedbydirectspreadfromadjacentorgans.Inmostcases,infectionspreadsfromthe
tube,andthelesionisseenonthesurfaceoftheovaries.Rarely,theinfectionextendsfromtheperitoneumto
theovary.Hematogenousspreadusuallyaffectsthecenteroftheovary,andtheperipheryappearsnormal.
Thecervixisinvolvedbyspreadfromtheendometriumoraspartofthehematogenousinfection.Tuberculous
infectionofthevaginaandvulvamayfollowinjuryorabrasionstothesestructureinthepresenceoftubercle
bacillifromtheuppergenitaltract,intestinaltract,orlungs.
Dellepianestatedthattheuseofantituberculousdrugshastendedtochangetheclinicalpictureofthedisease,
resultinginadecreasingincidenceofacuteformsandanincreasingincidenceofsubacuteandchronicforms.46
Onthebasisof965casesofgenitalTBinwhichthepathogenesiscouldbedefinedpreciselybyaseriesofclinical,
laboratory,radiologic,andlaparoscopicprocedures,hedescribedgenitalTBasprimaryin0.2%,hematogenous
inoriginin59.2%,anddescendingin40.6%.Thelatterrouteisbywayofthelymphaticsfromthelungstothe
intestinallymphnodesandthetubes.
TUBERCULOSISOFTHEENDOMETRIUM
Grossly,thesizeandshapeoftheuterusmayappearnormal.Thetuberculousprocessgenerallyislocalizedto
theendometrium,ismostextensiveinthefundus,anddecreasestowardthecervix.Themyometriumisnot
usuallyinvolved.Inpremenopausalpatients,muchoftheinfectedtissueisshedduringthemenstruation,onlyto
havetheendometriumreinfectedfromthetubeswitheachcycle.
IngenitalTB,thereisahighincidenceofinvolvementoftheendometrium.Schaeferreportedanincidenceof
5060%5Onuigbo,anincidenceof60%,47 andNogalesOrtizandcoworkersanincidenceof79%,25whereas
Sutherlandestimated90%involvementoftheendometriumingenitalTB.16
Inalargeseriesof1436cases,NogalesOrtizandcoworkersfound79%involvementusingextensiveendometrial
sampling.25Grossly,theendometriumappearsunremarkableinmostcases,probablybecauseofthecyclic
menstrualshedding.However,whenextensiveinvolvementoftheendometriumoccurs,theremaybeulcerative,
granular,orfungatinglesionspresent,ortheendometrialcavitymaybeobliteratedwithintrauterineadhesions.
Sometimes,themacroscopicappearancemayresemblecarcinoma,andTBhasbeensuggestedmicroscopically.
In2.5%ofcasesoftuberculousendometritis,NogalesOrtizandcoworkers,25SchenkerandMargalioth,48and
HasselgrenandBolin49notedtotaldestructionoftheendometriumwithresultingamenorrheasecondaryto
endorganfailureandpredispositiontopyometrashouldtheinternalosbecomesoccluded.
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Onhistologicexamination,thepictureisoneofinfrequent,usuallyisolated,smalltuberclesscatteredirregularly
throughtheendometrium.Inmostcases,thelesionsareextremelyscanty,andcarefulsearchthroughallthe
sectionsoftheendometriumremovedatcurettagemayrevealonlyoneortwofociofTB(Fig.4).
(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/004f.jpg)Fig.4.Tuberculous
endometritis.Photomicrographofasingletuberculousgranulomaisseenontheleft,consistingofcentral
epithelioidcells,withaLangerhanstypegiantcellsurroundedbyacuffoflymphocytes.Nocentralcaseation
ispresent.Thesurroundingendometriumappearscompletelynormaltheglandsareproliferative,andthere
isnoinfiltrateinthestroma,seenontheright.(100.)
TBoftheendometriumresemblesTBinothertissues,buttheadvancedstagescaseation,fibrosis,and
calcificationrarelyareseenduringthereproductiveperiodoftheregularcyclicalsheddingoftheendometrium.
Theclassiclesionintuberculousendometritisisthenoncaseatinggranuloma,composedofepithelialcells,
Langhansgiantcells,andlymphocytes.Thesegranulomataarelocatedthroughouttheendometriumbutoccurin
greaterdensityinthemoresuperficiallayers(Fig.5).Theyoccasionallyperforateintoglandlumina,causingan
acuteinflammatoryreactionandgivingtheappearanceofmicroabscesses.Endometrialglandsadjacentto
granulomatamaynotrevealasecretoryresponseormaybecomecompressed,resultingina
pseudoadenomatousappearance.25, 50, 51
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/005f.jpg)Fig.5.Tuberculous
endometrium.Amuchmorefloridpictureofnumerousgranulomatawithdenselymphocyteinfiltrateinthe
surroundingstromaisseeninthisphotomicrograph.(100.)
Mostoften,theendometriallesionconsistsofcircumscribedlesionsofendothelioidcellssurroundedbyazone
oflymphocytesandplasmacells.Theseinflammatorycellsmaybepresentinthestromawithoutfocallesions.
However,thegiantcellsarenotalwaysindicativeoftuberculousinfection.Endometrialtuberculouslesionsare
frequentlyfocalandimmaturebecausetheytendtobeshedmonthlyexceptinpostmenopausalwomenor
womenwithamenorrhea.Sutherlandstatedthattheendometriumisreinfectedonaregularbasisfromthetubes
orfrominfectionsofthebasalisbyorganismsinmenstrualbloodaftersloughingofthesuperficial
endometrium.52Thegranulomatouslesionsareusuallybestrecognizedoncycledays2426orwithin12hours
oftheonsetofmenses.50
TUBERCULOSISOFTHEOVARY
Thereisdisagreementintheliteratureregardingthefrequencywithwhichtheovariesareinvolved.Some
studiesestimate2030%,5whereasareviewofalargeseriesofpathologicspecimensfoundinvolvementinonly
11%ofcases.25Thisislikelyexplainedbyvaryingdefinitionsofinvolvement,becausethelattersourceusesa
stricterdefinitionoftrueparenchymalgranulomatousinvolvement.
Usually,theinvolvementisbilateral,althoughthiscannotalwaysberecognizedwithcertaintyatlaparotomy.
TwoformsofovarianTBaredescribed:perioophoritis,inwhichtheovarymaybesurroundedbyorencasedin
adhesionsandstuddedwithtuberclescausedbydirectextensionfromthetubeandoophoritis,inwhich
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infectionstartsinthestromaoftheovary,presumablyfromahematogenoussourcethatproducesacaseating
granulomawithintheparenchyma.5, 18, 25
PERIOOPHORITIS
Extensionofthetuberculousprocessfromthetubeinvolvestheovaryinatuboovarianmass,whichisfrequently
adherenttoomentumandintestines.Thisisthemostcommonformoftuberculousinvolvementoftheovary,
andtheresultinglesionisthatofperioophoritis,withtheextensionofthelesionfromtheperipherytowardthe
center.Thetoughtunicealbugineaisthoughttoprotecttheovariesfromtuberculousinfectionhence,theless
frequentinvolvementoftheovarycomparedwiththetube.
OOPHORITIS
Oophoritisisarelativelyrareconditionandusuallyfollowshematogenousspread.Typicaltuberclesorlarger
fociwithcaseouscentersmayberecognizedoncrosssectioninthehilumoftheovary.Thus,theovaryshouldbe
bisectedbeforeremovalifnocaseousfociarepresent,theovarymayberetained,andthepatientshouldbe
givenantituberculoustreatmentpostoperatively.
TUBERCULOSISOFTHECERVIX
Thecervixappearstobeinvolvedin525%ofcases,whereasinvolvementoftheexternalgenitaliaoccursonly
rarely.53TheusualincidenceofcervicalinvolvementingenitalTBis515%.However,NogalesOrtizandVillar
thoughtthatcervicallesionsweremorecommon,especiallyintheendocervix,whichwasfrequently
overlooked.53
Aswithotherpartsofthefemalegenitaltract,therearenomacroscopicchangesinthecervixthatarespecificfor
TB.Thecervixmayappearnormalorinflamed,anditsconditionmayresembleinvasivecarcinoma,bothgrossly
andwiththecolposcope.54, 55Themostcommontypeistheulcerativeform,althoughpapillomatousandmiliary
formsmayalsooccur.
NogalesOrtizandcoworkersstatedthatavelvety,polypoidappearanceisseenfrequently,25whereasulceration
ordestructionofsurfaceepitheliumislesscommon.
Thediagnosiscanbemadewithcertaintyonlybyhistologicorbacteriologicexamination.Ifbacteriologic
examinationofendocervicalmucuswasperformedfortuberculousinfection,asisdonewithinfertilityproblems,
anycasesoftuberculouscervicitiscouldpossiblybediscovered.56Thecytopathologicexaminationofthecervix
mayrevealmultinucleatedgiantcells,histiocytes,andepithelioidcellsarrangedinclusters,simulatingthe
appearanceofthegranulomatathatarecharacteristicofthePapanicolaou(Pap)smearincervicalTB.Theremay
beassociatedepithelialatypiafromwhichdyskaryoticcellsareshed.54, 57
Histopathologicexaminationrevealsgranulomatousinflammationandsometimesmarkedinflammatoryatypia
alongwithfrequenthyperplasticmucosalchanges.Caseationmaybeseen.Endocervicalinvolvementiscommon
andusuallyresultsinanincreasedsecretionofmucin.25Samalandcoworkersreportedcervicalinvolvementin
43.1%ofthecasestheystudied.58
TUBERCULOSISOFTHEVULVAANDVAGINA
5, 25
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TBofthevulvaandvaginaistherarestformofgenitalTB,occurringinlessthan2%ofcases.5, 25Inmostcases,
thelesionsappeartobesecondarytodiseasehigherupinthegenitaltractbut,rarely,thediseasemaybe
acquiredfromthemalepartnerwithaninfectedepididymisorseminalvesicles.Inthevulva,itbeginsasanodule
onthelabiaorinthevestibularregion,whichbreaksdownandformsanirregularraggedulcer,sometimeswith
sinusesdischargingcaseousmaterialandpus.TBofBartholinsglandisrare.Rarely,avulvarlesionpresentsasa
hypertrophic,irregularwartygrowthsometimesresemblingelephantiasis.Atuberculouslesioninthevagina
maysimulatecarcinomainitsgrossappearance.44, 59
ThemicroscopicappearanceissimilartoTBoccurringthroughoutthegenitaltract,withgranulomatous
inflammationtendingtocausecentralcaseationandanassociatedchronicinflammatoryinfiltrate.
TUBERCULOUSPERITONITIS
TuberculousperitonitisisseenincombinationwithfemalegenitaltractTBapproximately45%ofthetimeandis
thoughttoberesponsiblefortheoftenextensiveadhesionsseeninpatientswithpelvicTB.18Twotypesof
tuberculousperitonitishavebeendescribed:theplasticvarietyandtheserousvariety.
Theplasticvarietyislesscommonandischaracterizedbytenderabdominalmassesandanabdomendoughyto
palpation.Theserousvarietyisseenmorecommonlyandischaracterizedbyascitis,signsofperitoneal
inflammation,fever,abdominalpain,weightloss,andanorexia.Mostcasesoftheserousvarietyareinsidious.
Patientsmaybeasymptomaticormaypresentacutelywithchills,fever,ascitis,andsometimes,rebound
tenderness.Intheplasticvariety,onemayobservesymptomssuggestiveofpartialintestinalobstruction.
Withadvanceddiseases,allpelvicorgansaredenselymattedtogether,oftenwithtuberclesstuddingperitoneal
surface,fociofcaseation,andcalcifiedplaques,whichrepresentattemptsathealing.18, 34Theperitonealfluidis
exudativeincharacterandgenerallycontains5002000cells,withapredominanceoflymphocytes.
Withperitonitis,anassociatedpleuraleffusionisnotuncommon,althoughmostpatientshavenoparenchymal
abnormalitiesonchestradiograph.
CLINICALFEATURES
TheclinicaldiagnosisofgenitalTBrequiresahighindexofsuspicion.About20%ofpatientswithgenitalTBgive
ahistoryofTBintheirimmediatefamily.5Asarule,theywereexposedtoanadultwithTBduringchildhood.
Approximately50%ofpatientsmighthavehadtuberculouspleurisy,peritonitis,erythemanodosum,orrenal,
osseous,orpulmonaryTB.Ahistoryofprimaryinfertilityinawomaninwhomexaminationrevealsnoapparent
causeandwhogivesafamilyhistoryorpersonalhistoryofTBshouldarousesuspicionofgenitalTB.
Ahistoryofpoorgeneralhealthpersistingovermonthsoryearsandassociatedwithweightloss,unduefatigue,
lowgradefever,orvaguelowerabdominaldiscomfortisoftenelicitedinpatientswithgenitalTB.
Accordingtomostseries,patientswithgenitalTBwillgiveahistoryofpriordiagnosisortreatmentof
extragenitalTBapproximately3050%ofthetime.5, 9, 12
Age
FemalegenitalTBistypicallyunderstoodasadiseaseofyoungwomen,with80%to90%ofcasesdiagnosedin
patients2040yearsold,oftenduringworkupforsubfertility.5Althoughinmanydevelopingcountries,genital
TBismorecommonamongyoungerwomen,indevelopedcountriesmostpatientsareolderthan40years.12, 13
TripathyandTripathy11reportedthatthemeanageofpatientswhohadgenitalTBwas30.6yearsOjoand
Unuigbe27 reportedthat80.9%oftheirpatientswereinthe20to39yearoldagegroup.Ofthe1436casesof
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thediseasereportedbyNogalesOrtizandcoworkers,66%ofpatientswerebetween25and35yearsofageonly
11%werepostmenopausal.25GiniandIkerionwureportedthattheageoftheirpatientswithtuberculous
endometritisrangedfrom23to30years,withameanageof26.8years.29
In1982,SutherlandobservedthattheageincidenceofgenitalTBhadchangedandthattheproportionof
patientsolderthan49yearswashigherthaninthepast.40ReportsfromSwedenandScotlandalsosuggesta
trendtowardpresentationinwomenintheir40sto50s.12, 13
Samalandcoworkersreportedthat65.8%ofwomenwerebetween21and30yearsofage,theyoungestbeing12
yearsandtheoldest65yearsold,and64.2%werenulliparous.58
SYMPTOMS
Systemicsymptoms(Table2)tendtoberelativelymild,ifpresent,andmayincludeweightloss,fatigue,anda
tendencytowardapersistentmildeveningelevationoftemperature.Approximately11%ofpatientsare
asymptomatic.5, 12, 36, 37
Table2.Symptomsrelatedtogenitaltuberculosis
Systemic
Weightloss
Fatigue
Lowgradefever
Infertility
Primary
Secondary
Menstrualdisturbances
Amenorrhea
Menorrhagia
Metrorrhagia
Oligomenorrhea
Abdominalswelling
Postcoitalbleeding
Vaginaldischarge
Dyspareunia
InwomenwithgenitalTB,fourmajorpresentingcomplaintsaredescribedwithvaryingfrequencies:infertility,
abnormalbleeding,pelvicpain,andamenorrhea.
Infertility
14, 20, 60, 61

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Themostcommoninitialsymptomisinfertility.14, 20, 60, 61Approximately85%ofpatientswithgenitaltractTB

haveneverbeenpregnantintheremaining15%,symptomsofgenitalTBdevelopinonethirdtoonehalfwithin1
yearaftertheirlastpregnancywascompleted.Infertilityisthepresentingcomplaintin4050%ofpatientsin
mostlargeseriesstudied.33, 52, 62, 63
Sivanesaratnamandcoworkersreportedthatthemostcommoncomplaintinthegrouptheystudiedwas
infertility.21TripathyandTripathystatedthat64.2%oftheirpatientswithgenitalTBcomplainedofinfertility,
comparedwith22%inthecontrolgroup.11OjoandUnuigbereportedthat54.4%ofpatientswithgenitalTB
presentedwiththecomplaintofinfertility.27 deVynckandcolleaguesreportedthatinfertilityisthecommon
presentingsymptominwomenwithgenitalTB.28Dhillonandcoworkersalsoreportedthatinfertilitywasthe
maincomplaintingenitalTB.4
LowerAbdominalPain
Thesecondmostfrequentcomplaintislowerabdominalpainorpelvicpain,presentinapproximately25%to
50%ofpatients.12, 20, 52, 62Usually,thepainhasbeenpresentforseveralmonthsbeforethepatientseesa
gynecologist.Thepainisnotusuallysevereandmaybeaccompaniedbyswellingoftheabdomen,although
episodesofacutelowerabdominalpainowingtosecondaryinfectionbypyogenicorganismsmayoccur.The
numberofwomenwhohavepainasafeatureofpelvicTBisproportionaltothenumberofwomenwith
abdominalfindingsonphysicalexamination.37 WhenprogressionofgenitalTBtakesplace,thepelvicpain
becomesmoresevereandisusuallyaggravatedbycoitus,exercise,andmenses.
MenstrualDisorders
Thethirdmostcommonsymptomissomevarietyofmenstrualproblems.Abnormaluterinebleedingingenital
TBhasbeenreportedin10%to40%ofpatients.Patientsreportmenorrhagia,menometrorrhagia,
intermenstrualbleeding,oligomenorrhea,andpostmenopausalbleeding.36, 37
Samalandcoworkersstudied120casesofgenitalTBprovedbyhistopathology.Analysisoftheirmenstrual
historyshowedthatthecommonmenstrualdisorderoligohypomenorrheawasfoundin54%ofcases,
menorrhagiain19.9%ofcases,andpostmenopausalbleedingin1.6%ofcases.Historyofamenorrheawas
presentin14.3%cases.Therewere8casesofsecondaryamenorrhea(6.6%)and1casewasofprimary
amenorrhea.58TheystatedthatthegenitalTBwasadiseaseofvariedsymptomatology.Ahighdegreeof
suspicionandefficientinvestigationareimportantfordiagnosisandadequatemanagement.
AmongwomenofreproductiveagewithgenitalTB,menstrualirregularitiesdefineacommonformofthe
disorder.ThemenstrualcyclemaybenormalandundisturbedincasesofgenitalTB.Secretoryendometriumhas
beenfoundinalargenumberofpatients.Superficialtuberculousendometritisdoesnotinterferewiththe
secretoryresponseoftheendometriumtohormonalstimulation.58
DisturbancesofmenstruationingenitalTBdonotfollowthesamepatternindifferentcountries.Ylinen64noted
nomenstrualirregularitiesin56%ofpatientsinFinlandKirchhoff 65, 66describednormalmenstrualcyclesin
62%ofhispatientsinGermanyandSutherlandandGarrey67 inScotlandfoundnomenstrualproblemin46%of
theirpatients.Incontrast,Aldeaandcolleagues68foundnormalmenstruationinonly7.3%oftheirpatientsin
Romania,andMalkaniandRajani69reportedamenorrheain18%to53%oftheirpatients,dependingonthepart
ofIndiainwhichthepatientlived.TripathyandTripathystudiedthegroupof165womenwithhistologically
provenendometrialTBandcomparedthemwithacontrolgroupof50womenwithoutTB.11Theyreportedthat
menstrualirregularitieswereverycommon(85%)incasesofendometrialTB,amongwhichsecondary
amenorrheawasthemostcommondisorder(43.6%).
Therehasbeensomespeculationonthecauseofamenorrhea.Itiswellknownthatadvanced,activepulmonary
TBmayproduceamenorrhea,particularlyifitisassociatedwithfeverandweightloss.However,active
pulmonaryTBisrarelyfoundconcomitantlywithactivegenitalTB.Completedestructionoftheovarybygenital
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TBseldomoccurs,sothatovarianfailureisnotthecauseofamenorrhea.Themostlikelyexplanationisthat
givenbyMalkani70andNogalesOrtizandVillar,53whoattributedamenorrheatoendorganfailuresecondary
toendometrialcaseation.
GeneralMalaise
Ahistoryofpoorgeneralhealthpersistingoveraperiodofmonthsoryearsandassociatedwithweightloss,
unduefatigue,lowgradefever,orvaguelowerabdominalpainofteniselicitedinpatientswithgenitalTB.Some
patientsgaveahistoryofrecurrentpelvicinflammatorydiseasethathasnotrespondedtotheusualantibiotic
therapy.
OthersymptomsseenlessfrequentlywithpelvicTBincludevaginaldischarge,abdominalswelling,pelvic
relaxation,andsymptomsassociatedwithfistulaformation.40, 62, 71Uterovesical,tubointestinal,and
tuboperitonealfistulashaveallbeendescribed.33, 49TBissignificantbecauseitmayaffectanyorganinthe
body,mayexistwithoutmanifestingclinicalsignsandsymptoms,andmayrecurafterbeingapparently
arrested.72ThepresenceoflongstandinggenitalTBinwomenwithoutanysymptomshasbeenreported.18, 73
GenitalTBcanmimicovariancancer.74, 75, 76, 77 Thesepatientscommonlypresentwithadnexalmassesand
ascitis.Tofurtherconfusethepicture,serumCA125levelscanbeelevatedaswellingenitalTB,anddiagnosisis
oftenmadeonlyafterlaparotomy.74, 75, 76, 77
PHYSICALSIGNS
Mostseriessuggestphysicalexaminationcanbenormalinupto50%ofcasesoffemalegenitalTB.9, 12, 43When
abnormalfindingsarepresent,theyusuallyconsistofadnexalmassesorsignsofascitis.
PhysicalexaminationisimportantinestablishingadiagnosisofgenitalTB(Table3).However,itshouldbe
emphasizedthatnoabnormalfindingsmaybeapparentor,atbest,theremaybeonlyvagueones.Thereislittle
correlationbetweenpresentingcomplaintsandphysicalfindingsingenitalTB.Inall,3550%ofpatientshavean
entirelynormalexamination.36, 40Intheremainder,bimanualexaminationoftenrevealsanadnexalmassor
fixationofpelvicorgans.Tuberculoustuboovarianmassesarelesstenderthanthoseduetopyogenicinfection,
althoughsecondaryinfectionandacuteexacerbationmayproducesharppainandtenderness.Otherpelvic
lesions,suchasfibromyomas,ovariancysts,andadenomyosis,aswellascervicalcancer,maycoexistwithgenital
TB.Thepresenceofbilateraltuboovarianmassesinavirginwhohasahistoryofpulmonaryorextrapulmonary
TBshouldmaketheclinicianhighlysuspiciousofgenitalTB.
Table3.Physicalsignsingenitaltuberculosis
Normal
Abdominalmass
Pelvicmass
Adnexalmass
Abdominaltenderness
Pelvic/adnexaltenderness
Ascites
Excessivevaginaldischarge
Ulcerinthevulva,vagina,andcervix
Enlargeduteruswithpyometra
Fistula
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Sutherlandslargeseriesspinning30yearsshowedasignificantdecreaseintheincidenceofpalpableadnexal
masses,from52%of704patientsintheyears195160to26.5%intheyears197180.62Falkandassociates
studiedagroupof187patientsandreportedthatapproximately25%ofthepatientsintheirserieshadapalpable
adnexalmassonexamination,but11%ofthesewerefoundtobebenignovariantumorsormalignantlesionsin
theadnexa.12Adnexalmassesvaryinsizeandinconsistencyandmayresultfromthickened,edematoustubes,
pyosalpinges,aconglomerationofpelvisorgansmattedtogetherbyadhesions,oratuboovarianabscess.
Atemperaturegreaterthan38Cwasseeninapproximatelyonethirdofthe158casesofBrownandassociates
from1920to1950.78Superimpositionofacutebacterialinfection,gynecologicoperativeprocedures,ortrauma
topelvicorganshasbeenknowntocauseaflareupoflatentpelvicTB.79
Abdominalexaminationmayrevealadoughysensation,whichhasbeenascribedtotubercleformationonthe
intestinesandperitoneum.Ascitis,eithergeneralorsacculated,mayproducedistentionoftheabdomen.
Tuberculousascitiswithincreasedintraabdominalpressurehasbeenblamedforanoccasionalprimary
presentationsuchasuterineprolapseinanotherwiseasymptomaticpatient.71Irregularmassescausedbythe
mattingtogetherofintestines,omentum,andpelvicorgansmaybepalpated.Inanadolescentfemalepresenting
withascitis,pain,andlowgradefever,thecauseisfrequentlyTB.37
Inmenopausalwomen,genitalTBmaycauseanenlargeduterusthatistenseandtenderonexamination,the
resultofpyometraformation.79, 80Physicalexaminationmaysuggestovarianmalignancy.Afistuloustract
betweenthegenitaltractandthebowel,bladder,orcutaneousareamaybeidentified.Theseareusuallycaused
byruptureofatuberculouspyosalpinxintoadjacentorgans.Lesscommonfindingsincludelesionsofthecervix
andexternalgenitalia.
DIAGNOSIS
ThepossibilityofTBinfectionofthegenitaltractshouldalwaysbeconsidered,especiallyinapatientfroman
areawhereTBisendemic,apatientwithafamilyhistoryofotherexposuretoTB,orapatientwithsomeproven
extragenitalmanifestationsofthedisease.
Infertilityforwhichnoobviouscausecanbefound,chronicpelvicinflammatorydiseaserefractorytostandard
antibiotictherapy,oradnexaldiseasewithascitisinvirginfemalesshouldalertthecliniciantolookforTBofthe
genitaltract.
Inmostseries,ahistoryofpreviousdiagnosisortreatmentforextragenitalTBispresentin25%to50%of
patients.5, 10, 13, 20, 40, 62InSutherlandslargeseriesof638patients,80%hadahistoryofTBelsewhereinthe
bodyorhadevidenceofsuchalesiononchestorabdominalradiographorinurineculture.52Anegativechest
radiographdoesnotruleoutthediagnosisbecausemostpulmonarylesionsarearrestedbythetimethegenital
tractbecomesinvolvedinthediseaseprocess.
Routinelaboratorystudiesareoflittlevaluemostpatientshaveanormalwhitebloodcellcountwith
differential,althoughthereisatendencytolymphocytosis.Anemiaissometimesseen,whereasmicroscopic
examinationofurinemayshowhematuriaorabacteriuricpyuriaifthereisconcomitanturinarytract
involvement.38
LaboratoryInvestigations
ThediagnosisofTBisbasedontheidentificationofM.tuberculosisorothersoftheM.tuberculosiscomplex
M.bovis,M.africanum,andM.microtiinculture.Isolationofmycobacteriafromclinicalspecimensinpure
culturesrepresentsachallengebecauseoftheprolongedperiodofcultivationrequiredformostofthem.
CultivationofM.tuberculosisrequiresspecialculturemedia.ThemostpopularareLwensteinJensenorother
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eggbasedsolidmedia,Middlebrook7H10/7H11agar,Middlebrook7H9broth,andMiddlebrook7H12broth
thatismanufacturedasradiolabeledBACTEC(BectonDickinsonDiagnosticInstrumentSystems,Sparks,MD)
medium.81
TheeggbasedmediaarethemosttraditionalonesfortheisolationofM.tuberculosis,althoughittakes38
weekstoachievevisiblegrowth.Growthonagarbasedmediacanbedetectedwithin3weeksformostM.
tuberculosisisolates.TheBACTEC7H12brothcanbeusedforrapiddetectionofgrowth,oftenwithin1weekfor
mostisolates.Specimensareusuallycollectedinsterilecontainerswithliquidinthecaseoftissue(7H9brothor
saline)andtransportedtothelaboratoryindryice.
InvestigationstoconfirmthediagnosisofgenitalTBarelistedinTable4.
Table4.Investigationstoconfirmgenitaltuberculosis
Completebloodcount
Chestradiographs
Tuberculintest
Menstrualbloodforculture
Endometrialcurettage
Histologicexamination
CultureforMycobacteriumtuberculosis
Peritonealfluidforculture
Peritonealbiopsyforcultureandhistology
Hysterosalpingography
Ultrasonography
Cervicalcytology
Endoscopy
Laparoscopy
Hysteroscopy
Cystoscopy
Otherserologictests
ChestRadiograph
GiventhatgenitalTBisbelievedtobesecondarytoprimarypulmonaryinfectioninmostcases,itseemsintuitive
thatachestradiographmightbehelpfulinevaluatingthesepatients.Seriesthatlookedspecificallyatthisissue
foundchestradiographabnormalitiesinonly1050%ofcases.13, 14, 15, 43, 82Mostoftheabnormalitiesfound
weresuggestiveofpriorpulmonaryTB,whereasactivepulmonaryTBinassociationwithgenitalTBwasrare.13,
15, 82Signsofearlierpleurisyareofparticularinterestbecausepleuraleffusioninyoungpeoplemaybecaused
byTB.
TuberculinTest
ThetuberculinskintesthasbeenthetraditionalmethodofdemonstratinginfectionwithM.tuberculosis.7
Althoughthecurrentlyavailabletuberculinskintestsaresubstantiallylessthan100%sensitiveandspecificfor
thedetectionofinfectionwithM.tuberculosis,nobetterdiagnosticmethodshaveyetbeendevised.Thetestis
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basedonthefactthatinfectionwithM.tuberculosisproducessensitivitytocertainantigeniccomponentsofthe
organismthatarecontainedincultureextractscalledtuberculin.Twopreparationsoftuberculinarecurrently
licensedforuseintheUnitedStates:oldtuberculin(OT)andpurifiedproteinderivative(PPD)
Thereactiontointracutaneouslyinjectedtuberculinistheclassicexampleofadelayed(cellular)hypersensitivity
reaction.Characteristically,thisreactionbeginsat56hours,ismaximalat4872hours,andsubsidesovera
periodofdays.Unfortunately,notallpatientsinfectedwithM.tuberculosishaveareactiontothetuberculinskin
test.Thetypicalmethodofperformingthetuberculintestistheintracutaneous,orMantoux,method.Here0.1
mLofPPDisinjectedintracutaneouslyintothedorsalorvolarsurfaceoftheforearm.Adiscretewhealshouldbe
produced.Thetestisreadbetween48and72hoursaftertheinjection.Thebasisofreadingisthepresenceor
absenceofinduration.Thediameteroftheindurationshouldbemeasuredtransverselytothelongaxisofthe
forearmandrecordedinmillimeters.Theinterpretationofthetestshouldbeinfluencedbythepurposefor
whichthetestwasgivenandbytheconsequencesoffalseclassification.
Areactionofgreaterthanorequalto5mmisclassifiedaspositiveinpatientswithhumanimmunodeficiency
virus(HIV)infectionorthosewithriskfactorsforHIVinfectionwhohaveanunknownHIVstatus,inpatients
whohavehadrecentclosecontactwithinfectiousTB,andinthosewhohavechestradiographsconsistentwith
oldhealedTB.Areactionofgreaterthanorequalto10mmisclassifiedaspositiveinpersonswhodonotmeet
theaforementionedcriteriabutwhohaveotherriskfactorsforTB.Areactionofgreaterthanorequalto15mm
isclassifiedaspositiveinallothergroupsofpatients.
MenstrualBloodAnalysis
DefinitivediagnosisofTBrequiresisolationoftuberclebacilliviaculture,althoughdiagnosisbasedon
histologicallycharacteristicgranulomataisacceptedbymostauthorities.Mostexpertsrecommendsomeformof
endometrialsamplingforhistologicandmicrobiologicexaminationtomakethediagnosisofgenitalTB.Because
theendometriumisinvolvedinthemajorityofcasesandisreadilyaccessibletosampling,itisoftenthefirstsite
atwhichattemptsatdefinitivediagnosisaredirected.
Bacteriologicexaminationofmenstrualbloodwithacidfastbacilli(AFB)smearandcultureisrecommendedby
somehowever,sensitivityofthesetestsisquitelow.5Simonandcoworkersreportedthatmenstrualblood
collectedwithin12hoursoftheonsetofmensesandculturedwasfoundtobepositiveforM.tuberculosisin10%
ofcases.36ThereareacidfastorganismsotherthanM.tuberculosis,andthesemayoccasionallybemistakenfor
tuberclebacilli.deVynckandcolleaguesadvocatemenstrualbloodforculturetoidentifyM.tuberculosisusing
LwensteinJensenmedium.28Theyidentified36positiveculturesof451culturestested,andsubsequent
laparoscopicexaminationrevealedbilateraltubalblockin3andperitubaladhesionin17(47.2%)inthe
remaining16(44.5%),thepelviswasconsiderednormal.Theystatedthatradiologicexaminationofthechestand
histologicexaminationoftheendometriumshowednoevidenceofinfection.
ENDOMETRIALCURETTAGE.
Endometrialbiopsyisafrequentfirstdiagnosticstep,andalthoughitssensitivitysuffersfromsamplingerrors,it
canbeveryhelpfulifgranulomataarefoundor,lesscommonly,ifsmearsorculturesarepositiveforM.
tuberculosis.12, 15
AdefinitivediagnosisofTBrequiresisolationoftuberclebacilli,althoughmanyauthoritiesacceptadiagnosis
basedonhistologicexamination,whichconfirmsgranulomata.20, 37 Althoughthenewerculturetechniqueshave
increasedthegrowthrateoftheorganism,itstilltakes40daysormorefor75%ofallpositiveculturestoshow
growth.6AnAFBstainisrapidandrelativelysimpleandcouldbeusedinitiallytomakethediagnosiswhile
waitingforcultureresultstobeavailablehowever,itrequires10organisms/mLforapositivetest.
IninvestigatingthepossibilityofgenitaltractTB,themostaccessibletissueforstudywithahighfrequencyof
involvementistheendometrium.Thehistologicexaminationofendometrialtissuesremovedbybiopsyor
curettage,especiallyfromthecornualarea,affordsarapidmethodofdiagnosinggenitalTBinatleast50%of
cases.AFBstainandcultureand,occasionally,guineapiginoculation,yieldbettermicrobiologicassessment.The
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optimaltimeforsamplingisattheendofthemenstrualcycleorwithin12hoursaftertheonsetofmenstrualflow
toallowtheendometrialgranulomatamaximaltimetodevelop.Onenegativebiopsyoronenegativecurettage
doesnotexcludethediagnosisofgenitalTB.Czernobilskystatedthatserialsectionsneededtobestudied
becausethelesionsarefrequentlypatchy.50FalkandassociatesstatedthatapositiveendometrialcultureforTB
wasfoundonlyin25%ofcasesoftuberculousendometritis.12Dilationandcurettagemayincreasetheyieldon
endometrialspecimensmerelybyincreasingtheamountoftissueavailableforhistologicevaluationand
cultures.
Thedemonstrationoftuberculousendometritismaybeassumedtoindicatetuberculoussalpingitisinpractically
100%ofcases.Negativeendometrialevaluationmaybetheresultofsamplingerror,orthediseasemaybein
othergenitalorganswithoutanassociatedtuberculousendometritis.Sometimes,thediseaseisdiagnosedor
suspectedonlyatexploratorylaparotomywithsubsequentpositiveculturefortuberclebacilliorhistologic
confirmation.AFBcultureorstainofperitonealfluidshowsvariableresults,butthesensitivitycanbeincreased
byperitonealbiopsyforculture,stain,andhistologicevaluation.Laparoscopywithdirectedbiopsiesof
suspiciousareasmaybehelpfuliflessinvasivemethodsfailtoprovidetheneededdiagnosticinformation.
Tissuehasbeenobtainedwithpercutaneousneedletechniques,peritoneoscopy,culdoscopy,andlaparoscopy,
butallcarryasignificantriskofbowelinjurysecondarytoaclosedapproachinthepresenceofdenseadhesive
disease.Asmallopenbiopsycanobtaintissuemoresafely.34, 36, 52
RADIOGRAPHY
NocharacteristicradiographicfeaturesarepathognomonicforgenitaltractTB,althoughcertainfindingsshould
raisesuspicionofitspossibility.Barterandassociatesreportedthatanabdominalfilmmayshowcalcifiedpelvic
andabdominallymphnodes,acharacteristicandrecognizedsequelaofhealedgenitaltractTBs.83
HysterosalpingographymayrevealcertainabnormalitiesthatsuggestthepossibilityofpelvicTB.Theuterine
cavityisclassicallyshriveledanddeformed,withassociatedintrauterineadhesionsandlymphaticextravasation
(Fig.6).Thefallopiantubesoftenshowraggedoutlineswithmultiplestrictures,givingabeadedappearance(Fig.
7)insomepatients,theentiretubeappearsrigidandmayexhibitsmallterminalsacculationsoftheampullary
end(Fig.8).Fistuloustractsbetweenthegenitaltractandotherpelvicorgansmaybeidentified.Occlusionofthe
digitalendofthefallopiantubesiscommon,althoughmarkedhydrosalpinxisusuallyuncommon(Fig.9),
Calcificationoftheorgansmaybevisualized.84,85Ifawatersolublecontrastmediumisusedandtheusual
precautionsareobserved,complicationscanbeminimized.Hysterosalpingographyiscontraindicatedinthe
presenceofrecentacutepelvicinfection,andmanyreportsdescribedexacerbationofpelvicTBfollowingthe
procedure.86
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/006f.jpg)Fig.6.Radiographdemonstrates
lymphaticextravasation,adeformeduterinecavity,andanarrowrigidfallopiantubewithadilatedandclosed
fimbrialendontherightside.
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/007f.jpg)Fig.7.Thefallopiantubesshowa
rigid,raggedoutlinewithabeadedappearance.
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/008f.jpg)Fig.8.Theentirefallopiantube
appearsrigidandexhibitssmallterminalsacculations.
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(http://resources.ama.uk.com/glowm_www/graphics/figures/v1/0490/009f.jpg)Fig.9.Grossdilatationand
occlusionofbothfallopiantubesisvisibleonthisradiograph.
ULTRASONOGRAPHY
Highresolutionabdominalandtransvaginalultrasonographymaydemonstrateloculatedascitisbilateral,
predominantlysolid,adnexalmassescontainingscatteredsmallcalcificationthickenedomentumthickened
peritoneumandendometrialinvolvement,whichmightalertthecliniciantosuspectgenitaltractTB.87 ,88
CERVICALCYTOLOGY
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Khilnaniandcolleaguesreportedthatwhenthecervicalcytologicsmearrevealsthepresenceofclustersof
epithelioidcells,itmaybesuggestiveofatuberculouslesionofthecervix.24 AngrishandVerma,57Bhambaniand
coworkers,54 andMischandassociates89 alsoreportedthatthecytologicexaminationofthesmeartakenfrom
thecervixmaybeusefulinidentifyingcervicalTB.
ENDOSCOPY
Merchantusedendoscopy(laparoscopy,cystoscopy,hysteroscopy)inevaluatingwomenforpelvicTB.90Among
687patientswhounderwentlaparoscopy,pelvicTBwassuspectedin101(14.7%)fromtheappearancealone.
Definitiveevidencewasfoundin70cases.
deVynckandcolleaguesalsousedlaparoscopytodiagnoseandtoconfirmgenitaltractTB.28
RAPIDMOLECULARTECHNIQUES
OldermicrobiologicmethodsfordiagnosisofM.tuberculosisthatreliedonculturesandconventional
biochemicaltestsoftentookseveralweekstoyielddefinitiveresults.Giventheimportanceofrapiddiagnosisof
TBforbothanindividualandatpublichealthlevel,morerapiddiagnostictechniqueswereneeded.The
developmentofbrothbasedculturemedia,availablenowasacomponentofautomated,continuously
monitoredsystems,hasdecreasedaveragedetectiontimeforpositiveM.tuberculosisculturesto914days.91
ThemorerecentarrivalofmolecularmethodsthatcanreliablyidentifyM.tuberculosishasacceleratedthis
processevenfurther.
POLYMERASECHAINREACTION
TheDNAprobesprimarilysavetimebyprovidingarapidalternativetothelongerconventionalidentification
process.Since1987,DNAprobescomplementarytospeciesspecificsequencesofrRNAhavebeencommercially
availablefortheidentificationofM.tuberculosiscomplex,Mycobacteriumaviumcomplex,andothers.These
singlestrandedDNAprobes,labeledwithacridiniumester,hybridizewithcomplementaryrRNAsequencesof
thetargetorganisms.DNArRNAhybridsarecapturedbyantibodiesspecificforthem,andviasignal
amplificationtechniques,theseenzymeconjugatedantibodiesarethendetectedbyachemiluminescent
substratethatemitsalightmeasuredbyaluminometer.91
TheconceptofamplificationofdiscretefragmentsofbacterialDNAorRNAcreatedanewopportunityfor
makingthenucleicacidprobehybridizationmethodhighlysensitiveandopenedthepossibilityofdetectionand
identificationofmycobacteriadirectlyinthepatientsspecimen.Polymerasechainreaction(PCR)wasfirst
suggestedforthedetectionofM.tuberculosis.Theabilityofthetesttocreatea1billionfoldamplificationfrom
eachcopyoftargetDNAmeantthatfewerthan10inputmoleculesoftargetDNAcouldleadtoapositivesignal.
Thus,diagnosisusingtherawspecimencouldbecompletedinjustafewdaysorperhapsafewhoursafterarrival
ofthespecimen.
Basedonthespeciesinquestionandthenumberofmycobacterialorganismsinthesampletested,these
techniqueshaveshownvaryingsensitivitiesof47%to100%forM.tuberculosisand78%to100%forM.avium
complex.92Specificityisthoughttobehighalthough,notably,specimenscontainingbloodcanleadtofalse
positiveresultsowingtononspecificchemiluminescenceinthissituation.Thisproducesapotentialproblem
giventhebodilyfluidscultured,suchasbonemarrow,blood,andbloodtingedsputum.91
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Unfortunately,inreality,theseexpectationshavenotyetbeenfullyrealized.Theinsufficientsensitivitiesofthe
testhavemeantthatthesetestsarelimitedtosmearpositivesputumspecimensonlyandtheyarenotdesignated
forspecimensotherthansputum.However,amplificationtechniquescanbeusedforbrothculturesatthe
earliestpossibledetectionofgrowth.Undertheseconditions,diagnosismaybeobtainedwithin710dayswitha
sensitivityandspecificityof100%.
NUCLEICACIDAMPLIFICATIONTECHNIQUESFORTUBERCULOSIS
Duringthe1990s,severalnucleicacidamplification(NAA)techniquesevolvedthatdramaticallyalteredtheway
inwhichwecandetectandidentifyM.tuberculosis.Unlikethesignalamplificationtechnique,whichrelieson
largenumbersoforganismsfordetectionand,thus,isusefulonlyforculturedisolates,NAAtechniquesallowfor
detectionofM.tuberculosisfromsamplescontainingrelativelyfewM.tuberculosisbacilli.Forthisreason,NAA
techniquescanbeutilizedtoidentifyM.tuberculosisdirectlyfromclinicalspecimens,avoidingthemosttime
consumingaspectofM.tuberculosisidentification,thetimerequiredtoculturetheisolate.
Inthemid1990s,theUnitedStatesFoodandDrugAdministration(FDA)approvedtwodirectNAAtestsfor
identificationofM.tuberculosiscomplexinrespiratoryspecimensthatweresmearpositiveforAFB:theGen
ProbeM.tuberculosisDirect(MTD)testandtheRocheAmplicorMycobacteriumTuberculosisTest.93The
AmplicortestisaPCRbasedtestthatamplifiesM.tuberculosisDNA,whereastheGenProbeMTDtestisa
transcriptionmediatedamplificationtestthatamplifiesM.tuberculosisrRNA.TheGenProbeMTDtesttakes
only3hourstoperform.
WhenusedforAFBsmearpositiverespiratorysamples,theGenProbeMTDtestisquitereliable,withhigh
sensitivity(83%to100%),positivepredictivevalue(94100%),andnegativepredictivevalue(96100%)
reportedintheliterature.94, 95, 96ThishighlevelofaccuracyallowsforearlyidentificationofAFBaseitherM.
tuberculosisornontuberculousmycobacteria(NTM),andtreatment/perfectioncontroldecisionscanbebased
onthisinformation.
WhenusedinAFBsmearnegativerespiratorysamples,earlystudiessuggesteddiminishedreliabilityofthistest
withsensitivityof50%andpositivepredictivevalueof350%,althoughspecificityremainedhigh.93More
recentdatawithanew,enhancedMTDtest(MTD2)suggestthateveninAFBsmearnegativerespiratory
samples,sensitivityandspecificityapproach100%.96ManystudiessuggestthattheGenProbeMTDtestisalso
usefulinassessingextrapulmonaryspecimenswithhighsensitivity(84100%),specificity(98100%),and
positivepredictivevalue(90100%).94, 95, 96, 97 , 98
Thesenew,rapid,highlysensitivemoleculartechniquesdonotsolvealltheproblemsdetectingM.tuberculosis.
Likeanytest,NAAassaysarenotperfectandshouldbeusedonlyinconjunctionwithtraditionalcultureisolation
methodstomaximizesensitivityofthelaboratorydiagnosisofTB.CurrentNAAtechnologyallowsforthe
detectionofM.tuberculosisinpatientspecimenswithinhourscomparedwiththe1428daysrequiredfor
culture.Thepotentialclinicalbenefitsofthisearlydetection,forbothanindividualandatpublichealthlevel,are
unimaginable.
SEROLOGICDIAGNOSIS
Manyresearchlaboratorieshaveshownthatenzymelinkedimmunosorbentassay(ELIZA)measurementofthe
immunoglobulinG(IgG)antibodytomycobacterialantigenscanbeusedfortheserologicdiagnosisof
tuberculosis.LimiteddatasuggestthatELISAserologicdiagnosismaybeusefulfordiagnosisofextrapulmonary
TB.Otherserodiagnostictechniquessuchasradioimmunoassay(RIA),inhibitionofmonoclonalantibodies,and
latexagglutinationhavehadlessextensivestudybutappearpromising.7
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DRUGSENSITIVITYTEST
Detectionofdrugresistanceinatimelymannerisoneofthemostimportanttasksinthepropermanagementof
TBpatients.Thedecisionaboutwhethertoperformdrugsensitivitytestingdependsontheinitialassessmentof
clinicalandepidemiologicfactors.Initialsusceptibilitytestingshouldbedoneinpersonsknowntobeathigh
risk.Theseincludepatientswithahistoryofantituberculouschemotherapypatientsinageographicregionin
whichthereisahighprevalenceofdrugresistance,suchasAsia,Africa,andLatinAmericaandcontactsofknown
orsuspectedresistantcases.
DIFFERENTIALDIAGNOSIS
GranulomatouslesionotherthanTBaresarcoid,Crohnsdisease,actinomycosis,leprosy,granulomainguinale,
lymphogranulomavenereum,syphilis,histoplasmosis,brucellosis,berylliosis,silicosis,tularemia,andforeign
bodyreaction.Schistosomiasisandfilariasismaydirectlydamagethefallopiantubesandproducegranulomata
andmaypredisposetochronicinfection.2,6,45,99,100,101
Conditionssuchasacuteandchronicbacterialpelvicinfectionshouldalsobeconsideredwhenthereisascitisand
peritonitiscomplicatinggenitalTB.Otherconditionsthatproduceasimilarclinicalpicture,suchashepatitis,
cholecystitis,appendicitis,ovariancancer,andrenalandcardiacdiseases,shouldbeexcluded.6,34
COMPLICATIONOFGENITALTUBERCULOSIS
SubfertilityorSterility
DespiteeffectivetherapeuticregimensforgenitalTB,sterilityremainsamajorcomplication.Medicalregimens
havebeensuccessfulatalleviatingsymptomsofmenstrualdisordersandpain,whereasfollowupendometrial
samplingoftenrevealscurewithanappropriatedrugregimen.However,eveninpatientsconsideredtobe
cured,extensivedamagetothefallopiantubesandtheendometriumisoftenirreversible,andchancesof
successfulintrauterinepregnancydropsignificantly.Oneextensivereviewoftheliteraturepublishedin1976
describedonly31casesofsuccessfulpregnancyoutofnearly7000casesofgenitalTB.5Of187casesofgenital
TBinSwedenover196877,nointrauterinepregnanciesoccurredaftertherapy.12Somewhatmoreoptimistic
datacamefromareviewof710casesofgenitalTBinScotland,ofwhichtherehadbeen58intrauterine
pregnancies(35healthybabies,21abortions,and2neonataldeaths)bythetimeofpublication.82Obviously,
noneoftheseseriesutilizedtherecentmedicalregimensconsideredtobestandardofcareforthetreatmentof
extrapulmonaryTBtoday.
EctopicPregnancy
ThedamagetothefallopiantubescanbeextensiveandirreparableifgenitalTBisnotdiagnosedandtreated
earlyinitscourse.Aftermedicaltreatment,theriskofectopicpregnancyinpatientswithpelvicTBisestimated
tobe3372%.43
CongenitalTuberculosis
ArarebutpotentiallyseriouscomplicationoffemalegenitalTBiscongenitalTB.ConsideringthatgenitalTB
causessterility,casesofcongenitalTBinvolvingtransmissionfrommaternaltuberculousendometriumtothe
fetusarerare,withonlysome300casesreportedintheliterature.102CongenitalTBcanbeanoverwhelming
systemicinfectioninthenewbornandhasconsiderablemorbidityandmortalityifuntreated.102, 103.
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MANAGEMENT
OncethediagnosisofgenitaltractTBisconfirmed,itisimportanttoruleoutTBinotherpartsofthebody.A
chestradiographandthreeearlymorningsputumorgastricaspiratesamples,orearlymorningurinesamples
forAFBstainandcultureandintravenousurogram,arerecommended.104DalyandMonifreportedthat10%of
femaleswithgenitaltractTBalsoshowevidenceofrenalTB.37
Toplaneffectivetreatment,thegynecologistmustconsiderthefollowing:(1)IsactiveTBpresentelsewhere?(2)
Whatistheextentofthegenitaltractlesion?(3)WillmedicalmanagementcuregenitalTB?(4)Whenissurgical
managementneeded?(5)Ispregnancypossibleaftertreatment?
ThepresenceofactiveextragenitalfociofTB,asarule,israrewhenthegenitallesionisdiscovered.Theextent
ofgenitallesionmaybedividedintominimalandadvanced.MinimalgenitalTBisusuallyasymptomaticexcept
forsterility.Examinationofthepelvismaynotrevealanyabnormality.Itisusuallydiagnosedfromthe
bacteriologicorhistologicexaminationoftheendometriumorfromthebacteriologicexaminationofthe
menstrualblood.InadvancedgenitalTB,palpabletuboovarianmassesarepresent.Histologicandbacteriologic
examinationoftheendometriumormenstrualbloodconfirmsthediagnosisofTB.
TREATMENT
Inthepast,irradiation,naturalsunlight,vitamins,sanatoriumcareand,forpelvictuberculosisinparticular,
pelvicdiathermyandinjectionofoxygenintraperitoneally,haveallbeentried.Beforetheadventofeffective
chemotherapy,surgerywasthemainstayoftreatmentofgenitaltractTB,andpostoperativecomplicationssuch
asbowelfistula(14%)andmortalityfromtheprimarydisease(2.2%)werehigh.105
Unfortunately,therearesparse,prospective,controlledclinicalstudiesregardingtreatmentoffemalegenital
TB,agapthatisfoundinthebroadercontextofextrapulmonaryTB.Thesmallamountofdata,however,suggest
thatextrapulmonaryTBcanbeveryeffectivelytreatedwithsomestandardshortcourseregimen.106Experts
suggestthatextrapulmonaryTBmaybeeveneasiertotreatthanpulmonaryTBowingtothedecreased
concentrationoforganismsintheselesionsandtheincreasedaccessibilityofmanyofthesitesfor
antituberculousmedication.
Theadventofantituberculousdrugshasrevolutionizedthemanagementofthisdisease.Ifsurgicalintervention
isneeded,chemotherapymakesthisapproachsafer,easier,andmoreeffective.Threebasicprincipleshave
emergedintheyearsfollowingtheadventofchemotherapyforTB:
1.Theregimenfortreatmentmustcontainmultipledrugstowhichtheorganismissusceptible.
2.Thedrugsshouldbetakenregularly.
3.Thedrugtherapyshouldcontinueforasufficientperiodoftime.
ThetreatmentofextrapulmonaryTB,includinggenitaltractTB,isthesameasthetreatmentofpulmonaryTB
(Tables5and6).Thus,thecurrentstandardsinthetreatmentoftuberculosisare:
1.A6monthregimenconsistingofisoniazid(INH),rifampin(RIF)andpyrazinamide(PZA)for2months,
followedbyINHandRIFfor4months,isthepreferredtreatmentforpatientswithafullysusceptible
organismwhoadheretotreatment.Ethambutol(EMB)orstreptomycin(SM)shouldbeincludedinthe
initialregimenuntiltheresultsofdrugsensitivitystudiesareavailable,unlessthereislittlepossibilityof
drugresistance.Thisfourdrug,6monthregimeniseffectiveevenwhentheinfectingorganismisresistant
toINH.ThisrecommendationappliestobothHIVinfectedpatientsandthosewhoarenoninfectedwith
HIV.However,inthepresenceofHIVinfection,theclinicalcourseshouldbecloselymonitored,and
treatmentshouldbeprolongedifthecourseisdeterminedtobesloworsuboptimal.
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2.A9monthregimenofINHandRIFisacceptableinpatientswhocannottoleratePZA.EMBorSMshould
beincludeduntilthedrugsusceptibilitystudiesareavailable,unlessthereislittlepossibilityfordrug
resistance.Considerationshouldbegiventotreatingallpatientswithdirectlyobservedtherapy(DOT)
3.Themajordeterminantoftheoutcomeoftreatmentispatientadherencetothedrugregimen.Virtuallyall
treatmentregimensmaybegivenintermittentlyifdirectlyobserved,thusensuringadherence.
Table5.Drugregimensforgenitaltuberculosis
Initialtherapy
INH+RIF+PZAdailyfor2months
AddEMBorSMwherethereisahighrateofresistanceuntildrugsusceptibilitydataareknown
Continuationphase
INH+RIFdailyfor410months(total612months)
Addpyridoxine2550mgdailytoregimensthatincludeINH
EMB,ethambutolINH,isoniazidPZA,pyrazinamideRIF,rifampinSM,streptomycin.
Table6.Dosageofantituberculousdrugs
Dose(mg/kg)*
Regimen
INH
RIF
PZA
EMB
SM
Daily
5(300)
10(600)
1530(2000)
1525
15(1000)
2x/wk(DOT)
15(900)
10(600)
5070(4000)
50
2530(1500)
3x/wk(DOT)
15(900)
10(600)
5070(4000)
2530
2530(1500)
DOT,directlyobservedtherapyEMB,ethambutolINH,isoniazidPZA,pyrazanimideRIF,rifampinSM,
stretomycin.
*Maximumdailydoseisinparentheses.
DuttandStead,basedontheirstudyof478patientswithextrapulmonaryTBincluding65patientswith
genitourinaryTBfrom1978to1987,concludedthattreatmentwithshortcourseantituberculouschemotherapy
consistingofINH300mgorally4timesadayandRIF600mgorally4timesadayfor1month,followedby
INH900mgandRIF600mgtwiceaweekforanother8monthswassuccessfulin95%oftheircases.106
Aroraandcolleaguesinvestigatedtheefficacyofshortcoursechemotherapyonthespecificproblemrelatedto
genitalTBinasmallprospectivetrial.107 FortyonepatientswithprovengenitalTBweregiven
SM/INH/RIF/PZAfor2months,followedbyINH/RIFforanother7months.Thirtytwoofthesepatients
completedthefull9monthsoftherapyand,ofthesepatients,78%wereconsideredcured,definedasboth
symptomaticandhistologicmicrobiologicresolution.107
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AsimilaroutcomewasachievedbyJindalandassociatesinasmallprospectivestudyof14femalepatientswith
genitalTBwhoweretreatedwithdailyRIF450mgandINH300mgfor9months.Followupendometrial
biopsieswerenegativeinallpatientstreatedwiththisregimen.Threeoutof14patients(21%)conceivedafter
startingtherapy.108
DrugsinCurrentUse
ISONIAZID.
INHisthemostwidelyusedantituberculousagent.109Itisbactericidal,relativelynontoxic,easilyadministered,
andinexpensive.Absorptionfromthegutisnearlycomplete,anditishighlyactiveagainstM.tuberculosis.The
usualdoseis35mg/kgbodyweight.Hepatitisisthemajortoxiceffectandisincreasedwithincreasingageto65
years.110, 111Alcoholconsumptionisalsoidentifiedasariskcofactor.112, 113Peripheralneuropathy,mostlikely
duetointerferencewithpyridoxinemetabolism,isassociatedwithINHadministrationbutisuncommonata
doseof5mg/kg.Inpatientsatriskforperipheralneuropathy,concomitantpyridoxineadministrationis
recommended,anditisalsorecommendedinpatientswithseizuredisordersandinpregnantwomen.
RIFAMPIN.
RIFisbactericidaltoM.tuberculosis,relativelynontoxic,andeasilyadministered.Itisrapidlyabsorbedfrom
thegut.Itpenetrateswellintotissuesandcells.ThemostcommonadverseeffectofRIFisgastrointestinalupset.
Otherreactionsincludeskineruptions,hepatitis,andrarely,thrombocytopeniaandcholestaticjaundice.RIF
induceshepaticmicrosomalenzymesandmayaccelerateclearanceofdrugsmetabolizedbytheliver.114These
includemethadone,warfarinderivatives,glucocorticoids,estrogens,oralhypoglycemicagents,digoxin,
antiarrhythmicagents,theophylline,anticonvulsants,ketoconazole,andcyclosporine.BecauseRIFinterferes
withestrogenmetabolism,itcanlowertheeffectivenessoforalcontraceptives.Inadults,intermittent
administrationofRIFindoseslargerthan10mg/kgmaybeassociatedwiththrombocytopenia,influenzalike
syndrome,hemolyticanemia,andacuterenalfailure.RIFisexcretedinurine,tears,sweat,andotherfluids,and
itcolorsthemorange.Patientsshouldbeadvisedofthisdiscolorationandalsoofthepossibilityofpermanent
discolorationofsoftcontactlenses.
PYRAZINAMIDE.
PZAisbactericidalagainstM.tuberculosisinanacidicenvironmentandisactiveagainstorganismsin
macrophages.Absorptionfromthegastrointestinaltractisnearlycomplete.PZApenetrateswellintomost
tissues.Themostimportantsideeffectofthisdrugishepatotoxicity.However,theredoesnotappeartobean
increaseinhepatotoxicitywhenPZAisaddedtoaregimenofINHandRIFintheinitial2monthsoftherapy.
Hyperuricemiaappearsfrequently,butacutegoutisrare.34, 112Skinrashandgastrointestinalirritationarealso
seen.
ETHAMBUTOL.
EMBinusualdosesisgenerallyconsideredtohaveabacteriostaticeffectonM.tuberculosisbutmayhavea
bactericidaleffectwhenusedinhigherdosesinintermittenttherapy.Thedrugiseasilyadministeredandhasa
lowfrequencyofadverseeffects.Itaccumulatesinpatientswithrenalinsufficiency.Retrobulbarneuritisisthe
mostfrequentandseriousadverseeffectofEMB.Symptomsincludeblurringofvision,centralscotomata,and
redgreencolorblindness.112Thecomplicationisdoserelatedandoccursinlessthan1%ofpatientsreceivinga
dailydoseof15mg/kg,increaseswithadailydoseof25mg/kg,andisincreasedinpatientswithrenal
insufficiency.
STREPTOMYCIN.
SMisbactericidalinanalkalineenvironmentandisgivenparenterally.Excretionofthedrugisalmostentirely
renal.Ithasgoodtissuepenetration.ThemostcommonseriousadverseeffectofSMisototoxicity.115This
usuallyresultsinvertigo,buthearinglossmayalsooccur.Nephrotoxicitymayalsooccasionallyoccur.Atotal
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cumulativedoseofmorethan120gshouldnotbegivenunlessothertherapeuticoptionsarenotavailable.
OTHERDRUGSUSEDAGAINSTMYCOBACTERIUMTUBERCULOSIS.
OtherdrugsthathavebeenusedagainstM.tuberculosisandarecurrentlybeingused,especiallyinmultidrug
resistantdisease,areparaaminosalicylicacid(PAS),cycloserine,capreomycin,kanamycin,thiacetazone,
amikacin,ciprofloxacin,andofloxacin.CiprofloxacinandofloxacinarenotlicensedforthetreatmentofTB.
SUCCESSRATESANDFOLLOWUPS.
MalkaniandRajaniusedweeklybiopsiestofollowaseriesof30patientsreceivingantituberculousdrugsforthe
treatmentoftuberculousendometriosis.69Fromthe4thweek,thesepatientsshowedanincreasingnumberof
histologicallynegativeendometria,andafter12weeks,theendometriainall30werenegativebybiopsy.
AccordingtoKardos,tuberculousendometritismaybeconsideredcuredasseenonhistologicexaminationby
usingantimicrobialtherapyof3months'duration,althoughhenotedtherecurrenceofendometritiswithin45
yearsifthefallopiantubeswerenotremoved.116Schaeferreviewed387casesoftuberculousendometritis
treatedforperiodsaslongas4months.117 Twentytwopercentshoweddiseaserecurrencewithin3years.To
determinetheeffectofantituberculousdrugtherapyonthefallopiantubes,whichmaybethecauseofdisease
recurrence,andtoarriveattheoptimaldurationoftherapy,SchaefertreatedaseriesofpatientswithgenitalTB
forperiodsvaryingfrom6weeksto3yearsbeforeremovingthefallopiantubes.117 Inpatientswithminimal
genitalTB,noevidenceofactiveTBwasfoundinthetubesafter10monthsoftherapy.
SchaefersubsequentlyadvocatedaregimenoftreatmentusingINH300mgdaily,andEMB20mg/kgor
approximately1200mg/day.72At6monthsand12months,endometrialcurettingsorbiopsiesareexamined
bacteriologicallyandmicroscopically.If,duringthecourseoftreatment,theendometrialcurettingsbecome
positiveortuboovarianmassesappear,RIFinadoseof600mgdailyisaddedfor3months,andthepatientis
advisedtohavesurgery.SchaeferadvocatedtreatmentusingINHandEMBforatleast2yearsiftherewereno
complications.117 Subsequently,hispatientscontinuedtoreceiveINHforanindefiniteperiod.
Foradvanceddisease,SchaeferadvocatedINHandEMBforaperiodof34months,andifthetuboovarian
massstillpersisted,headvisedsurgeryfollowedbyantimicrobialtherapy.117
Ingeneral,over95%ofpatientstreatedforTBforthefirsttime,usingacombineddrugregimen,undergo
successfultreatmentiftheycompletetheprescribeddrugcourse.Mostpatientsbecomenoninfectiousvery
rapidly,usuallywithin2weeks.115Inpatientswhohavehadpreviouschemotherapy,whohavehadcontactwitha
INHresistantcase,orwhoacquiredtheirinfectioninanareawithahighprevalenceofresistantorganisms,such
asAsia,LatinAmerica,orAfrica,drugresistanceshouldbesuspectedanddrugsensitivitytestsshouldbe
performed.Carefulcomplianceisthemostimportantfactorinpreventingthedevelopmentofdrugresistance.34
CorticosteroidshavebeenproposedbysomeasanadjuvanttherapyinthemanagementofTBandmay
amelioratecertainaspectsoftheinflammatoryresponseinvolvedinthedisease.ElsbachandEdsallstatedthat
therewasnoevidenceofanadverseeffectonthecourseofthediseasewhenchemotherapywasadequate.118
Patientresponsetotreatmentshouldbemonitoredbydoingendometrialcurettage6and12monthsafterthe
initiationoftreatment.Patientsneedtobefollowedcloselyforanindefiniteperiod.Recurrenceor
disseminationtootherorgansisrarebutoccasionallyoccurs.Chestradiographs,urineculturesforM.
tuberculosis,anduterinecurettageshouldberepeatedattheendofthetreatmentcourse,witharepeat
curettageorendometrialbiopsyevery612months.Sutherlandsuggestedthatpatientsneededfollowup
assessmentforseveralyears.40, 52
SurgicalTreatment
TheroleofsurgeryinthetreatmentofgenitalTBinmoderntimesisclearlyasadjunctivetherapy.Giventhe
excellentresultsthatcanbeobtainedbytreatingextrapulmonaryTBwithantituberculouschemotherapy,
surgeryhasbecomethebackupplaninmostcases.Surgeryisadvocatedonlyifthereisnootherchoiceof
treatment.
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IndicationsforsurgicalinterventioninthemanagementofpelvicTBinclude(1)persistentandrecurrentdisease
despiteadequatetreatment(2)persistentorrecurrentpelvicmassesafter6monthsofadequatetherapy(3)
persistentorrecurrentsymptomssuchaspelvicpainandabnormalbleeding(4)apersistentnonhealingfistula
(5)multidrugresistantdiseaseand(6)concomitantgenitaltractneoplasiaorotherpathology.5, 9, 36, 37 , 40, 119
Whensurgeryisadvocated,thepatientshouldbegivenchemotherapyforatleast12weekspreoperatively.
Surgeryshouldbeperformedatmidcycleinpremenopausalpatients,andchemotherapyshouldbecontinuedfor
612monthspostoperatively.Underantituberculoustreatment,surgeryistechnicallymuchlessdifficult,and
morbidityandmortalityaresignificantlyreduced.Sutherlandreportedon77casesinwhichsurgerywas
undertakenduringantituberculousdrugtreatmentnopatientdevelopedafistula,andtherewasno
mortality.119Latecomplicationswereinfrequent.
WhenTBisfirstdiagnosedpostoperativelyafterhistologicexamination,antituberculoustreatmentisgiven
immediatelyandcontinuedfor612months.
Theoperationofchoiceistotalabdominalhysterectomywithbilateralsalpingooopherectomyfollowedby
hormonereplacementtherapy,especiallyinapremenopausalwoman.Ifthepatientispremenopausalandthe
ovarieslooknormal,theymaybeconserved.
GENITALTUBERCULOSISANDPREGNANCY
Ylinenstatedthattheprognosisforinfertilityseemsnearlyuniversalbecauseofthedifficultyofmakinganearly
diagnosisofgenitalTB.64Thosewhoreportsuccessfulpregnanciesattributethemtoearlytreatmentwith
antituberculousdrugsand,insomecases,totheuseofthesedrugscombinedwithsteroidtherapy.Halbrecht
usedantituberculousdrugsandsteroidsfor4months.120Followingthisregimen,3patientsof42became
pregnant,2hadintrauterinepregnancies,and1hadanectopicpregnancy.Ofthe12patientsinthisgroupwho
underwenttubalsurgery,noneconceived.Itisestimatedthatifoneorbothfallopiantubesarepatentatthestart
oftreatment,thepatienthasa50%chanceofconceivinganddeliveringachild.Schaeferreviewedmorethan
7000casesofgenitalTBfromtheliterature.121Amongthese,155womenachievedfulltermpregnancies,67had
miscarriages,and125hadectopicpregnancies.Over50%ofthewomenwhoachievedfulltermpregnancieswere
notadequatelydocumented.Inonly31of155patientswastheredefiniteevidenceoftuberculousinfection,as
assessedonthebasisofhistologicandbacteriologicevidence.Schaeferstatedthatalthoughpregnancymay
followprovedminimalTBinsomeinstances,patientswithadvanceddiseaseshouldbeconsideredinfertile.121
Aspreviouslynoted,themostcommonpresentingcomplaintforawomanwithgenitalTBisinfertility.Ahistory
ofapreviouspregnancymakesitmorelikelyforthediseasetohavebeenacquiredlaterinlife.
Despitetheadvancesinchemotherapeutictreatment,pregnancyafteradiagnosisofgenitaltractTBisrare,and
whenitdoesoccur,itismorelikelytobeanectopicpregnancyortoresultinspontaneousabortion.122Ifan
earlydiagnosisismadeandadequatetherapyisgivenimmediately,amorefavorableoutcomemaybe
expected.123Sutherlandreportedtheresultsoftreatmentof206womenwithgenitalTBwithSM,PAS,andINH
for1824months.124In19patients,surgerywasneededbecauseoffailureofmedicaltreatment45pregnancies
subsequentlyoccurredin26patients11wereectopicand11resultedinmiscarriage,buttherewere23live
birthsin14women,foraposttreatmentfertilityrateof6.7%.Tubalandendometrialdamageusuallypreventsa
normalconceptionandimplantation,eventhoughthefallopiantubesarepatent.TripathyandTripathyreported
that2of165womenwithgenitalTBhadfulltermnormaldeliveriesand3hadmiscarriagesafterantituberculous
treatmentfor18months.11OjoandUnuigbereportedthatnoneofthe22patientswithprovengenitalTB
conceivedafterantituberculoustreatment.27 Sutherland,inareviewof710cases,reported84pregnancieswith
only35healthybabies,2neonataldeaths,21miscarriages,and26ectopicpregnancies.82
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Merchanttreated101patientswhowerethoughttohavegenitalTB.Seventyhaddefinitiveevidenceof
tuberculosis.90All101patientsweretreated.Elevenwomen(15%)hadintrauterinepregnancy9delivered
normally,and2underwentmedicalterminationofpregnancy.Threepatientshadtubalpregnancies(4%).
deVynckandcolleaguesreportedthatoftheir34patientstreatedforTB,13(38.2%)becamepregnant.28Seven
ofthepregnancieswerespontaneous,5patientsbecamepregnantaftergameteintrafallopiantransfer(GIFT),
and1patientachievedpregnancybyinvitrofertilization(IVF).Twoabortionsoccurred,1inthespontaneous
group,andthepatientwhounderwentIVFtreatmenthadapretermdeliveryat26weeksgestationbecauseof
preeclampsiaandmultiplepregnancy.Twopatientsbecamepregnantbeforetreatmentstarted.
Tubalsurgeryhasapoorprognosis.Ifitistobeattempted,thepatientshouldbetreatedwithaprolonged
courseofchemotherapyandthediseasearrestedforatleast18monthsbeforesurgery.33Corticosteroidtherapy
hasbeentriedwithoutmuchsuccess.120
Falkandassociatespublishedaretrospectivestudyof187patientswithadiagnosisofgenitalTBwhowere
treatedbetween1968and1988.12Alltheirpatientshadchemotherapy,and101alsohadsurgery.In65.3%,the
diagnosiswasnotestablishedpreoperativelyandthepatientunderwentsurgeryforreasonsotherthanknown
TB.Attheend,only139caserecordscontainedadequateinformatio:105patients(76%)becamefreeof
symptoms,andtherewerenointrauterinepregnancies,buttherewere4tubalpregnancies(3of4occurredin
thesamepatient).
PunnonenandcoworkersstatedthatinfertilitywasoneofthemainsymptomsoffemalegenitalTB.14They
studiedsixpatientswithprovenTB.Allthepatientshadantituberculoustherapyfourconceived,butonlytwo
hadfulltermdeliveries.
Frydmanandcolleaguesreportedon22womenwithprovengenitaltractTBwhopresentedwithinfertilityand
whounderwentIVFandembryotransfer(ET)in49pregnancyattempts.125Sixpatientsconceivedandhad
babies.TheauthorsstatedthatIVFandETprobablyofferedabetterchanceofconceptionforthosepatientswho
hadgenitalTB.
SoussisandcolleaguesdescribedtheirattemptsatIVFandETin13patientswith21treatmentcyclesin
histologicallydocumentedgenitaltractTB.Sixintrauterinepregnanciesresulted(28.6%successrate).126
GurganandcoworkersevaluatedtheoutcomesofIVFandETinpatientswithprovengenitaltractTBcompared
withpatientswithoutthedisease.TheyconcludedthatpatientswithgenitalTBhadhigherbasalfollicle
stimulatinghormonelevels,requiredmoreexogenousgonadotropins,reachedlowerpeakestradiollevels,and
yieldedfeweroocytesandembryoswhencomparedwithpatientswhohadtubalfactorsbutnotuberculous
lesion.Furthermore,inwomenwithgenitalTB,theclinicalpregnancyratepercyclewaslower,andthe
spontaneousabortionratewashigher.127
Inarecentpublication,Namavarandassociatesstudiedretrospectively3088casesofTBfrom1989to199946
womenwerediagnosedtohavegenitalTB.128Thediagnosesin41caseswerebasedonthepathologiccriteriaof
tissuespecimens.Themeanageofthepatientsatthetimeofdiagnosiswas30.4years17.07%presentedwith
abdominalorpelvicpainand7underwentsurgery,3forabdominalmass,4fortuboovarianabscess.In31cases
(75.6%),TBwasdiagnosedduringinvestigationsperformedtoevaluatethecauseoftheirinfertilitythemost
commonprocedurewasendometrialcurettage(25cases).FemalegenitalTBaccountedfor1.32%ofall
tuberculouspatientsinthisstudy.Ofthese,75.6%wereinfertile.Tuberculousendometritiswasdetectedin
72.01%,tubalinvolvementin34.03%,ovarianlesionin12.9%,andcervicallesionin2.4%ofthepatients.This
studyconfirmsthestrongrelationshipbetweengenitalTBandinfertility.Thepossibilityofthisconditionshould
beconsideredintheevaluationofeveryinfertilepatientinareasinwhichTBisendemic.
Despitetheratherdismalprognosisconcerningsuccessfulpregnancyoutcomeinawomanwhohashadgenital
TBs,thepossibilityofthisdiseaseshouldbeconsideredinaninfertilepatientforwhomnoetiologyforinfertility
canbediscovered.Ifthediagnosisisconfirmed,conservativetreatmentisrecommended.Conceptiondoes
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occasionallyoccur,butthepregnancymustbemonitoredcarefullyforpossibilityofanectopicpregnancyor
miscarriage.Forthisgroupofwomen,IVFwithETisanoptiontoachievepregnancy.Thesuccessratefollowing
suchassistedreproductivetechniqueisnotasgoodthatinwomenwhohavenogenitaltractTB.
PERINATALOUTCOMEOFPREGNANCYFOLLOWINGTREATMENT
FORGENITALTUBERCULOSIS
FigueroaDamianandArredondoGarciastudiedtheimpactofTBonperinataloutcomeinacohortof25women
withTBtreatedattheNationalInstituteofPerinatologyinMexicoCityfromMarch1990toSeptember1995.129
Theywerecomparedwithacohortofnormalpregnantwomenmatchedbyage,gestationalage,and
socioeconomicstatus.Ninewomenstartedtreatmenteitherbeforeoratthebeginningofpregnancythe
remaining16startedthetreatmentforTBinthesecondorthirdtrimesterofgestation.Thirteenwomen(52%)
hadpulmonaryTB,7(28%)hadrenallesions,andtheremaining5hadlesionselsewhere.Obstetricmorbidity
andneonatalmortalityweresignificantlyhighinthegroupwithTBwhostartedthetreatmentlateinpregnancy.
Perinatalmorbiditywassimilarinpregnantwomenwhoreceivedtreatmentearlyinpregnancycomparedwith
thecontrolgroup.
TheprevalenceofTB,especiallyextrapulmonaryTB,isincreasingworldwide.However,weknowlittleaboutthe
outcomeofpregnancy.Janaandcoworkersstudiedthecourseofpregnancyandlaborandtheperinataloutcome
inthesewomenandtheirinfants.130From1983to1993,Janaandcoworkersstudied33pregnantwomenwho
hadextrapulmonaryTB:12hadlymphadenitis9hadintestinalTBand7hadskeletallesions,2withrenaland1
withendometriallesion.Ofthe33,29receivedantituberculoustreatmentduringpregnancy.Theoutcomewas
comparedwith132healthypregnantwomenwithoutTBwhowerematchedforage,parity,andsocioeconomic
status.
Tuberculousadenitisdidnotaffectthecourseofpregnancyorlaborortheperinataloutcomecomparedwiththe
controlgroup:21womenwithotherextrapulmonarylesionshadhigherratesofantenatalhospitalization(24%
versus2%)andinfantswithlowApgarscores(lessthanorequalto6)andlowbirthweight(lessthan2500g)
infants(33%versus11%).ExtrapulmonaryTBlesionsotherthanlymphadenitisareassociatedwithadverse
outcomefollowingpregnancyandchildbirth.
YipandcolleaguesstatedthatTBoftheendometriumisusuallyassociatedwithinfertility.IVFandETofferthe
onlyrealistictreatmentofinfertilityassociatedwithgenitalTB.131Yipandcolleaguesreportedonecaseof
spontaneousconceptionwithanormalpregnancyoutcomeinapatientwithM.tuberculosisoftheendometrium.
A34yearoldwomanwhohad10yearsofinfertilitywasinvestigated.Thepatientunderwentdiagnostic
laparoscopy,chromohydrotubation,andendometrialbiopsy,whichshowedpatencyofbothtubesandnormal
pelvicorganswithnoevidenceofendometriosisorpreviouspelvicinflammatorydisease.Therewasnothingin
herhistorytosuggestthatshehadtheriskofgenitalTB.Histologicexaminationoftheendometriumshowedno
granulomatahowever,cultureoftheendometriumyieldedM.tuberculosis.
Whenshewascalledbackforantituberculouschemotherapy,shewasfoundtobejustpregnantfollowingthe
biopsy.Antituberculouschemotherapywascommencedat14weeksgestationwithRIF,INH,PZA,and
pyridoxin.Thepregnancyremaineduneventful,andthepatientdeliveredanormalfemaleinfantweighing3380
gatterm.Thisisanextremelyrare,successfulevent,butthestandardmanagementstillremainsIVFandETfor
thisgroupofwomen.
FigueroaDamianandArredondoGarciastatedthattheincidenceofTBhasincreasedworldwide.132Itis
consideredthatpregnantwomenwillacquirethisinfectionmorefrequently.M.tuberculosisinfectionduring
pregnancymayrepresentariskformaternalandneonatalcomplications.Theseauthorsstudiedtheperinatal
eventsof35consecutivepregnanciescomplicatedbyTBfromMarch1990toJune1998105apparentlyhealthy
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pregnantwomenwereincludedascontrols,matchedinage,gestationalageonarrivaltotheclinic,and
socioeconomicstatus.Relativerisk(RR)with95%confidenceinterval(CI)wascalculated,andastratified
analysiswasalsoperformed.
Seventeen(48.5%)tuberculousmothershadapulmonaryTBand18(51.5%)hadanextrapulmonaryTB.The
neonatalmorbidityrateinchildrenborntowomenwithTBwas23%against3.8%ofthechildrenofthecontrol
group(p<0.05).TheaverageweightofnewborninfantsintheTBgroupwas285978.5g,whereastheaverage
weightoftheinfantsinthecontrolgroupwas3099484g(p=0.03).Theincidenceofprematurebirth,
perinataldeath,andweightatbirthlessthan2500gwashigherintheTBgroup.
AnactivevaccinationprogramwithvigilantsuspicionforTB,especiallyinendemicareas,willhelpourfuture
generations.
ACKNOWLEDGMENT
IwouldliketoexpressmygratitudetoDr.NanditaThakkarforhelpingmewiththereferences.
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Tuberculosis of The Female Genital Tract - GLOWM

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Themostcommoninitialsymptomisinfertility.14, 20, 60, 61Approximately85%ofpatientswithgenitaltractTB

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