JURNAL INTERNASIONAL

“KISTA OVARIUM(ovarian cysts)”

DISUSUN OLEH :

Nur Athifah
21906150
E Non Reguler

SEKOLAH TINGGI ILMU KESEHATAN MAKASSAR

2020
 Reviews

Treatment of ovarian
endometrial cysts in the
context of recurrence and
fertility
*IzabelaNowak-PsiorzA–D,F,*SylwesterM.CiećwieżA–D,F,AgnieszkaBrodowskaA,B,D,F,AndrzejStarczewskiA,B,D,F

DepartmentofGynecology,EndocrinologyandGynecologicOncology,PomeranianMedicalUniversity,

Szczecin,Poland A–researchconceptanddesign;B–collectionand/orassemblyofdata;C–

dataanalysisandinterpretation;

D – writing the article; E – critical revision of the article; F – final approval of the article

AdvancesinClinicalandExperimentalMedicine,ISSN1899-5276(print),ISSN2451-2680(online)AdvClinExpMed.2019;28(3):407–413

Address for correspondence

Sylwester Ciećwież Abstract
E-mail: s.ciecwiez@scipro.pl
Anapproachtoovarianendometrialcystshaschangedconsiderablyduringrece
ntyears,especiallyinregard to treatment of recurrent endometriosis, fertility
Funding sources
None declared sparing and infertility management. Surgical treatment is the primary
therapeutic option. The most efficient types of treatment are radical
procedures involving adhesiolysis, removal of the cyst along with its
Conflict of interest
None declared capsule and any remaining endometriotic foci. However,
smallasymptomaticcystsshouldnotbetreatedsurgically,especiallyinpatientso
* Izabela Nowak-Psiorz and Sylwester lderthan35years.Surgical
Ciećwież contributed equally to
this work
treatmentcanbeconsideredininfertilewomenandthosewhofailedtogetpregna
ntdespite1–1.5years
oftrials,aswellasincasesinwhichinvitrofertilizationisnotanoption.Alsolargecy
sts,withmorethan4cm
ReceivedonApril4,2017 indiameter,shouldbetreatedsurgicallyduetotheriskoftheirruptureortorsion.Th
ReviewedonMay6,2017 emostefficientpreventive
measureforrecurrentovarianendometriosisisunilateraloophorectomywithsp
AcceptedonMay5,2018
aringthecontralateralovary.
Suchaprocedureshouldbeconsideredinwomenwhoarenolongerinterestedinc
Published online on January 15, hildbearingorpresent
2019
withanotherendometrioticcystinthesameovary.Theroleofpharmacotherapyis
fairlylimited;itshould
beconsideredinpatientsinwhomdiffuseendometriosisisassociatedwithpain.
Therapeuticagentsfrom the following groups can be used: estrogen-
progestin preparation, gestagens, including progesterone-
releasingintrauterinesystemsandgonadotropin-
releasinghormoneagonists.Womenwithinfertilityshould
getpregnantassoonasp rs, invitrofertilizationshouldbethetreatmentofchoice.
ossible,andinpatientsw Key words: endometriosis, pharmacotherapy, surgical treatment,
hofailedtogetpregnanta endometrioma
nd/orareolderthan35yea

Cite as
Nowak-
PsiorzI,CiećwieżS,BrodowskaA,Starczew
skiA.
Treatmentofovarianendometrialcystsint
hecontextofre-
currenceandfertility.AdVClinExpMed.201
9;28(3):407–413.
doi:10.17219/acem/90767

DOI
10.17219/acem/90767

Copyright
© 2019 by Wroclaw Medical University

Thisisanarticledistributed
underthetermsofthe
Creative Commons Attribution
Non-Commercial License
(http://creativecommons.org
/licenses/by-nc-nd/4.0/)
Introduction
Endometrialovariancystsareoneofthemorecommongynecological disorders
found in
womenofreproductiveage.Theyarefrequentlythecauseofsurgicalinterventions,und
ertakennotonlybygynecologistsbutalsobypelvicsur-
geons.Therefore,atleastinthiscontext,endometrialovar-
iancystsshouldbeconsideredaninterdisciplinaryproblem.Endometriosis is a
chronicbenignestrogen-
dependentdisease.Itisobservedprimarilyinpatientsofreproduc-
tiveage,anditsprevalenceinthispopulationisestimatedat5–
10%.Endometriosisisdefinedasthepresenceofac-tive endometrial tissue outside
the
uterinecavity,usuallyontheperitoneumoftheminorpelvis,inthemyometrium,ovaries
andfallopiantubes,aswellasextraperitoneally.Endometrioticlesionscanbealsofo
undintheintestines,urinary bladder, lungs, and even in
thebrain.Basedonthelocalizationofthelesions,thediseaseisclassifiedasperiton
1 of,frequentlymassive,solidadhesionsbetweentheovary,
eal,ovarianordeepinfiltratingendometriosis. Etiopathogenesis of endometriosis is
still notfully un-
derstood.Thereareseveraltheoriesontheetiologyofthiscondition.Themostwidelya
cceptedoneisSampson’stheoryaccordingtowhichformationofectopicendome-
trial tissue is a consequence
ofretrogrademenstruation.Duringthisprocess,someoftheendometrialdebrisleavest
heuteruswithsmallvolumesofmenstrualblood,reachesabdominalcavityviathefallopi
2 especiallyinthecaseofrepeatedsurgeries.Moreover,one
antubesandisimplantedintoperitoneum,usuallywithinthepelvis. Furthermore,imm
uneandgeneticfactorsarepostulatedtoplayacrucial
3 sionsthatmayconsiderablyreducethemobilityofthefal-
role in the etiopathogenesis of endometriosis.
The most common manifestations of endometriosisin-
cludepainfulmenstrualperiodswithheavymenstrual bleeding, pelvic pain,
dyspareunia, infertility, and some-
timespainduringvoidingordefecation.Ovarianendome-
triosisisthemostcommonformofthiscondition.Ovarian
endometrialcysts(endometriomas)arefoundin20–55% of women
4
withendometriosis.
Anovarianmasscanbequalifiedasanendometrialcystbasedonitsultrasonographi
cpresentation,usingthecrite-
riathathavebeenpublishedbytheInternationalOvarianTumorAnalysis(IOTA)collabor
5
ationin2013. Thesecrite-
riaincludesize,shape,echogenicityofthelesion,structureofitscapsule,presenceofanyp
rojectionstothecyst’slumen,vasculature, and relationship
withsurroundinganatomicalstructures.Currently,differentialdiagnosisofendometrialc
ystsandovarianmalignanciescanbeconductedpromptlywiththeaidofanonlineapplic
6
ationavailableontheIOTAwebsite. Anotherparameterthatcanbeusedinthedif-
ferentialdiagnosisistheconcentrationofCA-
7 aswellasincasesinwhichinvitrofertilizationisnot
125,whichisusuallyslightlyelevatedinpatientswiththiscondition. Theapproachtoov
arianendometrialcystshaschangedconsiderably during recent
years,especiallyregard-ingthetreatmentofrecurrentendometriosis,fertilityspar-
ingandinfertilitymanagement.Currentrecommendationsofinternationalscientificbod
iesarebasedontheresults
of published meta-analyses and randomized trials.
Watchful waiting
Thereisageneralconsensusthatsmallovarianendo-
metrialcysts,upto3cmindiameter,shouldbeleftun-
1,8
treated. However,2questionsarise:whatisthemaxi-
maldurationoftheexpectantmanagementandshould
itbeconsideredinallpatientswithendometriosis?With
nodoubt,theexpectantmanagementisexcludedinwom-
enwithpelvicpain;insuchcases,surgeryisthetreat-
9
mentofchoice. However,isitthesamewithasymptomatic cases?
Itwasshownthattheformationofovarianendo-
metrialcystresultsinadecreaseinovarianreserve,which
progressesfurtherifthelesionpersistslongerorenlarges.
Thismayimpairfertility,i.e.,duetosignificantlylower
10
ovulationrateandprematuremenopause. Furthermore,
thepresenceofendometrialcystsresultsintheformation
fallopiantubeandbroadligamentoftheuterus,whichalso
decreasethelikelihoodofpregnancy.Allthisdatasup-
portssurgicaltreatment,especiallyinyoungwomenwith
11
infertility. However,surgicaltreatmentisalsoknown
todecreasetheovarianreserve,thuspromotingrepro- ductive aging and
12
accelerating the onset of menopause,
shouldconsidertheriskofpostoperativeadnexaladhe-
lopiantubesorresultintheircompleteobliteration.
Treatment of infertile women above 35 years of age should be discussed
separately. Surgical management
ofsuchpatientswillresultinadecreaseintheiralready
lowovarianreserve.Insuchcases,especiallyinwomen
withadvancedendometriosis,withmechanicalormale
factorinfertility,invitrofertilizationisanefficientop-
13
tion.AccordingtoTsoumpouetal., surgicaltreatment of patients prior to
implementation of assisted reproduc-
tivetechnologies(ART)doesnotimprovetheiroutcomes.
Theonlyexceptionpertainstolargeendometrialcysts that hinder access to
13
ovarianfollicles.
Tosummarize,oneshouldbecautiouswhenconsider-
ingsurgicaltreatmentofsmallovarianendometrialcysts.
Smallasymptomaticcystsshouldnotbetreatedsurgically,
especiallyinpatientsolderthan35years.Surgicaltreat-
mentshouldbeconsideredininfertilewomenandpatients
whofailedtogetpregnantdespite1–1.5yearsoftrials,
8
anoption. Alsolargecysts,withmorethan4cmindi-
ameter,shouldbetreatedsurgicallyduetotheriskoftheir rupture ortorsion.
Surgical treatment
Surgicaltreatmentistheprincipalmethodofendo-
metrialcystmanagement.Theleastefficienttechnique, nowadays considered
mostly obsolete, involves punctur-
ingthecystunderultrasonographicguidanceorduring
laparoscopy,aspirationofitscontents,irrigationand,
whenevernecessary,administrationofasealant.How-
ever,thisprocedurefrequentlyledtocomplications,such
astheformationofabscessesandperitonealadhesions. Moreover,upto80–
90%ofpatientspresentwithrecur-
14
rencealready6monthsaftertheprocedure. Another
surgicalprocedure,stillusedinmanycenters,isacys-
tectomywithirrigationofthelumenofthecystandco-
15
agulationofitscapsule. Bipolarcoagulation,optimally argon
coagulation, or laser coagulation should
16
usedtosparenormalovariantissue. Unfortunately,this
techniquealsodoesnotguaranteethecompletedestruc-
14
tionofthecapsuleofthecyst.SalehandTulandi showed
thatmorethanahalfofpatientspresentedwithrecurrent
cystsasearlyas2yearsaftertheprocedure,and42months
surgerytherecurrencerateincreasedto60%.
Currently,laparoscopyisconsideredthe“goldstandard”
inthemanagementofovarianendometrialcysts.Thelapa-
roscopicprocedureincludesfreeingtheovaryfromadhe-
sions,cystectomy,irrigationofthecyst,andcompleteexci-
sionofitswallwithleastpossibleinjurytonormalovarian
tissue.Bleedingvesselsshouldbecoagulatedwithabipolar
electrode,optimallyusingargonplasmacoagulation.Also,
allotherendometrioticfocipresentinthepelvisshouldbe
17,18
coagulatedcarefullywheneverfeasible. Theabovemen-
tionedtechniqueisassociatedwiththehighestpregnancy rates in patients with
18,19
infertility. Moreover,
movedovariancystcanbesubjectedtoahistopathologic
examination,whichisofvitalimportance,considering
0.9%ofendometriomasturnouttobema-
lignant.Inonestudy,upto13%ofendometriomaswere
20
eventuallyidentifiedasborderlineovariantumors. Theovarian-
sparingtreatmentwithcompleteremoval
ofthecapsuleofthecystresultsinaconsiderabledecrease in the endometrioma
recurrence rate. However, between
10%and40%ofthepatientsmaypresentwithrecurrent
cysts,andtherecurrenceratewasshowntoincreasewith the time elapsed
21,22
sincesurgery.
The severity of endometriosis turnedout to be a key
determinantofsustainedremissionaftersurgicaltreat- ment. The severity of
the disease is determined with
revisedAmericanSocietyforReproductiveMedicine
(rASRM)scoringsystem,andmanypreviousstudies
showedthatthehighertherASRMscoreandseverityofen-
21,23,24
dometriosis,thegreatertheriskofitsrecurrence.
Liuetal.showedthattherASRMseveritygradecorrelates
withtherecurrencerateofendometriosis,butitsprog- nostic value is relatively
25
poor. However, this
isnotsupportedbyalltheauthors.Forexample,Kogaetal.
didnotfindasignificantassociationbetweenthesever-
26
ityofendometriosisanditsrecurrencerate. Yunetal.
analyzedtheroleofvariouscomponentsoftherASRM
scoringsystemaspotentialriskmarkersforrecurrenten-
27
dometriosis. Theyshowedthattheriskofrecurrence
increasesconsiderablyinpatientswithadhesionsinvolving the ovaries
fallopian tubes and/or withcomplete
27
obliterationofthecul-de-sac. Consequently,thepres-
enceofadhesions,especiallyinvolvingadnexaandcul-de-
sac,seemstobeanimportantpredictorofrecurrence.Thishypothesiswasalsoconfirm
24,25,27
edbyotherauthors. Bilateralendometrialcystsaregenerallyconsideredtobe
aprognosticfactorofrecurrence,althoughnotallprevi- ous studies confirmed this
26
relationship. An association between the localization of the cyst and the
risk of re- currenceisunclear.However,theresultsofsomestudies
plasma 28
suggestthatendometriomaslocatedintheleftovaryare morelikelytorecur.
be
Also,theavailabledataonthein-
fluenceofthediameterofthecystontherecurrencerate
isinconclusive.Nevertheless,alargerdiameterofthecyst
isgenerallyconsideredanunfavorableprognosticfac-
21,26,29
tor. However,aminimumdiameterofthelesionasso-
post- ciatedwithunfavorableprognosishasnotbeenestablished
thusfar.Moreover,Ghezzietal.showedthatthediameter
28
ofthecysthasnoinfluenceontherecurrencerate. Simi-
24
larfindingswerealsoreportedbyPorporaetal.
Similarly,noconsensuswasreachedregardingtheinflu-
enceofthepatient’sageontheriskofrecurrence.Accordingto many researchers, young
age has
anunfavorableeffectonthedurationofremissionaftersurgicaltreatment.Thisisprobabl
yrelatedtothefactthatyoungerwomenpresentwith more aggressive forms of
21,25
endometriosisandhigherpostoperativebloodconcentrationsofestrogens. How-
26
ever,Kogaetal. didnotfindanassociationbetweenthepa-
30
there- tient’sageandthedurationofremission,andaccordingtoParazzinietal., theriskofr
ecurrenceincreaseswithage.Pregnancywasshowntoexertabeneficialeffectandtore-
thatca.0.8– ducetheriskofrecurrentendometriosis,andassuchisevenconsideredaprotectivefact
or.Elevatedconcentrationsofprogesteroneinpregnancymayinhibitthegrowthofen-
dometriotic foci and
23,31
attenuaterelatedinflammation. Arelativelylessoftenconsideredprognosticfa
ctorofre-currentendometriosisisthepreoperativelevelofCA-
125.AhighpreoperativelevelofCA-125waspostulatedtopre-
disposetorecurrence.Duetoitslowspecificity,thisanti-
genisnotusefulasadiagnosticmarkerofthedisease,butstillmayplayanimportantr
7
oleinthemonitoringofitstreatment. In turn, no associations
werefoundbetweenthepresenceofuterineleiomyomaoradenomyosisandre-
26
currence rate.
Nowadays,molecularbackgroundofendometriosisisasubjectofongoingres
earch.Consideringtheestro-gen-
dependenceofthedisease,estrogenreceptor(ER),presentin2forms,ER-αandER-
β,wasanobvioustargetofresearch.SomestudiesshowedanassociationbetweenER-
32
αpolymorphismandtheriskofrecurrence. Anotherriskmarkerforrecurrentendom
etriosismaybecyclo-oxygense-2. Increased activity of
thisenzyme,catalyzingsynthesisofprostaglandins,wasobservedinendometrioticlesi
ons in women who later
33
hypothesis presentedwithrecurrence. Themostefficientpreventivemeasureforrecurrento
varian endometriosis is unilateraloophorectomywithsparing the contralateral
ovary. Such a procedureshould
and/or
be considered in women who are no longerinterested
inchildbearingorpresentwithanotherendometriotic
cystinthesameovary.Importantly,theprocedureshould
beextendedtoadhesiolysisandtheremovalofallremain-
34
ingendometrioticfoci.Namnoumetal. demonstrated
thatresidualadhesionsandendometrioticfociareasso- ciatedwithan8-
foldincreaseinreoperationrisk.Hys-
terectomywiththeremovalofadnexacanbeanoption
inperimenopausalwomenwithendometrialcysts,diffuse
peritonealendometriosisordeepinfiltratingendometrio- sis, especially
35
concomitantpain.
Pharmacotherapy
Currently,pharmacotherapyisconsideredtoplayasec-
ondaryroleduringthepostoperativeperiod,andassuch is implemented only in
selected cases. Furthermore, pre-
operativepharmacotherapywasshowntoexertanunfa-
26
vorableeffectonovarianendometrialcysts.Kogaetal.
demonstratedthatpharmacotherapyconstitutesariskfac-
torforpostoperativerecurrence,sincecausingatrophy
andfibrosismayhinderintraoperativeidentificationofall
endometrioticfoci.Insuchcases,resectionismorelikely
26
tobeincompleteandismoretechnicallydemanding.
36
SimilarconclusionswerealsoreportedbyMuziietal.
Moreover,preoperativepharmacotherapywasshowntobe
associatedwithanincreaseintheproportionofdyskariotic
cellsandtoslowdowndevelopmentofeukaryoticcells within the cyst’swall.
Postoperative pharmacotherapy is
recommendedafterincompleteresectionofendometrioticfociorinpatientswith
concomitant pain. Endometriosis isanestrogen-de-
pendentconditionand,therefore,theprincipalaimofphar-
macotherapyistosuppressovarianfunctionandtopro-
motetheatrophyofendometrioticlesions.Therapeuticagentsfromthefollowinggr
oupscanbeused:estrogen-
progestinpreparation,gestagens,includingprogesterone-releasing intrauterine
systemsandgonadotropin-
releasinghormone(GnRH)agonists.Duetoitsmultiplesideeffects,danazol is no
longer
38
recommendedinpharmacotherapyofendometriosis. Frequently,theagentsmention
edabovearesimultaneouslyusedascontraceptives,and,therefore,specificagentssh
ouldbeselectedonanindividualbasiswith their potential side effects
takenintoconsideration.Two-component oral contraceptives playanimpor-
tantroleinthepreventionofrecurrentendometrioticlesionsandtheattenuationof
pain.Beneficialeffectsofthesepreparationsareassociatedwiththeinhibitionofo
vulation.Lessintensivemenstrualbleedingandlackof retrograde menstruation
preventendometrialdebrisspreadingoutsidetheuterus.Furthermore,estroprogestin
contraceptivessuppresstheproliferationofendometri-otic tissue. Their
superiority to
othertherapeuticoptionsisassociatedwiththeirsmallnumberofsideeffects,good
tolerance and reasonable price.
Duetothefrequentuseoforalcontraceptives,their
efficacywasasubjectofmanypreviousstudies.During a24-
39
monthpostoperativefollow-up,Seracchiolietal.
foundrecurrentendometriomasin29%ofwomenwhodid
notuseanycontraceptives,aswellasin14.7%and8.2%
ofpatientswhousedcyclicandcontinuouscontraceptives,
respectively.Thesamegroupshowedthatthediameter
ofrecurrentendometrialcystsinwomenwhousedhor-
monalpreparationswasmarkedlysmallerthaninpatients
with
whodidnotreceivethisformoftherapy.Also,thegrowth
rateofrecurrentlesionsintheformergroupwasreduced.
Themostbeneficialeffectswereobservedinpatientstak-
40,41 42
ingcontinuouscontraceptives. Zorbasetal. com- pared the effects of
continuous and cyclic contraceptives.
Theriskofrecurrenceturnedouttobemarkedlyhigher
inpatientsusingcycliccontraceptives(16.6%)thaninthose
undergoingcontinuoustherapy,probablyduetothefact
thatthelatterresultedinconstantsuppressionofinflam-
42 43
matoryprocesses. Cucinellaetal. analyzedtheefficacy
oforalcontraceptivesdependingonthetypeofprogestin
theycontained.Contrarytootherauthors,theyshowed that the type of progestin
(desogestrel, gestodene, dieno-
gest)exertednoeffectontheefficacyoforalcontraceptives
inthepreventionofrecurrentendometriosis.Incontrast,
theresultsofotherstudiespointtomorebeneficialeffects
ofdienogest,butthismaybeaconsequenceofitssyn- ergy with endogenous
44
estradiol. Surprisingly, however,
45
Muziietal. showedthatpostoperativeadministration oflow-
37 dosecontraceptivesdoesnotexertasignificantef-
45
fectontherecurrencerateofendometriosis, butmayonly
prolongthetimetorecurrence.Theabsenceofsignificant
effectsoftreatmentwithcontraceptivesontherecurrence
26
rateofendometriosiswasalsoreportedbyKogaetal.
However,thelatterauthorsanalyzedtheeffectsofshort- term administration of
oral contraceptives (<12 months) anditisgenerallybelievedthatitisthelong-
termther- apythatshowsthemostevidentbenefits.Furthermore,
theprotectiveeffectoforalcontraceptivesdramatically decreases after their
withdrawal. Consequently, continu-
ationofthetherapyisrecommendeduntilthepatientde- cides to
24,31
getpregnant.
Ofallgestagens,dienogestisusedismonotherapymost
often.Itinhibitsthegrowthofendometrioticfoci,mark-
edlyattenuatespainandrarelyproducessideeffectswhen
44,46
administeredat2mgperday. Theresultsofprevi-
ousstudiessuggestthatdienogesttherapymayalsoresult
47
inalowerrecurrencerateofendometriosis.According toYanaseetal., a6-
monthcyclictherapywiththisge-
stagenafterprevioussurgicaltreatmentofendometriosis
protectsagainsttherecurrenceofthedisease,andthis
protectiveeffectmaylastforapprox.4years.Similarfind-
22
ingswerealsoreportedbyOuchietal.
Alsolevonorgestrel-releasingintrauterinesystemsfound
anapplicationintheadjuvanttreatmentofendometriosis.
Theirprincipaladvantagesincludethepossibilitytoachieve and maintain high local
concentrations oflevonorgestrel
withoutconcomitantsuppressionoftheovary.Thesys-
8
temturnedouttobeparticularlyeffectiveinthecontrol insemination, althoughtheeffectivenessofthelatter
ofpain,butitsroleinthepreventionofrecurrentendo- 59,60
procedureinthissettingisoftenputintoquestion. In patients who failed to
metriosisisputintoquestion.Theonlydocumentedben- get pregnant and in women
48
eficialeffectwasalongertimetorecurrence. Another study compared the 8,59,60
olderthan35years,invitrofertilizationisthetreatment of choice. Surgical
efficacy of a levonorgestrel-releasing intrauterinesystemanddienogest- treatment should be limited sole-
containingoralcontra- ceptives.Whilethelatterturnedouttobemarkedlymore 13
effective in attenuating pain, they were onlyslightly more effective in lytothelargecyststhatmayhinderovarianpuncture,
49 andtothelesionsbeingsuspiciousformalignancybased on their
preventingrecurrence. ultrasonographicappearance.
GnRH analogues are another group of therapeu-
ticsthathavebeentestedfortheirpotentialapplication
inthepreventionofrecurrentendometriosis.Theirben-
eficialeffectswereobservediftheyhadbeenadministered foratleast6monthspost- Take-home message
surgery.However,a3-month
therapyexertedamarkedlylesspronouncedeffectonthere-
Inthispaper,wehavereviewedtheresultsofstudies
currencerates.Asidefromreducingtherecurrencerate,
conductedatvariouscentersovera30-yearperiod,todem-
GnRHanalogueswerealsoshowntoprolongthetimetore-
onstratetheefficacyofthetreatmentforovarianendome-
currence.However,thepotentialsideeffectsofthether- apy need to be
trialcystsinthecontextoftheirrecurrence.Tothebest
emphasized, as it was shown that even a6-
ofourknowledge,thenumberofsimilarreviewsissparse,
50
monththerapywithGnRHanaloguesmaypromote bonedemineralization. althoughsuchpublicationswouldwithnodoubtraise
Aromataseinhibitorsareanovelgroupoftherapeutics. theawarenessoftheappropriatetreatmentforthismost
51 commontypeofendometriosisamonggynecologists,
Alborzietal. comparedtheefficacyofaromataseinhibi-
torsandGnRHanaloguesinthepreventionofrecurrent endometriosis after andwouldsupportthemintheselectionofthemostef-
laparoscopic treatment. Both agents fectivetherapeuticoption.Still,coagulationofthecapsule
wereadministeredfor2months,andthenthepatientswere oftheendometrialcystwiththestate-of-the-artdevices,
followedupforanother12months.Therecurrencerate in patients treated with suchaslasersorplasmaknifes,ispreferredatsomecenters,
aromatase inhibitors was similar withoutconsiderationofrecurrenceratesaftersuchproce-
asinwomenwhoreceivedGnRHanalogues.Surprisingly, dures.Thepublisheddataandourownclinicalexperiences suggest that surgery
asimilarrecurrenceratewasalsoobservedinthecon- trols (patients without any should constitute the primary treat- ment for ovarian endometriosis. The most
pharmacotherapy). However, efficient types ofsurgeryareradicalproceduresinvolvingadhesiolysis,re-
itisthedurationofthetherapywhichprobablyhasacon- siderable effect on movalofthecystalongwithitscapsuleandanyremaining endometriotic foci. The role
itsoutcome. of pharmacotherapy is fairly limited;itshouldbeconsideredinpatientsinwhomdiffuse
endometriosisisassociatedwithpain.Womenwithinfer-
tilityshouldgetpregnantassoonaspossible,andinpa-
tientswhofailedand/orareolderthan35years,invitro
Management of endometrialcysts fertilizationshouldbethetreatmentofchoice.

inwomenwithinfertility
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scoresfromtherevisedAmericanFertilitySocietyClassificationSystem
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28. GhezziF,BerettaP,FranchiM,ParissisM,BolisP,Recurrenceofovar-
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Endometriosi..Determinantsofshorttermrecurrencerateofendo-
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31. GuoSW.Recurrenceofendometriosisanditscontrol.HumReprod
Update.2009;15(4):441–461.
32. LuisiS,GalleriL,MariniF,AmbrosiniG,BrandiML,PetragliaF.Estro-
genreceptorgenepolymorphismsareassociatedwithrecurrence
ofendometriosis.FertilSteril.2006;85(3):764–766.
33. YuanL,ShenF,LuY,LiuX,GuoSW.Cyclooxygenase-2overexpres-
sioninovarianendometriomasisassociatedwithhigherriskofrecur-
rence.FertilSteril.2009;91(4Suppl):1303–1306.
34. NamnoumAB,HickmanTN,GoodmanSB,GehlbachDL,RockJA.
Incidenceofsymptomrecurrenceafterhysterectomyforendome-
triosis.FertilSteril.1995;64(5):898–902.
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maiK,WahabN.Laparoscopichysterectomyversusabdominalhys-
terectomyforseverepelvicendometriosis.IntJGynaecolObstet.
2012;116(2):109–111.
36. MuziiL,MaranaR,CaruanaP,MancusoS.Theimpactofpreoperative
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excisionofovarianendometrioticcysts.FertilSteril.1996;65(6):1235–
1237.
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notimprovepatienthealth.FertilSteril.2004;81(3):487–492.
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2007;17(4):CD000068..
39. SeracchioliR,MabroukM,FrascaC,etal.Long-termcyclicandcon-
tinuousoralcontraceptivetherapyandendometriomarecurrence:
Arandomizedcontrolledtrial.FertilSteril.2010;93(1):52–56.
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agementofendometriosis:Anupdateforclinicians.HumReprod
Update.2006;12(2):179–189.
41. VercelliniP,SomiglianaE,DaguatiR,ViganoP,MeroniF,Crosig-
naniPG.Postoperativeoralcontraceptiveexposureandriskofendo-
metriomarecurrence.AmJObstetGynecol.2008;198(5):504.e1–5.
42. ZorbasKA,EconomopoulosKP,VlahosNF.Continuousversuscyclic
oralcontraceptivesforthetreatmentofendometriosis:Asystemat-
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43. CucinellaG,GraneseR,CalagnaG,etal.Oralcontraceptivesinthepre-
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IntJWomensHealth.2011;3:175–184.
45. MuziiL,MaranaR,CaruanaP,CatalanoGF,MarguttiF,PaniciPB.Post-
operativeadministrationofmonophasiccombinedoralcontracep-
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46. KogaK,TakamuraM,FujiiT,OsugaY.Preventionoftherecurrence
ofsymptomandlesionsafterconservativesurgeryforendometri-
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48. ChoS,JungJA,LeeY,etal.Postoperativelevonorgestrel-releasing
intrauterinesystemversusoralcontraceptivesaftergonadotropin-
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 The Effect of Using Combined Oral Ethinyl Estradiol and
Levonorgestrel in the Resolution of Menstrual Pattern
Disorder and Functional Ovarian Cyst
Najlaa Saadi Ismael* ,Sana Jafar Mohamed** ,Maha Atout*** ,Qutaiba Ahmed Al Khames Aga*
,Sura Yasir Taha Alkhammas****
*Philadelphia University, Faculty of Pharmacy ,Amman, Jordan ,**Alkansa’a Teaching Hospital, Mousl, Iraq,
***Philadelphia University, Faculty of Nursing ,Amman, Jordan ,*Philadelphia University, Faculty of Pharmacy,
****Fifth Year Student, Philadelphia University, Faculty of Pharmacy ,Amman, Jordan
Correspondence: nsaadi@philadelphia.edu.jo

(Ann Coll Med Mosul 2019; 41 (2):190-196).

Received: 7th Oct. 2019; Accepted: 13th Oct.2019.

ABSTRACT
Objectives: To evaluate the usefulness of combined oral contraceptives (ethinyl estradiol and
levonorgestrel) in resolving menstrual pattern disorder in reproductive-age women with a
functional ovarian cyst in Iraq.
Method:A longitudinal (before and after) , interventional study was used. Data were collected
at a single obstetrics and gynaecology outpatient clinic in Mosul City, Iraq. Participants: A
sample of 96 women aged between 15 and 45 years participated in the study. Participants
diagnosed with ovarian cysts were treated using an oral administration of contraceptive pills
(combination of ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg) on a daily basis for
a treatment duration of 2 months. The Outcome Measures are Menstrual pattern disorders
(dysmenorrhea, irregular menstrual cycle, and amenorrhea) and cyst dimensions were
recorded.
Results: After one therapy cycle, a statistically significant disappearance of menstrual pattern
disorder was observed (p=0.000). Cyst resolution was observed in 89.58% of the patients
(n=86), while mean ovarian cyst size fell from 4.452 ± 1.0603 cm at the start of therapy to
0 .451 ± 1.5613 cm(p = 0.000). 5 of the 10 persistent cysts disappeared after the second
cycle (2 months after the start of therapy) and complete cyst resolution was 94.8% (n = 91)
after two cycles. This indicated a further significant reduction of mean ovarian cyst size to
0.335 ± 1.4684 cm. However, no significant difference was observed between mean cyst
size in the first and second months of treatment (p=0.329).
Conclusion: Combined oral contraceptives (ethinyl estradiol and levonorgestrel pills) are
effective in relieving dysmenorrhea, irregular menstrual cycle, and amenorrhea. They also
hasten the disappearance of functional ovarian cysts, and are associated with high rates of
success in patients with functional ovarian cysts.

Keywords:Combined oral contraceptives pill’s, functional ovarian cysts.

D‫ استراديول وليفونورجستريل‬D‫ المركبه إيثينيل‬D‫تأثير استخدام حبوب منع الحمل الفمويه‬

‫في حل اضطراب نمط الحيض واالكيس المبيضي الوظيفي‬
‫ *الطالبة سرى ٍاسر طه‬،‫ قتَبة احمذ الخ َمس اغا‬، ***‫ مها عطعوط‬، **‫ سىاء جعفر محمذ‬، *‫وجالء سع ًذ اسما َعل‬
****‫الخماس‬
‫ جامعة‬،‫ ***كلَة التم ٍرض‬، ‫ العراق‬،‫ موصل‬،‫ **مستشفي الخىساء التع َل ٌم‬، ‫ االردن‬،‫ عمان‬،‫ جامعة فالدلفَا‬،‫صذلة‬ َ ‫*كلَة ال‬
،‫ جامعة فالدلفَا‬،‫صذلة‬
َ ‫كلَة ال‬، ‫ المرحلة الخامسة‬، ****‫ االردن‬،‫ عمان‬،‫ جامعة فالدلفَا‬،‫الصذلة‬
َ ‫ *كلَة‬، ‫ االردن‬،‫عمان‬، ‫فالدلفَا‬
‫ االردن‬،‫عمان‬
 ‫الخالصة‬ ‫ُ‪ٛٛ‬‬
‫ف‬ ‫‪ٚ‬ت انًشكبت )إ ‪ٚ‬ثإ‪ٛ‬ث<ُ ‪ٛ‬مم اسخشاد ٕل ن ٕ‬ ‫حبب يُغ انحًم انفً‬ ‫الهذف مه الذراسة‪ٓ :‬حذف ْ ِز ِز انذساست ٗإن حق ‪ٛ‬ى فائذة ٕ‬
‫ف ‪ٙ‬ف‬ ‫ان ‪ٛ‬ظ ‪ٙ‬‬ ‫بانكس ان ‪ٛ‬ب ‪ٙ‬ع ٕ‬ ‫س اإلَداب انًصاباث ‪ٛ‬‬ ‫فس ٍ‬ ‫انالح ‪ٙ‬‬
‫‪ٙ‬‬ ‫انحط ٖنذ انُساء‬ ‫فف حم اظطشاب ًػ ‪ٛ‬‬ ‫‪ٚ‬‬
‫سخسخش ‪ٚ‬مم( ‪ٙ‬‬ ‫‪ٔٚ‬‬
‫سخسخش ‪ٛ‬ن َٕٕٕفَ<‬
‫انؼشاق‪.‬‬
‫انخ ٕن ‪ٛ‬نذ<‬
‫انخ ٕ‬ ‫خاسخت أليشاض انُساء ٕٔ‬ ‫‪ٛ‬‬ ‫ػادة‬ ‫ف ‪ٛ‬‬ ‫الط ٍرقة‪ :‬حى اسخخذاو دساست غ ‪ٛ‬نت )قبم ٔبؼذ(‪ ،‬حذاخه‪ ٛ‬ت‪ .‬حى ًخغ انب اَاث ‪ٙ‬‬
‫شاسكشاسك ‪ٙ‬ف‬
‫ٍ‬ ‫‪ٛ‬ب ‪ُُ 51 ٔ 51‬ست‬ ‫ْس ب‪<ٍ ٍٛ ٛ‬‬ ‫ػاسْأ ًا‬
‫ػ <ٍْ ٍ‬ ‫يي ‪ 69‬ايشأة حخشٔأذ أ ً‬ ‫ػُت ٍ‬ ‫‪ٙ‬ف يذ ُت ان ٕصم ‪ ،‬انؼشاق‪ .‬انًشاسكاث‪ٛ :‬‬
‫‪ٛ‬‬
‫حبب يُُغ انحًم انفً ‪ٚ‬ت انًشكبت )إ ‪ٛ‬ث ‪ٛ‬م اسخشاد ٕل‬ ‫انذساست‪ .‬حى ػالج انًشاسكاث انًصاباث باألكاس انً ‪ٛ‬ب ‪ٛ‬عت باسخخذاو ٕ‬
‫سخ ‪ٚ‬‬
‫سخشم ‪،‬‬ ‫من َٕٕٕفَ< ‪ٛ‬‬
‫سخش ‪ٛ‬‬ ‫‪ٚ‬‬ ‫سخ‬‫ف ‪ٛ‬‬‫‪ ...0 ،‬يهغ ‪ٛ ٔ ،‬ن ٕ‬
‫انش ‪ٚ‬شت ‪ٛ‬غش انً خظًت ‪ ،‬اَقطاع‬ ‫انحط )ػسش انطًث‪ ،‬ان ٔذسة ٓ‬ ‫يقا ‪ٛ‬س انُُخائح ‪ ْ ٙ‬اظطشاباث ًػ ‪ٛ‬‬ ‫‪ٚ‬ش‪ٚ .‬‬ ‫ش ‪ٚ‬ش ٓش ٍ‪<ٍ ٚ‬‬ ‫‪ ..15‬يهغ( ‪ٛٚ<ٕٕٚٛ‬يي‪ٛ ٛ‬اا نًذة ٓ‬
‫انكس‪.‬‬ ‫حسدم أبؼاد ‪ٛ‬‬ ‫انطًث( ٔحى ‪ٛ‬‬
‫انحط) انق ًت االح ًخ ‪ٛ‬انت = ‪ٕ .(.....‬نحع‬ ‫إحصائت الظطشاب ًػ ‪ٛ‬‬ ‫‪ٛ‬‬ ‫الىتائج‪ :‬بؼذ ٔدسة ػالج ٔاحذة‪ٕ ،‬نحع اخخفاء ٘ر دالنت‬
‫يي ‪ 9.0..5 ± 5.514‬سى ‪ٙ‬ف‬ ‫يخسػ حدى ‪ٛ‬كس انً ‪ٛ‬بط ٍ‬ ‫‪ٛ‬ح اَخفط ٕ‬ ‫ف ‪ٛ‬ح ٍ‪<ٍٛ‬‬ ‫شظ )ػذد= ‪ٙ ، ( 89‬‬ ‫ي انً ٗ‬ ‫ف ‪ٍ ٪ 86.18‬‬ ‫انكس ‪ٙ‬‬ ‫اَحالل ‪ٛ‬‬
‫خ ِد بؼذ ان ٔذسة انثا َ‬ ‫‪ٛ‬‬ ‫‪ٛ‬‬ ‫‪ٚ‬‬
‫يي أصم ‪ .5‬اكاس ٕي ٕ‬ ‫انق ًت االح ًخ انت = ‪ .(.....‬اخخفج ‪ٍ 1‬‬ ‫بذات انؼالج ٗإن ‪ 5.1950 ± .515‬سى) ‪ٛ‬‬
‫س‪ٛ‬ح‪ْ .‬زا ‪ٛ‬شش ٗإن اَخفاض‬ ‫سح ٔد ٍ‪<ٍٛ‬‬‫نهكس ‪) ٪ 65.8‬ػذد = ‪ (65‬بؼذ ٔد ‪ٛ‬‬ ‫‪ٚ‬ش بؼذ بذء انؼالج( كٔاكا ٌ االَحالل انكايم ‪ٛ‬‬ ‫)ش ‪ٚ‬ش ٓش ٍ‪<ٍ ٚ‬‬ ‫‪ٛ‬ت ٓ‬
‫‪ٛ‬‬
‫يخسػ حدى كس‬ ‫كبش ب ٍ‪<ٍ ٛ‬‬
‫‪ٛ‬ب ٕ‬ ‫٘‬
‫يخسػ حدى كس انً ‪ٛ‬بط ٗإن ‪ 5.5985 ± ..100‬سى‪ٔ .‬يغ رنك ‪ ،‬نى ‪ٚ‬الحع أ فشق ‪ٛ‬‬ ‫‪ٛ‬‬ ‫ف ٕ‬ ‫كبش آخش ‪ٙ‬‬ ‫‪ٛ‬‬
‫يي انؼالج) انق ًت االح ًخ ‪ٛ‬انت=‪)923.0‬‬ ‫‪ٙ‬ف األ ٓشش األٔ ٗن انثا ‪ٛ‬ت ٍ‬
‫سخسخش ‪ٚ‬مم فؼانت ‪ٙ‬ف ‪ٛ‬‬ ‫‪ٚ‬‬ ‫‪ٔٚ‬‬
‫سخسخش ‪ٛ‬ن َٕٕٕفَ<‬ ‫حبب يُغ انحًم انفً ‪ٚ‬ت انًشكبت ‪ٚ‬إ ‪ٛ‬ث ‪ٛ‬م اسخشاد ٕل ‪ٛ‬ن ٕ‬
‫حخفف‬ ‫ف‬ ‫االستىتاج‪ :‬حؼخبش ٕ‬
‫ػسش انطًث ‪ ،‬ان ٔذسة انش شت ‪ٛ‬غش انً خظًت ‪ ،‬اَقطاع انطًث‪ً .‬كا أ ٓا حسشع اخخفاء ‪ٛ‬اكاس ان ‪ٛ‬بط ان ظ ‪ٛ‬فت ‪ٔ ،‬حشحبػ‬ ‫‪ٚ‬‬
‫ان ‪ٛ‬ظ ‪ٛ‬فت‪.‬‬‫االكاس انً ‪ٛ‬ب ‪ٛ‬عت ٕ‬ ‫يي ‪ٛ‬‬ ‫‪ٍٛ ٚ‬‬
‫انالح ؼ ا َؼ‪َٛ‬ا<ٍَ ٍ‬
‫‪ٙ‬‬ ‫ف انً ‪ٚ‬شعاث‬ ‫بًؼذالث َداذ ػ ‪ٛ‬انت ‪ٙ‬‬

‫‪ًٕٚ‬ف يشكبيشكبّ ‪ٛ ،‬أكاس ‪ٛ‬يبط ‪ٛ‬ظ ‪ٛ‬فت‪.‬‬

‫حبب يُُغ ًحم فً ّ‪ًّٕ<ٚ‬‬ ‫َ‬
‫المفتاحة‪ٕ :‬‬ ‫الكلمات‬
INTRODUCTION

D ue to the emergence of periodic physical assessments and ultrasonography, the diagnosis of ovarian cysts, which are
classified as fluid-filled sacs located within an ovary containing either a liquid or semiliquid substance, has become a more
straightforward task1,2. Almost all ovarian cysts identified in reproductive-age females are physiological (functional) rather than
pathological, a category which can be subdivided into the following two types: firstly, follicular cysts; and secondly, cystic
corpus luteum3. In pre-and post-menopausal females, Greenlee, Kessel4, found that reports of ovarian cyst prevalence vary
significantly from 8% to 18%, while Grimes, Jones5, identified ovarian cysts as a fundamental gynaecological concern for
reproductive-age females globally.
In terms of the cause of follicular cysts, the evidence indicates that over the menstrual cycle’s early proliferative phase, a
collection of follicles grows in response to the secretion of folliclestimulating hormone and luteinising hormone. In turn, a single
follicle emerges as dominant, continually expanding until it reaches around 2.5 cm to 3.0 cm. In the event that fluids in a follicle
other than the dominant one are not resorbed and continually grow, this is classified as a follicular cyst. As visualised by
ultrasonographic assessment, follicular cysts are characterised by thin walls, their vascular nature, and a single chamber,
which contains anechoic fluid which leads to posterior acoustic enhancement6. Follicular cysts can range from 3cm to 8cm,
and when these cysts grow rapidly, rupture, or haemorrhage, this can produce discomfort and pain. The formation and slow
involution of the corpus luteum takes place 6 weeks after ovulation, the latter process lasting the course of the menstrual cycle
until menstruation. In certain cases, fluid may remain and continue to gather inside the corpus luteum, thus giving rise to a
corpus luteal cyst. According to Dupuis and Kim7 , corpus luteal cysts are dissimilar to follicular cysts in that they are
characterised by comparatively thick, irregular walls.
While public health initiatives such as screening and period physical assessments have improved diagnosis rates for ovarian
cysts, along with the development of ultrasonography2, surgical interventions are necessary for the removal of persistent,
painful, or large cysts, which can in turn lead to oophorectomy5. As noted by Bottomley and Bourne8 , it is worth emphasising
that the majority of ovarian cysts are identified by chance, typically as a result of routine pelvic or ultrasonographic evaluation.
Despite the fact that simple ovarian cysts cannot be considered precursor lesions to malignant ovarian cancer, it is necessary
to conduct effective assessments to confirm the lack of solid or papillary structures prior to the diagnosis of an ovarian cyst as
a simple ovarian cyst. Although progression to malignancy is rare, follow-up examinations are essential9,10.
The combined oral contraceptive pill (COCP), frequently referred to as the birth control pill (or simply “the pill”), contains
small doses of a progestin and an oestrogen-like hormone, comparable to the naturally-occurring progesterone and oestrogen
produced by the female body. The COCP is regularly administered as a preventive agent, and according to some healthcare
professionals, the medication represents an effective treatment agent for ovarian cysts10. Due to this, birth control pills were
introduced into joint clinical practice at the beginning of the 1970s5. As noted by Bottomley and Bourne8, certain ovarian cysts
are linked to both acute and chronic complications, and so the role played by the COCP as a treatment agent for
gynaecological conditions is important to recognise11.
Dysmenorrhea refers to the uncomfortable cramping that originates within the uterus over the course of menstruation. The
condition is a prevalent cause of pelvic pain and menstrual disorder, and it stems from the secretion of prostaglandins which
induce uterine muscle contractions12. In the case of primary dysmenorrhea, the condition is classified as uncomfortable
menses for females with healthy pelvic anatomy, and it typically begins during adolescence. Contrastingly, secondary
dysmenorrhea, which can start long after menarche, is classified as menstrual pain arising from a health condition (e.g., pelvic
inflammatory disease, intrauterine devices, endometriosis, infertility issues, ovarian cysts, adenomyosis, irregular cycles,
uterine myomas, cervical stenosis, or intrauterine adhesions)13. According to Sanghera, Roberts14, certain contraceptive
medications containing hormones are associated with reduction of dysmenorrhea.
The landscape of public health in Iraq, a developing country, is affected by a range of political considerations. Nevertheless,
the literature is scarce in Iraq regarding the utility of combined oral contraceptive administration for the improvement of
menstrual pattern disorder for reproductive-age females suffering from functional ovarian cysts. Therefore, this study evaluates
the usefulness of combined oral contraceptives (ethinyl estradiol and levonorgestrel) in resolving menstrual pattern disorder in
women of reproductive age with a functional ovarian cyst in Iraq.

PATINTS AND METHODS

Design
Alongitudinal(before and after study) interventional study design was adopted to evaluate the usefulness of combined oral
contraceptives(ethinyl estradiol and levonorgestrel) in menstrual pattern disorder for reproductive-age women with a functional
ovarian cyst in Mosul City, Iraq.

Selection and Description of Participants

This study was conducted at a single obstetrics and gynaecology outpatient clinic in Mosul City, Iraq. A convenience sample
comprising 105 reproductive-age females was recruited for the study. Only 96 women were eligible and willing to participate
over the study period, with a response rate of 90%. The inclusion criteria for the participants were as follows:(a) Reproductive
age (15-45 years); (b) Currently suffering from dysmenorrhea, irregular menstrual cycle, or amenorrhea; (c) Diagnosed with
ovarian cysts; (d) No evidence of renal, liver, or cardiovascular disease; (e) Not hypertensive; (f) Not receiving any medication
at the time of the study; and (g) Neither a smoker nor an alcoholic.

Technical Information
Data were collected between 1 December 2017 and 1 December 2018. The participants were recruited during visits to an
obstetrics and gynaecology outpatient clinic in Mosul City, Iraq. The diagnosis of prospective participants’ ovarian cysts took
place over the course of the following phases: firstly, a physical assessment was performed to facilitate a clinical diagnosis;
and secondly, transvaginal ultrasonography was performed as expectant management for two months with no resolution of the
gynaecological issue and no disappearance of the ovarian cyst. Combined oral contraceptive pills(COCPs) containing ethinyl
estradiol(0.03 mg) and levonorgestrel(0.15 mg) were administered on a daily basis for a 2-month period. Over the treatment
duration, patients received baseline (pretreatment) and monthly ultrasonography assessments involving transvaginal
ultrasound to assess changes in size, resolution, or complications.

Ethics
The purpose of the study was explained to each prospective participant in order to ensure voluntary and informed consent.
Further to this, information sheets and recruitment pamphlets relating to the details of the study were distributed during the
meeting. Prospective participants were assured that their participation would have no effect on their treatment, and that they
would not be exposed to harm.

Statistical Analysis
Data were analysed using the Statistical Package for Social Sciences (SPSS) (version 25).
Descriptive statistics were applied to determine the mean and standard deviation (M ± SD) for quantitative data, while non-
parametric variables were expressed as counts and percentages. The McNemar test was used to test significance for non-
parametric variable, while X was used to test significance for quantitative variables. A probability value (p value) of less than
0.05 was considered statistically significant.

RESULTS
Table 1 provides an overview of the participants’ demographic characteristics. The participants, all female, were aged 15-45
(30.75 ± 8.36). Most participants were married (90.6%), relatively few were single (7.3%), and only 2.1% were widowed.
Additionally, the majority of the detected cysts were simple and unilateral with mean 4.45 ± 1.06.
Table 1: Participants’ demographic characteristics
Total participants (n = 96)
Mean ± SD
Age (Years)
30.75 ± 8.36

Marital status (count and percentage)

Single 7 (7.3%)
Married 87 (90.6%)

Widowed 2 (2.1%)

As shown in Table 2, cysts were categorised based on their size, revealing that most (n = 72) were unilateral with a diameter
of 3-5 cm. 24 cysts were more than 5 cm in diameter.

Table 2: Characteristics of ovarian cystsby age group.

Location
Age Unilateral/ Group Size (cm)
Bilate
ral
Laterality
Right left 3-5cm > 5cm
15-25 7 18 19 6
years

26-36 10 31 31 10
years

37-45 16 13 1 22 8
years

Total 33 62 1

Table 3: Effect of oral contraception on gynaecological condition.

Gynaecological Before After P

Condition reatment Treatmen value
t
Dysmenorrhea 43 1 0.000*
(44.8%) (s)
amenorrhea 36 (37.5%) 1 0.000*(s)
Irregular 63 1 0.000*
Menstrual (65.6%) (s)
cycle
* McNemar test
The mean difference is significant at the 0.05 level
Forty three participants (44.8%) presented with dysmenorrhea, 36 (37.5%) had menorrhea, and 63 (65.6%) suffered from
irregular menstrual cycles. All participants received medical treatment with COCPs (containing ethinyl estradiol, 0.03 mg, and
levonorgestrel, 0.15 mg) table 3 .
After a single therapy cycle, a statistically significant disappearance was observed for menstrual pattern disorder (including
dysmenorrhea, irregular menstrual cycle, and amenorrhea) (p = 0.000). Ovarian cyst resolution was observed in 86 (89.58%)
of the 96 patients Table 4 .
Table 4: Disappearance rates of functional ovarian cysts in management in patients for terminal period
Outcome Count and Percentage

Disappearance after
one therapy cycle 86 (89.58%)

Disappearance after
two therapy cycles 5 (5.2%)

Persistence of cyst 5 (5.2%)

Mean ovarian cyst size dropped from 4.452 ± 1.0603 cm at the start of therapy to 0.451 ± 1.5613 after therapy (p = 0.000). 5
of the 10 persistent cysts disappeared after the second cycle (2 months after start of therapy), and complete cyst resolution
was observed for 91 participants (94.8%) after two cycles. The mean significant reduction for ovarian cysts was 0.335 ± 1.4684
cm. However, no significant difference was observed between mean cyst sizes in the first and second months of
treatment(p=0.329) Tables 5, 6, and 7 .

Table 5: Difference in ovarian cyst size before and after one month of treatment

Ovarian Cyst Size Mean ± SD Number of Patients (96)

P value
Ovarian Cyst 4.452 ±
Size Before Treatment 1.0603
Ovarian Cyst Size 0.000*
(s)
After One Month 0.451 ±
of Treatment 1.5613

Based on estimated marginal means *The mean difference is significant at the 0.05 level
Adjustment for multiple comparisons: Bonferroni.

Table 6: Difference in ovarian cyst size before and after two months of treatment

Ovarian Cyst Size Mean ± SD Number of Patients (96)

P value
Ovarian Cyst Size 4.452 ±
Before Treatment 1.0603
Ovarian Cyst Size
0.000
After Two Months 0.335 ±
of Treatment 1.4684

Based on estimated marginal means * The mean difference is significant at the 0.05 level
Adjustment for multiple comparisons: Bonferroni

Table 7: Difference in ovarian cyst size before and after one and two months of treatment,
respectively

Ovarian Cyst Size Number P value of Patients (96)

Mean ± SD
Size of Ovarian Cyst 0.329
After One Month of 0.451 ±
Treatment 1.5613

Size of Ovarian Cyst 0.335 ±

After Two Month of 1.4684
Treatment

Based on estimated marginal means *The mean difference is significant at the 0.05 level
Adjustment for multiple comparisons: Bonferroni For the 5 cysts which were persistent after 2 months of COCP treatment,
surgical intervention was undertaken using an open technique (laparotomy) or a minimally invasive technique (laparoscopy).
Small incisions were applied, and in the course of operating, pathological cysts were identified in each case.

DISCUSSION
It is well-documented that due to the administration of COCPs, cyst incidence has fallen. This is because COCPs suppress
ovulation, thus meaning that eggs are not released from the ovaries12. With this in mind, healthcare professionals began to
treat cysts with COCPs, understanding that this would hasten the disappearance of the condition 5. It is also worth noting that
because COCP administration abbreviated mean cyst duration, they could be used as valuable pharmacological agents in
managing accompanying menstrual conditions15. According to Bottomley and Bourne8, it is possible to safeguard against
recurrent cyst rupture or haemorrhage with COCPs administration, and early COCPs were lnked to a lower incidence of
functional ovarian cysts16.
The evidence shows that morbidity and quality of life fall and rise, respectively, with the use of COCPs. One of the principal
ways to account for this finding is that COCPs reduce the incidence of ovarian cysts, and as such, prevent the emergence of
painful conditions such as menstrual cramps, menstrual bleeding issues, ovulation pain, and endometriosis symptoms(e.g.,
pelvic pain). As emphasised by Brynhildsen 17, COCPs can be used to treat dysmenorrhea, hirsutism, and acne vulgaris. More
specifically, the levonorgestrelreleased intrauterine system is a reversible way in which to treat dysmenorrhea and
menorrhagia14. This study’s findings are also consistent with Cochrane reviews addressing the impact of COCPs on functional
ovarian cyst resolution. The reviews reported that no significant differences could be observed between therapeutic
interventions in functional ovarian cysts and no intervention, noting that cyst resolution occurs spontaneously in almost all
case, irrespective of treatment. Nevertheless, it is worth emphasising that these trials included relatively small sample sizes,
and a high level of heterogeneity was observed5,16.
Consistent with Bernardi M ea al 12, this study attests to the statistically significant impact that COCPs administration has on
dysmenorrhea, irregular menstrual cycle, and amenorrhea in reproductive-age females suffering from functional ovarian cysts.
As reported elsewhere in the literature, COCPs bring rapid relief and regulatory benefits to the pain associated with
menstruation, including irregular bleeding and uncomfortable periods, and they can be used to treat symptomatic menorrhagia
and primary dysmenorrhea11,18,19. The results presented in this study are in agreement with this evidence, and at the same
time, show that COCPs can hasten the complete resolution of functional ovarian cysts. However, it is worth noting that several
months of watchful waiting could be necessary for the achievement of similar success rates, and this could represent a viable
alternative to oral contraceptive therapy. In addition, surgical evaluation of persistent ovarian cysts is essential.
This study’s limitations, including its use of the convenience sampling technique and the method used to estimate the
sample size, could have affected the generalisability of the findings to other settings. Therefore, future studies should be
pursued in which larger sample sizes are utilised. At the same time, probability sampling techniques should be employed to
ensure that the study population is representative of the target population. Finally, to determine whether statistically significant
differences exist between watchful waiting of cysts and active pharmacological intervention in cyst development through COCP
administration, future studies should consider employing control groups in the context of a randomised controlled trial.

CONCLUSION
Combined oral contraceptives (ethinyl estradiol and levonorgestrel pills) are effective in relieving dysmenorrhea, irregular
menstrual cycle, and amenorrhea. They also hasten the disappearance of functional ovarian cysts, and are associated with
high rates of success in patients with functional ovarian cysts.

DECLARATION OF INTEREST
Statement
The research has no conflict of interest and is not funded from any source.

Acknowledgments
The authors wish to express their profound gratitude to the women who participated in this study who so willingly gave their
time and were crucial to the data collection process. This study would not have been possible without their cooperation.

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8.Bottomley C, Bourne T. Diagnosis and management of ovarian cyst accidents. Best practice & research Clinical obstetrics &
gynaecology. 2009;23(5):711-24.
9.Glanc P, Benacerraf B, Bourne T, et al. First International Consensus Report on Adnexal Masses: Management
Recommendations.
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2017;36(5):849-63.
10.Grimes DA, Jones LB, Lopez LM, et al. Oral contraceptives for functional ovarian cysts. The Cochrane database of
systematic reviews. 2011(9):Cd006134.
11.Carey MS, Allen RH. Non-contraceptive uses and benefits of combined oral contraception. The Obstetrician &
Gynaecologist. 2012;14(4):223-8.
12.Bernardi M, Lazzeri L, Perelli F, et al.Dysmenorrhea and related disorders. F1000Research. 2017;6:1645-.
13.Unsal A, Ayranci U, Tozun M, et al. Prevalence of dysmenorrhea and its effect on quality of life among a group of female
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menorrhagia: an economic evaluation alongside a randomised controlled trial. PLoS One. 2014;9(3):e91891.
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16.Grimes DA, Jones LB, Lopez LM, et al. Oral contraceptives for functional ovarian cysts. The Cochrane database of
systematic reviews. 2009(2):Cd006134.
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18.Latthe P, Mignini L, Gray R, et al. Factors predisposing women to chronic pelvic pain: systematic review. BMJ (Clinical
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Ultrasound Obstet Gynecol 2017; 50: 20 – 31

Published online 7 June 2017 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.16002

Outcome of fetal ovarian cysts diagnosed on

prenatal ultrasound examination: systematic
review and meta-analysis
F. BASCIETTO1, M. LIBERATI1, L. MARRONE1, A. KHALIL2, G. PAGANI3, S. GUSTAPANE1,
M. LEOMBRONI1, D. BUCA1, M. E. FLACCO4, G. RIZZO5, G. ACHARYA6,7, L. MANZOLI4 and
F. D’ANTONIO6,7
1
Department of Obstetrics and Gynaecology, SS. Annunziata Hospital, G. D’Annunzio University of Chieti-Pescara, Chieti,
Italy; 2Fetal
Medicine Unit, St George’s University of London and St George’s University Hospitals NHS Foundation Trust, Molecular and
Clinical Sciences Research Institute, London, UK; 3Department of Obstetrics and Gynaecology, Fondazione Poliambulanza,
Brescia, Italy;
4
Department of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy; 5Department of Obstetrics and
Gynaecology,
University of Rome, Rome, Italy; 6Women’s Health and Perinatology Research Group, Department of Clinical Medicine,
Faculty of Health Sciences, UiT – The Arctic University of Norway, Tromsø, Norway; 7Department of Obstetrics and
Gynaecology, University Hospital of Northern Norway, Tromsø, Norway

KEYWORDS: fetal ovarian torsion; outcome; ovarian cysts; ultrasound

Methods The electronic databases MEDLINE and

ABSTRACT
Objective To explore the outcome of fetuses
with a prenatal diagnosis of ovarian cyst.
EMBASE were searched using keywords and
word vari- ants for ‘ovarian cysts’, ‘ultrasound’ and
‘outcome’. The following outcomes in fetuses with
a prenatal diagnosis of ovarian cyst were
explored: resolution of the cyst, change of
ultrasound pattern of the cyst, occurrence of
ovarian torsion and intracystic hemorrhage, need
for postnatal surgery, need for oophorectomy,
accuracy of
prenatalultrasoundexaminationincorrectlyidentifyi
ng ovarian cyst, type of ovarian cyst at
histopathological analysis and intrauterine
treatment. Meta-analyses using individual data
random-effects logistic regression and meta-
analyses of proportions were performed. Quality
assessment of the included studies was
performed using the Newcastle– OttawaScale.
ResultsThirty-
fourstudies(954fetuses)wereincluded. In 53.8%
(95% CI, 46.0 – 61.5%) of cases for which
resolution of the cyst was evaluated (784
fetuses), the cyst regressed either during
pregnancy or after birth. The likelihood of
resolution was significantly lower in
complexvssimplecysts(oddsratio(OR),0.15(95%C
I,
0.10–0.23))andincystsmeasuring40mmvs<40mm
≥ ajor
(OR, 0.03 (95% CI, 0.01– 0.06)). Change in
ultrasound pattern of the cyst was associated
with an increased
riskofovarianloss(surgicalremovalorautoamputati
on) (pooled proportion, 57.7% (95% CI, 42.9 –
71.8%)).
Theriskofovariantorsionwassignificantlyhigherfor
Correspondence to: Prof. F. D’Antonio, Women’s Health and Perinatology Research Group, Department of Clinical
Medicine, Faculty of Health Sciences, UiT – The Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø,
Norway (e-mail: francesco.dantonio@uit.no)
Accepted: 10 June 2016
cystsmeasuring 40 mm compared with <40
≥ mm(OR,
30.8 (95% CI, 8.6 – 110.0)). The
likelihoodofhavingpostnatalsurgerywashigherin
≥ patients with
cysts40mmcomparedwith<40mm(OR,64.4(95%C
I,
23.6–
175.0))andincomplexcomparedwithsimplecysts,
irrespective of cyst size (OR, 14.6 (95% CI, 8.5–
24.8)).
Incasesundergoingprenatalaspirationofthecyst,rat
eof recurrence was 37.9% (95% CI, 14.8–
64.3%), ovarian
torsionandintracystichemorrhagewerediagnoseda
fter birth in 10.8% (95% CI, 4.4 – 19.7%) and
12.8% (95% CI, 3.8 – 26.0%), respectively, and
21.8% (95%CI,
0.9 – 40.0%) had surgery after birth.
ConclusionSizeandultrasoundappearancearethem
determinantsofperinataloutcomeinfetuseswithova
rian cysts. Copyright 2016 ISUOG. Published
by John Wiley &SonsLtd.
INTRODUCTION
Ovariancystsarethemostcommonabdominalanoma- lies
diagnosed in female fetuses, with an estimated incidence of
1
about 1 in 2600 pregnancies . Although the pathophysiology of
ovarian cysts has not yet been elucidated fully, they are usually
a benign functional
anomalyresultingfromexcessivestimulationofthefetal ovaries by
placental and maternal hormones. They are common in
pregnancies complicated by maternal dia- betes, pre-eclampsia
or rhesus isoimmunization. They are diagnosed most often
during the third trimester,
especiallyafter28weeks’gestation1,2.Ovariancystsare
categorized according to their sonographicappearance
Fetalovariancysts 21

into the following two groups: (1) simple cysts, which are usually anechoic, information on the population was included to avoid overlapping populations.
round, unilocular and thin walled,mea- suring >2 cm, and (2) complex cysts, For those articles in which information was not reported but the methodology
which are usually thick walled and heterogeneous, containing hyperechoic was such that this information would have been recorded
components, free-floating material or intracystic septa- tions, and are initially,theauthorswerecontacted.Onlyfull-textarticles were considered eligible
commonly considered the result of ovarian torsion or intracystichemorrhage 3. for the inclusion. Case reports,
Optimal management of fetal ovarian cysts is unclear and the evolution of conferenceabstractsandcaseserieswithfewerthanthree
this anomaly is variable. Although the majority regress either during casesofsuspectedovariancyst,irrespectiveofwhetheror not the anomaly was
pregnancy or after birth,torsionandhemorrhagecanoccurantenatally,thus isolated, were also excluded inorder to avoid publicationbias.
increasingtheriskofsurgicalinterventionandovarianloss after birth. Prenatal Quality assessment of the included studies was performed using the
aspiration of the cyst is performed Newcastle– Ottawa Scale (NOS). According to the NOS, each study is
occasionally,especiallyinthecaseoflargelesions,inorder judged on three broad perspectives: selection of the study groups,
topreventintrauterinetorsion,whichmayleadtoovarian autoamputation or the comparability of the groups and ascertainment of the outcome of interest 6.
need for oophorectomy. However, whether this improves neonatal outcome Assessment of the selection of a study includes evaluation of the
in these fetuses is yet to be established. Furthermore, the accuracy of representativeness of the exposed cohort, selection of the non-exposed
antenatalultrasoundexaminationincorrectlyidentifying cohort, ascertainment of exposure and demonstration that the outcome of
fetalovariancystsisunknown.Gastrointestinal,renaland genital anomalies are interest was not present at the start of the study. Assessment of the
commonly misdiagnosed asovarian cysts2. It is yet to be ascertained whether comparability of the study includes evaluation of the comparability of cohorts
the ultrasound appearance of the cyst can predict the postnatal outcome or on the basis of the design or analysis. Finally, ascertainment of the outcome
be used to guide prenatal management in thesecases. of interest includes evaluation of the type of assessment of the outcome of
The aim of this systematic review was to explore the outcome of fetuses interest, and length and adequacy of follow-up 6. According to the NOS,
with prenatally diagnosed ovarian a study can be awarded a maximum of one star for each numbered item
cystsandtoquantifytheaccuracyofantenatalultrasound examination in correctly within the Selection and Outcome categories and a maximum of two stars
identifying theseanomalies. can be given for Comparability.
The incidence of the following outcomes was analyzed in fetuses with a
prenatal diagnosis of an ovarian cyst: resolution of the cyst in utero or after
birth; change of ultrasound pattern from simple to complex cyst; occur-
SUBJECTS AND METHODS renceofovariantorsionandintracystichemorrhage;need for postnatal surgery;
ovarian loss due to oophorectomy or salpingo-oophorectomy; false-positive
Protocol, eligibility criteria, information sources rate of prenatal ultrasound diagnosis; histopathological type of ovarian
and search cyst;andintrauterinetreatment.Casesundergoingprena-
talintervention(cystaspiration)wereevaluatedseparately in terms of: resolution
This review was performed according to an a-priori protocol of the cyst, recurrence of the cyst,
recommended for systematic reviews and meta-analyses4. The electronic increaseincystsizeafteraspiration,changeofultrasound pattern after
databases MEDLINE and EMBASE were searched on 11 February 2016 intervention, evidence of torsion or hem- orrhage after intervention or at birth,
utilizing combinations of relevant medical subject heading terms, keywords need for surgery and preterm delivery or miscarriage due to the invasive
and word variants for ‘ovarian cysts’, ‘ultra- procedure.
sound’and‘outcome’(TableS1).Thesearchandselection All of these outcomes were assessed in the overall population of fetuses
criteriawererestrictedtotheEnglishlanguage.Reference with a prenatal diagnosis of an ovarian cyst. Furthermore, a subanalysis
listsofrelevantarticlesandreviewswerehand-searched for additional according to the appearance (simple vs complex) and size (<40 mm vs 40
reports. PRISMA guidelines were mm) of the cyst was carried out. Cyst size of 40mmwasusedasthecut-
followed5.ThestudywasregisteredwiththePROSPERO database offasthishasbeencommonly reported in the literature to represent the highest
(registration no.CRD42016035594). centile of cystsize.
≥ ascertainment of data on resolution and change in ultrasound
For
appearance of the cyst, the anomalies were
categorizedaccordingtotheirfirstultrasoundappearance and size, and the
Study selection, data collection and prevalence and risks of torsion, hemorrhage, surgery and need for
data items oophorectomywere

Twoauthors(F.B.andL.Mar.)independentlyreviewedall abstracts. Agreement

regarding their potential relevance was reached by consensus; full-text
copies of eligible papers were obtained and the same two authors
independently extracted relevant data regarding study characteristics and
pregnancy outcome. Inconsistencies were discussed by the two authors and
a consensus reachedordiscussedwithathirdauthor.Ifmorethanone study was
published for the same cohort with identical
endpoints,thereportcontainingthemostcomprehensive
22
ascertained from the postnatal ultrasound examination or, if not available, the
last scan in pregnancy.
Cases that underwent cyst aspiration in utero were analyzed separately
and were not included in the main analyses. Preterm delivery or miscarriage
was considered to be caused by fetal therapy if it occurred within 15 days of
the intervention.
Only studies reporting a prenatal diagnosis of ovarian cyst were
considered suitable for inclusion in the current systematic review. Postnatal
studies or studies from which cases diagnosed prenatally could not be
extracted were excluded. Pediatric and surgical series including only
symptomatic cases or patients undergoing surgical treatment were also
excluded. Studies published before the year 2000 were not included, as we
considered that the advances in prenatal imaging techniques and the
improvements in diagnosis and definition of fetal anomalies made these
studies less relevant. Finally, studies not providing clear classification of the
anomaly were not considered suitable for inclusion in the currentreview.
Statistical analysis
Thestrengthofassociationbetweenultrasoundcharacter-
isticsofthecystandeachobservedoutcomewasexplored. For quantification of
the incidence of these outcomes, meta-analyses of proportions using a
random-effects model were used to combine data. Funnel plots display- ing
the outcome rate from individual studies vs their precision (1/standard error)
were carried out with an exploratory aim (data not shown). Tests for funnel-
plot asymmetry were not used when the total number of pub- lications
included for each outcome was less than 10. In this case, the power of the
test is too low to dis- tinguish chance from real asymmetry 7–10. Between-
study heterogeneity was explored using the I2 statistic, which
representsthepercentageofbetween-studyvariationthat is due to
heterogeneity rather thanchance10.
Furthermore, we evaluated separately the association between ovarian
cyst type (complex or simple) and size ( 40 mm or <40 mm) and six
clinical outcomes (change of ultrasound pattern (simple cysts becoming
complex),≥ cyst resolution, torsion, hemorrhage,postnatal surgery, ovarian
loss or oophorectomy). We stratified the meta-analyses, exploring
combinations of cyst type and size, thus performing a total of eight direct
comparisons for each of the outcomes (excluding change of ultrasound
pattern): (1) complex vs simple cysts, (2) all cysts40 mm vs <40 mm, (3)
simple cysts 40 mmvs <40 mm,
(4)complexcysts ≥ 40mmvs<40mm,(5)complexcysts 40 mm
vssimple cysts 40 mm, (6) complexcysts
≥ ≥
<40 mm vssimple cysts 40 mm, (7) complex cysts 40 mm vs
≥
simple cysts <40 mm and (8) complexcysts
≥ ≥
<40 mm vs simple cysts <40 mm.≥
We included observational cohort studies inwhich:
(1) many comparisons reported zero events in onegroup,
(2) several comparisons reported zero eventsinboth
groupsand(3)exposedandunexposedgroupsizeswere
Bascietto et al.
frequentlyseverelyunbalanced.Insuchcases,manyofthe most commonly used
meta-analytical methods,including
thoseusingriskdifference(whichcouldbeusedtohandle total zero-event
studies), can produce biased estimates when events are rare 11,12. When
many studies are also substantiallyunbalanced,thebestperformingmethodsare
the Mantel – Haenszel odds ratio (OR) without zero-cell continuity
corrections, logistic regression and an exact method 13,14. Mantel – Haenszel
ORs cannot be computed in studies reporting zero events in both groups, the
exclusion of which may, however, cause a relevant loss of information and
the potential inflation of the magnitude of the pooled exposure effect 11.
Therefore, to keep all studies in the analyses, we performed all meta-
analyses using individual data random-effects logistic regression, with single
study as the cluster unit. The pooled datasets with individual data were
reconstructed usingpublished
2 2×tables. When one of the overall pooled arms showed no event, we used
exact logistic regression.
As a likely consequence of non-randomization, dissim- ilarity of the
populations and lack of fixed criteria for when to treat, several of the
comparisons showed an
extremeimbalanceinthesuccessratebetweenthegroups being compared (e.g.
44/67 vs 0/69). In addition to the
computationalissues,insuchcasestheORsmaybeoflim- ited interest and
sensitivity, and specificity may be more informative. We thus computed the
overall sensitivity and specificity (and related 95% CI) for each compari-
sonaccordingtotheefficient-scoremethod(correctedfor continuity) described
byNewcombe14.
All analyses were performed using Stata version 13.1 (2013; Stata Corp.,
College Station, TX, USA).
RESULTS
Study selection and characteristics
A total of 1483 articles were identified, of which
52 were assessed for eligibility for study inclusion (Table S2). Thirty-four
studies including a total of 954 fetuses with a prenatal diagnosis of
ovarian cysts were included in the systematic review (Table 1 and
Figure1) 15–48 .
Quality assessment of the included studies was performed using the NOS
for cohort studies (Table 2). Most of the included studies showed an overall
good quality with regard to selection and comparability of the study groups
and ascertainment of the outcomes of interest. The main weaknesses of the
studies were their retrospectivedesign,smallsamplesizeandlackofdetailed
ultrasound characteristics of the cysts in some of the includedstudies.
Synthesis of results
Resolution of the cyst
Twenty-ninestudiesincluding784fetuseswithaprenatal diagnosis of ovarian
cyst evaluated resolution of thecyst.
 Fetalovariancysts 23

Table 1 Characteristics of studies on fetuses with prenatally diagnosed ovarian cysts included in systematic review

GA at Cy
Imaging technique
Study Fet diagnosis st Age Age
Study Countr u (weeks)* diam at at
y design Prenatal s eter surge follow-
Postnatal e (mm)* ry* up*
s
(n
)
Catania (2016) 15 Italy Ret US US, 2 33 (22 to NS NS 5
ro MRI 5 39)
y
Thakkar (2015)16 UK Ret US US 3 NS NS NS N
ro 4 S
Nakamura Japan Ret US US 3 32 (22 to 47 (17– NS N
(2015)17 ro 3 37) 79) S
Marchitelli France Ret US US, 1 NS NS NS N
ro MRI 7 S
18
(2015)
Ac¸ıkgo¨z(2015)19 Turkey RetroUS US,MRI 17 30±6.4 39.8±13.4 NS NS
Jwa (2015)20 Japan Retr US,MRIUS 21 33.9 (29.9 to 37 (15– 52) 1 day to 4 NS
o 36.9) mo
Papic (2014)21 UK Retr US US 25 NS 55.1 (24 – 12 (3 – 64) NS
o 150) wk
Karakus¸ Tur R U U 3 33.1
28.4 ±to3.2
(23 37) 41.5(10– NS 3 mo
(2014)22 key etr S S 7 60) 2 – 4 mo 2 – 9 mo
Turgal (2013) 23 Tur o 2 40.9 (11–
9 to 39 + 2) 90)
key R U U
etr S S
o
Amari (2013)24 German Retr US NS 35 32 + 0 (14 NS NS NS
y o +6
Dimitraki Greece Retr US US 16 32.4 (30 to 37.7 (21– 1 mo 3 – 12
Nemec (2012)28 Austria Re US, MRIUS 1 31+2(23+0 NS NS N
to 35+5) tro 6 S 3y
Noia (2012)29 Italy US US 32 (27 to36) 46 (31– NS 6y
Re 1 74) 2
tro 3 mo
to
32 + 4)
Aqrabawi Jor R US US 1 NS 30 – 100 NS 1
(2011)30 dan etr US US 2 34 (32 53.0 (25– 1– mot
Akin (2010)31 Tur o US US 1 to38) 80) 23days
days o 11.6) y
(1.3–
Zampieri Italy Re US US, 5 34 (32 to 50.0 (27– NS 1– 5 y
(2008)34 tro MRI 7 37) 75)
Godinho Portugal Re US US 5 31 +35)6 (29 38.3 (29 – 10– 11 NS
(2008)35 tro to 60) days
Shimada Japan Re US US 1 Third 46.6 (23 – Within 10 mo 2 mo
(2008)36 tro 6 trimester 75)
Monnery-Noche´ France Re US US 6 33 (24 43.5 (17– 3 (0 – 119) 3 mo
(2008)37 tro 5 to39) 130) days (11 days to
Galinier (2008)38 France US US 6 y)
Re 7 32 (26 43.5 (20 – NS 11 mo
tro 9 to39) 90)
(6 mo to 10
Kwak (2006)39 South Re US US 1 34 (30 to 49 (33 – 1 day to 3 y)
Korea tro 7 38) 78) wk 1– 24 mo
Foley (2005)40 Australia Re US US 1 Second to 39.6 (7– 7– 8 mo 12.9 mo
tro 1 third 70)
trimester (3 mo to 6 y)
Enr´ıquez Spain Re US, US, 1 33 to 37 24 – 112 NS 3 – 15 mo
(2005)41 tro MRI MRI 8
Comparetto Italy Re US US 3 34 (32 to 27– 75 NS 1– 5 y
tro 2 37)
(2005)42
Quarello France Re US US 1 3 N NS NS
(2003)43 tro 2 1 S
± GA, gestational age; mo, months; MRI, magnetic
Only first author of each study is given. *Median (range), range, mean or mean SD.
resonance imaging; NS, not stated; Prosp, prospective; Retro, retrospective; US, ultrasound; wk, weeks; y, years.

About half of all cysts resolved during pregnancy orafter birth (pooled thansimplecystsorcystsmeasuring<40mm,respectively (Table3).
proportion (PP), 53.8% (95% CI,
46.0 – 61.5%)) (Figure 2a). Resolution of the cyst occurred in 69.4% (95%
CI, 59.0 – 79.0%) of simple cysts and in 84.8% (95% CI, 70.0 – 95.2%) of
cysts measuring <40 mm. The proportions of cases with resolution of the
cyst according to size and ultrasound appearance are reported in Table S3.
Complex cysts(OR,
0.15 (95% CI, 0.10– 0.23)) and cysts measuring ≥ 40 mm
(OR,0.03(95%CI,0.01–0.06))werelesslikelytoregress
Change of ultrasound pattern, ovarian torsion
and intracystic hemorrhage
More than 20% (PP, 23.6% (95% CI, 14.4– 34.4%))
of all simple cysts demonstrated a change in ultrasound pattern to that of a
complex cyst during pregnancy or at birth (Figure 2b). The risk of change
in ultrasound pattern during pregnancy was significantly higher in cysts 40
mm compared with those <40 mm (OR, 3.16 (95% CI, 1.02 – 9.7); I2 , 0%).
In those cases, the occurrence of ovarian loss, either due to surgical
removal or ovarian autoamputation, was high (PP, 57.7% (95% CI, 42.9 –
71.8%); I2,7.1%). ≥
24 Bascietto et al.

Table 2 Quality assessment of studies in systematic review

Identification

Records identified through database

Additional records identified through according to Newcastle– Ottawa Scale

search othersources Author Selection Outcome Comparability

(n = 1477) (n = 6)
15
Catania (2016)
Thakkar (2015)16
Recordsafterduplicatesremoved Nakamura (2015)17
(n = 1483) Marchitelli
Screening

(2015)18Ac¸ıkgo¨z(2
015)19Jwa (2015) 20
Papic (2014)21
Records screened Recordsexcluded Karakus¸ (2014) 22
(n = 1483) (n = 1431)
Turgal(2013)23
Amari(2013)24
Dimitraki (2012)25
Eligibility

Full-text articles excluded, with Gaspari (2012) 26

Full-text articles assessed for
Lecarpentier (2012)27
eligibility reasons
(n = 52) (n = 18) Nemec (2012)28
Noia (2012)29
Aqrabawi (2011)30
Akin (2010)31
Studiesincludedin
Eleftheriades (2010)32
qualitative synthesis
(n = 34) Ben-Ami(2010)33
Zampieri (2008)34
Included

Godinho(2008) 35
Studies included in quantitative synthesis Shimada(2008)36
Monnery-Noche´ (2008)37
(meta-analysis) Galinier (2008)38
(n = 34)
Kwak(2006)39
Foley(2005)40
Enr´ıquez (2005)41
Figure 1 Flowchart of inclusion of studies in systematic review. Comparetto (2005)42
Quarello (2003)43
Mittermayer (2003)44
The overall incidence of ovarian torsion of the cyst was 21.8% (95% Heling (2002)45
CI, 15.2– 29.2%) (Figure 2c).The
Bagolan(2002)46
corresponding values for torsion in simple and complex cysts were 6.0%
(95% CI, 3.6 – 8.9%) and 44.9%(95% Perrotin(2000)47
CI, 31.7– 58.4%), respectively (Table S4). The risk of ovarian torsion was Luzzatto (2000)48
significantly higher in cysts 40 mm compared with those <40 mm,
≥ Only first author of each study is given. A study can be awarded a
irrespective of their ultrasound appearance (OR, 30.8 (95% CI, 8.6 – 110.0))
(Table 4). Furthermore, risk of torsion was significantly higher for complex maximum of one star for each numbered item within Selection and
cysts than for simple cysts (OR, 59.1 (95% CI, 24.7– 141.0)). Outcome categories and a maximum of two stars for
Intracystic hemorrhage occurred in 6.8% (95% CI, Comparability.
3.7 – 10.8%) of cases (Figure 2d, Table S5). The risk of
hemorrhage was significantly higher for complex vs sim-
ple cysts (OR, 28.6 (95% CI, 4.9 –∞ )), for cysts ≥ 40 mm The likelihood of having surgery was higher in patients with cysts 40 mm
vs <40 mm (OR, 31.7 (95% CI, 3.7– 270.0)) and for compared with <40 mm (OR, 64.4 (95% CI, 23.6 – 175.0)) and in complex
cysts compared with simple cysts, irrespective of the cyst size (OR, 14.6
simple cysts ≥ 40 mm vs <40 mm (OR, 63.4 (95% CI, (95% CI, 8.5– 24.8)) (Table 6).
10.7– ∞)) (Table5). Ovarianloss,duetooophorectomyorsalpingo-oophor- ectomy, occurred in
25.1% (95% CI, 17.2– 34.0%) of cases that underwent surgery (Figure 2f,
Table S7). Both complex cysts (OR, 35.1 (95% CI, 17.0– 72.7))and
cysts 40 mm (OR, 58.9 (95% CI, 19.2– 181.0)) were
Surgery significantly associated with an increased risk of ovarian loss (Table 7).
Thirty studies including 761 fetuses with a prenatal diag- nosis of ovarian
cyst explored the incidence of postnatal surgery. Overall, 39.5% (95% CI,
30.1– 49.3%) of fetuses with a prenatal diagnosis of ovarian cysts
confirmed at birth had surgical intervention (Figure 2e). The cor- responding
Intrauterine treatment
values in fetuses with simple and complex ovarian cysts were 24.6% (95%
Twelve studies including 56 fetuses that underwent intrauterine aspiration of
CI, 14.2– 36.9%) and
the cyst were included in the systematic review. After aspiration of the cyst,
64.8% (95% CI, 52.2– 76.3%), respectively (TableS6). the inci- dence of recurrence was 37.9% (95% CI, 14.8– 64.3%),
 Fetalovariancysts 25

(a) Study n/N

Thakkar
Nakamura 0.74(0.56–0.87) 25/34
Marchitelli 0.55(0.36–0.73) 17/31
Catania 0.12(0.01–0.36) 2/17
Açıkgöz 0.30(0.13–0.53) 7/23
Jwa 0.36(0.13–0.65) 5/14 (b) Study n/N
Papic 0.64(0.35–0.87) 9/14
Nakamura 0.10(0.01–0.30) 2/21
Turgal 0.31(0.11–0.59) 5/16
0.90(0.68–0.99) 18/20 Jwa 0.20(0.03–0.56) 2/10
Karakuş
0.71(0.54–0.85) 27/38 Papic 0.25(0.03–0.65) 2/8
Amari
0.51(0.34–0.69) 18/35 Turgal 0.00(0.00–0.23) 0/14
Dimitraki
Gaspari 0.94(0.71–1.00) 16/17 Karakuş 0.04 (9.4E-4–0.19) 1/27
Nemec 0.60(0.15–0.95) 3/5 Dimitraki 0.00 (0.00–0.26) 0/12
Aqrabawi 0.31(0.11–0.59) 5/16 Gaspari 0.20 (5.1E-3–0.72) 1/5
Akin 1.00(0.63–1.00) 8/8
Nemec 0.00(0.00–0.31) 0/10
Eleftheriades 0.17(0.04–0.41) 3/18
0.86(0.42–1.00) 6/7 Akin 0.36(0.13–0.65) 5/14
Ben-Ami 0.07 (1.7E-3–0.32) 1/15 Eleftheriades 0.00(0.00–0.52) 0/5
Zampieri 0.58(0.44–0.71) 33/57 Ben-Ami 0.71(0.42–0.92) 10/14
Godinho 0.60(0.15–0.95) 3/5 Godinho 0.40(0.05–0.85) 2/5
Shimada 0.63(0.35–0.85) 10/16 Shimada 0.27(0.06–0.61) 3/11
Galinier 0.44(0.33–0.55) 36/82
Monnery-Noché 0.39(0.25–0.54) 19/49
Kwak 0.63(0.38–0.84) 12/19
Foley 0.27(0.06–0.61) 3/11 Galinier 0.51(0.37–0.65) 28/55
Enríquez 0.61(0.36–0.83) 11/18 Kwak 0.21(0.05–0.51) 3/14
Comparetto 0.50(0.32–0.68) 16/32 Foley 0.73(0.39–0.94) 8/11
Mittermayer 0.72(0.59–0.83) 42/58 Mittermayer 0.04 (9.4E-4–0.19) 1/27
Heling 0.53(0.40–0.66) 34/64 Bagolan 0.21(0.09–0.38) 7/34
Bagolan 0.42(0.30–0.54) 28/67
Luzzatto 0.44(0.22–0.69) 8/18
Luzzatto 0.63(0.42–0.81) 17/27
Combined 0.54(0.46–0.62) 420/784 Combined 0.24(0.14–0.34) 102/364
0.0 0.2 0.4 0.6 0.8 1. 0.00 0.24 0.48 0.72 0.96
0
Proportion (95% CI) Proportion (95% CI)

(c) Study n/N (d)

Nakamura 0.13 (0.04–0.30) 4/31 Study n/N
Catani 0.56(0.30–0.80) 9/16 Catani 0.00 (0.00–0.21) 0/16
a 0.14(0.02–0.43) 2/14 a 0.07 (1.8E-3–0.34) 1/14
Açıkgöz 0.69(0.39–0.91) 9/13 Açıkgöz 0.00(0.00–0.25) 0/13
Papic 0.15(0.02–0.45) 2/13 Turgal 0.00(0.00–0.09) 0/38
Turgal 0.03(6.7E-4–0.14) 1/38 Karakuş 0.00(0.00–0.23) 0/14
Karakuş 0.07(1.8E-3–0.34) 1/14 Dimitraki 0.00(0.00–0.52) 0/5
Dimitraki 0.20 (5.1E-3–0.72) 1/5 Gaspari 0.17(0.02–0.48) 2/12
Gaspari 0.08(2.1E-3–0.38) 1/12 Nemec 0.00(0.00–0.37) 0/8
Nemec 0.00(0.00–0.37) 0/8 Aqrabawi 0.06 (1.4E-3–0.27) 1/18
Aqrabawi 0.28(0.10–0.53) 5/18
Akin Akin 0.00(0.00–0.41) 0/7
0.14(3.6E-3–0.58) 1/7
Eleftheriades Eleftheriades 0.00 (0.00–0.15) 0/22
0.18(0.05–0.40) 4/22
Ben-Ami Ben-Ami 0.18(0.09–0.30) 10/57
0.11(0.04–0.22) 6/57
Zampieri Zampieri 0.40(0.05–0.85) 2/5
0.00 (0.00–0.52) 0/5
Godinho Godinho 0.21(0.05–0.51) 3/14
0.21(0.05–0.51) 3/14
Shimada Shimada 0.06(0.02–0.15) 4/67
0.54(0.41–0.66) 36/67
Monnery-Noché Monnery-Noché 0.06(0.02–0.14) 5/82
0.39(0.28–0.50) 32/82
Galinier Galinier 0.00(0.00–0.20) 0/17
0.24(0.07–0.50) 4/17
Kwak Kwak 0.00(0.00–0.28) 0/11
0.09(2.3E-3–0.41) 1/11
Foley Foley
0.12(0.01–0.36) 2/17 0.00(0.00–0.20) 0/17
Enríquez Enríquez
Comparetto 0.19(0.07–0.36) 6/32 0.31(0.16–0.50) 10/32
0.20(0.10–0.34) 10/50 Comparetto 0.04 (4.9E-3–0.14) 2/50
Mittermayer
0.11(0.04–0.24) 5/46 Mittermayer 0.17(0.08–0.31) 8/46
Heling
0.45(0.32–0.57) 29/65 Heling 0.00(0.00–0.06) 0/65
Bagolan
0.22(0.15–0.29) 174/674 Bagolan 0.07(0.04–0.11) 48/630
Combined
Combined
0.00 0.24 0.48 0.72 0.96 0.0 0.3 0.6 0.9

Proportion (95% CI) Proportion (95% CI)

(e) Study n/N (f)

0.14 (0.02–0.43) 2/14 Study n/N
Thakkar
Nakamura 0.45(0.27–0.64) 14/31 Nakamura 0.10(0.02–0.26) 3/31
Marchitelli 0.13(0.02–0.40) 2/15 Jwa 0.00(0.00–0.23) 0/14
Catania 0.81(0.54–0.96) 13/16 Papic 0.54(0.25–0.81) 7/13
Açıkgöz 0.29(0.08–0.58) 4/14 Turgal 0.15(0.02–0.45) 2/13
Jwa 0.36(0.13–0.65) 5/14
Karakuş 0.08(0.02–0.21) 3/38
Papic 0.85(0.55–0.98) 11/13
Turgal 0.15(0.02–0.45) 2/13 Dimitraki 0.07(1.8E-3–0.36) 1/14
Karakuş 0.29(0.15–0.46) 11/38 Gaspari 0.40(0.05–0.85) 2/5
Amari 0.12(0.01–0.36) 2/17 Nemec 0.17(0.02–0.48) 2/12
Dimitraki 0.07(1.8E-3–0.34) 1/14 Aqrabawi 0.00(0.00–0.37) 0/8
Gaspari 0.40(0.05–0.85) 2/5 Akin 0.78(0.52–0.94) 14/18
Nemec 0.25(0.05–0.57) 3/12
Aqrabawi Eleftheriades 0.14(3.6E-3–0.58) 1/7
0.00(0.00–0.37) 0/8
Akin 0.83 (0.59–0.96) 15/18 Ben-Ami 0.09(0.01–0.29) 2/22
Eleftheriades 0.14(3.6E-3–0.58) 1/7 Zampieri 0.00(0.00–0.06) 0/57
Ben-Ami 0.32(0.14–0.55) 7/22 Godinho 0.20 (5.1E-3–0.72) 1/5
Zampieri 0.42(0.29–0.56) 24/57 Shimada 0.50(0.23–0.77) 7/14
Godinho 0.40(0.05–0.85) 2/5 Monnery-Noché 0.46(0.34–0.59) 31/67
Shimada 0.50(0.23–0.77) 7/14
0.96(0.87–0.99) 64/67 Galinier 0.34(0.24–0.45) 28/82
Monnery-Noché
Galinier 0.48 (0.36–0.59) 39/82 Kwak 0.29(0.10–0.56) 5/17
Kwak 0.41(0.18–0.67) 7/17 Foley 1/11
0.09(2.3E-3–0.41)
Foley 0.18(0.02–0.52) 2/11 Enríquez
0.41(0.18–0.67) 7/17
Enríquez 0.41(0.18–0.67) 7/17 Comparetto
0.50(0.32–0.68) 16/32
Comparetto 0.50(0.32–0.68) 16/32 Mittermayer
Mittermayer 0.26(0.15–0.40) 13/50 0.26(0.15–0.40) 13/50
Heling
Heling 0.65(0.50–0.79) 30/46 0.26(0.14–0.41) 12/46
Bagolan
Bagolan 0.45(0.32–0.57) 29/65 0.43(0.31–0.56) 28/65
Luzzatto
Luzzatto 0.30(0.14–0.50) 8/27 0.30(0.14–0.50) 8/27
0.39(0.30–0.49) 343/761 Combined
Combined 0.25(0.17–0.34) 194/685
0.6 0.8 1.0 0.00 0.24
0.0 0.2 0.4 0.48 0.72 0.96
Proportion(95%CI) Proportion (95%CI)

Figure 2 Pooled proportions for: (a) resolution of cyst; (b) change of ultrasound pattern in cyst from simple to complex; (c) ovarian torsion;
(d) intracystic hemorrhage; (e) postnatal surgery; and (f) ovarian loss, in fetuses with ovarian cysts. n/N, numbers of cysts.
 26 Bascietto et al.

Table 3 Pooled odds ratios (ORs) for likelihood of resolution of fetal ovarian cyst, according to cyst size and/or ultrasound appearance

Stud Fetuses Sensitivity* Specificit

ies y*
Variable (n) (n/N vs n/N) Pooled P (%) (%)
OR
Complex vs simple cysts 20 68/224 vs 0.15 <0.0 58.6 77.3
231/341 (0.10 – 01 (52.5 – (72.0 –
0.23) 64.6) 81.8)
Cysts ≥ 40 mm vs cysts <40 mm 16 60/192 vs 0.03 <0.0 87.4 71.3
149/168 (0.01 – 01 (80.8 – (64.6 –
0.06) 92.1) 77.2)
Simple cysts ≥ 40 mm vs <40 mm 16 45/134 vs 0.02 <0.0 84.8 75.7
140/156 (0.00 – 01 (76.1– (68.7 –
0.06) 90.8) 81.5)
Complex cysts ≥ 40 mm vs <40 mm 9 17/54 vs 25/28 0.06 <0.0 92.5 59.5
(0.01 – 01 (78.5 – (43.3 –
0.21) 98.0) 74.0)
Complexcysts≥40mmvs simplecysts≥40mm 11 19/60vs42/83 0.40 0.02 50.0 68.9
2
(0.18 – 0.88) (38.8 – (55.6 –
61.2) 79.8)
Complexcysts<40mmvssimplecysts≥40mm 11 26/30vs39/73 4.93 0.01 10.5 60.0
5
(1.36– (3.0 – (47.1–
17.8) 25.7) 71.7)
Complex cysts ≥ 40 mm vs simple cysts <40 12 20/62 vs 71/83 0.04 <0.0 77.8 78.0
mm (0.01 – 01 (64.1– (67.9 –
0.12) 87.5) 85.7)
Complex cysts <40 mm vs simple cysts <40 11 26/30 vs 64/74 0.56 0 25.6 71.1
mm (0.09 – . (9.6 – (60.5 –
3.38) 5 58.0) 79.9)
Values in parentheses are 95% CI. *Computed for reverse outcome ‘no resolution’.

Table 4 Pooled odds ratios (ORs) for likelihood of ovarian torsion in fetuses with ovarian cyst, according to cyst size and/or ultrasound
appearance

Fetuses Sensitivity Specificit

y
Variable Studies (n/N vs n/N) Pooled P (%) (%)
(n) OR
Complex vs simple cysts 19 139/253 vs 59.1 <0.0 95.2 67.3
7/242 01
(24.7 – (90.0 – (62.1–
141.0) 97.9) 72.2)
Cysts ≥ 40 mm vs cysts <40 mm 13 45/116 vs 30.8 <0.0 93.8 62.4
3/121 (8.6 – 01 (81.8 – (55.1–
110.0) 98.4) 69.3)
Simple cysts ≥ 40 mm vs <40 mm 12 14/82 vs 1/123 26.7 0.002 93.3 64.2
(3.3 – (66.0 – (56.9–
214.0) 99.7) 70.9)
Complex cysts ≥ 40 mm vs <40 mm 9 37/61 vs 16.2 <0.0 92.5 55.6
3/33 (4.3 – 01 (78.5 – (41.5–
61.6) 98.0) 68.8)
Complex cysts ≥ 40 mm vs simple cysts ≥ 40 9 37/61 vs 82.0 <0.0 97.4 61.9
mm 1/40 (9.1–∞)*
(19.3– 01 (84.6 – (48.8–
743.0) 99.9) 73.6)
Complex cysts <40 mm vs simple cysts ≥ 40 9 3/35 vs 1.8
0.6 60.0 52.9
mm 2/38 (0.2 – (17.0– (45.0–
Values in parentheses are 95% CI. *Exact logistic regression as no logistic regression model was possible due to zero events in reference
group. ∞, infinity.

whereas an increase in cyst size occurred in 6.9% (95% CI,2.0–

14.5%)ofcases.Almosthalfofthecystsaspirated in utero did not recur, either False-positiverateofprenataldiagnosis
during pregnancy or after birth (PP, 48.9% (95% CI, 25.0 – 74.0%)). and histopathologicalassessment
Change of
ultrasoundpatterninthecystafteraspiration,fromasim- Thefalse-positiverateofprenatalultrasoundexamination detecting fetal ovarian
pletocomplexappearance,occurredin7.9%(95%CI, cysts was 7.5% (95%CI,
2.6 – 15.8%) of cases, whereas ovarian torsion and intra- cystic hemorrhage 4.4–11.4%).Ofthesecaseswithmisdiagnosisofovarian cyst, almost half
were diagnosed after birth in 10.8% (95% CI, 4.4 – 19.7%) and 12.8% (95% were gastrointestinal anomalies (PP, 54.1%(95%CI,28.1–
CI, 3.8 – 26.0%) of the treated cases, respectively. The rate of preterm 78.9%)).Furthermore,urogenital
delivery or miscarriage due to the invasive procedure was 5.1% (95% CI, andrenalanomalieswerediagnosedincorrectlyasovarian cysts in 14.9% (95%
CI, 6.6 – 25.6%) and 10.3% (95% CI,4.0–
0.7– 13.0%; 1/44; I 2, 0%) and 21.8% (95%CI,0.9–
19.1%)ofcases,respectively(TableS8).
40.0%)hadsurgeryafterbirth(Table8and Figure3).
Histopathological assessment of the ovarian cyst following surgery was
available for 385 cases. The majority of cysts were either follicular or theca
lutein (93.0% (95% CI, 87.7– 96.8%)), and cystadenoma and
 Fetalovariancysts 27

Table 5 Pooled odds ratios (ORs) for risk of intracystic hemorrhage in fetuses with ovarian cyst, according to cyst size and/or ultrasound
appearance

Studi Fetuses Sensitivit Specificity

es y
Variable ( (n/N vs n/N) Pooled P (%) (%)
n OR
)
Complex vs simple cysts 1 19/210 vs 28.6 <0.0 100 51.8
7 0/205 01
(4.9 – ∞)* (79.1– (46.7 –
100) 56.8)
Cysts ≥ 40 mm vs cysts <40 mm 1 2/15 vs 0/35 3
2.8 0.0 100 72.9
2 1 02 (82.0 – (57.9–
100) 84.3)
.
7
(0.6–∞)*
(3.7–
270.0)
Simple cysts ≥ 40 mm vs <40 mm 1 20/70 vs 0/115 63.4
(0.0–∞)* <0.0 100 69.7
0 01 (80.0 – (62.0 –
100) 76.5)
(10.7–
∞)*
Complex cysts ≥ 40 mm vs <40 mm 7 5/44 vs 1/26 (1.7–∞)*
0.4 83.3 39.1
(0.3 – (36.5 – (27.4 –
28.5) 99.1) 52.1)
Complex cysts ≥ 40 mm vs simple cysts ≥ 40 7 5/44 vs 0/28 4.6 0.16 100 41.8
Values in parentheses are 95% CI. *Exact logistic regression as no logistic regression model was possible due to zero events in reference
group. ∞, infinity.

Table 6 Pooled odds ratios (ORs) for likelihood of postnatal surgery in fetuses with ovarian cyst, according to cyst size and/or ultrasound
appearance

Stud Fetuses Sensitivity

ies
Specificity
Variable (n) (n/Nvsn/N) PooledOR P (%) (%)
Complex vs simple cysts 22 197/290vs77/292 14.6 <0.0 71.9 69.8
01
(8.5 – 24.8) (66.1–77.1) (64.3–
74.8)
Cysts ≥ 40 mm vs cysts <40 mm 15 96/138vs9/140 64.4 <0.0 91.4 75.7
(23.6 – 01 (83.9–95.8) (68.5–
175.0) 81.8)
Simple cysts ≥ 40 mm vs <40 mm 14 67/90vs1/133 3998 <0.0 98.5 85.2
(233– 01 (91.0–99.9) (78.4–
68626) 90.2)
Complex cysts ≥ 40 mm vs <40 mm 11 56/75vs7/42 48.8 <0.0 88.9 64.8
(10.4– 01 (77.8–95.0) (50.6–
229.0) 77.0)
Complex cysts ≥ 40 mm vs simple cysts ≥ 40 11 58/75 vs23/48 17.7 <0.0 71.6 59.5
mm (4.4 – 01 (60.3–80.8) (43.3–
71.3) 74.0)
Complex cysts <40 mm vs simple cysts ≥ 40 11 7/44vs23/46 0.2 0.016 23.3 38.3
mm (0.1– 0.8) (10.6–42.7) (26.4–
51.8)
Complex cysts ≥ 40 mm vs simple cysts <40 13 61/80 vs1/72 2015 <0.0 98.4 78.9
mm (71.0– 57 01 (90.2–99.9) (68.8–
179) 86.5)
Complex cysts <40 mm vs simple cysts <40 12 7/48vs1/70 45.3 0.040 87.5 80.5
mm
(1.2– 1722) (46.7–99.3) (74.3–
85.5)
Values in parentheses are 95% CI.

teratoma were diagnosed in 2.1% (95% CI, 0.9 – 3.7%) outcome and are associatedwithanincreasedriskofovariantorsion,
and 1.5% (95% CI, 0.5– 2.9%) of cases, respectively (Table S9).

DISCUSSION
Main findings
The findings from this systematic review showed that a large proportion of
fetal ovarian cysts regress either during pregnancy or after birth. Simple cysts
may change in ultrasound appearance during pregnancy and become
complex, which is associated with an increased risk of ovarian loss. The size
and appearance of the cyst are the major determinants of perinatal
intracystic hemorrhage and need for oophorectomy. The false-positive rate
of prenatal ultrasound examination in the detection of fetal ovarian cysts is
low, although it is not uncommon for gastrointestinal, renal and urogenital
anomalies to be misdiagnosed as ovarian cysts. The very small number of
included cases precluded extrapolation of robust evidence on the value of
intrauterine treatment of ovarian cysts.

Strengths and limitations

Thesmallnumberofcasesinsomeoftheincludedstudies, their retrospective
non-randomized design, different periodsoffollow-
up,dissimilarityofthepopulations(due to various inclusion criteria) and lack of
fixed criteria for whentotreatandpostnatalconfirmationrepresentthe
 28 Bascietto et al.

Table 7 Pooled odds ratio (OR) for likelihood of ovarian loss at surgery (due to oophorectomy or salpingo-oophorectomy) in fetuses with ovarian
cyst, according to cyst size and/or ultrasound appearance

Stud Fetuses Sensitivity

ies
Specificity
Variable (n) (n/Nvsn/N) PooledOR P (%) (%)
Complex vs simple cysts 20 139/263vs17/276 35.1 <0.00 89.9 67.6
1
(17.0– 72.7) (82.9–93.3) (62.4–
72.2)
(13.8– ∞)*
Cysts ≥ 40 mm vs cysts <40 mm 15 76/138vs5/140 58.9 <0.00 93.8 68.5
(19.2– 1 (85.6–97.8) (61.5–
181.0) 74.8)
Simple cysts ≥ 40 mm vs <40 mm 13 26/84vs0/129 80.3 <0.00 100 69.0
1 (84.0–100) (61.8–
75.4)
Complex cysts ≥ 40 mm vs <40 mm 10 42/62vs4/38 21.8 <0.00 91.3 63.0
(5.8 – 1 (78.3–97.2) (48.7–
81.9) 75.4)
Complexcysts≥40mmvssimplecysts≥40mm 10 42/62vs10/62 (500.0 – ∞)*
35.0 <0.00 80.8 72.2
(5.93 – 1 (67.0–89.9) (60.2–
206.0) 81.8)
Complex cysts <40 mm vs simple cysts ≥ 40 10 4/40vs10/40 1.6 0 28.6 45.5
mm (0.2 – . (9.6–58.0) (33.3–
Values in parentheses are 95% CI. *Exact logistic regression as no logistic regression model was possible due to zero events in reference
group. ∞, infinity.

Table 8 Pooled proportions (PPs) for different outcomes in fetuses with ovarian cyst treated prenatally

Outcome Studies Fetuses Raw proportion I2 PP (%)

(n) (n/N) (%) (%
)
Recurrence of cyst 1 19/56 33.93 (21.8– 7 37.88 (14.8–
2 47.8) 4 64.3)
Resolution of cyst 1 31/56 55.36 (41.5– 7 48.86(25.0–
2 68.7) 0 73.0)
Increase of cyst size 1 2/56 3.57 (0.4 – 12.3) 0 6.90 (2.0 –
2 14.5)
Change of ultrasound pattern of cyst from simple to 1 2/56 3.57 (1.0– 12.1) 0 7.90 (2.6 –
complex 2 15.8)
Ovarian torsion 1 4/56 7.14 (2.0 – 17.0) 0 10.83 (4.4 –
2 19.7)
Intracystic hemorrhage 1 5/56 8.93 (3.0 – 19.6) 35. 12.78 (3.8 –
2 3 26.0)
Surgery 1 9/56 16.07 (7.6 – 40. 21.81 (0.9 –
2 28.3) 5 38.0)
Preterm birth or miscarriage 6 1/44 2.27 (0.1– 12.0) 0 5.10 (0.7 –
13.0)
Values in parentheses are 95% CI.

major limitations of this systematic review. Assessment of the potential

publication bias was also problematic because of the nature of the outcome
evaluated (outcome rates, with the lefthand side limited to a value of zero),
which limits the reliability of funnel plots, and because of the small number of
individual studies, which strongly limits the reliability of formaltests.
Most of the observed outcomes were reported in only a limited
proportion of the included studies.
Furthermore,wecouldnotstratifytheanalysisaccording to different cut-offs for
cyst size in view of the fact that the majority of these were reported in
only a few studies, thus considerably limiting the interpretation of the results.
The ascertainment of some of the outcomes observed, such as surgery or
need for oophorectomy, was also considerably biased by the different
postnatal managementstrategiesadoptedindifferentcenters.Large lesions
usually undergo surgical intervention,irrespective of the presence of
symptoms, in order to reduce the risk of complications, such as torsion and
hemorrhage, which may lead to ovarian loss. In this scenario, the results
from this systematic review may have overestimated some of the adverse
outcomes associated with ovarian cysts.
The assessment of the role of intrauterine therapy was also problematic.
Ovarian cysts usually regress during pregnancy and, thus, the role of in-utero
cyst aspiration in preventing the occurrence of torsion or hemorrhage
couldnotbequantifiedcompletely.Furthermore,thevery
smallnumberofincludedcases,differentgestationalages
atintervention,timepointsatpostnatalfollow-upandlack of ascertainment
according to cyst size and appearance did not allow us to draw any
conclusion on the role of prenatal cyst aspiration in the management of
ovarian cysts. Therefore, an adequately powered randomized control trial is
needed in order to ascertain the value of prenatal cystaspiration.
Despitetheselimitations,thepresentreviewrepresents the best published
estimate of the investigated outcomes in fetuses diagnosed with
ovariancysts.
Implications for clinical practice
Prenatal and postnatal management of fetal ovarian cysts
ischallenging.Theevidenceissparseandisderivedmainly
frompostnatalseriesreportinghighratesofcomplications
andneedforsurgicalintervention.Thefindingsfromthis
systematicreviewshowedthatultrasoundappearanceand
Fetalovariancysts 29

(a)

Study n/N (b) Study n/N

Catani 1.00(0.16–1.00) 2/2 Catania 0.00(0.00–0.81) 0/2

a 0.00(0.00–0.71) 0/3 Açıkgöz 0.67(0.09–0.99) 2/3

Açıkgö 0.00(0.00–0.41) 0/7 Jwa 1.00(0.59–1.00) 7/7

z 0.67(0.38–0.88) 10/15 Noia 0.33(0.12–0.62) 5/15

Jwa 1.00(0.03–1.00) 1/1 Nemec 0.00(0.00–0.98) 0/1

Noia 0.50 (0.07–0.93) 2/4 Galinier 0.00(0.00–0.60) 0/4

Nemec 1.00(0.03–1.00) 1/1 Kwak 0.00(0.00–0.98) 0/1

Galinier 0.00(0.00–0.98) 0/1 Enríquez 0.00(0.00–0.98) 1/1

Kwak 1.00(0.16–1.00) 2/2 Mittermayer 0.00(0.00–0.84) 0/2

Enríquez 0.33(8.4E-3–0.91) 1/3 Heling 0.33 (8.4E-3–0.91) 1/3

Mittermayer 0.00(0.00–0.23) 0/14 Bagolan 0.86(0.57–0.98) 12/14

Heling 0.00(0.00–0.71) 0/3 Perrotin 1.00(0.29–1.00) 3/3

Bagolan 0.38(0.15–0.64) 19/56 Combined 0.49(0.25–0.73) 31/56

Perrotin 0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00
Combined Proportion (95% CI) Proportion (95% CI)

(c)
Study n/N (d) Study n/N
Catania
0.00(0.00–0.84) 0/2 Catania 0.00(0.00–0.84) 0/2
Açıkgöz
0.67 (0.09–0.99) 0/3 Açıkgöz 0.00(0.00–0.71) 0/3
Jwa
0.00(0.00–0.41) 0/7 Jwa 0.00(0.00–0.41) 0/7
Noia
0.07 (1.7E-3–0.32) 1/15 Noia 0.00(0.00–0.22) 0/15
Nemec
0.00(0.00–0.98) 0/1 Nemec 0.00(0.00–0.98) 0/1
Galinier
0.00(0.00–0.60) 0/4 Galinier 0.00(0.00–0.60) 0/4
Kwak 1/1
0.00(0.00–0.98) 0/1 Kwak 1.00(0.03–1.00)
Enríquez 0/1
0.00(0.00–0.98) 0/1 Enríquez 0.00(0.00–0.98)
Mittermayer 0/2
0.00(0.00–0.84) 0/2 Mittermayer 0.00(0.00–0.84)
Heling 0/3
0.33(8.4E-3–0.91) 1/3 Heling 0.00(0.00–0.71)
Bagolan 0/14 1/14
0.00(0.00–0.23) Bagolan 0.14(0.02–0.43)
Perrotin 0/3 0/3
0.00(0.00–0.71) Perrotin 0.00(0.00–0.71)
Combined 2/56 2/56
0.07(0.02–0.15) Combined 0.08(0.03–0.16)
0.0 0.2 0.4 0.6 0.8 1.0 0.00 0.25 0.50 0.75 1.00
Proportion (95% CI) Proportion (95% CI)

(e) Study n/N (f) Study n/N

Catani 0.00(0.00–0.84) 0/2 Catani 0.00(0.00–0.84) 0/2

a 0.00(0.00–0.71) 0/3 a 0.67(0.09–0.99) 2/3

Açıkgö 0.00(0.00–0.41) 0/7 Açıkgö 0.00(0.00–0.41) 0/7

z 0.13(0.02–0.40) 2/15 z 0.00(0.00–0.22) 0/15

Jwa 0.00(0.00–0.98) 0/1 Jwa 0.00(0.00–0.98) 0/1

Noia 0.00(0.00–0.60) 0/4 Noia 0.00(0.00–0.60) 0/4

Nemec 0.00(0.00–0.98) 0/1 Nemec 1.00(0.03–1.00) 1/1

Galinier 0.00(0.00–0.98) 0/1 Galinier 1.00(0.03–1.00) 1/1

Kwak 0.00(0.00–0.84) 0/2 Kwak 0.00(0.00–0.84) 0/2

Enríquez 0.00(0.00–0.71) 0/3 Enríquez 0.00(0.00–0.71) 0/3

Mittermayer 0.14(0.02–0.43) 2/14 Mittermayer 0.07 (1.8E-3–0.34) 1/14

Heling 0.00(0.00–0.71) 0/3 Heling 0.00(0.00–0.71) 0/3

Bagolan 0.11(0.04–0.20) 4/56 Bagolan 0.13(0.04–0.26) 5/56

Perrotin 0.0 0.2 0.4 0.6 0.8 1.0 Perrotin0.00 0.25 0.50 0.75 1.00
Combined Combined
Proportion (95% CI) Proportion (95% CI)

(g) Study n/N

Catania 1.00 (0.16–1.00) 2/2
Açıkgö 0.33(8.4E-3–0.91) 1/3
(h) Study n/N
z 0.00 (0.00–0.41) 0/7
Jwa
Catani 0.00(0.00–0.84) 0/2
Noia 0.07 (1.7E-3–0.32) 1/15
Nemec 1.00 (0.03–1.00) 1/1 a Jwa 0.00(0.00–0.41) 0/7
Galinier 0.25(6.3E-3–0.81) 1/4
Noia 0.07 (1.7E-3–0.32) 1/15
Kwak 1.00(0.03–1.00) 1/1
Enríquez 0.00(0.00–0.98) 0/1 Heling 0.00(0.00–0.71) 0/3
Mittermayer 0.00(0.00–0.84) 0/2
Bagolan 0.00(0.00–0.23 0/14
Heling 0.00(0.00–0.71) 0/3
Bagolan 0.14(0.02–0.43) 2/14 0/3
Perrotin 0.00(0.00–0.71)
Perrotin 0.00(0.00–0.71) 0/3
9/56 Combined 0.05 (6.8E-3–0.13) 1/44
Combined 0.22(0.09–0.38)
0.00 0.25 0.50 0.75 1.00 0.0 0.3 0.6 0.9
Proportion(95%CI) Proportion (95%CI)
Figure 3 Pooled proportions for perinatal outcomes of: (a) recurrence of cyst; (b) resolution of cyst; (c) increase in cyst size; (d) change of
ultrasound pattern in cyst; (e) ovarian torsion; (f) intracystic hemorrhage; (g) surgery; and (h) preterm birth or miscarriage, in fetuses with
ovarian cyst treated by intrauterine aspiration.
30
cyst size are the major determinants of perinataloutcome in these cases and
can be used to tailor the optimal postnatal management of affectedpatients.
Simple cysts may occasionally change their ultrasound appearance and
become complex, either during preg- nancy or after birth, and this was
associated with a significantly increased risk of ovarian loss due to surgical
oophorectomy or ovarian autoamputation. Ultrasound surveillance of the
fetus should be scheduled in order to look for early signs of complications of
the cyst, such as an increase in size or appearance of intracystic echoes.
However, the optimal perinatal management of these cases is
controversial49,50. Iatrogenic preterm delivery and prompt surgical intervention
may further compro- mise these patients on the basis that ovarian function
might have already been compromised. In this scenario, especially in cases
remote from term, ultrasound mon- itoring of the cyst seems the most
reasonable and safe option.
Complex cysts have been reported to be strongly asso- ciated with
ovarian torsion requiring oophorectomy 1,2. In the present review, the
likelihood of surgical removal of the ovary was higher in large and complex
cysts. Despitethis,notallcomplexcystsshowedsignsoftorsion, thus questioning
whether postnatal intervention should be arranged immediately after birth in
newborns with complexlesions.
The role of intrauterine aspiration of the ovarian cyst is controversial 51.
The findings from this systematic review suggest that almost half of the
ovarian cysts aspiratedinuteroregressduringpregnancyorafterbirth.
Furthermore, the risks of torsion, hemorrhage and need for postnatal surgical
intervention are relatively small. However, these findings come from
retrospective series including mainly highly selected cases. The very small
number of included studies, different timepoints at fetal intervention and
follow-up and variation in cyst size and appearance did not allow us to draw
any robust conclusion. Aspiration of the cyst in utero might be
considered,especiallyinthecaseoflargecystspresenting
beforeterm,inordernottocompromisethereproductive capacity of the fetus in
adult life or in case of the cyst causing compression on adjacent structures,
leading tobowelobstructionorimpairedflowintheductusvenosus. However, a
randomized and adequately powered control trial is needed in order to
ascertain the role, if any, of intrauterine aspiration of the cyst in the
prenatal management of ovariancysts.
Ovarian cysts are one of the most common abdominal
cysticanomaliesdiagnosedprenatally.Thepresentreview showed that a small
proportion of renal, gastrointestinal and genital anomalies can be
misdiagnosed as ovarian cysts. Almost 15% of complex urogenital
anomalies, such as persistence of urogenital sinus or cloaca, were
misdiagnosed as ovarian cysts. Because these anomalies
areassociatedwithworsepostnatalandsurgicaloutcomes compared with
ovarian cysts, a thorough ultrasound examination should be arranged in order
to not misdiagnose them as ovariancysts.
Bascietto et al.
In conclusion, a large proportion of fetal ovarian cysts diagnosed
prenatally regress during pregnancy or after birth. The risk of torsion is
particularly high in the case of large cysts. The change of ultrasound pattern
of the cyst during pregnancy is associated with a high risk of ovarian loss.
The size and appearance of the cyst are the major determinants of
perinatal outcome and are associated with an increased risk of ovarian
torsion, intracystic hemorrhage and need for oophorectomy.
Futurerandomizedtrialsareneededinordertoascertain
theroleoffetaltherapyinthemanagementofthesecases.
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SUPPORTING INFORMATION ON THE INTERNET

The following supporting information may be found in the online version of this article:
Table S1 Search strategy using MEDLINE and EMBASE
Table S2 Excluded studies and reason for exclusion
Table S3 Pooled proportions of rate of resolution of fetal ovarian cysts either during pregnancy or after birth
Table S4 Pooled proportions of occurrence of ovarian torsion in fetuses with a prenatal diagnosis of ovariancyst
Table S5 Pooled proportions of occurrence of intracystic hemorrhage in fetuses with prenatal diagnosis of ovariancyst
Table S6 Pooled proportions of rate of postnatal surgery in fetuses with prenatal diagnosis of ovarian cyst
Table S7 Pooled proportions of rate of ovarian loss at surgery (due to oophorectomy or salpingo-oophorectomy) in fetuses with pre
Table S8 Pooled proportions of rate of false-positive diagnoses of ovarian cyst according to cyst type
Table S9 Pooled proportions of different histopathological diagnoses of fetal ovarian cysts
International Journal of Reproduction, Contraception, Obstetrics and Gynecology
Chanu SM et al. Int J Reprod Contracept Obstet Gynecol. 2017 Oct;6(10):4642-4645
www.ijrcog.org
pISSN 2320-1770 | eISSN 2320-1789

DOI: http://dx.doi.org/10.18203/2320-1770.ijrcog20174456
Original

Research Article Clinico-pathological profile of ovarian

cysts in a tertiary care hospital

Sairem Mangolnganbi Chanu1, Biswajit Dey2*, Vandana Raphael2,
Subrat Panda1, Yookarin Khonglah2

1
Department of Obstetrics and Gynecology, 2Department of Pathology, NEIGRIHMS, Shillong, Meghalaya, India

Received: 13 August 2017

Accepted: 09 September 2017

*Correspondence:
Dr. Biswajit Dey,
E-mail: drbish25@rediffmail.com

Copyright:the terms of the Cre © the author(s), publisher and licensee Medip Academyative Commons Attribution Non-
Commercial License, which perm. This is an open-access article distributed under its unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: Ovarian cystic neoplasms are common in gynaecological practice. These may pose diagnostic difficulty to the
pathologists. This study was conducted to analyse the clinical and histological profile of ovarian cystic
neoplas
ms.
Methods: This is a retrospective study done from January 2016 to April 2017 in a tertiary care hospital in North East India. All the
patients, who were clinically and radiologically diagnosed as ovarian cysts, which had histopathological confirmation were
included in the study. Data including the age, parity, clinical symptoms, laterality and
histopathological findings were analysed.
Results: A total of 101 patients operated for ovarian cysts in the study period were analysed. The most common clinical
presentation was lower abdominal pain. There were 11 (10.9%) malignant cases, 4 (4%) were intermediate grade and borderline
in nature, and 85 (84.1%) cases were benign in nature. There was 1 (1%) case of metastasis to ovary. Mature cystic teratoma
was most common (20.8%) histopathological diagnosis. The second most common cyst

was serous cystadenoma (19.8%).

Conclusion: Ovarian cysts are commonly encountered in gynaecological practice and equally encountered by the
pathologists. Most commonly found ovarian cysts were mature cystic teratoma followed by serous cystadenoma.
Keywords: Cyst, Cystadenoma, Laparotomy, Teratoma
INTRODUCTION
Ovarian cysts though mostly benign pose a diagnostic dilemma to the gynaecologist as well as to the pathologist. Ovarian
cysts are seen in all age groups, and are subdivided in physiological and pathological cysts.1 They can be solid, cystic or can
have both solid and cystic components. Physiological cysts are mainly follicular and luteal cysts. Pathological cysts can be
benign, borderline or intermediate grade and malignant in nature.1,2 Benign ovarian cysts are the fourth leading gynaecological
cause of hospital admissions and, ovarian malignancies constitute the sixth leading cause of cancer in women and the fourth
common cause of cancer related death in females.3,4 Until these lesions attain a large size or cause signs and symptoms, they
escape detection. Preoperative diagnosis of ovarian cysts largely depends on clinical examination, radiological imaging and
tumour markers.5 However, sometimes it may be difficult to differentiate between benign and malignant ovarian cysts. A
thorough histopathological examination is therefore necessary to confirm the nature of the ovarian cysts.3

Management of the ovarian cysts depend on the age, menopausal status, pregnancy, and their nature. 6 Physiological cysts
require no treatment unless secondarily complicated.2 Prognosis of the neoplastic cysts largely depends on the histological
type and grade.3

October 2017 · Volume 6 · Issue 10 Page

There is paucity of literature regarding the ovarian cysts from the north-eastern region of India. The present study was
undertaken to study the clinical and histopathological pattern of ovarian cysts in a tertiary care institute in north-east India.

METHODS
This is a retrospective observational study done over a period of 1 year 4 months from January 2016 to April 2017 in a tertiary
care teaching hospital in Northeast India. All the patients, who were clinically and radiologically diagnosed as ovarian cysts,
which had histopathological confirmation were included in the study.

All the cases underwent oophorectomy or hysterectomy with bilateral/unilateral salpingectomy. Most of the cases were
operated laparoscopically. Laparoscopy was done under general anesthesia and by using a 7 mm Karl Storz laparoscope with
a 30-degree deflection angle telescope. However, a few patients, who had large mass and unfit for laparoscopic surgery,
underwent conventional laparotomy under regional anesthesia.

Clinical details regarding patients’ age, parity, presenting symptoms and laterality of the cysts were obtained from hospital
records for analysis.

Specimens were sent and fixed in 10% formalin for pathological examination. Gross and histopathological information
regarding the nature and typing of the ovarian cysts were noted. Tissue samples of the ovarian specimens were routinely
processed and embedded in paraffin. The formalin-fixed, paraffin-embedded tissue sections were stained with haematoxylin
and eosin stain for light microscopic examination. Special stains and immunohistochemical stains were done wherever
applicable for diagnosis.

RESULTS
A total of 101 patients operated for ovarian cysts in the study period were analysed. The age of the patients ranged from 18
years to 83 years with a mean age of 38.41 (4.32) years. The ovarian cysts were most commonly seen in the age group 30-39
years.

In terms of parity, there were 79 (78.1%) patients, who were multiparous and the rest 22 (21.8%) were nulliparous. The most
common clinical presentation was lower abdominal pain (29.7%), followed by pain with lump (22.8%) and menorrhagia (14.9%)
(Table 1).

Laterality of the ovarian cysts was studied. Out of 101 cases, right ovary was involved in 43 (42.6%) cases and left ovary was
involved in 39 (38.6%) cases. Bilateral ovaries were involved in 19 (18.8%) cases.
Histopathological data of the 101 cases were analysed
(Table 2). There were 11 (10.9%) malignant cases, 4 (4%) were intermediate grade and borderline in nature, and 85 (84.1%)
cases were benign in nature. There was 1 (1%) case of metastasis to ovary. Mature cystic teratoma was most common
(20.8%) histopathological diagnosis (Figure 1a). The second most common cyst was serous cystadenoma (19.8%) (Figure 1b)
followed by haemorrhagic corpus luteal cyst (15.8%). Serous cystadenocarcinoma (Figure 1c) and mucinous
cystadenocarcinoma (Figure 1d) constituted 5.9% and 3.0% of cases respectively. Omental metastasis was seen in 3 cases
while colon was involved in 1 case.

Table 1: Clinical presentation of the cases.

Number of Percentag
Clinical presentation patients e (%)
Pain lower abdomen 30 29.7
Abdominal lump 10 9.9
Pain lower abdomen with
lump 23 22.8

Amenorrhoea 10 9.9
Menorrhagia 15 14.9
Polymenorrhagia 07 6.9
 Post-menopausal bleeding
12 11.9

Retention of urine 02 2.0

Table 2: Histopathological findings of the cases.
Histopathological Number of
Percenta
ge findings patients
Mature cystic teratoma 21 20.8
Serous cystadenoma 20 19.8
Mucinous cystadenoma 05 5.0
Serous cyst adenofibroma 01 1.0
Cystic fibroma 01 1.0
Sertoli Leydig cell tumour-
01 1.0 intermediate
grade
Mucinous borderline
03 3.0 ovarian tumour
Serous
06 5.9
cystadenocarcinoma
Mucinous
03 3.0
cystadenocarcinoma
Teratoma with malignant
02 2.0 transformation
Haemorrhagic corpus
16 15.8 luteal cyst
Endometriotic cyst 15 14.8
Follicular cyst 06 5.9
Metastasis 01 1.0
Total 101 100
Most of the cases were operated laparoscopically. However, the malignant cases, unfit for laparoscopic surgery, underwent
conventional laparotomy. The benign ovarian cysts, which were large in size and unfit for laparoscopic surgery, underwent
conventional laparotomy. Intra-operative frozen sections were done in doubtful cases. Out of 11 malignant cases, there was 1
case with colonic involvement and 3 cases with Omental metastasis.

Figure 1a, 1b, 1c and 1d: (a) Section from mature cystic teratoma showing cartilage, sebaceous glands and
squamous epithelium, (H and E, 40x). (b) Section from serous cystadenoma showing cyst lined by
ciliated columnar epithelium (H and E, 400x). (c)
Section from serous cystadenocarcinoma showing psammoma bodies (H
and E, 400x). (d) Section from mucinous adenocarcinoma showing glands
lined by
mucinous epithelium infiltrating the stroma, (H and E, 100x).

DISCUSSION
Ovarian cysts present with a variety of clinical manifestations. For a definitive management of ovarian cysts, it is important to
differentiate between the physiological and pathological cysts. Further it is essential to differentiate the pathological cysts into
benign, borderline and malignant. 6 A multimodal approach including clinical features, ultrasonography and tumour markers CA-
125 is required for a definitive preoperative diagnosis. However, histopathology remains the mainstay of diagnosis. 7

The age of the patients ranged from 18 years to 83 years. The age range varies in different series. The age range was 6 years
to 70 years by Pudasaini et al, whereas it was 15 years to 70 years by Kant et al.1,2 The age range was 3 months to 77 years in
the study by Abduljabbar et al.8

The most common clinical presentation was lower abdominal pain (29.7%), followed by pain with lump (22.8%). These findings
are comparable with Kant et al.2 Out of total 101 cases; bilateral ovarian involvement was seen in 18.8% of cases. The finding
is similar to Pudasaini et al, who reported 18.6% of bilateral ovarian involvement. 1 Abduljabbar et al also reported 18.9% of
bilateral involvement of ovaries. 8

In the present study, there were 85 (84.1%) benign cases and 11 (10.9%) cases were malignant in nature. Pudasaini et al from
the neighboring country Nepal reported 87.3% of benign ovarian cyst and 12.7% of malignant ovarian cyst.1 Kant et al from
Kashmir valley reported 71.8% of benign cystic neoplasms and 28.12% of malignant cystic neoplasms. 2 In a study by Jones
KD from the United Kingdom, benign cysts constituted 88.5% and malignant cysts constituted 8.3% of cases. 9

There were 4 (4%) cases of ovarian cysts, which were intermediate grade and borderline in nature in the present study. Kant et
al from Kashmir valley and Neelgund et al from Pondicherry reported 1.9% and 3.25% of borderline ovarian cystic
neoplasms.2,7 Jones KD from the United Kingdom reported 2.5% cases of borderline ovarian tumours. 9

In the present study, mature cystic teratoma (20.8%) was the most common benign neoplasm followed by serous
cystadenoma (19.8%). However, in most of the series, serous cystadenoma is the most common benign ovarian cystic
neoplasm.1,2,7 Serous cystadenomas are the most common benign surface epithelial neoplasms of ovary while mature cystic
teratomas are the most common ovarian germ cell neoplasms. 1,2 Mature cystic teratomas are the most common ovarian
neoplasms found in
adolescents.10

The incidence of malignant transformation in teratoma is estimated to be 0.17-2%. 10 In the present study, there were 2 cases
(2.0%) of teratoma with malignant transformation. Serous cystadenocarcinoma was the most common (5.9%) malignant cystic
ovarian malignancy. This is comparable with findings of Pudasaini et al. 1
However, Kant et al reported mucinous cystadenocarcinoma as the most common cystic ovarian malignancy. 2 Metastasis to
ovary from gastrointestinal tract was found in 1 case (1%) in the present study. Pudasaini et al reported 3.1% cases of
metastasis to ovary whereas Powari et al reported 5% of cases.1,11

The variations of the findings among the different studies could be explained by different duration of study period, geographical
and racial variations. Among the physiological cysts found in the present study were haemorrhagic corpus luteal cyst (15.8%)
and endometriotic cyst (14.8%). In a study done by Choi et al, corpus luteal cysts were the most common among hemorrhagic
ovarian cysts.12

The management of ovarian cysts depends on the accurate pre-operative determination regarding the benign or malignant
nature of the ovarian cysts.6,7 Surgical management is recommended in patients with cysts size more than 5 cm in diameter
and/or elevated serum levels of CA-125. Symptomatic patients should be managed surgically irrespective of age, status of
menopause and radiological findings. 6

CONCLUSION
Mature cystic teratoma was the most common ovarian cyst followed by serous cystadenoma in the present study in contrast to
most other studies. A thorough knowledge of the benign, borderline and malignant ovarian cysts as well as of their regional
variations is desirable for both the gynaecologists and the pathologists.

Funding: No funding sources

Conflict of interest: None declared
Ethical approval: The study was approved by the Institutional Ethics Committee

REFERENCES

1. Pudasaini S, Lakhey M, Hirachand S, Akhter J, Thapa B. A study of ovarian cyst in a tertiary hospital of Kathmandu
valley. Nepal Med Coll J. 2011;13:39-41.
2. Kant RH, Rather S, Rashid S. Clinical and histopathological profile of patients with ovarian cyst presenting in a tertiary
care hospital of Kashmir, India. Int J Reprod Contracept Obstet Gynecol 2016;5:2696-700.
3. Dhakal R, Makaju R, Bastakoti R. Clinicomorphological spectrum of ovarian cystic lesions. Kathmandu Univ Med J.
2016;14:13-6.
4. Sen U, Sankaranarayanan R, Mandal S, Ramanakumar AV, Parkin DM, Siddiqi M. Cancer patterns in India: the first
report of Kolkata cancer registry. Int J Cancer. 2002;100:86-91.
5. Gurung P, Hirachand S, Pradhanang S. Histopathological study of ovarian cystic lesions. J Inst Med. 2013;35:44-7.
6. Knudsen UB, Tabor A, Mosgaard B, Andersen ES, Kjer JJ, Hahn-Pedersen S, et al. Management of ovarian cysts. Acta
Obstet Gynecol Scand. 2004;83:1012-21.
7. Neelgund S, Hiremath P. A retrospective study of ovarian cysts. Int J Reprod Contracept Obstet Gynecol. 2016;5:1969-
73.
8. Abduljabbar HS, Bukhari YA, Al Hachim EG, Alshour GS, Amer AA, Shaikhoon MM, et al. Review of 244 cases of ovarian
cysts. Saudi Med J. 2015;36:834-8.
9. Jones KD. The prevalence and age distribution of ovarian cysts among women attending a London teaching hospital. J
Obstet Gynaecol. 2001;21:70-1.
10. O’Neill KE, Cooper AR. The approach to ovarian dermoids in adolescents and young women. J Pediatr Adolesc Gynecol.
2011;24:176-80.
11. Powari M, Dey P, Gupta SK, Saha S. Metastatic tumors of the ovary: a clinicopathological study. Indian J Pathol
Microbiol. 2003;46:412-5.
12. Choi HJ, Kim SH, Kim SH, Kim HC, Park CM, Lee HJ, et al. Ruptured corpus luteal cyst: CT findings. Korean J Radiol.
2003;4:42-5.

Cite this article as: Chanu SM, Dey B, Raphael V,

Panda S, Khonglah Y.Clinico-pathological profile of ovarian cysts in a tertiary care hospital . Int J Reprod Contracept Obstet
Gynecol 2017;6:4642-5.

ID Design Press, Skopje, Republic of Macedonia

Open Access Macedonian Journal of Medical Sciences. 2018 Mar 15; 6(3):519-
522. https://doi.org/10.3889/oamjms.2018.128
eISSN: 1857-9655
Case Report

Acupuncture
Treatment of
Subfertility and
Ovarian
Endometrioma

Jihe Zhu1, Blagica Arsovska2, Andrijana Sterjovska-Aleksovska3, Kristina Kozovska1*

1
Faculty of Medical Sciences, University Goce Delchev, Shtip, Republic of Macedonia; 2Institute of Biology,
Faculty of Natural Sciences and Mathematics, Skopje, Republic of Macedonia; 3University Clinic of
Gynecology and Obstetrics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje,
Republic ofMacedonia

Copyright: © 2018 Jihe Zhu, Blagica Arsovska, Andrijana Sterjovska-Aleksovska, Kristina Kozovska. This is an open-access article
distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
Funding: This research did not receive any financial support
Citation: Zhu J, Arsovska B, Sterjovska- Competing Interests: The authors have declared that no competing interests exist
Aleksovska A, Kozovska K. Acupuncture
Treatment of Subfertility and Ovarian
Endometrioma. Open Access Maced J Med Sci.
2018 Mar 15;
6(3):519-522.
https://doi.org/10.3889/oamjms.2018.128
Keywords: Acupuncture; Subfertility;
Endometrioma; Traditional Chinese medicine
*Correspondence: Kristina Kozovska. Faculty of
Medical Sciences, University Goce Delchev,
Shtip, Republic of Macedonia. E-mail:
tongdatang-tcm@hotmail.com
Received: 22-Nov-2017; Revised: 14-Dec-2017;
Accepted: 06-Feb-2018; Online first: 05-Mar-
2018
Abstract subfertility, etc. Traditional Chinese Medicine (TCM) is effectively treating subfertility associated
with endometriosis for years, and the treatment gives positive results in achieving pregnancy. With
BACKGROUND: Ovarian the acupuncture treatment, blood circulation is promoted, external physical factors - eliminated,
endometriotic cysts, also known the stasis is dissolved, the menstrual cycle is regulated, and inflammation is diminished.
as ‘chocolate’ cysts or ovarian
endometriomas, appear as CASE REPORT: Our treated patient is 29-year-old woman diagnosed with ovarian endometrioma,
endometrial tissue outside the slightly - elevated prolactin levels and inability to get pregnant after trying for two years. Ningteen
uterine cavity which grows acupuncture treatments were done on the meridians of Pericardium, Spleen, Stomach, Liver, Ren
inside ovaries. Endometriotic Mai, Kidney, Large intestine, Du Mai and Bladder. After the acupuncture treatments, the
cysts can cause chronic pelvic endometrioma was decreased in size and the patient got pregnant spontaneously in a shortperiod.
pain, dysmenorrhea,
dyspareunia, impairment of CONCLUSION: Acupuncture, as part of the TCM, gives positive results and can successfully add
ovarian function in regards to up to variety of non - surgical infertility treatment options in women with endometrioma(s).

Introduction
Ovarian endometrioma is a benign, estrogen-
dependent endometriosis cyst found in women of reproductive
age. Infertility/subfertility is associated with ovarian
endometriomas; although the exact cause is unknown, oocyte
quantity and quality are thought to be affected. “Chocolate”
endometriotic cysts occur in 10% of women in the most
reproductive years from the age of 25 to 40. The most common
locations of endometrial cells implantation are in the ovaries and
the peritoneum [1]. These cysts are filled with brown - coloured
unclotted thick old blood resembling liquid chocolate, so that’s why
they are called ‘chocolate’ cysts. Some cysts do not cause any
symptoms, but some cause problems like irregular periods, pain
and even infertility [2]. Symptoms that may occur are very painful
periods, excessive swelling during the period, low - abdominal
cramping, painful sexual intercourse or pain during physicalactivity,
chronic pelvic pain, etc. [3]. TCM treats a wide range of disorders
including infertility due to ovarian endometriomas. Regarding TCM,
ovarian cysts may present with kidney yang and yin deficiency
(kidney energy is responsible for human reproduction), and if the
energy is weak to circulate and warm the blood, it will stagnate.
Cysts also may present with liver Qi stagnation or can be caused
by excessive dampness, which is caused by fluid and blood stasis
and, accumulated in the abdomen, it slowly becomes phlegm.
Regarding TCM, if the blood doesn’t circulate properly and freely
throughout the body, then blood stagnation occurs, leading to
disease. Some scientists say that endometriosis is an autoimmune
disease, although this is neither well understood nor proven.
However, autoimmune diseases can be dissolved with series of
acupuncture treatments. Acupuncture improves immune response
and liver function, which stimulates the nervous system to release
neurotransmitters and hormones, reduces stress,
improvesthebloodandenergycirculationthroughout
the whole body, reduces the chances of blood stagnation (which causes Both gynaecologists, separately, suggested
infertility and pain) and balances the energy in the body [4] [5]. hysterosalpingography or laparoscopic (LPSC) examination of tubal patency
together with simultaneous LPSC removal of the cyst, but the patient rejected
the suggestion for X-ray diagnostic and invasive surgical procedures (due to
personal preferences) and decided to turn to acupuncture treatment. The
patient opted only for acupuncture, as a treatment option of couple’s
subfertility. Nineteen acupuncture treatments were done in 4 months, starting
Case report from 29th March until 26th July 2016. Acupuncture treatments were done once
a week, in a TCM and Acupuncture Outpatient Clinic in Skopje, Republic of
Macedonia, by a licensed medical doctor - specialist in TCM and
acupuncture, on room temperature, with 35 - 40 minutesduration.
Our patient is a 29-year-old woman, with body mass index of 20,
non - smoker, a lawyer, with no previous history of the abdominal surgeries,
diagnosed with primary subfertility and endometrioma of the left ovary. The
couple was unable to achieve pregnancy after trying for two years. Before
coming to our TCM outpatient clinic, the patient has visited a couple of
outpatients – medical –office - gynaecologists for fertility tests. The
investigations are shown, as follows. PAP smear was normal, and
microbiology swabs’ cultures were negative. All program parameters were
within normal limits, thus excluding the male factor of infertility. 3 rd – day –
menstrual - cycle hormonal panel (FSH, LH, E2, PRL, TSH, T3, T4) showed
results within reference ranges for the age and the menstrual cycle phase,
with the exception of slightly-elevated prolactin, measuring PRL = 32.7 ng/mL
(ref. range 1.9 - 25.0 ng/mL). No anti – Mullerian - hormone (AMH)
measurements were done, but transvaginal ultrasound (TVUS) antral follicle
count (AFC) was 13. Few months’ series of 2D/3D/4D transvaginal
ultrasounds (with foliculometry) proved existence of normal ovulatory regular
menstrual cycles (sonohysterography showed normal size and morphology of
uterine cavity, and serial TVUSs showed proper endometrial thickness during
periovulatory days, presence of monthly ~20 mm leader - follicle in the right or Figure 2: Endometrioma and folicules, left ovary, before treatment
in the left ovary as well as ultrasound signs of ovulation in both ovaries
interchangeably, regular presence of corpus luteum in the luteal phase,
besides the constant presence of one endometriotic cyst measuring 37.8 x
23.9 mm in the left ovary (Figure 1), with a typical endometrioma appearance Fine sterile disposable 0.25 x 25 mm needles were used for the
of homogenous low - level internal echoes and thickwalls). treatment (manufactured by Wuijuiang City Medical & Health Material Co.,
LTD). Acupuncture treatments were being done in points located on the
meridians of Pericardium, Spleen, Stomach, Liver, Ren Mai, Kidney, Large
intestine, Du Mai and Blader. The couple was advised to continue with
regular spontaneous intercourses during periovulatory days of the cycle. After
only 4 months of acupuncture treatments, the couple achieved spontaneous
pregnancy. Follow - up TVUS showed viable intrauterine one – embryo -
pregnancy and yellow body of pregnancy on the left ovary, as well as a
decrease of the left - ovarian endometriotic cyst dimensions to 24.2 x 22.2
mm (Figure 3).

Figure 1: Endometrioma 38 x 24mm, left ovary, before acupuncture

treatment

Figure 3: Reduced endometrioma 24x22mm, left ovary, after

acupuncture treatment

Discussion
A condition such as infertility can be very scary, emotionally
draining and disappointing for young couples, especially for women who are
trying to conceive pregnancy for the first time. Ovarian cysts appear mostly
during a woman's childbearing years. Some cists are functional and benign,
but some are cancerous [6]. In our case, the patient had benign left
- endometriotic ovarian cyst (Figure 2), with normal, ovulatory, regular, but
very painful, menstrual cycles, without even knowing such cyst existed.
Several investigations and ultrasound images of the ovaries and uterus had
been done, due to unsuccessful spontaneous attempts to conceive a
pregnancy, which lasted for 2 years. TVUS images showed visible
endometriotic cyst of the left ovary and lab investigations showed slightly
elevated prolactin levels. Ovarian cysts don’t always manifest symptoms like
chronic lower abdominal pain, breast tenderness, irregular menstrual periods,
nausea, dizziness, painful sex (which is a case in our patient), but according
to the TCM there are other symptoms and physical signs that can identify
possible presence of cysts, such as pale tongue, poor appetite, depression,
mood swings, constipation/diarrhea, pale face, sweating, etc. TCM suggests
a couple of additional causes for endometriomas, such as stress as well as
spleen, kidney, liver and lung Qi deficiency [7]. Also, the three main
pathological factors that may affect the development of ovarian cysts
according to TCM are blood stasis, phlegm and dampness, and each of these
factors needs time to develop. Dampness and phlegm appear due to
imbalanced spleen energy. The excessive dampness in the system gradually
transforms into phlegm and manifests in the body as masses, lumps and
cysts of various kinds, including ovarian cysts. The diet is the key for good
kidney health - no alcohol, sweets, fatty, raw and cold food and beverages,
only warm liquids and cooked vegetables. The major factor in causing
infertility and cysts is the blood stasis when the blood is not flowing easily and
smoothly along the pathways. The pain is always a side effect of blood
stagnation, and the liver is the organ where the stasis is forming because of
the liver stores blood and regulates menstruation [8]. The acupuncture points
located on the meridians of Pericardium, Spleen, Stomach, Liver, Ren Mai,
Kidney, Large intestine, Du Mai and Blader are chosen so to bust the yang
energy, nourish the kidneys, disperse stagnation, move the blood stasis,
tonify the kidneys, transforms the phlegm and dampness and important
immune factors which protect the placenta and the embryo are increased [9]
[10].
Moreover, the patient option to choose a mode of non - invasive
(less - invasive) non - surgical ‘expectant management’ and treatment with
acupuncture maybe found its justification in the ongoing controversy on the
surgical treatmentof
Zhu et al. Acupuncture Treatment of Subfertility and Ovarian Endometrioma
endometriomas: whether to operate them or not? Accepted guidelines say
that the surgical removal of endometriomas is not an absolute necessity in all
cases of infertility before starting with infertility treatments [11]. The
laparoscopic cystectomy procedure strips the cyst wall – the portion of the
cyst containing the endometrial tissue. The benefits of this procedure include
decreased recurrence rates, a significant reduction in pelvic pain and
increase in spontaneous pregnancy rates following surgery, due to decreased
ovarian inflammation which can lower follicular density. However, the main
controversy associated with cystectomy is that it damages or removes healthy
ovarian cortex and follicles, leading to a decrease in ovarian reserve following
the procedure. In a meta-analysis comparing eight studies of ovarian
endometrioma surgical treatment, the patients who had either unilateral or
bilateral cystectomy had significantly lower AFC and AMH levels following the
surgery than before it. Ovarian failure, a serious risk associated with
cystectomy, has been reported after bilateral endometrioma cystectomy, with
rates ranging from 2.3 to 3.03%. In addition to potentially removing healthy
cortex, inflammation after surgery could further damage the cortex or
decrease vascularisation. The damage caused by scar tissue may reduce the
volume of the healthy ovary, and scar tissue may interfere with oocyte
retrieval later on [12]. Furthermore, the European Society of Human
Reproduction and Embryology ESHRE recommend laparoscopic surgery only
in the treatment of endometriomas that are more than 4 cm in diameter, which
is not a case in our patient. Many studies show that there is the difference in
fertilisation/implantation/clinical pregnancy rates between patients with and
without the presence of ovarian endometriosis [13]. But non - surgical
‘expectant’ management is also an optional potential treatment plan, as
recent literature suggests that ovarian endometriomas do not negatively affect
IVF/spontaneous pregnancy outcomes. However, much more research is
needed to establish how ovarian endometriosis management affects infertility
treatments and gross perinatal outcomes [11][13].
In conclusion, acupuncture, as part of the TCM, gives positive
results and can successfully add up to variety of non - surgical infertility
treatment options in women with endometrioma(s). With the acupuncture
treatments, we succeeded both to help patient get pregnant spontaneously in
a short period, as well as to decrease dimensions of the ovarian
endometrioma.
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