Alison Taylor, ABC of Subfertility

49 Pages·2003·1.87 MB·English

by  Peter Braude

ABC of subfertility
Extent of the problem
AlisonTaylor
Oneinsixcoupleshaveanunwanteddelayinconception.
Definitionsofsubfertility
Roughlyhalfofthesecoupleswillconceiveeither
spontaneouslyorwithrelativelysimpleadviceortreatment.The Subfertilityisafailuretoconceiveafteroneyearofunprotected
regularsexualintercourse.Subfertilitycanbeprimaryorsecondary
otherhalfremainsubfertileandneedmorecomplextreatment,
Primarysubfertility—adelayforacouplewhohavehadnoprevious
suchasinvitrofertilisationandotherassistedconception
pregnancies
techniques;abouthalfofthesewillhaveprimarysubfertility.
Secondarysubfertility—adelayforacouplewhohaveconceived
Mostcouplespresentingwithafertilityproblemdonothave
previously,althoughthepregancymaynothavebeensuccessful(for
absoluteinfertility(thatis,nochanceofconception),butrather example,miscarriage,ectopicpregnancy)
relativesubfertilitywithareducedchanceofconception
becauseofoneormorefactorsineitherorbothpartners.Most
coupleswithsubfertilitywillconceivespontaneouslyorwillbe
amenabletotreatment,sothatonly4%remaininvoluntarily
cwhitihldoleustst.rAeastemaechntc,oreulpatlienhgatshaespuobtestnatniatilablecnheafnitcoefotfrecaotnmceeinvtintog n rate 1.0
o
trheaeliirstcihcaanpcpersaoisfacloonfctehieviandgdneadtubreanlelyfiitsoimffeproedrtabnyttrtoeagtmiveenat oncepti 0.8
options. ulative c 0.6
m
u
C
Chance of spontaneous conception 0.4
Conceptionismostlikelytooccurinthefirstmonthoftrying 0.2
(abouta30%conceptionrate).Thechancethenfallssteadilyto
about5%bytheendofthefirstyear.Cumulativeconception
0
ratesarearound75%aftersixmonths,90%afterayear,and 0 2 4 6 8 10 12 14
95%attwoyears.Subfertilityisdefinedasafailuretoconceive Months
afteroneyearofunprotectedregularsexualintercourse.Itis
usuallyinvestigatedafterayear,althoughforsomecouplesit Cumulativeconceptionrateinthefirstyearoftrying
maybeappropriatetostartinvestigationssooner.The
likelihoodofspontaneousconceptionisaffectedbyage,
previouspregnancy,durationofsubfertility,timingof
Prior pregnancy (x1.8) Cumulative average rate
intercourseduringthenaturalcycle,extremesofbodymass,
<36 months infertility (x1.7) Male/tubal defect (x0.5)
andpathologypresent.Areasonablyhighspontaneous
pregnancyratestilloccursevenafterthefirstyearoftrying. Female <30 years (x1.5) Endometriosis (x0.4)
Age birth rate 50
Aftehmestirarolleantagega3es0.sTsohacineadtrieoednaureclyxtii4os0tnssi.bnFeoftewrrewteiolnitmysueisnbgfaergreteaidltiet3yst5ai-nn3d9wiyonemcarreesnatshiinneg mulative live 3400
chanceofconceivingspontaneouslyisabouthalfthatofwomen Cu
aged19-26years.Thenaturalcumulativeconceptionrateinthe
20
35-39agegroupisaround60%atoneyearand85%attwo
years.
10
Thismarked,agerelateddeclineinspontaneousconception
isalsomirroredintheoutcomeofassistedconception
treatment.Recentevidenceshowsthatmalefertilityalso 0
0 6 12 18 24 30 36
declineswithage.Geneticdefectsinspermandoocytesthatare
Months
likelytocontributetoimpairedgametefunctionandembryonic
developmentincreasewithage.Theagerelateddeclinein
Cumulativelivebirthrateandprognosticinfluenceofhistoryandfindings
femalefecundityiscausedbyasteadilyreducingpoolof incouplesnotconceivinginthefirstyearoftrying.Thepresenceof
competentoocytesintheovaries. endometriosis,tubalfactor,orsuboptimalspermqualitymayhalvethe
likelihoodofspontaneousconception.DatafromCollinsetal(seeFurther
readingbox)
Durationofsubfertility
Thelongeracouplehastotrytoconceive,thesmallerthe
chanceofspontaneousconception.Ifthedurationof Socialchangesmeanthatmorecouples
subfertilityislessthanthreeyears,acoupleis1.7timesmore aredelayingthestartoftheirfamilyuntil
likelytoconceivethancoupleswhohavebeentryingforlonger. womenareintheirlate30sandthisbrings
asubstantialreductionintheirlikelihood
Withunexplainedsubfertilityofmorethanthreeyears,the
ofconception
chancesofconceptionoccurringareabout1-3%eachcycle.
Previouspregnancy
Whenadelayinconceptionhasnoobviouscausethe
likelihoodofconceptionisincreased1.8-foldifthecouplehas Factorsaffectingfertility
secondaryratherthanprimarysubfertility. Increasedchanceofconception
x Womanagedunder30years
Timingofintercourseduringovulatorycycle x Previouspregnancy
Thechanceofconceptioninanovulatorycycleisrelatedtothe x Lessthanthreeyearstryingtoconceive
dayinthecycleonwhichintercoursetakesplace.Thewindow x Intercourseoccurringduringsixdaysbeforeovulation,particularly
twodaysbeforeovulation
ofopportunitylastssixdays,endingonthedayofovulation.A
x Woman’sbodymassindex(BMI)20-30
studybyDunsonetal(2002)showedthattheprobabilityof x Bothpartnersnon-smokers
conceptionrosefromsixdaysbeforeovulation,peakedtwo x Caffeineintakelessthantwocupsofcoffeedaily
daysbeforeovulation,thenfellmarkedlybythedayof x Nouseofrecreationaldrugs
ovulation.Thisshowsthatspermneedtobedepositedinthe Reducedchanceofconception
femalegenitaltractbeforeovulationtomaximisechancesof x Womenagedover35years
conception.Thisisconsistentwiththeprogesteroneinduced x Nopreviouspregnancy
changesincervicalmucusthatoccurimmediatelyafter x Morethanthreeyearstryingtoconceive
ovulationandimpedethepenetrationofsperm. x Intercourseincorrectlytimed,notoccurringwithinsixdaysbefore
ovulation
x Woman’sBMI <20or >30
Weight
x Oneorbothpartnerssmoke
Pregnancyislesslikelyifthewoman’sbodymassindex(BMI) x Caffeineintakemorethantwocupsofcoffeedaily
(weight(kg)/(height(m)2))is >30or <20.WomenwithaBMI x Regularuseofrecreationaldrugs
>30needadviceaboutmodifyingtheirdietanddoingmore
exercisetoloseweightandtheyshouldaimforaBMI <30.
WomenwithaBMI <20shouldbeadvisedtogainweight
andreduceexerciseiftheyareexercisingexcessively.Being
considerablyunderweightisassociatedwithanincreasedriskof
miscarriageandintrauterinegrowthretardation.
Obesityisalsoassociatedwithan
Otherfactorsaffectingfertility
increasedriskofmiscarriageandobstetric
Thechanceofconceptionmaybereducedbysmoking,caffeine, complicationssuchashypertension,
anduseofrecreationaldrugs.Theeffectofsomeofthese gestationaldiabetes,thromboembolism,
factorsmaybeattributedinparttoanassociationwithother andcomplicateddelivery
factorsthataffectfertility,suchasanincreasedriskofsexually
transmittedinfection.
Theeffectofalcoholonfertilityisnotclearastheresultsof
studiesareconflicting.Somestudieshavefoundimpaired
fertilityinwomendrinkingmorethanfiveunitsofalcohola Ithasbeenestimatedthatsmokersare3.4
week,whereasothershavefoundthatlowtomoderatealcohol timesmorelikelytotakemorethanayear
consumptionmaybeassociatedwithahigherconceptionrate toconceivethannon-smokers,andineach
thaninnon-drinkers.Excessalcoholconsumptioninmencan cyclesmokershavetwothirdsthechance
contributetoimpotenceanddifficultieswithejaculationand ofconceivingcomparedwithnon-smokers
mayimpairspermatogenesis.
Is subfertility getting more common?
Fecundityratesmaybedeclining.However,itisdifficultto
separatechangesinsocialbehaviourandtrendsindelaying
startingafamilyfromotherfactorsthatmightreducethe
chanceofconception,suchasenvironmentalfactors.Several
studieshavereportedasteadydeclineinmeanspermcounts
overthepastfewdecadesinEuropeandtheUnitedStates.
Theyalsoreportedthattheincidenceoftesticulartumours,
cryptorchidism,andhypospadiasisincreasing.Skakkebaeketal
(1994)havesuggestedthatariseinenvironmentaloestrogenic
pollutantsmaybecausingthesechanges.
Major causes of subfertility
Themajorcausesofsubfertilitycanbegroupedbroadlyas
ovulationdisorders,malefactors(whichincludedisordersof Beingunderweightand
exercisingexcessivelycan
spermatogenesisorobstruction),tubaldamage,unexplained,
increasetheriskofanovulation,
andothercauses,suchasendometriosisandfibroids.The subfertility,andintrauterine
proportionofeachtypeofsubfertilityvariesindifferentstudies growthretardationin
andindifferentpopulations.Tubalinfertilityismorecommon pregnancy
inthosewithsecondarysubfertilityandinpopulationswitha
higherprevalenceofsexuallyacquiredinfections.
The impact of subfertility
Preconceptionadvice
Pre-existingmedicalproblems*
Theimpactofexperiencingdifficultyconceivingshouldnotbe
x Stabilisemedicalconditionsandensurethatmedicalcontrolis
underestimatedforcouplespresentingwiththeproblem.Many
optimal
finditstressfultoseekprofessionalhelpforsuchanintimate x Checkthatdrugsneededaresafeforuseinpregnancyanddonot
problemandfeelasenseoffailureathavingtodoso.Itisnot affectspermfunction
uncommonfortheproblemtoputastrainontherelationship x Whereappropriate,referwomantoanobstetricphysicianfor
andmanycouplesexperienceadeteriorationintheirsexual adviceonimplicationsoftheconditioninpregnancy
relationshipwhichexacerbatestheproblem.General Weight
practitionerscanprovideinvaluablesupporttocouples x CheckBMI
x AdviseonweightgainorlosswhereBMIis <20or >30
undergoinginvestigationandtreatmentandforthosefaced
withintractableinfertility. Smoking
x Advisebothpartnerstostopsmoking
Recreationaldrugs
Preconception advice x Advisebothpartnerstostopusingrecreationaldrugs
Folicacid
Ifacoupleareconsideringstartingafamilytheymayapproach x Womenwhoaretryingtoconceiveshouldtakefolicacid
theirgeneralpractitionerforadviceonconceiving.Areasfor supplements(0.4mg)dailytoreducetheriskofneuraltubedefects.
discussionshouldincludethingsthatmayimprovethechances Womenwithahistoryofneuraltubedefectorepilepsyshouldtake
ofconceptionorincreasethechanceofasuccessfuloutcometo 5mgdaily
thepregnancy(byminimisingtheriskofabnormalityorof Virologyscreening
pregnancyrelatedcomplicationsforbabyandmother). x Screenforrubellaimmunityandofferimmunisationtothosenot
immune
x ConsiderscreeningforHIVandhepatitisBandCingroupsatrisk
Managing subfertility
Prenataldiagnosis
x Tellolderwomenaboutoptionsforprenataldiagnosis
Acouplepresentingwithadelayinconceptionshouldbedealt
Timingofintercourse
withsympatheticallyandsystematicallyaccordingtoalocally x Checkcouple’sunderstandingofovulatorycycleandrelatemost
agreedprotocolofinvestigations.Manyoftheseinvestigations fertiledaystothelengthofwoman’scycle
canbestartedbythecouple’sgeneralpractitionerand x Advisethatintercourseoccursregularly.Twotothreetimesaweek
completedinsecondarycare.Acooperativeapproachallows shouldcoverthemostfertiletime
promptdiagnosisoftheproblem,afterwhicharealistic Factorsaffectingfertility
discussioncantakeplaceabouttheprognosis—thecouple’s x Discussanyfactorsineitherpartner’shistorythatmightwarrant
chanceofconceivingspontaneouslyandofconceivingwith earlyreferralforspecialistinfertilityadvice
differenttreatmentoptions.Formulatingaplanofactionwith *Forexample,hypertension,diabetes,epilepsy,thyroiddisorder,cardiac
thecouplecanhelpeasesomeofthedistressassociatedwith problems,anddrughistory
theproblem.
The role of general practitioners
Furtherreading
Generalpractitionersareoftenthefirstcontactforcouples
concernedabouttheirfertility.Theycanofferadviceand x Managementofinfertilityinprimarycare:Theinitialinvestigation
andmanagementoftheinfertilecouple.Evidencebasedclinical
supportthatcanalleviateanxiety.Theirroleincludesgiving
guidelines,1998
generalpreconceptionadvice,takingahistory,andstarting
www.rcog.org.uk/guidelines.asp?pageID=108&GuidelineID=25
appropriatetests.Theyshouldtrytoseebothpartnerstogether, x BalenAH,JacobsHSInfertilityinpractice.ChurchillLivingstone:
althoughthismaybedifficultiftheyareregisteredwith London,1997
differentpractices.However,thecoupleshouldbeencouraged x BolumarF,OlsenJ,BoldsenJ.Smokingreducesfecundity:a
toapproachtheproblemtogetherandmustunderstandthat Europeanmulticenterstudyoninfertilityandsubfecundity.The
theywillbothneedinvestigation.Generalpractitionerscanalso EuropeanStudyGrouponInfertilityandSubfecundity.AmJ
Epidemiol1996;143:578-7
ensurepromptandappropriatereferral,andadviseonlocal x BolumarF,OlsenJ,RebagliatoM,Saez-LloretI,BisantiL.Body
servicesavailableinsecondaryandtertiarycareandlocal
massindexanddelayedconception:aEuropeanmulticenterstudy
fundingpoliciesforinvestigationandtreatment. oninfertilityandsubfecundity.AmJEpidemiol2000;151:1072-9
x CollinsJA,BurrowsEA,WillanAR.Theprognosisforlivebirth
TheABCofsubfertilityiseditedbyPeterBraude,professorandhead amonguntreatedinfertilecouples.FertilSteril1995;64:22-8
ofdepartmentofwomen’shealth,Guy’s,King’s,andStThomas’s x FormanR,Gilmour-WhiteS,FormanN.Drug-inducedinfertilityand
SchoolofMedicine,London,andAlisonTaylor,consultantin
sexualdysfunction.Cambridge:CambridgeUniversityPress,1996
reproductivemedicineanddirectoroftheGuy’sandStThomas’s x SkakkebaekNE,GiwercmanA,deKretserD.Pathogenesisand
assistedconceptionunit.Theserieswillbepublishedasabookinthe
managementofmalefertility.Lancet1994;343:1473-9
winter. x DunsonDB,ColomboB,BairdDD.Changeswithageinthelevel
Competinginterests:Nonedeclared. anddurationoffertilityinthemenstrualcycle.HumReprod
2002;17:1399-403
BMJ2003;327:434–6
ABC of subfertility
Making a diagnosis
AlisonTaylor
Couplespresentatasurgeryorclinicbecausetheyhavenot
conceivedasquicklyastheyhadexpected.Someareconcerned
theremaybeseriousproblemthatwillstopthemhavinga
family.Subfertilityinvestigationsdeterminewhetheraproblem
existsandenablearationaldiscussionaboutoptionsfor
treatment.Thetreatmentmayincludewaitingfora
spontaneousconception.Someofthedistressassociatedwith
subfertilitymaybereducedbyapromptandsystematic
protocolofinvestigationsthatallowscouplestomovequicklyto
themostappropriatetreatment.
Investigations: who and when
Subfertilityisdefinedasfailuretoconceiveafteroneyearof
unprotectedregularsexualintercourse.Althoughusuallyit
wouldbereasonabletostartinvestigationsafterthistime,earlier
Coupleconsultingdoctor
investigationsandreferralmaybejustifiedwherethereare
importantfactorsineitherpartner’shistory.
Factorsthatmaywarrantearlyreferralorinvestigation*
Awoman’sageisoneofthemainfactorsaffectingher
chanceofconception.Thechancesofmosttreatmentsbeing Female
x Age >35years
successfularereducedsubstantiallyafterawomanreaches35 x Previousectopicpregnancy
yearsandbecomenegligiblebyhermid-40s.Hence,ifcouples x Knowntubaldiseaseorhistoryofpelvicinflammatorydiseaseor
aretogainthemaximumbenefitfromthemostappropriate sexuallytransmitteddisease
treatment,investigationsshouldbestartedpromptly(aftersix x Tubalorpelvicsurgery
monthsoftryingifthewomanisover35)andcompleted x Amenorrhoeaoroligomenorrhoea
accordingtoalocallyagreedprotocolbetweengeneral x Presenceofsubstantialfibroids
practitionersandhospitalproviders.Couplescanthenbe Male
counselledabouttheimplicationsoftestresults,anda x Testicularmaldescentororchidopexy
x Chemotherapyorradiotherapy
managementplanagreedthattakesintoaccountthetestresults
x Previousurogenitalsurgery
andthecouple’sbeliefsandwishes. x Historyofsexuallytransmitteddisease
Atinitialpresentationbothpartnersshouldhaveahistory x Varicocele
takenandbeexamined.Regularintercoursetwotothreetimes
*Beforeayear
aweekshouldbeadvised,butbasalbodytemperaturechartsare
nothelpfulandshouldbeavoided.
Thefemalepartnerofcouplespresenting
A rational approach to investigation withsubfertilityshouldhavetheirrubella
statuscheckedsothatifimmunisationis
Initialinvestigationsshouldbecompletedwithinthreetofour requireditwillnotdelayanytreatment
monthsandshouldestablishthefollowingpoints.
x Doesthewomanovulate?
x Ifnot,thenwhynot?
x Isthesemenqualitynormal? Initialinvestigationsthatcanbedoneinprimarycare
x Istheretubaldamageoruterineabnormality? Female
x Luteinisinghormone,folliclestimulatinghormone(FSH),and
Bothpartnersmustbeinvestigatedbecauseanappropriateplan
estradiolconcentrations—shouldbemeasuredinearlyfollicular
ofmanagementcannotbeformulatedwithoutconsideringboth
phase(days2to6)
maleandfemalefactorsthatmayoccurconcurrently.Initial x Progesteronetest—shouldbedonemid-lutealphase(day21or
investigationscanbestartedinthecommunity,withthe sevendaysbeforeexpectedmenses)
assessmentoftubalpatencytakingplaceinhospital x Thyroidstimulatinghormone,prolactin,testosteronetest—should
bedoneifwoman’scycleisirregular,shortened,orprolongedorif
progesteroneindicatesanovulation
Starting investigations in primary care x Rubellaserologytest—shouldbecheckedevenifthewomanhas
beenimmunisedinpast
Doesthewomanovulateandifnotwhynot? x Cervicalsmear—shouldbecarriedoutasnormalscreening
TheUKRoyalCollegeofObstetriciansandGynaecologists’ protocol
x Transvaginalultrasoundscan—shouldbedoneifthereisthe
guidelinesincludecheckingamid-lutealphaseprogesteroneto
possibilityofpolycysticovariesorfibroids
confirmovulationinaregularcycle.Timethesampleatthe
Male
correctphaseofthecycle(sevendaysbeforeexpectedmenses).
x Semensampleforanalysis—sampleshouldbetakenaftertwoor
Wherecyclesareirregularorthewomanhasoligomenorrhoea
threedays’abstinenceandrepeatedaftersixweeksifabnormal
(acyclelengthof >35days)orpolymenorrhoea(<25days),
ovulationisunlikelyandsoaprogesteronetestisoflittlevalue.
Thyroidstimulatinghormone,testosterone,andprolactin
concentrationsneedbecheckedonlyifcyclesareirregularor
absent,suggestinganovulation,galactorrhoea,orsymptomsof
thyroiddisorder.Transvaginalultrasonographyisasimple
investigationthatwilldetectpolycysticovariesanduterine
fibroids.Luteinisinghormone,FSH,andestradiolshouldbe
checkedearlyinthecycle(days2to6).
Issemenqualitynormal?
Themalepartnershouldhaveasemenanalysisandifsome
parametersareabnormal,thenasecondtestshouldbedonesix
weekslater.Ideallythesamplesshouldbeanalysedinthe
laboratoryusedbythefertilityclinictowhichthecouplewillbe HyCoSyshowingpatencyandflowthroughonecornuof
theuterus
referred.Moredetailedspermfunctiontestsarenotneededasa
routinepartoftheinitialinvestigations.Thepostcoitaltestis
unreliableandisnolongerrecommendedasaroutine Completinginvestigationsinsecondarycare
investigation.
Female
Investigationsstartedinprimarycareshouldbecompleted Assesstubalstatusanduterinecavity
inadedicatedreproductivemedicineorfertilityclinic. x HSG
x HyCoSy
x Laparoscopyanddyetestwithhysteroscopy
Male
Investigations in secondary care
Ifazoospermiaispresent
x FSH,luteinisinghormone,andtestosterone(withorwithout
Istheretubaldamageoruterineabnormality? prolactin,thyroidstimulatinghormone)tests
Assessmentofawoman’stubalstatusanduterinecavitycanbe x Cysticfibrosisscreeningandkaryotypeif <5×106/ml
performedby x Centrifugationofejaculateandexaminationofpelletfor
x Hysterosalpingography(HSG) spermatozoa
x Hysterosalpingo-contrastsonography(HyCoSy) x Testicularbiopsyorexploration
x Laparoscopyanddyetestwithhysteroscopy. Ifoligozoospermiaandsignsofhypogonadotrophichypgonadism
x FSH,luteinisinghormone,prolactinthyroidstimulatinghormone,
Testsfortubalpatencyshouldtakeplaceinthefirst10daysofa
andtestosteronetest
cycletoavoidthepossibility,howeverunlikely,ofdisruptingan
earlyspontaneouspregnancy.Unlesscervicalscreeningfor
chlamydiahasbeenperformed,prophylacticantibioticssuchas
doxycyclineandmetronidazoleshouldbegiventominimisethe
riskofinfectiondevelopingaftertheprocedure.
HSGandHyCoSy
HSGandHyCoSyare“dynamic”outpatientinvestigationsdone
byinsertingacatheterintothecervicalcanal,afterwhich
contrastisinjectedintotheuterinecavity.HSGusesrealtime
xrayimagingtofollowtheflowofcontrastintothetubesand
spillintotheperitonealcavity,whereasHyCoSyuses
ultrasonography.Bothgiveinformationabouttheshapeofthe
uterinecavity.HyCoSygivesextrainformationbecausean
ultrasoundscanofthepelvisisperformedatthesametime,
allowingthedetectionoffibroidsorpolycysticovaries.
Hysterosalpingogramshowinganormalpelvis
Laparoscopyanddyetest
Alaparoscopyanddyetestneedsgeneralanaesthesiaand
carriesthehazardsoflaparoscopy.However,itgives
informationaboutthedegreeofanytubaldamagepresentand
enablesendometriosistobedetected.Additionally,laparoscopic
treatmentsuchasdiathermyorlaserablationofendometriosis
orsalpingolysisorsalpingostomymaybedoneatthesame
time.HyCoSyandHSGcanbeusedasaninitialscreen,
reservinglaparoscopyforpatientswithahistoryorsymptoms
indicatingariskoftubaldamageorendometriosis,andfor
thosewhohaveanabnormalHSG.Ifinvestigationofthemale
partnershowssubstantiallyimpairedsemenquality,suchthat
assistedconceptiontreatment(forexample,intracytoplasmic
sperminjection)islikely,tubalassessmentmaynotbeneeded.
However,informationabouttheuterinecavitymaybehelpfulif Laparoscopyshowinganormalpelviswithpassageofblue
ultrasonographyshowsthepresenceofsubmucosalfibroids. dyethroughthefimbrialendofthelefttube
Further investigation of azoospermia
Investigatingazoospermia,bysiteofabnormality
in secondary care
Obstructive Non-obstructive
Post-testicular Testicular Hypothalamic-
Wheretheinitialsemenanalysisrevealsazoospermiaa
pituitary
centrifugedsampleshouldbeexaminedforsperminthepellet.
Congenital Vasalaplasia, Geneticcauses, Kallman’ssyndrome,
Evenifonlyafewspermcanbeidentified,intracytoplasmic causes cysticfibrosis, cryptorchidism, isolatedFSH
sperminjectioncanbeofferedaseffectivetreatmentto mulleriancysts anorchia deficiency
circumventtheinfertility. Acquired Gonorrhoea, Radiotherapy, Craniopharyngioma,
Ifazoospermiaisconfirmeditisimportanttodistinguish causes chlamydia, chemotherapy, pituitarytumour,
betweenobstructiveandnon-obstructiveazoospermia. tuberculosis, orchitis,trauma, pituitaryablation,
prostatitis, torsion anabolicsteroids
Inobstructiveazoospermia,spermatogenesisisnormalbut
vasectomy
thereisablockintheepididymisorvasdeferens.Ifcongenital
Testicular Normal Small,atrophic Small,prepubertal
absenceofvasdeferensissuspected,bothpartnersshould
size
undergocysticfibrosisscreeningbecausemanyofthesemen
FSH Normal Raised Low
willcarryoneofthecysticfibrosismutations.Innon-obstructive
Testosterone Normal Low Low
azoospermia,spermatogenesisisimpaired.Thisimpairment
maybecausedbytesticularfailure(sotheman’skaryotype
shouldbecheckedandmultipletesticularbiopsymayshow
isolatedfociofspermatogenesis)orduetoafailuretostimulate
spermatogenesisbythehypothalamicpituitaryaxis
(hypogonadotrophichypogonadism).Althoughrare,this
conditionshouldbedetectedasthesepatientsrespondto
gonadotrophintreatment.
Interpretingresultsofinvestigationsoffemalepartners
Test Result Interpretation
Interpreting results and discussing Progesterone <30nmol/l Anovulation:
Checkcyclelengthandtimingin
treatment options
mid-lutealphase;completeother
endocrinetests;scanforpolycystic
Femalepartner ovaries;adviseonweightgainor
Wheretheprogesteroneconcentrationislowtakethefollowing loss;mayneedovulationinduction;
steps. clomifeneshouldnotbestarted
x Checkthelengthofthecycleinwhichthesamplewastaken withouttubalpatencytest
x Ensurethatsamplewastakeninthemid-lutealphase—that FSH >10IU/l Reducedovarianreserve:
Mayrespondpoorlytoovulation
is,sevendaysbeforeexpectedperiod
x Ensurethatotherendocrinetestsarecompleted induction;mayneedeggdonation
x Anultrasoundscanisvaluabletodiagnosepresenceof Luteinising >10IU/l Maybepolycysticovaries:
hormone Ultrasonographytoconfirm
polycysticovariesifanovulationisconfirmedortheluteinising
Testosterone >2.5nmol/l Maybepolycysticovaries:
hormoneortestosteroneconcentrations,orboth,areraised
Ultrasonographytoconfirm
x Adviseaboutweightgainorlosstoachieveabodymass >5nmol/l Congenitaladrenalhyperplasia:
index(weight(kg)/(height(m)2))of20-30.Thisisthekeyto Check17-OHPandDHEAS
successfultreatment. Prolactin >1000IU/l Maybepituitaryadenoma:
Asingleraisedearlyfollicularphasefolliclestimulating Repeatprolactintoconfirmraised
hormone(FSH)concentrationisapoorprognosticindicator concentration;exclude
hypothyroidism;arrangemagnetic
forwomentryingtoconceive.Itimpliesareducedovarian
resonanceimageorcomputed
reserveandthepossibilityofincipientprematureovarian
tomogram;ifconfirmed
failure.Thisisdifficulttotreatbecausetheresponsetoovarian hyperprolactinaemiastart
stimulationislikelytobepoor.Refractorycasesmayneedegg dopamineagonist
donation. Rubella Non-immune Offerimmunisationandonemonth
AfteranabnormalhysterosalpinogramorHyCoSy,further contraception
tubalassessmentbylaparoscopywillbeneeded.Themain HSGor Abnormal Maybetubalfactor:
treatmentoptionsinclude: HyCoSy Arrangelaparoscopyanddyetestto
x Surgery(openorlaparoscopic) evaluatefurther;maybe
x Transcervicaltubalcannulation intrauterineabnormality—for
x Invitrofertilisation. example,fibroidoradhesions;
evaluatefurtherbyhysteroscopy
Thechoiceofprocedurewilldependonfactorssuchasthe
Laparoscopy Blockedtubes Tubalfactorconfirmed:
degreeoftubaldamage,thesemenquality,andthepatient’s anddye Possiblysuitablefortranscervical
age.Intrauterinelesionssuchassubmucousfibroidsor cannulation,surgeryorinvitro
adhesionsneedfurtherevaluationbyhysteroscopy,atwhich fertilisation(alsodependsonsemen
timetheymayberesected. quality)
Endometriosis Endometriosis:
Assessseverity;maybenefitfrom
Malepartner
diathermyorlaserablation;medical
Semensamplescanvarygreatly.Ifthesemenvolumeislow, suppressionnothelpfulforfertility
checkwhethercollectionoftheejaculatewascomplete.Ifthe Mayneedinvitrofertilisation
firstpartoftheejaculate,whichcontainsmostofthesperm,
DHEAS=dihydroepiandrosteronesulphate;
missedthepot,theresultswillnotberepresentative. 17-OHP=17-hydroxyprogesterone
Lubricantsformasturbation—forexample,soaporKYjelly
Interpretingasemenanalysis
maybespermicidalandtheiruseshouldbeavoided.Ifthemale
partnerhasdifficultyproducingasamplebymasturbationthen Parameter Normal Commentsifabnormal
anon-spermicidalcondomcanbeused. Volume 2-5ml Iflow,checkifcollectionwas
Therapeuticdrugsthatmaybeassociatedwithimpaired incomplete(“missedthepot”)
spermatogenesisincludechemotherapy,sulfasalazine,and Count >20×106/ml Repeatsample.Checkthatno
acuteillnessoccurredintwo
cimetidine.
monthsbeforesample.Lifestyle
Abnormalsemenqualitiesareanindicationforearly
adviceonsmoking,alcohol,and
referraltoafertilityclinic,preferablyoneofferingafullrange drugs.If <10×106/mlinvitro
ofassistedconceptiontechniques. fertilisationorintracytoplasmic
sperminjection.Referearly
Conclusion Motility >50% Repeatsample;referearly
progressively
motile
Coupleswhopresentwithsubfertilityrarelyhaveabsolute
>25%rapidly
infertility(thatis,nochanceofconceptionspontaneously).
progressive
Factorsthatarecontributingtotheproblemusuallycause
Morphology >15%normal Repeatsample;referearly
relativesubfertility(thatis,areducedchanceofconceiving shape
spontaneously)toagreaterorlesserdegree,andtheremaybe
relevantfactorsinbothpartners.
Investigationsshouldfollowasystematicprotocoldesigned
toidentify:
x Tubaloruterineabnormalities Furtherreading
x Anovulation
x Impairedspermatogenesis. x RoyalCollegeofObstetriciansandGynaecologistsevidencebased
clinicalguidelines.Initialinvestigationandmanagementofthe
Promptinvestigationandappropriatereferralallowa subfertilecouple.London:RCOGPress,1998
x TempletonA,AshokP,BhattacharyaS,GazvaniR,HamiltonM,
coupletoreceiveadviceandtreatmenttohelpthemreachtheir
MacMillanS,etal.EvidencebasedfertilitytreatmentLondon:RCOG
goalofapregnancymorequickly,andmayalleviatesomeofthe
Press,London,2000
distressassociatedwithsubfertility.Doctorsinprimarycarecan x BalenA,JacobsH.Infertilityinpractice.2nded.London:Churchill
haveaninvaluableroleinstartingthisprocessandproviding Livingstone,2003
supportduringfurtherinvestigationandtreatment. x TempletonA,AshokP,BhattacharyaS,GazuaniR,HamiltonM,
MacMillanS,etal.ManagementofinfertilityfortheMRCOGand
TheABCofsubfertilityiseditedbyPeterBraude,professorandhead beyond.London:RCOGPress,2000
ofdepartmentofwomen’shealth,Guy’s,King’s,andStThomas’s
SchoolofMedicine,London,andAlisonTaylor,consultantin
reproductivemedicineanddirectoroftheGuy’sandStThomas’s Competinginterests:Nonedeclared.
assistedconceptionunit..Theserieswillbepublishedasabookinthe
winter.
BMJ2003;327:494–7
Amemorablepatient
Bella and the blood sample
Shedidn’tspeakanyEnglishandhadaterribletemperaftera smallbloodsampleforresearchpurposes.Chimpanzeesare
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particularlyproblematic.Alongstandingneedlephobiawasone immunodeficiencyvirus,asimilarsituationobservedinavery
oftheleastseriousissues.Itwasfeltthatthebestpolicywouldbe smallminorityofthepatientsinfectedwithHIV-1whomwesee.
tosedateherfirst,andwediscussedthiswhileshesatthere Unravellingthehostfactorsinvolved,whysomeindividuals
grumbling.HerfavouritedrinkwasCoca-cola,althoughshe becomeinfectedanddonotdevelopdisease,mayleadto
rarelyhadit,soweplacedasmallamountofabenzodiazepinein promisingnewtreatments.
amugful.Shespatoutthefirstmouthfuldisdainfully,andthe
Thecollaborationworksbothways:wegetourbloodsamples,
second.Theneedlephobiawasnowveryapparent.
andthestaffatLondonZoo,whoarealwaysinneedofmedical
Weweretoldthateverytwomonthsshehadanentiretubof
equipment,getsomeofourredundantanaestheticmachines.
BenandJerry’sChocolateChipCookieDoughicecream—her
absolutefavourite,whichsurelywouldn’tfail.Wedutifullyplaced JustinStebbing registrar
thesedativeinatuboftheicecream.Shegrabbeditandtook
FrancesGotch headofdepartment
whatseemedlikeanenormousmouthful,shovellingitinwithher
lefthand,asherrightwasweak.Shespatitoutagainandlooked BrianGazzard professorofmedicine,departmentofimmunology,
absolutelyfurious.Westoodwellawaybeforeshecouldshowher ChelseaandWestminsterHospital,London
displeasureinmorepracticalways,butshecalmlyproceededto
Wewelcomearticlesupto600wordsontopicssuchas
scoopupsomeofherexcrementthatwasonthefloor,placeitin
Amemorablepatient,Apaperthatchangedmypractice,Mymost
thetub,andhandthisbacktous.Theonlyoptionleftwasto
shootherwithatranquilliserdart. unfortunatemistake,oranyotherpiececonveyinginstruction,
Bellaisa42yearoldchimpanzeeatLondonZoo,and,justlike pathos,orhumour.Pleasesubmitthearticleonhttp://
anyotherpatient,shehadherownparticularwayoftellingusto submit.bmj.comPermissionisneededfromthepatientora
“getlost.” relativeifanidentifiablepatientisreferredto.Wealsowelcome
WehaveacollaborationwiththeZoologicalSocietyofLondon contributionsfor“Endpieces,”consistingofquotationsofupto80
sothat,whentheyanaesthetisetheirnon-humanprimatesfor words(butmostareconsiderablyshorter)fromanysource,
reasonsconcernedonlywiththehealthofthatanimal,wetakea ancientormodern,whichhaveappealedtothereader.
ABC of subfertility
Anovulation
DianaHamilton-Fairley,AlisonTaylor
Disordersofovulationaccountforabout30%ofinfertilityand
oftenpresentwithirregularperiods(oligomenorrhoea)oran GnRH Hypothalamus
absenceofperiods(amenorrhoea).Manyofthetreatmentsare Positive feedback/stimulation
simpleandeffective,socouplesmayneedonlylimitedcontact Negative feedback
withdoctors.Thismakesiteasierforacoupletomaintaina
privatelovingrelationshipthaninthestressful,more LH FSH Apintuteitraioryr
technologicalenvironmentofassistedconception.However,not
allcausesofanovulationareamenabletotreatmentby
ovulationinduction.Anovulationcansometimesbetreatedwith
medicalorsurgicalinduction,butitisthecauseofthe
anovulationthatwilldeterminewhetherovulationinductionis
possible.Thevariousoptionsarediscussedlaterinthisarticle.
Estradiol and Corpus Follicles
progesterone luteum Ovary
Causes suitable for ovulation
Dominant
induction
follicle
Hypothalamic-pituitarycauses
Hypogonadotrophichypogonadismischaracterisedbya Estradiol
selectivefailureofthepituitaryglandtoproduceluteinising Ovulation
hormoneandfolliclestimulatinghormone.Thecommonest
causeisexcessiveexercise,beingunderweight,orboth.Women
Hypothalmic-pituitary-ovarianaxis(FSH=folliclestimulatinghormone;
whohavealowbodymassindex(weight(kg)/(height(m)2))(for GnRH=gonadotrophinreleasinghormone;LH=luteinisinghormone)
example, <20)orwhoexerciseexcessively—forexample,
gymnasts,marathonrunners,ballerinas—maydevelop
amenorrhoeabecauseofaphysiologicalreductioninthe
hypothalamicproductionofgonadotrophinreleasinghormone.
Womenwhoareunderweightfortheirheightwhentheyget Causesofanovulationsuitableforovulationinduction
pregnantaremorelikelytohave“smallfordates”babies;and treatment
childrenofwomenwhohaveeatingdisordersaremorelikelyto
Hypothalamic
beadmittedtohospitalwithfailuretothrive. x Lowconcentrationofgonadotrophinrealeasinghormone
Sheehan’ssyndrome(panhypopituitarism),causedby (hypogonadotrophichypogonadism)
infarctionoftheanteriorpituitaryvenouscomplex(usually x Weightorexerciserelatedamenorrhoea
aftermassivepostpartumhaemorrhageortrauma),and x Kallman’ssyndrome
Kallman’ssyndrome(amenorrhoeawithanosmiacausedby x Stress
x Idiopathic
congenitallackofhypothalamicproductionofgonadotrophin
Pituitary
releasinghormone)arerare.Childrentreatedfora
x Hyperprolactinaemia
craniopharyngiomaorsomeformsofleukaemiamayhave x Pituitaryfailure(hypogonadotrophichypogonadism)
hypogonadotrophichypogonadismsecondarytocerebral x Sheehan’ssyndrome
irradiation,whichmayaffectthehypothalamusorthepituitary. x Craniopharyngiomaorhypophysectomy
Hyperprolactinaemiaisusuallycausedbyapituitary x Cerebralradiotherapy
microadenoma.Thisleadstoareductionintheproductionof Ovarian
pituitaryluteinisinghormoneandfolliclestimulatinghormone. x Polycysticovaries
Althoughthecommonestpresentationissecondary Otherendocrine
amenorrhoea,somewomenmaypresentwithgalactorrhoea.A x Hypothyroidism
smallernumbermayhaveheadachesordisturbedvisionthat x Congenitaladrenalhyperplasia
mayindicateamacroadenoma,whichneedsurgent
investigationandtreatment.Amicroadenomaiseasilytreated
withdrugswithasubsequentresumptionofmensesand
fertility.
Ovariancauses
Polycysticovarysyndromeisthecommonestcause(70%)of
anovulatorysubfertility.Theprimaryabnormalityseemstobe
Transvaginalscanofa
anexcessofandrogenproductionwithintheovarythatleadsto polycysticovary.Typically10or
therecruitmentoflargenumbersofsmallpreovulatoryfollicles, morefolliclesof<10mmin
whichfailtorespondtonormalconcentrationsoffollicle diameter(“stringofpearls”)
areinasingletransverseor
stimulatinghormone.Thus,adominantfollicleisrarely
longitudinalsectionthrough
produced.Womenwithpolycysticovarysyndromecommonly theovary.Stromaldensityand
presentintheirlateteensorearly20swithhirsutism,acne,or ovarianvolumeincrease