针刺自然和对照卵巢过度刺激周期治疗不明原因不孕症前瞻性分析 Treatment o.doc

针刺自然和对照卵巢过度刺激周期治疗不明原因不孕症前瞻性分析 Treatment o How tocite thispaper:Cai,L.H.,Hai,R.H.,Zhang,B.,Wen,Y.F.,Zeng,M.H.and Jiang,M.B. (xx)Treatment ofUnex-plained Infertilityby Acupuncture in Naturaland Control Ovarian HyperstimulationCycles:A ProspectiveAnalysis.Advances inReproductive Sciences,2,88-92.Treatment ofUnexplained Infertilityby Acupuncture in Naturaland ControlOvarian HyperstimulationCycles:A ProspectiveAnalysis LiuhongCai1*,Rihan Hai2,Bin Zhang3,Yanfei Wen1,Minhui Zeng1,Manbo Jiang31Center for Reproductive Medicine,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou,China2Department of Acupuncture,The ThirdAffiliated Hospital,Sun Yat-sen University,Guangzhou,China3Department ofInfertility andSexual Medicine,The ThirdAffiliated Hospital,Sun Yat-sen University,Guangzhou,China Received29Septemberxx;revised30Octoberxx;aepted10NovemberxxCopyright?xxby authorsand ScientificResearch PublishingInc.This workis licensedunder theCreative CommonsAttribution InternationalLicense(CC BY).Abstract Acupuncture is animportant methodof treatmentin Chinesemedicine.The objectiveof this study was to evaluatethe efficacy of acupunctureas an adjuvant treatment for unexplained infertility.Here weconducted a prospective study,with dataconsisting of acupuncture group(38cases)and control group(42cases).Infertility evaluation workup consistedof semenanalysis,ovulation as-sessment,hysterosalpingogram(HSG)and bloodanalysis.The patientsin acupuncture group re-ceived3acupuncture sessions,and eachat sevenacupuncture points(EX-CA1,CV4,CV6,SP10,ST36,SP6,and KI3).The sessionstarted12days beforemenstruation andcontinued for10days.The patientsin control group did not receive acupuncture.All patientstried1-3natural cycles3months after HSG test,if notpregnant,underwent1-3cycles ofcontrol ovarianhyperstimulation(COH)and timed intercourse.Pregnancy wasevaluated bymeasurement ofbloodhuman cho-rionic gonadotrophin(-hCG)and subsequenttrans-vaginal ultrasound.No significantdifference ofclinical pregnancy rate wasfound between the acupuncture group and the control group,how-ever,numbers of COH cycles were significantlyless andmore pregnanciesourred in natural cycle in theacupuncture group.We concludedthat acupuncture can be used as anadjuvanttreat-mentfor unexplained infertility.Although acupuncture did not increase the cumulative pregnancy rate,it decreasedthe number of COH cycles andmore patientsgot pregnantin natural cycles afterreceiving acupuncture.*Corresponding author.L.H.Cai etal.89Keywords Acupuncture,Unexplained infertility,ControlOvarianHyperstimulation,Pregnancy1.Introduction Infertilityaffects10%-15%of thereproductive agegroup.Aording toThe PracticeCommittee of the Amer-ican Society forReproductive Medicine(ASRM),after thestandard infertilityevaluationworkupof semenanalysis,assessment of ovulation,hysterosalpingogram(HSG),and,if indicated,tests for ovarian reserveand laparoscopy,approximately15%to30%couples were assigned adiagnosis of unexplained infertilitydue tono abnormalityrevealed12.For unexplained infertility,intrauterine insemination(IUI)or invitro fertilization(IVF)can bea goodchoice,but bothlay aheavy economicburden onpatients.Acupuncture isa traditional Chinese treatment,widely practicedand nowalso aeptedin thewestern worldfor the treatment ofobstetric andgynecologic or infertile issues3-6.We havebeen practicingacupuncture for unexplainedinfertilitytreatment formany years.In this study weprospectively analyzedthe datato evaluatethe effectof acupuncturein treatmentofunexplainedinfertility.2.Methods2.1.Study Designand SubjectsThis isaprospectivestudy implementedat TheThirdAffiliated Hospital,Sun Yat-Sen University,between Marchxxand Augxx.The studygroup eligibilitycriteria included:infertility duration3years;age of22-35years;presence ofregular menstrual cycles andovulation;absence oftubal obstructionon HSG;sperm concentration15million/ml andtotal spermnumber39million/ml aording to WHOcriteria1.All womenunderwent atraditional Chinesemedicine(TCM)diagnosis.Exclusion criteriawere the presence ofendocrinologic disease(PCOS,etc.);use ofnonsteroidal anti-inflammatory drugsor corticosteroids;clinical findingsor HSGresults suggestingpel-vic inflammatorydisease;thepresenceof undiagnoseduterine bleeding;refusal toundergo COH.The patientswilling toreceiveacupuncture wereassignedto acupuncturegroup,otherwise tocontrolgroup.The studywas conductedin aordancewith theDeclaration ofHelsinki,and wasapproved by the ReproductiveEthics Com-mittee of the ThirdAffiliatedHospitalof SunYat-sen University.2.2.Workup forEvaluation ofInfertility Patients were asked to ewith theirhusbands.First,husbands receivedphysical examination and wereasked todo semenanalysis.Then,wives wereasked tomonitor ovulationby ultrasoundfor atleast1cycle andtest hormoneon day2to day5of menstruationcycle.At thesame time,antibodies,such asanti-HCG antibodies,anti-sperm antibodies,anti-ovarian antibodies,anti-sperm antibodies,anti-cardiolipin antibodies,anti-zona pel-lucida antibodies,etc,were tested.Thyroid function,including TSH,FT3,FT4,were tested.Vaginal dischargeexaminationandultrasound examinationof pelvicorgans wereconducted.HSG:Patientswerescheduled between the7th and12th dayof theirmenstrualcycle(3-7days aftermenstr-uation).Contraindications includedpregnancy,vaginal inflammatorydisease andsevere allergyagainst iodinecontrast agents.Half anhour beforeHSG,a spasmolyticagent,atropine,was injected.Antibiotic prophylaxiswas prescribedafterHSG.The cervicalos wascannulated usinga catheterwith3ml balloon.When thecatheter wasin place,water-soluble iodinatedcontrast mediumwas appliedunder X-ray.An injectionof10ml contrast medium outlinedthe cornual,isthmic andampullary portionsof thetubes,and showedcontrastmediumspillage into the abdominalcavity.If oneor bothtubes showedno contrastspillage into the abdominalcavity,the possi-bility oftubal spasmwas excludedby increasinginjection pressureand contrastmedium administration.Nine radiographswere takenafter contrastmedium administrationin eachpatient,including imagesof theearly andplete fillingphases of the uterine cavity,outlining of the fallopiantubes and the contrastspillage into the abdominalcavity.Delayed imagewas taken30minutes afterremoval of the instrumentfrom thecervix.Following theexamination,the radiologistevaluated theimages independently.L.H.Cai etal.902.3.Acupuncture TreatmentEach patientfrom acupuncturegroup underwenta totalof3acupuncture sessions,each sessionperformed12days beforemenstruation,for10days continuously.In allsessions,thetreatmentwas performedby thesame acupuncturist,with more than20years ofexperience in acupuncture.The needleswere manuallyinserted bila-terally andstimulated toobtain deqi andkept for20minutes.The followingpoints for acupuncturewerese-lected:EX-CA1:ZigongOn thelower abdomen,4cun belowthe centreof theumbilicus and3cun lateralto Zhongji(RN3);CV4:GuanyuanOn themidline,3cun inferiorto theumbilicus;CV6:QihaiOn themidline,1.5cun inferiortotheumbilicus;SP10:XuehaiWith theknee inflexion,2cun superiortothesuperior border of thepatella,on thebulge ofthe medialportion ofthe quadricepsfemoris muscle;ST36:Zusanli3cun belowST35one fingerwidth lateralfrom theanterior crestofthe tibia,in thetibialis anteriormuscle;SP6:Sanyinjiao-3cun directlyabove the tip ofthe medial malleolus on the posteriorborderofthetibia;KI3:TaixiIn depres-sion midwaybetweenthetip ofthe medialmalleolus andthe attachmentoftheAchilles tendon,level withthetipofthemedialmalleolus.2.4.Natural CycleAfter HSG,both groupswere instructedto tryup to3natural cyclesor untilpregnancy ourred.They wereaskedtomonitor ovulationand were administered10,000IU ofhCG(Lizhu Phamacy,China)to triggerovula-tion whenleading folliclereached a diameter of18mm.2.5.Controlled OvarianHyperstimulation(COH)Both groupswere instructedto tryup to3COHcycle.Urinary hMGand hCGwere usedforovarianstimulation.Ovulation inductionwas startedbetween day2and day5of menstruationcycleinpatients whohad noresidual cystslarger than20mm bybasal transvaginalultrasound monitor.All patientsinitially received75IU/day hMGfor5days.Follicle growthwas measuredultrasonographically every1-5days.Initial dosewas increasedor decreasedbetween37.5-75IU/day aordingto folliclesize andnumber.Blood estriol,LH andP levelswere monitoredand recordedon hCGinjection day.When1-3follicles reachedadiameterof18mm,10,000IU ofhCG wasadministered totrigger ovulation.Cycle wascancelled whenmorethan3mature follicleswere ob-served.Patients conductedtimed coitus36-48hours afterthe hCGinjection.Dydrogesterone Tablets(Solvay Pharmaceuticals)wereadministeredto supportthe lutealphase for12days.Patients withpositive hCGreceived progesteronesupport untiltwelve weeksof gestation.If thehCG resultwas negative,another COHcycle wasinitiated.2.6.Pregnancy EvaluationPatients whoseurine testresults werepositive hada repeatblood testto ascertaina healthyincrease inbeta hCGlevels.An intrauterinegestational sacand presenceof fetalcardiac activityconfirmed theviable clinicalpreg-nancy.Patients whoexperienced pregnancyloss afterthe sacwas visualizedwere consideredas clinicalmiscar-riages.Chemical pregnancywas confirmedbythedetection ofserum-hCG on the14th dayafter ovulation.2.7.Statistical AnalysisData wereanalyzed bySPSS version13.0for Windows(SPSS Inc.,Chicago,Illinois,USA).Continuous va-riables(age,duration of infertility,total motilesperm count,initial andtotal doseofovulationinduction agent,follicle countand sizeand endometrialthickness)were presentedas meanSD.Categorical variableswere presentedas frequencyand percentage.Studentsttest wasused topare normallydistributed continuousva-riables andMann-Whitney Utest forvariables withoutnormal distribution.Categorical variableswere -pared usingthe chi-square test.A two-tailed p value of0.05was consideredstatistically significant.3.Results Totally92case wererecruited,from which12patients werelost orrefused tofollow theprotocol.From there-maining80patients,42were incontrolgroup and38inacupuncturegroup.The parisonofthe two groupsis L.H.Cai etal.91summarized inTable1.4.Discussion Theprincipal treatmentsforunexplainedinfertility includetimedintercourseand lifestylechanges,COH,intra-uterine insemination(IUI)orinvitro fertilization(IVF)7.The proceduresof IUIand IVFare moreexpensive andtake longertime.Acupuncture hasalways beenapplied toreproductive treatmentin China.Western medicinemay exertinflu-ence onneuroendocrine system,immunological functionsand evensignal pathwayin considerationwhen dis-cussing theefficacyofacupuncture andthese stillcontinue tobe studied.The Chinesemedicine evaluatesthe effectofacupuncturefrom anoverall perspective.In Chinesemedicine,reproductive functionrelates notonly toreproductive organs,but alsotothekidney,the liver,andtheheart.That iswhy weusually selectmany acu-puncture pointsbesides Zigongwhen performingtreatment.Acupunctureisrooted intraditionalChinesemedi-cine(TCM)and emphasisesindividualised treatmentaordingtoTCM patterns8,here wemodify ouracu-points basingonthemost frequentlyused ones,such assanyinjiao(SP6),Guanyuan(CV4),Zhongji(CV3)and Zigong(Ex-CA1)being.A meta-analysis of27studies involving2939cycles revealedthat thepregnancy rateper cyclewas8%with gonadotropintreatment aloneand18%with gonadotropintreatment binedwith IUI9.In thisstudy,a cu-mulative pregnancyrate of24%for controlgroupand29%for acupuncturegroup wasachieved,and nosignifi-cant differenceswere foundbetweenthe2groups.Hysterosalpingography mayhave contributedpartly tothe highpregnancyrate.The primaryrole ofHSG isto evaluatethe morphologyandthepatency ofthe fallopiantubes10,and hasa mechanicalwashing effectontheuterinecavityand tubes,increasing thechance ofspon-taneous pregnancy,especially withoil-based contrast.Therefore,following anormal HSG,in ourcenter,we remendedup to3cycles asexpected durationof spontaneous pregnancy.This wasvaluable,because1couple fromcontrolgroupand3from acupuncturegroup achievedspontaneous pregnancy.Although nosignificant differenceswere found in pregnancyrate achievedby2study groups,it waseasier foracupuncturegroupto achievespontaneouspregnancy innaturalcycle.Regarding COH cycles,significantly fewercycleswereneeded inacupuncturegroup.This suggestedthat thoughacupuncturedidnotincrease thecumulative pregnancyrate,it diddecrease theexpected time,both inCOH andnaturalcycles.The reasonthat weneed notwait toomany cyclesalso baseon studiesresults.Unexplained infertilityalso meansthe possibilitythat someabnormality hasnot beendetected.For thosewomen withunexplainedinfertilitywith atleast threefailed cyclesofCOHand IUI,laparohysteroscopy revealedthat pelvicabnormalities werefoundin36.7%women andhysteroscopy showed6.7%intrauterine lesions11.This kindof patientshas rela-tively lowchance ofa suessfulpregnancy,and assistedreproductive technologiesshould beconsidered.Limitation ofthisstudyis thatthe smallnumberofsamples,and weneed moredetailed dataabout theme-chanism ofacupuncture.5.Conclusion Theresults ofthisstudyindicate thatacupuncturecanbeusedasanadjuvant treatmentforunexplainedinfertile-Table1.Comparison ofthetwogroups.Control group(n=42)Acupuncture group(n=38)pvalueAge(years)28.24.70Duration ofinfertility(years)1.80.45Primary infertility(cases)22130.102hMG doses(ampoules)12.00.87Mature eggs1.560.881.670.910.684COH cycles2.120.561.480.370.01Total clinicalpregnancy(cases)10110.272Spontaneous pregnancy(cases)130.341Biochemical(cases)110.728Miscarriage priorto12weeks(cases)200.495L.H.Cai etal.92ity.Although acupuncturedidnotincreasethecumulativepregnancyrate,it decreasedthe timeto achievepreg-nancyinCOHcycles.Funding Thiswork wassupported byGuangdong ProvinceScience andtechnology project(xxB021800091).References1The PracticeCommittee ofthe AmericanSociety forReproductive Medicine (xx)Effectiveness andTreatment forUnexplained Infertility.Fertility andSterility,86,S111-S114.ncbi.nlm.nih/pubmed/17055802dx.doi/10.1016/j.fertnstert.xx.07.14752The PracticeCommittee ofthe AmericanSocietyforReproductiveMedicine (xx)Optimal 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(xx)Influence ofAcupuncture onthe Outesofin Vitro FertilisationWhen EmbryoImplantation HasFailed:A ProspectiveRandomised ControlledClinical Trial.Acupuncture in Medicine,31,157-161.aim.bmj./content/31/2/157.long dx.doi/10.1136/acupmed-xx-0102694Smith,C.A.and Betts,D. (xx)The PracticeofAcupunctureand Moxibustionto PromoteCephalic Versionfor Womenwith aBreech Presentation:Implications forClinical Practiceand Research.Complementary TherapiesinMedicine,22,75-80.ncbi.nlm.nih/pubmed/24559820dx.doi/10.1016/j.ctim.xx.12.0055Smith,C.A.,de Lacey,S.,Chapman,M.,Ratcliffe,J.,Norman,R.J.,