有关不孕不育研究与管理的英国指南 Investigating and treating subfertility.ppt

UnitedKingdomguidelinesforinvestigationandmanagementofinfertility,MasoudAfnanUnitedFamilyHealthcare,有关不孕不育研究与管理的英国指南,Outline目录,PhilosophyofNICEguidanceNICE（英国国家卫生医疗质量标准署）的指导理念Diagnosis诊断Whentotreat治疗时机Treatment处置,NICEversusprofessionalguidelinesNICE与专业指南左图为2013年2月发布的临床指南下图为更新至2015年3月的指南,Levelsofevidence依据的等级,RCT实验的Meta分析和系统回顾,至少一个随机对照实验,至少一个设计良好的对照实验,至少一个设计良好的准实验,设计良好的描述性实验，例如对比研究、相关性分析、病例研究等,专家报告、观点；官方临床经验等,Asurveyofclinicaltrialsofantibioticprophylaxisincolonsurgery:evidenceagainstfurtheruseofno-treatmentcontrols.MLBaum,DSAnish,TCChalmers,HSSacks,HSmithandRMFagerstrom,NewEnglJMed305(1981),pp.795799关于在结肠手术中预防性使用抗生素的临床实验的调查研究：证据提示在进一步的临床试验中不得使用空白对照组,5,图表显示通过预防性使用抗生素减少的结肠手术术周死亡情况,等级划分临床证据的质量和建议的可靠性,临床指南和其依据的临床证据和评价具有同等效力，GRADE的目标是让临床医生更容易的评估建议的可靠性。,Qualityofevidenceforeachoutcome,Studydesign实验设计Studyquality实验质量Consistency实验一致性Directness实验直接相关性,GRADEworkinggroup,BMJ,2004,临床结果证据的质量,Qualityofevidence实验证据的质量,Theextenttowhichonecanbeconfidentthatanestimateofeffectiscorrect.在多大程度上，人们可以相信预估结果是正确的呢.,GRADEworkinggroup,BMJ,2004,高中低很低,预估结果不受其他实验的影响,预估结果可能受其他实验的影响,预估结果很可能受其他实验的影响,预估结果本身就非常的不确定,Infertility不孕不育,“Failuretoconceiveafter12monthsduringwhichthereissexualintercoursewithnouseofcontraception”“女性在1年不采取避孕措施的性交后未能成功妊娠”Prevalence:1in7couples患病率：七分之一（每七对夫妇有一对不孕不育）,Aimsofinvestigations调查目的,Toscreen筛查Tomakeadiagnosis诊断Topredictoutlook预后Evers,2002Lancet:360,151-159,Investigationsinthefemale女性调查,Routine常规检查Testofovulation排卵检查Endocrinescreeninanovulatorywomen不排卵女性的内分泌筛查Testsoftubalpatency输卵管通畅试验Others其他检查Chlamydiascreen衣原体筛查Uterineassessment子宫的评估Potentialscreeningtests潜在筛查Predictionofpoorresponse不良反应的预测,Testofovulation排卵检查,Goldstandardispregnancy妊娠是排卵的金标准Historyofregularcyclesassociatedwith95%chanceofovulationBehreetal,HR2000在常规的月经周期下，有95%的排卵几率Othertestsinferential其他测试推论Menstrualcyclehistory月经周期的历史Mid-lutealserumprogesterone黄体血清孕酮Ultrasound:labourintensive超声:密集性Endometrialbiopsy:invasive子宫内膜活检:侵袭性,Anovulation:endocrinetests排卵障碍：内分泌检查,Alsotestforthyroiddisease(TSH),LH,Testosterone,促卵泡激素雌二醇催乳素病变部位,同时也要检查甲状腺疾病（促甲状腺激素），黄体生成素，睾酮,PCOS:Rotterdamconsensuscriteria多囊卵巢综合征：鹿特丹会议专家推荐标准,Oligoand/oranovulation排卵少和/或不排卵Clinicalandbiochemicalsignsofhyperandrogenism临床和生化检查显示雄激素过高Polycysticovaries多囊性卵巢Exclusionofotheretiologies(Cushings,adrenalhyperplasia)排除其他病因（库欣综合征，肾上腺增生症）,HumanReproduction,2004,Tubalevaluation:predictivevalue输卵管检查：预测价值敏感性特异性,Landetal,1998,Moletal,1999,子宫输卵管造影,病史,衣原体抗体检查,Shouldlaparoscopybemandatoryintheworkupoftheinfertilecouple?(LavyetalEJOGRB2004)腹腔镜检查是否应该强制性用于不孕夫妇的检查？,Retrospectivestudyof86patients有关86名患者的回顾性研究LaparoscopycanbeomittedinnormalHSGfindings在HSG正常的患者中腹腔镜检查可以省略Laparoscopyshouldbeperformedifbilateralocclusion在双侧输卵管闭塞的患者中腹腔镜检查应该实施,HSGvsLap:pregnancyrate子宫输卵管造影vs腹腔镜：妊娠率,Moletal,1999,RoutineHysteroscopy常规子宫镜检查,Uterineabnormalitiesin10-15%Wallach,197210-15%子宫异常CausalrelationshipbetweenfibroidsandsubfertilityunconfirmedDonnez,2002有关子宫肌瘤和生育能力低下的因果相关性尚未得到证实Fibroidsreducechanceofconception子宫肌瘤减小妊娠概率Hart,2001NoRCTsorcontrolledstudies没有随机对照实验或者对照研究Noevidenceforroutinehysteroscopy没有关于常规子宫镜检查的临床证据NICE2004,LaparoscopyvHSGvUltrasound腹腔镜检查V子宫输卵管造影V超声检查,Diagnosisoftubalblockage(laparoscopyasgoldstandard)腹腔镜检查是诊断输卵管阻塞的金标准Ultrasound超声检查Sensitivity敏感性95%(78-99%)Specificity特异性93%(89-96%)HSG子宫输卵管造影Sensitivity敏感性94%(74-99%)Specificity特异性92%(87-95%),Maheux-Lacroixetal2014HR,Semenanalysis精液分析,Volume精子计数Concentration浓度Motility(%)能动性Normalmorphology正常形态Non-routine:非常规检查：DNAfragmentationDNA分裂指数Anti-spermantibody抗精子抗体Viabilitytests发育能力测试,AUC:Motility能动性O.54Morphology形态学0.56,Sripadaetal,Fertil.Steril.2009,AgeandFSH:areaunderROCcurve年龄和促卵泡激素：受试者特征曲线下面积Chuangetal,2003.FertilSteril.79(1);6368,Broekmansetal,2006,BasalserumFSH:基础血清促卵泡激素：testaccuracy测试准确度SummaryROCcurve:37studies,Poorovarianresponse卵巢反应低下,Non-pregnancy未妊娠,Broeretal,2008,AntralFollicleCountvsAntiMullerianHormone窦卵泡计数vs抗穆氏管荷尔蒙,Poorovarianresponse卵巢反应低下,Non-pregnancy未妊娠,Basictests基础检查,Mid-lutealprogesterone(D21in28daycycle)黄体中期孕酮检查（28天月经周期的第21天）Rubellascreen风疹病毒筛查Semenanalysis精液分析Tubalassessment输卵管评估,Bongaarts1975adaptedbyteVeldeetal.2000),怀孕的概率,红线指刚停止采取避孕措施蓝色指1年内未妊娠绿色指3年内未妊娠,Chancesofgettingpregnantwithinthenextmonth次月怀孕的概率,www.freya.nl/probability.php.,Treatmentsusedininfertility治疗不孕不育的方法,Tubal输卵管:IVF体外受精,tubalsurgery输卵管手术Male男性:IUI人工授精,IVF体外受精/ICSI卵胞浆内单精子注射,DIAnovulation不排卵女性:ovulationinduction诱导排卵Endometriosis子宫内膜异位症:surgery手术,IUI人工授精,IVF体外受精Unexplained无法解释的原因:expectant期待疗法,empirical经验主义,Malefactorinfertility男性不孕症,人工授精vs按时规律性交,手术或栓塞vs不予处置,人工授精vs经宫颈受精（捐精）,Anovulation不排卵症,TreatmentOR(95%CI)Clomiphenevsnotreatment3.41(1.23to9.48)Hughesetal.2003,CochraneFSHvsHMG0.89(0.53to1.49)Nugentetal.2003,CochraneGnRHagonistinPCOS1.50(0.72to3.12)Hughesetal.2003,Cochrane,克罗米芬vs不予处置,促卵泡激素vs促性腺激素,促性腺激素释放激素激动剂在多囊卵巢综合征中应用,ClomiphenevLetrozole克罗米芬v来曲唑,LegroetalNEJM2014,rFSHvurinarygonadotrophinsforovarianstimulationinARTcycles重组人卵泡促激素vs促性腺激素在辅助生殖技术周期卵巢刺激作用,CochraneDatabaseSystRev.2011Feb16;Recombinantversusurinarygonadotrophinforovarianstimulationinassistedreproductivetechnologycycles.vanWelyM,KwanI,BurtAL,ThomasJ,VailA,VanderVeenF,Al-InanyHG,EndometriosisandInfertility(RCOG)子宫内膜异位症与不孕不育（英国皇家妇产科学会）,Noroleformedicaltreatment药物治疗没有作用(A)Milddisease:Laparoscopicablationmayimprovefertility(A)病情较轻时：腹腔镜下切除可能提高生育能力Milddisease:IUI+SOhelpful(A)病情较轻时：人工授精+超促排卵Moderatedisease:surgerymayimprovefertility(B)病情中等时：手术可能提高生育能力,Mildendometriosisandinfertility:laparoscopicsurgery轻度子宫内膜异位症与不孕不育：腹腔镜手术,Jacobsonetal,2003,Cochrane,Mildendometriosis:IUI+superovulation轻度子宫内膜异位症：人工授精+超促排卵,PetoOR(95%CI),0.512510,OR2.7(1.2to5.8),Tummon1997,Fedele1992,Favourscontrol,FavoursIUI/SO,Unexplainedinfertility(UI)原因不明的不孕不育,Prevalence20%-30%发病率20%-30%Documentedovulation常规排卵Normalsemenparameters精液参数正常Patentfallopiantubes输卵管正常,ClomifeneinUnexplainedInfertility克罗米芬在原因不明的不孕不育中的应用,Anti-oestrogen雌激素拮抗物Correctssubtleovulatoryproblems纠正排卵问题Endometrialthinning子宫内膜薄化Multi-follicularovulation多囊卵巢Oraltablet(days2-6)口含片Inexpensive便宜Multiplepregnancy多胎妊娠,Clomifeneinunexplainedinfertility克罗米芬在原因不明的不孕不育中的应用,0.990.61,1.60,0.750.43,1.31,Livebirth,Pregnancy,Hughesetal,2009,CochraneLibrary,Intra-uterineinsemination(IUI)+SO人工授精+超促排卵,Overcomeshostilecervicalfactors克服不良的子宫颈因素Ensuresproximityofsperm&egg保证精子和卵子结合LessinvasivethanIVF比体外受精微创CheaperthanIVF比体外受精便宜SO:riskofmultiplepregnancy超促排卵：多胎妊娠的风险,Verhulstetal,Cochrane2006,StimulatedIUIvsstimulatedTI:livebirth宫腔内人工授精vs阴道内人工授精：活胎,1.590.88,2.88,Veltman-Verhulstetal,Cochrane2011,NaturalcycleIUIvsstimulatedIUI:livebirth自然周期的人工授精vs刺激下人工授精：活胎,2.021.18,3.45,FavoursIUI,FavoursIUI+SO,IUIalonevsexpectantmanagement单一人工授精vs期待疗法,1.600.92,2.78,Veltman-Verhulstetal,Cochrane2011,StimulatedIUIvsexpectantmanagement:livebirth刺激下人工授精vs期待疗法：活胎,0