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

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,有关不孕不育研究与管理的英国指南 Investigating and treating subfertility,Outline,目录,Philosophy of NICE guidance,NICE,（英国国家卫生医疗质量标准署）的指导理念,Diagnosis,诊断,When to treat,治疗时机,Treatment,处置,NICE versus professional guidelines,NICE,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,Levels of evidence,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,A survey of clinical trials of antibiotic prophylaxis in colon surgery:evidence against further use of no-treatment controls.ML Baum,DS Anish,TC Chalmers,HS Sacks,H Smith and RM Fagerstrom,New Engl J Med 305(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。,Quality of evidence for each outcome,Study design,实验设计,Study quality,实验质量,Consistency,实验一致性,Directness,实验直接相关性,GRADE working group,BMJ,2004,临床结果证据的质量,Quality of evidence,实验证据的质量,The extent to which one can be confident that an estimate of effect is correct.,在多大程度上，人们可以相信预估结果是正确的呢,.,GRADE working group,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,“,Failure to conceive after 12 months during which there is sexual intercourse with no use of contraception,”,“,女性在,1,年不采取避孕措施的性交后未能成功妊娠,”,Prevalence:1 in 7 couples,患病率：七分之一（每七对夫妇有一对不孕不育）,Aims of investigations,调查目的,To screen,筛查,To make a diagnosis,诊断,To predict outlook,预后,Evers,2002 Lancet:360,151-159,Investigations in the female,女性调查,Routine,常规检查,Test of ovulation,排卵检查,Endocrine screen in anovulatory women,不排卵女性的内分泌筛查,Tests of tubal patency,输卵管通畅试验,Others,其他检查,Chlamydia screen,衣原体筛查,Uterine assessment,子宫的评估,Potential screening tests,潜在筛查,Prediction of poor response,不良反应的预测,Test of ovulation,排卵检查,Gold standard is pregnancy,妊娠是排卵的金标准,History of regular cycles associated with 95%chance of ovulation,Behre et al,HR 2000,在常规的月经周期下，有,95%,的排卵几率,Other tests inferential,其他测试推论,Menstrual cycle history,月经周期的历史,Mid-luteal serum progesterone,黄体,血清孕酮,Ultrasound:labour intensive,超声:密集,性,Endometrial biopsy:invasive,子宫内膜活检:,侵袭性,Anovulation:endocrine tests,排卵障碍：内分泌检查,FSH,E2,Prolactin,Site of lesion,Low,低,Low,低,Normal,正常,Hypothalamus,下丘脑,Normal,正常,Normal,正常,Normal,正常,Hypo-pit-ov axis,下丘脑,-,垂体,-,卵巢轴,High,高,Low,低,Normal,正常,Ovary,卵巢,Low,低,Low,低,High,高,Central,中枢,Also test for thyroid disease(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:Rotterdam consensus criteria,多囊卵巢综合,征：鹿特丹会议专家推荐标准,Oligo and/or anovulation,排卵少和,/,或不排卵,Clinical and biochemical signs of hyperandrogenism,临床和生化,检查显示,雄激素过,高,Polycystic ovaries,多囊性卵巢,Exclusion of other etiologies(Cushing,s,adrenal hyperplasia),排除其他病因（库欣综合征，肾上腺增生症）,Human Reproduction,2004,Tubal evaluation:predictive value,输卵管检查：预测价值,敏感性 特异性,Land et al,1998,Mol et al,1999,子宫输卵管造影,病史,衣原体抗体检查,Should laparoscopy be mandatory in the work up of the infertile couple?,(Lavy et al EJOGRB 2004),腹腔镜检查是否应该强制性用于不孕夫妇的检查？,HSG,检查结果,样本量,腹腔镜检查结果一致,腹腔镜检查结果不一致,正常或单侧闭塞,63,60,3(5%),双侧闭塞,23,16,7(30%),Retrospective study of 86 patients,有关,86,名患者的回顾性研究,Laparoscopy can be omitted in normal HSG findings,在,HSG,正常的患者中腹腔镜检查可以省略,Laparoscopy should be performed if bilateral occlusion,在双侧输卵管闭塞的患者中腹腔镜检查应该实施,HSG vs Lap:pregnancy rate,子宫输卵管造影,vs,腹腔镜：妊娠率,Lap,HSG,无闭塞,单侧闭塞,双侧闭塞,总计,无闭塞,11%,0%,0%,11%,单侧闭塞,8%,12%,0%,20%,双侧闭塞,9%,5%,3%,17%,总计,28%,17%,3%,Mol et al,1999,Routine Hysteroscopy,常规子宫镜检查,Uterine abnormalities in 10-15%,Wallach,1972,10-15%,子宫异常,Causal relationship between fibroids and subfertility unconfirmed,Donnez,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,Fibroids reduce chance of conception,子宫肌瘤减小妊娠概率,Hart,2001,No RCTs or controlled studies,没有随机对照实验或者对照研究,No evidence for routine hysteroscopy,没有关于常规子宫镜检查的临床证据,NICE 2004,Laparoscopy v HSG v Ultrasound,腹腔镜检查,V,子宫输卵管造影,V,超声检查,Diagnosis of tubal blockage(laparoscopy as gold standard),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-Lacroix et al 2014 HR,Semen analysis,精液分析,Volume,精子计数,Concentration,浓度,Motility(%),能动性,Normal morphology,正常形态,Non-routine:,非常规检查：,DNA fragmentation DNA,分裂指数,Anti-sperm antibody,抗精子抗体,Viability tests,发育能力测试,AUC:,Motility,能动性,O.54,Morphology,形态学,0.56,Sripada et al,Fertil.Steril.2009,Age and FSH:area under ROC curve,年龄和促卵泡激素：,受试者特征曲线,下面积,Chuang et al,2003.Fertil Steril.79(1);6368,0.63,(0.60,0.66),),0.55,(0.51,0.58),0.62,(0.58,0.65),Pregnancy,妊娠,Age&FSH,年龄,&,促卵泡激素,FSH,促卵泡激素,Age,年龄,Broekmans et al,2006,Basal serum FSH:,基础血清促卵泡激素：,test accuracy,测试准确度,Summary ROC curve:37 studies,Poor ovarian response,卵巢反应低下,Non-pregnancy,未妊娠,Broer et al,2008,Antral Follicle Count vs Anti Mullerian Hormone,窦卵泡计数,vs抗穆氏管荷尔蒙,Poor ovarian response,卵巢反应低下,Non-pregnancy,未妊娠,Basic tests,基础检查,Mid-luteal progesterone(D21 in 28 day cycle),黄体中期孕酮检查（,28,天月经周期的第,21,天）,Rubella screen,风疹病毒筛查,Semen analysis,精液分析,Tubal assessment,输卵管评估,Bongaarts 1975 adapted by te Velde et al.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,Chances of getting pregnant within the next month,次月怀孕的概率,尝试妊娠的月份数,3,6,9,12,24,36,Age 25,18,15,12,10,6,3,Age 30,16,13,11,9,4,2,Age 35,12,9,7,6,2,1,Age 40,7,5,4,3,1,0.5,used in infertility,治疗不孕不育的方法,Tubal,输卵管,:IVF,体外受精,tubal surgery,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,DI,Anovulation,不排卵女性,:ovulation induction,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,Male factor infertility,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,Treatment,OR(95%CI),Clomiphene vs no treatment3.41(1.23 to 9.48),Hughes et al.2003,Cochrane,FSH vs HMG0.89(0.53 to 1.49),Nugent et al.2003,Cochrane,GnRH agonist in PCOS 1.50(0.72 to 3.12),Hughes et al.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,Clomiphene v Letrozole,克罗米芬,v,来曲唑,Clomiphene(n=376),Letrozole(n=374),Significance,Ovulation rates,排卵率,48.3%,61.7%,P=0.001,Live birth rates,活产率,19.1%,27.5%,P=0.007,Pregnancy loss,流产率,29.1%,31.8%,NS,Twins,双胞胎,7.4%,3.4%,NS,Congenital anomalies,先天异常,1,4,P=0.65,Legro et al NEJM 2014,rFSH v urinary gonadotrophinsfor ovarian stimulation in ART cycles,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,Type of urinary gonadotrophin v rec FSH,LB or OP with urinary,LB or OP with rFSH,Relative effect,(95%CI),Number of participants(studies),Quality of the evidence(GRADE),All urinary gonadotrophins,245/1000,239/1000,OR 0.97(0.87 1.08),7339,(28 studies),high,HMG/HMG-HP,255/1000,223/1000,OR 0.84(0.72-0.99),3197,(11 studies),High,FSH-P,170/1000,205/1000,OR 1.26(0.96 1.64),1430,(5 studies),High,FSH-HP,267/1000,273/1000,OR 1.03(0.86 1.22),2712,(13 studies),High,OHSS,19/1000,22/1000,OR 1.18(0.86 1.61),7740,(32 studies),High,Cochrane Database Syst Rev.2011 Feb 16;,Recombinant versus urinary gonadotrophin for,ovarian stimulation in assisted reproductive technology cycles.van Wely M,Kwan I,Burt AL,Thomas J,Vail A,Van der Veen F,Al-Inany HG,Endometriosis and Infertility,(RCOG),子宫内膜异位症与不孕不育（英国皇家妇产科学会）,No role for medical treatment,药物治疗没有作用,(A),Mild disease:Laparoscopic ablation may improve fertility(A),病情较轻时：腹腔镜下切除可能提高生育能力,Mild disease:IUI+SO helpful(A),病情较轻时：人工授精,+,超促排卵,Moderate disease:surgery may improve fertility(B),病情中等时：手术可能提高生育能力,Mild endometriosis and infertility:laparoscopic surgery,轻度子宫内膜异位症与不孕不育：腹腔镜手术,Jacobson et al,2003,Cochrane,Mild endometriosis:IUI+superovulation,轻度子宫内膜异位症：人工授精,+,超促排卵,Peto OR(95%CI),0.5 1 2 5 10,OR 2.7(1.2 to 5.8),Tummon 1997,Fedele 1992,Favours control,Favours IUI/SO,Unexplained infertility(UI),原因不明的不孕不育,Prevalence 20%-30%,发病率,20%-30%,Documented ovulation,常规排卵,Normal semen parameters,精液参数正常,Patent fallopian tubes,输卵管正常,Clomifene in Unexplained Infertility,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,Corrects subtle ovulatory problems,纠正排卵问题,Endometrial thinning,子宫内膜薄化,Multi-follicular ovulation,多囊卵巢,Oral tablet(days 2-6),口含片,Inexpensive,便宜,Multiple pregnancy,多胎妊娠,Clomifene in unexplained infertility,克罗米芬在原因不明的不孕不育中的应用,0.99 0.61,1.60,0.75 0.43,1.31,Live birth,Pregnancy,Hughes et al,2009,Cochrane Library,Intra-uterine insemination(IUI),+,SO,人工授精,+,超促排卵,Overcomes,hostile cervical factors,克服不良的子宫颈因素,Ensures proximity of sperm&egg,保证精子和卵子结合,Less invasive than IVF,比体外受精微创,Cheaper than IVF,比体外受精便宜,SO:risk of multiple pregnancy,超促排卵：多胎妊娠的风险,Verhulst et al,Cochrane 2006,Stimulated IUI vs stimulated,TI:live birth,宫腔内人工授精,vs,阴道内人工授精：,活胎,1.59 0.88,2.88,Veltman-Verhulst et al,Cochrane 2011,Natural cycle IUI vs stimulated,IUI:live birth,自然周期的人工授精,vs,刺激下人工授精：活胎,2.02 1.18,3.45,Favours IUI,Favours IUI+SO,Expectant,期待疗法,N=127,IUI+COH,人工授精,+,控制性超排卵,N=126,Mean(SD)years of infertility,不孕不育的平均时间,2.0(0.5),1.9(0.5),Mean(SD)female age(years),女性平均年龄,33(3.4),33(3.1),Ongoing pregnancy,继续妊娠率,40(32%),34(27%),(RR 0.85,95%CI 0.63 1.1),IUI alone vs expectant management,单一人工授精,vs,期待疗法,1.60 0.92,2.78,Veltman-Verhulst et al,Cochrane 2011,Stimulated IUI vs expectant management:livebirth,刺激下人工授精,vs,期待疗法：活胎,0.82 0.45,1.49,Veltman-Verhulst et al,Cochrane 2011,IVF in unexplained Infertility,体外受精在原因不明的不孕不育中的应用,Widely accepted treatment,是被广泛接受的治疗,Bypasses potential reproductive problems,绕过可能的生殖障碍,Demonstrates fertilisation,明确的受精,Live birth rate 20-30%,活胎率,20-30%,Invasive,侵袭性操作,Expensive,价格昂贵,IVF vs expectant management,体外受精,vs,期待疗法,Pandian et al,2004,Cochrane Library,3.24 1.07,9.80,IVF vs SO/IUI:live birth,体外受精,vs,超促排卵,/,人工授精：活胎,Pandian et al,2012,Cochrane Library,1.09 0.74,1.59,2.66 1.94,3.63,Conclusions,总结,No role for routine use of tests of ovarian reserve,没有必要进行常规的卵巢储备功能检查,Specific treatment for anovulation,endometriosis,tubal disease,对于不排卵症、子宫内膜异位症和输卵管疾病患者需要特殊治疗,IVF/ICSI for moderate severe male infertility,对中重度男性不孕症患者可采取体外受精,/卵胞浆内单精子注射,IVF for tubal and all prolonged subfertility,对于输卵管引起的和其他原因的长期生育能力低下的患者采取体外受精治疗,