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1、Infertility and Infertility and Assisted Assisted Reproductive Technologies Reproductive Technologies 不孕症与不孕症与辅助生殖技术辅助生殖技术XIN LUXIN LUObstetrics & Gynecology Hospital Fudan University ContentsContentsnInfertilitynDefinition;nCauses;nExaminations and Diagnosis;nTreatment;nAssisted Reproductive Te
2、chnologies (ART) ;nIntrauterine insemination ( IUI);nIn vitro fertilization and embryo transfer (IVF-ET);nIntracytoplasmic sperm injection (ICSI); nGamete intrafallopian transfer (GIFT); Definition of Infertility Definition of Infertility 不孕症定义不孕症定义 Infertility is defined two years of unprotected in
3、tercourse without pregnancy. (WHO, one year)Primary Infertility : no previous pregnancies 原发不孕原发不孕 have occurred; Secondary Infertility: a prior pregnancy has 继发不孕继发不孕 occurred;Female Reproductive duct Female Reproductive duct anatomy anatomy 女性生殖道解剖女性生殖道解剖Female Female ovary 卵巢卵巢fallopian 输卵管输卵管 ut
4、erus 子宫子宫cervix 宫颈宫颈Vagina 阴道阴道女性生殖生理女性生殖生理n1. 下丘脑下丘脑-垂体垂体-卵巢轴内分泌调节卵巢轴内分泌调节 Femal Male ( H-P-O) (H-P-T) GnRH GnRH FSH,LH FSH,LH E/P T 4. 3.输卵管输卵管 2. 卵巢周期性排卵卵巢周期性排卵 5. 宫颈宫颈 6. 下生殖道下生殖道下丘脑下丘脑卵巢卵巢垂体垂体卵巢卵巢Causes Causes 原因原因Causes PercentageFemale factors 40-55 %Male factors 25-40 %Both male and female f
5、actors 20 %Immunologic unexplained factors 10 % 1. Hypothalamic dysfunction; 2. Pituitary Insufficiency; 3. Ovarian factor (peripheral defect); 4. Others: thyroid or adrenal dysfunction;Ovulatory dysfunctionOvulatory dysfunction排卵障碍排卵障碍hypothalamuspituitaryovaryPelvic factors Pelvic factors 盆腔因素盆腔因素
6、 1. Tubal factors: injury, blockage, adhesion 2. Uterine factors: cogenital anatomic abnormalities endometrium disorder, tumor 3. Cervical factors: infection, cogenital abnormalities 4. Extra-genital tract factors; infection, cogenital abnormalitiesMale Factors Male Factors 男方因素男方因素 1. Abnormal sper
7、matogenesis congenital; chronic diseases; infectious factors; 2. Obstructive: sperm transport abnormalities; 3. Immunologic factors; 4. Endocrine disorders; 5. Sexual dysfunction; Both Male and Female FactorsBoth Male and Female Factors 1. No demonstrable cause; 2. Psychological factors; 3. Immunolo
8、gic factors; count for 10%; autoimmune response; auto-antibodies; Examination and Diagnoses检查和诊断检查和诊断nInitial Visit 初诊初诊nThe initial visit is the most important;nThe infertility is a problem of couple;nThe male partner should be present;nHistory: both male and female;nThe guide to diagnostic and tre
9、atment plans; Examinations 检查检查nHistory collection;nFemalenPhysical examination;nBimanual examination(双合诊)双合诊);nRectal-Vaginal-examination (三合诊);三合诊);nLaboratory;nAssistant imaging;nMalenPhysical examination;nLaboratory-Semen analysis; Examinations (for female) 女方检查女方检查nSpecial Laboratory Examinatio
10、ns: semen analysis(精液分析)精液分析); hormone measurement; sperm penetration assay (SPA)精子穿透试验精子穿透试验; postcoital examinition of cervical mucus (性交后宫颈粘液试验)(性交后宫颈粘液试验) anti-sperm immunologic examination;nAssistant imaging : Unltrasound 超声超声; Hysterosalpingogram 子宫输卵管碘油造影子宫输卵管碘油造影; Hysteroscopy 宫腔镜宫腔镜;nLaparo
11、scopy 腹腔镜;腹腔镜; Methods to monitor ovulation监测排卵的方法监测排卵的方法nLuteinizing Hormone monitoring: LH surge; after 34-36 hr occur ovulation;nBasal Body Temperature: simple, cheap, biphasic pattern;nMid-luteal serum progesterone: 3ng/mL, peak;nPremenstrual molimina: 95% presence;nMucus change: thick and cellu
12、lar, no crystalline fern;nUltrasound monitoring: follicle size 21-23 mm, fluid in the cul-de-sac. Normal Values for Semen AnalysisNormal Values for Semen Analysis 精液分析正常值精液分析正常值volume 2.0 mLsperm concentration 20 x 106 /mLmotility 50 %normal morphology 15 %WBC 1x106 /mLData from WHO, 1999 Please kee
13、p in mind: 1. Cycle of Spermiogenesis takes about 74 days; 2. Semen parameters in males may vary; 3. Abnormal semen analysis should repeat at least once; Examination and Diagnoses Initial evaluationHistoryPhysical examIrregular mensesNo ovulation HSG orHysteroscopyAbnormal of uterineNormalevaluation
14、HSGTubal blockageAbnormal Semen analysisanovulation Tubal factorunexplainedUterine factorMale factorFurther Investigate and Treatment Treatment principle for female factors Causes Treatment induction of ovulation; tuboplasty, microsurgery; medication or surgery; immune inhibition; anovulationTubal f
15、actorAnatomic factorimmunologicazoospermiagenetic diseaseafter surgeryFailure aboveAssisted Reproductive Technologies(ART) 辅助生育技术辅助生育技术unexplained Induction of ovulationInduction of ovulation 诱发排卵诱发排卵-1-1 1. Clomiphen 氯米芬:氯米芬:ER binding GnRH , FSH/LH dosage:50 mg, period day 5th, 5 days; 2. Gonadotr
16、opin therapy 促性腺激素治疗:促性腺激素治疗: Indications: Hypogonadotropic hypogonadism; Pituitary dysfunction; COH in IVF; (COH : controlled ovarian hyperstimulation) HMG: human menopausal gonadotropins; FSH 75 IU/LH 75 IU, IM or SC; Recombinant FSH: 75 IU, SC; 3. HCG 绒毛膜促性腺腺激素绒毛膜促性腺腺激素: 5000-10000 IU; Induction
17、of ovulationInduction of ovulation 诱发排卵诱发排卵-2-24. Gonadotropin releasing hormone agonist (GnRH-a a):hypothalamic factor, as COH; protocol: according the every GnRH-a a component and feature, the time of start and discontinuation are different; zoladex; decapeptyl, dipherenline, enantone;5. Bromocrip
18、tine 溴隐停溴隐停: high PRL; Assisted Reproductive Assisted Reproductive Technologies (ART) Technologies (ART) 辅助生育技术辅助生育技术nIntrauterine insemination ( IUI); 宫腔内人工授精宫腔内人工授精;nIn vitro fertilization and embryo transfer (IVF-ET); 体外受精与胚胎移植体外受精与胚胎移植;nIntracytoplasmic sperm injection (ICSI); 单精子卵泡浆注射;单精子卵泡浆注射;
19、nGamete intrafallopian transfer (GIFT); 配子输卵管移植配子输卵管移植; Intrauterine insemination Intrauterine insemination ( IUI) ( IUI) 人工授精人工授精nIndications: 1. as treatment of male factor infertility; 2. psychological factors; 3. unexplained infertility; 4. genetic defects;nTypes: 1. artificial insemination with
20、 husbands sperm (AIH); 2. artificial insemination by donor (AID); nMethod: placement of about 0.3 ml of washed, processed and concentrated sperm into the intrauterine cavity by trans-cervical catheterizaion.In vitro fertilization and embryo In vitro fertilization and embryo transfer (IVF-ET) transfe
21、r (IVF-ET) 体外受精与胚胎移植体外受精与胚胎移植nIndications: 1. tubal factor; 2. endometriosis; 3. unexplained infertility; 4. IUI failure; 5. Immunologic factors;nMethod: 1. Superovulation: COH, GnRH-a/a/FSH(HMG)/HCG; 2. Aspiration of eggs; 3. Fertilization with capacitated sperm; 4. Culture of fertilized egg in the
22、 lab; 5. Replacement of fertilized egg into the uterus;Intracytoplasmic sperm injection 单精子卵泡浆注射单精子卵泡浆注射 (ICSI)nMicromanipulation technique;nIndications: 1. as treatment of male factor infertility: epididyma obstruction, azoospermia, retrograde ejaculation; 2. IVF failure;nSurgical sperm recovery fo
23、r ICSI: 1. Percutaneous epididymal sperm aspiration (PESA); 2. Percutaneous testicular sperm fine-needle aspiration (TESA); nComplications: karyotypic abnormalities; other genetic defects;Gamete intrafallopian Gamete intrafallopian transfer (GIFT) transfer (GIFT) 配子输卵管移植配子输卵管移植nIndications: 1. unexp
24、lained infertility; 2. endometriosis; 3. IUI failure; 4. Premature ovarian failure (POF); 5. Immunologic factors;nMethod: 1. Superovulation is induced as IVF-ET; 2. HCG injection is given; 3. Follicle are aspirated via laparoscopy; 4. Sperm mixed with egg; 5. Replacement of fertilized egg into fallo
25、pian tube;ART Complications辅助生育技术并发症辅助生育技术并发症nMultiple gestations 多胎妊娠多胎妊娠;nPre-eclampsia 产前子痫产前子痫;nOvarian hyperstimulation syndrome (OHSS) 卵巢过激综合征卵巢过激综合征; ;nPremature birth 早产早产;nLow birth weight 出生低体重出生低体重;nLong term emotional, social and psychological impact 长期影响(情绪,社会,精神)长期影响(情绪,社会,精神); Ovarian HyperStimulation Syndrome (OHSS)卵巢过度刺激综合征卵巢过度刺激综合征nCauses: 1. HCG injection-trigger; 2. VEGF 3.
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