不孕症与辅助生殖技术.ppt

Infertility and Assisted Reproductive Technologies 不孕症与辅助生殖技术,XIN LU Obstetrics & Gynecology Hospital Fudan University,Contents,Infertility Definition; Causes; Examinations and Diagnosis; Treatment; Assisted Reproductive Technologies (ART) ; Intrauterine insemination ( IUI); In vitro fertilization and embryo transfer (IVF-ET); Intracytoplasmic sperm injection (ICSI); Gamete intrafallopian transfer (GIFT);,Definition of Infertility 不孕症定义,Infertility is defined one year of unprotected intercourse without pregnancy. (WHO) Primary Infertility : no previous pregnancies 原发不孕 have occurred; Secondary Infertility: a prior pregnancy has 继发不孕 occurred;,Age and Infertility 年龄与不孕,age fertility abortion Fertility rate 35 yr 54% 24.6% 40 yr 51.0% female male 10 20 30 40 50 60 70,Female conceiving,Risk of Smoking,Smoking Risk Knowledge of Risk Lung cancer 99% Respiratory 99% Heart disease 96% Miscarriage 39% Osteoporosis 30% Ectopic pregnancy 27% Infertility 22% Early menopause 17%,Female Reproductive duct anatomy 女性生殖道解剖,Female ovary 卵巢 fallopian 输卵管 uterus 子宫 cervix 宫颈 Vagina 阴道,Male Reproductive duct anatomy 男性生殖道解剖,Male testis 睾丸 epididymis 附睾, prostate 前列腺 vas deferens 输精管 seminal vesicals 精囊 bulbourethral glands 尿道球腺 ejaculatory duct 射精管 urethra 尿道,Female Reproductive Physiology 女性生殖生理,1. 下丘脑-垂体-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 2. 卵巢周期性排卵 5. 宫颈 6. 下生殖道,hypothalamus,ovary,pituitary,子宫,ovary,4. 子宫,Normal Gestation -the beginning of human,Follopian tube Uterine ovary oocyte Cervix Extra-genital tract sperm,Causes 原因,Causes Percentage Female factors 40 % Male factors 30-40 % Both male and female factors 10-20 % Immunologic unexplained factors 10 %,1. Hypothalamic dysfunction; 2. Pituitary Insufficiency; 3. Ovarian factor (peripheral defect); 4. Others: thyroid or adrenal dysfunction;,Ovulatory dysfunction 排卵障碍,hypothalamus,pituitary,ovary,Pelvic factors 盆腔因素,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 abnormalities,Etiology Related Disorders,Ovulatory dysfunction PCOS Hypothalamic-pituitary Age-related POF Tubal disease PID Uterine abnormalities Congenital Leiomyomas Asherman syndrome Other Endometriosis PCOS=polycystic ovarian disease POF= premature ovarian failure PID= pelvic inflammatory disease,Male Factors 男方因素,1. Abnormal spermatogenesis congenital; chronic diseases; infectious factors; 2. Obstructive: sperm transport abnormalities; 3. Immunologic factors; 4. Endocrine disorders; 5. Sexual dysfunction;,Both Male and Female Factors,1. No demonstrable cause; 2. Psychological factors; 3. Immunologic factors; count for 10%; autoimmune response; auto-antibodies;,Summary-Infertility Causes,Factors from either or both partners may contribute to difficulties in conceiving; THEREFORE It is important to consider all possible diagnosis before pursuing invasive treatment.,Examination and Diagnoses 检查和诊断,Initial Visit 初诊 The initial visit is the most important; The infertility is a problem of couple; The male partner should be present; History: both male and female; The guide to diagnostic and treatment plans;,Examinations 检查,History collection； Female Physical examination; Bimanual examination（双合诊）; Rectal-Vaginal-examination (三合诊）； Laboratory; Assistant imaging; Male Physical examination; Laboratory-Semen analysis;,Examinations (for female) 女方检查,Special Laboratory Examinations: semen analysis（精液分析）; hormone measurement; sperm penetration assay (SPA)精子穿透试验; postcoital examinition of cervical mucus （性交后宫颈粘液试验） anti-sperm immunologic examination; Assistant imaging : Unltrasound 超声; Hysterosalpingogram 子宫输卵管碘油造影; Hysteroscopy 宫腔镜; Laparoscopy 腹腔镜；,Hysterosalpingogram (HSG),LAPAROSCOPY in INFERTILITY,Methods to monitor ovulation 监测排卵的方法,Luteinizing Hormone monitoring: LH surge; after 34-36 hr occur ovulation; Basal Body Temperature: simple, cheap, biphasic pattern; Mid-luteal serum progesterone: 3ng/mL, peak; Premenstrual molimina: 95% presence; Mucus change: thick and cellular, no crystalline fern; Ultrasound monitoring: follicle size 21-23 mm, fluid in the cul-de-sac.,Basal Body Temperature (BBT),Normal Values for Semen Analysis 精液分析正常值,volume 2.0 mL sperm concentration 20 x 106 /mL motility 50 % normal morphology 15 % WBC 1x106 /mL Data from WHO, 1999 Please keep 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 evaluation History Physical exam,Irregular menses No ovulation,HSG or Hysteroscopy Abnormal of uterine,Normal evaluation,HSG Tubal blockage,Abnormal Semen analysis,anovulation,Tubal factor,unexplained,Uterine factor,Male factor,Further Investigate and Treatment,Treatment principle for female factors,Causes Treatment induction of ovulation； tuboplasty, microsurgery； medication or surgery； immune inhibition；,anovulation,Tubal factor,Anatomic factor,immunologic,azoospermia,genetic disease,after surgery,Failure above,Assisted Reproductive Technologies (ART) 辅助生育技术,unexplained,Induction of ovulation 诱发排卵-1,1. Clomiphen 氯米芬：ER binding GnRH , FSH/LH dosage：50 mg, period day 5th， 5 days； 2. Gonadotropin therapy 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: 5000-10000 IU;,Induction of ovulation 诱发排卵-2,4. Gonadotropin releasing hormone agonist (GnRH-a)：hypothalamic factor, as COH; protocol: according the every GnRH-a component and feature, the time of start and discontinuation are different; zoladex; decapeptyl, dipherenline, enantone; 5. Bromocriptine 溴隐停: high PRL;,Assisted Reproductive Technologies (ART) 辅助生育技术,Intrauterine insemination ( IUI); 宫腔内人工授精; In vitro fertilization and embryo transfer (IVF-ET); 体外受精与胚胎移植; Intracytoplasmic sperm injection (ICSI); 单精子卵泡浆注射； Gamete intrafallopian transfer (GIFT); 配子输卵管移植;,Intrauterine insemination ( IUI) 人工授精,Indications: 1. male factor infertility; 2. psychological factors; 3. unexplained infertility; 4. genetic defects; Types: 1. artificial insemination with husbands sperm (AIH); 2. artificial insemination by donor (AID); Method: 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 transfer (IVF-ET) 体外受精与胚胎移植,Indications: 1. tubal factor; 2. endometriosis; 3. unexplained infertility; 4. IUI failure; 5. Immunologic factors; Method: 1. Superovulation: COH, GnRH-a/FSH(HMG)/HCG; 2. Aspiration of eggs; 3. Fertilization with capacitated sperm; 4. Culture of fertilized egg in the lab; 5. Replacement of fertilized egg into the uterus;,Intracytoplasmic sperm injection 单精子卵泡浆注射 (ICSI),Micromanipulation technique; Indications: 1. as treatment of male factor infertility: epididyma obstruction, azoospermia, retrograde ejaculation; 2. IVF failure; Surgical sperm recovery for ICSI: 1. Percutaneous epididymal sperm aspiration (PESA); 2. Percutaneous testicular sperm fine-needle aspiration (TESA); Complications: karyotypic abnormalities; other genetic defects;,Gamete intrafallopian transfer (GIFT) 配子输卵管移植,Indications: 1. unexplained infertility; 2. endometriosis; 3. IUI failure; 4. Premature ovarian failure (POF); 5. Immunologic factors; Method: 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 fallopian tube;,ART Complications 辅助生育技术并发症,Ovarian hyperstimulation syndrome (OHSS) 卵巢过激综合征; Multiple gestations 多胎妊娠; Pre-eclampsia 产前子痫; Premature birth 早产; Low birth weight 出生低体重; Long term emotional, social and psychological impact 长期影响（情绪，社会，精神）;,Ovarian HyperStimulation Syndrome (OHSS) 卵巢过度刺激综合征,Causes: 1. HCG injection-trigger; 2. VEGF 3. high estrogen level 4. Inflammatory media and cytokines Patho-physiological mechanism: local and systemic increase in capillary permeability Clinical finding: 1. abdominal discomfort, nausea, vomiting, pain 2. pleural effusion, chest pain, shortness of breath 3. ascites, increased abdominal girth, weight gain 4. decreased urine output, oliguria 5. liver and renal function failure,Classification and Staging of Ovarian Hyperstimulation Syndrome,Grade 1: Abdominal distention/discomfort Grade 2: Grade 1 plus nausea and vomiting or diarrhea Ovaries enlarged 5-12 cm Grade 3: Sonographic evidence of ascites Grade 4: Clinical evidence of ascites or hydrothorax or difficulty breathing Grade 5: All of the above plus decreased blood volume, hemoconcentration , diminished renal perfusion and function and coagulation abnormalities,Ovarian HyperStimulation Syndrome (OHSS) 卵巢过度刺激综合征,Examinations: 1. Complete blood account, liver function, BUN 2. Prothrombin time, partial thromboplastin time 3. Chest X-ray 4. Transvaginal ultrasound 5. Oxygen saturation 6. Fluid balance 7. Serum HCG measurement 8. Pelvic exam is contraindicated; Treatment: 1. Prevention of OHSS 2. Follow-up: Vital signs, fluid intake and output measurement 3. Admission to hospital,No conception 1year Age= 35 HSG Semen analysis CD#3FSH Normal Abnormal Normal Abnormal Surgical correction Irregular Reg