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1、Infertility and Assisted Reproductive Technologies 不孕癥與輔助生殖技術(shù),XIN LUObstetrics & Gynecology Hospital Fudan University,Contents,Infertility Definition; Causes; Examinations and Diagnosis; Treatment;Assisted R
2、eproductive Technologies (ART) ; Intrauterine insemination ( IUI); In vitro fertilization and embryo transfer (IVF-ET); Intracytoplasmic sperm injection (ICSI); Gamete intrafallopian transfer (GIFT);,Definition of
3、Infertility 不孕癥定義,Infertility is defined one year of unprotected intercourse without pregnancy. (WHO)Primary Infertility : no previous pregnancies 原發(fā)不孕 have occurred; Secondary Infertilit
4、y: a prior pregnancy has 繼發(fā)不孕 occurred;,Age and Infertility 年齡與不孕,age fertility abortion Fertility rate
5、 35 yr 54% 24.6% >40 yr 51.0% female
6、 male
7、 10 20 30 40 50 60 70,,,,,,,,,,,,,,,,,Female conceiving,Risk of Smoking,Smoking Risk Knowledge of Risk Lung cancer
8、 99% Respiratory 99% Heart disease 96% Miscarriage 39% Osteoporosis 30% Ectopic pr
9、egnancy 27% Infertility 22% Early menopause 17%,,,Female Reproductive duct anatomy 女性生殖道解剖,Female ovary 卵巢fallopian 輸卵管 uterus
10、子宮cervix 宮頸Vagina 陰道,Male Reproductive duct anatomy 男性生殖道解剖,Male testis 睪丸epididymis 附睪,prostate 前列腺vas deferens 輸精管seminal vesicals 精囊bulbourethral glands 尿道球腺ejaculatory duct 射精管urethra 尿道,Female Repr
11、oductive Physiology 女性生殖生理,1. 下丘腦-垂體-卵巢軸內(nèi)分泌調(diào)節(jié) Femal Male ( H-P-O) (H-P-T)
12、 GnRH GnRH FSH,LH FSH,LH
13、 E/P T 4. 3.輸卵管 2. 卵巢周期性排卵
14、 5. 宮頸 6. 下生殖道,hypothalamus,ovary,pituitary,子宮,,ovary,,,,,,4.子宮,,,,,,,,,,,,Normal Gestation-----
15、the beginning of human,,,,,,,,,,,Follopian tube Uterine ovary oocyte Cervix
16、 Extra-genital tract sperm,,,,,,,,,,,,,,,,Causes 原因,Causes PercentageFemale factors 40 %Male factors 30-4
17、0 %Both male and female factors 10-20 %Immunologic unexplained factors 10 %,,,,,,,1. Hypothalamic dysfunction; 2. Pituitary Insufficiency; 3. Ovarian factor (periphera
18、l defect); 4. Others: thyroid or adrenal dysfunction;,Ovulatory dysfunction排卵障礙,hypothalamus,pituitary,ovary,,,Pelvic factors 盆腔因素,1. Tubal factors: injury, blockage, adhesion 2. Uterine factors:
19、 cogenital anatomic abnormalities endometrium disorder, tumor 3. Cervical factors: infection, cogenital abnormalities 4. Extra-genital tract factors; infection, cogenital abnormalities,Etiolo
20、gy Related Disorders,Ovulatory dysfunction PCOS Hypothalamic-pituitary Ag
21、e-related POFTubal disease PIDUterine abnormalities Congenital
22、 Leiomyomas Asherman syndromeOther EndometriosisPCOS=polycystic ovarian disease POF= premature ovarian
23、failure PID= pelvic inflammatory disease,,Male Factors 男方因素,1. Abnormal spermatogenesis congenital; chronic diseases; infectious factors; 2. Obstructive: sperm
24、transport abnormalities; 3. Immunologic factors; 4. Endocrine disorders; 5. Sexual dysfunction;,Both Male and Female Factors,1. No demonstrable cause; 2. Psychological factors; 3. Immunolog
25、ic factors; count for 10%; autoimmune response; auto-antibodies;,Summary--Infertility Causes,Factors from either or both partners may contribute to difficulties in conceiving;
26、 THEREFORE It is important to consider all possible diagnosis before pursuing invasive treatment.,Examination and Diagnoses檢查和診斷,Initial Visit 初診The initial visit is
27、 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 檢查,History collection;FemalePhys
28、ical examination;Bimanual examination(雙合診);Rectal-Vaginal-examination (三合診);Laboratory;Assistant imaging;MalePhysical examination;Laboratory---Semen analysis;,Examinations (for female) 女方檢查,Special Laboratory
29、 Examinations: semen analysis(精液分析); hormone measurement; sperm penetration assay (SPA)精子穿透試驗(yàn); postcoital examinition of cervical mucus
30、 (性交后宮頸粘液試驗(yàn)) anti-sperm immunologic examination;Assistant imaging : Unltrasound 超聲; Hysterosalpingogram 子宮輸卵管碘油造影;
31、 Hysteroscopy 宮腔鏡;Laparoscopy 腹腔鏡;,Hysterosalpingogram (HSG),LAPAROSCOPY in INFERTILITY,,Methods to monitor ovulation監(jiān)測(cè)排卵的方法,Luteinizing Hormone monitoring: LH surge; after 34-36 hr
32、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 crystall
33、ine 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 mLsperm con
34、centration ≥ 20 x 106 /mLmotility ≥ 50 %normal morphology ≥ 15 %WBC < 1x106 /mLData from WHO, 1999 Please keep in mind: 1
35、. 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
36、exam,Irregular mensesNo ovulation,HSG orHysteroscopyAbnormal of uterine,Normalevaluation,HSGTubal blockage,Abnormal Semen analysis,,,,,,,anovulation,Tubal factor,unexplained,Uterine factor,Male factor,,,,,,,,,,,F
37、urther Investigate and Treatment,Treatment principle for female factors,Causes Treatment induction of ovulation; tuboplasty,
38、 microsurgery; medication or surgery; immune inhibition;,anovulation,Tubal factor,Anatomic factor,immunologic,azoo
39、spermia,genetic disease,,,,,after surgery,Failure above,,,,,Assisted Reproductive Technologies(ART) 輔助生育技術(shù),unexplained,,Induction of ovulation 誘發(fā)排卵-1,1. Clomiphen 氯米芬:ER binding GnRH , FSH/LH dosage:50 mg,
40、 period day 5th, 5 days; 2. Gonadotropin therapy 促性腺激素治療: Indications: Hypogonadotropic hypogonadism; Pituitary dysfunction; COH in IVF; (C
41、OH : controlled ovarian hyperstimulation) HMG: human menopausal gonadotropins; FSH 75 IU/LH 75 IU, IM or SC; Recombinant FSH: 75 IU, SC; 3. HCG 絨毛膜促性腺腺激素: 5000-10000
42、IU;,,,,Induction of ovulation 誘發(fā)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
43、 of start and discontinuation are different; zoladex; decapeptyl, dipherenline, enantone;5. Bromocriptine 溴隱停: high PRL;,Assisted Reproductive Technologies (ART) 輔助生育技術(shù),Intrauteri
44、ne insemination ( IUI); 宮腔內(nèi)人工授精;In vitro fertilization and embryo transfer (IVF-ET); 體外受精與胚胎移植;Intracytoplasmic sperm injection (ICSI); 單精子卵泡漿注射;Gamete
45、intrafallopian transfer (GIFT); 配子輸卵管移植;,Intrauterine insemination ( IUI) 人工授精,Indications: 1. male factor infertility; 2. psychological factors; 3. unexplained in
46、fertility; 4. genetic defects;Types: 1. artificial insemination with husband’s sperm (AIH); 2. artificial insemination by donor (AID); Method: placement of about 0.3 ml of washe
47、d, processed and concentrated sperm into the intrauterine cavity by trans-cervical catheterizaion.,In vitro fertilization and embryo transfer (IVF-ET) 體外受精與胚胎移植,Indications: 1. tubal facto
48、r; 2. endometriosis; 3. unexplained infertility; 4. IUI failure; 5. Immunologic factors;Method: 1. Superovulation: COH, GnRH-a/FSH(HMG)/HCG; 2. Aspiration of
49、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 單精子卵泡漿注射 (ICSI),Mi
50、cromanipulation technique;Indications: 1. as treatment of male factor infertility: epididyma obstruction, azoospermia, retrograde ejaculation; 2. IVF failure;Surgical sperm recovery f
51、or ICSI: 1. Percutaneous epididymal sperm aspiration (PESA); 2. Percutaneous testicular sperm fine-needle aspiration (TESA); Complications: karyotypic abnormalities;
52、 other genetic defects;,Gamete intrafallopian transfer (GIFT) 配子輸卵管移植,Indications: 1. unexplained infertility; 2. endometriosis; 3. IUI failure; 4. Premature ovarian failure (POF
53、); 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;
54、 5. Replacement of fertilized egg into fallopian tube;,ART Complications輔助生育技術(shù)并發(fā)癥,Ovarian hyperstimulation syndrome (OHSS) 卵巢過(guò)激綜合征;Multiple gestations 多胎妊娠;Pre-eclampsia 產(chǎn)前子癇;Premature
55、 birth 早產(chǎn);Low birth weight 出生低體重;Long term emotional, social and psychological impact 長(zhǎng)期影響(情緒,社會(huì),精神);,Ovarian HyperStimulation Syndrome (OHSS)卵巢過(guò)度刺激綜合征,Causes: 1. HCG injection-trigger; 2. VEGF
56、 3. high estrogen level 4. Inflammatory media and cytokinesPatho-physiological mechanism: local and systemic increase in capillary permeabilityClinical finding: 1. abdominal di
57、scomfort, nausea, vomiting, pain 2. pleural effusion, chest pain, shortness of breath 3. ascites, increased abdominal girth, weight gain 4. decreased urine output, oliguria 5.
58、liver and renal function failure,Classification and Staging of Ovarian Hyperstimulation Syndrome,Grade 1: Abdominal distention/discomfortGrade 2: Grade 1 plus nausea and vomiting or diarrhea Ovar
59、ies enlarged 5-12 cmGrade 3: Sonographic evidence of ascitesGrade 4: Clinical evidence of ascites or hydrothorax or difficulty breathingGrade 5: All of the above plus decreased blood volume,
60、 hemoconcentration , diminished renal perfusion and function and coagulation abnormalities,,,Ovarian HyperStimulation Syndrome (OHSS)卵巢過(guò)度刺激綜合征,Examinations: 1. Complet
61、e blood account, liver function, BUN 2. Prothrombin time, partial thromboplastin time 3. Chest X-ray 4. Transvaginal ultrasound 5. Oxygen saturation 6. Fluid ba
62、lance 7. Serum HCG measurement 8. Pelvic exam is contraindicated; Treatment: 1. Prevention of OHSS 2. Follow-up: Vital signs, fluid intake and output measurement
63、 3. Admission to hospital,No conception 1year Age= 35 HSG Semen analysis CD#3FSH Normal Abnormal
64、 Normal Abnormal Surgical correctionIrregular Regular Infertility Normal AbnormalMenses Menses Speci
65、alist SATSH, PRL CD#21 P4 Normal Unexpl
66、ained InfertilityCD#21 P4 3 cycles of clomiphene citrate normalTreat abnormal treatment with timed intercourse
67、Abnormal TSH, PRL or referral to infertility specialist Abnormal P4 Infertili
68、ty Treatment with replacement Specialist or clomiphene citrate,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,復(fù)習(xí)思考題,1. 試述女性不孕的主要原因?2. 女性不
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