1. INFERTILITY

2. DEFINITION of Infertility What is Infertility? Infertility is defined two years of unprotected intercourse without pregnancy. (WHO, one year) Primary Infertility : no previous pregnancies have occurred; Secondary Infertility: a prior pregnancy has occurred;

3. Causes Causes Percentage Female factors 40-55 % Male factors 25-40 % Both male and female factors 10 % unexplained factors 10 %

4. Female Factors Ovulatory dysfunction: 1. Hypothalamic dysfunction; 2. Pituitary Insufficiency; 3. Ovarian factor (peripheral defect); 4. Others: thyroid or adrenal dysfunction; Pelvic factorsP: 1. Tubal factors: injury, blockage, adhesion; 2. Uterine factors; 3. Cervical factors; 4. Extra-genital tract factors;

5. Female Factors Follopian tube Uterine ovary oocyte Cervix Extra-genital tract sperm Hypothalamus Pituitary ThyroidAdrenal

6. Male Factors 1. Abnormal spermatogenesis congenital; chronic diseases; infectious factors; 2. Obstructive; 3. Immunologic factors; 4. Endocrine disorders; 5. Sexual dysfunction;

7. Both Male and Female Factors 1. No demonstrable cause; 2. Psychological factors; 3. Immunologic factors; count for 10%; autoimmune response; auto-antibodies;

8. Initial Visit 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;

9. Examinations Physical examination; Bimanual examination Rectal-Vaginal-examination Laboratory; Assistant imaging;

10. Examinations Laboratory: semen analysis hormone measurement; sperm penetration assay (SPA) postcoital examinition of cervical mucus immunologic examination; Assistant imaging : Unltrasound Hysterosalpingogram Hysteroscopy Laparoscopy

11. 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 anovulationTubal factor unexplained Uterine factorMale factor Further Investigate and Treatment

12. Normal Values for Semen Analysis Volume > 2.0 mL Sperm concentration > 20 million/mL Motility >50 % morphology >30 % normal Data from WHO, 1992

13. Methods to monitor ovulation 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.

14. Treatment-female factor Causes Treatment induction of ovulation ； tuboplasty, microsurgery ； medication or surgery ； immune inhibition ； anovulation Tubal factor Anatomic factor immunologic azoospermia genetic disease after surgery Assisted Reproductive Technologies (ART) unexplained

15. Induction of ovulation 1. Clomiphen ： ER binding GnRH,FSH/LH dosage ： 50 mg, period day 5th ， 5days ； 2. Gonadotropin therapy ： Indications: Hypogonadotropic hypogonadism; Pituitary dysfunction; COH (controlled ovarian hyperstimulation) in IVF; HMG: human menopausal gonadotropins; FSH 75 IU/LH 75 IU, IM or SC; Recombinant FSH: 75 IU, SC; 3. HCG: 5000-10000 IU;

16. Induction of ovulation 4. Gonadotropin releasing hormone agonist (GnRH-  ) ： hypothalamic factor, as COH; protocol: according the every GnRH-  component and feature, the time of start and discontinuation are different; zoladex; decapeptyl, dipherenline, enantone; 5. GnRH antagonist; 6. Bromocriptine 溴隐停 : high PRL;

17. Assisted Reproductive Technologies (ART) Intrauterine insemination ( IUI) In vitro fertilization and embryo transfer (IVF-ET) Intracytoplasmic sperm injection (ICSI); Gamete intrafallopian transfer (GIFT)

18. Intrauterine insemination ( IUI) Indications: 1. as treatment of male factor infertility; 2. psychological factors; 3. unexplained infertility; 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 washed, processed and concentrated sperm into the intrauterine cavity by trans-cervical catheterizaion.

19. In vitro fertilization and embryo transfer (IVF-ET) Indications: 1. tubal factor; 2. endometriosis; 3. unexplained infertility; 4. IUI failure; 5. Immunologic factors; Method: 1. Superovulation: COH, GnRH-  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;

20. Gamete intrafallopian transfer (GIFT) 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;

21. ART Complications Multiple gestations Pre-eclampsia Ovarian hyperstimulation syndrome (OHSS) Premature birth Low birth weight Long term emotional, social and psychological impact