1. Infertility He-Feng Huang Women’s Hospital, School of Medicine, Zhejiang University

2. Where we come from?

4. Infertility Definition: The inability to achieve pregnancy after regular unprotected intercourse for a period of 1 year. Primary infertility: never conceived within 1 year Secondary infertility: after a previous pregnancy, unable to conceive again within a 1 year period.

5. Etiology Female factors Male factors Female and male factors

6. Female Factor Ovulatory disorders Tubal factors Uterine factors Cervical factors Vulval and vaginal factors

7. Ovulatory disorders Hypothalamic dysfunction Pituitary dysfunction Ovarian factor Others Hypothalamic-pituitary- ovary axis

8. Hypothalamic dysfunction Psychological factors: Stress, Disturbance, Anorexia derived from mental stimulus Chronic consumptive diseases: Tuberculosis, Severe malnutrition, Anorexia nervosa

9. Pituitary dysfunction Pituitary tumors: Pituitary adenoma Pituitary lesions: Empty sella syndrome Sheehan’s Syndrome

10. Ovarian factors PCOS LUFS POF Ovary insensitivity syndrome Congenital abnormality Surgery or X-ray Ovarian endometriosis Ovarian tumor

11. PCOS Symptom Menses disturbance and infertility hirsutism, acne, obesity ( BMI ≥ 25 ) Diagnosis （ 1 ） irregular menses or anovulation （ 2 ） experimental or clinical hyperandrogenism （ 3 ） polycystic ovarian morphology observed by ultrasound Accord with 2 points of the three. Follow-up for whole life

12. Others Thyroid disorder Adrenal dysfunction

13. Tubal factors Inflammation Surgery of ectopic pregnancy Tubal ovarian effusion Ectopic pregnancy Tubal blockage, hydrosalpinx (HSG ）

14. Tubal ligation Tubal abnormality Tubal factors Tubal ligation Tuberculosis fallopian tube

15. Increase of tubal factors STD Repeated intro-uterine manipulation Repeated drug abortion

16. Uterine factors Uterine developmental abnormality Congenital absence of the uterus Uterine malformation Endometrial abnormality Endometrial tuberculosis Asherman syndrome Uterine tumor

17. Uterine developmental abnormality

18. Intrauterine adhesions fibroid

19. Male factors Semen abnormality Oligospremia, Aspermia, Asthenospermia Sperm transport abnormality Endocrine disorders Sexual dysfunction Immunological factors

21. Male and female factors Psychological factors Subfertility Immunological factors

22. Classification

23. Investigation and Diagnosis Male investigation History: general health, medications, lifestyle and reproductive health General examination Specific examination ： abnormality of genitals seminal analysis

24. Volume ≥ 2.0ml PH 7.2~7.5 Density ≥ 20×10 /ml Count ≥ 40×10 /every ejaculation ≥ 50% sperm progressive motility (grade a+b) or ≥ 25% sperm rapid progressive motility (grade a) Grade a: rapid progressive motility Grade b: slow progressive motility Morphology ≥ 15% Survive rate ≥ 58% WBC ≤ 1×10 6 6 6 Normal Seminal analysis （ Fourth/Fifth version ） Volume ≥ 1.5ml PH 7.2~7.5 Density ≥ 15×10 /ml Count ≥ 39×10 /every ejaculation ≥ 32% sperm progressive motility (grade a+b) Grade a: rapid progressive motility Grade b: slow progressive motility Morphology ≥ 4% Survive rate ≥ 50% WBC ≤ 1×10 6 6 6 Fourth versionFifth version

25. Female Investigation History General examination Specific examination Others

26. Specific examination Ovarian examination Ovulation monitor Luteal function Ovarian reserve

27. Ovarian function Ovulation monitor 1 、 Basic body temperature 2 、 Cervical mucus 3 、 Vaginal cytological test 4 、 Ultrasound monitor 5 、 Serum or urinary LH peak 6 、 Serum E 2 and P levels 7 、 Endometrial biopsy 8 、 Laparoscopy

28. Follicular development and ovulation

29. Biphasic basal body temperature

30. monophasic basal body temperature

31. Low estrogenHigh estrogen

32. Cervical mucus

33. Fern crystallization

34. Proliferative endometriumSecretory endometrium

36. Luteal function 1 、 BBT 2 、 Endometrial biopsy 3 、 Serum E2 and P levels

37. Ovarian reserve 1 、 Age 2 、 Antral follicle count (AFC) 3 、 Basic FSH 、 E2 4 、 CC stimulating test 5 、 GnRH-a stimulating test 6 、 AMH 、 Inhibin B

38. Tubal investigation Hydrotubation Hysterosalpinography (HSG) Laparoscopy Hysterosalpingography by Ultrasound

39. Hydrotubation

40. HSG normal figure

41. Laparoscopy ： methylene blue liquid

42. Postcoital test Cervical hostility Hysteroscope Laparoscopy

43. Postcoital test

44. Cervical hostility Hysteroscope Laparoscopy

45. Cervical hostility

46. Postcoital test Cervical hostility Hysteroscope Laparoscopy

47. Endometriosis （ Endometriosis （ Laparoscopy)

48. Treatment of infertility 1.Treatment of genitals organic disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

49. 1. Genitals organic disease Genital malformations Genital inflammation Uterine Myoma Endometriosis ----Etiology combined treatment: Infection control, Surgery

50. 2.Tubal infertility Fallopian tube obstraction: Fallopian tube glue loose solution operation Salpingostomy Tubo-uterine implantation Tubal anastomosis Fallopian tubes were partial unobstructed: Liquid instillation Physical therapy Traditional Chinese Medicine

51. 3. Asherman syndrome Principle of Management: Separate adhesions Prevention of adhesion recurrence Promote endometrium repair Methods Hysteroscope management of intrauterine adhesion Estrogen promote endometrium regeneration Intrauterine device (IUD)

52. 1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4.Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

53. Drugs for ovulation induction CC HMG FSH: u-FSH, FSH-HP, r-FSH HCG GnRH （ LHRH ） GnRH analog ： GnRH agonist GnRH antagonist bromocriptine

54. The first R-GN （ Gonal- F+Lhadi+Ovidrel=FSH+LH+HCG ） IVFbaby—Sebastian （ 1997.5.7 ）

55. 1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

56. 1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

57. 1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.Treatment of tubal inflammation 6.ART

58. 1.Reproduction-related disease 2.Induction of ovulation 3.Luteal support 4. Improvement of cervical mucus 5.treatment of tubal inflammation 6.ART

59. Summary: Infertility-treatment Azoospermia Genetic disease After surgery Assisted Reproductive Technologies (ART) Unexplained Causes Treatment Anovulation Induction of ovulation Tubal factor Tuboplasty Anatomic factor Microsurgery Immunologic Medication or surgery Immune inhibition

60. ART Assisted Reproductive technology AID or AIH Artificial insemination IVF-ET In vitro fertilization-embryo transfer

61. AIH or AID AIH (artificial insemination with husband sperm) IUI (Intrauterine insemination ） IVI (Intravaginal insemination) ICI (Intracervical insemination) ITI (Intratubal insemination) IPI (Intraperitoneal insemination) IFI (Intrafollicle insemination) AID (artificial insemination by donor)

62. IVF-ET Indication Tubal infertility Endometriosis IUI failure Unexplained infertility Immunological infertility Oligospermia

63. IVF-ET

65. Other technology derived from IVF Crypreservation of embryos Oocyte donation and embryo donation Surrogate mother GIFT (Gamete intrafallopian transfer) ZIFT (Zygote intrafallopian transfer) ICSI PGD

66. ICSI (Intracytoplasmic sperm injection)

68. PGD Preimplantation genetic diagnosis

69. PGD indication ★ X-linked chromosome disease ★ Chromosome abnormality (number/structure) ★ Monogenic diseases PGS: Preimplantation genetic screen Advanced age History of habitual abortion Failure of IVF for several times

70. PGD technique Blastomere Biopsy FISH Single cell PCR Interphase nuclear conversion Whole genomic amplification,WGA Comparative genomic hybridization, CGH

71. PGD

73. 14 三体 正常 14 三体， 13 单体 Robertsonian translocation （ 13q14q ）

74. X-linked agammaglobulinemia

76. IVF-ET protocol Patients preparation COH Oocyte retrieval In vitro fertilization Embryo trasfer Luteal support Follow up

78. Complication of ART OHSS Ectopic pregnancy and abortion Multiple pregnancy － multiple pregnancy reduction

79. Transvaginal ultrasound-guided selective fetal reduction

80. In vitro maturation (IVM) Immature oocytes Mature oocytes embryos

81. Ethic of ART (Chinese government)  The government does not support nor approve the practice of human clones  Forbid performing ART for single woman  Forbid Manufacturing Oocytes  Forbid commercial trial of zygotes and embryos  Forbid multiple pregnancy dominated ART  Forbid gender selected ART without medical indication  Forbid surrogate motherhood

82. Ethic of ART Challenge the course of natural reproduction Danger of inbreeding Commercial trial of zygotes and embryos Uncertainty of parenthood Risk of oocyte donation Controversy between clone and traditional family formation Clone criminality Challenge of the definition of “human” ART related regulations and laws