Infertility, In Vitro Fertilization (IVF) and Genetic Testing

1. Infertility, In Vitro Fertilization (IVF) and Genetic Testing Michele Evans, M.D.

2. Outline • Infertility • Treatment options • In Vitro Fertilization • Genetic Testing • Preconception • Preimplantation • Prenatal • Controversies

3. Normal Fertility Hull, et al: Br Med J 1985:291;1693

4. Overview of Infertility • Definition: 1 year of well-timed, unprotected intercourse without a pregnancy • 10-15% of population is infertile (subfertile)

5. Causes of Infertility

6. Female Reproductive Organs

7. FSH (+) E2 (-) Developing follicle FSH=Follicle Stimulating Hormone E2=Estradiol Physiology

8. Causes of Female Infertility • Ovary • Tubes • Uterus • Cervix • Hormones • Chromosomes

9. Causes of Female Infertility - Ovary • AGE • Problems with ovulation • Premature ovarian failure

10. Ovary - Female Age • Women are born with their lifetime egg supply • 4 million at 20 weeks gestation • 400,000 at birth • 100,000 eggs left at time of puberty • Fertility initially declines at age 27 • Significant decline at age 37-38 • Rare pregnancies after age 44

11. Percentage of Married Women Who are Infertile From 3 national U.S. surveys Menken et al, Science 1989;23:1389

12. Ovarian Reserve Testing

13. Clinical pregnancy per cycleas function of both FSH and age Pearlstone et al, Fertil Steril 1992:58:674

14. Prevalence of genetically abnormal oocytes in infertile women Abnormal (%)

15. Ovary - Ovulation

16. Ovary - Ovulation • History • Regular menses (90%) • Premenstrual symptoms • Patient self-testing • BBT, urinary ovulation kits (LH) • Laboratory tests • Mid-luteal serum progesterone > 10 ng/mL • Endometrial biopsy

17. Ovary - Causes of Anovulation • Hormone imbalance • Obesity • Anorexia • Significant stress • Patients display: • Irregular menstrual cycles • Skipped cycles • Minimal or absent premenstrual symptoms

18. Ovary – Premature Ovarian Failure • Menopause prior to age 40 • ↓Estrogen • ↑FSH • Causes • Autoimmune • Genetic • Idiopathic • 1-2% pregnancy rate

19. Causes of Female Infertility – Fallopian Tubes • Infection (chlamydia) • Endometriosis • Tubal ligation (female sterilization)

20. Open Tubes

21. Blocked Tubes

22. Female Infertility - Uterus • Uterus • Fibroids • Polyps • Mullerian (congenital) defects • Absent • Bicornuate/Septum • Asherman’s syndrome

23. Female Reproductive Organs

24. Female Infertility • Uterine muscle tumor • Benign (>95%) • 25-30% of women

25. Normal Shape of Uterus

26. Fibroid Uterus

27. Female Infertility - Uterus • Uterus • Tumors • Fibroids • Polyps • Mullerian defects (congenital) • Absent uterus • Bicornuate/septate • Asherman’s syndrome

28. Mullerian Defect

29. Treatment with Hysteroscopy

30. Treatment with Laparoscopy

31. Female Infertility - Uterus • Uterus • Tumors • Fibroids • Polyps • Mullerian defects (congenital) • Absent uterus • Bicornuate/septate • Asherman’s syndrome

32. Female Infertility - Cervix • Cervix • Post-surgical • Stenosis • Mucus changes

33. Female Infertility - Hormones • Endocrine abnormality (hormones) • Thyroid • Prolactin • Polycystic ovary syndrome (PCOS) • Estrogen, insulin • Hypothalamic hypogonadism • Stress • Exercise (ballet dancer)

34. Other Causes of Female Infertility • Others • Chromosome abnormalities • Turner’s syndrome (XO) • Androgen Insensitivity (XY) • Male pseudohermaphrodite • Female phenotype • Blind vaginal canal • Inguinal hernia (50%)

35. Causes of Male Infertility • Abnormality in sperm production • Abnormality in sperm function • Obstruction in the ductal system

36. Male Reproductive Organs

37. Sperm: Semen Analysis • Volume: > 2 mL • Concentration: > 20,000,000 per mL • Motility: > 50% • Normal morphology: > 40% normal • Krueger strict criteria: > 14% normal • Best predictor of fertilizing ability

38. Normal Sperm Morphology

39. Abnormal Morphology

40. Abnormal Morphology

41. Sperm • How many are needed for fertilization? • Natural conception • 20,000,000 • Intra-uterine insemination • 1,000,000 • In-vitro fertilization (IVF) • 10,000 • Intra-cytoplasmic sperm injection (ICSI) • 1

42. Fertilization • Binding to zona pellucida • Penetration of oocyte • Decondensation and aster formation • Pronucleus formation

43. Causes of Male Infertility • Abnormality in sperm production • Abnormality in sperm function • Obstruction in the ductal system

44. Abnormalities of Sperm Production • Genetic • Y chromosome microdeletions • Damage to testes – anatomical • Cryptorchidism • Varicocele • Infection • Mumps orchitis • Gonadotoxins

45. Abnormalities of Sperm Function • Antisperm antibodies • Genital tract inflammation • prostatitis • Varicocele • Failure of acrosome reaction • Problems with sperm binding/penetration

46. Obstructions in Ductal System • Vasectomy • Congenital bilateral absence of the vas deferens • Epididymis/ejaculatory ducts • Congenital or acquired

47. Male Infertility - Lifestyle • Tobacco • Marijuana • Alcohol • Cocaine • Steroids (can be permanent) • Heat • Exercise

48. Infertility: Initial Evaluation • Eggs • Ovulation • Egg quality • Sperm • Presence • Quality • Gamete transport/Implantation • Hysterosalpingogram

49. Unexplained Infertility • Work-up is negative • 15-20 % of couples

50. Treatments • Observation (improve timing) • Clomiphene citrate + intrauterine insemination (IUI) • FSH + IUI • IVF • Egg donation