1. Fertility Diagnosis and Therapy 2008 Gad Lavy, M.D. New England Fertility Institute Lifeline Cryogenics

2. The New Technology and the Aging Ovary  Improvement in diagnosis and therapy  Aging and its impact on fertility  The Approach to the “older infertile couple”  More aggressive diagnostic and therapeutic approach  ART  IVF  PGD  Egg donation  Freezing of embryos, eggs and ovarian tissue  Team approach to fertility therapy

3. Infertility Dx and Rx  Success in Diagnosis  Success in Therapy

4. Improved Success  Better Diagnostics: fewer cases of unexplained infertility.  PCOS  Ovulatory dysfunction  Imaging  Endometrial function  Better Therapy: Higher overall success.  Surgery  Ovulation induction  IVF and related procedures

5. Aging Population  Age at marriage  Age at first pregnancy

6. Age and Fertility

7. Age and IVF Success IVF success: Effect of age and number of eggs

8. The aging Ovary (and testicle)  Decreased Ovarian Reserve (DOR)  Lower conception rates  Higher rates of pregnancy loss  Higher incidence of Congenital defects

9. Menopausal ovary The Aging Ovary Normal ovary Fewer eggs Decreased egg quality

10. A Practical Approach to the aging ovary  Aggressive Diagnosis and therapy  Expand Treatment options

11. Diagnosis: The evaluation cycle  Baseline hormones  Ovulation profile  Imaging: HSG, Sono- HSG, MRI  Semen Analysis  Other: Genetic studies, immune workup etc

12. Therapy-The aging ovaries  IVF  Pre-implantation Genetics (PGD)  Egg Donation  Egg Freezing/Ovarian tissue freezing

13. In Vitro Fertilization and Embryo Transfer (IVF-ET)

14. IVF  Intra-cytoplasmic Sperm injection (ICSI)  Assisted zona Hatching (AZH)  Day 4-5 transfer and improved culture media  Cryopreservation of embryos

15. ICSI Poor sperm quality Zona Pellucida hardening Poor egg-sperm interaction

16. Assisted Zona Hatching (AZH) Improved Implantation Zona Hardening

17. Improvements in culture conditions- Blastocyst transfer

18. PGD  Micromanipulation: remove a single blastomere from an 8-cell embryo without damaging the embryo  Genetic testing  FISH  PCR

19. PGD: Fluorescent In Situ Hybridization (FISH)

20. PGD- Indications  Chromosomal disorders  Single gene defects (CF, Thalassemia, Sickle cell disease)  Recurrent pregnancy loss  Repeat IVF failures  Severe male factor

21. How is PGD performed? Ovarian Stimulation IVF Blastomere Biopsy on Day 3 Genetic Analysis Transfer of Unaffected Embryo Outcome Chromosomally Normal Baby

22. PDG- Clinical outcomes  Identify normal embryos  Fewer embryos to transfer  Know when not to transfer  Reduce pregnancy loss and anomalies

23. Third Party Reproduction  Egg donation  Embryo donation  Gestational surrogacy

24. Egg Donation: Indications  Ovarian Failure.  Poor egg quality.  Recurrent IVF failure.  Recurrent pregnancy loss  Genetic defects precluding normal pregnancy.

25. The Egg Donation Process  The process involves IVF.  The resulting offspring will carry genetic material of the donor and the male partner.

26. The Egg Donation Process  Donor and recipient cycles are synchronized.  Eggs taken from the donor after ovarian stimulation.  Eggs are fertilized with recipient partner’s sperm.  Embryos transferred to the uterus of a hormonally primed recipient.

27. Egg Donation: The Process  Donor  Synchronize cycle with recipient  Ovarian stimulation  Egg retrieval  Recipient  Synchronize cycle with donor  Preparation of the uterus  Fertilization  Embryo transfer

28. Egg Donation: The donors  Donor recruitment: Who are the donors?  Donor Screening: How are they tested?  Donor matching: How do I pick a donor?

29. Egg Donation: The recipient couple  Medical Screening  The Mock cycle  Psychological issues  Legal Issues  Ethical concerns: Disclosure

30. Cryopreservation of embryos, eggs and ovarian tissue

31. IVF and Cryopreservation of Embryos  Advantages:  Well established method.  High success.  Disadvantages:  More difficult for unmarried women.  Limited number of embryos  Delay in cancer therapy due to the IVF process.  Contraindication to ovarian stimulation in Estrogen sensitive tumors.

32. Egg Freezing-Applications  Ovarian malignancies  Ovarian surgery  Aging  Egg banks

33. Egg Freezing  Advantages  No need for ovarian stimulation  No need for fertilization  Enables preservation of eggs prior to surgery chemo or aging  Disadvantages  Lower survival  Possible damage to mitotic spindle  Still experimental

34. Egg Freezing At NEFI  Technique: New Advancements in cryopreservation.  Candidates  Cancer and chemo  Egg bank  Preservation of reproductive potential  Age <38  FSH <12  Good Survival/fertilization and embryo development  Ready to launch

35. Summary  Technology is developing rapidly  Ovarian aging is a major factor  ART is limited but can offer help for the aging ovary.

36. However  Don’t Delay.  Discuss all options early.  Consult or refer if needed.

37. CT State Mandate for Fertility Therapy  Benefits  Diagnostics  Ovulation therapy/inseminations X3  IVFx1  Limitation  Age <40  Look Back:  Time with current carrier: at least one year  Excludes self insurers, religious organizations etc.

38. Return to referring MD Delay in referral

39. Return to referring MD Length of clomid therapy by PMD

40. A Team Approach  The primary caregiver  The infertility specialist  Physician  Nurse/midwife/NP  Laboratory  Emotional counseling and support

41. We would like to thank our sponsor:  Organon

42. Thank you for coming. Gad Lavy, M.D. F.A.C.O.G. New England Fertility Institute Lifeline Cryogenics