Individualizing Ovarian Stimulation Protocols for IVF

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Have you experienced poor response to IVF medications? Been told you had "Empty Follicle Syndrome?" Had lots of eggs retrieved but very few fertilized? Experienced Ovarian Hyperstimulation Syndrome? All of these issues can be tied to or affected by your protocol of stimulation. Dr. Geoffrey Sher presents his approach to customizing ovarian stimulation based on 30 years' experience in the IVF field. He outlines a number of his stimulation protocols and discusses the factors that can cause IVF failure due to improper stimulation protocols.

Individualizing Ovarian Stimulation Protocols for IVF

  1. 1. GEOFFREY SHER M.D.
  2. 2. Submit additional questions on our discussion boards at: forums.haveababy.com Or my blog: www.IVFAuthority.com
  3. 3. Schedule a consultation with me: 800-780-7437 Visit our Website: www.haveababy.com
  4. 4. THE MOST IMPORTANT DETERMINANT OF IVF OUTCOME:
  5. 5. Embryo Development Fisch et al., 2001 16-18 Hrs. Post Fertilization Day 2 - Cleaved Embryo Day 3 - 8-Cell Embryo Day 5-6: Expanded Blastocyst
  6. 6. Embryo “Competence”
  7. 7. Embryo “Competence”
  8. 8. MATURE EGG (M-2)
  9. 9. Meiosis Meiosis
  10. 10. Blastocysts (Hatching)
  11. 11. No embryology laboratory can yield “competent” quality embryos out of “aneuploid” eggs!
  12. 12. Factors in IVF that Govern Embryo Aneuploidy  Woman’s age  Protocol for controlled ovarian stimulation (COS)  Embryology Laboratory
  13. 13. Determining the Best Protocol for Controlled Ovarian Stimulation 1. Age 2. Ovarian Reserve (FSH/AMH/inhibin-B) 3. Previous Response to COS
  14. 14. Orchestration of Follicle/Egg Development  IN THE STROMA:  LH promotes production by stroma/theca of male hormone (androgen)  IN THE FOLLICLE:  FSH converts testosterone to estradiol  THE EGG IS THE CONDUCTOR OF FOLLICLE EVENTS
  15. 15. Ovary Stroma/Theca (Produces Androgen) Follicle Egg Granulosa Cells (Produce Estrogen)
  16. 16. Role of Ovarian Male Hormones (Androgens) A small amount testosterone is essential for follicle and egg development Excessive testosterone is a cause of poor follicle and egg development.
  17. 17. Who is Most Vulnerable to Excessive Androgens?  Older Women  Women with ovarian Lesions (cysts, endometriomas & tumors)  Women with polycystic Ovarian Syndrome (PCOS)
  18. 18. Effects of Excessive Androgens  Poor-follicle development (premature luteinization, “empty” follicles)  Poor- egg/embryo quality (increased aneuploidy)  Poor- endometrial development  Poor-endometrial development and implantation rate  Poor -IVF Success
  19. 19. What leads to Increased Exposure to Androgens?  HIGH LH  Age  Ovarian resistance / failure  PCOS  INAPPROPRIATE OVARIAN STIMULATION PROTOCOLS  “Flare protocols”  Clomiphene  Menotropins  OVARIAN LESIONS  Endometriomas  Functional cysts  Tumors  ANDROGEN ADMINISTRATION  Testosterone  DHEA?
  20. 20. How to Limit Exposure to Androgens  Limit exposure to exogenous LH Use purified FSH  Treat ovarian lesions pre-COS  Endometriomas  Cysts  Suppress endogenous LH pre-COS  Use “long” GnRH agonist / antagonist protocols (esp. in DOR and PCOS)  Avoid “flare” protocols (esp. in DOR & PCOS)  Avoid Clomid/Femara 
  21. 21. Drugs Used for Ovarian Stimulation  Clomid/Femara  Gonadotropins (Folistim, Puregon, Gonal-F ,Bravelle, Menopur)  Agonists (Lupron, Superfact)  Antagonists (Ganirelix, Cetrotide, Orgalutron)  hCG (Pregnyl, Profasi, Novarel, Ovidrel)  Estrogen (I.M. estradiol valerate, estrogen skin patches, oral estrace)
  22. 22. Long Pituitary Agonist-Down-Regulation Protocol Agonist (Lupron/ Buserelin) FSH(Follistim/ Gonal-F/ Puregon) 10 days + Menses 5-10 days Menses 7-14(+) days hCG 10,000U Ovidrel 500mcg
  23. 23. Agonist/ Antagonist Conversion Protocol (A/ACP) BCP Agonist (Lupron/ Buserelin) 10 days + Menses 5-10 days Menses Antagonist (Ganirelix/Cetrotide/Orgalutron) FSH (Follistim) FSH +HMG (Menopu) 7-14 (+) days hCG 10.000U Ovidrel 500mcg
  24. 24. Short Agonist (Micro) “Flare” Protocol Agonist (Lupron/ Buserelin) 7-14(+) days Spontaneous Menstruation FSH(Follistim/ Gonal-F/ Puregon) hCG 10,000U Ovidrel 500mcg
  25. 25. Short Antagonist Protocol Antagonist (Ganirelix/’Cetrotide/Orgalutron) FSH(Follistim/ Gonal-F/ Puregon) Day 6-8 Menses hCG 10,000U Ovidrel 500mcg
  26. 26. Mini-IVF / EZ-IVF Clomiphene/ Femara Day 2 Menses Day5 (Menotropin) +/7-10 (+) days hCG 10.000U Ovidrel 500mcg
  27. 27. Natural Cycle IVF (Monitoring) US/ blood LH Day 1 Menses Day 10 +/-hCG 10.000U Ovidrel 500mcg
  28. 28. Additional Considerations 1. Under-response A/ACP+E2V  Human Growth hormone  DHEA  Egg Donor Over-response (Hyperstimulation - OHSS)  “Prolonged Coasting” Thin Uterine Lining  Viagra Premature Luteinization (“Premature LH Surge”) “Empty Follicle” Syndrome  2. 3. 4. 5.
  29. 29. Under-Response  A/ACP + E2V  Human Growth Hormone (HGH)?  DHEA??  Egg Donor
  30. 30. Agonist/ Antagonist Conversion with Estrogen Priming (A/ACP+ E2V) BCP Agonist (Lupron/ Buserelin) Antagonist (Ganirelix/Cetrotide/Orgalutron) Estrogen (E2V) FSH (Follistim) Priming 10 days+ Menses 5-10 days 7-10 days Menses 5 days FSH + Menotropin (Menopur) 4-14 days hCG
  31. 31. Who Can Benefit from A/ACP + E2V? 1. Advanced Maternal Age: (41+) 2. Women With Decreased Ovarian Reserve: (AFC/AMH/FSH)
  32. 32. Over-Response/Hyperstimulation (OHSS) “Prolonged Coasting”
  33. 33. Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) through “Prolonged Coasting” Agonist FSH >25 follicles (50%=14MM+) E2 = >2500pg/ml 7-10 days 36 hrs E2=<2500pg/ml 2-5days STOP FSH!! Initiate “coasting” Stop ER “coast” + hCG-10,000U
  34. 34. A THIN UTERINE LINING & VIAGRA 1. 2. 3. 4. 5. 6. Endometritis Surgical Clomiphene DES PCOS Reduced uterine blood flow  Age  Adenomyosis  fibroids
  35. 35. Endometrial Lining (Pre-Viagra)
  36. 36. Endometrial Lining (Post-Viagra)
  37. 37. Triggering Ovulation 36 Hrs. Prior to ER  hCGu 10,000 IU (Pregnyl/Profasi/Novarel)  hCGr (Ovidrel), if used ideally should be 500mcg.  Criteria:  2 lead follicles at least 18mm in diameter  1/2 of total number of follicle at least 15mm in diameter  Endometrial lining at least >9mm with trilaminar pattern
  38. 38. Thank You! If you would like to schedule a consultation with Dr. Sher, please call 1-800-780-7437 Read Dr. Sher’s Blog at: www.IVFauthority.com SIRM Website: www.haveababy.com

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