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IVM/IVF in PCOS (PCO-Like Ovaries)

IVM/IVF in PCOS (PCO-Like Ovaries). Milton Ka Hong Leong MDCM DSc(McGill) FRCS(C) FRCOG FACOG FHKCOG Director, IVF Centre HK Sanatorium & Hospitals Specialist in Reproductive Medicine Adjunct Professor, Department Obstetrics & Gynecology McGill University,Montreal, CANADA. PCOS.

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IVM/IVF in PCOS (PCO-Like Ovaries)

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  1. IVM/IVF in PCOS (PCO-Like Ovaries) Milton Ka Hong LeongMDCM DSc(McGill) FRCS(C) FRCOG FACOG FHKCOG Director, IVF Centre HK Sanatorium & Hospitals Specialist in Reproductive Medicine Adjunct Professor, Department Obstetrics & Gynecology McGill University,Montreal, CANADA

  2. PCOS • Commonest endocrine disorder in women • May be 80% anovulatory infertility? • Ovulation induction required • Most are clomiphene responsive • Cumulative pregnancy rates lower than non-PCOS patients • Balen 2002 2004

  3. PCOS • Ovulation Induction: • Low dose - reduced response • Higher dose - over-response • Leading to multiple pregnancies • Higher risk OHSS

  4. PCOS and IVF • IVF is an effective, may be preferred choice of therapy because of the problems associated with ovulation induction • Significantly more oocytes • Lower fertilization rate • Dor et al, Homburg et al Kodama et al

  5. PCOS and IVF • Pregnancies were comparable to non-PCOS patients • Increased miscarriage rate • FSH requirement leads to under or over response • Higher cancellation rate • Much higher chance of OHSS

  6. OHSS in IVF • Prevalent Factors: • Age -younger • BMI - thinner • PCOS • PCO-like ovaries >10 follicles • Ovarian volume > 10 cu mm • LH/FSH > 2 • Hyperandrogenism

  7. OHSS in IVF • Preventive Measures • Identify Risks - Low(er) FSH? No Help • Use GnRh-ant - ? 50% • Coasting E > 3000pg/ml but preg rate oocyte quality • Cancel cycle - patient reluctant • No hCG - use GnRH-a • No transfer - cryo-preservation • Albumin, hydroxyaethyl starch solution • High Dose Progesterone, no Luteal hCG

  8. PCOS, OHSS and IVF • Risk up 5-30 fold (6-30%) • Estradiol >3000pg/ml • # Follicles >20

  9. OHSS in PCOS Undergoing IVF • Preventive Measures: • Pre-treat with laparoscopic drilling • Use GnRH-ant then GnRH-a to trigger • Metformin (as short as 28 days) • No Transfer, Cryopreservation • Early Aspiration of Follicles - 2 operations • Conversion to IVM • IVM with and/or without stimulation

  10. Role of Metformin in PCOS Patients In Clomiphene responsive pts, no difference in LBR In Clomiphene resistant patients: Higher LBR when metformin added to Clomiphene to Laparoscopic drilling in IVF cases In IVF patients add metformin reduces OHSS

  11. Progress in IVM • Edwards 1965 : 1st in vitro matured oocyte • Veeck 1983 : 1st IVM pregnancy from an ovum derived from a • stimulated cycle • Cha et al. 1991 : the first pregnancy from in-vitro matured oocytes derived from a caesarean section donor • Trounson et al. 1994: IVM in women with PCOS • improvements in culture condition and transfer techniques have demonstrated that IVM is an effective treatment for women with PCO or PCOS. • In general, clinical pregnancy and implantation rates for infertile women with PCO or PCOS have reached approximately 30-35% and 10-15%, respectively, (Chian et al., 2004).

  12. IVM/IVF in PCOS

  13. Advantages of IVM • No/minimal stimulation: less OHSS less long term effect safety factor – cancer patients • Flexible start time, no preparation • Cancer patients no theoretical and actual risk (esp br ca) can treat anytime

  14. IVM/IVF • Best candidates • under 35 • PCOS or PCO-like ovaries To stimulate or not to stimulate, that is the question………………

  15. IVM/IVF vs IVF for PCOS Child TJ, et al,2002

  16. Over responders • Risk of OHSS • Treatment options • Cancel cycle • Coasting • No embryo transfer • Convert to IVM

  17. Over responders Prolonged Coasting • Aim: To prevent hyperstimulation • Practice: Coast till E2 ≤ 3000 pg/mL • Sher, 1995 Start when 30% follices > 15 mm • Nilsson, 1999 When 3 follicles > 17mm

  18. IVM stimulation

  19. IVM/IVF in PCOS/PCO-Like Pts 2007

  20. FSH Priming or Not?

  21. Biological data and birth reports after in vitro maturation from unstimulated cycles in polycystic ovarian syndrome patients Du AL,et al ,2005

  22. Natural cycle IVM results (McGill University)

  23. Natural cycle IVM (summary) McGill Seoul Maria Sun Yat-sen HKSH Total No of cycles 35 128 13 17 193 Mean age 33.1±3.4 29 35.1±4.4 Oocytes collected 284 1043 207 166 1700 Maturation rates(%) 226 (80%) 733(70.3%) 104(50.3%) 110(66.3%) 1173 (69%) Fertilizaiton rates(%) 188 (83%) 580(79.1%) 87(83.8%) 89(80.9%) 944 (80.5%) Embryo transferred 2.5±8.6 4.0±1.6 4.6±2.5 2.3±1.0 No of ET cycles 35 123 13 17 188 Clinical PR(%) 14(40%) 36(29.3%) 2(19.5%) 4(23.5%) 56 (29.8%)

  24. FSH priming for obtaining more oocytes or enhancing oocyte maturation(Mikkelsen et al., 1999; 2001; Suikkari et al., 2000). • However, the results were conflicting

  25. IVM stimulation

  26. Table . Number of oocytes obtained for in vitro maturation and rates of maturation, fertilization, cleavage and pregnancy in women inunstimulated and FSH-primed groups Mikkelsen AL et al,2001

  27. In-vitro maturation outcomes between the FSH-primed and no FSH treatment groups NO FSH + FSH P No of cycles 13 30 OPU day folic(mm) 6.4 ±0.7 8.1 ±1.9 <0.001 Oocytes collected 15.9 ±7.3 18.5 ±6.7 >0.05 No. of MTII 8.0 ± 3.9 11.1 ±5.2 0.065 No. of Fertilized 6.7 ±3.5 8.3 ±3.6 >0.05 Embryo transferred 4.6±2.5 4.6 ±2.0 >0.05 Clinical PR(%) 2(19.5%) 11(36.7%) 0.132 Sun Yat-sen University 2006

  28. Clinical variables and outcome of FSH-primed (Group A) and non-FSH-primed (Group B)(PCOS) Lin YH et al 2003

  29. IVF CENTRE (HKSH) data 2004-2005

  30. Conclusions • PCOS poses as a problem in ovulation induction • IVF may be treatment of choice for PCOS, but OHSS has to be controlled • IVM/IVF can circumvent problems with ovulation induction • Stimulated or not, it is safe, effective • More studies have to be done, especially in follow-up of children IVM/IVF SHOULD BE TREATMENT OF CHOICE

  31. HCG priming or not ?

  32. How to improve pregnancy rate in IVM Dr Milton Ka Hong Leong MDCM DSC (McGill) FRCS(C) FRCOG FACOG FHKCOG Specialist in Reproductive Medicine Adjunct Professor,Department of Obstetrics & Gynecology McGill University

  33. The advantages of IVM

  34. How to improve the pregnancy rate in IVM?

  35. The percentage of oocytes achieving maturation at 48 h was significantly higher in the HCG-primed group than in the non-HCG-primed group. • Ooycte maturation was hastened in the HCG-primed group. • There were no significant differences in the rates of ooycte fertilization and cleavage in these two groups. Chian RC,et al. 2000

  36. Stimulation protocol Best candidates: women under 35 years of age who have polycystic-like ovaries • Stimulate or not • With or without HCG priming

  37. Chian RC,et al. 2000

  38. Chian RC,et al. 2000

  39. Is ICSI essential for IVM?

  40. Reports of inseminationof human in vitro-matured oocytes are scarce. • In the study by Barnes et al. (1996), 43% of mature oocytes from normal ovaries and 26% of in vitro matured oocytes from PCOSwomen fertilized after insemination. • The reason for poor fertilizationrates after standard insemination has been thoughtto depend on altered characteristics of zona pellucida as aresult of the longer culture time before insemination.

  41. Comparison of outcomes between IVM-IVF and IVM-ICSI in all patients without hormonal priming Viveca Hum Reprod 2005

  42. Comparison of outcomes between IVM-IVF and IVM-ICSI in women with presumed ovulatory, regular cycles Viveca Hum Reprod 2005

  43. Ooycte-secreted factors enhance oocyte developmental competence during IVM

  44. Hussein TS,et al.2006

  45. Hussein TS,et al.2006

  46. Hussein TS,et al.2006

  47. Hussein TS,et al.2006

  48. Selection Method

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