In vitro maturation of oocytes as a promising treatment option for infertile couples: a transdisciplinary study Beum Soo An, Junling Chen Xi-Kuan Chen, Jack Huang Se-Hyung Park, Qiuying Yang

Mar 20,06OMNI2 Background In-vitro maturation (IVM)  Immature eggs are retrieved from ovary and mature in laboratory.  Once eggs are matured, in vitro fertilization (IVF) is then performed.

Mar 20,06OMNI3 Background  In vitro maturation (IVM) of oocytes vs. conventional in vitro fertilization (IVF)  Proposed advantages of IVM:  Simplify treatment and reduces cost  Avoids potential side effects-weight gain, bloating, breast tenderness, nausea, mood swings, and OHSS  Fear of potential risk of malignancy associated with repeated cycles of ovarian stimulation.

Mar 20,06OMNI4 Overall Objective To assess biological, clinical, psychological and economical impact of in vitro maturation (IVM) of eggs

Mar 20,06OMNI5 3 Pillars IVM Pillar 1: Biology Pillar 2: Clinical, psychological, economical Pillar 3: Population

Pillar I: Biological assessment of IVM

Mar 20,06OMNI7 Biological approach for IVM group Objectives  To compare life cycles and occurrences of disease from IVF and IVM treated offspring  To compare gene profile in maternal placenta of IVM and IVF derived embryos

Mar 20,06OMNI8 Hypotheses  IVM or IVF offspring have no difference in life cycles and occurrences of diseases.  Maternal placentas from IVM or IVF embryos do not have different gene profile.

Mar 20,06OMNI9 Research design  Using animal models (mouse or rat), we will compare life cycles and occurrences of diseases after IVF or IVM  We will analyze gene profile in the maternal placenta using microarray after IVF or IVM embryo injection, and confirm this by real time PCR and western blot in the different gestational stages

Pillar II: Clinical, psychological, economical impact of IVM

Mar 20,06OMNI11 Objectives To evaluate:  Efficacy of IVM-pregnancy and live birth rates.  Safety of IVM-complication rates  Cost of health service  Psychological impact on infertile couples

Mar 20,06OMNI12 Hypotheses  IVM treatment will result in comparable clinical efficacy as standard IVF (i.e. pregnancy and live birth).  IVM decreases the risk of maternal complications and does not increase the risk of fetal, neonatal and long term complications.  IVM is more cost effective than IVF  IVM reduces psychological stress of infertile couples

Mar 20,06OMNI13 Research Design  Multicenter prospective randomized control trial comparing IVM to IVF  Cohort study-follow up babies from IVM vs. IVF and spontaneous pregnancy -1 year  Health economic analysis  Psychological assessment using validated structured questionnaire  Focus group discussion-clinicians, nurses, clients

Mar 20,06OMNI14 Outcomes  Efficacy of IVM vs. IVF:  Fertilization  Implantation  Pregnancy  Live birth  Safety of IVM vs. IVF:  Maternal complications (i.e. OHSS, miscarriage)  Fetal complications (i.e. congenital anomalies)  Newborn (Gestational age, birth weight, APGAR)  Follow up of IVM vs. IVF vs. spontaneous pregnancy babies as a cohort  Cost-effectiveness of IVM vs. IVF  Impact of IVM and IVF treatment on psychological well being of infertile couples.

Pillar III: IVF and pregnancy complication and birth outcomes: a population based study

Mar 20,06OMNI16 Objective To assess the effects of IVF and IVM on pregnancy complications and perinatal outcomes

Mar 20,06OMNI17 Methods-subjects  A population-based retrospective cohort  Niday Perinatal Database, Ontario  births in Ontario every year  births with assistant reproduction technology

Mar 20,06OMNI18 Methods-exposure and control  Exposure: IVF and IVM  Control: spontaneous pregnancy  Frequency matched by:  Year of birth  Postal code of residence  Plurality  Parity  Maternal age

Mar 20,06OMNI19 Outcome  Pregnancy complications:  Gestational hypertension  Preeclampsia  Eclampsia  Gestational diabetes  Obstetric complications  Placenta previa  Placenta abruption

Mar 20,06OMNI20 Methods-outcomes  Birth outcomes:  Birth defects  Apgar score  Gestational age: Preterm birth  Birth weight: LBW, SGA  Mortality  Fetal death (≥20 gestational weeks)  Early neonatal death  Late neonatal death

Mar 20,06OMNI21 Methods-confounders  Aboriginal status  First language of mother  Maternal age  Parity  Initiation time of prenatal care  Maternal smoking  Reproductive history  Induction during labor  C-section

Mar 20,06OMNI22 Timetable and Budget  Timetable  Preparation and coordination (6 months)  Implementation (4 years)  Report writing (6 months)  Budget

Mar 20,06OMNI23 Research Team  Biologists  Clinicians  Psychologists  Ethicists  Epidemiologists  Lawyers

Mar 20,06OMNI24 Interaction and integration IVM Pillar 1: Biology Pillar 2: Clinical, psychological, economical Pillar 3: Population Health Policy makers

Mar 20,06OMNI25  STIRRHS  Mentors  Dr. Raymond Lambert  Dr. Marcel Melancon  Dr. Roger Pierson  Dr. Peter Leung (UBC)  Dr. Seang Lin Tan (McGill)  Dr. Mark Walker (U Ottawa)  Dr. Shi Wu Wen (U Ottawa) Acknowledgement