In vitro maturation of oocytes as a promising treatment option for infertile couples: a transdisciplinary study

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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

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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.

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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.

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Overall Objective

• To assess biological, clinical, psychological and
  economical impact of in vitro maturation (IVM) of
  eggs

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3 Pillars
IVM
Pillar 2 Clinical, psychological, economical
Pillar 3 Population
Pillar 1 Biology
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Pillar I Biological assessment of IVM

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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

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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.

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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

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Pillar II Clinical, psychological, economical
impact of IVM

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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

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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

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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

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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.

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

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Objective

• To assess the effects of IVF and IVM on
  pregnancy complications and perinatal outcomes

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Methods-subjects

• A population-based retrospective cohort
• 2004-2008 Niday Perinatal Database, Ontario
• 120 000 births in Ontario every year
• 900-1000 births with assistant reproduction
  technology

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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

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Outcome

• Pregnancy complications
• Gestational hypertension
• Preeclampsia
• Eclampsia
• Gestational diabetes
• Obstetric complications
• Placenta previa
• Placenta abruption

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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

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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

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Timetable and Budget

• Timetable
• Preparation and coordination (6 months)
• Implementation (4 years)
• Report writing (6 months)
• Budget

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Research Team

• Biologists
• Clinicians
• Psychologists
• Ethicists
• Epidemiologists
• Lawyers

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Interaction and integration
IVM
Pillar 2 Clinical, psychological, economical
Pillar 3 Population
Pillar 1 Biology
Health Policy makers
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Acknowledgement

• 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)