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 20,06 OMNI 2

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 1:

Biology

Pillar 2:

Clinical, psychological, economical

Pillar 3:

Population

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

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 ratesCost of health servicePsychological 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

Mar 20,06 OMNI 13

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.

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 statusFirst language of motherMaternal ageParity Initiation time of prenatal careMaternal smokingReproductive history Induction during laborC-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

BiologistsCliniciansPsychologistsEthicistsEpidemiologistsLawyers

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Interaction and integration

IVM

Pillar 1:

Biology

Pillar 2:

Clinical, psychological, economical

Pillar 3:

Population

Health Policy makers

Mar 20,06 OMNI 25

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