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ART-IVF:the Long and Short of it
Professor Ernest Hung Yu NGDepartment of Obstetrics & Gynaecology
The University of Hong Kong
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The Nobel Prize in Physiology or Medicine 2010
Robert G. Edwards for “Development of In Vitro Fertilization”
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Louise Brown: First test-tube baby
9 October, 1978
12 July 2008
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Key developments in assisted reproduction
Year Event Key investigators
1880 First attempts at IVF in mammalian eggs Schenk
1890 First successful egg recovery from rabbit Heap
1893 First successful embryo culture Onanoff
1930 First successful IVF in mammalian eggs resulting in a livebirth Pincus
1952 Time of ovulation established in human beings by laparoscopy Rock
1971 First human blastocyst seen in vitro Steptoe and Edwards
1972 Mouse embryo successfully cryopreserved and thawed with survival Wilmut
1978 Birth of Louise Brown, first human born after IVF Steptoe and Edwards
1983 First pregnancy after replacement of cryopreserved embryo Trounson
1990 Preimplanation genetic diagnosis first described Handyside
1992 Intracytoplasmic sperm injection Palermo
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IVF procedure1. Ovarian stimulation2. Egg collection3. Fertilization 4. Embryo transfer
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IVF
PeriodEgg
retrievalEmbryo transfer Pregnancy test
Stimulation of ovaries
fertilization
Antagonist
Agonist (nasal spray) or
Luteal phase support
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Common protocols
1 2 3 4 5 6 7 8 9 10
GnRH agonist protocol rFSH
GnRH Agonist
hCG
GnRH antagonist protocol
1 2 3 4 5 6 7 8 9 10
rFSH
GnRH Antagonist
hCG
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Ovarian stimulation
Poor ovarian responsescycle cancellationpoor pregnancy rates
Excessive ovarian responsesrisk of ovarian hyperstimulation syndromehigh E2 detrimental to the outcome (Ng et al., 2000)
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Strong association between number of eggs and live birth rate
Live birth rate rose with an increasing number of eggs up to 15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs
9
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Tests of ovarian reserve
Ultrasound markers
1. Antral follicle
count
2. Ovarian volume
3. Ovarian stromal
vascularity
Hormonal markers
1. Anti-Mullerian
hormone
2. FSH
3. Inhibin
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Aims of ovarian reserve testing
1. To counsel patients about the likely ovarian response
2. To individualise stimulation regimes and FSH dose
3. NOT to advise against treatment in couples with “poor prognosis”
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AFC and AMH in prediction of ovarian response and non-pregnancy
Poor ovarian response Non-pregnancy
(Broer et al, F&S 2008)
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1,156 women in the first IVF cycle Cumulative live birth in the fresh plus all the frozen
embryo transfers after the same stimulation cycle Both AMH and AFC were not significant predictors
of cumulative live birth after adjusting for age and number of embryos available for transfer.
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Prediction of cumulative live birth
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Prediction of cumulative live birth
ROC curve for prediction ofcumulative live birth
0
20
40
60
80
100
0 20 40 60 80 100100 - Specificity (%)
Sens
itivity
(%) AFC
AMHAgeDiagnonal
AUC SE 95% CI
AFC 0.617 0.0174 0.587 to 0.647AMH 0.646 0.0170 0.616 to 0.675
Age 0.648 0.0170 0.618 to 0.677
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Oocyte retrieval under transvaginal ultrasound guidance
Risks Bleeding Pelvic infection Injury Abdominal pain
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Sperm washing
Centrifugation
Semen Abnormal sperm
Normal sperm with good motility
Culture medium
Low densityHigh density
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Fertilization methods
Culture medium
1. Conventional insemination 2. Intracytoplasmic sperm injection-injecting single sperm into an egg Severe male factors