ART-IVF: the Long and Short of it

ART-IVF:the Long and Short of it

Professor Ernest Hung Yu NGDepartment of Obstetrics & Gynaecology

The University of Hong Kong

The Nobel Prize in Physiology or Medicine 2010

Robert G. Edwards for “Development of In Vitro Fertilization”

Louise Brown: First test-tube baby

9 October, 1978

12 July 2008

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

IVF procedure1. Ovarian stimulation2. Egg collection3. Fertilization 4. Embryo transfer

IVF

PeriodEgg

retrievalEmbryo transfer Pregnancy test

Stimulation of ovaries

fertilization

Antagonist

Agonist (nasal spray) or

Luteal phase support

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

Ovarian stimulation

Poor ovarian responsescycle cancellationpoor pregnancy rates

Excessive ovarian responsesrisk of ovarian hyperstimulation syndromehigh E2 detrimental to the outcome (Ng et al., 2000)

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

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

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”

AFC and AMH in prediction of ovarian response and non-pregnancy

Poor ovarian response Non-pregnancy

(Broer et al, F&S 2008)

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.

Prediction of cumulative live birth

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

Oocyte retrieval under transvaginal ultrasound guidance

Risks Bleeding Pelvic infection Injury Abdominal pain

Sperm washing

Centrifugation

Semen Abnormal sperm

Normal sperm with good motility

Culture medium

Low densityHigh density

Fertilization methods

Culture medium

1. Conventional insemination 2. Intracytoplasmic sperm injection-injecting single sperm into an egg Severe male factors