ART-IVF: the Long and Short of it Professor Ernest Hung Yu NG Department 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, July 2008

Key developments in assisted reproduction YearEventKey investigators 1880First attempts at IVF in mammalian eggsSchenk 1890First successful egg recovery from rabbitHeap 1893First successful embryo cultureOnanoff 1930First successful IVF in mammalian eggs resulting in a livebirthPincus 1952Time of ovulation established in human beings by laparoscopyRock 1971First human blastocyst seen in vitroSteptoe and Edwards 1972Mouse embryo successfully cryopreserved and thawed with survivalWilmut 1978Birth of Louise Brown, first human born after IVFSteptoe and Edwards 1983First pregnancy after replacement of cryopreserved embryoTrounson 1990Preimplanation genetic diagnosis first describedHandyside 1992Intracytoplasmic sperm injectionPalermo

IVF procedure 1. Ovarian stimulation 2. Egg collection 3. Fertilization 4. Embryo transfer

IVF Period Egg retrieval Embryo transfer Pregnancy test Stimulation of ovaries fertilization Antagonist Agonist (nasal spray) or Luteal phase support

Common protocols GnRH agonist protocol rFSH GnRH Agonist hCG GnRH antagonist protocol rFSH GnRH Antagonist hCG

Ovarian stimulation Poor ovarian responses  cycle cancellation  poor pregnancy rates Excessive ovarian responses  risk of ovarian hyperstimulation syndrome  high 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 l Poor ovarian response l 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

AUCSE95% CI AFC to AMH to Age to 0.677

Oocyte retrieval under transvaginal ultrasound guidance Risks l Bleeding l Pelvic infection l Injury l Abdominal pain

Sperm washing Centrifugation Semen Abnormal sperm Normal sperm with good motility Culture medium Low density High density

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