New Developments in Assisted Reproduction Cork Fertility Centre Dr John Waterstone

Ovarian Reserve Women are very different to men with regard to reproductive ageing. A woman’s entire lifetime’s supply of eggs is present at birth. Decreasing ovarian reserve is inevitable with increasing age, resulting in complete infertility by age 40-50. Decreasing ovarian reserve has a significant negative effect on a couple’s reproductive prospects from age 37 onwards but earlier for some women. Ovarian reserve is a measure of how well the ovaries are still functioning at a certain point in time.

Measures of Ovarian Reserve FSH (Follicle Stimulating Hormone) - lower is better (Normal <10 iu/L) test cycle day 2-4 fluctuates between cycles when ovarian reserve poor AMH (Anti Mullerian Hormone) higher is better (normal>5pmol/L) less fluctuation between cycles

Measures of Ovarian Reserve Antral Follicle Count (AFC) higher is better 5-10 AF’s per ovary –normal reserve <3 AF’s per ovary –poor reserve >10-15 AF’s per ovary – ‘polycystic’ Menstrual cycle length – shortening cycles indicate deteriorating ovarian reserve

Polycystic Ovaries & PCOS Most women with polycystic ovaries do not have polycystic ovary syndrome PCOS = PCOD = Stein Levinthal Syndrome PCOS = Polycystic Ovaries + Oligo or Amenorrhoea Variable abnormalities in PCOS Raised LH Raised Androgens Hirsutism Obesity Impaired Glucose Tolerance

Management of PCOS Good ovarian reserve but may be difficult to manage. May succeed on first cycle of OII with Clomid May undergo OII, IUI, Ovarian drilling, IVF IVF also difficult because of risk of Ovarian Hyperstimulation Syndrome (OHSS) Metformin –no longer recommended for OII nor as an adjunct to IVF; may help patients lose weight.

Tests of Tubal Function Laparoscopy - Gold standard test - Carried out at Bon Secours Hospital Detects adhesions /endometriosis Hystero Salpingography (HSG) - Less invasive - Carried out Bon Secours Hospital Does not detect adhesions/endometriosis Hystero Contrast Salpingography (HyCoSy) - Poor diagnostic test - No longer used at Cork Fertility Centre

Pre-IVF Surgery for Hydrosalpinges Communicating hydrosalpinges must be removed or blocked proximally prior to IVF

Tertiary Care – AR Options Ovulation Induction (Clomid or low dose FSH) IUI (low dose FSH) IVF / ICSI (LHRH analogue, high dose FSH injections, egg collection, embryo transfer)

Embryo Transfer

Intracytoplasmic sperm injection (ICSI) ~ 40% of IVF cycles involve insemination by ICSI

TESE ICSI/TESE appropriate for primary azoospermia and post vasectomy

Day 2 - Day 3 Embryo Development

Day 5 Embryo development

Day 5 Embryo Transfer Advantages Embryo Selection Reduction in number of embryos for ET resulting in reduction in multiple gestations

Egg Donation For patients with poor ovarian reserve Alternative to adoption or childlessness Success Rate ~ 50% per cycle Known v Anonymous Donors Remuneration of Donors (Europe v USA) Reproductive Tourism

Egg Donation at Cork Fertility Centre Egg Donation available since 2006 Donors almost all known to recipient couple Live Birth Rate (per embryo transfer) for 2006 – 2010: 61%

Cryopreservation of Gametes & Embryos Cryopreservation of semen – successful & robust Cryopreservation of viable embryos – technically easy Cryopreservation of unfertilised eggs technically difficult but useful for: creating donor egg banks preserving fertility in young cancer survivors preserving fertility in women deferring reproduction

CFC IVF/ICSI Success Rates 2010 Live birth rates per Embryo Transfer Patient Age <35 35-37 38-40 41-42 >42 Cork Fertility Centre 2010 49% 46% 35% 22% 8.5% Success Rates” which quote “pregnancies” or “pregnancy rates” are misleading as a significant proportion of early pregnancies miscarry