Single Embryo Transfer

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Single Embryo Transfer Rachel Cutting Principal Embryologist Chair Association of Clinical Embryologists

Summary Background to change in UK policy National data Strategies Embryo selection Practical requirements New technologies Shared experience

History 2001 HFEA Directive: Maximum transfer 2 embryos < 40 yrs unless exceptional circumstances 2004 HFEA Code of Practice 6th Edition: Women aged < 40 receive no more than 2 embryos

Multiple pregnancy is the single biggest risk of fertility treatment to mother and child

HFEA commissioned an Expert Group Report Published October 2006 Consultation on policy options recommended in the report April - July 2007

Multiple births stakeholder group

Published strategy Year 1 target 24% Year 2 target 20% Year 3 target 15% Year 4 target 10% January 2009 April 2010 April 2011 Oct 2012

UK Data

eset is increasing esets as a percentage of all embryo transfers, 2008 to 2010

Blastocyst transfers increasing Blastocyst transfers as a percentage of all embryo transfers, 2008 to 2010

Multiple pregnancy rate decreasing Monthly multiple pregnancy rate (% of pregnancies), 2008 to 2010

Centre performance: Year 3 (first 7 months)

The challenge for centres!

Twice The Joy, Twice the Love, Twice The Blessing From Above Headline from a news paper!

Funding for Treatment UK wide variation No funding at all 1 cycle no frozen cycles 1 full cycle Funded cycles must accompany eset programme

The 4 key points for successful Patient selection eset Day of embryo transfer Embryo Selection Cryopreservation strategies

Day 2 Patients <37 years, 1 st cycle (all donor egg patients) I top grade 2-3 top grade embryos 4+ Top grade embryos embryo SET Culture to day 3 Culture to day 3 3 1-2 top grade 0 top grade 1-2 top grade 2+ top grade embryos embryos embryos embryos Eset day 3 DET day 3 eset day 3 eset day 3 and cryo OR and cryo and cryo Culture to day 5 5 0 good blastocysts 1+good blastocyst 2 BT if available esbt and cryo

Embryo Selection Evidence suggests that embryo quality is the most predictive factor for outcome of treatment, with a correlation existing between early embryo morphology and implantation rate

Evidence blastocyst transfer Higher pregnancy and live birth rates for selected patient populations Blake DA, et al Cochrane Database Syst Rev., 2007; (4): CD002118 Papanikoloau EG, et alhum Reprod., 2005; 20 911): 3198-203 Styer A, et al Fertil. Steril. Epub 2007 Jul 17 Systematic review and meta-analysis demonstrated a much improved live birth rate compared to the early cleavage stage when equal numbers of embryos were replaced Papanikolaou EG, et al Hum Reprod., 2008; 23 (1): 91 9

Blastocyst Grading

Blastocyst grading - I Grade 3 Grade 4 Grade 5 Grade 2 Grade 6 Grade 1 EXPANSION STATUS

Blastocyst grading - II ICM TROPHECTODERM Grade B Grade A Grade a Grade E Grade b Grade C Grade D Grade c

Time lapse

Time lapse No detrimental effect Uninterrupted culture Overcomes static assessment Rules out embryos (0-3 cells) Encouraging data Need to validate algorithms Large scale multicentre studies Further evidence may mean shift to d2/3 ETs

Is blastocyst quality a good predictor of outcome?

Pregnancy rates related to blastocyst grade Number of top quality* blasts transferred 0 (n=52) 1 (n=56) 2 (n=14) Singleton rate 25.4% 54.3% 75% Twin rate 1.9% 7.1% 35.7%

Cryopreservation

Cryopreservation Many studies have shown pregnancy rates were significantly lower for patients having eset for individual fresh and frozen cycles NEED EFFECTIVE CRYOPRESERVATION PROGRAMMES BUT the cumulative live birth rates between the DET and eset groups were not significantly different.

Evidence Recent developments using vitrification appear to result in significantly improved survival rates Learning curve!

2. Multiple Birth Targets our experience: 2009: 24% 2010: 20% 2011: 15% 2012: 10%

UK year 3 results (HFEA) Age eset Preg Rate` eset MPR DET Preg Rate DET MPR <35 42 1.7 39 35.2 35-37 37.6 1.6 35.4 28.9 38-39 34.4 <1 30.6 24.7 All ages 39.6 1.5 34 30.2

How to reduce the MBR further? Patients who go against our advice (Twin rate 8/21 = 38%) Patients aged 37-39 first cycle Patients with 2 blastocysts which don t meet cryo criteria FERs when previous cycles failed

Conclusions Multiple pregnancy is avoidable eset must be implemented Blastocyst transfer may help eset Team work essential Effective counselling of patients Confidence and consistency