future of ivf frozen better than fresh · to determine if a policy of freezing created embryos,...

Life without artificial cold is hard to imagine in the developed world.

But it all started 200 years ago with some giant ice cubes

Abha Maheshwari Consultant Reproductive Medicine & Surgery

NHS GRAMPIAN

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Future of IVF – Frozen better than Fresh ?

What is in-vitro Fertiliztion (IVF)?

Fertilisation to Embryo

Day 1 Day 2

Day 3 Day 5

Fate of Embryos

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To achieve ...........

IVF league table

Healthy mum & a healthy baby

Long term health

How do we get eggs?

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OHSS- A price we have to pay!

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Safety- singleton pregnancies

Obstetric/ perinatal outcomes

Outcome Overall effect (RR, 95%CI)

APH 2.49 (2.30-2.69)

Congenital anomalies 1.67(1.33-2.09)

Hypertension 1.49 (1.39-1.59)

PPROM 1.16 (1.07-1.26)

Caesarean Section 1.56(1.51-1.60)

Birth weight < 2500gm 1.65(1.56-1.75))

Birth weight<1500gm 1.93 (1.72-2.17)

Perinatal mortality 1.87(1.48-2.37)

Delivery at < 37 weeks 1.54 (1.47-1.62)

Delivery at < 32 weeks 1.68 (1.48-1.91)

Transfer to NICU 1.58 (1.42-1.77)

Gestational diabetes 1.48 (1.33-1.66)

Induction of Labour 1.18 (1.10-1.28)

Small for Gestation age 1.39 (1.27-1.53)

Long term costs to NHS

USA data (< 35 years old)

Year Live birth/ started cycle implantation rate

2013 40.1% 39.5%

2012 40.6% 37.4%

2011 40.1% 36%

2010 41.7% 36.9%

2009 41.4% 35.6%

2008 41.3% 34.1%

2007 39.9% 32.6%

IVF is not good!

IVF is here to stay!

Something need to change!

Endometrium and

implantation

Evans et al., 2014 Hum Reprod Update

Why could success rates be better?

Ovarian

stimulation

Embryo

transfer

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Outcome RR (95% CI)

Small Gestational Age 0.45 (0.30,0.66)

Birth Weight <2500gm 0.69 (0.62,0.76)

Delivery at <37 Weeks 0.84 (0.78,0.90)

APH 0.67 (0.55,0.81)

Perinatal Mortality 0.68(0.48,0.96)

Lower risk of ectopic

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Clinical pregnancy rates –

Frozen embryo transfer

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Graduation Gifts for future

WIN-WIN-WIN situation

Frozen embryo transfer

Healthier pregnancies

Better pregnancy

rates

OHSS free clinics

Planned weekend work load

Unknowns

• Which patients to freeze – all?

• When embryos are not good?

• Is it clinically effective?

• Is it cost effective?

• Is it acceptable?

• Recent concerns about LGA babies

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Evidence from HFEA data

Fertil Steril . Maheshwari A, et al. 2016

FREEZE ALL

FRESH

EMBRYO

TRANSFER

To determine if a policy of freezing created embryos,

followed by thawed frozen embryo transfer is a more

clinically effective, safer and cost effective way to

provide in-vitro fertilization when compared with the

current practice of transferring fresh embryos.

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Primary Outcome

• Healthy baby rate:

– Term

– Singleton

– Live birth

– Appropriate weight for gestation

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Secondary Outcomes• Complication of IVF treatment

– OHSS

• Complications in pregnancy

– Miscarriage

– Pre-eclampsia

– Antepartum haemorrhage

– Multiple pregnancy

– Low birth weight

– Preterm delivery

– Small for gestational age

– Congenital anomaly

– Perinatal mortality

• Clinical effectiveness

– Live birth rate

– Pregnancy rate

• Effectiveness of the process of

freezing embryos

– Failure of embryos to survive after

thawing

• Health economic outcome

– Costs to the health service

– Modelled long-term costs (broader

societal costs)

• Evaluation of emotional state

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Participating Centres

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Future recruiting centres:

- King’s College Hospital

- Nurture, Nottingham

- Jessop Wing, Sheffield

Recruitment Target:

1086 Couples

Current recruiting centres:

- Aberdeen Maternity Hospital - Homerton Hospital

- Guy’s & St Thomas’ - Hammersmith Hospital

- Liverpool Women’s - St Mary’s, Manchester

- Princess Anne, Southampton - Birmingham Women’s

- St Bartholomew’s Hospital

- Oxford Fertility

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It does not end with E-Freeze

• 90% consenting for long term follow up

• Cumulative live birth rate

• Follow up of children born 1,5,10.... years

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International Collaboration