Cryopreservation of oocytes for social or medical reasons:Is there a difference?

Dr Gillian LockwoodMedical DirectorMidland Fertility Services

Prospects for Oocyte Cryopreservation

‘Fertility preservation’ for young cancer patients‘Fertility extension’ for social reasons

Increased (and safer!) chances of pregnancy for IVF patients with ethical objections to embryo freezing‘Better ‘matching’ and ‘quarantining’ for egg donation recipients ?‘Maternal’ donor eggs for girls diagnosed with Turner Syndrome

Cancer: The Scale of the ProblemCancer: The Scale of the Problem

Childhood Cancer- A success story1in 500 children will develop cancer before age 1573% overall cure rate (ISD, Scotland)By 2010, one in 715 adults will be a long term survivor of childhood or adolescent cancerFertility prospects are identified as a

specific anxiety for patients and their parents

Malignancies in Young Women

Damage to the ovary following cancer therapy is very age dependentExposure to high-doses of alkylating agents and ovarian radiation are associated with an increased risk of both acute ovarian failure and premature menopause

Malignancies in Women

Gynaecological cancers generally affect older womenSignificant subset of young women with gynaecancer are of childbearing ageDelayed childbearing is commoner in women who develop cancer

Breast Cancer: Incidence rises

Breast cancer is the most common cancer in England (32% of all female cancers)25% of women diagnosed with breast cancer are pre-menopausal10-20% of newly diagnosed breast cancers occur in women of normal childbearing ageIncidence: 120 cases per 100000 womenMortality: 29 deaths per 100000 women:

Risk factors: late pregnancy, low parity, obesity

Total numbers of follicles in human ovaries (showing bi-exponential fall from 37 years)

(After Faddy et al 1992)

age (years)

No.

of f

ollic

les

(thou

sand

s)

0 10 20 30 40 500.1

1

10

100

1000

Ovarian reserve and reproductive choicesOvarian reserve and reproductive choices

OocyteOocyte cryopreservation (precryopreservation (pre--chemo) requires chemo) requires normal ovarian reservenormal ovarian reserveAMH estimation allows rapid and reliable assessmentAMH estimation allows rapid and reliable assessment

Women with poor reserve may well be able to Women with poor reserve may well be able to conceive spontaneously, but should be counselled conceive spontaneously, but should be counselled against delayagainst delay

‘Age plus a decade’ equals ‘reproductive age’‘Age plus a decade’ equals ‘reproductive age’

Is there a ‘need’ for social egg freezing ?

EducationLater marriageEconomic independenceA ‘technical fix for a biological problem’The Media…..

Female Age, SocioFemale Age, Socio--biology and Infertility in Europebiology and Infertility in Europe

The average age of first maternity in the UK has risen from 23 to 29 in one generationThe average number of babies per woman in the EU is 1.5

50% of UK women aged 30 who expressed a desire for motherhood had failed by 4020% of UK women are childless

Age-related sub-fertility is the fastest growing cause of infertility referred for treatment

0

5

10

15

20

25

30

35

womanwants baby

womandoesn't

Has a partnerNo partner

Probability of a baby at 35 : Probability of a baby at 35 : Based on childless womanBased on childless womanwith degree and average earningswith degree and average earnings

%%

Source: National StatisticsSource: National Statistics

National Sample Survey of 1876 childless women in their 30s: British Household Panel

Only 49.8% of women who said they intended to have a child did so within 6 yearsChildless women characteristically overestimate their number of remaining ‘childbearing’ yearsHigh-earning women who postponed motherhood were more likely to have a child at older ages Anne Anne BerringtonBerrington : Southampton : Southampton UnivUniv

Women and the ‘fertility penalty’

A third of women will return to a less well paidjob than before they gave birth.

The average woman foregoes £564K in earnings over her lifetime if she has a first child at 24 compared to a childless woman

If she waits until 28 she will forego £165K

Bridget Jones: Heroine or victim?

What is ‘poor Bridget’ to do?

Education till 21 (50% graduate workforce)Training till 25Meet Mr Right (39% divorce rate)Meet Mr Right Mk II (65% divorce rate)Mortgage deposit?Now aged 3638% of Bridgets who want to get pregnant won’t

Maternal Age and Fetal lossDanish data Andersen et al 2000

01020

304050

607080

15 20 25 30 35 40 45

sp abortionectopicstillbirth

Maternal age at conception(1.2 Million pregnancies)

%

Why are older women having IVF?

In 2006 in the UK, 6174 treatment cycles for women aged 40-45 using their own eggs were performed15.5% of all cycles!

The results are desperately poor but the‘patients’ autonomy’ must be respected And what is the alternative?

The reality: IVF LBR (HFEA data)

Age 40 12.1%Age 41 10.3%Age 42 7.6%Age 43 4.9%Age 44 2.6%Age 45 1.6%

In what other branch of medicine would we let patients insist that we perform an elective operation with <5% chance of it working?

The Medium Is the Message

Beverley D’Angelo

Twins Aged 49

Portrait of a ‘social’ egg freezer

Aged 36College educated and in full-time employment (teacher, nurse, accountant, shop-owner)Never been pregnantRecently broke up after a long term relationship over his ‘failure to commit’Always assumed and hoped she would ‘get married and have kids’Scared of ‘seeming desperate’ in a new relationship!

Human oocyte cryopreservation

First pregnancies achieved in 1980’s Chen (1986) and Al Hasani et al (1987)

Low fertilisation rateLow survival rates Hardening of zonaPossible spindle damage

Our program at MFS

Initially set up to offer fertility preservation to oncology patients

Obtained licence to freeze and store MII oocytes in early 2000. Licence revised later that year for use.

Frozen a total of 732 oocytes for 66 patients (not all oncology patients).

Reasons for Oocyte Cryopreservation66 patients

Fertility PreservationFertility Preservation(31)(31)

47.0%47.0%12.1%12.1%

15.2%15.2%

25.7%25.7%

OtherOther(8)(8)Ethical/Religious Ethical/Religious

objections to objections to embryo freezingembryo freezing

(10)(10)

Social reasonsSocial reasons(17)(17)

Emily:the UK’s first‘frozen egg’ babynow 7

Results – Frozen/thawed oocytes compared with frozen/thawed embryos

MFS data for 8 years of embryo freezing between 2000-2008

28% Clinical Preg. rate/transferImplantation rate of 14.2%

MFS data for 7 years oocyte freezing between 2001 – 2008

26.4% Clinical Preg. rate/transferImplantation rate of 18.3%

The Future

VitrificationKuwayama (ESHRE 2006) Kato Clinic, TokyoSurvival rate of 94.5%,Fertilisation rate of 90.5%,Good cleavage rate of 50%Pregnancy rate of 41.9%

Choline Chloride ?Substituting sodium chloride to

help protect membranePolscope

Visualise the reformation of the spindle

What’s the Evidence?

Oktay, Cillit and Bang (2006)Meta-analysis of efficiency of oocyte cryopreservationIVF with unfrozen eggs compared to IVF with slow frozen eggs OR of live birth per injected oocyte of 1.5 (1.26-1.79)With vitrification OR much lower

What is the proper comparator?

What’s the latest evidence?

Cobo, Kuwayama,Perez et al (2008)30 oocyte donors and 30 recipientsVitrification by cryotop method with warming and ICSI after one hour (survival rate 96.7%)There was no difference in FR (76.3% vs 82.2%),BFR etc23 ETs in vitrification group. Pregnancy rate was 65.2%, IR was 40.8% and miscarriage rate was 20%

What is the proper comparator?

Vitrification: Is it safe?

Concerns because of the high concentrations of cryoprotectant requiredRecent evidence for less damage to spindle integrity and chromosome alignment ( Huang et al 2007) compared to ‘slow freeze’ eggs.Recent report of obstetric and perinatal outcome of 200 babies born from vitrified oocytes (165 pregnancies) (Ri-Cheng Chian et al 2008)No increased risks identified

To conclude….The science

Oocyte freezing does have it’s place, especially giving hope to women whose fertility will become impaired by time Published results are improving rapidlyPregnancy rates and Implantation rates are at least as good as for embryo freezingNew techniques, such as vitrification using ‘slush nitrogen’ at -210oC, may be the way forward

So is there a difference?

Success not guaranteed?

Nothing to lose?

Unproven safety record?

To conclude….The ethics

Women are trying to get pregnant when olderThey want their own ‘genetic’ childThere are fewer donor eggs anyway….Should we encourage (or even allow) a ‘trade’ in donor eggs?Pregnancy rates (with vitrification) are similar to ‘fresh’when using ‘young’ eggs

Is society ready to think that age may be a treatable pathology? Will oocyte freezing come to be seen as significant and revolutionary as the introduction of the OCP?

Social egg freezingdoesn’t mean this is inevitable…

Thank you for your attention.Thank you for your attention.

www.midlandfertility.com