1. Cryopreservation of oocytes for
social or medical reasons:
Is there a difference?
Dr Gillian Lockwood
Medical Director
Midland Fertility Services

2. 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

3. Cancer: The Scale of the Problem
Childhood Cancer- A success story
1in 500 children will develop cancer before
age 15
73% overall cure rate (ISD, Scotland)
By 2010, one in 715 adults will be a long
term survivor of childhood or adolescent
cancer
Fertility prospects are identified as a
specific anxiety for patients and their
parents

4. Malignancies in Young Women
Damage to the ovary following cancer therapy is
very age dependent
Exposure to high-doses of alkylating agents and
ovarian radiation are associated with an increased
risk of both acute ovarian failure and premature
menopause

5. Malignancies in Women
Gynaecological cancers generally affect older
women
Significant subset of young women with gynae
cancer are of childbearing age
Delayed childbearing is commoner in women who
develop cancer

6. 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-menopausal
10-20% of newly diagnosed breast cancers occur in
women of normal childbearing age
Incidence: 120 cases per 100000 women
Mortality: 29 deaths per 100000 women:
Risk factors: late pregnancy, low parity, obesity

7. Total numbers of follicles in human ovaries
(showing bi-exponential fall from 37 years)
(After Faddy et al 1992)
No. of follicles (thousands)
1000
100
10
1
0.1
0 10 20 30 40 50
age (years)

8. Ovarian reserve and reproductive choices
Oocyte cryopreservation (pre-chemo) requires
normal ovarian reserve
AMH estimation allows rapid and reliable assessment
Women with poor reserve may well be able to
conceive spontaneously, but should be counselled
against delay
‘Age plus a decade’ equals ‘reproductive age’

9. Is there a ‘need’ for social egg freezing ?
Education
Later marriage
Economic independence
A ‘technical fix for a
biological problem’
The Media…..

10. Female Age, Socio-biology and Infertility in Europe
The average age of first maternity in the UK
has risen from 23 to 29 in one generation
The 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 40
20% of UK women are childless
Age-related sub-fertility is the fastest growing
cause of infertility referred for treatment

11. Probability of a baby at 35 : Based on childless woman
with degree and average earnings
% 35
30
25
20
15 Has a partner
No partner
10
5
0
woman woman
wants baby doesn't Source: National Statistics

12. 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 years
Childless women characteristically
overestimate their number of remaining
‘childbearing’ years
High-earning women who postponed
motherhood were more likely to have a child
at older ages
Anne Berrington : Southampton Univ

13. Women and the ‘fertility penalty’
A third of women will return to a less well paid
job 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

14. Bridget Jones: Heroine or victim?

15. What is ‘poor Bridget’ to do?
Education till 21 (50% graduate workforce)
Training till 25
Meet Mr Right (39% divorce rate)
Meet Mr Right Mk II (65% divorce rate)
Mortgage deposit?
Now aged 36
38% of Bridgets who want to get pregnant won’t

16. Maternal Age and Fetal loss
Danish data Andersen et al 2000
80
70
% 60
50
sp abortion
40
ectopic
30 stillbirth
20
10
0
15 20 25 30 35 40 45
Maternal age at conception
(1.2 Million pregnancies)

17. Why are older women having IVF?
In 2006 in the UK, 6174 treatment cycles for
women aged 40-45 using their own eggs were
performed
15.5% of all cycles!
The results are desperately poor but the
‘patients’ autonomy’ must be respected
And what is the alternative?

18. 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?

19. The Medium
Is the Message

20. Beverley D’Angelo
Twins Aged 49

22. Portrait of a ‘social’ egg freezer
Aged 36
College educated and in full-time employment
(teacher, nurse, accountant, shop-owner)
Never been pregnant
Recently 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!

23. Human oocyte cryopreservation
First pregnancies achieved in 1980’s
Chen (1986) and Al Hasani et al (1987)
Low fertilisation rate
Low survival rates
Hardening of zona
Possible spindle damage

24. 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).

25. Reasons for Oocyte Cryopreservation
66 patients
Other Fertility Preservation
Ethical/Religious (31)
(8)
objections to
embryo freezing
(10) 12.1%
15.2% 47.0%
25.7%
Social reasons
(17)

26. Emily:
the UK’s first
‘frozen egg’ baby
now 7

27. Results – Frozen/thawed oocytes
compared with frozen/thawed embryos
MFS data for 8 years of embryo freezing between 2000-2008
28% Clinical Preg. rate/transfer
Implantation rate of 14.2%
MFS data for 7 years oocyte freezing between 2001 – 2008
26.4% Clinical Preg. rate/transfer
Implantation rate of 18.3%

28. The Future
Vitrification
Kuwayama (ESHRE 2006)
Kato Clinic, Tokyo
Survival 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 membrane
Polscope
Visualise the reformation of the
spindle

29. What’s the Evidence?
Oktay, Cillit and Bang (2006)
Meta-analysis of efficiency of oocyte cryopreservation
IVF 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?

30. What’s the latest evidence?
Cobo, Kuwayama,Perez et al (2008)
30 oocyte donors and 30 recipients
Vitrification 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 etc
23 ETs in vitrification group. Pregnancy rate was
65.2%, IR was 40.8% and miscarriage rate was 20%
What is the proper comparator?

31. Vitrification: Is it safe?
Concerns because of the high concentrations of
cryoprotectant required
Recent 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

32. 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 rapidly
Pregnancy rates and Implantation rates are at least
as good as for embryo freezing
New techniques, such as vitrification using ‘slush
nitrogen’ at -210oC, may be the way forward

33. So is there a difference?
Success not guaranteed?
Nothing to lose?
Unproven safety record?

34. To conclude….The ethics
Women are trying to get pregnant when older
They want their own ‘genetic’ child
There 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?

35. Social egg freezing
doesn’t mean
this is inevitable…

36. Thank you for your attention.
www.midlandfertility.com