1) Assisted reproductive techniques like egg freezing allow women to preserve their fertility for medical or social reasons. 2) Freezing eggs through vitrification has improved significantly and can provide pregnancy success rates similar to fresh eggs. 3) While egg freezing is accepted to preserve fertility for young cancer patients, there is debate around its use for social reasons due to concerns about unrealistic expectations of future fertility and the ethics of commercializing human eggs.

1. Assisted Reproductive Techniques :
Horizon of Hope
Moderator : Dr. Bharati Dhorepatil

3. "Destiny is not a matter of chance,
it is a matter of choice."
Winston Churchill

4. Freezing eggs

5. Never
mind
there’s
Always
Solutions!

6. • Freezing eggs:
Is it worthwhile?
Apple and Facebook offer to freeze eggs for female staff -
Telegraph
Apple and Facebook offer to freeze eggs for female staff
Facebook has started offering female staff up to $20,000 to
have their eggs frozen and Apple will pay for its female
employees to go through the same process from January

7. Prospects for Oocyte Freezing
• ‘Fertility preservation’ for young cancer patients
• Increased (and safer!) chances of pregnancy for IVF patients
with ethical objections to embryo freezing
• ‘Fertility extension’ for social reasons?
• Better ‘matching’ and ‘quarantining’ for egg donation
recipients ?
• ‘Maternal’ donor eggs for girls diagnosed with Turner Syndrome

8. 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
• Future fertility prospects are identified as a specific
anxiety for young women and their parents
‘Age plus a decade’ equals ‘reproductive age’ following
chemotherapy

9. Acute ovarian failure is not the only issue
• 1041 women diagnosed with cancer between 18 and 40
• 640 received chemotherapy alone
• Acute ovarian failure (AOF) reported for 8%,10%,9% and 10%
for HD, NHL, Br Ca and GI cancer
• AOF increased significantly with age (p< 0.05)
• Infertility in non-AOF patients was reported as 40% at age 35
• Probability of early menopause was 25% at age 30
Letoumeau et al Cancer August 2011

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

11. Age-related meiotic segregation errors in mammalian
oocytes are preceded by depletion of Cohesin and Sgo2
(Lister et al 2010 Current Biology)

12. The perils of ‘perpetual postponing’
• The risk of permanent childlessness and female age at time of
starting to try to conceive is….
• 6% at age 30
• 14% at age 35
• 35% at age 40
• Just postponing a first conception attempt from 25 to 30 years
reduces mean number of children from 2 to 1.7, increases infertility
prevalence from 9.8 to 15.8% and increases ‘incomplete’ families
from 14.8 to 24%
(Leridon INED France)

13. Unreasonable expectations…
• 59% of childless women aged 35-39 still planned
to have a baby
• 30% aged 40-45 did too!
(Sobotka, Austrian survey data)

14. Estimated childlessness at age 45 years for the NCDS cohort
and (optimistic!) projections for the BCS70 cohort

15. 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?

16. Human oocyte cryopreservation
• First pregnancies achieved in 1980’s
Chen (1986) and Al Hasani et al (1987)
• Procedure abandoned for approx.
10 years due to poor results
Low fertilisation rate
Low survival rates
Hardening of zona
Possible spindle damage

17. • Vitrification
Kuwayama
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

18. Slow cooling
(Whittingham et al., Science
1972,
Willmut et al., Life Science
1972)
- 0.3°C/min
Vitrification
(Rall and Fahy 1985)
- 50.000°C/min
2 sec.

19. 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?

20. • Nagy,Chang,Shapiro et al Fertil and Steril (2010)
• 10 oocyte donors and 20 recipients
• Vitrification for a minimum of one hour
(survival rate 87.5%, FR 87% and BFR 68%)
• 15 of 20 recipients became pregnant with 26/47 (55%)
embryos implanting and 26 live born infants
• 2 further pregnancies were established from
supernumery frozen embryos
• All outcomes were similar when compared to cycles using
the SAME oocyte donors in fresh cycles

21. 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

22. Reasons for oocyte cryopreservation
157 patients (2009)
Fertility Preservation
(58)
36.9%10.7%7.4%
45.0%
Other
(17)
Ethical/Religious
objections to
embryo freezing
(13)
Social reasons
(69)

23. Results – Frozen/thawed oocytes compared with
frozen/thawed embryos
MFS data :
25% Clinical Preg. rate/transfer
Implantation rate of 12.6%
MFS data:
21.4% Clinical Preg. rate/transfer
Implantation rate of 17.4%

24. To conclude….We have the technology
• Women are trying to get pregnant when older
• They want their own ‘genetic’ child (or children!)
• There are few 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

25. We accept oocyte freezing for young
cancer patients: So is there a difference
with ‘social’ egg freezers?

26. To conclude….The ethics
• Governments have tried bribing, bullying and lecturing but
still women are trying to get pregnant when older
• ‘Brute Biology’ means that women will live to 80 but most
will be functionally infertile by 40
• Why are we uncomfortable with social egg freezing?
• Will ‘social’ oocyte freezing come to be seen as significant
and revolutionary as the introduction of the OCP?

27. Thank you for your attention