Eggs - The Portland Hospital

Beyond the Media Hype:
The truth about Egg Freezing
James D M Nicopoullos
Consultant Gynaecologist
Subspecialist Reproductive Medicine
"This is now becoming quite a big business. It's really not likely to work," Lord
Winston says, quoting figures showing that the overall success rate from egg
freezing is less than 10 per cent.
"That's not to say it shouldn't be done, provided it's safe. But I don't think people
who are having eggs frozen realise just how low their chances of having a baby
are."
Biological
Clock
Social
Change
Scientific
Progress
Eggs
Before birth
7 million eggs
At birth
2 million eggs
First period
0.5 million eggs
Menopause
No eggs
Eggs
Every month a female produces one egg
Eggs
Every month a female produces one egg
1 x 12 x 40 = 480 eggs
Eggs
Every month a female produces one egg
1 x 12 x 40 = 480 eggs
But she has 480,000 eggs
Eggs
Every month a female produces one egg
1 x 12 x 40 = 480 eggs
But she has 480,000 eggs
what happens to all of the other
follicles???
Inefficient process
1-2 million primordial
follicles at birth
400,000 at puberty
400- 500
ovulations
99%
atresia
12
Chromosomes on a meiotic spindle in egg
Older eggs are more likely to retain
an extra copy of a chromosome
or to expel a whole pair resulting in
MONOSOMY / TRISOMY
Egg must expel half of each pair of chromosomes
to be ready for fertilisation by a sperm
13
Age on Natural Conception
11%
8%
5%
5%
3.5%
2%
IVF outcome related to age
(All ages)
Lister data: 2005 - 2013
IVF outcome related to age: 4 – 6 eggs
(All ages)
Lister data: 2005 - 2013
http://ohiorepromed.com/
Egg Donation
( age of recipient)
Lister
% abnormal embryos divided by age
egg
<35
35-39
40-42
>42
# day 5
embryos donors years old years old years old years old
1-3
4-6
7-10
> 10
30%
32%
51%
66%
83%
23%
37%
48%
69%
87%
38%
42%
52%
73%
78%
33%
41%
49%
59%
83%
Ata et al. (2012): 262 cycles, 1618 embryos. Linear regression analysis: Euploidy
significantly decreased with age (p<0.001) but NOT with cohort size.
Biological
Clock
Social
Change
Scientific
Progress
Delaying pregnancy – a modern
phenomenon
Relative changes in age-specific conception
Office of National Statistics
Average Female Age undergoing
IVF Treatment at Lister
“ They never tell the press if the gorgeous
eggs which made those beautiful babies
possible were chosen from a catalogue of
college prom queens at $10,000 a go”
Biological
Clock
Scientific
Progress
Social
Change
Challenges of Egg Freezing
• Problems with freezing
– Ice formation
– Lethal concentration of solutes
SLOW-FREEZING
• Older method
• Time-consuming and expensive
• Lower survival and pregnancy rates
• Lower levels of Cryoprotectant
• Takes 2 hours to freeze through
a series of cooling steps
• 0.3C/min initially to -30
• 50C/min thereafter to 150C
VITRIFICATION
Minimises crystallisation by
producing “glass-like” state
•Newer method
•Takes seconds and cheap
•Better survival and pregnancy rates
•High Levels of Cryoprotectant
• Shrinks embryo
• Reduces Water content
•Rapid Cooling
• 20,000C/min
Oktay et al, 2006
SLOW – FREEZING
1996 - 2005
VITRIFICAION
2003 - 2005
Fertilisation rate
64.9%
74.2%
Clinical Pregnancy /
thawed oocyte
2.3%
4.8%
Clinical Pregnancy /
transfer
20.6%
45.5%
Implantation Rate
10.1%
17.1%314
ASRM 2012
“The success of oocyte cryopreservation has
improved dramatically over the past decade,
and preliminary data for safety are reassuring.
Therefore, this technique should no longer be
considered experimental”
ESHRE 2012
BFS / RCOG 2015
BFS / RCOG endorse the procedure for
medical reasons but not as a way to delay
childbearing as a lifestyle choice.
“Too early to be sure the freezing methods
used are safe in the long-term, besides which
the procedure is very involved and has no
guarentee of success”
An Egg Freezing Consultation
Assess Fertility Status
• Transvaginal Scan
• Assessment of ovarian reserve
– FSH / LH / Oestradiol
– Antral Follicle Count
– Anti-Mullerian Hormone
AMH Normogram
Age
10th
25th
50th
centile centile centile
(Adapted from Nelson et al, 2010)
75th
centile
90th
centile
25
6
11
24
-
-
30
4
7.5
17.5
-
-
35
3
5
10
21
-
40
1.5
2.5
5
11
21
45
-
1
2.5
5
9
Number of eggs related to AMH
(All ages)
Lister data: 2005 - 2013
Options for a single women
• Conception asap
– Treatment now with Donor sperm
– Pregnancy now with Mr Not so Right
• Nothing
– Await Mr Right and natural conception
• Fertility Preservation
– Egg freezing
– Embryo freezing
IVF outcome related to age
(All ages)
Lister data: 2005 - 2013
Options for a single women
• Conception asap
– Treatment now with Donor sperm
– Pregnancy now with Mr Not so Right
• Nothing
– Await Mr Right and natural conception
• Fertility Preservation
– Egg freezing
– Embryo freezing
Egg Freezing Cycle
• Ovarian stimulation
– 2 weeks daily injections of FSH
– Preventing ovulation
• Downregulation or antagonist
– Ultrasound scans (x 3-4)
– Blood tests
Monitoring
http://www.infertility-info.org/
Egg Collection
http://ohiorepromed.com/
Assisted Conception Cycle
Stimulation
Monitoring
Egg Collection
Assisted Conception Cycle
Stimulation
Monitoring
Egg Collection
Insemination
Fertilisation
Embryo culture
Embryo Transfer
Luteal support
Assisted Conception Cycle
Stimulation
Egg Stripping
Monitoring
Assess Maturity
Egg Collection
Egg Vitrification
Insemination
Fertilisation
Embryo culture
Embryo Transfer
Luteal support
Egg Thaw
ICSI
Success Rates
HFEA UK data
FOI – 2005 - 00316
• 2009 – 2014
– 22,993 eggs frozen
– 4,555 thawed in 582 cycles
•
•
•
•
•
19.8% utilisation
40% fertilisation rate
106 Livebirths
21.8% PR / thaw cycle
18.2% LBR / thaw cycle
?
Sibling Ooctyes (Rienzi et al, 2010)
Sibling Oocytes, Cobo et al, 2010
National USA (SART) Data 2013
comparing fresh donor eggs
with frozen eggs
Age <35: 38,300 eggs collected
1 in 15 eggs
Lister Data: 2005 - 2013
Lister Data : 2005 - 2013
• Age <35
– 6.6% of eggs give livebirth
– 1 in 15
• Age 35 - 40
– 5.0% of eggs give livebirth
– 1 in 20
• Age > 40
– 1.8% of eggs give livebirth
– 1 in 55
Number of eggs related to AMH
(All ages)
Lister data: 2005 - 2013
Factors to Consider
Physical
• Hormonal effects of stimulation
• Ovarian hyperstimulation syndrome
– Severe <1%
• Pelvic infection
– 1 in 500-1000
• Injury to blood vessels or other pelvic organs
– 1 in 2500
• Risks from GA / sedation
– 1 in 10,000 adverse reaction
Financial
• London clinic
– Mean cost £3370 / freeze cycle
– Drug cost £700 - £1000
– Package prices for 3 cycles
Long term safety
• Freezing safety
– Lower obstetric risk
• Low Birth weight / Prematurity / PNM
– No increase risk in childhood outcomes
• Setti et al, 2013
– Compared pregnancies with fresh and frozen
eggs in same women
• No difference in miscarriage rate
• No difference in risk of low birth weight
• No difference in risk of birth defects
Long term safety
• Chance of conception / miscarriage based on
age of Egg
• Many pregnancy/delivery complications
based on age of mother
–
–
–
–
–
Pre-eclampsia
Diabetes
Preterm delivery
Growth restriction
Caesarean / Instrumental rates
Psychological / Social
•
•
•
•
•
Failed Egg Survival
Failed Egg Fertilisation
Failed Embryo Development
Negative Pregnancy Outcome
Psychological / Emotional
• ? Delay trying naturally / seeking partner
Failed Insurance Policy?
“I am aware that freezing my eggs does not
guarantee my future fertility and should not be seen
as a definitive alternative to natural conception”
“I am aware that freezing my eggs should not give
me the security to delay natural conception and this
would in fact be detrimental to overall chances of
conception”
Decision-making
• 2011 Questionnaire survey
• Women aged 21 – 40
– 31.5% would consider freezing
– 98% would do it again
– 71% would do at a younger age
“Some insurance is better than none at all”
“I don’t want to regret not doing it……”
Moving forward
•
•
•
•
•
Long term safety / efficacy
Improved education of fertility decline
Improved education of fertility options
Moral / Religious objections?
Ethical issues
– Access limited to more affluent?
– Age-limit / Welfare of child?
– Encourage women to defer childbearing?
Is it really the answer?
Stopping the biological clock
through egg freezing has long been
the ultimate feminist fantasy.
Daily Mail, November 2012