The Latest and Greatest on Egg
Freezing
Jennifer Hirshfeld-Cytron,
MD/ MSCI
1
© Fertility Centers of Illinois
2
© Fertility Centers of Illinois
TIME IS NOT OUR FRIEND
3
© Fertility Centers of Illinois
Impact of age: decreased fecundability
• Fertility and fecundity decrease with age
• Increased number of US women delay childbearing
4
© Fertility Centers of Illinois
Speroff L and M Fritz 2005; Chapter 27; 1016.
Ventura SJ et al. 2008 National vital statistics reports
2008:16(5)
Malizia BA et al. NEJM 2009; 360: 236-43.
Aneuploidy increases with maternal
age
n=5,515 Blastocysts; p<0.0001
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
<35 Years
Euploid
Aneuploid
5
© Fertility Centers of Illinois
35-37 Years
38-40 Years
41-42 Years
43+ Years
CCRM unpublished, personal communication
Surrogate markers of ovarian reserve
•
Ovarian reserve testing
– Age
– Day 3 FSH
• >10mIU/mL abnormal
– Day 3 estradiol
– Anti-müllerian hormone
• Related to onset of menopause
• <0.16 predicts onset of menopause
within 9 years
• Decrease precedes changes in other
conventional parameters
– Ovarian volumes
– Antral follicle count
6
© Fertility Centers of Illinois
Ovarian reserve summary
• Age is most important predictor of reserve
• Ovarian reserve testing predicts # oocytes that
can be retrieved
• Abnormal testing demonstrates a smaller resting
follicular pool and is correlated with worse
outcomes
7
© Fertility Centers of Illinois
ART canNOT overcome age
• Success of ART is dependent on age
• In woman with DOR and/or advanced age donor
egg is often necessary
Donor oocytes
Autologous oocytes
8
© Fertility Centers of Illinois
Learning Objectives
• Explore ART technologies that have allowed for
improvement in egg freezing
• Discuss ASRM recommendations regarding egg
freezing
• Describe current clinical success with egg
freezing
• Address potential patient and societal costs with
egg freezing
9
© Fertility Centers of Illinois
HISTORY OF OOCYTE
VITRIFICATION
10
© Fertility Centers of Illinois
Oocyte Cryopreservation




11
Chen, 1986: First reported live birth
No partner needed
Time, hyperstimulation required, poor thaw techniques
Why poor survival of frozen oocytes vs embryo?
 Initial slow freeze method
 Fragility of meiotic spindle
 Ice crystal formation (mature oocyte large H20 vol)
 Hardening zona pellucida effect fertilization
© Fertility Centers of Illinois
Oocyte Cryopreservation:
Improve Survivability
• How?
– Vitrification Protocols: Fast freeze
• ↓ ice formation; ↑ oocyte survival
• Pregnancy rates from vitrification EQUIVALENT
to embryo in young woman
– Not considered investigational in Europe
– Not considered experimental by ASRM
12
© Fertility Centers of Illinois
13
© Fertility Centers of Illinois
Slide Courtesy of Dr. Juergen Liebermann
Egg Freezing AS GOOD AS fresh
14
© Fertility Centers of Illinois
Oocyte vitrification does NOT increase
aneuploidy
• Sibling oocyte study
– Pts < 35y/o undergoing 1st IVF cycle
– Normal ovarian reserve parameters
– CCS on blastocysts
– Double embryo transfer, one from each group
– Gender determination or DNA fingerprinting in
singletons to learn which embryo implanted
– No differences in aneuploidy rates,
implantation rates, pregnancy rates , live birth
rates between groups
Forman E., et al. Fertil Steril 2012
15
© Fertility Centers of Illinois
Infant Outcomes
• Initial retrospective data suggest frozen eggs
BETTER outcomes as infants are larger
16
© Fertility Centers of Illinois
Infant Outcomes
• Noyes 2009  systematic review
• Over 900 babies born without an apparent
increase in congenital anomalies
– Overall anomaly rate was 1.3%
• To date >1500 babies born without an increase
in anomalies noted.
Noyes N. et al., Reprod Biomed Online 2009
– Registries are needed
17
© Fertility Centers of Illinois
Egg Freezing AS GOOD fresh
• THEREFORE ASRM REMOVED
EXPERIMENTAL LABEL TO MATURE
EGG FREEZING
• STILL EXPERIMENTAL ACCORDING
TO INSURANCE COMPANIES AND
NOT COVERED
18
© Fertility Centers of Illinois
ASRM Practice Committee, Fertil Steril 2013
ASRM GUIDELINES
19
© Fertility Centers of Illinois

Fertilization/pregnancy rates from IVF/ICSI are
similar for fresh oocytes vs vitrified/warmed
oocytes

No increase in chromosomal abnormalities, birth
defects, or developmental deficits

Insufficient evidence to recommend for egg
donation or for “circumventing reproductive aging
in healthy women”
“Based on the current state of evidence, modern
procedures to cryopreserve oocytes should no longer
be considered experimental. The American College of
Obstetricians and Gynecologists’ Committee on
Gynecologic Practice endorses the joint document and
encourages its use by Fellows. There are not yet
sufficient data to recommend oocyte
cryopreservation for the sole purpose of
circumventing reproductive aging in healthy women.”
USES OF OOCYTE VITRIFICATION
22
© Fertility Centers of Illinois
Uses of oocyte vitrification
• Limited insemination
– Ethical indications
• Autologous banking
– Cancer
– Cytotoxic chemotherapy
– Conditions that cause POF
• Turner/Mosaic Turner syndrome
– Elective
• Donor egg banks
23
© Fertility Centers of Illinois
Limited insemination
• Feb 2004 Italian legislature passed
– Limitations on ART
– No more than 3 oocytes can be fertilized at one time
during an IVF cycle
– All resultant embryos must be transferred
– Supernumary oocytes could be cryopreserved but
supernumary embryos could not
– Pregnancy rates were low
– Triplet rates were high
– Advances in field of oocyte vitrification
24
© Fertility Centers of Illinois
EGG VS.
EMBRYO
Married – freeze embryos
Single – freeze eggs
25
© Fertility Centers of Illinois
Hirshfeld-Cytron et al 2011
Autologous oocyte banking: mosaic
Turner syndrome
•
•
•
•
26
Born with same size follicular pool
Follicles undergo rapid atresia
Ovarian failure in late teens/early 20s
Potential to undergo ovarian stimulation/oocyte
banking before onset of ovarian failure
– Would require PGD in future
– Careful cardiac screening
© Fertility Centers of Illinois
Autologous oocyte banking: other
indications
• Fragile X/Fragile X pre-mutation
– 15% chance of ovarian failure in 20’s and 30’s
• BRCA mutation
– Recommended oophorectomy by age 40
27
© Fertility Centers of Illinois
Autologous oocyte banking: delayed
motherhood
• “Social egg banking”
• Increasing area of interest and application of technology
• Many unanswered questions
– Who should freeze?
• balance between waiting too long and
unnecessary procedure
– What is the optimal age to freeze?
– How long are frozen eggs good for?
– How old is too old to use eggs?
28
© Fertility Centers of Illinois
Donor oocyte banks- DEBU
•
Excellent application of the available technology
# oocytes banked
14521
#oocytes survived
6518 (86%)
# Day 3 ET /# Embryos
# Day 5/6 ET /# Embryos
D3 ongoing Preg % / ET
29
463/1.9
649/1.5
151 (33%)
D5 ongoing Preg % / ET
336 (52%)
CLINICAL PREGNANCY/ET
51.80%
ONGOING/ET
43.79%
# of Cycles with Vit Blasts
551 (45%)
© Fertility Centers of Illinois
HOW MANY IS ENOUGH?
31
© Fertility Centers of Illinois
Fertile = Infertile Data?
Number of Eggs
Retrieved
32
© Fertility Centers of Illinois
How many frozen eggs does one
need?
• Sibling oocyte study age 30-39
– Infertile patients undergoing IVF
– 22 patients who had > 8 oocytes at retrieval
– Half of each cohort were vitrified and half
were used fresh
– Only embryos from vitrified oocytes were
transferred
Chang et al., Fertil Steril 2013
33
© Fertility Centers of Illinois
How many frozen eggs does one
need?
•
Outcomes compared between patients 30-36 and 37-39
n=12
N=29
Chang et al., Fertil Steril 2013
34
© Fertility Centers of Illinois
How many frozen eggs does one
need?
• Limitations
– History of infertility
– At least one prior failed IVF cycle
– Likely an over-estimation of numbers needed
for a patient without infertility
35
© Fertility Centers of Illinois
Success STILL age dependent
6 oocytes
age 25 =
40%
chance
live birth
6 oocytes
age 35 =
23%
chance
live birth
Cil AP, et al., Fertil Steril 2013
36
© Fertility Centers of Illinois
Egg Freezing Risk Calculator
•
37
http://www.fertilitypreservation.org/
© Fertility Centers of Illinois
Don’t Wait to Freeze Your Eggs…
38
© Fertility Centers of Illinois
Do women who freeze their eggs use
them?
39
© Fertility Centers of Illinois
40
© Fertility Centers of Illinois

51% anticipated future use

95% would do it again
 76% at a younger age

10% non-bankers had regret

45%would have banked if cheaper

No differences in relationship status, attempting
conception or not conceiving within 1 year
41
© Fertility Centers of Illinois
Summary
• Age related infertility is one of the biggest
challenges of modern medicine
• Oocyte pool is fixed and declines with age
• Ovarian reserve testing shows size of recruitable
follicle pool
• Oocytes can be cryopreserved with IVF success
rates similar to fresh IVF cycles
42
© Fertility Centers of Illinois
Conclusions
• Oocyte vitrification is a viable option for fertility
preservation
• Multiple cycles may be needed to have an
adequate group of available oocytes
• Oocyte banks will likely become as ubiquitous as
sperm banks
43
© Fertility Centers of Illinois
THANK YOU
44
© Fertility Centers of Illinois
LIFEFINDSAWAY.ORG
To promote health and alleviate the mental and physical distress of
individuals and couples diagnosed with infertility through education and
financial assistance
Sunday, June 27, 2015
45
© Fertility Centers of Illinois
Sunday, September 20, 2015