Vitrification: "Robots" versus Human Comparing automated vitrification outcomes Zsolt Peter NAGY, M.D., Ph.D. HCLD Scientific Director Reproductive Biology Associates Atlanta, USA The 5th World congress of the INTERNATIONAL SOCIETY FOR FERTILITY PRESERVATION Vienna, Austria | November 16-18, 2017
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Vitrification: Robots versus Human Comparing …cme-utilities.com/mailshotcme/Material for Websites/ISFP...comparing fresh with vitrified oocytes. Donor and non-donor oocyte studies.
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Vitrification:
"Robots" versus Human
Comparing automated vitrification outcomes
Zsolt Peter NAGY, M.D., Ph.D. HCLD
Scientific Director
Reproductive Biology Associates
Atlanta, USA
The 5th World congress of the
INTERNATIONAL SOCIETY FOR FERTILITY PRESERVATION
Vienna, Austria | November 16-18, 2017
Disclosure
Direct stockholder: My Egg Bank/Prelude
Scientific Advisory Board: Cooper Surgical/Origio
Paid Consultant: EMD-Serono
Speakers bureau: MERCK MSD
Vitrification
of mouse
embryos
Vitrification
of mouse
oocytes
Vitrification
of bovine
blastocysts
1972 1973/1974 1985 1989 1993 1996 1997 1983 1999
Ultrarapid
Vitrification
with EM
grids
OPS
Ultrarapid
Vitrification
Cryoloop
Ultrarapid
Vitrification
Slow
freezing
of mouse
embryos
Slow
freezing of
domestic
animal
embryos
Slow
freezing of
human
embryos
Slow
freezing
of human
oocytes
Oocyte Freezing History
2002 2004 2013
Cryotop
Vitrification
Kuwayama
Egg Vitrif.
Studies for
Egg Banking
Fertility
Preservation
Egg Cryo
ASRM 2013
Egg cryo Not
experimental
2006
Start of Donor
Egg Banks
IVI – RBA/MEB
2015
Start of routine
FP Medical,
Social, - AFP
2009
1972 (Whittingham et al., Wilmut)
Oocyte cryopreservation
Number of Live Births 1986 to 2008
Adapted with permission. Noyes N, Porcu E Borini A. Reprod BioMed Online 2009.
http://www.rbmonline.com/Article/3971 [e-pub ahead of print on 8 April 2009].
RBA/MEB
3000+ IVI
9000+
2016
RoW
15000+
• Government restrictions / legislation
• Fertility preservation
• Medical
• Social
• Emergency cycle management
• Failure to obtain sperm
• Elective cycle management
• Ethical/Religious reasons
• Ovarian hyperstimulation syndrome (OHSS)
• Donor egg banking
Why to cryopreserve eggs?
Challenge: Efficiency
100-150 cryo eggs 1 pregnancy
(= 10-15 patients / trials)
1986-2006
(slow freezing)
Need for an efficient technique
Challenge: Solved today?
4-5 cryo eggs 1 pregnancy
After 2007
Need for an efficient technique
Handling and results with
“traditional” Vitrification
0%
20%
40%
60%
80%
100%
50% VS 75% VS 100% VS
0.1µl
0.5µl MDS
1µl
1.5µlP
roba
bilit
y of
vitr
ifica
tion
The use of minimum volume allows a reduction
in the CPA concentration.
0.2mm
1.6mm
1.1mm
0.6mm
0.05-0.1 µl
0.3-0.6 µl 1-1.5 µl
Arav, 1992
Probability of vitrification= cooling and warming rate x viscosity
volume
The effect of volume on the probability of
vitrification
Review of literature: meta-analysis of randomized controlled trials
Cobo and Diaz, FS 2011
Forest plots of clinical pregnancy rate per warmed oocyte for studies comparing fresh with vitrified oocytes. Donor and non-donor oocyte studies.
Potdar et al., RBMonline, 2014
zona pellucida
hardening
membrane
permeability
Cytoplasmic and
Cytoskeleton damage
Meiotic spindle
depolymerization
Impact on oocyte
physiology
Polar body
degeneration/fusion
Safety Issues / Experimental Data
Oocyte vitrification and embryonic
aneuploidy
Forty-four patients with a mean age of 29.9 ± 2.3, 588 eggs Forman et al.
FS 2012
Safety Issues / Experimental Data
Effects of slow freezing (DNA repair, cell cycle and chromosomal
stability) are more deleterious for biological functions than those
observed for vitrification (ubiquitination).
Monzo et.al. Hum Reprod 2011
Oocyte vitrification does not disturb embryonic metabolomic
profiles.
Dominguez, Fertil Steril 2013 0,01
0,012
0,014
0,016
0,018
0,02
0,022
0,024
0,026
0 10 20 30 40 50 60 70
Re
lati
ve
In
ten
sit
y (
a.u
.)
Oocyte
L-Tyrosine
Slow freezing has a dramatic effect on cell physiology whereas
vitrification appears to have limited effect.
Gardner et.al. Theriogenology 2007
Slide courtesy of Dr. Cobo
Efficiency: Results
Efficiency: Results
Donor Egg Banking
RBA experience on oocyte freezing
Cryo Egg Fresh Egg
Recipients 20 10
M2 Egg/Pat 7.7 31.7
Es for ET (x) 47 (2.4) 19 (2.1)
Es for Cryo (x) 31 (1.5) 141 (16)
PR (IR) 75% (54%) 56% (47%)
Cumulative PR 85% 78%
Recipients Pregnant 17 7 Nagy et al, 2009
Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking. Nagy ZP, Chang CC, Shapiro DB, Bernal
RBA experience on oocyte freezing Clinical evaluation of the efficiency of an oocyte donation program using egg cryo-banking. Nagy ZP, Chang CC, Shapiro DB, Bernal
RBA experience: IVF patients 30–39 years Prospective controlled study to evaluate laboratory and clinical outcomes of oocyte vitrification obtained in in vitro fertilization patients aged 30 to 39 years.
Chang CC, Elliott TA, Wright G, Shapiro DB, Toledo AA, Nagy ZP. FS 2013
NEED 12 EGGS NEED 30 EGGS
Safety
Oocyte cryopreservation
Live Birth Data from Egg Cryo from RBA Including deliveries until the end of 2011