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CLINICA VALLE GIULIA, Rome
The outcome of oocyte freezing as
compared with embryo freezing
Filippo Maria Ubaldi
M.D. M.Sc.
3° Congress of Society of Reproductive Medicine
Antalya 5-9 October 2011
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Oocyte cryopreservation
“Need” or “no need”?
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Oocyte cryopreservation
“No need”
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Oocyte cryopreservation
No need?
Medical reason
Malignant diseases
Surgical ovary removal
Polycystic ovary
Hyperstimulation syndrome
Premature menopause etc.
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Oocyte cryopreservation
No need?
Logistic reasons
Sperm collection problem
Legal reasons
Restrictions in embryo cryopreservation
Fate of embryos of separated couples
Social reasons
Wish to delay motherhood
Moral reasons
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Oocyte cryopreservation
No need?
Oocyte donation
Oocyte banks may result in
- widespread availability
- shortened, eliminated waiting list
- safety (quarantine)
- choice
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Oocyte cryopreservation
In Italy
from march 2004 to may 2009 (Law 40/2004)
we could only cryopreserve oocytes
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Lab outcomes: vitrification, infertile population
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Laboratory outcomes
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Cumulative ongoing pregnancy rates: vitrification
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Study design
o The study was design as a prospective longitudinal
cohort study.
o The baseline characteristics, embryological data,
clinical and ongoing pregnancy rate were analyzed
on a per cycle basis.
o The cumulative pregnancy rate obtained with fresh
and vitrified oocytes from the same stimulation cycle was analyzed on a per patient basis.
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Material & methods
o All consecutives patients undergoing ICSI treatment
in the Centre for Reproductive Medicine GENERA
between September 2nd 2008 and May 15th 2009
were considered for this study
o Only patients with supernumerary oocytes available
for cryopreservation were included. A single fresh
attempt was included for each patient
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Clinical results
69/120 = 57,5% ongoing pregnancy rate
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Embryo freezing: cumulative pregnancy rates
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Embryo freezing: cumulative pregnancy rates
36%
Ubaldi et al., 2004
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Cumulative pregnancy rate: <38 y. (Ubaldi, 2004)
Fresh ET
Fresh+frozen
All patients (with frozen embryos)
232
232
Clinical preg. after fresh ET
113
113
Clinical preg. after 1°thawed ET
-
33
Clinical preg. after 2°thawed ET
-
10
113
156
Total clinical pregnancies
Cumulative clinical preg.rate/patient (%)
113/232 (48,7)
156/232 (67,2)
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Oocyte vitrification: cumultive ongoing pregnancy rates
69/120 = 57,5% ongoing pregnancy rate
VS
<38 y: frozen embryos 156/232 = 67,2% clinical pregnancy rate
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Oocyte cryopreservation
In Italy
from may 2009 (Supreme Court 151/2009)
we can also cryopreserve embryos
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Study design
•
•
•
Retrospective observational study
All consecutives patients undergoing fresh ICSI treatment
where oocyte cryopreservation was performed (first period
under the Law limitation: September 2008 – May 2009) and all
consecutives patients undergoing fresh ICSI treatment where
embryo cryopreservation was performed (second period
without Law limitation: September 2009 – May 2010)
Primary outcome: cumulative ongoing pregnancy rate obtained
with fresh + vitrified oocytes (first period) or with fresh +
vitrified embryos (second period). Warming cycles were
included until December 2009 and December 2010, respectively
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Cryopreservation method
• Vitrification protocol : Kuwayama method (2005,2007)
• Cryoprotectants: 15% DMSO 15% EG
• Tool: Cryotop (open system)
Rienzi et al., Hum Reprod 2010
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Baseline patient’s characteristics
Oocyte Group Embryo Group
p
182
156
182/428 (42.5)
156/532 (29.3)
P<0.0001
35.81±4.19
36,10±3,67
ns
6.5±2.2
6.75±2.6
ns
Agonist protocol (%)
143/182 (78.6)
108/156 (69.2)
ns
Antagonist protocol (%)
39/182 (21.4)
48/156 (28.8)
ns
No. patients
% of the stimulated patients
Mean age (mean+SD)
Mean basal FSH (mean+SD)
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Fresh and warming cycles laboratory outcomes
Oocyte Group
Embryo Group
p
Inseminated MII (mean±SD)
2.9±0.4
6.2±2.0
P<0.000
2 PN (mean±SD)
2.6±0.6
5.1±1.8
P<0.000
Top quality embryos (mean±SD)
1.5±0.96
2.2±1.6
P<0.000
Embryo transferred (mean±SD)
2.5±0.6
2.2±0.8
P<0.002
Oocyte/embryo vitrified (mean±SD)
6.2±3.1
2.3±1.6
P<0.000
Oocyte/embryo warmed (mean±SD)
4.2±1.2
2.1±0.8
P<0.000
Oocyte/embryo survived (mean±SD)
3.8±0.9
2.0±0.7
P<0.000
Inseminated MII (mean±SD)
2.9±0.2
-
2 PN (mean±SD)
2.5±0.6
-
Top quality embryos (mean±SD)
1.5±0.9
-
Embryo transfer (mean±SD)
2.4±0.8
2.0±0.7
Fresh cycle: laboratory outcome
Warmed cycles: laboratory outcomes
P=0.03
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Fresh cycles: overall results
Oocyte Group
Embryo Group
182
156
35.81±4.19
172
36,10±3,67
144
ns
ET %
172/182 (94,5)
144/156 (92,3)
ns
Clinical pregnancy rate per cycle
77/182 (42,3)
78/156 (50,0)
ns
Clinical pregnancy rate per ET
77/172 (44,8)
78/144 (54,2)
ns
Implantation rate %
101/435 (23,2)
111/342(32,4)
P<0,004
9/77 (11,7)
9/78 (11,5)
ns
68
69
Ongoing pregnancy rate per fresh cycle %
68/182 (37,4)
69/156 (44,2)
ns
Ongoing implantation rate
90/435 (20,7)
101/342 (29,5)
P<0,005
No. of cycles
Mean age (M±SD)
No. of ET
Abortion rate %
N ongoing pregnancy fresh
p
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Warmed cycles: overall results
Oocyte Group Embryo Group
p
No. of cycles
115
78
No. of ET
111
77
ET %
111/115 (96,5)
77/78 (98,7)
ns
Clinical pregnancy rate per cycle
35/115 (30,4)
21/78 (26,9)
ns
Clinical pregnancy rate per ET
35/111 (31,5)
21/77 (27,2)
ns
Implantation rate %
43/266 (16,1)
22/156 (14,1)
ns
6/35 (17,1)
5/21 (23,8)
ns
29
16
Ongoing pregnancy rate per vitrified cycle %
29/115 (25,2)
16/78 (20,5)
ns
Ongoing implantation rate
35/266 (13,2)
16/156 (10,2)
ns
Abortion rate %
N ongoing pregnancy vitrified
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Cumulative ongoing pregnancy
rate after the fresh cycle, first
warming cycle and second
warming cycle.
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Cumulative ongoing pregnancy rate after the
fresh cycle, first and second warming cycle
Overall
Oocyte
Embryo
p
Fresh
68/182 (37.4)
69/156 (44.2)
ns
I warming cycle
84/182 (51.6)
85/156 (54.5)
ns
II warming cycle
97/182 (53.3)
85/156 (54.5)
ns
N° of cycles per patient
1.63
1.50
509 oocytes and 178 embryos still available in the pregnant patient groups
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Cumulative ongoing pregnancy rate after the fresh cycle,
first and second warming cycle according to female age
≤34 yrs
Oocyte
Embryo
35-37 yrs
Oocyte
Embryo
38-40 yrs
Oocyte
Embryo
41-43 yrs
Oocyte
Embryo
Fresh cycle 29/72 (40.3) 29/57 (50.9) 20/48(41.7) 25/44 (56.8) 15/41(36.6) 13/43 (30.2) 4/21 (19.0) 2/12 (16.7)
I warming
45/72 (62.5) 34/57 (59.6) 23/48 (47.9) 29/44 (65.9) 20/41(48.8) 18/43 (41.9) 6/21 (28.6) 4/12 (33.3)
cycle
II warming
45/72 (62.5) 34/57 (59.6) 24/48 (50.0) 29/44 (65.9) 21/41 (51.2) 18/43 (41.9) 7/21 (33.3) 4/12 (33.3)
cycle
p = ns in any analyzed group
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Cumulative ongoing implantation rate after
fresh and warming cycle
Overall
Oocyte
Embryo
p
Fresh
90/435 (20.7)
101/342 (29.5)
p = 0.005
Warming cycles
35/266 (13.1)
16/156 (10.2)
ns
Fresh+ warming
(cumulative)
128/701 (17.8)
117/498 (23.5)
p = 0.03
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Conclusion
In this study we have compared two different policies applied on
the general infertile population:
- limited number of inseminated oocytes and oocyte cryopreservation
- higher number of inseminated oocytes and embryo cryopreservation
Same vitrification approach was used in both groups.
According to our results when embryo selection is possible a
significantly higher ongoing implantation rate can be achieved
in the fresh cycle.
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Conclusion
•
The cumulative ongoing pregnancy rate is similar in both
groups when including the warming cycles. The cumulative
ongoing implantation rate is higher in the frozen embryo
group
•
Slightly more transfers are necessary in the oocyte group as
compared to the embryo group to reach the same results
•
With oocyte cryopreservation no supernumerary embryos are
created (only oocytes with no related ethical and moral issues)
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Conclusion
•
Although the limits of the study design, with oocyte
cryopreservation it is possible to achieve good
cumulative clinical results in a standard infertility
population
•
A prospective randomized trial is needed to assess the
efficacy of oocyte vs embryo cryopreservation
CLINICA VALLE GIULIA, Roma
SALUS, Marostica (VI)
GENERA, Umbertide (PG)
Ginecologia:
Embriologia:
Filippo Ubaldi
Laura Rienzi
Stefania Romano
Roberta Maggiulli
Laura Albricci
Antonio Capalbo
Nicoletta Barnocchi
Benedetta Iussig
Sara Fusco
Federica Sanges
Catello Scarica
Elena Ievoli
Elena Baroni
Antonio Ciconte
Silvia Colamaria
Fabrizio Fiorini
A. Giallonardo
Madda Giuliani
Fabio Sapienza
Mauro Schimberni
Silvia Venanzi
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