Transcript Slayt 1

Oocyte Donation; Factors
Influencing The Outcome
Mustafa BAHÇECİ,M.D
Ulun ULUĞ, M.D.
German Hospital and Bahceci Women Health
Care Center
Istanbul, Turkey
First pregnancy with donated oocyte (Lutjen et
al, 1984)
Oocyte donation was performed in almost 10%
of all ART cycles carried out in US (CDC report,
1999)
SART stats, 2005
Oocyte donated ET contributes 12.1 % of
all ART cycles (over 13.000 cycles)
60
52,2
50
40
35,3
30
20
Live Birth Rate
10
0
Non
donated
Fresh
ET
Donated
Fresh
ET
Cumulative Pregnancy rates following Oocyte
donated Embryo transfers
(Remohi et al, Fertil Steril 1997)
100
90
80
70
60
50
40
30
20
10
0
94,8
86,3
75,3
53,4
CPR (%)
1st
cycle
2nd
cycle
3rd
cycle
4th
cycle
Why oocyte donation programs are more
successful in terms of achieving pregnancy;
despite to advanced recipient age ?

Oocyte factor:
Younger oocytes
Capable for conception based on previous reproductive
history

Endometrial factor
The recipient's endometrial receptivity is dissociated from
folliculogenesis since it is artificially prepared to be more
uniform and similar to that of a natural menstrual cycle
Indications for oocyte donation program
1.
2.
3.
4.
5.
6.
7.
8.
Premature ovarian failure
Poor responder
Menopause (surgical, radiotherapy, chemotherapy)
Advanced maternal age
Recurrent implantation failure
Poor oocyte quality
Genetic
Combined
Factors that can be detrimental for the
outcome
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Donor Age and ovarian reserve
COH for donor
Number of oocytes retrieved
Serum E2 levels of both donor and recipient
Recipient Age
Endometrial Thickness
Indication for oocyte donation
Embryo transfer timing and status
Luteal phase support
…..
…..
Pregnancy follow up
Prenatal complications and dilemmas
Gestational diabetes (?)
Chronic Hypertension
Preeclampsia
Preterm delivery
Third trimester hemorrhage
Aortic dissection (Turner syndrome)
How to screen for aneuploides ?
Donor Selection
Normal physical and gynecological examination
Uneventful medical history
No family history of hereditary or chromosomal
diseases
Tested for STD
Normal ovarian reserve (BAF by USG)
Preferably uneventful (+) conception history ?
In a study of 257 ET oocyte donation cycles,
neither the age of donors, nor the ovarian
reserve or ovarian response variables were
significantly related to implantation and
pregnancy
(Mirkin et al, JARG, 2003)
Donor Age and Outcome
Yoon et al, ASRM, 2005
Retrospective analysis of 109 cycles
Mean donor age
Pregnancy (+)
Pregnancy (-)
p
30.2 ±3.6
32.1 ± 4.3
0.01
Donor age
<30
>34
p
Pregnancy rate (%)
50.0
18.2
0.01
COH for Donors
1. Long GnRH-agonist (mostly preferred)
2. Multiple dose GnRH-antagonist
Although late onset OHSS is not considered, early onset
OHSS could be associated
Multiple Antagonist
protocol
 Time saving
 Less injections
 Less OHSS
Similar outcome compared to long agonist
Prapas et al, Hum Reprod, 2005
Alternative preparation of donors; a patient
friendly approach
 In vitro maturation of oocytes collected from
unstimulated ovaries for oocyte donation
Holzer et al, Fertil Steril
8.7 mature oocytes per patient
18.2% implantation rate
50% clinical pregnancy rate
Number of Oocytes Retrieved and pregnancy
(Letterie et al, JARG 2005)
Number of oocytes
<5
6-10
11-15
16-20
21-25
>25
PR (%)*
67
50
44
56
49
61
Cryopreservation (%)
0
51
55
50
42
60
* Not significant (ANOVA)
Estradiol Levels in donor and outcome
(Pena et al, Hum Reprod, 2002)
• Retrospective analysis of 330 consecutive fresh oocyte donation cycles
E2 pg/ml
1499 <
1500-2999
>3000
Clinical pregnancy
rate per ET (%)
38.0
41.2
47.7
Ongoing/delivered
rate per ET (%)
33.8
34.6
44.0
All not-significant (ANOVA)
Estradiol (pg/ml) Level in Recipient and
Outcome
(Remohi et al, Hum Reprod 1997)
E2 pg/ml
<100
100-199
200-299
300-399
>400
PR (%)
46.2
50.8
55.3
39
47.2
IR (%)
12.2
19
21
14.7
16.7
All not-significant (ANOVA)
Endometrial Thickness and Pregnancy
(Remohi et al, Hum Rep 1997)
Thickness
<7mm
7-9.9mm
10-11.9mm
>12mm
PR (%)*
46.7
45.3
42.5
54.8
IR (%)
13.4
14
15.4
26.1
*All not significant(ANOVA)
Endometrial Thickness and Implantation (2)
Remohi et al
There was a weak but significant correlation between endometrial thickness
Endometrial Thickness and Pregnancy
70
68
60
50
50
53
49
40
30
20
PR (%)
20
10
0
<6
mm
6 mm 7 mm 8 mm
>9
mm
P<0.05
Noyes et al, Fertil Steril, 2001
Recipient Age and Pregnancy
(Soares et al, JCEM 2005)
Age (yrs)
<40
40-44
45-49
>49
PR (%)a
48.8
51
45.5
35.4
IR (%)
20.7
20.7
17.2
13.2b
a
Not significant
b p=0.01
ANOVA
Recipient Age and Outcome (2)
(Soares et al)
Age Groups (yrs)
<45
≥45
p
Implantation Rate
(%)
20.7
16.8
0.02
Pregnancy Rate
(%)
49.8
44.4
0.04
Miscarriage Rate
(%)
16.8
23.3
0.03
Recipient Age and Outcome (3)
(Toner et al, Fertil Steril, 2002)
Analysis of SART stats between ’96-’98
17339 cycles
1. Older recipient age was associated with statistically reduced implantation,
clinical pregnancy and delivery rates.
2. This effect appeared among recipients in their late 40s, and become more
pronounced at age ≥50 years
Does Ovarian function of Recipient
have any impact on the outcome ?
 The use of GnRH-a in women receiving oocyte donation
does not affect implantation rates (Remohi et al, 1994)
 No differences were found according to whether ovarian
function was present or absent in the recipient (Moomjy
et al, 2000)
Multivariate Analysis
Soares et al, JCEM 2005
(over 3000 ET cycles)
Dependent
variables
Independent Variables
PR
IR
Miscarriage
Age
0.79
0.58
0.24
Endometrial Thickness
0.65
0.96
0.24
Days of Estradiol therapy*
0.01
0.02
0.38
Serum Estradiol
0.80
0.53
0.12
Good quality Embryos
0.008
* 7 weeks or more
0.2
Number of Embryos Transferred and
Pregnancy
(Mirkin et al, JARG 2003)
50
45
40
35
30
*
25
PR (%)
Multiple (%)
20
15
10
5
0
2 ET
3 ET
PR, non significant
* p<0.05
4 ET
Almost 40% of all conceptions from oocyte donation were
twin or high order pregnancies
(ASRM/SART, Fertil Steril, 2004)
Single Embryo transfer in Recipients
(Soderstrom-Antilla et al, Hum Reprod, 2003)
Retrospective analysis of 127 oocyte donation cycles
No. of ETs
Age of recipient Clinical pregnancy
woman
rate (%)
Delivery
rate (%)
eSET
49
33.4 ± 5.3
40.8
32.6
DET
78
35.5 ± 4.4
41.0
32.1
Indications for Oocyte donation and
Pregnancy
Garcia-Velasco et al, Fertil Steril 2003
(shared oocytes study)
Pregnancy (+)*
(n=365)
Pregnancy (-)
(n=365)
POF (%)
44.5
44.3
Genetic (%)
1.5
1.9
RIF (%)
29.1
27.2
Poor responder (%)
17.6
19.7
RPR (%)
2.2
2.5
Others (%)
5.1
4.4
p: not significant
Oocyte donation provides similar success rates when applied to women with
a variety of reproductive disorders and recurrent miscarriages
Budak et al, Fertil Steril (in press)
Male Factor and Pregnancy
(Garcia-Velasco et al)
Pregnancy (+)
(n=365)
Pregnancy (-)
(n=365)
P
Normozoospermic (%)
35.1
38.6
NS
Asthenospermic (%)
32.9
26
NS
Oligozoospermic (%)
1.4
3.3
NS
Teratozoospermic (%)
0.5
0.6
NS
OAT (%)
6.8
4.4
NS
32
33
NS
Azoospermia
Non ejaculated (%)
(epid/test)
Totally 12 patients
Intra and Interdonor Variabilities
(Mirkin et al, JARG 2003)
 There was no impact of additional stimulations on the
donors’ ovarian responses
 CPR was not significantly different when comparing
results of consecutive cycles
 Donors who achieved a pregnancy were more consistent
in demonstrating success in subsequent cycles
Cleavage state vs blastocyst ET
Budak et al, Fertil Steril 2007
(over 7000 ET cycles)
IR (%)
PR (%)
Ongoing PR (%)
Day 2-3
34.8
50.5
45.9
Day 5-6
49.9
63.4
58.7
*Statistical comparisons were not performed
Effect of day of transfer on implantation and
pregnancy outcome in oocyte donors
(Schoolcraft and Gardner, Fertil Steril, 2000)
Day 3
Day 5
116
113
39.9 ± 0.43
41.3 ± 0.41
NS
Implantation rate
(fetal sac) (%)
47.1
65.8
<0.01
Clinical pregnancy
rate per retrieval (%)
75.0
87.6
<0.05
Multiples (%)
40.5
44,2
NS
No. of patients
Age
Does Recipient’s body habitus have adverse
impact on outcome ?
Body mass index and uterine receptivity in the oocyte donation model
(Wattankumtornkul et al, Fertil Steril 2003)
Patients were segregated to 4 groups according to BMI (<19, 20-24, 25-30, >30)
Pregnancy rates did not differ
between groups
The area under the curve, 0.51 (95% CI 0.41–0.62) suggests
no relationship between BMI and implantation
Conclusion
Prognostic factors can differ in oocyte
donation programs than homologues IVF
programs
Ovarian Response
IVF
Oocyte Donation
Age
important
not as much
Infertility etiology
important
not
COH protocol
important
not
Oocyte number
important
not
Estradiol levels
important
not
Duration of treatment
important
to some extent
Embryo quality
important
important