Doç. Dr. Ulun Uluğ & Mustafa Bahçeci

1. Oocyte Donation; FactorsOocyte Donation; Factors
Influencing The OutcomeInfluencing The Outcome
Mustafa BAHÇECİ,M.DMustafa BAHÇECİ,M.D
Ulun ULUĞ, M.D.Ulun ULUĞ, M.D.
German Hospital and Bahceci Women HealthGerman Hospital and Bahceci Women Health
Care CenterCare Center
Istanbul, TurkeyIstanbul, Turkey

2.  First pregnancy with donated oocyte (Lutjen etFirst pregnancy with donated oocyte (Lutjen et
al, 1984)al, 1984)
 Oocyte donation was performed in almost 10%Oocyte donation was performed in almost 10%
of all ART cycles carried out in US (CDC report,of all ART cycles carried out in US (CDC report,
1999)1999)

3. SART stats, 2005SART stats, 2005
 Oocyte donated ET contributes 12.1 % ofOocyte donated ET contributes 12.1 % of
all ART cycles (over 13.000 cycles)all ART cycles (over 13.000 cycles)
35,3
52,2
0
10
20
30
40
50
60
Non
donated
Fresh
ET
Donated
Fresh
ET
Live Birth Rate

4. Cumulative Pregnancy rates following OocyteCumulative Pregnancy rates following Oocyte
donated Embryo transfersdonated Embryo transfers
(Remohi et al, Fertil Steril 1997)(Remohi et al, Fertil Steril 1997)
53,4
75,3
86,3
94,8
0
10
20
30
40
50
60
70
80
90
100
1st
cycle
2nd
cycle
3rd
cycle
4th
cycle
CPR (%)

5. Why oocyte donation programs are moreWhy oocyte donation programs are more
successful in terms of achieving pregnancy;successful in terms of achieving pregnancy;
despite to advanced recipient age ?despite to advanced recipient age ?

Oocyte factor:Oocyte factor:
Younger oocytesYounger oocytes
Capable for conception based on previous reproductiveCapable for conception based on previous reproductive
historyhistory

Endometrial factorEndometrial factor
The recipient's endometrial receptivity is dissociated fromThe recipient's endometrial receptivity is dissociated from
folliculogenesis since it is artificially prepared to be morefolliculogenesis since it is artificially prepared to be more
uniform and similar to that of a natural menstrual cycleuniform and similar to that of a natural menstrual cycle

6. Indications for oocyte donation programIndications for oocyte donation program
1.1. Premature ovarian failurePremature ovarian failure
2.2. Poor responderPoor responder
3.3. Menopause (surgical, radiotherapy, chemotherapy)Menopause (surgical, radiotherapy, chemotherapy)
4.4. Advanced maternal ageAdvanced maternal age
5.5. Recurrent implantation failureRecurrent implantation failure
6.6. Poor oocyte qualityPoor oocyte quality
7.7. GeneticGenetic
8.8. CombinedCombined

7. Factors that can be detrimental for theFactors that can be detrimental for the
outcomeoutcome

Donor Age and ovarian reserveDonor Age and ovarian reserve

COH for donorCOH for donor

Number of oocytes retrievedNumber of oocytes retrieved
 Serum ESerum E22 levels of both donor and recipientlevels of both donor and recipient

Recipient AgeRecipient Age

Endometrial ThicknessEndometrial Thickness

Indication for oocyte donationIndication for oocyte donation

Embryo transfer timing and statusEmbryo transfer timing and status

Luteal phase supportLuteal phase support

……....

……....

Pregnancy follow upPregnancy follow up

8. Prenatal complications and dilemmasPrenatal complications and dilemmas
 Gestational diabetes (?)Gestational diabetes (?)
 Chronic HypertensionChronic Hypertension
 PreeclampsiaPreeclampsia
 Preterm deliveryPreterm delivery
 Third trimester hemorrhageThird trimester hemorrhage
 Aortic dissection (Turner syndrome)Aortic dissection (Turner syndrome)
 How to screen for aneuploides ?How to screen for aneuploides ?

9. Donor SelectionDonor Selection
Normal physical and gynecological examinationNormal physical and gynecological examination
Uneventful medical historyUneventful medical history
No family history of hereditary or chromosomalNo family history of hereditary or chromosomal
diseasesdiseases
Tested for STDTested for STD
Normal ovarian reserve (BAF by USG)Normal ovarian reserve (BAF by USG)
Preferably uneventful (+) conception history ?Preferably uneventful (+) conception history ?

10.  In a study of 257 ET oocyte donation cycles,In a study of 257 ET oocyte donation cycles,
neither the age of donors, nor the ovarianneither the age of donors, nor the ovarian
reserve or ovarian response variables werereserve or ovarian response variables were
significantly related to implantation andsignificantly related to implantation and
pregnancypregnancy
(Mirkin et al, JARG, 2003)(Mirkin et al, JARG, 2003)

11. Donor Age and OutcomeDonor Age and Outcome
Yoon et al, ASRM, 2005Yoon et al, ASRM, 2005
Retrospective analysis of 109 cyclesRetrospective analysis of 109 cycles
Pregnancy (+)Pregnancy (+) Pregnancy (-)Pregnancy (-) pp
Mean donor ageMean donor age 30.230.2 ±±3.63.6 32.132.1 ±± 4.34.3 0.010.01
Donor ageDonor age <30<30 >34>34 pp
Pregnancy rate (%)Pregnancy rate (%) 50.050.0 18.218.2 0.010.01

12. COH for DonorsCOH for Donors
1.1. Long GnRH-agonist (mostly preferred)Long GnRH-agonist (mostly preferred)
2.2. Multiple dose GnRH-antagonistMultiple dose GnRH-antagonist
Although late onset OHSS is not considered, early onset
OHSS could be associated

13. Multiple AntagonistMultiple Antagonist
protocolprotocol
 Time savingTime saving
 Less injectionsLess injections
 Less OHSSLess OHSS
Similar outcome compared to long agonist
Prapas et al, Hum Reprod, 2005

14. Alternative preparation of donors; a patientAlternative preparation of donors; a patient
friendly approachfriendly approach
 In vitro maturation of oocytes collected fromIn vitro maturation of oocytes collected from
unstimulated ovaries for oocyte donationunstimulated ovaries for oocyte donation
Holzer et al, Fertil SterilHolzer et al, Fertil Steril
8.7 mature oocytes per patient8.7 mature oocytes per patient
18.2% implantation rate18.2% implantation rate
50% clinical pregnancy rate50% clinical pregnancy rate

15. Number of Oocytes Retrieved and pregnancyNumber of Oocytes Retrieved and pregnancy
(Letterie et al, JARG 2005)(Letterie et al, JARG 2005)
Number of oocytesNumber of oocytes <5<5 6-106-10 11-1511-15 16-2016-20 21-2521-25 >25>25
PR (%)*PR (%)* 6767 5050 4444 5656 4949 6161
Cryopreservation (%)Cryopreservation (%) 00 5151 5555 5050 4242 6060
* Not significant (ANOVA)

16. Estradiol Levels in donor and outcomeEstradiol Levels in donor and outcome
(Pena et al, Hum Reprod, 2002)(Pena et al, Hum Reprod, 2002)
EE22 pg/mlpg/ml 1499 <1499 < 1500-29991500-2999 >3000>3000
Clinical pregnancyClinical pregnancy
rate per ET (%)rate per ET (%)
38.038.0 41.241.2 47.747.7
Ongoing/deliveredOngoing/delivered
rate per ET (%)rate per ET (%)
33.833.8 34.634.6 44.044.0
• Retrospective analysis of 330 consecutive fresh oocyte donation cycles
All not-significant (ANOVA)

17. Estradiol (pg/ml) Level in Recipient andEstradiol (pg/ml) Level in Recipient and
OutcomeOutcome
(Remohi et al, Hum Reprod 1997)(Remohi et al, Hum Reprod 1997)
EE22 pg/mlpg/ml <100<100 100-199100-199 200-299200-299 300-399300-399 >400>400
PR (%)PR (%) 46.246.2 50.850.8 55.355.3 3939 47.247.2
IR (%)IR (%) 12.212.2 1919 2121 14.714.7 16.716.7
All not-significant (ANOVA)

18. Endometrial Thickness and PregnancyEndometrial Thickness and Pregnancy
(Remohi et al, Hum Rep 1997)(Remohi et al, Hum Rep 1997)
ThicknessThickness <7mm<7mm 7-9.9mm7-9.9mm 10-11.9mm10-11.9mm >12mm>12mm
PR (%)PR (%)** 46.746.7 45.345.3 42.542.5 54.854.8
IR (%)IR (%) 13.413.4 1414 15.415.4 26.126.1
**All not significant(ANOVA)

19. Endometrial Thickness and Implantation (2)Endometrial Thickness and Implantation (2)
Remohi et alRemohi et al
There was a weak but significant correlation between endometrial thickness

20. Endometrial Thickness and PregnancyEndometrial Thickness and Pregnancy
20
50
53
49
68
0
10
20
30
40
50
60
70
<6
mm
6 mm 7 mm 8 mm >9
mm
PR (%)
Noyes et al, Fertil Steril, 2001
P<0.05

21. Recipient Age and PregnancyRecipient Age and Pregnancy
(Soares et al, JCEM 2005)(Soares et al, JCEM 2005)
Age (yrs)Age (yrs) <40<40 40-4440-44 45-4945-49 >49>49
PR (%)PR (%)aa
48.848.8 5151 45.545.5 35.435.4
IR (%)IR (%) 20.720.7 20.720.7 17.217.2 13.213.2bb
aa
Not significantNot significant
bb
p=0.01p=0.01
ANOVAANOVA

22. Recipient Age and Outcome (2)Recipient Age and Outcome (2)
(Soares et al)(Soares et al)
Age Groups (yrs)Age Groups (yrs)
<45<45 ≥≥4545 pp
Implantation RateImplantation Rate
(%)(%)
20.720.7 16.816.8 0.020.02
Pregnancy RatePregnancy Rate
(%)(%)
49.849.8 44.444.4 0.040.04
Miscarriage RateMiscarriage Rate
(%)(%)
16.816.8 23.323.3 0.030.03

23. Recipient Age and Outcome (3)Recipient Age and Outcome (3)
(Toner et al, Fertil Steril, 2002)(Toner et al, Fertil Steril, 2002)
Analysis of SART stats between ’96-’98Analysis of SART stats between ’96-’98
17339 cycles17339 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

24. Does Ovarian function of RecipientDoes Ovarian function of Recipient
have any impact on the outcome ?have any impact on the outcome ?
 The use of GnRH-a in women receiving oocyte donationThe use of GnRH-a in women receiving oocyte donation
does not affect implantation rates (Remohi et al, 1994)does not affect implantation rates (Remohi et al, 1994)
 No differences were found according to whether ovarianNo differences were found according to whether ovarian
function was present or absent in the recipient (Moomjyfunction was present or absent in the recipient (Moomjy
et al, 2000)et al, 2000)

25. Multivariate AnalysisMultivariate Analysis
Soares et al, JCEM 2005Soares et al, JCEM 2005
(over 3000 ET cycles)(over 3000 ET cycles)
DependentDependent
variablesvariables
Independent VariablesIndependent Variables PRPR IRIR MiscarriageMiscarriage
AgeAge 0.790.79 0.580.58 0.240.24
Endometrial ThicknessEndometrial Thickness 0.650.65 0.960.96 0.240.24
Days of Estradiol therapyDays of Estradiol therapy** 0.010.01 0.020.02 0.380.38
Serum EstradiolSerum Estradiol 0.800.80 0.530.53 0.120.12
Good quality EmbryosGood quality Embryos 0.0080.008 0.20.2
* 7 weeks or more

26. Number of Embryos Transferred andNumber of Embryos Transferred and
PregnancyPregnancy
(Mirkin et al, JARG 2003)(Mirkin et al, JARG 2003)
0
5
10
15
20
25
30
35
40
45
50
2 ET 3 ET 4 ET
PR (%)
Multiple (%)
*
PR, non significant
* p<0.05

27. Single Embryo transfer in RecipientsSingle Embryo transfer in Recipients
(Soderstrom-Antilla et al, Hum Reprod, 2003)(Soderstrom-Antilla et al, Hum Reprod, 2003)
Retrospective analysis of 127 oocyte donation cyclesRetrospective analysis of 127 oocyte donation cycles
No. of ETsNo. of ETs Age of recipientAge of recipient
womanwoman
Clinical pregnancyClinical pregnancy
rate (%)rate (%)
DeliveryDelivery
rate (%)rate (%)
eSETeSET 4949 33.4 ± 5.333.4 ± 5.3 40.840.8 32.632.6
DETDET 7878 35.5 ± 4.435.5 ± 4.4 41.041.0 32.132.1
Almost 40% of all conceptions from oocyte donation were
twin or high order pregnancies
(ASRM/SART, Fertil Steril, 2004)

28. Indications for Oocyte donation andIndications for Oocyte donation and
PregnancyPregnancy
Garcia-Velasco et al, Fertil Steril 2003Garcia-Velasco et al, Fertil Steril 2003
(shared oocytes study)(shared oocytes study)
Pregnancy (+)Pregnancy (+)**
(n=365)(n=365)
Pregnancy (-)Pregnancy (-)
(n=365)(n=365)
POF (%)POF (%) 44.544.5 44.344.3
Genetic (%)Genetic (%) 1.51.5 1.91.9
RIF (%)RIF (%) 29.129.1 27.227.2
Poor responder (%)Poor responder (%) 17.617.6 19.719.7
RPR (%)RPR (%) 2.22.2 2.52.5
Others (%)Others (%) 5.15.1 4.44.4
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)

29. Male Factor and PregnancyMale Factor and Pregnancy
(Garcia-Velasco et al)(Garcia-Velasco et al)
Pregnancy (+)Pregnancy (+)
(n=365)(n=365)
Pregnancy (-)Pregnancy (-)
(n=365)(n=365)
PP
Normozoospermic (%)Normozoospermic (%) 35.135.1 38.638.6 NSNS
Asthenospermic (%)Asthenospermic (%) 32.932.9 2626 NSNS
Oligozoospermic (%)Oligozoospermic (%) 1.41.4 3.33.3 NSNS
Teratozoospermic (%)Teratozoospermic (%) 0.50.5 0.60.6 NSNS
OAT (%)OAT (%) 6.86.8 4.44.4 NSNS
AzoospermiaAzoospermia
Non ejaculated (%)Non ejaculated (%)
(epid/test)(epid/test)
3232 3333 NSNS
Totally 12 patients

30. Intra and Interdonor VariabilitiesIntra and Interdonor Variabilities
(Mirkin et al, JARG 2003)(Mirkin et al, JARG 2003)
 There was no impact of additional stimulations on theThere was no impact of additional stimulations on the
donors’ ovarian responsesdonors’ ovarian responses
 CPR was not significantly different when comparingCPR was not significantly different when comparing
results of consecutive cyclesresults of consecutive cycles
 Donors who achieved a pregnancy were more consistentDonors who achieved a pregnancy were more consistent
in demonstrating success in subsequent cyclesin demonstrating success in subsequent cycles

31. Cleavage state vs blastocyst ETCleavage state vs blastocyst ET
Budak et al, Fertil Steril 2007Budak et al, Fertil Steril 2007
(over 7000 ET cycles)(over 7000 ET cycles)
IR (%)IR (%) PR (%)PR (%) Ongoing PR (%)Ongoing PR (%)
Day 2-3Day 2-3 34.834.8 50.550.5 45.945.9
Day 5-6Day 5-6 49.949.9 63.463.4 58.758.7
*Statistical comparisons were not performed

32. Effect of day of transfer on implantation andEffect of day of transfer on implantation and
pregnancy outcome in oocyte donorspregnancy outcome in oocyte donors
(Schoolcraft and Gardner, Fertil Steril, 2000)(Schoolcraft and Gardner, Fertil Steril, 2000)
Day 3Day 3 Day 5Day 5
No. of patientsNo. of patients 116116 113113
AgeAge 39.9 ± 0.4339.9 ± 0.43 41.3 ± 0.4141.3 ± 0.41 NSNS
Implantation rateImplantation rate
(fetal sac) (%)(fetal sac) (%)
47.147.1 65.865.8 <0.01<0.01
Clinical pregnancyClinical pregnancy
rate per retrieval (%)rate per retrieval (%)
75.075.0 87.687.6 <0.05<0.05
Multiples (%)Multiples (%) 40.540.5 44,244,2 NSNS

33. Does Recipient’s body habitus have adverseDoes Recipient’s body habitus have adverse
impact on outcome ?impact on outcome ?
Body mass index and uterine receptivity in the oocyte donation modelBody mass index and uterine receptivity in the oocyte donation model
(Wattankumtornkul et al, Fertil Steril 2003)(Wattankumtornkul et al, Fertil Steril 2003)
Patients were segregated to 4 groups according to BMI (<19, 20-24, 25-30, >30)Patients were segregated to 4 groups according to BMI (<19, 20-24, 25-30, >30)
The area under the curve, 0.51 (95% CI 0.41–0.62) suggests
no relationship between BMI and implantation
Pregnancy rates did not differ
between groups

34. ConclusionConclusion
 Prognostic factors can differ in oocytePrognostic factors can differ in oocyte
donation programs than homologues IVFdonation programs than homologues IVF
programsprograms

35. IVFIVF Oocyte DonationOocyte Donation
AgeAge importantimportant not as muchnot as much
Infertility etiologyInfertility etiology importantimportant notnot
COH protocolCOH protocol importantimportant notnot
Oocyte numberOocyte number importantimportant notnot
Estradiol levelsEstradiol levels importantimportant notnot
Duration of treatmentDuration of treatment importantimportant to some extentto some extent
Embryo qualityEmbryo quality importantimportant importantimportant
OvarianResponse