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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)
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Oocyte Donation; Factors Influencing The Outcome Mustafa BAHÇECİ,M.D Ulun ULUĞ, M.D. GermanHospitaland Bahceci WomenHealthCareCenter 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)
Cumulative Pregnancy rates following Oocyte donated Embryo transfers(Remohi et al, Fertil Steril 1997)
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 • 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 • 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
COH for Donors • Long GnRH-agonist (mostly preferred) • 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 • Invitromaturation of oocytescollectedfromunstimulatedovariesforoocytedonation Holzer et al, Fertil Steril 8.7 matureoocytesperpatient 18.2% implantation rate 50% clinicalpregnancy rate
Number of Oocytes Retrieved and pregnancy(Letterie et al, JARG 2005) * Not significant (ANOVA)
Estradiol Levels in donor and outcome (Pena et al, Hum Reprod, 2002) • Retrospective analysis of 330 consecutive fresh oocyte donation cycles All not-significant (ANOVA)
Estradiol (pg/ml) Level in Recipient and Outcome(Remohi et al, Hum Reprod 1997) All not-significant (ANOVA)
Endometrial Thickness and Pregnancy(Remohi et al, Hum Rep 1997) *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 P<0.05 Noyes et al, Fertil Steril, 2001
Recipient Age and Pregnancy(Soares et al, JCEM 2005) aNot significant b p=0.01 ANOVA
Recipient Age and Outcome (3)(Toner et al, Fertil Steril, 2002)Analysis of SART stats between ’96-’9817339 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 Recipienthave 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 AnalysisSoares et al, JCEM 2005(over 3000 ET cycles) * 7 weeks or more
Number of Embryos Transferred and Pregnancy(Mirkin et al, JARG 2003) * PR, non significant * p<0.05
Single Embryo transfer in Recipients(Soderstrom-Antilla et al, Hum Reprod, 2003)Retrospective analysis of 127 oocyte donation cycles • Almost 40% of all conceptions from oocyte donation were twin or high order pregnancies (ASRM/SART, Fertil Steril, 2004)
Indications for Oocyte donation and PregnancyGarcia-Velasco et al, Fertil Steril 2003(shared oocytes study) 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) 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 ETBudak et al, Fertil Steril 2007(over 7000 ET cycles) *Statistical comparisons were not performed
Effect of day of transfer on implantation and pregnancy outcome in oocyte donors(Schoolcraft and Gardner, Fertil Steril, 2000)
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