IVFte GnRH Antagonist Protokolleri

IVFte GnRH Antagonistleri: Dikkat Edilmesi Gereken KonularProf. Dr. Tayfun BagisAcbadem University

Meta-analyses of GnRH Antagonistsvs GnRH Agonists: Pregnancy OutcomesThe 2 studies had different results for pregnancy outcomes*Live birth rate included ongoing pregnancies (Al-Inany) or calculated rates (Kolibianakis).OR = odds ratio.1. Al-Inany et al. Cochrane Database Syst Rev. 2006;3:CD001750.2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.Al-Inany1Kolibianakis2OR0.820.8695% CI0.69-0.980.72-1.02P value0.030.085Live Birth Rate* in Meta-analyses,GnRH Antagonists vs GnRH AgonistsDifferences in Study Design/Data Handling May Have Affected Results of Meta-analyses of GnRH Antagonists vs GnRH Agonists3,1763,865Total patientsLive birth rate* (All 22 studies included;in 12/22 studies, live births estimated)Ongoing pregnancy or live birth rate (Only 15 studies evaluable, n=2,973)Primary outcome2227No. of studies includedDec 2005Feb 2006Last date searchedKolibianakis2Al-Inany1CharacteristicNoYesIncluded nonpeer-reviewed data*Ongoing pregnancies were converted to live birth equivalents. Live births = 84% of number viable at week 7 or 92% of number viable at week 12 of gestation.1. Al-Inany et al. Cochrane Database Syst Rev. 2006;3:CD001750.2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.NoYesIncluded studies on IUIIUI = intrauterine insemination.Meta-analyses Confirm That GnRH Antagonists Have a Better Safety Profile vs GnRH AgonistsAl-Inany1Kolibianakis2Duration of analog treatment20.90 days(95% CI 22.20, 19.60)19.48 days(95% CI 21.05, 17.91)Duration of ovarian stimulation1.54 days(95% CI 2.42, 0.66; P=0.0006)1.13 days(95% CI 1.83, 0.44)Risk ofsevere OHSSOR 0.61(95% CI 0.42, 0.89; P=0.01)RR 0.46*(95% CI 0.26, 0.82; P=0.01)Interventionsto prevent OHSSOR 0.44(95% CI 0.21, 0.93; P=0.03)*For every 59 women treated with a GnRH agonist vs GnRH antagonist, 1 additional case of severe OHSS will occur.RR = risk ratio.1. Al-Inany et al. Cochrane Database Syst Rev. 2006;3:CD001750.2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.Kolibianakis2LH riseOR 8.27(95% CI 3.82-17.90)LH surgeOR 4.05(95% CI 1.53-10.72)2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.

Siklus ncesi problemlerEstrogen ProgesteronSenkronizasyon (oosit says)Fleksibilite (hafta sonu plan)OKS Does the efficacy of GnRH antagonists change with contraceptive pill pre-treatment?OCP pre-treatmentRate difference in ongoing pregnancy per woman: -5% (95% CI: -10 to -1), p = 0.02

1. Griesinger et al. Fertil Steril. 2008:90;1055-1063.2. Update Griesinger et al. submitted

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Siklus bandaki problemlerGn ne zaman balanmal (2-3)?Korpus luteum rescue (P4 ykseklii)D2 P4 lmProblems at the beginning of cycle.Cycle day 2 Transvaginal US + (if desired) hormonal profile

Ongoing PRNormal-P groupHigh-P groupPPer started cycle31.8 (124/390)5 (1/20)0.011Per oocyte retrieval33.8 (124/367)6.3 (1/16)0.026Per ET36.9 (124/336)6.3 (1/16)0.014Ongoing IR21.1 (151/714)3.6 (1/28)0.028Progesterone on HCG day1.1 (0.8)1.2 (1.3)NSKolibianakis 2004

AN=102MODAN=66PFemale age32.024.931.744.80.711Duration of infertility (years)4.33.13.93.30.444BMI (kg/m2)24.074.323.43.60.374Gravida0.641.030.370.80.077Cycle no1.630.901.921.290.102Antral follicle count13.66.414.65.30.381ACIBADEM EXPERIENCEANTN=20MODAN=20PTotal gonadotrophin dose1829.77341661.24820.116E2/HCG day1483.11319.91858.91452.50.140P/HCG day0.680.330.840.460.032Endometrium/HCG day10.92.0711.22.590.419No. Follicle >10mm/HCG11.055.812.645.270.091AMODAPP/HCG day 1.2% 6.8%16.40.108OR 1.409 CI %95 (0.728-2.726)34Antagonist balama problemleriSD 4? SD5? SD6? Fleksible?Siklus bandan itibaren?Modifiye protokoller?Antagonist dozu?

1- At least one follicle measuring >14 mm2- Estradiol levels >600 pg/ml3- LH levels >10 IU/l

Retrieved oocytes12.1MII %75.8Fertilization %58.7ET number1.9Cryo number2.4Ongoing IR %26.5Ongoing PR/Cycle39.7Ongoing PR/Retri39.7Ongoing PR/ET42.4

The Ganirelix dose-finding study group. Hum Reprod. 1998.The Ganirelix dose-finding study group. Hum Reprod. 1998.

E2 response (defined as posttreatment/pretreatment E2 ratio)Upper quartileMiddle quartileLower quartilePOocyte yield15.2 (7.5)13.1 (7.9)11.8 (5.6)1 ng/mL) European trial 1.5%North American trial1.5%European and Middle East trial0.4%GnRH agonist control group (pooled data)0.8%

Premature luteinizationp1.2 ng/ml No Premature luteinizationP1.5 ng/ml)

Luteal faz problemlerVaginal & IM Progesteron?GnRH agonist suplementasyonu?