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IVF’te Doğal Siklus, Minimal Stimülasyon: Kime? Gerçek bir
alternatif mi?
Prof.Dr.Tayfun BAĞIŞ15/05/2013
TJOD
Terminology Aim Methodology
Natural cycle IVF Single oocyte No medicationNo luteal support
Modified NC IVF Single oocyte HCG only, antagonist, and/or FSH/HMG add back (up to 150 IU)Luteal support (HCG or P)
Mild IVF 2-7 oocytes Fixed low dose FSH/HMG (up to 150 IU), oral compounds and antagonist
Conventional IVF ≥8 oocytes Conventional FSH/HMG dose, agonist or antagonist
Current ovarian stimulation approaches Mild stimulation approaches
Time consuming and complex stimulation regimens
Less complexLess time consuming
High costs Cheaper (making IVF more accessible for a broader patient population)
Much patient discomfort Reduced chances for discomfort
Short-term complications—ovarian hysterstimulation syndrome (OHSS)
Reduced chances for complications
High drop-out rates Reduced chances for drop-out
Supraphysiological steroid levels with possible implications
Effects on oocyte qualityEffects on endometrial receptivity
Emphasize additional pregnancy chances from cryopreserved embryos
Reduced chances for cryopreserved embryos
Emphasize maximizing pregnancy rates per cycle Emphasize maximizing chances for healthy children born per started treatment at reasonable cost, patient discomfort and chances for complications
NATURAL CYCLE IVF AND
MNC IVF
• The per cycle costs of NC IVF is 20-23% of stimulated IVF.
4 cycles NC IVF
Cumulative PR 46 %LBR 32%
(Nargund et al., 2001)
501 cyclesIn cycles <40 years
NC IVF MS P
Cycles with oocytes 61.3 % 77.5 % 0.03PR/cycle 9.3 % 24.2 % 0.01PR/ET 18.4 % 36.7 % 0.01
No difference in women older than 40 years
POR N:136
390 cycles
CONTROL N:28
79 cycles
P
Cycles with oocytes 75 % 78 % NSCycles with ET 42 % 59 % 0.011(+) HCG/cycle 4.6 % 15.2 % 0.0005LBR/cycle 2.6 % 8.9 % 0.006(+) HCG/patient 12.5 % 35.7 % 0.003LBR/patient 7.4 % 25 % 0.005
MNC IVF
Nonrandomized studies in POR patients
Success rates 0-14%
Elizur et al., 2005; Castelo-Branco et al., 2004; Kolibianakis et al., 2004; Weghofer
et al., 2004; Hur et al., 2005
MNC IVF Pelinck 2006
Cycles started 844
Cycles canceled before HCG 3 %
OR planned 90.5 %
Planned OR canceled 9 %
OR performed 82.3%
OR successful 75.3%
Fertilization/OR 71.9%
Embryo transfer 37.6 %
OPR/cycle 8.3%
OPR/ET 22.1%
CLOMIPHENE CITRATEbased protocols
window
threshold
recruitment
menses
selection dominance
atresia
FSH
leve
lFo
llicl
e si
ze
Luteo-follicular transitison
CONCLUSIONS:Strength:• GnRH antagonist advantages• Reduced complexity, patient discomfort and risk• Reduced cost• Beneficial effect on oocyte/embryo quality
Weakness:• Lower PR/cycle• Excessive responses• Cost of medications is still high• Less margin for suboptimal laboratory performance• Fewer embryos for cryopreservation• Difficult programming of the cycle