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