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The freeze-all strategy in IVF: who benefits?
Primary Objective: To test the hypothesis that in women undergoing IVF/ICSI a freeze-all strategy results in higher ongoing pregnancy rates compared to IVF/ICSI with fresh embryo transfer.
Multicentre, marker RCT with a cost-effectiveness analysis.
Subfertile women between 18 and 43 years of age undergoing IVF/ICSI.
Postpone the first embryo transfer to the next menstrual cycle. Therefore we freeze all embryos at day 3 or 4 and transfer them in unstimulated cycles. In both study arms markers for endometrium receptivity will be collected for marker analysis.
The study will be a marker based superiority study with a sample size calculated by 1000 simulations. We assume an ongoing pregnancy rate of 14% following a fresh embryo transfer in women with high progesterone levels, an ongoing pregnancy rate of 30% following the fresh embryo transfer in women with low progesterone levels, and 30% ongoing pregnancy rate following frozen-thawed embryo transfer in high or low progesterone. The estimated distribution of progesterone used for the sample size calculation was a normal distribution with a mean of 2.5 mmol/L and a standard deviation of 1.1 mmol/L. We set the alpha for the overall treatment success (hypothesis 1) at an alpha of 3%; the interaction of treatment success with progesterone (hypothesis 2) at an alpha of 2%. With this we keep the alpha level constant at 5%. Under these assumptions a sample size of 855 women is needed to keep the power for either of the hypotheses to be significant at 80%. Since we anticipate a 5% lost to follow up, 900 women need to be randomized
The economic evaluation will be designed from a healthcare and from a societal perspective. The economic evaluation will be designed as a cost-effectiveness analysis. The time horizon will be from randomisation until positive pregnancy test leading to the ongoing pregnancy. If no ongoing pregnancy occurs, costs from randomisation until the last thawed embryo transfer of that cycle is conducted will be calculated. Cost-effectiveness of each strategy (freeze-all strategy or a fresh embryo transfer) will be presented as cost per ongoing pregnancy and costs per live birth as well as average costs per woman. Longer-term costs, i.e. costs of delivery and perinatal costs, will be determined if sufficient funds are available.
A total of 48 months will be needed.
Dr. F. Mol
dr. M. van Wely
Centre for Reproductive Medicine
Academic Medical Centre, the Netherlands
T: +31 20 5665810