The increasing trend to perform more pre-implantation genetic testing cycles for aneuploidy, especially in the United States ( 2), has also contributed to an increase in the total number of FET cycles ( 1).ĭespite the increase in FET, the most optimal priming protocol of the endometrium is still a matter of debate ( 5). The main contributor of the increasing trend for FET is an increase in freeze-all cycles in 2016, of all oocyte retrievals, the rates of freeze-all were 26.5%, 19.2% and 8.5% in Australia and New Zealand, United States and Europe, respectively ( 1). In Europe, a similar trend, however with a certain delay is seen among all embryo transfers, the proportion of FET cycles increased from 28% in 2010 to 34% in 2016 ( 3, 4). Among all embryo transfers, the proportion of FET cycles was 77.0% as reported by the most recent update from the United States nationwide database ( 2). The number of FET cycles started to surpass fresh transfer in the United States and Australia and New Zealand in 20, respectively ( 1). Over the last decade, efficient and safe vitrification techniques, alongside an increase in “freeze-all” cycles have contributed to a marked increase in frozen embryo transfer (FET) cycles globally ( 1). The place of progesterone rescue protocols in patients with low serum progesterone levels one day prior to warmed blastocyst transfer in hormone replacement treatment and natural cycles is likely to be intensively explored in near future. Recently available evidence clearly indicates that, in hormone replacement treatment and natural cycles, there might be marked inter-personal variation in serum progesterone levels with an impact on reproductive outcomes, despite the use of the same dose and route of progesterone administration. Time corrections, due to inter-personal differences in the window of implantation or day of vitrification (day 5 or 6), should be explored further. Regarding warmed blastocyst transfer and frozen embryo transfer timing, the evidence suggests the 6 th day of progesterone start, LH surge+6 day and hCG+7 day in hormone replacement treatment, true natural cycle and modified natural cycle protocols, respectively. Currently, low-quality evidence indicates that, natural cycle, either true natural cycle or modified natural cycle, is superior to hormone replacement treatment protocol. Well-designed trials comparing various frozen embryo transfer protocols in terms of live birth rates, maternal, obstetric and neonatal outcome are urgently required.
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