A suggestion originated in the early 2000s that the high hormone levels derived from a stimulated IVF cycle would encourage a non-receptive, out-of-phase endometrium, the concept arose that adopting a freeze-all approach would not only minimize the risk of ovarian hyper response syndrome but maybe even improve pregnancy rates in the general IVF population. The Freeze all Embryos or Fresh Transfer strategy was initially a ‘rescue’ strategy for women at high risk of ovarian hyperstimulation syndrome; however, this approach has been extended to other indications as a scheduled strategy to improve implantation rates.
The latest clinical meta-analysis of fresh vs frozen transfers, now involving 5379 eligible subjects and 11 trials, found eFET associated with a higher live birth rate only in hyper-responders. There was no outcome difference between fresh and frozen in normal responders, nor in the cumulative live birth rate of the two overall groups. Now, here is where it gets complicated.
The CDC described the increase in the number of elective FET cycles between 2007 and 2016 as ‘dramatic’, rising steeply from almost zero to more than 60,000 cycles per year. In its summary of US activity for 2016 the CDC seems unequivocal – at least, based on its observational registry data – that rates of pregnancy and live birth are higher after frozen transfers than after fresh. Yet the (published, peer-reviewed, or randomized clinical trial) so far has not shown a large difference. It seems to be a case where the clinical trials have not caught up with clinical practice, and because there is clear evidence that for hyper responders outcomes are better, many clinics are now relying on a Freeze all Embryos or Fresh Transfer strategy to reduce this poor outcome.
Mathilde Bourdon et al., (RBMO, 2021) recently summarized the evidence in The freeze-all strategy after IVF: which indications?
The use of this strategy is steadily increasing in ART cycles with various indications
1. To counter the risk of late pregnancy- induced ovarian hyperstimulation syndrome (OHSS) in patients who experienced an excessive ovarian response to stimulation
2. The existence of endometrial anomalies, e.g. thin endometrium, polyps, associated metrorrhagia, submucosal leiomyomas and endometritis, or elevated progesterone levels on the last day of stimulation.
3. The aim was to limit the risk of implantation failure or was used as a ‘scheduled’ strategy before the beginning of ovarian stimulation in various indications, including preimplantation genetic testing (PGT).
4. Ovarian stimulation with IVF and intracytoplasmic sperm injection (ICSI) cycles could have a negative effect on endometrial receptivity, generalization of the freeze-all strategy to the overall IVF/ICSI population has since been implemented in a number of centers.
5. A recent meta-analysis, the transfer of day-5 blastocysts was associated with significantly higher pregnancy rates compared with the transfer of day-6 blastocysts as the intrinsic embryo implantation potential in day-6 blastocysts is impaired (Bourdon et al., 2020a), an asynchrony between the endometrium and day-6 blastocysts is also a possibility, reported significantly lower live birth rates in fresh day-6 compared with fresh day5 blastocyst transfers, whereas this difference was not found with frozen embryo transfer
6. It may also be caused by a failed implantation process, possibly related to the endometrial changes that impair endometrial receptivity in fresh autologous IVF/ICSI cycles
7. Freeze-all strategy increase the chances of a live birth in women with repeated IVF/ ICSI failures, women with at least one failed fresh blastocyst transfer have a significantly greater probability of a live birth with the ‘freeze-all’ and subsequent thawed approach than with another fresh cycle
8. IVF is associated with an increased risk of thromboembolic diseases (pulmonary embolism and venous thrombosis), with a doubling of risks during pregnancies resulting from ART.
