How did a Freeze-All embryo strategy become the industry norm? 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 embryo approach would not only minimize the risk of ovarian hyper response syndrome (OHSS) but maybe even improve pregnancy rates in the general IVF population. 

Whether the freeze-all embryo strategy does increase IVF success rates is still up for debate. Over 11 clinical trials and 5000 eligible subjects later, eFET was found to be 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. 

But, 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 over a Fresh Transfer strategy to reduce this poor outcome. 

Who should consider a “Freeze-all” Embryo Strategy?

According to RBMO, Depending on the clinical setting, IVF deferred frozen embryo transfer could provide significant advantages over fresh embryo transfer for the following reasons: 

If you’re at Risk for OHSS: 

The first obvious candidate based on the above data are women who are at risk for OHSS (ovarian hyperstimulation syndrome). Mild OHSS happens in up to a third of all IVF cycles while more moderate to severe OHSS happens only 3 percent to 8 percent of the time.

OHSS is often seen in women with PCOS or high responders. Women with over 25 eggs retrieved are more likely to suffer from severe OHSS.

If you have known endometrial anomalies:

Thin endometrium, polyps, associated metrorrhagia, submucosal leiomyomas and endometritis, or elevated progesterone levels on the last day of stimulation, a freeze-all should be considered as surgery or a long lupron protocol may be required before transfer.

If you are using PGT:

If you have known genetic issues or are looking to rule them out and increase your implantation success with PGT, you will be required to freeze all embryos as you wait for the test results.  

Endometrial receptivity:

Ovarian stimulation with IVF and intracytoplasmic sperm injection (ICSI) cycles may have a negative effect on endometrial receptivity due to higher estrogen and progesterone levels. If you receptivity is in question, an ERA test may be recommended before you transfer your embryos, and therefore a freeze-all strategy would be implemented.

If you have a day 6 or 7 Blastocyst:

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 

If you’ve had a failed Fresh Transfer:

Freeze-all strategy increases 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 

If you are at high risk of a thromboembolic event:

Fresh transfers are associated with an increased risk of thromboembolic diseases (pulmonary embolism and venous thrombosis), with a doubling of risks during pregnancies than those who conceive naturally or with a FET. That’s because a fresh embryo transfer is preceded by an elevated level of oestradiol and consequently a hypercoagulation state. Therefore, a freeze-all strategy could be the best option to limit the thromboembolic risks induced by ART treatments in women who are at high risk of a thromboembolic event.