What is “elective freeze all cycles” – and when it can be used?

The approach, a technique which is called a “freeze all” policy, had been described many years ago which basically tried to get the embryos and freeze them all. They divide the treatment in two parts: the first part in which we focus on the ovaries and on getting the oocytes and then a second part in which we focus on the endometrium and the embryo transfer. I’m personally a fan of this type of approach because we are starting to see in the literature that we have a small, not too much but small chance, better chance of getting pregnant. What’s the justification for this, this is that when we do the ovary stimulation, we sort of force nature because we want to have as many eggs as possible so, we force one of those menstrual cycles by giving a higher dose of gonadotropin that can affect the endometrium and one of the things is that the window of implantation can be moved because we are sort of moving out of physiology so, that can happen, it’s actually a pretty decent theory. We started to do this freeze all policy and we find out that nowadays, that we have the vitrification protocols which works really well in the laboratory, we can do this with a lot of confidence and with a lot of good results. Back in time when we didn’t have vitrifications, when we used a slow freezing, we had really worse results because the technique of freezing was not that good but nowadays with vitrification this result policy it’s actually a very good one in my personal opinion.

This is where the doctor may decide that in essence of having a fresh transfer on the cycle, fresh cycle of treatment you’ve had, to instead freeze all the embryos and have no embryo transfer at all and then in a subsequent a frozen embryo transfer cycle, have one or two embryos put back. The reason, some doctors suggest this is they believe that it could help increase the implantation rate and the success and live birth rate, the reason is that during a fresh IVF cycle ,the woman’s body is receiving a lot of medication in order to stimulate the cycle, to produce more eggs and some believe is that this excessive amount of hormones and medication that are inside the body may interfere with implantation of the embryos and therefore it may be better to allow the body to go back to a more or less normal state after two, three months following this treatment, to wait and then come back for a frozen cycle transfer. I think the fertility field is quite divided on whether it is useful or not. Some clinics or doctors routinely do it and they have increased rates and some don’t believe that it actually does help and it may just delay the treatment and pregnancy for some women who are actually the ages against them and therefore they prefer that this is done as a fresh cycle rather than delayed to a cycle that is a frozen cycle later.

“Elective freeze all cycles” is another really interesting topic and it’s certainly been an area of raging debate within the IVF community over the last few years. So instead of having a fresh embryo transfer, you opt to freeze all of the embryos (usually at the blastocyst stage which is going to be Day 5) and not have a fresh transfer. You then recover from your fresh transfer and have your frozen embryo transfer a month to two or three later and the theory behind it is that the high estrogen levels that are produced during a fresh cycle, they can affect the regulation of over 200 genes in your endometrium and that altered gene expression can then affect the implantation and also you’ve had the trauma of an egg collection (it’s you’ve been through a minor surgery) so it’s not always the safest time to do a fresh transfer and you should have a frozen transfer. So some clinics based on the initial evidence opted to do pure “freeze all cycles” and not do fresh transfers anymore and that was the sort of the trend for a while and then it sort of swung back towards a fresh transfer. The interesting point is that there was a big data publication a couple years ago by all of the cycles registered in America which I think was about 84 000 cycles and they found that the “freeze all” approach only benefited high responders so if they had more than 15 eggs collected, those high estrogen levels did affect the endometrium and also it wasn’t safe for those patients to have embryo transfer because what happens is if you’re at risk of hyperstimulation because of the IVF drugs but then, if you get pregnant and you’re on that borderline, the pregnancy then kicks out the same hormones that you would and tips you into what’s called secondary hyperstimulation and then you can get quite sick and you’re at risk of the pregnancy complications because you can’t be treated as effectively as you would be if you weren’t pregnant. So freeze all should definitely be used in those approaches of high responders. The other interesting aspect of the “freeze all” is data which we’ve recently published which looks at applying “freeze all” to specific groups and in that group is slow growing blastocyst” so, if you culture your embryos to Day 5 and you don’t have any what we call fully expanded blastocysts, what would normally happen is you would still have the best one or two embryos back, the other ones would be cultured at Day 6 and potentially frozen on Day 6. What our data shows is actually if you don’t do the transfer on Day 5, culture the embryos to Day 6 and freeze them effectively, you can then put those embryos (Day 6 embryos) back in a frozen cycle but on a day five endometrium and you cheat a day out of the embryo development because you’ve managed to get an expanded blastocyst. Therefore the blastocyst is at the right stage to actually be ready to implant into your endometrium because if you would put a slow growing blastocyst back on day five, it may have run out of time to actually implant into your endometrium. So by doing this applied freeze all approach you benefit the embryos an extra day and actually we saw that in some cases for good quality blastocysts frozen on Day 6 that actually doubled to chances of implantation and even those poorer quality embryos, as long as they made an expanded blastocyst, they still had a significantly improved chance of pregnancy by putting it back on day five (assuming they survived the freezing procedure which normally 97 – 98%). So it’s about applying “freeze all” to specific groups rather than blank “freeze all” approach.

A new cryopreservation method where now the embryos if we perform the so-called “freeze all” – meaning we freeze all the embryos and perform the transfer later. Now, the current cryopreservation methods are so gentle that the embryos can withstand the cryopreservation very well and without any lowering of their success rates. Thanks to that, we don’t need to focus on the endometrium.

The introduction of vitrification into our clinical practice, opens new roads of treatment options for us. So, soon after vitrification came into our life, into our laboratory routines, options such as the elective freeze all became available and produced a higher benefit for our patients. It seems that couples and women in particular that are high responders or at the risk of hyperstimulation syndrome, do not need any longer to proceed to an embryo transfer. We can provide them with the option of safely storing the embryos thanks to vitrification and so allow these ladies, for the body to regain its private functionality and once the body and the endometrium is back to normal, to proceed to embryo transfer. By doing so and thanks to elective freezing approaches, we may achieve to reduce the risk of hyperstimulation after transfer and it seems that we have improved our overall chances for a successful outcome since the endometrium environment is much more favorable for implantation when it’s not affected by the stimulation regime.

This is a very critical point and it differs upon the stages of endometriosis. So sometimes it could be better to postpone the embryo transfer and do “freeze all embryos”. So you are having this storm of hormones settling down, your body is just going back to normal and proceeding with frozen embryo transfer and this can even increase the cumulative frequency in cases of endometriosis. So don’t worry about the quality of the eggs – end point – live birth rate, miscarriage rate are similar to non-endometriotic patients.

Not and there is no evidence that it does and I stand corrected but I am one of those sad people who spend most of his time with the evidence and that’s why probably I was late for this.
Freeze all is a technique that has emerged recently. Initially people suggested that it may be more successful if you put the embryos on ice and then prepare the lining and put them back inside but currently really the most sensible use is to use it as a safety net because if a patient at risk of getting very sick by condition called Ovarian Hyperstimulation Syndrome because her ovaries are packed with eggs (even if you give her a smaller dose of the medication she is likely to produce 30 or 35 eggs). In the old days, some patients were getting very very sick and they could go to intensive care in a critical condition and life’s threatening. Having the freeze old technique in addition to some special medication now, we can provide safe stimulation, we get as many eggs as safely possible because we know that we will fertilize them and grow them to Day 5 and then keep them on ice in the freezer and the patient after the storm is over, she can come and get prepared for her frozen embryo transfer. If her cycles are regular and she’ll ovulate, she will do it in a natural cycle without medication (she can have an organic baby). If however her cycles are irregular, she can have a medicated cycle or modified natural cycle which is safer and effective and that’s some approach that I personally use because then I don’t have sleepless nights worrying about the risk of hyperstimulation which is one of the most serious complications of IVF.

I have to say that the “freeze all” strategy is gaining popularity worldwide and today, it represents the alternative approach to the fresh embryo transfer. “Freeze all” means that all the available embryos are cryopreserved avoiding the fresh transfer that will be instead programmed later. The transfer will then take place separately from ovarian stimulation and some advantage will be the optimisation of the response and lower risk of the ovarian hyperstimulation syndrome. In women that suffer from Ovarian Hyperstimulation Syndrome, it is highly recommended.

During a normal IVF cycle, one or two fresh embryos are transferred a few days after the egg collection and if there are any remaining good quality embryos, they are frozen. In “elective freeze all cycle”, all the embryos, created using IVF or ICSI, are frozen, so that no embryos are transferred in the fresh cycle. A few months later, the embryos are thawed and transferred to the woman’s womb in what is called a frozen embryo transfer cycle. According to HFEA, “elective freeze all cycle” is rated amber – meaning that there is conflicting evidence from RCTC as to whether it is effective at improving the chances of having a baby and this is for most fertility patients. There is some evidence that the lining of the womb can be affected by the body’s hormonal response to fertility drugs, something that makes the implantation of the embryo more difficult. Freezing the embryos allows them to be transferred to the woman when the womb lining is better developed. Although there is some research suggesting that frozen embryo transfers increase pregnancy rates compared to fresh embryo transfers, there’s not enough evidence to support that “freeze all cycles” are safer and more effective. However, for certain groups of patients, “freeze all cycles”, have proved to be effective at reducing ovarian hyperstimulation syndrome. Finally concerning the safety of the procedure, one should always consider the risk that one or more embryos may not survive the processes of freezing and thawing.