In the past , the standard was – Transfer the best, freeze the rest ! Is a freeze all policy better today ?

Vitrification

In a conventional IVF cycle , usually several embryos are generated and the best looking embryos (usually a couple of embryos ) are transferred to the uterus.  The remaining embryos are frozen and are used during subsequent embryo transfer attempts. 

How is an embryo frozen ? What happens to the embryo when it is frozen ? Freezing of embryo involves the use of cryogenic temperatures (below -150°C) and cryoprotectants
( substances which are used to protect the biological materials from damage due to freezing) .  Embryos which are frozen at such cold temperatures remain without any change in their functionality or in their genetic make-up for centuries. The embryos remain ‘frozen in time’ – metabolically inactive ! The length of time an embryo is frozen will not affect its quality in anyway.

What are the methods used for freezing embryos ?

There are two methods which are widely used for freezing embryos : slow freezing and vitrification.

The older slow-freezing techniques used a lower concentration of cryoprotectants. As the name suggests, freezing is achieved slowly, in a step-by-step manner and such programmed cooling requires costly instruments which could cool the embryos steadily by maintaining appropriate temperatures. It is also a time-consuming process and this technique doesn’t prevent the formation of ice crystals in embryos. These ice crystal can kill the embryo during freezing and thawing, as a result of which their survival rate was never optimal.

Vitrification is a technique in which the cells are cooled ultrarapidly (at an extremely high cooling rate) . It needs a much higher concentration of cryoprotectants. The advantage of vitrification is that ice crystal formation within the cells is totally prevented. It transforms the cytoplasm within the cells into an amorphous glassy state. This technique doesn’t need expensive equipment; but does require experience and expertise.

Which embryo freezing technique is the best ?

Scientific studies have showed that vitrifying embryos resulted in better embryo survival after thawing. Vitrified embryos also had a much higher proportion of intact blastomeres (individual cells of cleavage stage embryos) when compared to embryos frozen using slow freezing technique. The post-warming morphology of the embryos is excellent and the pregnancy rate and implantation rate is found to be better with vitrified embryos. All these beneficial effects are attributed to the lack of ice crystal formation in vitrified embryos which in turn prevents injuries due to ice formation. Hence vitrification is the current preferred method of freezing embryos in most IVF clinics world-wide.

Why is embryo freezing important ?

Freezing embryos helps in utilizing the extra embryos produced during an IVF cycle in an efficient manner and hence the need for discarding supernumerary embryos is prevented.  When an embryo is discarded a life that might have the potential to develop into a full-fledged baby is lost. Since we still do not have accurate technology to pinpoint which embryo will develop into a baby, discarding human embryos becomes an ethical issue. Embryo freezing helps in addressing this ethical issue effectively. Freezing embryos also alleviates the need for further ovarian stimulation cycles when an embryo transfer attempt fails. Hence the financial and physical distress associated with a new IVF cycle is circumvented. The success rate of an IVF cycle naturally increases when there are many frozen embryos available since many more embryo transfer attempts could be made.

Is a fresh embryo transfer better than frozen embryo transfer ?

Before the introduction of vitrification for human embryo freezing, fresh embryo transfer had a higher success rate. With the introduction of vitrification , this scenario has changed dramatically.  When embryos are vitrified , the success rate of a frozen embryo transfer is equal to that of a fresh embryo transfer - or is even higher. Hence the statement ‘ Transfer the best, freeze the rest’ is no longer valid today !

Why is a frozen embryo transfer better than a fresh embryo transfer in terms of IVF success rates ?

1)  Vitrification for embryo freezing has led to a better survival rate of post-thawed embryos ; in good clinics, the survival is nearly 100% , and not a single blastomere is lost as a result of the freezing and   thawing.

2)  The endometrial receptivity is found to be excellent during a frozen embryo transfer cycle. During an IVF stimulation cycle (fresh cycle) the estrogen level in the body rises too high and such high estrogen levels are shown to be deleterious for optimal endometrial receptivity. A FET simulates a better and more natural endometrial environment when compared to a fresh IVF cycle. Embryo-endometrial synchrony can also be better achieved in a FET cycle.

If this is so, then is a freeze all policy better today ?

The data from randomised trials favour frozen embryo transfer as compared to a fresh embryo transfer (although larger trials are needed to confirm these results). Kato clinic in Japan , which does about 10000 cycles per year , performs only FET for all its patients and their reported success rate is very high ! It’s high time that all the IVF clinics and patients think of freezing all the embryos obtained during an IVF cycle and transfer them sequentially so that the chance of achieving a pregnancy increases. Apart from the positive aspects of FET described above , there is one more valid reason for opting to do a frozen embryo transfer. We still do not have a valid, fool-proof technique to determine which embryo has the potential to develop into a baby. Embryos which are selected to be transferred to the uterus using microscopic morphological criteria fail to achieve a viable pregnancy many a time. Many good looking embryos fail to implant  and many poor looking embryos do turn into a much desired baby. In such a situation, freezing all the embryos and transferring them sequentially might improve the odds of pregnancy when undergoing an IVF cycle.

Hence a freeze all policy is definitely a better option today and FET will soon replace fresh embryo transfer in the near future !

So if your fresh embryo transfer did not work, do not panic. A frozen embryo transfer is no less efficient than a fresh embryo transfer. Before starting an IVF cycle it is important for you to make sure that the IVF clinic you select has an embryo freezing facility - and , more importantly , that they use the vitrification technique for embryo freezing.