In the UK, the HFEA (Human Fertilisation and Embryology Authority) has set an initial time limit of 10 years to store embryos. This means that a patient whose first cycle of IVF is unsuccessful can return for another attempt using one or more of her stored embryos, or a woman who has a child can come back for a second cycle of treatment to attempt another pregnancy with a thawed sibling embryo.
Cryopreservation can also be used to preserve the fertilised eggs of women with malignant diseases such as cancer or leukaemia, who have to undergo radiatiotherapy or chemotherapy that may make them sterile. With the approval of the genetic parents, frozen embryos can also be donated to other infertile couples, or for research.
At very low temperatures, many degrees below that in a domestic deep freeze, the degradation and decay of all biological tissues is slowed right down so a live embryo can be held in suspended animation for many years. Embryos are stored in liquid nitrogen at around -200º C. About 80 percent of the air we breathe is made up of gaseous nitrogen, a relatively inert and safe gas at room temperature. When cooled to around -196º C, it becomes liquid. Plant and animal cells contain water, so an embryo cannot be plunged straight into liquid nitrogen as this would cause jagged ice crystals to form. So the embryos are bathed in a solution of ‘antifreeze’, such as glycerol, called a cryoprotectant, to get rid of most of the water in the cells, so minimising the risk of ice formation.
Embryos are stored in specially designed freezing machines, programmed by computers to freeze embryos (and other tissue) at a precise and usually slow, controlled rate. Once calibrated, the machine reproduces the precise rate of freezing and thawing required, ensuring maximum viability of the tissue to be cryopreserved. Eggs and sperm, and ovarian and testicular tissue each require a different recipe to assure the best storage without damage.
Safety is a concern. Embryos seem less likely to produce a pregnancy after freezing and thawing. Clinics have varying data, because there is no standard way of reporting the results of embryo freezing, but human embryos after thawing and transfer may often be only half as likely to produce a baby as those that have been transferred fresh. Certainly, after slow freezing microscopic damage can occasionally be seen. Most embryos are frozen at four- to eight-cell stage. Microscopic inspection after the thawing of what was an eight-cell embryo before freezing frequently shows that some of its cells are dying, missing or fragmented. However, several thousand normal babies have been born after embryo freezing in spite of this, and there is no evidence of any increase in fetal abnormality. But we do not know with absolute certainty what problems may become apparent as these children grow up.
One concern is the cryoprotectants in which the embryo is bathed before cryopreservation. There are various different compounds; one of the most common is sucrose, and another dimethylsulphoxide (DMSO) a powerful solvent that penetrates cell walls very quickly, which in high doses has been associated with mutation of the DNA in cells. DMSO could just possibly dissolve other mutagens within it that go on to cause mutation.
To get round some of this problem, there has been recent emphasis on a process called vitrification. This involves the extremely rapid freezing of cells or an embryo after immersion in a concentrated solution of cryoprotectant. As with all procedures this assumes that cryoprotectants are not biologically harmful. Vitrification gives better clinical results for freezing many cells, including sperm, eggs and possibly embryos during early development. While this seems true in the short-term and more embryos survive after vitrification, the long-term effects may be different. Although vitrification is widely regarded as the best and safest process, its potential effect on gene function is poorly understood. One of the problems is that if freezing did occasionally cause mutation, the effect would be unlikely to show up during infancy, such problems usually manifest themselves much later in life. This is not saying that embryo freezing causes cancer or infertility, just that it should still be considered more cautiously than it sometimes is at least until the children produced from frozen embryos are fully grown.
Limitations on embryo freezing are a ‘counsel of perfection’. The pressure on clinics and their patients to do everything to avoid multiple pregnancy is now so great that, after a successful IVF cycle yielding several embryos, more women are having single embryos transferred whilst the rest are stored frozen for a later treatment.
In the absence of clear evidence that embryo freezing is harmful, the following are clearly situations when freezing is completely justified:
Despite countless breakthroughs in medical science, we still do not understand why some pregnancies will end in tragedy. For most of us, having a child of our own is the most fulfilling experience of our lives. All of us can imagine the desperation and sadness of parents who lose a baby, and the life-shattering impact that a disabled or seriously ill child has on a family.
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