At last, a breakthrough in freezing technology has improved IVF embryo survival rates and provided new hope for infertile couples. In this article, London Women’s Clinic discusses how the technique of vitrification has changed IVF treatment.
Vitrification is now the preferred freezing method at IVF clinics
There has been a freezing revolution in the IVF lab. Some would say it's a slow revolution, because the technique of vitrification was first described more than 20 years ago, but in the past few years, as demands on embryo freezing have grown throughout the world, more and more IVF clinics are turning to this new fast-freeze technique whose results have been remarkable, to say the least. Vitrification is now the favoured freezing method at most of the world's IVF clinics, including the London Women’s Clinic.
Freezing has long been an essential component of the fertility clinic, first for the storage of donated sperm (required by law to be frozen) and later for the preservation of spare IVF embryos. However, the conventional technique of dunk-freeze in liquid nitrogen was relatively slow and allowed ice crystals to form in and around the frozen cells.
The problems of conventional embryo freezing methods
What studies have found was that the ice crystals were damaging some of the embryos. Post-thaw survival rates varied between 50 and 60%, but there was still a significant number which did not survive.
All that changed with the wider introduction - first in Japan - of the flash-freeze vitrification technique which, by protecting the cells with chemicals, reduces them to a glass-like state (and their temperature to almost minus 200oC) in just a few seconds. Vitrification differs from traditional cooling and preservation techniques because it allows instantaneous glass-like solidification of embryos without the formation of ice crystals. Since no ice crystals form, a much greater percentage of embryos survive thawing following vitrification.
The new vitrification technique has a higher embryo survial rate
Many trials have now shown that the outcome of frozen IVF cycles is better when embryos are vitrified than when stored by conventional slow freezing. Survival rates have been consistently shown to be well over 90 per cent, with a commensurate improvement in pregnancy and birth rates. Last year, a study from the Middle East reported ongoing pregnancy rates in vitrified cycles (41%) almost double those found in slow-freeze cycles (21%).
What the new technique means for IVF treatment
The wider use of a more effective and reliable preservation method has had several consequences for IVF clinics and patients over and above the better survival of embryos.
1. Fewer embryos need to be transferred
Because the preservation and survival of spare embryos is more reliable, clinics and their patients are more encouraged to transfer fewer embryos in the first fresh treatment cycle. All embryos can be transferred, but just one or two at a time.
In 2008, the British Fertility Society (BFS), following a recommendation of the Human Fertilisation and Embryology Authority (HFEA), described single embryo transfer as 'the only effective method to reduce IVF multiple pregnancy rate, the single biggest health risk to both mother and child associated with fertility treatment'. The key to an effective single embryo transfer policy, added the BFS, is an effective frozen embryo replacement programme to maximise cumulative live birth rates per stimulated cycle. 'This means spare high-quality embryos harvested from an ovarian stimulation cycle can be frozen, stored and subsequently reimplanted if pregnancy does not result from the initial cycle,' said the BFS. 'This avoids the need for women to undergo further costly cycles of ovulation stimulation to harvest more eggs.'
2. Traditional egg freezing is no longer controversial
Because of its patchy survival rates, embryo freezing by conventional methods is viewed as controversial in some cultures. Indeed, in Italy in 2004 new laws were introduced which outlawed the freezing of embryos. The freezing of eggs (as of sperm), because there had been no conception, was associated with none of these ethical dilemmas.
However, studies of egg preservation showed that the ice crystals which formed during conventional freezing caused damage to the genetic composition of the egg - and very few embryos, and even fewer pregnancies, were derived from frozen eggs. In fact, for more than two decades egg freezing remained one of the big challenges in reproductive medicine, and it was not until the wider use of vitrification that the preservation of eggs became a possibility and then a reality. Much of the research in egg freezing has recently been driven by Italy, where embryo freezing (until very recently) has been banned.
3. Vitrification provides a solution for cancer patients
The 'preservation' of fertility in young women facing the prospect of cancer treatment is another development made possible by the availability of efficient freezing programmes. Chemotherapy and radiotherapy can both cause damage to the normal function of the ovaries, such that cancer patients must often accept infertility as the price of their treatment. This is a growing problem for many young women because cancer treatments are becoming more and more successful and more and more patients are surviving their disease.
For young patients, the possibility of parenthood can be conserved beyond cancer treatment by freezing - and there are now multiple studies describing the preservation of eggs and ovarian tissue. However, while the studies are numerous, the actual successes recorded in healthy births are much fewer, and fertility preservation remains very much an experimental procedure. The most remarkable stories have come from Belgium, Denmark and the USA following ovarian tissue storage before cancer treatment and, following subsequent transplantation of the thawed tissue, a restoration of the menstrual cycle and spontaneous pregnancy. More likely scenarios are expected from the much now simpler technique of egg freezing by vitrification; thawed eggs would be fertilised as in routine IVF, and transferred as a single (or double embryo transfer).
Vitrification increases the success rates of IVF
Despite these exciting developments, by far the most visible effect of vitrification will be seen in routine IVF and storage of embryos for use in subsequent cycles. And, as fewer and fewer embryos are transferred in first 'fresh' cycle, more and more will stored for later use. In Europe, the transfer of thawed frozen embryos presently accounts for around one-quarter of all IVF and ICSI procedures, but all experts agree that that proportion is now on the increase.
Also, pregnancy rates from frozen cycles are rapidly increasing. In 2001, the European pregnancy rate (per embryo transfer) was 16.4 per cent; in 2006 this rate had risen to 21.6 per cent. Although this remains below that reported from fresh transfers (around 33 per cent), it is still a remarkable increase in just five years. And, when adjusted according to age, the European results showed not much difference in pregnancy rate per cycle in the 35-39 year age band between frozen embryos (18.6 per cent) and fresh (26.1 percent ICSI, 27.9 percent IVF).
Indeed, a recent review of embryo and egg preservation reported that cumulative delivery rates of 50-60 per cent in younger patients were now likely using frozen embryos. These rates may now be even higher when preservation is by vitrification.