IVF produces healthier children when embryos are frozen and thawed before being transferred to the womb, according to new research.
Babies born from frozen IVF embryos are less likely to be born prematurely or underweight than are those conceived during fresh treatment cycles, three independent teams of scientists have found. One of the studies also recorded lower rates of stillbirth and early death among frozen-embryo babies.
The results, from researchers based in the United States, Australia and Finland, suggest that far from being riskier than conventional IVF, as is generally thought, cycles using frozen embryos may actually be safer.
The research is particularly significant because separate teams from three countries have reached the same conclusion, each using large samples including thousands of IVF cycles. A fourth team, from Denmark, also reported similar findings earlier in the year.
Scientists said the work would be important because women are increasingly encouraged to use just one fresh embryo during IVF, to guard against damaging twin and triplet births, and to freeze any that are left over for later use. It will dispel doubts about whether this policy trades the risks of multiple births for hazards associated with frozen embryos.
Allan Pacey, secretary of the British Fertility Society, said: “This all works to the advantage of single embryo transfer. It suggests it might be better from the point of view of a healthy child to go for frozen embryos, which is an integral part of the strategy. People shouldn’t be scared of frozen embryos.”
The studies, presented at the American Society for Reproductive Medicine conference in San Francisco, do not explain why babies born from frozen embryos seem to do better, but there are several hypotheses.
When fresh embryos are used in treatment, women may still be under the influence of powerful hormonal drugs used to stimulate their ovaries into producing extra eggs, or the anaesthetics used during egg collection. Either of these may interfere with the endometrial lining of the womb, and thus with the formation of the placenta.
Another possibility is that as some frozen embryos generally fail to survive thawing, this effectively “weeds out” those that are of poor quality. A third possibility is that women who produce lots of good quality embryos are more likely to have frozen cycles, and also have a lower risk of complicated pregnancies.
“These findings are really quite interesting,” Dr Pacey said. “It kind of defies logic to a certain extent. It seems to be an issue with the formation of the placenta, but how it has an effect isn’t known.
“This may be a bit of biology that has escaped most people. The assumption has always been that if the endometrium [the womb lining] is thick, it’s functional. In an IVF cycle, the endometrium looks normal on ultrasound, but perhaps there is something subtle going on.”
Despite their apparent health benefits, however, frozen IVF cycles are unlikely to supplant fresh ones as the routine option because they have a lower success rate. In Britain, 24.4 per cent of fresh cycles lead to a live birth, compared to 17.4 per cent of frozen cycles. There were 33,916 fresh cycles performed in 2006, and 7,911 frozen cycles.
“Frozen embryo transfers are not as successful as fresh ones in terms of getting a pregnancy,” Dr Pacey said. “So it may be that we have to balance the health of children against chances of success."
The first of the new studies, led by Suleena Kansal Kalra, of the University of Pennsylvania, compared 4,796 frozen cycles to 10,992 fresh cycles in which surplus embryos were available for freezing.
For singleton babies, fresh cycles were 50 per cent more likely than frozen ones to lead to low birth weight, and 10 per cent more likely to lead to premature birth. For twins, both risks were 25 per cent higher for fresh embryos than for frozen.
“Fresh embryo transfer is significantly associated with low birth weight and pre-term delivery in both singletons and twins,” Dr Kansal Kalra said.
In the Australian study, a team led by Professor Gordon Baker, of Royal Women’s Hospital in Melbourne, compared all IVF singleton births in the city’s IVF units between 1991 and 2004. It found that 11 per cent of fresh embryo babies were born underweight and 12.3 per cent were born prematurely, compared to 6.5 per cent and 6.9 per cent of frozen embryo babies. The rate of perinatal death was also higher among the fresh group, at 1.87 per cent compared to 1.16 per cent.
The Finnish study, from Oulu University Hospital, compared 2,052 frozen embryo singleton babies to 2,343 born after fresh IVF cycles, and found those in the latter group were 35 per cent more likely to be born prematurely and 64 per cent more likely to be born underweight.
“Frozen embryo transfer singletons have better outcomes compared with singletons born after fresh embryo transfer, when examining birth weight or gestational age at birth,” the scientists said.
Some scientists believe that frozen embryo transfer may also have advantages for IVF success, even though its pregnancy rates have traditionally been lower than for fresh cycles. A new cryopreservation technique called vitrification allows more embryos to survive thawing than the older slow-freezing method on which these comparisons are based, and using it could help by allowing doctors to transfer embryos when the womb is most receptive.
Mandy Katz-Jaffe, of the Colorado Centre for Reproductive Medicine, said: “In a normal IVF cycle, patients have their embryo transfer while the uterus is still affected by the drugs they take to stimulate the ovaries. Vitrification allows the patient’s body to get rid of the drugs, and to grow a new endometrial lining.”
