MONDAY, Jan. 26, 2004 (HealthDayNews) -- In a new study that might give the assisted reproduction community pause, scientists have found mouse embryos that were cultured for longer periods of time before being transplanted into the mother seemed to have anxiety and memory disturbances after they were born.
Although the findings can' be directly extrapolated to human in vitro fertilization (IVF), there may be some implications because human embryos are now often allowed to develop longer outside the uterus.
In humans, assisted reproductive technology usually generates more eggs, and therefore more embryos, than could possibly be transferred to the mother. So, there is a premium put on trying to determine which embryos are the "best" candidates for transplantation.
"Clinicians want to identify the best embryos, but they want to transfer as few as possible. And the reason for that is that everyone agrees that multiple pregnancy is not a good thing," says Richard Schultz, a biology professor at the University of Pennsylvania and senior author of the study, which appears in this week's issue of the Proceedings of the National Academy of Sciences. "Clearly, the solution is to transfer a single embryo, but, even more, we need to identify the best embryo."
Over the past five or so years, the strategy has been to hold off on moving embryos over to the uterus.
"The best way to maintain high pregnancy rates and eliminate or minimize higher-order multiples is to culture the embryos for extra days and allow us to pick out the very best for transfer," explains Dr. Alan Copperman, director of reproductive endocrinology at Mount Sinai Medical Center in New York City. "One or two embryos are leading the pack. They have divided the most, they have a thick inner cell mass, they have a nice regular embryonic surface. It's survival of the fittest, Darwinism in a dish."
According to Schultz, however, there really is no objective way to identify the embryo that can go the distance. Moreover, the strategy could have unforeseen consequences later in life.
"One of the things that we do know from model systems is that when you put embryos in culture and you culture them, they undergo a number of changes in response to being in an environment that they're not accustomed to," Schultz says. "Just because you have offspring coming out doesn't mean that they're totally normal."
Research done in England found children whose mothers were undernourished or malnourished managed to get enough sustenance to survive as fetuses but have a higher propensity for obesity, diabetes, cardiovascular disease and more later in life.
"There is concern in the basic research community whether it's actually a good idea to be culturing longer, because perhaps they are undergoing changes that have long-term effects," Schultz says.
For this study, Schultz and his colleagues transferred mouse embryos that had been cultured in different culture media into one foster mother and compared them with embryos that had been conceived in vivo. At 4 to 6 months of age, the cultured mice seemed to have lower anxiety levels, different locomotor activity and a compromised ability to retain spatial information.
Dr. Owen Davis, president of the Society for Assisted Reproductive Technology and associate director of IVF at Weill-Cornell Medical College in New York City, points out that certain areas, such as sensory and motor development, showed no differences. And the differences in anxiety were seen only in males, he adds.
Also, rodent findings are not enough for many human clinicians.
"First and foremost, we should always use caution when evaluating animal studies and trying to apply them to humans," Copperman says. "The genetics are different, laboratory culture conditions are different, and even the tests of outcome like behaviors are dramatically different. A study like this should in no way set off panic among infertile couples trying to conceive."
"We have 25 years of experience with IVF and more than 1 million offspring worldwide, some of whom are having their own children," Davis adds. "They are not echoing the problems that have been found in the IVF model. It is difficult to translate from mice to humans."
Schultz, though, says a word of caution is in order. "We're not saying the IVF kids are dumb or anything like that," he says. "The feeling of people like myself and many in the basic research community is that the implementation of these procedures is far outpacing the underlying science."
"There should be more of an effort to know the constraints and limitations and to develop prospective studies where you would basically follow the offspring cradle to grave, and resolve once and for all whether there are long-term risks associated with the procedure, and what are the magnitude of the risks," he adds.
More information
For more on assisted reproductive technology, visit the U.S. Centers for Disease Control and Prevention or Resolve: The National Infertility Association.
