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Scientists try to build a better 'womb' for IVF

Forsaking a Petri dish for this silicone 'womb-on-a-chip,' Tokyo scientists are experimenting with growing mouse embryos, in hopes of improving current human in-vitro fertilization techniques. Forsaking a Petri dish for this silicone "womb-on-a-chip," Tokyo scientists are experimenting with growing mouse embryos, in hopes of improving current human in-vitro fertilization techniques.
Email|Print| Text size + By Sharon Guynup
Globe Correspondent / October 22, 2007

In a University of Tokyo laboratory, a pipette-wielding technician delicately positions 10 mouse eggs on a razor-thin microchip lined with a "bed" of cultured uterus tissue.

Next, the technician adds sperm cells, fertilizing the eggs. Three tiny tubes snake from the silicone device, and over the next 48 to 72 hours, a pulsing micro-pump washes the early embryos with rhythmic waves of a culture fluid that helps them grow, in an attempt to simulate what happens in the womb. Then, the embryos are removed, and the healthy ones are implanted into the actual wombs of mother mice.

Teruo Fujii and his colleagues believe their "womb-on-a-chip" is superior to growing embryos in the static environment of a Petri dish, the way in-vitro fertilization clinics now prepare embryos for implantation into a mother's womb. Eventually, they hope it will lead to better outcomes for infertile women.

"This is a new way to culture embryos in an environment that is closer to what happens inside the body," he said in an interview. Although results in mice so far are only slightly better than with the current method, Fujii dreams of building an automated device that takes in eggs and sperm at one end and delivers healthy human embryos out the other with near-assembly line results.

Others are pursuing even more futuristic goals. Cornell University scientists built an artificial womb from cultured layers of mouse uterine tissue in 2003. Although embryos implanted and began to grow, they didn't survive, and while the studies continue, they have been placed on the back burner.

For now, Fujii and other researchers developing technologies that try to mimic the womb are focused on improving in vitro fertilization - and progress is needed. Just 29 percent of couples who attempted IVF in 2005 gave birth to a child, according to the Centers for Disease Control and Prevention in Atlanta. That was up from 24.7 percent in 1998, but still far from reliable enough for infertile couples, who often attempt IVF multiple times. A CDC report issued in 2002 found that among US women of childbearing age, 10 percent had consulted a doctor for infertility.

Some people are worried by increasingly artificial means of reproduction, said Josephine Johnston, a researcher at the Hastings Center, a bioethics think tank in Garrison, N.Y. One concern is that "assisted reproduction" will help - and encourage - women to have children ever-later in life.

"It's a mistake to think you can put pregnancy off, because it might not be successful," Johnson said. "There is also significant concern about women having babies in their 50s and 60s, perhaps because of elevated risks for both mom and baby - and questions about an older mom's physical ability to raise that child to adulthood."

Such concerns have not deterred Fujii, who earlier this year reported on the results of his "womb-on-a-chip" experiments with mice. Sixty percent of attempts produced healthy embryos, compared with the 52 percent from the standard in-vitro fertilization method, according to data Fujii presented at the European Society of Human Reproduction & Embryology meeting in Lyon, France.

After implantation, 44 percent of the microchip-grown embryos developed into healthy fetuses, compared with 40 percent of Petri dish-produced embryos.

A Petri dish is very different from the dynamic liquid environment inside the Fallopian tube and the uterus, explained Matt Wheeler, a reproductive biologist at the University of Illinois in Urbana-Champaign, who is trying to perfect a microchip for livestock embryos. The chips gently bathe embryos in nutrients, proteins, and other factors they need to develop, and also wash away waste.

Since garnering university and government approvals in March, Fujii's team is now attempting to create human embryos in its "womb-on-a-chip." The technology might be available to would-be parents in five years, he said, but it could take longer to perfect - and to prove it safe.

Another innovation is afoot at the University of Michigan in Ann Arbor, based on a technology originally developed to rapidly change Braille displays to help blind people read their e-mail. Shu Takayama's team has engineered a tubeless, portable microchip housed in an inch-square casing. The chip rests on an array of computer-controlled pins that move up and down to adjust the flow of nutrients from a reservoir of fresh culture media and remove waste. In 2006, the American Society of Reproductive Medicine recognized this device as one of the top innovations in the field.

After conducting animal tests that Takayama said are "encouraging enough to commercialize the technology," the scientists have developed a prototype chip with Incept BioSystems, based in Ann Arbor and Woburn, Mass. He said they are now "working towards translating this technology for humans."

Alta Charo, professor of law and bioethics at the University of Wisconsin-Madison, noted that there is always a level of uncertainty when research moves from animals to humans. Though these concerns are not unique to reproductive technologies, they are viewed with greater alarm, with some believing that assisted reproduction and reproductive research, especially that involving human embryos, should be banned. Charo argues otherwise.

"There's a tremendous instinct to assume that if you think something is immoral, the government should forbid it," Charo said. "Under the Constitution, we tolerate diversity of moral viewpoints and do not view the government as the arbiter of a particular moral vision."

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