THE children of the future may be conceived and spend their first few days of
development on a computer-controlled chip.
In a move recalling Aldous Huxley’s famous production lines for making babies
in Brave New World, researchers in the US are building a “chip” that
can automatically carry out all the steps involved in IVF, from fertilising eggs
to preparing embryos for implantation. Ultimately, such devices—which
amount to artificial reproductive tracts—may even be able to sort and test
embryos for genetic flaws.
So far researchers David Beebe and Matthew Wheeler have built prototypes that
can carry out the major steps involved in IVF, though not all on the same chip.
Far more mouse embryos develop successfully on these devices than by traditional
methods.
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The researchers say they expect the technology will first be used for
livestock production, but their eventual aim is to use it for human embryos. The
work could be the first step towards a future in which IVF becomes the norm,
says George Seidel, a reproductive physiologist at Colorado State University in
Fort Collins. “Fifty or 100 years from now, our in vitro procedures for parts or
even all of pregnancy may end up being safer than dealing with the various
things that occur in the body—in terms of viruses that the mother comes
across, toxins, and so on.”
In conventional IVF, sperm and eggs are dumped into a Petri dish where the
fertilised eggs grow until they’re ready to be implanted. As embryos need
different culture media at different stages, embryologists transfer them from
one dish to another via a pipette. “It’s like being plucked out of the Atlantic
Ocean and stuck into the Pacific Ocean,” says Beebe, a biomedical engineer at
the University of Wisconsin, Madison.
So Beebe and Wheeler, an embryologist at the University of Illinois at
Urbana-Champaign, designed a device to mimic conditions inside a female’s
reproductive tract. The device, made of a transparent elastomer, resembles a
small glass slide and contains a network of tiny channels, each around 0.2
millimetres in depth and width. The researchers connect the channels to
programmable syringe pumps, which can move embryos around and add or remove
fluids.
To test the device, the team cultured mouse embryos to see how many developed
to the “blastocyst” stage, ready to be implanted. “In 48 hours, in the
traditional Petri dish, none of them made it to the blastocyst stage. In our
channels, about 75 per cent made it,” says Beebe. “The embryos were transplanted
into hosts and live pups were born. So there doesn’t appear to be any
detrimental effect.”
The researchers also used the device to remove the “zona pellucida” shell
that encases early embryos. In human IVF, this “assisted hatching” can be used
to encourage implantation. Traditionally, the embryo is put into an acid medium
and quickly removed when the embryologist sees the zona break up.
But waiting this long may damage the embryos. By washing acid over mouse
embryos “parked” in a microchannel on a chip
(see Graphic), the team found even
with a brief exposure, the zona broke up after the acid was removed. “People
have been leaving embryos in the acid too long,” says Beebe.
In a separate experiment, the team matured mouse eggs inside the channels,
then fertilised them by squirting sperm over them. Eventually they hope to
integrate all the steps into a single artificial reproductive tract.
Crucially, the chip-like device not only allows many embryos to be cultured
at once, it allows each one to be individually manipulated and tracked in
separate channels. That should make it easier to weed out poor-quality embryos
before implantation. Embryologists already inspect embryos under the microscope,
and some IVF clinics also measure their consumption of oxygen and glucose and
the amount of carbon dioxide they release. All this could be done more routinely
on a reproductive chip, says Beebe.
In time, the device could even make it easier to carry out pre-implantation
genetic diagnosis, where a few cells are removed to screen embryos for genetic
disorders. “That involves more sophisticated manipulation than our current
devices can do. But it is something we are working on,” says Beebe.
But quality control raises ethical issues, says Tom Shakespeare of the
Policy, Ethics and Life Sciences Research Institute in Newcastle. “If we are
talking about maximising the chances of becoming pregnant and carrying to term,
then there’s less argument. But if we are talking about either reducing genetic
diversity or indeed enhancing selection then there are major questions.”
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More at:
IEEE Transactions on Biomedical Engineering (vol 48, p 570)