Scientists concoct new
recipe for IVF success
BY RUTHANN RICHTER
Researchers at Stanford
have developed a novel technology to minimize the number
of high-risk multiple births resulting from in vitro
fertilization (IVF). While preliminary, the initial
results suggest that the new approach may represent an
important advance over standard IVF techniques, said
principal investigator Barry Behr, director of Stanford's
IVF and Assisted Reproductive Technology Laboratory.
So far, the new technology
has been applied in seven IVF patients at Stanford, all
women from the Bay Area, he said. "We're extremely
excited because we have done seven patients and all seven
are pregnant," Behr said. "It's a great
start."
The new approach uses a
special recipe for a nutrient-rich culture medium to keep
artificially fertilized embryos growing in the lab for a
few extra days.
In the standard IVF
procedure, reproductive specialists nurture a batch of
embryos in a laboratory culture for three days and then
transfer four to six of the embryos into the woman's
uterus. About one-third of the time, this results in the
implantation of more than one embryo.
A significant number of
such cases involve triplets or quadruplets, making for a
risky pregnancy, said Dr. Amin Milki, medical director of
Stanford's IVF program and an associate professor of
gynecology and obstetrics. Couples with these
"high-order" multiple pregnancies face the
troubling dilemma of proceeding despite the risk of
complications or considering a selective reduction, in
which doctors remove one or more embryo to give the
pregnancy a better chance of succeeding.
By lowering the incidence
of high-order multiples, the new approach should make
that dilemma much less likely to arise.
Using the enriched culture
medium, the Stanford team can now grow embryos in the lab
for five days instead of just three. By Day 5, the embryo
has reached a developmental milestone called the
blastocyst stage. This makes it much easier for
scientists to discern which embryos are the most viable,
Behr said.
With each of the first
seven patients, Behr and his colleagues were able to
select just two or three embryos for implantation. All
seven women became pregnant. As of early March,
ultrasound tests indicated that at least three of the
women were carrying only one child and two others were
carrying twins, Behr said. None has been found to have
triplets, he added.
"This is a case where
scientific research has led to direct benefits for
patients," said Behr, who carried out the lab
research on the new technique.
In addition to reducing
risky multiple births, the new technique theoretically
could improve IVF pregnancy rates by more closely
mimicking nature's timing. Day 5 is just the right
moment, physiologically speaking, for embryo transfer
because that's when implantation naturally occurs, Behr
explained. A three-day-old embryo, in contrast, is
transferred into the uterus at a time when it normally
would be traveling through a fallopian tube.
Timing could well make a
difference in IVF pregnancy rates, Behr said, because of
the constantly changing metabolic needs of the embryo, as
well as the changes taking place in a woman's
reproductive tract as the embryo passes through. Animal
studies conducted at other institutions have suggested
that embryos transferred on Day 5 are more in sync with
their environment and are more likely to implant, he
noted.
For now, however, that
advantage remains hypothetical in humans. "At the
very least," said Behr, "the new technique
should allow us to maintain the [existing IVF] pregnancy
rate while avoiding the high-order multiple
pregnancies."
Milki, who treats many of
the IVF patients at Stanford, said he believes the
technique's main advantage is that it enables scientists
to select embryos for implantation more carefully because
the least viable candidates can be identified by Day 5.
"The primary
demonstrated benefit is avoiding high-order multiple
births without sacrificing the success rates," Milki
said. "Is it possible it might increase the success
rate because it's more physiologic? That may be, but we
don't have the studies to prove that. Although the
initial data seem to suggest there might be a higher
pregnancy rate, it is important not to jump to
conclusions based on seven patients."
The first Stanford
patient, a 33-year-old woman living in San Jose, had
tried to get pregnant for three years. She was reluctant
to try traditional IVF, however, because she worried
about the risk of triplets or quads and could not accept
the idea of a selective reduction, she said. When Milki
raised the possibility of trying the new technique, she
agreed.
Milki transferred two
five-day-old embryos into her womb on Dec. 20. A week
later, she and her husband learned she was pregnant.
"I couldn't believe it," said the expectant
mother, who asked to remain anonymous. "I was so
excited. It's wonderful."
A month later, doctors
confirmed that she was carrying a single child.
The new technique was made
possible by a clearer understanding of the needs of the
embryo in the earliest stages of its development, said
Behr, who holds a PhD in reproductive biology and
specialized certification in embryology.
In the past, scientists
have been able to sustain embryos in the lab for five
days, but they had to use a culture medium containing
blood serum from other people as well as cells from cows,
monkeys, rats or other animals. These
"co-cultures," while effective in stimulating
embryo growth, are rarely used in the United States
because they carry a major risk of contamination and may,
in some cases, be toxic to the embryo, Behr said.
The development of safer
cultures began in the mid-1990s with work by Australian
researcher David Gardner, who examined the concentrations
of specific nutrients in the female reproductive tract to
learn about the environments that bathe the embryo as it
develops under natural conditions. Behr then built on
this work to develop his own lab cultures.
Initially, Behr nurtures
the embryo in a buffered salt solution containing a
single amino acid and other non-sugar energy sources.
Then, for the last few days before implantation, the
embryo grows in a rich solution of amino acids and sugar.
"We're setting up the
embryos to metabolize efficiently so they can make it to
the blastocyst stage before they poop out," Behr
said. "It's like giving people the right vitamin
supplements so they can run a marathon. We're giving them
the right nutrients so they can remain healthy to survive
to this stage." SR
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