CHILDREN conceived by an artificial fertilisation technique in which a sperm
is injected into an egg have higher rates of genetic abnormalities than children
conceived naturally. Now researchers say the technique itself, rather than
faulty sperm from infertile men, may be to blame.
The finding has emerged from the first studies of the technique, known as
intracytoplasmic sperm injection (ICSI), in primates other than humans.
“Ironically, the babies are the guinea pigs and the monkeys are the next step,”
says Gerald Schatten of the Oregon Health Sciences University in Portland, who
led the new investigation.
Worldwide, more than 20 000 children have been conceived with the help of
ICSI since 1992. The technique was first used for men whose sperm were unable to
fertilise an egg, but it is increasingly replacing conventional IVF even when
the sperm are healthy, as it guarantees fertilisation. Some large medical
centres already use it for more than half of all IVF procedures.
One study of ICSI children showed they have twice the incidence of birth
defects compared with children conceived naturally (This Week, 22 November 1997,
p 5). Such birth defects include missing or extra sex chromosomes. A possible
explanation for this is that many men who donated sperm would have been
infertile, and so more likely to have damaged sperm.
But now Schatten and his team have shown in tests using eggs and sperm from
rhesus monkeys that the technique itself might cause the damage. The team found
that ICSI can puncture the meiotic spindle, a net that surrounds chromosomes and
draws them to the proper place during cell division (Nature Medicine,
vol 5, p 431). Most fertility centres use a structure called the polar body to
work out where the spindle is so they can avoid hitting it, but Schatten found
the polar body can move around, suggesting it is not a reliable guide.
The study also showed that with ICSI, sperm retain packaging proteins and
protective coats that don’t normally enter the egg, and that cell division is
delayed because the sperm DNA remains too condensed. “The egg can sense that
`look, we’re not properly set up to continue with DNA synthesis’,” says
Schatten, who adds that no one knows if the delay poses any risk.
Experts in male fertility welcome Schatten’s work, although they say it only
confirms suspicions and is unlikely to affect the popularity of ICSI. Dolores
Lamb of Baylor College of Medicine in Houston, Texas, says she is not surprised
that sperm retain protective proteins, because the act of injecting a sperm
bypasses the processes in which the egg removes some proteins.
Gianpiero Palermo, a pioneer of ICSI at the Cornell Medical Center in New
York City, says that deviations from natural fertilisation need further
investigation. However, he says he has always assumed that ICSI would sometimes
hit the meiotic spindle surrounding chromosomes: “We weren’t so naive.”
Palermo argues that the high rate of chromosome abnormalities in ICSI
children could still be accounted for by abnormal sperm. “In the largest
centres, like ours, I think it’s pretty safe,” he says. Cornell Medical Center
plans to start a follow-up study of ICSI children in July.