'Forgotten' drug lets women have IVF without side-effects
HUNDREDS of infertile women could be spared the most distressing side effects of IVF by a drug regime too rarely used in Britain, a leading specialist said yesterday.
Newer fertility drugs that act quickly without triggering menopausal symptoms can be as effective as standard therapies but are offered by only one in twenty British clinics, according to Bill Ledger, Professor of Obstetrics and Gynaecology at the University of Sheffield.
Gonadotrophin-releasing hormone (GnRH) antagonists were developed in the 1990s and are used in 80 per cent of IVF cycles in Scandinavian countries. They halve the length of a cycle and avoid side effects of hormonal drugs such as hot flushes, night sweats, mood swings and insomnia.
They also significantly lower the risk of ovarian hyperstimulation syndrome, the most dangerous complication of IVF apart from multiple births.
Despite these advantages, GnRH antagonists are unpopular with British fertility doctors, who consider that they slightly reduce the chances of a successful pregnancy compared with traditional long-protocol IVF drugs. Professor Ledger said that many clinics were too frightened of falling in the success-rate league tables.
Early clinical trials of GnRH antagonists found that they produced an average of 1.0 to 2.3 fewer eggs and 0.2 to 0.5 fewer good-quality embryos in each cycle. Pregnancy rates were slightly lower, but not statistically significant. Professor Ledger said the studies took place before most doctors had experience of the new drugs.
Success rates in clinics that regularly use GnRH antagonists are now comparable to those using older drugs. The one trial that examined clinics experienced in the new regime had found no appreciable difference in pregnancy rates. “The uptake of these drugs has been slower because of the conservative nature of IVF in Britain,” he said. “Clinics are terrified of a drop of a few points in their success rates if they switch.”
IVF involves stimulating ovaries to over-produce eggs, so that a dozen or so can be harvested and fertilised at the same time. For this to happen, it is necessary first to stop the normal menstrual cycle using drugs that block the action of GnRH, traditionally done with a class called GnRH agonists.
These drugs stimulate a flare in hormone levels before they fall, and must be given for two to three weeks before the ovaries can be stimulated and egg collection can begin. This long period is responsible for the menopausal symptoms.
GnRH antagonists work differently, neutralising the hormone’s action completely so that the pituitary gland cannot respond. There is no hormone spike and a cycle is “downregulated” much more quickly.
This means that GnRH antagonists can be given six days after a woman has started taking drugs to stimulate her ovaries. Treatment continues only for the critical period in which downregulation is essential, about five days, and does not continue for long enough to cause side effects.
Newer fertility drugs that act quickly without triggering menopausal symptoms can be as effective as standard therapies but are offered by only one in twenty British clinics, according to Bill Ledger, Professor of Obstetrics and Gynaecology at the University of Sheffield.
Gonadotrophin-releasing hormone (GnRH) antagonists were developed in the 1990s and are used in 80 per cent of IVF cycles in Scandinavian countries. They halve the length of a cycle and avoid side effects of hormonal drugs such as hot flushes, night sweats, mood swings and insomnia.
They also significantly lower the risk of ovarian hyperstimulation syndrome, the most dangerous complication of IVF apart from multiple births.
Despite these advantages, GnRH antagonists are unpopular with British fertility doctors, who consider that they slightly reduce the chances of a successful pregnancy compared with traditional long-protocol IVF drugs. Professor Ledger said that many clinics were too frightened of falling in the success-rate league tables.
Early clinical trials of GnRH antagonists found that they produced an average of 1.0 to 2.3 fewer eggs and 0.2 to 0.5 fewer good-quality embryos in each cycle. Pregnancy rates were slightly lower, but not statistically significant. Professor Ledger said the studies took place before most doctors had experience of the new drugs.
Success rates in clinics that regularly use GnRH antagonists are now comparable to those using older drugs. The one trial that examined clinics experienced in the new regime had found no appreciable difference in pregnancy rates. “The uptake of these drugs has been slower because of the conservative nature of IVF in Britain,” he said. “Clinics are terrified of a drop of a few points in their success rates if they switch.”
IVF involves stimulating ovaries to over-produce eggs, so that a dozen or so can be harvested and fertilised at the same time. For this to happen, it is necessary first to stop the normal menstrual cycle using drugs that block the action of GnRH, traditionally done with a class called GnRH agonists.
These drugs stimulate a flare in hormone levels before they fall, and must be given for two to three weeks before the ovaries can be stimulated and egg collection can begin. This long period is responsible for the menopausal symptoms.
GnRH antagonists work differently, neutralising the hormone’s action completely so that the pituitary gland cannot respond. There is no hormone spike and a cycle is “downregulated” much more quickly.
This means that GnRH antagonists can be given six days after a woman has started taking drugs to stimulate her ovaries. Treatment continues only for the critical period in which downregulation is essential, about five days, and does not continue for long enough to cause side effects.
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