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Thursday, September 23, 1999
Scientists reverse menopause
Woman made fertile again: Groundbreaking ovary graft to be reported next
week in Toronto
Roger Highfield
The Daily Telegraph
Scientists have reversed menopause for the first time, in a treatment that raises the
prospect of ovary banks being established to extend female fertility into old age.
Ovary grafts could be used to treat sterility caused by premature menopause, protect
fertility in those undergoing cancer treatment, delay menopause so that elderly women
could conceive, and perhaps even help to ameliorate the effects of ageing.
An Anglo-American team has carried out the first successful ovary graft, a new kind of
transplant that promises to have a more profound effect on human fertility. The operation
that paved the way to these developments, carried out on a 30-year-old American woman,
will be reported next week in Toronto by the leading figure in the field, Roger Gosden of
Leeds University in England, at the annual meeting of the American Society for
Reproductive Medicine.
''This is proof of the principle that ovary grafts could be used to rescue fertility.
There is no reason why ovaries could not be stored for decades,'' said Prof. Gosden, 51,
who will move next month to Montreal's Royal Victoria Hospital, which is affiliated with
McGill University.
After a graft, ''there is a good prospect the ovary would continue to function
long after the menopausal age.''
Prof. Gosden is set to move to Canada after becoming disillusioned at the backlash against
biotechnology that has broken out in Britain. ''With all the fuss over GM [genetically
modified] food and so on, it is difficult to be a scientist in Britain,'' he said.
The ovaries are almond-shaped glands within which the female sex hormones oestrogen and
progesterone are produced and which contain cavities, called follicles, in which eggs
develop. Ovary grafts have a number of medical uses, but the longer-term applications will
rekindle ethical debate of the kind that greeted the news six years ago that women in
their 50s and 60s had become pregnant after egg donation.
The ability to use grafts to restore the fertility of middle-aged or even elderly women
will raise the question of exactly when is a woman too old to bear children. The children
would be brought up by people of grandparent age, and face being orphaned early. As well,
the women are at greater medical risk.
The work also raises more extraordinary, and speculative, possibilities: The use of
ovarian tissue from an aborted foetus could restore the fertility of an elderly woman,
though any children she bore would have the foetus as their biological mother.
Prof. Gosden masterminded the ovary graft operation, but it was carried out last February
at New York Methodist Hospital by Dr. Kutluk Oktay, who had worked with him in Leeds.
The patient, Margaret Lloyd-Hart, had an ovary cryogenically preserved after it had been
surgically removed in May, 1998, in Arizona to treat a benign medical condition. It was
the patient's only ovary; the first was excised when she was 17 years old because of a
cyst.
For the transplant, Dr. Oktay thawed 60 of the 72 segments of the frozen ovarian tissue,
washed them in special solutions and stitched them together to form a chain of tissue, a
process that took four hours.
Dr. Oktay transplanted the tissue into the patient's pelvic wall, close to the ovary's
original location.
The surgery was done laparoscopically, using tiny instruments to avoid a large incision.
Recently, the reconstructed ovary was stimulated with hormones and persuaded to produce an
egg. This marks a medical milestone as it is the first time that a sterile, surgically
menopausal woman has had her fertility restored. Egg production is ''a good sign.''
''It has kicked in earlier than we thought, and the blood supply is looking excellent,''
said Ms. Lloyd-Hart, a Middle-Eastern dancer. There is a fair chance that ovulation and
the menstrual cycle will return. ''Whether she will benefit long-term remains to be
seen,'' said Prof. Gosden.
Not all of the segments of tissue were used, so that if the transplant does not take, or
declines in activity, surgeons can attempt the procedure again. ''Ovarian tissue banking
and transplantation will find many more applications in the future,'' said Dr. Oktay.
The hope is that one day ovarian tissue from women suffering cancers, such as Hodgkin's
disease or leukaemia, will be routinely removed before chemotherapy or radiotherapy. The
"rind" of the ovaries, the cortex containing the eggs, would be frozen, and then
replaced some time -- even years -- afterward.
Hundreds of cancer patients have had ovarian tissue banked. However, none has had ovarian
tissue re-implanted, so the operation marks an encouraging sign that this effort will one
day be successful. ''With this technology, women who need chemotherapy or radiation
therapy for cancer treatment and want to preserve their fertility will be able to bank
their ovarian tissue and have it transplanted when their cancer treatment is
complete," said Dr. Oktay.
''It will also enable patients to prolong their reproductive life span, as banked ovarian
tissue does not 'age.' "
Ovary grafts may even help arrest aging. Hormone replacement therapy for women has become
part of mainstream medical practice, preserving healthy arteries and bones. Another
possibility would be ovary transplants from another donor. ''I
have already encountered the case of an overseas woman doctor who had a child born with
Turner's syndrome, which causes sterility,'' said Prof. Gosden. ''The mother now hopes to
store part of her own ovary so that the daughter might one day have the option of becoming
pregnant with her mother's eggs.''
Transplants could raise another extraordinary possibility: the transplant of ovarian
tissue from an aborted foetus to restore female fertility. Foetal ovaries are the best
source of foreign tissue because the older the donor, the fewer the eggs, and because
there may be fewer rejection problems because foetal tissue is better tolerated. Such a
transplant could benefit women who had not stored their own tissue. However, a woman who
had received foetal tissue would not have children who were genetically her own: they
would be a result of the combination of genes from the father and
the aborted foetus.
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