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Nine months ago, he said he could turn back her biological clock. Now time is running out

Steve Connor
Monday 08 November 1999 00:02 GMT
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MARGARET LLOYD-HART was not alone when she flew to New York in February for a pioneering transplant operation. On the next seat was a canister containing her ovary, deep frozen since she had it removed the previous year.

It was the second time Mrs Lloyd-Hart, then 29, had lost an ovary - the first was at the age of 17 following an ovarian cyst - and now she wanted the second one put back.

The surgically-induced menopause she suffered and the hormone replacement therapy (HRT) needed to cope with her mood swings were not compatible with her career as a dancer. She longed to have regular menstrual cycles.

If the operation succeeded it would represent the start of a revolution for women. Not only would it pave the way to curing premature menopause, it would raise the possibility of new fertility treatments for cancer patients and delaying or reversing the menopause in older women.

A successful operation would also raise the prospect of young professional women "banking" their ovaries in early life so they could have them returned years later after establishing their careers. This would keep their eggs more youthful and increase the chances of having babies in middle age.

Mrs Lloyd-Hart's surgeon, Kutluk Oktay, director of reproductive endocrinology and infertility at the New York Methodist Hospital, began preparations at 7am on 18 February by carefully stitching together 60 of the 72 segments of ovary tissue in the canister.

Over the following four hours he sewed a chain of tissue, which he then inserted through the pelvic wall using a "keyhole" laparoscope to avoid a large incision and so improve recovery time.

A statement released by the hospital four days later said that, while the transplant had gone smoothly, it would be between six and nine months before Dr Oktay could determine whether the ovarian tissue was fully functional and producing hormones.

"Ovarian tissue banking and transplantation will find many more applications in the future," Dr Oktay said in February when the details of the operation were released.

"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," he said.

"It will also enable patients to prolong their reproductive life span, as banked ovarian tissue does not age."

In September the story was splashed across the front pages of the newspapers. The headlines read: "The menopause is reversed" and "How to beat the biological clock". It was claimed that women as old as 70 would be able to have babies in the "medical revolution".

With the November date set for proof of success now approaching, it seems that the experiment has been only partial effective for Mrs Lloyd-Hart, who continues to have HRT and cannot ovulate without the aid of drugs.

Ultrasound scans have shown that her replaced ovarian tissue does develop follicles - the fluid-filled cavities in which eggs develop - but they do not mature to bursting point, when the egg and hormones are released.

"She is actually making follicles on her own - in other words, she continues to develop eggs in that ovary. The graft seems to be functioning," Dr Oktay said.

"It is still not completely satisfactory to her for her hormonal symptoms. However, the graft in a way is fertile in that if she wanted to have a pregnancy, we could achieve one," he said.

Earlier this year, after treatment with drugs, the doctors managed to achieve a successful ovulation, but this has not happened naturally, which Dr Oktay puts down to Mrs Lloyd-Hart's intensive exercise regime, which is known to disrupt menstrual cycles of athletes and dancers.

"The ovary is producing hormones, it is producing an egg, but up to now it is not producing the level of hormones that she personally would like to have, so that is why she is supplementing herself," Dr Oktay said.

"As far as I'm concerned the ovary is functional and we could get a pregnancy out of this if she wanted, but it's not want she wants."

The work was the culmination of a series of earlier experiments conducted on animals. Dr Oktay had worked at Leeds University with Professor Roger Gosden, now at McGill University in Montreal, who had successfully transplanted an ovary into a sheep that had gone on to become pregnant.

Mrs Lloyd-Hart had read about the animal experiments on the Internet, and she asked Professor Gosden for his advice. He referred her to Dr Oktay, who was making a name for himself as an authority on reproductive medicine at the New York Methodist Hospital in Brooklyn.

During his time at Leeds, Dr Oktay had successfully transferred human ovarian tissue into laboratory mice and got them to develop mature human eggs.

Mrs Lloyd-Hart said she decided to have her ovary cryogenically frozen and stored because of the possibility that one day she might want to have children. "If it was possible not to burn a bridge, then I would rather not," she said. "This was my last ovary, and I did not like the idea of just throwing it away."

Dr Oktay said that he still intended to go ahead with further ovary transplants despite the disappointments suffered by Mrs Lloyd-Hart.

He has already identified a handful of young women between the ages of 18 and 20 who will undergo cancer treatment and who want to have their ovaries stored for the future. "I think these would be the right patients to judge this procedure by," Dr Oktay said.

HORMONE LOSS: THE MENOPAUSE

THE MENOPAUSE occurs in most women between the ages of 45 and 50 and is defined as the time of life when the regular menstrual cycle stops. Although a perfectly natural phenomenon, the menopause can result in unpleasant side effects and a significant increase in health risks.

Every woman is born with her quota of immature egg cells, some of which will develop each month to be released from the ovary during ovulation. This monthly maturation process is associated with a cyclical release of the two main female hormones, oestrogen and progesterone.

The menopause occurs when the quota of eggs runs out and the production of oestrogen and progesterone falls dramatically. Other organs of a post- menopausal woman produce only about 10 per cent of the oestrogen herovaries made before the change.

As a result of these hormonal changes, many women experience quite severe side-effects during the menopause. Sudden sensations of intense heat can spread from the chest and face and can last for several minutes. After an initial outbreak of sweating, women can feel chilled, and the episode can cause palpitations and general anxiety as well as loss of sleep. Falls in oestrogen also cause a thinning of the vaginal tissues, making sexual intercourse painful, as well as increasing the risk of developing osteoporosis - bone thinning - and heart disease.

Many women have found that hormone replacement therapy (HRT) can significantly improve the symptoms as well as decreasing the risk of more long-term problems, such as the bone wasting typical in older, post-menopausal women.

STEVE CONNOR

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