Advances Made for Infertile Women

Monday, June 26th 2000, 12:00 am
By: News On 6

BOLOGNA, Italy (AP) — Scientists have for the first time transplanted defrosted human ovarian tissue into a mouse, extracted eggs and made them potentially fertilizable — an advance that could allow women to delay motherhood or safely restore fertility to women who need to have their ovaries removed.

Scientists said the technique, which is to be presented Monday at a four-day conference of the European Society of Human Reproduction and Embryology, would be most effective if women freeze their ovarian tissue in their early 20s, because a woman's capacity to produce eggs diminishes with age.

``We have a very good option for men who are having chemotherapy — we freeze their sperm,'' said the project's leader, Dr. Ariel Revel, an Israeli doctor who is working at the University of Toronto. ``We don't have anything for women. This shows that this could be one of the ways.''

Revel's method uses animals to foster ovaries until the eggs are grown large enough to be extracted and stimulated to reach maturity in the lab.

In the past, scientists have grafted tissue into animals and detected small eggs, but this is the first group to obtain mature, potentially fertilizable eggs.

Another method used in experiments last year has also been considered a promising approach to restore fertility. Doctors were able to transplant the ovarian tissue of a 30-year-old woman back into her body to help her overcome the discomforts of premature menopause. She ovulated and had a normal menstrual period.

Scientists presented that method mainly as a way for women undergoing cancer treatment to regain their fertility after chemotherapy. But the ovarian tissue of women who have cancer can contain cancer cells. Mouse studies have shown that cancer can be transferred to mice when cancerous ovarian tissue is implanted in their bodies.

``The idea is to find a mechanism to resolve her fertility, using her own eggs, without transferring cancer back into her body,'' said Dr. John Yovich, director of the Pivet Medical Center in Perth, Australia, who was not connected to the research.

``Both of those channels are interesting,'' Yovich said. ``But the cross-species work is fraught with disaster on an ethical level. There's a risk of transferring mouse diseases to the woman.''

A method avoiding animals is preferable, Yovich said. But so far scientists have been unable to remove ovarian tissue and mature the eggs from start to finish in the lab, without using a surrogate body.

Revel acknowledged there is a concern about cross-species transplants, but said his method has ways to protect the egg from disease.

In a string of experiments, Revel's group removed ovarian tissue from two women in their 20s about to undergo surgery for endometriosis, a womb-linked pelvis disease.

Eight or 10 slivers of ovarian tissue the size of a fingertip were grafted onto the back muscles of mice that had been genetically engineered to have no immune system so that their bodies would not reject the human tissue.

The mice were injected with human fertility drugs to stimulate growth of ovarian follicles — the sacs that contain the eggs.

The follicles, and the eggs inside them, are at various stages of development. The larger eggs die from the shock of the transplant, but the smaller ones can survive and grow.

Within days, new blood vessels form and supply the graft with blood. The tissue was left in the mouse for about three months until the small follicles grew big enough to respond to the hormone injections.

The tissue was then removed from the mouse, the eggs extracted and brought to maturity in the lab.

One mouse that produced an egg, produced a second the following month from the same fragment of ovarian tissue.

``It's behaving just like a human ovary,'' Revel said.

Revel said the eggs look normal and he believes the chances that such an egg could produce life are high.

Simply extracting eggs from the body and freezing them has not proven very successful because they are damaged by the process. The approach also may not be practical.

Statistics presented at the conference indicate that while 60 percent of defrosted sperm is viable, there's a less than one percent chance that an egg would recover, which means 100 eggs would have to be frozen to achieve one pregnancy, Revel said.