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Ovarian transplant offers hopeInvalid word space value <br> Experimental technique gives women being treated for disease a new chance at having children

For young women, cancer is different.

Chemotherapy and radiation often leave them infertile. The prospect of a childless future and premature menopause is a devastating experience that can influence treatment decisions.

Now doctors are closing in on a way to help by removing a woman's ovaries and reimplanting them years later when she is healthy again.

Buffalo native Ann Dauer played a major role in the medical advance.

Her baby, due in the next few days, will mark the first successful birth after an ovarian tissue transplant in North America and only the second in the world. It also will be the first birth ever from an ovarian transplant grafted under a woman's skin.

For the 33-year-old Dauer, the birth brings to a happy end a long journey during which she endured contradictory diagnoses, months of cancer treatment and the uncertainty of whether she and her husband, Greg, would enjoy a family.

"I can't wait to meet this little girl," Dauer said in an interview late last week from her home in Canton, Ohio, where she now lives. "I feel as though she went through everything I did."

The experimental procedure could protect the ovaries of thousands of women and children who receive toxic treatments for cancer and other diseases, such as endometriosis. Longer term, if proven safe and effective, the technique may allow healthy women to delay childbirth until later in life.

A woman's eggs can be removed, fertilized and the embryos frozen for later use when there is time to undergo ovarian stimulation and egg retrieval.

But many women and children don't have enough time before therapy starts, or a potential sperm donor.

The procedure is considered promising, but experimental. It should be used in cancer patients and not be offered or marketed as a way to defer reproductive aging in healthy women, according to the American Society for Reproductive Medicine, which issued new guidelines last year on freezing eggs or ovarian tissue.

"Today, more women are aware of the consequences of treatment, and are freezing their ovarian tissue," said Dr. Kutluk Oktay, associate professor of reproductive medicine and obstetrics and gynecology at New York-Presbyterian Weill Cornell Medical Center. "In the next five to 10 years, those women will be coming back for their frozen tissue, and we'll see more demand for this procedure."

Hodgkin's lymphoma

Dauer was diagnosed with Hodgkin's lymphoma, a form of cancer, in early 2001, when she was a physical education teacher and coach at Williamsville North High School. A month later, while undergoing chemotherapy, her fiance, Greg, proposed and they set a wedding date for the spring of 2002.

"I told Greg that he could walk, move on, that he didn't sign up for this. He told me we were in it together," Dauer said.

Doctors here had talked optimistically about a recovery, but when Dauer was scanned for tumors in January 2002 with the expectation that none would be present, it was clear she was not in remission. Instead, the cancer seemed to be growing quickly.

Ann and Greg immediately changed their wedding plans and got married two days later in a small ceremony in Buffalo, allowing her to take advantage of his more comprehensive health insurance policy.

"One of the biggest lessons I learned is the importance of getting second and even third opinions. If I had not, I wouldn't be here," Dauer said.

By then, the couple was living in Detroit, where Greg, a plant manager for American Axle & Manufacturing, had been transferred. A week after the wedding, Dauer visited Memorial Sloan-Kettering Cancer Center in New York City, where physicians found that she suffered from a rare combination of Hodgkin's and non-Hodgkin's lymphomas.

The outlook wasn't great. There was a 25 percent chance of beating the condition, the doctors told Dauer. Moreover, the recommended treatment, a stem-cell transplant from cells harvested from her own bone marrow combined with chemotherapy, carried a 10 percent chance of death and would leave her unable to have children.

There was not enough time before treatment started for a standard egg retrieval. So she visited Oktay, who since 1999 had been removing women's ovaries in an attempt to preserve fertility in patients with cancer or other conditions.

Oktay had been able to fertilize previously frozen eggs in the patients, but none of them had achieved a viable pregnancy.

The main goal of cancer treatment is survival. But with medical advances improving survival rates, fertility has taken on greater importance.
A large survey published last year in the Journal of Clinical Oncology, for instance, found that young women facing breast cancer are concerned about preserving their ability to have children after treatment and that their concern is often overlooked by their doctors.

Dauer knew the feeling.

"The attitude of some of the doctors I met was that I was fighting for my life, so why should I care about my ovaries. But the oncologist at Sloan-Kettering was a mother. She understood," said Dauer.

A month after her second cancer diagnosis, in early 2002, Oktay removed one of her ovaries in a simple procedure. The ovary that contains the immature eggs is then separated from connective tissue and cut into dime-size pieces. The pieces are mixed with antifreeze substances, slowly frozen and stored in liquid nitrogen.

"Technology is amazing"

When needed, pieces are thawed and grafted back to their original place in the patient's pelvis or, with less discomfort and risk, grafted underneath the skin in the forearm or lower abdomen. In a few months, the transplanted pieces, which may contain hundreds of immature eggs, cause the woman's hormones to kick in, reversing menopause.

The biggest risk is the possibility that transplanted ovarian tissue harbors cancer cells, said Oktay.

Dauer went through her cancer treatment followed by two years of waiting to see if the tumors returned. Cancer-free, she asked Oktay to start slowly thawing the ovarian tissue, which he transplanted in August 2004 under the skin just below her belly button.

"The technology is amazing and the implications great when you think about medicine in the future," said Greg.

Eggs from the inserted tissue grew, and Dauer could feel them as they formed. The plan was to retrieve the eggs eventually and perform in vitro fertilization. But to Oktay's surprise, Dauer conceived naturally from the existing ovary that went through the chemotherapy and premature menopause.

Oktay said he believes the transplanted tissue "jump-started" the menopausal ovary.

The same thing may have occurred in the first frozen ovarian tissue transplant that led to a birth last year in a Belgium cancer patient. Oktay said it's impossible to know if that birth resulted from an egg that came from the mother's ovary or from the grafted tissue.

"What's happened in these cases opens up a new angle that must be explored," Oktay said. "If this idea of jump-starting the ovary is correct, it could make the procedure simpler. Perhaps you wouldn't have to preserve so many eggs."

Regardless, for the Dauers, the expected birth of a baby girl is the fulfillment of their dreams.

"We always stayed positive," she said. "We never gave up hope."


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