The following article appeared in the Science / Health Section of theOctober 26, 1999 edition of the New York Times.



October 26, 1999

Experiment Seeks to Protect Ovaries From Cancer Treatment

Diagram Removed for Safekeeping


An experimental operation last Thursday that one doctor called "great work" but another called "preposterous," surgeons in Brooklyn removed a woman's ovaries, sliced them into thin strips and implanted them into her arm.

Andrea Mohin/The New York Times

Dr. Kutluk Oktay sliced a cervical-cancer patient's ovaries on Thursday as he prepared to implant them into her arm at New York Methodist Hospital in Brooklyn. The purpose of the experiment is to protect the ovaries from radiation and thus prevent premature menopause.

The patient, in her 30's, has cervical cancer, and the reason for the seemingly outlandish procedure was to protect her ovaries from the radiation treatment she will be getting. The radiation would very likely damage her ovaries and plunge her prematurely into menopause, bringing on the bone-thinning disorder osteoporosis and other problems caused by the sudden loss of estrogen. (Menopause can be forestalled by estrogen-replacement therapy, but the woman, who allowed a reporter and photographer to watch the operation only on the condition of anonymity, refused the pills in favor of the experimental surgery.)

Now, when her pelvis is irradiated, she will simply have to raise her arm over her head to keep the ovarian tissue out of the way. No one knows whether ovarian tissue can live in a person's arm, but the surgeon who devised the procedure, Dr. Kutluk Oktay of New York Methodist Hospital in Brooklyn, said he hoped the strips would survive and act like a normal ovary, producing enough estrogen to prevent menopause.

Although the patient in Brooklyn wanted the ovarian surgery to prevent menopause, Dr. Oktay said that if the method worked, the real goal was to use it to preserve fertility in young women hoping to have children after being treated for cancer. Eggs might be easily harvested from a patient's arm, he said, and used for in vitro fertilization, in which they would be fertilized in the laboratory and then implanted in the patient's uterus to start a pregnancy.

The research is part of a larger pattern of efforts to find ways to enable people to have families after being treated for cancer, particularly young people who have good odds of being cured of certain cancers like leukemia and bone tumors.

The approach is in a highly experimental field that has yet to make parents of anyone. Nonetheless, many patients have pinned their hopes on the research.

For young people with cancer, particularly those who have not yet had children, it can be devastating to learn that the chemotherapy and radiation given to save their lives will also leave them sterile. Taking steps to try to have children later may be the utmost expression of faith and hope.

But only men have been able to plan for a future, by having sperm frozen before undergoing radiation or chemotherapy. Women have not had a similar option.

Eggs, unlike sperm, do not survive freezing. Fertilized eggs do, but women with cancer may not be able to spend the time and take the hormones needed to stimulate the ovaries to produce the eggs needed for in vitro fertilization.

"For women who have not completed their families, being a parent is very, very important," said Dr. Lynn Hartmann, an oncologist at the Mayo Clinic in Rochester, Minn. "They may have a cancer with a good prognosis. To look for options for these women is very important."

One option under study is to remove an ovary, freeze it before cancer treatment and reimplant it later. The technique works in animals; mice and sheep have given birth after having frozen ovaries reimplanted.

Although some clinics have been experimentally freezing human ovaries, and at least one is selling the service, no woman has yet had a baby as a result.

But in September, Dr. Oktay and his colleagues announced that frozen ovarian tissue had begun working again after being reimplanted in the patient, a young woman whose ovaries had been removed at another hospital because of a noncancerous disorder. One of the ovaries turned out to be healthy and was cut into strips and frozen, and two years later, when the patient was 30, Dr. Oktay's team sewed the strips to a scaffold made of surgical foam, which they implanted in her abdomen.

A few months later, given hormones that made eggs mature, the woman ovulated and then had a menstrual period. Her case was the first on record in which frozen ovarian tissue began to function again. (She may be able to become pregnant, but would need in vitro fertilization, because her Fallopian tubes were removed.)

Dr. Oktay cautions that ovary freezing is unlikely to work for women over 30, because they have fewer eggs than younger women, and some eggs are lost in the processing. By the time the tissue is thawed, he said, there may not be enough healthy eggs left to achieve a pregnancy or to produce the hormones needed to keep menopause at bay.

That limitation on freezing for women in their 30's helped inspire him to try last week's operation. A standard procedure for sparing the woman's ovaries had been rejected: doctors sometimes surgically relocate the ovaries within the abdomen to get them out of the way of radiation. But in this case, the doctors did not think it would work.

So Dr. Katherine Economos removed the patient's ovaries, and Dr. Oktay sliced them into 16 thin strips that he and Dr. James Rucinski could slip under the skin of the arm. The strips would be better able than large segments to absorb nutrients from the nearby tissue and establish a blood supply.

The idea is not as farfetched as it may seem: a similar technique has been used successfully for about 20 years in operations on the parathyroid glands, which are sometimes transferred from the neck to the arm.

Still, no one knows whether it will work with ovaries. The woman will receive chemotherapy with the radiation, and the doctors could not be certain that the low doses given for cervical cancer would not harm the ovarian tissue. Higher doses given for other types of cancer do cause infertility.

The team estimated that it would take six months before they could tell whether the tissue was doing its job. Only one other woman has undergone the procedure, about six months ago, and Dr. Oktay said he still could not tell whether it had succeeded.

In any case, even if the strips do work, there is no telling how long they will last.

"We're taking a chance," Dr. Economos said.

Dr. Oktay said it might eventually be possible to combine the two techniques he has been studying. If the fresh tissue transplanted into his patients' arms works, he said it might also work to put frozen ovarian strips -- from a patient whose ovary had to be removed before chemotherapy, for instance -- back into the arm instead of the pelvis. The advantage, he said, is that it would be much easier to harvest eggs from the arm for in vitro fertilization. But women with intact Fallopian tubes might prefer to have the tissue put back into the abdomen, to give them a chance to become pregnant naturally, without in vitro fertilization.

Dr. James Grifo, director of reproductive endocrinology at New York University Medical Center, said that for now, ovary freezing and relocating should be performed only as research, as Dr. Oktay is doing, and not offered to patients as if they were a proven treatment.

Patients must be informed that no babies have been born as a result, Dr. Grifo emphasized, adding that publicity about the research had misled people into thinking that the procedures had already been shown to work. He said some women had mistakenly believed that they could postpone childbearing, freeze an ovary and get it back years or even decades later to start a family. There is no proof that can be done, and it may not be good for a woman to have a healthy ovary removed needlessly.

Implanting sliced ovaries in the arm is not as farfetched as it seems.

Cancer patients who will become sterile anyway have less to lose by giving up an ovary, but they also must be told that the procedure is highly experimental, Dr. Grifo said. He does not perform it or recommend it.

"I had a patient with breast cancer who wanted me to take out her ovary and freeze it," he said. "I said I couldn't do it. When I told her we don't know if you can make viable eggs, she just lost it. People don't want to hear the truth. The technology is not there.

"Why would I expose somebody to the risks of general anesthesia and surgery, and then freeze the ovaries by techniques nobody has shown you can get a viable egg from? Why would you have eggs taken out at a time when you're very sick, so on top of the disease you're going through an expensive, time-consuming, physically draining procedure?"

Dr. Maurie Markman, director of the Cleveland Clinic Cancer Center, called the ovary transplant into the patient's arm "preposterous," adding: "An operation on a lady with advanced cancer so she can have estrogen coming out of her arm, so she can avoid taking a pill? It's nuts." But he said that if effective techniques were developed to preserve women's fertility after cancer treatment, "I wouldn't have a problem with that."

Dr. Grifo said: "This is great work. It should continue. There's a lot of things we can learn by doing it."

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