An Oregon research team delivers a monkey from an egg drawn from ovarian material

03/11/04

Oregon scientists have harvested an egg from bits of ovarian tissue planted in a monkey's belly, fertilized it and -- with help from a surrogate monkey mother -- delivered Brenda, a healthy baby rhesus macaque.

The feat proves that primates' eggs can survive "ovarian tissue transplant," a procedure designed to maintain fertility in females whose ovaries are damaged by diseases or medical treatments, such as chemotherapy. Such health concerns leave several hundred thousand women infertile each year.

Brenda's birth at Oregon National Primate Research Center is reported today in the journal Nature. On Tuesday, a New York doctor reported fertilizing an egg from an ovarian tissue transplant in a woman who had breast cancer. Although no pregnancy resulted, doctors expect a human success soon.

"I think it's feasible that we'll have a live birth from frozen ovarian tissue within a year or two," said Dr. David Lee, one of the Oregon Health & Science University researchers who helped produce Brenda. "I think the two (studies) together show we're getting a lot closer."

Ovarian tissue transplant has produced baby eggs and sheep before, but Brenda's birth last March marks the first success in a primate, Lee said.

"It brings an air of optimism to have a life. . . in something so close to humans," Lee said.

The news may offer hope to many women who now face premature menopause from diseases, such as ovarian cancer; or treatments, such as radiation or chemotherapy. Ovarian tissue transplant could let those women have a child with the mother's normal genetic contribution -- 23 chromosomes from a mature egg.

The procedure is not cloning, in which an embryo gets a full set of 46 chromosomes from one parent. Instead, eggs from a tissue transplant are fertilized in a lab with sperm, contributing 23 different chromosomes from the father. Doctors can implant resulting embryos into the mother's uterus, if it is not damaged, or use a surrogate mother.

Women with fertility-threatening illnesses now can try to create and freeze embryos through in-vitro fertilization before their disease treatment. But that is time-consuming and impossible when serious diseases need fast treatment. Some doctors try to harvest and freeze eggs before disease treatment. But that also takes weeks and has limited success. Moreover, young girls can't consider those procedures.

In theory, transplanting ovarian tissue avoids some of those problems: Doctors would remove one ovary, in a relatively simple and quick surgery, before treating the disease. The woman would keep her other ovary, in case it survives treatment. Young girls, theoretically, could have ovarian tissue frozen until they are ready to bear children.

But the still-experimental procedure has risks, said Dr. Kutluk Oktay, the Cornell University researcher who reported the human embryo. Doctors must be careful that transplanted tissue is free of disease, if the woman had cancer. And egg cells can be damaged during processing and transplantation.

Oktay said he created two human embryos, but one was abnormal and did not grow beyond the three-cell stage. The second embryo seemed genetically healthy, and he does not know why it failed to take hold. Oktay said he could not rule out problems with the embryo, but noted that fewer than 20 percent of pregnancies succeed when doctors implant just one embryo fertilized in a lab dish.

"The simple answer is it was just a matter of odds," he said.

Seven monkeys used

In Oregon, Lee and coworkers took ovaries from seven rhesus monkeys. They cut tiny slices of the outer layer, or cortex, which contains thousands of "primordial follicles" -- immature eggs surrounded by supporting cells. They then put the slices back into the monkeys' arms and bellies.

The doctors cut the tissue thin to help it absorb nutrients and oxygen from its surroundings, until the body grows new blood vessels to feed the transplant, Lee said. The small slices also help doctors infuse a protective fluid through the tissue, which is required if they need to freeze the slices. Freezing is important in women, such as Oktay's patient, who face whole-body chemotherapy. Women who only face damage to their reproductive organs could have ovarian slices transplanted into other body parts without freezing, as happened with Brenda's mother.

When doctors transplant tissue slices back into the body, blood vessels grow to feed them within months. At the same time, the ovarian tissue's supporting cells start pushing immature eggs to mature -- a process doctors can aid with drugs.

Doctors know the transplant has progressed when they see renewed cycles of sex hormones. Oktay's patient had a more dramatic sign: She could feel a pea-sized lump in her abdomen as the follicle developed.

Lee said the Oregon researchers actually fertilized two eggs, both taken from a slice of ovary in a monkey's abdomen. Only one grew inside the surrogate monkey's womb into a viable baby.

Having succeeded with Brenda, Lee said, OHSU researchers are now trying to create a baby monkey with eggs from transplanted ovarian tissue that has been frozen.

On the human end, Oktay and other doctors continue to work with women worldwide, including Oktay's breast cancer survivor.

"The final test," Oktay said, "is a viable pregnancy and a live baby."