Ovarian Tissue Successfully Transplanted in Sisters

THURSDAY Aug. 2, 2007 -- For the first time, a woman whose ovaries were damaged by drug and radiation treatments has undergone a successful transplant of ovaries from her genetically non-identical sister, Belgian researchers report.

According to the report, the 2005 transplant restored ovarian function to Teresa Alvaro, now 35, and she started to menstruate. After a year, two oocytes (precursors to the ovum) were taken from the patient's ovaries and fertilized producing two embryos, according to the report in the Aug. 2 issue of Human Reproduction. Those embryos did not lead to successful pregnancies, however.

Nevertheless, the procedure does support the "restoration of ovarian function after transplantation of ovarian tissue from genetically un-identical sisters," said lead researcher Dr. Jacques Donnez, head of the department of gynecology and professor and chairman at the Catholic University of Louvain in Brussels.

Previously, other researchers had successfully transplanted ovarian tissue between genetically identical twin sisters.

The most important factor here is that it does not seem necessary to use powerful immunosuppressive therapy to maintain the transplant, Donnez said. Drugs typically used to suppress an immune response against the transplant can damage a growing embryo, he explained.

This method of restoring ovarian function might be used when a woman has undergone chemotherapy or radiation, which can destroy ovarian function, Donnez said. "Women can also have ovarian tissue frozen before undergoing treatment and transplanted back after the end of chemotherapy," he said.

But oncologists don't often propose this option, Donnez said.

Although the possibility of oocyte donation from her sister, Sandra Alvaro, was discussed, the patient refused this option, Donnez said. Teresa wanted the transplant, because she considered that having a baby of her own was more natural than egg donation, Donnez said.

Teresa Alvaro had lost ovarian function due to treatments she received to fight a rare blood disorder called beta-thalassemia. In 1990, when she was 20, she underwent bone marrow transplant to help cure the disorder, using marrow donated by Sandra, then 17 years of age. It was discovered that the sisters had an identical "human leukocyte antigen" (HLA) type -- meaning that Teresa's immune system would not reject her sister's marrow or other tissue as "foreign."

Donnez's team knew that because the sisters' HLA type allowed their genetically different cells to coexist successfully, there was no need for immunosuppressive treatment to prevent the ovarian transplant from being rejected.

After six months, Teresa Alvaro started menstrual bleeding. That, along with her hormone levels, confirmed that ovarian function had been restored. Her menstrual cycles have continued ever since, the researchers reported.

After a year, doctors took two oocytes from her ovary and fertilized them with her husband's sperm. One of the embryos developed to the two-cell stage and the other to the three-cell stage. However, both stopped developing, so they were not transferred to her uterus.

Why the embryos didn't develop is not clear, but this also happens during normal cycles of IVF, Donnez said. However, it's too early to know whether this procedure would ever be successful in letting a woman get pregnant and give birth to a live baby, he said.

"The first thing the gynecologist and oncologist need to think about before chemotherapy is to propose cryopreservation [freezing] of ovarian tissue before chemotherapy. That's the first option," Donnez said. "The second option is cryopreservation of embryos," he said. "But even when tissue isn't preserved, we have some hope that transplanting ovarian tissue will restore function."

Donnez hopes in the future that immunosuppressive drugs can be developed that will not be toxic to embryos, making ovarian tissue transplantation a wider option for women.

One expert is unsure about the practicality of ovarian transplantation.

"This is another step in ovarian transplantation," said Dr. Richard J. Paulson, a professor of obstetrics and gynecology and chief of the division of reproductive endocrinology and infertility at the University of Southern California Keck School of Medicine, Los Angeles.

Paulson is skeptical, however, that the technique is very practical. "Why on earth would you bother to do this, when you can clearly do egg donation from the one sister to the other," he said. "That would have had a higher success rate -- instead, they are goofing around with this transplantation of the ovarian cortex."

Posted: August 2007


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