Ovarian Tissue Transplantation Works Despite Genetic Differences

BRUSSELS, Belgium, Aug. 2 -- For the first time, ovarian tissue transplantation between nonidentical sisters has successfully restored fertility, which opens the door for transplantation between compatible, unrelated women.

The transplant of ovarian tissue between a 32-year-old Belgian woman and her 35-year-old sister who had premature ovarian failure restored menstruation and produced viable eggs, reported Jacques Donnez, M.D., Ph.D., of the Catholic University of Louvain here, and colleagues.

Importantly, the researchers noted in Human Reproduction, the women were HLA-indentical because of an earlier bone marrow transplant to the recipient.

"Our findings offer hope to young patients facing premature ovarian failure, who have not had the chance to cryopreserve their oocytes, embryos or ovarian cortex," Dr. Donnez said.

Furthermore, the procedure could theoretically be used between unrelated women if they were HLA compatible and had a prior bone marrow transplant to the recipient, he speculated.

The case report follows the group's pioneering work on autotransplantation of frozen ovarian tissue in 2004.

Since then, another group led by Sherman J. Silber, M.D., of the Infertility Center of St. Louis in St. Louis, Mo., advanced the field by reporting successful pregnancy after transplantation of fresh ovarian tissue between identical twin sisters. (See A First: Baby Born After Ovarian Transplant Restores Fertility)

It was this report in 2005 that led the transplant recipient, Teresa Alvaro, to Dr. Donnez.

In 1990, she had undergone chemotherapy and radiotherapy for a bone marrow transplant from her sister Sandra Alvaro to treat the inherited blood disorder b-thalassemia.

At that time no procedures were available to preserve fertility. Teresa Alvaro stopped menstruating during treatment, with complete ovarian failure confirmed early in 2005.

"A few months later I happened to read an article on an American woman who got pregnant after she had ovarian tissue transplanted from her twin sister," she said in a prepared statement. "I didn't hesitate for a second and went to see Prof. Donnez together with my sister."

Dr. Donnez discussed egg donation with Teresa Alvaro, but she refused this option and requested a graft. Furthermore, "her sister expressly asked to be the tissue donor and refused to undergo ovarian stimulation for oocyte donation," he noted.

HLA group analysis showed complete compatibility between the two women, "proving that no immunosuppressive treatment would be necessary," the researchers wrote.

So, in February 2006, the two were anesthetized and underwent laparoscopic surgery together.

Three small sections of ovarian tissue were removed from Sandra Alvaro and immediately sutured to one of her sister's atrophied ovaries. Both women were discharged from the hospital the next day.

Seven months later, Teresa Alvaro resumed menstruation and vaginal echography revealed a follicular structure in the graft, confirming restoration of ovarian function.

At one year, doctors retrieved two mature eggs from her and fertilized them with her husband's sperm using intracytoplasmic sperm injection because of his low sperm count.

By 24 hours, one of the embryos had developed to the two-cell stage and the other to the three-cell stage. But they did not develop further and so were not transferred to her uterus, the investigators wrote.

Two further stimulation cycles failed to yield an egg, but Teresa Alvaro was still satisfied.

"The operation was a success," she said. "I can get pregnant the natural way. That's something I could never have hoped for a couple of years ago."

Dr. Donnez noted that failure of embryos to develop also occurs during normal cycles of in vitro fertilization and that the patient was planning further attempts.

He and his colleagues concluded, "these promising results should encourage continued efforts to preserve fertility in patients having to undergo chemotherapy and/or radiotherapy."

But, Dr. Silber commented that these efforts are already moving ahead.

He said his group have already performed one similar transplant between genetically distinct sisters and has another three scheduled, with publication planned at that point.

However, he noted, it may be 20 to 30 years before the field reaches the point where compatible unrelated women could provide donor tissue.

"That's going to take further advances in immunosuppression," Dr. Silber said.

Although kidney transplant survivors have given birth safely while on mild immunosuppression, "to be able to get away with mild immunosuppression, you have to have a good match," he said, noting that only a quarter of sisters are good HLA matches.

For now, "I think it's going to be a tremendous alternative for a very small number of patients that have premature ovarian failure," he said, adding, "It's simple enough that many surgeons around the world can do it."