A Belgian woman who had pieces of her ovaries surgically removed and frozen seven years ago, before cancer chemotherapy left her sterilized, gave birth yesterday to a healthy baby after doctors transplanted the ovarian tissue back into her abdomen, researchers reported.
The birth -- the first from frozen ovarian tissue, her doctors said -- suggests that many of the thousands of girls and women who each year are made infertile by cancer treatments may soon be able to preserve the option of having children later.
If the procedure proves safe, doctors said, it could even become an attractive possibility for women who are healthy but want to delay childbearing a decade or two.
Immature eggs, which lay nestled in girls' ovaries from birth, age throughout life but are not thought to age while frozen. And because the major impediment to fertility in older women is the age of the eggs, rather than the womb, women in their forties, fifties or older may be able to become pregnant by having preserved ovarian tissue reimplanted after decades in the freezer.
"It's quite exceptional," said Wulf Utian, a gynecologist and executive director of the North American Menopause Society in suburban Cleveland. "This woman has essentially been restored to a normal reproductive state after having been made temporarily menopausal by chemotherapy."
Utian and others warned that despite evidence to the contrary, there remains a small chance that one of the woman's chemotherapy-damaged ovaries may have recovered sufficiently to have given rise to the pregnancy.
That lingering doubt -- along with many uncertainties about the procedure's safety for women and for their babies -- mean the technique should still be considered experimental, experts said.
Several previous efforts to achieve pregnancy from thawed ovarian tissue failed -- in some cases, probably because of an inadequate blood supply after being put back in the body.
In some cases, the bits of tissue, each of which can contain hundreds of immature eggs, have been transplanted to novel locations -- including, in at least one case, under the skin of a woman's forearm. That approach made it easy to tell when the woman was ovulating -- a tiny bump would appear under her skin -- and the egg could be removed with a needle for fertilization in a lab dish with her husband's sperm.
The events leading to yesterday's delivery of an eight-pound girl to a 32-year-old Belgian cancer survivor began seven years ago when the woman -- who was identified by news services as Ouarda Touirat -- had Hodgkin's lymphoma diagnosed. The treatment usually destroys the ovaries' reproductive potential.
Before the woman was treated, Jacques Donnez and colleagues at Catholic University of Louvain in Brussels took five samples, each about a quarter of an inch wide and half an inch long, from her left ovary. Four of those were chopped into a total of 70 tiny cubes of tissue, each about one-sixteenth of an inch square. The cubes and the single strip were then frozen in liquid nitrogen.
The woman received six months of chemotherapy and radiation treatments, after which tests indicated her ovaries had stopped functioning.
Early last year, the woman decided she wanted to have a child, so the surgeons transplanted the one tissue strip and all of the cubes into a small furrow they created in the woman's pelvic space, close to her right ovary. Five months later, tests indicated those tissues were producing hormones, and she started having menstrual cycles. After another five months, she became pregnant without technical intervention.
Kutluk Oktay, a reproductive endocrinologist at Cornell University's Weill Medical College in New York, who has pioneered the use of frozen ovarian tissue, said he was concerned about the lack of definitive proof that the egg that led to the pregnancy came from transplanted tissue. But he said he was "cautiously optimistic" that the experiment was successful.
Tests during the years after the woman's cancer treatment hinted that her left ovary might have produced eggs as many as three times. But ultrasound images indicated that the pregnancy occurred after a mature egg erupted on the woman's right side, where the transplanted tissues were. By contrast, there was no sign of egg production in either ovary during the cycle leading to the pregnancy -- "crucial" evidence, the doctors reported, that the child was conceived from an egg that matured within one of the transplanted tissues.
That egg would then travel down a fallopian tube and be fertilized during sex.
"Our findings open new perspectives for young cancer patients facing premature ovarian failure," the team wrote in today's online version of the British medical journal the Lancet, which posted the report within hours of the girl's birth.
Although the baby appears healthy, no one knows how freezing affects immature eggs. R. Alta Charo, an associate dean of law and a bioethicist at the University of Wisconsin at Madison, said experiments such as the Belgian one need special scrutiny, because "the risks are carried not just by the patient but also by the next generation."