Medical treatments such as chemotherapy, radiation and surgery cause premature menopause and infertility in hundreds of thousands of women each year. Prof. Kutluk Oktay, obstetrics and gynecology, at Weill Cornell Medical College, published a study in a prestigious medical journal, The Lancet, on March 13, which has created hope that this side effect may be reversible.
Oktay reported that his group of physician-scientists from the Center for Reproductive Medicine and Infertility at the New York-Presbyterian Hospital/Weill Cornell Medical Center is the first in medical history to successfully create a human embryo from frozen and transplanted ovarian tissue.
According to Dr. Zev Rosenwaks, co-author of the study and the director of the CRMI, this success creates the possibility that women and children might have their ovaries removed and frozen before undergoing medical treatments that would destroy the organs. The frozen tissue might — even years after surgery — be used to reverse menopause and restore fertility after completion of the ovary-damaging treatment.
The Lancet paper states that the ovarian tissue used in this study was taken from a thirty-year-old woman before she underwent chemotherapy for breast cancer. It was thawed out six years later, after she had recovered from her cancer. Fifteen pieces of the tissue were then implanted under the skin of her abdomen.
Within three months of transplantation, the tissue began to function, creating ovarian hormones and eggs. The eggs were harvested every month and fertilized in-vitro. Over a period of eight months, 20 eggs were collected, and eight determined to be of sufficient quality for fertilization, the study reported.
Of these eight eggs, the researchers were able to fertilize two; one of these two developed normally to the four-celled embryo stage. This embryo was placed into the patient’s uterus, but did not result in a pregnancy. Oktay said that “the chances of pregnancy with a single embryo are limited, probably less than ten percent, so we’re going to keep trying.”
Eggs obtained from frozen and transplanted ovarian tissue have created successful pregnancies in animal models, including sheep and rodents, Oktay said. Also promising is the fact that the procedure was not seen to increase the rate of birth defects in these animals.
Oktay said that “with each cycle [of egg collection] we refined the procedure” for harvesting the eggs. Thus, the rates at which eggs suitable for in-vitro fertilization can be obtained and fertilized to produce normal embryos are uncertain.
The Lancet study states that the low success rate for fertilization may be due to differences in the temperature of and blood supply to the ovarian tissue when located under the skin, rather than in its normal pelvic region.
Oktay said that he and his team “think [they] need to collect [the eggs] early and [allow them to] mature in-vitro.” Although “success rates are likely to be somewhat lower” than for normal in-vitro fertilization, he projected that viable eggs might be obtained and successfully fertilized at about one third the rate seen with normal in-vitro fertilization.
Although it has not yet resulted in a pregnancy, Oktay said, the freezing of the ovaries for later transplantation is currently an available option for patients about to undergo ovary-damaging treatments for diseases such as cancer, lupus, anemia or several types of hematologic and bone diseases.
This procedure is currently performed only in efforts to preserve fertility but, once a successful pregnancy has been achieved, Oktay said, future studies may attempt to determine the safety and efficacy of the technique in delaying menopause and aging in patients whose ovaries are threatened only by age.
The next steps in his research, Oktay said, are to produce the first baby from an egg obtained from frozen ovarian tissue, to evaluate the healthiness of such children, and determine the long-term safety of the procedure for the women in whom the ovarian tissue is implanted.
Dr. Erkan Buyuk, Dr. Lucinda Veeck, Dr. Nikica Zaninovic, Dr. Kangpu Xu, Dr. Takumi Takeuchi, and Dr. Michael Opsahl co-authored The Lancet publication with Oktay and Rosenwaks.
Archived article by Marianne Spatz