Birth of a healthy monkey following ovarian tissue transplant may lead to new methods for preserving fertility in cancer survivors
Scientists at Oregon Health & Science University have significantly advanced a procedure aimed at preserving fertility in female cancer survivors. The research has resulted in the first successful birth of a primate following a procedure called ovarian tissue transplant. The female rhesus monkey was born at the OHSU Oregon National Primate Research Center. Details of this breakthrough are printed in the March 11, 2004, edition of the journal Nature.
"With some of the most successful but aggressive cancer treatments, such as chemotherapy or radiation therapy, up to 90 percent of women prematurely lose the ability to have children," said David Lee, M.D., assistant professor of obstetrics and gynecology, reproductive endocrinology and infertility in the OHSU School of Medicine. Lee is also an assistant professor of pediatrics at the school and first author of the Nature paper. "We believe this breakthrough may be a major step in preserving fertility for young cancer survivors. In the future this procedure could allow a significant number of these cancer survivors to conceive and have healthy children."
Lee collaborated on this research with Don Wolf, Ph.D., a scientist at the ONPRC. Wolf also is a professor of obstetrics and gynecology, and physiology/pharmacology in the OHSU School of Medicine.
To simulate the loss of fertility and the hormone production changes in women battling cancer, the scientists laparoscopically removed the ovaries of seven anesthetized female monkeys. Researchers then transplanted some of each monkeys' own ovarian tissue back into the now infertile animals. The tissue was implanted in the arm, abdomen or kidney. Four monkeys had transplants to both the arm and abdomen, two to the kidney and abdomen, and one to the arm only. The research team then monitored hormone production in the animals and the development of follicles, cavities in the ovarian tissue where eggs (ova) develop.
"What we witnessed in a matter of months was the resumption of hormone cycles very similar to normal fertile animals," explained Wolf. "In addition, some of the monkeys began producing eggs. We then fertilized some of the eggs through intracytoplasmic sperm injection and implanted the resulting embryos in surrogate monkey mothers. Following the normal five-month monkey gestation period, a healthy female infant was born."
The animal's name is BRENDA. Her name stands for Bilateral oophorectomy and Resumption of ENDocrine function with Abdominal follicles and pregnancy.
Previous studies using different methods resulted in hormone production in monkeys. However, until now, no sterile monkey undergoing ovarian tissue transplant has produced fertilizable eggs or offspring.
The oocyte was retrieved seven months after tissue grafting," explained Richard Yeoman, Ph.D., an embryologist at the ONPRC. "Oocyte maturation from the earliest stage normally takes three to four months in humans and monkeys; therefore, this follicle grew and developed entirely after transplantation which is impressive considering the quality of the embryo and the healthy infant."
The researchers suggest that in the case of human treatment, one ovary might be removed at the time cancer is diagnosed in a patient. The ovarian tissue would be frozen and then implanted after the patient was cured of cancer. It is hoped that this tissue would result in normal hormone production and the return of egg production for the patient.
"Once perfected, this procedure would be especially valuable for women battling cancer early in life," added Lee. "The next step is to attempt this procedure using frozen ovarian tissue, mimicking the same conditions required in the case of a cancer patient hoping to re-establish fertility where the patient may wait months to years before attempting to become pregnant."
Additional OHSU scientists involved in this research include: David Battaglia, Ph.D., Richard Stouffer, Ph.D., Mary Zelinski-Wooten, Ph.D., and John Fanton, D.V.M.
The National Institutes of Health, the OHSU Foundation, Doernbecher Children's Hospital Foundation, the Autzen Foundation and the American College of Obstetrics and Gynecology in conjunction with the Solvay Corporation funded this research.
The ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International.
OHSU includes the schools of dentistry, medicine, nursing and science and engineering; OHSU Hospital and Doernbecher Children's Hospital; numerous primary care and specialty clinics; multiple research institutes; and several outreach and community service units.