Jones Institute study seeks to preserve fertility in young cancer patients

Each year, 50,000 women in the United States under the age of 40 are diagnosed with cancer. One in 1,000 girls will be diagnosed with and survive childhood cancer.
For these young cancer patients, the very treatment that is often the best hope to save their lives can also rob them of their dreams to one day have children. Chemotherapy and radiation cause premature ovarian failure in a significant proportion of these women. Bone marrow or stem cell transplants -- combined with other adjuvant treatments that are used in many forms of pediatric cancer -- cause a loss of ovarian reserve in 95 percent of patients.

A new study underway at the EVMS Jones Institute for Reproductive Medicine seeks to give these women and girls a chance to become pregnant by removing and freezing ovarian tissue prior to their cancer treatment and then replacing it when the patient is ready to have children. The study also offers options for women whose fertility has been compromised by other conditions, such as endometriosis or removal of an ovary for a benign cyst.

“This is a chance to preserve fertility in patients who have had very limited options before,” said Laurel Stadtmauer, M.D., Ph.D., associate professor of obstetrics and gynecology and principal investigator of the study.

Freezing and transplanting ovarian tissue is still a mostly experimental procedure. So far, only three women in the world have given birth as a result. At the Jones Institute, researchers transplanted ovarian tissue that resulted in ovulation in primates as early as 1998.

Researchers at the Jones Institute are also studying the freezing of unfertilized eggs, which is a challenge because eggs do not freeze as well as ovarian tissue or as fertilized eggs, which are routinely frozen as part of in vitro fertilization. Eggs are more susceptible to damage during freezing and thawing, such as a hardening of the protective casing that inhibits sperm penetration.

There are advantages to freezing ovarian tissue because it does not require pretreatment with fertility medication, and young cancer patients who need to start chemotherapy right away do not have time to wait for the fertility drugs to work, according to Stadtmauer. Both techniques -- ovarian tissue freezing and egg freezing -- are more practical for young girls or single patients because they do not require sperm prior to freezing.
Another benefit to using ovarian tissue is that the transplanted ovaries will produce hormones, which inhibit menopausal symptoms in young patients with premature ovarian failure.

Stadtmauer is educating local oncologists about the study so they can inform patients who are at high risk of premature ovarian failure.

After a patient gives consent and researchers determine she has normal ovarian function before chemotherapy, doctors use a laparoscopic procedure to remove one ovary or a piece of one ovary through the patient’s abdomen. The tissue is sectioned in small trips that are then immersed in a special substance with protective freezing agents and placed in a machine which freezes the tissue at a temperature below minus 110 degrees Celsius. The tissue is stored in vials within liquid nitrogen tanks.
When the patient is ready to become pregnant, the strips are removed from the tanks, thawed and transplanted via another laparoscopic procedure. If an entire ovary was removed, it is transplanted onto the remaining ovary.

Because it could be many years until some of the patients are ready to have children, it could take some time before researchers know how successful the procedure is, Stadtmauer said. So far, only a handful of patients have had tissue removed and none have had it transplanted. When at least 10 patients have had tissue transplanted, researchers should be able to determine the viability of the procedure, she said.
Fertility preservation has long been a personal research interest for Stadtmauer.
“The whole area is really moving very rapidly in terms of successes,” Stadtmauer said. “What’s encouraging is that there has been recent success in culture media and better understanding as to how to maintain the eggs to survive the freezing and thawing. In addition, we are studying new rapid methods of freezing eggs called vitrification.”
If ovarian tissue freezing and transplantation eventually becomes more commonplace, it could also be an option for women who choose to postpone pregnancy but are approaching menopause, or who have not yet found a partner.

(Reprinted with permission from The EVMS Chronicle)