Preserving options, sustaining hope

Thanks to a transatlantic collaboration forged by Pasquale Patrizio, M.D., professor of obstetrics, gynecology and reproductive sciences and director of the Yale Fertility Center (YFC), patients in the New Haven area, including women newly diagnosed with cancer who wish to preserve fertility during chemotherapy or radiation, can now reap the benefits of a new, uniquely successful form of the egg-freezing technique known as oocyte cryopreservation (OC).

Although OC has been attempted in various forms for about 15 years, it has had a disappointing track record—producing about two babies for every 100 eggs frozen—because of damage done to eggs by freezing.

The new method, which involves bathing eggs in protective solutions, slow-cooling them with liquid nitrogen to minus 321 F and thawing them according to special protocols, doubles the success rate to five or six babies per 100 eggs, an enormous advance over traditional OC, says Patrizio. By comparison, in vitro fertilization (IVF) using fresh eggs has a success rate of eight or nine pregnancies per 100 eggs.

Patrizio says that because eggs are not fertilized before freezing, the OC technique has particular appeal for three groups of patients: women diagnosed with cancer at reproductive age, those who oppose embryo-freezing on ethical grounds and those who wish to postpone childbearing for personal or economic reasons but wish to use a future partner’s sperm. In December the School of Medicine’s Institutional Review Board (IRB) approved the use of the new OC method, and by the end of February, women from all three groups had already frozen eggs at the YFC.

Emre U. Seli, M.D., assistant professor of obstetrics, gynecology and reproductive sciences, says that preserving fertility is especially meaningful for women with cancer. “Anyone who has had someone with cancer in their family knows that quality of life, the way you spend your day after the diagnosis, is dependent on your hope,” Seli says. “That this procedure gives you hope is very important.”

The OC modifications were devised over the course of two years at Tecnobios Procreazione, a private fertility clinic in Bologna, Italy, in response to a 2004 Italian law that bans the freezing of human embryos for IVF and allows only three eggs per patient to be fertilized by donor sperm. The law permits OC, because it employs unfertilized eggs that have not developed into embryos.

“Those two years have been very difficult for our patients and for us,” explains Tecnobios Director Andrea Borini, M.D. “I have had the honor to lead a team of very strong people expending a great deal of energy to get better and better results after the law was passed.”

The modifications to OC pioneered at Tecnobios clearly give superior results to older techniques, but there is much to be learned about why they work so well. Because of Yale’s research prowess in human fertility, Borini shared the methods with Patrizio, an Italian native, who will pursue further refinements.

“It’s an advantage having this program at Yale, which is a powerhouse of facilities to study subtle changes in success due to small changes in the protocols,” says Patrizio, who is joining Dagan Wells, Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences, in molecular analyses of frozen oocytes to better understand the basic biology of OC. Borini says that the collaboration with Yale is “the result of a strong friendship between Dr. Patrizio and me that started almost 15 years ago when we were at the beginning of our careers in infertility. I am very happy that Yale started this program, and I hope that more advances will be achieved.”

The American Society for Reproductive Medicine, which classifies OC as an experimental procedure because of its historically low success rate, recommends IRB approval for all OC services, a policy that Patrizio believes is in the best interest of patients. "We are offering a service to the community that was not available, we are doing it with the best people in the world, and we are following the guidelines,” he says. “The patient has the benefit of having the latest technology, but in an academic center overseen by an IRB.”

Patrizio and his colleagues are busy spreading the word about OC, particularly among local oncologists, who can now offer their patients a new option to preserve fertility. “We didn’t feel comfortable offering this service even a year ago because the results were dismal, fluctuating between a 1 and 2 percent success rate,” Patrizio explains. “But once there was improvement, which is remarkable in terms of the numbers, we wanted to jump in and do it right.”