[April 2007] Freezing eggs can preserve fertility in women beginning cancer treatment. Now Yale and Israeli scientists are working to see if an entire ovary can remain viable after cryopreservation.
In mid-December, Pasquale Patrizio, MD, professor of Obstetrics, Gynecology and Reproductive Sciences, sat at a laboratory in his Long Wharf offices, hypodermic in hand, and perfused a human ovary with the chemicals that would render it receptive to storage in a frozen state, a process known as whole ovary cryopreservation. The next step was to place the ovary in a device that uses liquid nitrogen to lower its temperature to as low as -40 degrees Celsius. The ovary would then be thawed and in vitro tests conducted to determine its viability.
The question foremost on Patrizio’s mind was this: Could the frozen ovary survive the freezing and thawing process and be reimplanted to restore fertility?
In this case the question was hypothetical. The ovary’s donor had a genetic susceptibility to cancer and was having both ovaries removed as a preventative measure. (She provided them to Yale investigators to help advance the science of fertility.) But if the process can be perfected, Patrizio said, it will provide another tool for physicians hoping to preserve fertility in young cancer patients who might be left sterile by chemotherapy or radiation.
Already, patients at Yale have the option of preserving individual eggs through a new procedure called oocyte cryopreservation, developed in Italy and refined by Patrizio and colleagues at Yale and in Italy over the past two years. The experiment in December marked the first effort to freeze an entire human ovary, according to Patrizio, director of the Yale Fertility Center.
Charles J. Lockwood, MD, chair of obstetrics, gynecology and reproductive sciences, said the procedure represents a significant advance in providing options for women wishing to preserve their fertility. “We have invested considerable time and money in an effort to push the envelope in understanding how to preserve ovarian function following cryopreservation, since this approach could maximize the chance of both preserving fertility options and avoiding premature menopause in cancer survivors,” he said.
The ovary-freezing experiment stems from previous work in Israel, published in Human Reproduction in 2005, in which scientists removed ovaries from sheep, froze them, thawed them and returned them to the sheep. Experiments in vitro and in vivo showed that the ovaries were viable and that the sheep maintained ovulation. “This is the first time that a whole organ has been frozen and come back to life,” said Amir Arav, DVM, PhD, chief scientist at Core Dynamics, the Israeli company that performed the experiments.
Arav, a colleague of Patrizio’s for 20 years, came to Yale in December to teach the procedure and carry out the first tests using human ovaries. If proven successful, the procedure would offer a much-needed alternative to existing methods. Cryopreservation of oocytes—which can take four weeks—may not be an option for patients who require immediate treatment for cancer.
Until now, only sections of the ovary, including the follicles, had been preserved by freezing. But this technique has had limited success because the follicles suffered ischemic damage during the freezing/thawing process.
Under the new procedure one ovary will be removed before cancer treatment and frozen and the other will be left in place. If the remaining ovary is damaged by chemo- or radiotherapy, the frozen ovary will be thawed and transplanted into the patient. Patrizio’s group is also investigating whether with this new method the ovary’s follicle-bearing cortex can be better preserved and produce viable eggs once reinserted.
Patrizio and colleagues plan to do 10 in vitro tests to ensure the success of the procedure before attempting it on a patient. They hope to offer the procedure later this year.
This article originally appeared in the February 2007 edition of the Yale Practice Newsletter.