Embryos, Eggs and Ethics : Research on Cell Freezing at UCI Draws National Attention

In one corner of a tiny laboratory at UCI Medical Center stand three large, temperature-controlled tanks holding an ethical dilemma for Dr. Ricardo Asch.

Inside are thousands of frozen embryos, speck-size potential human beings formed by the merging of sperm and egg within a test tube. They were created to help the hospital’s fertility clinic, through in-vitro fertilization, successfully impregnate women who otherwise would be childless.

The problem now is what to do with the leftovers--the clinic has 5,500 embryos, suspended at a chilly 196 degrees below zero Celsius, in tanks at UCI Medical Center and Saddleback Memorial Medical Center. And the stockpile is building at a rate of 180 embryos a month.

Asch, the clinic’s medial director, observes that the embryos pose a potentially thorny legal debate. Since many were created by husbands and wives, exactly who owns them if the couples divorce? He also feels morally responsible for protecting these seeds of life.

“What if someone breaks in and steals the embryos?” he said. “Or what if there is a fire or earthquake and they are destroyed?”

Enter researcher Debra Gook, an Australian biochemist who is trying to develop a technique for freezing human eggs so they can be stored and fertilized just before being implanted in a uterus, thus eliminating any need to stockpile embryos.

Until recently, however, Gook faced a dilemma of her own: She couldn’t fully test the procedure at Melbourne’s Royal Women’s Hospital, where she heads a research team, because it is within the Australian state of Victoria, which forbids--for a combination of legal and religious reasons--the creation of human embryos for experimentation. She was effectively stopped from learning if frozen eggs will develop normally after they are fertilized.

So last week Gook came to the UCI Center for Reproductive Health to collaborate with Asch in a project that may be beneficial for both. And their research is drawing a national spotlight. It will be featured in a segment of NBC’s “First Person with Maria Shriver” on Channel 4 Monday at 10 p.m.

In an interview last week, Gook said she is “very hopeful” that she can solve a puzzle that, for more than a decade, has frustrated scientists unable to find an effective method for freezing eggs without destroying their delicate chromosome structure.

While there have been a handful of reports since the mid-1980s of babies born from eggs that were frozen and thawed before insemination, no technique has produced the kind of consistent results necessary to be adopted as a fertility tool.

Freezing eggs would offer numerous advantages.

Gook said her major objective is to help young female cancer patients. If such patients could have their healthy eggs extracted and frozen before undergoing potentially ovary-destroying chemotherapy, she said, they could preserve the option of bearing children after hopefully conquering their disease.

Similarly, researchers observe that women with progressive, ovary-destroying diseases like endometriosis could benefit from saving their eggs.

In addition, career women who want to postpone childbearing until later in life, even until after menopause, could freeze their eggs before the eggs deteriorate with age and become infertile. Studies have shown that women can still carry pregnancies in their womb long after their ovaries no longer function.

Giving women the ability to become mothers in middle age and beyond, researchers observe, would make them more reproductively “equal” to men, who have always had this option.

Also, egg banks could be formed, similar to existing sperm banks, which would allow women who are unable to produce viable eggs of their own to shop for eggs donated by women with matching physical characteristics.

Finally, most fertility experts would eagerly welcome a procedure that would permit the freezing of eggs rather than the current widespread practice of freezing human embryos, which has raised considerable ethical, legal and religious controversy.

Among the concerns is just when does an embryo, which has all the genetic components of a new individual, acquire a “right to life.”

“Under current legal or religious rules, an egg and embryo are very different,” said Jacques Cohen, scientific director at Cornell University Medical School, where scientists are also searching for an effective egg freezing technique. “Biblically, conception is the start of new life and the law has been founded around it.”

Dr. Alan DeCherney, chairman of the department of obstetrics and gynecology at the Tufts University School of Medicine and president-elect of the American Fertility Society, agreed that “the egg is not as controversial” and that freezing eggs would be the best way to go.

A key stumbling block for scientists has been that eggs are more easily harmed by the freezing-thawing process than embryos, which have been successfully frozen for a decade. Cooling frozen eggs has either caused the tiny protein threads called “microtubules,” which hold together chromosomes, to disintegrate or the membrane covering the egg to harden and become impervious to sperm.

So women who go to doctors for in-vitro fertilization have their eggs extracted and immediately inseminated. The resulting embryos are frozen when they divide to about four cells for implantation in the uterus at a later date.

Since not all embryos produce a pregnancy, it is common practice to store some extras. Some babies have been born from embryos stored as long as eight years and theoretically frozen embryos could be kept alive indefinitely.

Asch, a longtime pioneer in the field of assisted fertilization, said there are now “millions” of frozen embryos worldwide and he is increasingly distressed about the ever-expanding number.

Sometimes, he said, couples who complete their families don’t want to make the emotionally difficult decision to destroy surplus embryos, give them away or release them for research. So the embryos remain in a frozen limbo.

“It is my ethical problem,” said Asch, who is sometimes asked by his patients to make these hard choices. He declines. By leaving it up to the physician, he said, the parents “let the doctor play too close to God.”

For the last five years, Gook has been researching a “slow-freeze, fast-thaw” technique for preserving eggs, and she said the results are highly promising.

The eggs are treated with protective chemicals and frozen with liquid nitrogen. They cool very slowly over an hour and a half to 30 degrees below zero Celsius and then are rapidly chilled to 150 degrees below zero Celsius in about 20 minutes. Later, they are thawed by placing them at room temperature.

Of the human eggs that Gook freezes and thaws, she said 40% survive the process and are able to be fertilized. That compares favorably to a 60% success rate in the test tube fertilization of eggs that have never been frozen, she said. In previous research, she said, only 30% of the eggs survived the freezing and very few of those could be fertilized.

Gook’s next step--to determine if thawed and fertilized eggs can consistently develop into normal embryos--can’t be researched at her own laboratory because of Victoria state’s moratorium on the creation of embryos for experimental purposes.

Dr. Colin Matthews, president of the Fertility Society of Australia, said Victoria’s aggressiveness in restricting research stems from the region’s early leadership in in-vitro experimentation, which prompted strong opposition from church groups that worried about scientists “playing with life” and from feminist organizations objecting that women’s bodies were being used for research.

In California, however, neither the law nor the medical profession pose a barrier to her work. “Dr. Asch has been very keen for me to come there and the people in Australia are not that keen,” Gook said.

DeCherney said 20 years ago a federal ethics advisory board met to set national guidelines on fertility research in the United States but failed to reach any conclusions and disbanded. He said that, nonetheless, American scientists know that this kind of research always walks a sensitive line, with the possibility of regulation if there is a public outcry.

Gook’s experiment at UCI will take a month, she said, during which time the 37-year-old researcher plans to freeze, thaw and fertilize about 100 human eggs. She said she will wait about five days for each embryo to divide, then stop the embryo’s growth with chemicals and study it for any chromosome damage.

Also joining the research team at UCI will be Gerald Schatten, professor of zoology and molecular biology at the University of Wisconsin. Asch said Schatten has developed an innovative technique using dye and a special high-powered microscope to analyze the viability of human eggs after they have been frozen and thawed.

Asch, whose patients have agreed to donate eggs for the research, said once the egg freezing technique has proven reliable, he would be willing to use it at his clinic.

“This is great because it will give us a final answer,” said Gook, who expects that women will begin conceiving babies from unfrozen eggs within a year.

Success Rates

Women facing chemotherapy or ovary-destroying diseases or who want to bear children at an older age may be candidates for having their unfertilized eggs frozen for future use. Currently eggs must be fertilized, becoming embryos, before they can be frozen for storage, which raises ethical and legal concerns.

* Eggs: Fast-frozen, unfertilized eggs are stored until needed, then thawed; 40% of the eggs were successfully fertilized in a laboratory test.

* Test-tube: Never-frozen eggs are inseminated; nearly 60% are successfully fertilized.

* Embryos: Eggs are inseminated and resulting embryos are frozen; more than 60% produced births.

* Sperm: Frozen sperm is stored until needed, then thawed; more than 90% produced births.

Sources: UCI Center for Reproductive Health, Encyclopedia Britannica; Researched by APRIL JACKSON / Los Angeles Times