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Researchers Say Embryos in Labs Are Not Available

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    Researchers Say Embryos in Labs Are Not Available

    August 26, 2001

    Researchers Say Embryos in Labs Are Not Available

    Don Standing for The New York Times
    Dr. John Garrisi, the chief embyrologist at St. Barnabas Medical Center in Livingston, N.J., with a storage tank used for frozen embryos. The Job Nobody at the Fertility Clinic Wants (August 26, 2001)

    f scientists want to develop new supplies of embryonic stem cells, they may have to take the bold and controversial step of creating human embryos expressly for research, many leading fertility experts say.

    Tens of thousands of embryos are frozen at fertility centers, and a widespread assumption in the debate over stem cell research has been that scientists can use them.

    But in clinics around the country, embryologists and doctors tell the same story: almost every embryo is spoken for. The vast majority of couples use their frozen embryos, or plan to use them, in attempts at pregnancy. It may be that embryos will become available if there are concerted efforts to encourage couples to donate them. But so far, very few couples have agreed to do so.

    An alternative, creating human embryos and nurturing them solely for experiments that will destroy them leaves even many supporters of the research deeply uneasy.

    The harsh truth about the status of the frozen embryos "changes the debate," said Dr. Thomas Pool, scientific director of the Fertility Center of San Antonio. If the embryos already existed, were unwanted byproducts of in vitro fertilization, and were never going to be used to make babies, Dr. Pool said, people could ask, "Could I save them and do some good with them?" That was "a warm and fuzzy way for people to get around the question of making them," he added. "It's an easy way to not have to come back to the salient question: What are these things that we make in I.V.F. labs?"

    This conundrum does not arise in the area where President Bush has proposed allowing federally financed research. He would permit work to go ahead on existing lines of stem cells Mr. Bush says there are 60 lines, while others say there may be as few as a dozen usable ones.

    Rather, the issue comes up when scientists try to develop new stem cells, abroad or with private money. Some say this is necessary because the existing lines are insufficient and may not be safe for human use.

    Most of these human cells were exposed to mouse cells while being coaxed to grow in the laboratory, to prevent them from developing prematurely. This has raised the question of whether mouse cells could transmit viruses to human patients.

    There are no national data on the number of frozen embryos. But the Society for Assisted Reproductive Technology says that most of the approximately 400 American clinics that offer in vitro fertilization also freeze embryos. The frozen embryos are one to five days old and consist of one to 120 cells. They are less than three-thousandths of an inch in diameter.

    Some clinics routinely ask patients if they want to donate embryos for research. Others the majority, fertility experts say do not ask.

    One clinic that asks is the Institute for Reproductive Medicine and Science of St. Barnabas Medical Center in Livingston, N.J., one of the nation's largest fertility centers. Embryologists there have frozen 11,402 embryos since August 1995, from a total of 1,595 patients. Many used their embryos. One woman gave hers up for adoption, which was privately arranged. That left 6,284 in storage, from 1,006 patients. Of those patients, 191 signed or said they would sign a form directing that their embryos be discarded.

    But only 22 patients signed or indicated a desire to sign a form allowing their embryos to be used for research, although Dr. John Garrisi, the chief embryologist there, said that he was certain many who no longer wanted their embryos would donate them for research if he asked them personally.

    Patients at the Jones Institute for Reproductive Medicine of Eastern Virginia Medical School, another large center, are also asked to donate embryos for research. Embryologists there froze about 15,000 embryos in the last 15 years, two-thirds of which were used by the couples that owned them. About 200 embryos might be available for research according to forms signed by patients, said Dr. William Gibbons, a reproductive endocrinologist there. And that, he said, might not be enough to generate any stem cells.

    Dr. Zev Rosenwaks, who heads a large fertility center at the Weill Medical College of Cornell University, said that his patients, too, almost always keep their embryos. But, Dr. Rosenwaks said, over "many many years," about 100 to 200 couples agreed to donate embryos for research. That could be enough for stem cell research, he said, although he is not doing such work.

    Boston I.V.F., a group of fertility clinics based in Waltham, Mass., recently agreed to supply Harvard researchers with frozen embryos for stem cell research. Dr. Michael Alper, the group's medical director, estimated that the clinics had several thousand frozen embryos and that a small percentage of patients had indicated they no longer needed theirs. Two months ago, Boston I.V.F. began asking these patients to donate their embryos. "We've had several patients already who agreed," Dr. Alper said.

    In San Antonio, Dr. Pool does not offer patients the option of donating embryos for research. He stores about 2,000 frozen embryos, he said, and almost no one discards them.

    Dr. Richard Rawlins, laboratory director at the Rush Center for Advanced Reproductive Care in Chicago, said patients there were not asked about donating embryos. In Dr. Rawlins's 17 years at Rush, he said, only one couple broached the subject. Three couples in the last three years have asked to have their embryos discarded. He is storing embryos for about 250 couples, most of whom will use them, he said.

    Even if scientists did want to use frozen embryos at fertility centers, there would be hurdles to overcome, Dr. Gibbons said. Each patient who has agreed to donate embryos must be contacted and agree to the particular stem cell project. Then scientists must buck the odds in getting the embryos to grow and isolating stem cells from them.

    Those odds can be long.

    Dr. Gibbons said that even if every one of the 200 embryos at the Jones Institute that might be available were used and were in the best possible condition, 50 or fewer would grow to the blastocyst stage. That is the stage, at about five or six days, when scientists can try to isolate stem cells. On average, only a small fraction of blastocysts yield stem cells.

    "There is no guarantee that we would get any stem cells from those 200 frozen embryos," Dr. Gibbons said.

    "We hear all this stuff about how all these embryos are available," he added. "But we just didn't think there was much there."

    Dr. Gibbons said it was the dire lack of frozen embryos available for research that led his group to make its own, a controversial experiment the Jones Institute reported last month. Even then, only 3 out of 110 embryos yielded stem cells. The embryos were ideal, made from the eggs and sperm of young and healthy volunteers and never frozen.

    The frozen embryos at fertility centers are much less robust, medical experts say. Dr. Pool said that until recently, he and others froze many embryos that were of poor quality and would never grow. And, he added, they put them in solutions that were not optimal, so even healthy embryos frozen in previous years may not grow into blastocysts.

    Another difficulty is that most frozen embryos are from older women who had trouble conceiving, said Dr. Jacob Mayer, director of the embryology lab at the Jones Institute. Their embryos are less likely to grow, he said, and stem cells derived from them may be of lesser quality.

    Dr. Barry Behr, who directs the in vitro fertilization laboratory at Stanford University and at four other California fertility centers, said that if he wanted to make stem cells, he would do the same thing the Jones Institute scientists did.

    "The few dribs and drabs of embryos that are released by our patients are never going to be enough to generate high-quality cells," Dr. Behr said. "By far, by far, the vast majority of embryos that are frozen are not good. If we thawed 10,000 embryos, we would get 100 or so that are viable blastocysts."

    But although the chances of frozen embryos being viable are small, fertility experts say, patients and their doctors still cherish every one.

    For patients, they represent a chance at future fertility, which is why so few want to give them up.

    In a sense, said Dr. Jacques Cohen, the director of research at St. Barnabas, an infertile couple's decision to keep their frozen embryos is not so different from a fertile couple's decision not to be sterilized after their family is completed.

    The embryos take on additional value, doctors and embryologists say, because obtaining them is so expensive and emotionally draining.

    A patient has typically spent years trying to have a baby, and invested huge sums usually more than $10,000 a month for the fertility center and $3,200 a month for drugs. A medical team has worked intensively to induce her ovaries to produce eggs. A team of embryologists, laboring in a tension-filled atmosphere, has manipulated the microscopic eggs to produce an embryo.

    "It is a clump of cells, but it is a very important clump of cells," Dr. Garrisi said. "It may not be a human being, but it certainly has potential and I think it deserves respect that is greater than that accorded to an egg or sperm. An embryo is more important if for no other reason than all the work it takes to get it."

    Some scientists predict that the promise of stem cell research may encourage more couples to donate embryos for that purpose.

    "I think that patients will come forward," said Dr. Alan DeCherney, a fertility expert at the University of California in Los Angeles and editor of the journal Fertility and Sterility.

    But that remains to be seen. At Columbia University's fertility center, only two patients so far have asked about donating frozen embryos for stem cell research. But, said Dr. Mark V. Sauer, the center's director, neither responded when asked for more information.

    At the Jones Institute in Virginia, where scientists are clearly interested in the work, no one has offered to donate embryos, Dr. Mayer said.

    But, he said, "I did get an e-mail from another embryologist who indicated she had a patient who wanted to donate frozen embryos for stem cells." It was forwarded to him from the Society for Assisted Reproductive Technology.

    And what did he tell the embryologist? "I passed the e-mail on to someone else," Dr. Mayer said.