By Rick Weiss
Stacie McBain was just 20 years old last fall when doctors told her the cancer treatment she needed would leave her infertile. But there was hope: an $11,000 experimental procedure in which researchers would remove pieces of her ovaries and freeze them for later use.
The novel approach was not guaranteed to work. But McBain jumped at the opportunity after the doctors running the experiment told her that animal studies had been successful.
"I love kids and I always wanted to have them," McBain said in a recent interview. "They said they'd tried it in sheep and it worked."
What McBain and her parents were not told, however, was that only one sheep has ever become pregnant by this method.
That kind of omission would be unusual in most medical research settings. Yet by fertility clinic standards, several experts agreed, McBain was relatively well informed; she at least was told she was part of an experiment.
Fertility clinics receive no government funding, so the women who use them are not covered by federal laws that protect human subjects in research. And although doctors in all types of medicine have the prerogative to try novel techniques that may help their patients, reproductive technology is evolving so fast that the line between cutting-edge medicine and using women as guinea pigs is no longer clear, observers say.
"We have in many respects far better protections for hamsters than for human fertility patients," said R. Alta Charo, a professor of law at the University of Wisconsin and a member of the National Bioethics Advisory Commission, which is investigating abuses of human subjects in research.
"We can tell you how many swabs are used on animals in a year in this country, but we can't tell you how many people were involved in fertility research in this country or how many adverse events there were or anything," Charo said. "We require all of that for non-human animals, but not for people."
Unlike the high-profile legal cases that have emerged recently in the reproductive technology arena dramatic cases of embryos placed in the wrong women or of babies created from dead people's sperm or eggs abuses of research subjects in the fertility field remain largely invisible. The scope of the problem remains unknown, since there is no system of oversight.
But more than 1,000 women undergo in vitro fertilization procedures every week in this country, and countless others receive other kinds of fertility treatments. And at least some of the recent exciting breakthroughs in reproductive medicine, critics say, have been the result of ethically questionable practices, in which women served as subjects in ill-defined research projects or their eggs or embryos were sidetracked to laboratories without the donors' knowledge, to be used in experiments and eventually tossed in the garbage.
Fertility doctors say they are just trying to give women the best odds of getting pregnant. Patients want nothing less than the latest technology, they say, even if it is still experimental. And, they argue, since the federal government has decided not to fund fertility research, it is up to the private sector to conduct that work.
"Many patients feel they have the right to the most innovative treatment around, especially since a lot of them are paying out of pocket," said Mark Sauer, chief of reproductive endocrinology at Columbia-Presbyterian Medical Center in New York.
Others, however, say the lack of regulations over fertility research makes it too easy to cross the line from assistance to experimentation especially since these patients' urgent desire for a baby makes them especially susceptible to exploitation.
"It's an extremely vulnerable patient group," said Gary Ellis, director of the office for Protection From Research Risks at the National Institutes of Health. "Desperation reigns."
Help, Hope and Harm
The clinic had McBain sign a consent form, for example, that says in part "we cannot guarantee that you will benefit" from the procedure. Yet accompanying materials refer to "extraordinary results" in sheep and call the experimental procedure "a revolutionary improvement" in fertility preservation for women with cancer.
Such mixed messages are at best confusing and at worst unethical, but are not uncommon in the fertility arena, according to Lori Andrews, a professor of law and bioethics at Chicago-Kent College of Law. "Patients are being told they're getting the latest clinical evaluation and treatment, but they're rarely told that there have only been, say, three births before," Andrews said.
Michael S. Opsahl, a physician at Genetics & IVF, said human studies of frozen ovary transplants were justified because many sheep that have undergone the procedure have regained normal hormonal cycles, even if they have not become pregnant yet, suggesting that they could become pregnant. Equally important, he said, is the sense of empowerment a cancer patient can gain from trying something experimental. "It really does give them some hope," Opsahl said. "They are willing to take the chance because there are no alternatives."
Indeed, McBain says she has no regrets about going ahead with the treatment. "It made me feel easier, knowing that I had some babies on ice," said the Macomb, Mich., woman, who calls the frozen tissue slices her parents' "grandcicles."
It's a classic bioethical dilemma, Andrews said: No one wants to undermine a cancer patient's hopes or place undue restrictions on new and reasonably promising techniques for infertile women. At the same time, people should not underestimate the harm that can come from raising false hopes. And in reproductive medicine, she said, false hopes are the great untallied commodity.
"In other areas of medicine, if you do something terribly wrong, the patient usually gets worse. But in the fertility business, when the success rate is only 20 percent, you can do a lot of wrong to a lot of people and they just disappear into that 80 percent," Andrews said. "So you can try all kinds of things. You can harm these people psychologically and financially and it doesn't show up as physical harm. That's why we need to pay more attention to consumer protections in this area."
Experimenting With Eggs
The research required many eggs to practice on, said Joe B. Massey, the clinic's director, so doctors there turned to women who were donating eggs to infertile women and used some of the leftover eggs for their research. "We call it sharing with the lab," he said.
RBA researchers used such eggs, in some cases without the donor's knowledge, to try various freezing and thawing techniques until they found a way that seemed not to damage the eggs, Massey said. Some eggs that looked good after thawing were mixed with sperm to see if a normal embryo would develop.
"When we started getting some [embryos] that lived, we approached a patient," Massey said. "We told her, we don't know if this will work. We won't charge you, but if we make an embryo with one of these thawed eggs and your husband's sperm, would you take it?"
The woman, who like many fertility patients could barely afford her treatments, said yes. Last year, she became the first in this country to give birth to a baby from a frozen egg.
The experience with frozen eggs at RBA demonstrates the ease with which women's eggs may be diverted for research and the ease with which new fertility techniques can be tried on women. And although that story had a happy ending, some question whether she would have gone ahead with it had she and the researchers been fully aware of the uncertainties of the procedure.
Very little is known about whether freezing might damage the genetic material inside eggs and boost a woman's odds of giving birth to a deformed baby. Indeed, a few months after the Atlanta woman gave birth to her apparently healthy baby, researchers in Korea published a report suggesting that the freezing process often does damage the DNA inside human eggs a finding that Massey said has made him rethink the wisdom of making babies from frozen eggs.
"I must say, it makes me want to take another look at this," Massey said. "It raises a real caution flag."
Questions of Consent
"People are going to these clinics with the hope of bringing home a baby, not to participate in research," said Ami Jaeger, principal of the BioLaw Group, a Santa Fe, N.M.-based organization that provides legal and consulting services in genetics and assisted reproduction. "But they may be more inclined to say yes to some of these offers if they think it will get them better care."
Federal research guidelines provide explicit protections to make sure that people are not coerced into participating in research. But there is no mechanism for reviewing such offers in the private fertility sector. In one recent case, for example, a woman from Texas felt she was misled by a fertility clinic that offered her a discount if she would donate half of her eggs. But when she looked into whether the clinic's offer violated any medical or ethical rules of conduct, she quickly became lost in a regulatory void.
"I found out there is nothing out there to protect me as a consumer; no legal recourse, no statute," said the woman, Carol Garcia of Austin. "Technically I wasn't even their patient yet."
Ethics Review Optional
Massey said his clinic used to show its research protocols to the review board at a nearby hospital, but the hospital dropped out of that role some time ago. "They didn't want to look at this strange stuff," Massey said. "Why would they take the potential medical legal risk on embryo freezing, for crying out loud, when no one knew if it would work?"
Instead, Massey said, the clinic simply worked without any outside review for a while, and lately has been using an agency that reviews research proposals for $1,500 apiece a system that some have criticized as being potentially problematic, since for-profit ethics review companies may be disinclined to be tough on their paying customers.
"There is a real concern that these companies are going to be under pressure to make sure they are not financially a burden to their clients," said the University of Wisconsin's Charo. "There's very little accountability."
At the Genetics & IVF Institute, McBain was assured that the frozen embryo procedure had passed muster with an IRB. But the five-person review board that gave that green light consisted of three of the clinic's own doctors and the director's administrative secretary all of whom stand to profit at least indirectly from the business and a lawyer who is a close friend of one of the clinic's doctors. Opsahl, the overseeing physician, said the experiments were also approved by an IRB at the nearby hospital where McBain's surgery was performed.
In addition, because of a federal regulatory quirk, many fertility center laboratories are not subject to the inspections and proficiency testing imposed upon other medical laboratories in this country.
"A fertility doctor can literally set up a lab in his garage and hire his son or daughter who might have a bachelor's degree to run it, and it would be perfectly legal," said Brooks A. Keel, professor of obstetrics and gynecology and associate dean for research at the University of Kansas School of Medicine in Wichita. "A woman gets more regulatory oversight when she gets a tattoo than when she gets IVF."
Medical laboratory rules in the United States break down along gender rules, Keel said. Labs that conduct sperm counts or other kinds of semen analysis are subject to the Clinical Laboratory Improvement Amendments of 1988, an act of Congress that sets strict quality control standards for medical laboratories and requires lab directors to have a minimum level of training.
But labs that deal with women's eggs are exempt from those standards or at least claim they are, by arguing that egg manipulations are not "diagnostic tests." Keel, who is president-elect of the American Association of Bioanalysts, which represents laboratory professionals, is spearheading an effort to persuade the department of Health and Human Services to bring fertility labs under the 1988 law's federal regulatory umbrella.
Policy and Enforcement
"These patients understand that no one in society supports their problem, so many seek an opportunity to participate in a protocol," said Richard T. Scott Jr., of the Institute for Reproductive Science at St. Barnabas Hospital in Livingston, N.J. "Personally, I think there is a lot of good work being done."
Moreover, some doctors said, it is paternalistic to presume that fertility patients many of whom are very well educated and informed need to be protected from their doctors or themselves. "It can be a slippery slope kind of question, where at some point people are going too far, but mostly these women know what they are doing," said Richard Paulson, director of reproductive endocrinology and infertility at the University of Southern California.
Things may be getting better. Many clinics now use institutional review boards, and consent forms are becoming more complete and routine especially at the larger of the nation's 300 or so fertility clinics.
Sauer, the chief of reproductive endocrinology at Columbia-Presbyterian in New York, said he thinks a split is occurring in the fertility field, with larger centers adhering more closely to standards that would apply in the federal sector while some smaller clinics are cutting corners to break into the field.
"There is an increasing amount of cavalier behavior out there, even though the stuff we've done is with strict protocols and approval of institutional review boards," Sauer said. "We don't really have a public policy for fertility patients in this country. I wish we did."
The question of what that policy should be or how it should be enforced remains one of the most difficult now facing the field of reproductive medicine. Sauer and many other doctors argue that it would be unusual and inappropriate to impose federal regulations on a specific branch of medicine, and they fear that such rules could stifle the rapid progress now sweeping through the field. Professional standards promulgated by groups such as the American Society for Reproductive Medicine would be preferable, Sauer said.
Critics counter that voluntary professional standards are too easily breached and offer no mechanism for surveillance or enforcement. And while states could pass laws restricting embryo research in various ways, only 10 have done so and each one differently, creating a confusing regulatory patchwork.
Congress has passed a law that requires the Centers for Disease Control and Prevention (CDC), along with various professional societies, to start collecting data from fertility clinics. Perhaps, some said, there is a way to expand that federal infrastructure to include some kind of scientific and ethical oversight.
Solutions may come to light this week when the CDC and other organizations convene in Washington to discuss these and other regulatory options. Representatives from the United Kingdom, Australia, France, Canada and various consumer organizations will meet for the first time to try to create a regulatory scheme appropriate to this country's unique constellation of conditions, including the federal government's desire to distance itself from embryo research, the intense demand for high-tech medical care and the need to protect consumers.
At a minimum, said Bartha Maria Knoppers, a professor at the University of Montreal Law School, the United States needs some kind of centralized data collection system that would clarify the extent of questionable research practices in the fertility field. Today, Knoppers said, "you don't have the statistics, the oversight or the accountability that allows you to answer the question of whether women are being harmed. And that in itself is a very worrisome situation."
© Copyright 1998 The Washington Post Company