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P&S Journal

P&S Journal: Fall 1996, Vol.16, No.3
Ethics in Medicine (Second in a Series): Assisted Reproduction

By Devera Pine

Once Just a

Solution to

Tubal Disease,

Now an

Answer to

Other Parenting


Eighteen years after Louise Brown made the cover of People magazine as the world's first test tube baby, in vitro fertilization has become a fact of life. Now known as assisted reproduction, or AR, the field has advanced far beyond the relatively simple technique of fertilizing an egg in a petri dish and reimplanting it in the mother's uterus.

New and increasingly complicated techniques for getting sperm to meet egg are emerging, increasing the number of otherwise infertile couples who are able, in some way, to conceive a child. But these advances, in turn, are generating their own set of ethical and social issues. Some of these issues have been aired in high-profile court cases and media stories, but most are quietly resolved by medical practitioners working in the field.

"AR technology has leapt forward so quickly that in certain ways it has become the easier part of the procedure. The harder part has been deciding how to use some of the procedures, especially when we're considering doing things that are new and unconventional," says Dr. Jane Rosenthal, assistant clinical professor of psychiatry and team psychiatrist with the in vitro fertilization division in the Department of Obstetrics and Gynecology. Some of the new eyebrow-raising capabilities of AR include enabling postmenopausal women to have babies; freezing embryos so that a woman undergoing cancer treatment or other reproductively risky medical procedures might still have babies when she recovers; "washing" sperm to allow HIV-positive men to become fathers; and altering the egg to make it easier for sperm to fertilize it.

These new techniques, plus the huge sums of money that can be made with AR and the proliferation of less-than-scrupulous clinics promoting still-unproven technology, make the field of AR a veritable quagmire of controversy. "AR is having an effect similar to birth control pills, in a way," says Dr. Ralf Zimmermann, assistant professor of obstetrics and gynecology and of psychiatry. "It is revolutionizing the reproductive process."

Perhaps the newest of the AR controversies is the trend in some clinics to offer AR to HIV-positive men. Columbia's clinic has seen an increase in these kinds of requests as some HIV-positive men place their hopes on a new procedure that separates the sperm from the semen to reduce the viral load. The "cleansed" sperm are then used in standard in vitro fertilization procedures: The egg is fertilized outside the woman's body then deposited in her uterus where it can implant for a pregnancy. Some AR clinics claim this procedure reduces the likelihood that the woman will be exposed to HIV. So far, however, Columbia's clinic has refused to perform the procedure on the grounds that it is risky and unproven.

Jonie Mosby Mitchell was 52 when she conceived Morgan Bradford by AR.
"Even though the sperm is separated from the semen, there's still a chance that both the mother and child could be infected," says Dr. Mark Sauer, chief of reproductive endocrinology and director of the Department of Obstetrics and Gynecology's division of assisted reproduction. No studies have shown the technique effectively reduces the viral load. "It would be hard to sell the procedure as a clinical trial because of ethical problems it presents."

As HIV continues to become more widespread, chances are Columbia will get more requests for the procedure. The Assisted Reproductive Technologies Clinic has seen cases where routine testing of applicants has revealed that one member of a couple is HIV-positive. The clinic's response in these cases is to deny couples AR services but provide them with HIV counseling.

Another complex ethical question is whether the clinic should "bank" the embryos of a woman about to undergo cancer treatment. As the odds of surviving cancer improve, more women are asking to have their eggs fertilized via IVF before cancer treatment and the resulting embryos banked.

This presents several problems. First, the question of whether AR will put the patient under too great a risk: In a woman who has recovered from breast cancer, for instance, the increased estrogen levels of pregnancy might raise the odds of the cancer returning. Many also raise concerns about the fate and rights of a child conceived in this manner whose mother dies prematurely from her disease.

Then, a dilemma faces the male partner and the AR team if the woman does not survive the initial bout of cancer and leaves behind "orphan" embryos. What happens to the embryos?

Viable, unclaimed embryos are a temptation, given the economic incentives of AR. Last year, two University of California doctors fled the country after they were accused of harvesting eggs, fertilizing them, and implanting them in women without the consent of the donors. At least 10 babies were born as a result of the alleged improper use of eggs, which were implanted into more than 60 women.

In intracytoplasmic sperm injection, an oocyte is placed up against a large holding pipette to keep it in place while another pipette injects a single sperm cell. A successful procedure produces a normally fertilized oocyte with two pronuclei, visible in approximately 14 to 16 hours. Twenty-four hours later, a dividing pre-embryo results, shown here in the eight-cell stage.

Unethical activity can happen because no governmental system exists to monitor assisted reproduction clinics. The clinics are not regulated by federal agencies and laws or, for the most part, by state laws. Instead, most clinics voluntarily follow the ethical guidelines of the American Society for Reproductive Medicine, a professional society. In addition, clinics affiliated with university hospitals and other medical institutions may have access to an in-house ethics board. At Columbia, Dr. Sauer is a member of the medical ethics committee and Dr. Rosenthal has attended discussions on AR.

Still, with the kinds of possibilities presented by the California scandal, many clinics refuse to bank embryos. Taking that kind of no-compromises stance can be difficult. "There have been cases where women with advanced cervical cancer want their eggs fertilized and banked so that they can get pregnant when they 'get better.' How can we say we won't bank them?" says Dr. Georgiana Jagiello, the Virgil G. Damon Professor of Obstetrics and Gynecology and professor of genetics and development.

Postmenopausal women seeking to have a baby via AR present a similar dilemma. At Columbia's clinic, women are accepted up to age 55. Yet, says Dr. Sauer, Italian doctors have used AR to impregnate a 62-year-old, and the technology could probably even be used on 70-year-olds. "The issue is whether the unborn child has rights to parentage," he says. "How long will the mother live?"

On the other side of this issue, people who are 45 to 50 years old might make better parents than people in their 30s who are still struggling with careers and finances, says Dr. Zimmermann. "They're between parents and grandparents."

One woman who has worked through these issues is Jonie Mosby Mitchell, a country music singer and mother of 4-year-old Morgan Bradford, who was conceived by AR when Ms. Mosby Mitchell was 52 years old. At the time, Ms. Mosby Mitchell was the oldest woman on which AR had been used successfully.

Ms. Mosby Mitchell, who was Dr. Sauer's patient, has four children from her first marriage and an adopted daughter from her current marriage. She and her husband decided to try AR instead of adopting again because AR gave them more control than the adoption process offered, she says.

Ms. Mosby Mitchell describes pregnancy and birth at age 52 as "fun," though she wouldn't recommend it for most people. "When you're determined, nothing hurts." As for concerns that she might die while Morgan is still young, Ms. Mosby Mitchell is not particularly worried. Morgan's extended family of older brothers and sisters would be available to take care of him if anything happened to her, she says. Plus, old age runs in Ms. Mosby Mitchell's family: Her mother is 91. "Age doesn't make a difference to me," she says. "The alternative would be for [Morgan] not to exist."

Like many women who undergo AR, Ms. Mosby Mitchell had her baby with the help of eggs donated by a younger woman. For many people, this presents another ethical question. At Columbia and many other clinics, the donors are often college-age women who are paid to donate eggs anonymously. "Younger donors are at a premium from a medical point of view because the younger the eggs, the better the chances of pregnancy," says Dr. Rosenthal. "But if a 20-year-old donor has problems with infertility at age 30, will she regret her decision to donate eggs?" Though infertility resulting from egg donation itself is a rare problem, a woman might still feel that later infertility problems were connected, notes Dr. Rosenthal. Experts also worry that donors will want to claim "their" child. In addition, concern has been raised that the hormones used to stimulate ovaries, enabling egg donation, may increase the risk of ovarian cancer.

For egg donor Susan Scott, also a former patient of Dr. Sauer, the positives of egg donation outweighed the negatives. Ms. Scott, a 33-year-old owner of a travel agency and mother of two, had her first child early-at age 22-because of severe endometriosis. "I was lucky to get pregnant," she says. "It was a tough time for me." Her difficulties motivated Ms. Scott to become an egg donor when programs were first developed: Her eggs, which she began donating in 1987, have resulted in the birth of six healthy children. Today, many clinics seek to limit the number of times a woman can donate eggs, but no formal guidelines exist.

Ms. Scott compares the feeling of the births that her eggs generated to the emotions of giving birth to her own children. "I was the happiest person in the world," she says. "Through the donor program I got to relive that feeling." Yet Ms. Scott says she never feels the children from her eggs belong to her, partly because the program allowed her to meet the families receiving her egg donations. "It doesn't bother me. I'm honored by it-it thrills me to no end. They're all part of wonderful families. They're happy and healthy, with parents who love them."

Today, many programs frequently use eggs from anonymous donors, something Ms. Scott says she would not do. "I think that anonymous donors will have regrets later," she says. "I think they will suffer from not knowing how the kids turn out." Many of the anonymous donors like the ambiguity of the situation-not knowing if there is a resulting pregnancy and not knowing the recipient involved. To them, eggs are genetic material, not babies, says Dr. Rosenthal.

No studies have been done to assess the impact on young women of donating eggs, and only scant and preliminary studies exist on the social and psychological effects of being an AR child. Drs. Rosenthal, Sauer, and Zimmermann have begun a cross-sectional study to follow AR patients from the past five years and will begin a prospective study on AR patients and the resultant families. The study will aim for a complete picture of the effect of having a baby by AR on the lives of the families involved. "If the couple has previous children, how do they feel when the mother has another child?" says Dr. Zimmermann. "How does the life of the couple change after they have a child? We may find that the quality of life improves for these couples because they've made a conscious decision to have a child, whereas many 'natural' pregnancies might not be so well-planned."

By answering these and other questions, the studies will offer a unique look at AR. In the past, such questions have not been answered: "The consequences of what we do have not been tracked, primarily because of a lack of commitment and money to fund it," says Dr. Rosenthal. "Also, people move or they decide they don't want to tell their child. It's daunting and chilling. Yet it's crucial work. We have to assess the outcome of what we've done so far. That way we'll be able to say, for instance, that we've set an age limit on AR based on what we've learned about couples we've tracked, rather than making arbitrary decisions based on individual opinions or gut instincts."

Over the Line?

Although 18 years of using in vitro fertilization has shown it to be safe, newer procedures for fertilizing eggs can be more controversial. In a technique known as intracytoplasmic sperm injection, or ICSI, a single sperm is injected directly into an egg to fertilize it. The fertilized egg is then implanted in the woman's uterus. While ICSI is not controversial, other techniques are: Some procedures aim to aid the fertilization of the egg by partially dissecting the zona pellucida, the outer layer of the egg. The extent to which these procedures might cause congenital abnormalities is still undetermined. Also, injecting a sperm into the egg or cutting through the egg's outer layer might allow fertilization of an egg by a sperm that would otherwise not reach the egg because of defects. Some clinics may abuse otherwise acceptable procedures by not testing the male for genetically abnormal sperm.

Overall, says Dr. Sauer, "alternative parenting" arrangements have increased, partly because of AR. Not only are women in their 50s and 60s having babies, but so too are same-sex couples and single women. "And the further we get from the original intended use of AR-helping young women with tubal disease-the greater the debate," says Dr. Sauer.

Dr. Rosenthal agrees. "There's a lot of uncertainty as to the outcomes and implications of creating families by these new methods. While on one hand there are loads of ethical issues, when you see how transforming it can be for these couples, you see that AR has made a monumental contribution."

A Fertility Clinic Reborn

Dr. Mark Sauer
Drawing on a long history of innovative clinical research, Dr. Mark Sauer, director of the division of assisted reproduction, has slowly but steadily expanded and updated CPMC's Assisted Reproductive Technologies Clinic. Since his arrival here in July 1995, Dr. Sauer has supervised the purchase of new equipment, expanded the staff, and introduced updated AR procedures. The clinic moved into expanded quarters in the Atchley Pavilion, and a downtown center is expected to open late this year.

Dr. Sauer is considered a pioneer in assisted reproduction. His research at the University of Southern California enabled menopausal women in their 40s and 50s to benefit from AR. As part of a fellowship in reproductive endocrinology at UCLA, Dr. Sauer was involved in the first embryo donation program in the United States.

His current plans for the clinic include accelerating research on the freezing and banking of human eggs and embryos, continuing to work with applying embryo donation for women of older reproductive ages, and taking other steps to "make CPMC the center for innovative clinical research on assisted reproduction."

The Chicken or the Egg in the Ethics of AR

As the medical community rushes to develop ever more effective techniques of assisted reproduction (AR), are we as a society shirking our responsibility to deal directly with the ethical questions these techniques pose?

In a span of less than 20 years, the field has gone from fertilizations in petri dishes to manipulation of eggs to development of techniques for postmenopausal women to have babies. The driving force behind each of these technological advances has been a combination of scientific ingenuity and public demand for assisted reproduction.

But, asks Dr. Barron Lerner, the Arnold P. Gold Foundation Assistant Professor of Medicine in the Center for the Study of Society and Medicine: "Should we always do what the market will bear? Or should society become more involved in these decisions?"

Certainly, each new technological innovation has stretched the concept of what is considered "natural." "The first IVF baby was considered 'unnatural,' but now IVF is considered pretty reasonable," says Dr. Lerner. And, says Dr. Mark Sauer, chief of reproductive endocrinology and director of the assisted reproduction division, the practice of medicine itself isn't really natural. "In the tradition of medicine, you attack frontiers that have been traditionally left untampered."

Both doctors agree that at some point a line will have to be drawn. "Genetic manipulation is just down the road from reproductive technology," says Dr. Lerner. Some genetic technology-such as prenatal testing for Down's syndrome-is already in use and commonly accepted as beneficial. But using technology to create human beings who are "more desirable" is only one step away. (For more on genetics and ethics, see "Genetics: What to Know and When and Why," Spring 1996).

Asks Dr. Lerner: What if technology is used to manipulate embryos to obtain children with superior intelligence, an athletic build, or a certain hair color? The likelihood that we will soon have the capacity to "design" babies is not so outrageous anymore. "In general, technology pushes forward while society is still debating," says Dr. Lerner. "But we ought to think hard about letting technology dictate what's going to be done."

copyright ©, Columbia-Presbyterian Medical Center

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