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The Canary in the Medical Coal Mine

By Michael Cook

A steroid is being used off-label early in pregnancy to “normalise” the gender of the foetus.

By and large, genetic engineering of human embryos is still science fiction. But there are other ways to alter the development of an unborn child.

Bioethicist Alice Dreger, of Northwestern University Feinberg School of Medicine in the US, and colleagues recently documented in the Journal of Bioethical Inquiry extensive off-label use of a synthetic steroid, dexamethasone, which is being used to engineer the development of foetuses for sex normalisation purposes.

There is another sensational angle to her study: some doctors may be using the drug to allay parents’ fears that their daughters might become lesbians. The gay press was outraged.

Off-label use of dexamethasone involves women who are at risk of having a daughter with congenital adrenal hyperplasia (CAH), which can lead to the birth of girls with intersex or more male-typical genitals and brains.

One solution is to give the mothers dexamethasone as early as the fifth week of pregnancy to try to “normalise” development. Because the drug must be administered before doctors can detect whether the foetus is female or is CAH-affected, only one in eight of those exposed are the target type of foetus.

Dreger and her colleagues drew up a long list of ethical problems with off-label use of this drug. They include:

• administering a high-risk treatment even though nearly 90% of the foetuses exposed cannot benefit;

• informing women that the treatment is safe when there is no scientific evidence of this; and

• evidence from Sweden that there are serious health risks.

But the researchers had bigger fish to fry. In their eyes the use of this powerful drug is “a canary in the modern medical mine”. They wrote: “This case appears to be representative of problems endemic in modern medicine, problems that threaten the health, lives and rights of patients who continue to become unwitting subjects of (problematic) medical experimentation.”

They suggest that there has been “a major failure of the layered systems designed to protect subjects of research, especially pregnant women and their fetuses” – not just with dexamethasone.

Another area that merits investigation is IVF. A recent article in Reproductive BioMedicine Online (a journal founded by Bob Edwards, a Nobel laureate for his work in IVF) contained some startling admissions. IVF doctors routinely ignore safety and efficacy concerns when developing new techniques for overcoming infertility, wrote Rachel Brown and Joyce Harper of University College London:

In 1978, the first child conceived by IVF was born. In the following 33 years, numerous technologies and techniques have been developed... However, these techniques have rarely been robustly tested and approved before they are routinely offered to infertile couples. In other cases, a development in our scientific understanding of a technique has failed to be quickly incorporated into clinical changes. This raises the concern that some of the techniques offered to some patients offer little or no benefit, and in the worse cases [are] not confirmed to be safe.

Brown and Harper worry that even riskier techniques such as artificial gametes are being developed, yet the IVF industry may not be ready to change its ways to put patient safety first and to use randomised trials to test safety and efficacy.

The troubling use of drugs for sex normalisation probably involves only a few thousand children, but five million IVF babies have been born since 1978. One major IVF technique, intra-

cytoplasmic sperm injection, has never been tested in trials. Its popularity is growing even though it has been associated with an increase in the incidence of birth defects.

What explains this indifference to normal standards of medical research? Here’s my theory: modern medicine is a consumer transaction in which outcomes are measured not by health but by customer satisfaction. When this happens, an unborn child can become a commodity and its rights and interests may have little weight compared with their parents.

A comment by a leading American paediatrician cited in Dreger’s article sums the situation up very concisely: “It seems to me that the main point of prenatal therapy is to allay parental anxiety. In that construct, one must question the ethics of using the fetus as a reagent to treat the parent, especially when the risks are non-trivial.”

Michael Cook is editor of the bioethics newsletter BioEdge.