Abnormal patterns of gene expression may be tied to in vitro fertili zation. / SANDY HUFFAKER/GETTY IMAGES

By GINA KOLATA


Over the past 30 years, in vitro fertilization has been reassuringly safe. Millions of healthy children have been born and developed normally. And the first IVF baby, Louise Brown, born in England on July 25, 1978, now has her own child, conceived without the technique.

But researchers have always wondered whether there might be subtle changes in an embryo that is grown for several days in a petri dish, as IVF embryos are - and, if so, whether would there be any consequences.

Now, with new epidemiological studies and techniques that allow scientists to probe the genes of embryo cells, some tentative answers are starting to emerge.

The issues have nothing to do with the chances that a woman will have twins, triplets or even, as just happened in California, octuplets. Instead, they involve questions of whether there are changes in gene expression or in developmental patterns.

For example, some studies indicate that there may be some abnormal patterns of gene expression associated with IVF and a possible increase in rare but devastating genetic disorders that appear to be directly linked to those unusual gene expression patterns. There also appears to be an increased risk of premature birth and of babies with low birth weight.

In November, the Centers for Disease Control and Prevention published a paper reporting that babies conceived with IVF, or with a technique in which sperm are injected into eggs, have a slightly increased risk of several birth defects, including a hole between the two chambers of the heart, a cleft lip or palate and an improperly developed esophagus.

The study involved 9,584 babies with birth defects and 4,792 babies without. Among the mothers of babies without birth defects, 1.1 percent had used IVF or related methods, compared with 2.4 percent of mothers of babies with birth defects.

The findings are considered preliminary, and researchers say they believe IVF does not carry excessive risks. There is a 3 percent chance that any given baby will have a birth defect.

But the real question - what is the chance that an IVF baby will have a birth defect? - has not been definitively answered. The C.D.C. study provides comparative risks but not absolute risks.

Yet even though the risks appear to be small, researchers who are studying the molecular biology of embryos grown in petri dishes say they would like a better understanding of what happens.

But following babies born after IVF or intracytoplasmic sperm injection is not easy. And if problems emerge from epigenetic changes, they may not be apparent until adulthood.

“When you send questionnaires, the tendency is for the couple who may have had a problem or who think they have a problem to answer that questionnaire,”said Dr.Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York Weill Cornell Center.

Those who do not respond tend to be parents whose children seem fine, skewing the data.