Hopes and Risks Study suggests tie between cancer, fertility drugs

September 07, 1993|By Kelly Costigan | Kelly Costigan,Contributing Writer Universal Press Syndicate

Joan Kiplinger vividly remembers the night in February when she heard that the "miracle" fertility drugs she had taken to try to get pregnant could lead to ovarian cancer. The assertion, broadcast on ABC's "20/20," focused on a Stanford University study that found that women who had taken fertility drugs were many times more likely to get the disease. Several years ago, Ms. Kiplinger went through eight cycles of in vitro fertilization, complete with regular injections of the fertility drug Pergonal.

"It is a cruel joke on all of us who have undergone this treatment," says Ms. Kiplinger, 40, a Connecticut resident who eventually adopted a child. "Not only have many failed to get pregnant, but now we face this possibility."

Ms. Kiplinger is not alone in her anger. The almost 2 million women who've taken the drugs and the doctors who've administered them have been stung by scientific doubts about the medications that support a $1 billion-a-year infertility treatment business.

Infertility can be caused by such conditions as failure to ovulate, blocked fallopian tubes and endometriosis (in which tissue that lines the uterus migrates to other parts of the abdomen). To "cure" the problem, specialists once resorted to such useless measures as giving women thyroid hormones. In the past 30 years, however, three drugs have revolutionized the field. With them, doctors at the nation's 275 infertility clinics now help thousands of frustrated women a year go home with babies.

The first to hit the market, in 1967, was Clomid, a pill that's still the initial drug given to infertile women. Clomid prods ovaries that aren't producing eggs to release at least one per cycle. In 1969 came two more powerful drugs, Pergonal and human chorionic gonadotropin (HCG), which stimulate the growth, maturation and release of multiple eggs per cycle.

"Pergonal was a remarkable breakthrough," says Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York Hospital-Cornell Medical Center in Manhattan.

In a typical procedure, an infertile woman injects herself with Pergonal over several days to increase the eggs ready for release during her cycle from the normal one to as many as five or 10. She then injects HCG once to release the eggs from the sacs of the ovaries. Thirty-six hours later, the sperm can be inserted to meet the eggs in the fallopian tube (artificial insemination). Or the eggs can be removed and combined with sperm, and the resulting embryos transferred back into the uterus (in vitro fertilization).

Getting pregnant is a long shot for all women, mostly because so many embryos are simply not healthy enough to implant and grow. For women with extra difficulties, Pergonal creates some hope. With in vitro procedures at Dr. Rosenwaks' center, a woman who gets one embryo has a 15 percent chance of taking home a baby; a woman who produces four embryos has a 43 percent chance. While these aren't the greatest success rates, many infertile couples have been willing to pay the sometimes enormous bills. In vitro, for instance, costs $6,000 to $10,000 per cycle.

The drugs' long-term health impacts have never been thoroughly studied. The only large study of fertility drugs, done in Israel and published in 1987, found no connection with ovarian cancer, but it failed to track subjects into their 50s and 60s, when the disease usually appears. And the original clinical studies required for Food and Drug Administration approval weren't designed to detect links with such a rare disease.

The study published last November in the American Journal of Epidemiology was the first to suggest the drugs might not be safe. Led by a team at Stanford, researchers from 14 institutions around the country pooled and re-crunched the data from several smaller studies in an effort to pinpoint risk factors for ovarian cancer. They found that taking fertility drugs increased a woman's risk of ovarian cancer by three times. (Normally, 3 percent of women get the disease.) Women who had taken the drugs but never gotten pregnant were at even higher risk.

"We've just got this worrisome hint that something might be going on," says Alice Whittemore, the Stanford epidemiologist who led the team. "That is why everyone is so concerned." It doesn't calm nerves to know that the hard-to-detect cancer kills more than half its victims within five years.

Cancer theories support link

The possible link between fertility drugs and ovarian cancer fits the theories about what triggers the disease. When a woman ovulates, each ovary must rupture to release its eggs; that tiny hole must then be repaired. One idea is that something occasionally goes awry during the repair process -- a mutation, xTC perhaps -- that signals cells to grow uncontrollably.

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