Two weeks ago, Brianna Morrison gave birth to six babies in Minneapolis. Less than a day later, Jenny Masche delivered six babies in a Phoenix hospital. Both of the women had been treated for infertility and had used fertility-enhancing drugs.
The two families expressed joy, but many fertility doctors were dismayed. For years, doctors have been pushing to lower the rate of multiple births due to fertility treatment. Not only had two headline-grabbing births occurred in the same week, but several recent scientific papers also revealed mixed results in the eight-year effort to reduce the U.S. multiple-birth rate.
One paper, published last month in the reproductive journal Fertility and Sterility, found that although the rate of higher-order multiples (triplets or more) has declined, the rate of twin births has increased.
"Higher-order multiples are not considered a success of assisted reproductive technology," says Dr. Anne Lyerly, chairwoman of the ethics committee for the American College of Obstetricians and Gynecologists. Twin births, although seldom as medically complicated as higher-order multiples, are not ideal either, she says. "Success is really defined now as a singleton gestation."
Earlier this month, the organization released a statement in the journal Obstetrics and Gynecology on the ethical issues related to multiple-gestation pregnancies -- urging doctors to strive to avoid them and to clarify for patients the risks that arise in such pregnancies.
Most of the decline in multiple births is because doctors have begun limiting the number of embryos transferred during in vitro fertilization to as few as possible -- ideally, just one.
But the use of fertility drugs that induce or enhance ovulation remain "the loose cannons in the armamentarium used to induce pregnancies," according to an editorial by Dr. Howard W. Jones, a prominent fertility specialist in Norfolk, Va., published in March in Fertility and Sterility.
"With IVF, there is great progress. But with infertility drugs, it's cruder and more unpredictable," says Dr. Steven J. Ory, president of the American Society for Reproductive Medicine. In multiple-gestation pregnancies, women have increased risk of gestational diabetes, bleeding and preeclampsia (dangerously high blood pressure). Infants born as multiples are almost always premature and have higher rates of low birth weight, cerebral palsy, developmental delays, birth defects and death. Even twins, who usually survive, are hospitalized twice as long as singletons and have much higher medical costs over the first five years. Cost of multiple births can easily top $100,000.
The recent sextuplet births are no exception to such perils. As of Friday, three of the Morrison babies had died and the other three were in critical condition. The babies were born after only 22 weeks of pregnancy, the threshold of viability. The survivors are being cared for at Children's Hospital in Minneapolis.
The Masche babies were born after 30 weeks' gestation and are in better shape, although all but one weighs less than 3 pounds. Jenny Masche suffered acute heart failure following delivery because of blood lost during the Cesarean section, according to her doctor at Banner Good Samaritan Medical Center. She is recovering. "We sort of wince when these stories occur," Ory says. "We're certainly hopeful for the patients. But the public is largely unaware of the problems and complications many of these families face."
The public often only sees the celebrated side of multiple births, such as the recent 10th birthday party for the Boniello sextuplets of New York who, at the time of their births, were only the third set of sextuplets born in the United States to survive.
In vitro versus drugs
Women undergoing IVF today face a much lower risk of multiple pregnancy than they once did. As IVF techniques have improved, doctors are finding they can achieve high pregnancy rates -- especially in women younger than 35 -- while transferring only one or two embryos to the uterus. Early in the evolution of IVF, it was common for doctors to transfer six or more, hoping that one would be viable.
According to a paper to be published August in Fertility and Sterility, the percentage of clinics transferring just two embryos to a majority of women younger than 35 increased from 3.3% in 1996 to 49.9% in 2003.
But fertility drugs used to induce ovulation are cheaper than IVF and are still used by many women. Because the results can be harder to control than IVF, the drugs can carry a higher risk of multiple births. The May Fertility and Sterility study estimated the percentage of multiple births due to ovulation induction drugs at 21% for twins, 37% for triplets and 62% for quadruplets.
Fertility drugs are given to a woman who does not ovulate so that her ovaries will release at least one mature egg. Conception can occur naturally, via artificial insemination, or the eggs can be used in IVF.
In many cases, Ory says, diligent monitoring of a patient taking fertility drugs can help prevent a multiple gestation pregnancy. If an exam shows that the woman may be producing too many eggs, the cycle can be stopped before conception. "In some cases, the patients have not been monitored as closely as is recommended," Ory says.
But reproductive medicine still produces occasional surprises. Dr. David A. Grainger, president of the Society for Assisted Reproductive Technology, says he once used fertility drugs and artificial insemination to help an infertile woman become pregnant, and she gave birth to a healthy baby. Two years later, doctor and patient agreed to the same course of treatment. The patient conceived six babies.
"I would never have predicted that," says Grainger, of Wichita, Kan. "I think there are some of these cases that absolutely catch clinicians by surprise. Fortunately, they are rare."
The use of fertility drugs has a place in treatment, says Dr. Eric Surrey, medical director of the Colorado Center for Reproductive Medicine. "Many women don't ovulate. There is no reason to go straight to IVF if we can stimulate ovulation with medication."
Most often, doctors try to stimulate ovulation with a drug called clomiphene citrate, which carries about an 8% chance of producing twins but a very low risk of higher-order multiples. Drugs called gonadotropins, however, are more powerful and produce a higher risk of multiple births, Surrey says.
"The percent of patients we administer those to with artificial insemination is very low," Surrey says of gonadotropins. "The reason is that multiple pregnancy rates can't be controlled very well. And the pregnancy rates aren't very good."
Some doctors refuse to use gonadotropins and artificial insemination in younger women because of the unpredictable outcome, Ory says.
In his editorial in the March issue of Fertility and Sterility, Jones noted that no national organization "has been bold enough to offer guidelines attempting to control and monitor multiple pregnancies because of ovulation induction and ovulation enhancement."
Price factors in
The cost of treatment often persuades couples to try infertility drugs instead of opting for the more predictable IVF, Grainger says. One cycle of IVF can cost $10,000 while fertility drugs can cost a few hundred dollars.
In the long-run, insurers may save money by steering more women to IVF instead of using gonadotropins, Grainger says. But "even some states with mandatory insurance for IVF still require couples to undergo three cycles of ovulation induction and artificial insemination before IVF. You would think the payers would be all over this. There is a big disconnect."
Couples who risk a multiple gestation pregnancy may also have to face the difficult prospect of selective reduction, in which the doctor aborts one or more of the fetuses to improve the likelihood that the remaining ones will be born healthy.
According to news reports, both the Morrisons and Masches were offered selective reduction but declined.
Selective reduction is an uncomfortable issue for doctors and patients, says Lyerly, an associate professor of obstetrics and gynecology at Duke University. ACOG's ethics committee statement urges doctors and patients to discuss pros and cons of treatments that may result in a multiple gestation pregnancy including selective reduction.
But, she says, "There are tremendous challenges .... When you're trying to become pregnant, it's really hard to think about bad or truly tragic outcomes."
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