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Multiple Births: The More the Merrier?

Jody Kirsch says she was shocked when she learned she was going to have triplets. "I knew that there possibly could have been multiples, but when I thought 'multiple,' I thought twins — never triplets," she recalls. "When the doctor saw the three sacs [by ultrasound] and said, 'there's one, there's two, there's three,' I just couldn't believe it."

But Jody's experience is becoming increasingly common. For American women in their thirties, like Jody, the rate of multiple births has jumped by 400 percent in just the last five years. For women in their forties, the multiples rate has skyrocketed 1000 percent. In 1997 alone, U.S. women ages 45-49 had as many sets of twins as were born to the same age group during the entire decade of the 1980s.

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This particular baby boom is mostly attributable to the increasing use of fertility treatments, however, it is not necessarily a source of pride to most assisted reproduction specialists. Widely publicized pregnancies involving "high order multiples" (triplets or more) have provoked harsh criticism, even from fertility doctors themselves, because of the risks to both mother and babies.

"This shouldn't be a contest. When we see fives, sixes, sevens, eights — I'm sure we'll be seeing nine at some point—I think that's a horrible outcome," says Jody's fertility specialist, Dr. Alan Copperman, Director of Infertility at Mount Sinai Medical Center in New York. "I wish these couples well," he explains, "I hope that each of these babies does just fine, but in the majority of cases, these kids are going to have problems, so this is not something to celebrate. This is not a good day for reproductive medicine when we help a couple get pregnant with sextuplets. That should help us reevaluate what medications we're using, what treatments we're using, and how we're using them."

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The two most commonly employed assisted-reproduction techniques today are fertility drugs and in vitro fertilization (IVF). Synthetic hormones like Clomid and Serophene are generally the first line of treatment for infertile couples. By stimulating a woman's ovaries to release eggs, they make it more likely she'll conceive naturally. If that fails, IVF requires using the same drugs to provoke the release of eggs, which can then be harvested and fertilized outside the woman's body. The resulting embryos are allowed to develop for a few days in a culture medium, then placed in her uterus in the hope that at least one will implant there and begin a pregnancy.

Both methods assume that most of the eggs a woman releases won't be fertilized, or if they are, that most will not successfully implant and continue growing into a fetus. Even so, responsible doctors usually hedge against the possibility of high-order multiples by closely monitoring women only taking drugs. If ultrasound reveals that too many eggs are present, the couple is advised to abstain from trying to conceive during that cycle.

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IVF guidelines recommend for women under 35 that no more than three embryos be placed in the uterus during a single cycle, and no more than four for a woman over 35. There is no U.S. law regulating the number of embryos transferred, but in Europe, laws do limit IVF practitioners to placing only two embryos per cycle.

Still, betting that most attempts are likely to fail leads to surprising payoffs like Jody's after she underwent IVF at age 34. "They put back three embryos," she recalls, "One was great, one was good, and one was okay—that was how they said it—and I said, 'alright, let's just hope one of them takes,' and they all took!"

Economics also propel some couples to take the chance of having multiples by allowing as many as seven IVF-created embryos to be introduced into to the uterus at once. According to Dr. Daniel Kenigsberg, Co-Director of Long Island IVF at Mather Hospital in New York, "Some couples are more anxious than others to be aggressive. There is a big push by the patients to maximize their chance of pregnancy in just one try because oftentimes these procedures are not covered by insurance and are expensive to the tune of $8,000 to $10,000 per procedure."

Insurance coverage for IVF is mandated in only a handful of states: Arkansas, Hawaii, Illinois, Maryland, Massachusetts, Montana, and Rhode Island.

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While using fertility drugs alone is relatively affordable, it's also the approach that offers the least control. Whether due to inadequate monitoring or a couple's decision to ignore warnings when a large number of eggs is detected, the majority of very high-order multiple pregnancies result from using just fertility drugs.

Well-publicized examples include the McCaughey septuplets born in Iowa in November 1997 and the Chukwu octuplets born in Texas a year later, both cases involving women in their twenties who only took fertility drugs. While the McCaughey and Chukwu families expressed their joy at having so many children at once, news stories about these dramatic pregnancies and deliveries prompted considerable criticism because of their inherent dangers.

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"The risks of multiple gestation for the mom include diabetes, serious blood pressure problems, and bed rest for many months," explains Dr. Copperman, "For the fetuses, the most common risk is prematurity. Babies are being born three and even four months prematurely when they are part of a higher-order gestation. There are problems with the lungs, the eyes, the brains—every major organ system. The baby really needs at least seven or eight months inside to fully mature."

One of the Chukwu babies died shortly after the octuplets' birth, four months premature, and the rest required months of hospitalization. The McCaugheys have disclosed some of the serious problems their babies, born nine weeks early, are experiencing. Two of the seven suffer from different forms of cerebral palsy which prevent them from walking or even sitting up, and scans reveal they have underdeveloped areas in their brains. A third baby requires feeding through a tube in her stomach.

Jody's triplets, Amanda, Hunter and Alexi, were born six weeks early, with only minor complications. Hunter remained on a respirator for a few days and the girls were placed under sun lamps to treat jaundice. But the risks of severe complications, even in a triplet pregnancy, are fueling a drive within the assisted reproduction community toward greater caution and a shift toward techniques that reduce or eliminate the chance of high-order multiples.

"Multifetal pregnancy is a problem that must be solved," one recent editorialist wrote in Fertility & Sterility, the journal of The American Society for Reproductive Medicine (ASRM). The ASRM has urged revision of IVF guidelines to lower the recommended number of embryos placed in women under 35 to two instead of three. The Society has also touted a new IVF technique called blastocyst transfer, which increases pregnancy rates while requiring fewer embryos to be transferred, as "the most promising clinical trend in in vitro fertilization."

Blastocyst Transfer: Later is Better Typically, IVF embryos are transferred to a woman's uterus after two or three days in a culture where they've grown to a size of about eight-to-12 cells. But recently new growing media have made it possible to culture embryos for five or six days before being transferred. The extra time allows them to grow to the larger and more differentiated blastocyst stage. Since generally only the healthiest embryos in a group will survive the additional days, those eventually transferred are of high quality and more likely to result in a successful pregnancy.

Scientists also suspect that blastocyst transfer may be more effective because it is closer to what happens in the body after normal conception. A naturally-conceived embryo is still developing in the fallopian tube at day two or three after fertilization, so the uterine environment might be hostile to an embryo at that stage in some way that is not yet fully understood. By day five, though, a normal blastocyst would already have arrived in the uterus, so a transferred blastocyst may adapt more readily to that environment too.

So far, studies have demonstrated pregnancy rates of 40 percent to 60 percent using the blastocyst transfer technique, compared with the average IVF success rate of 9 percent to 25 percent. And, because of the increased chances for pregnancy, Dr. Kenigsberg points out, "It allows us to put back fewer embryos at one time and avoid the problem of multiple pregnancies, and specifically high-order pregnancies. It's obviously much more natural and much healthier for women to have one baby at a time."

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