For couples spending thousands -- or tens of thousands -- of dollars trying to conceive, a multiple pregnancy can seem like hitting the jackpot. That's how Lisa Owen of Frederick felt in 2001 when she and her husband, Alex, learned she was carrying triplets.

The couple's initial shock when her sonogram showed three heartbeats quickly turned to enthusiasm. After nine separate insemination attempts (which had produced one son and multiple miscarriages), they'd finally have a big family all at once.

But fertility specialists don't see triplets as a bonus.

Multiple-gestation pregnancies -- even just with twins -- increase the expectant mother's risk of high blood pressure, gestational diabetes, bleeding and cesarean section, according to Resolve, the National Infertility Association.

Babies born of such pregnancies are at higher risk for premature birth, low birth weight, developmental disabilities, respiratory and eye complications, and cerebral palsy. While a single-born U.S. child born in 2001 faced a 6 out of 1,000 chance of dying by its first birthday, according to the Centers for Disease Control and Prevention (CDC), the risk for twins was nearly fives times as great (30 of every 1,000), for triplets 12 times (71 of every 1,000), and for quadruplets 21 times (127 of every 1,000).

As a result, most reproductive endocrinologists now encourage couples attempting to get pregnant to use methods less likely to produce multiples. And next month the Society for Assisted Reproductive Technology (SART), a leading professional group of in vitro fertilization clinics, plans to urge its members to institute new methods to reduce risk of multiple births.

Three's Company

A single, healthy baby is the ideal outcome of fertility treatments, says David Hoffman, a reproductive endocrinologist with IVF Florida Reproductive Associates in Margate, Fla., and past president of SART.

The problem is that since most couples pay out of pocket for fertility treatments, many want to "maximize their pregnancy potential" with each try, Hoffman said. And maximizing potential can translate into taking bigger risks.

Lisa Owen describes her pregnancy and the birth of her triplets as easy. Of course, everything's relative. During her 33 1/2 -week pregnancy (a normal full-term singleton pregnancy is 40 weeks), the 5-foot 6-inch mom ballooned from 125 pounds to 190. The skin across her stomach was pulled so taut that it felt to her like it was burning. She spent the last month on bed rest, hooked up twice a day to a home uterine activity monitor and a pump that injected drugs to halt tiny contractions that were too subtle for her to feel.

After a cesarean delivery, her three baby boys spent the first three weeks of their lives in neonatal intensive care, even though they were large for triplets (two were 5 pounds, 9 ounces, the other 4 pounds, 14 ounces). But by the time they were 2 months old, Tanner, Hunter and Walker Owen were all robust and above the 50th percentile on the infant weight charts for non-premie children.

The boys, healthy and strong, will turn 3 years old next month.

Not everyone is so lucky.

Marie Duncan of Dover, N.H., carried her triplets to 36 weeks before her blood pressure suddenly shot up and doctors performed an emergency cesarean. On May 14 they delivered Colby (5 pounds, 15 ounces), Hope (5 pounds, 3 ounces) and Liette (4 pounds, 3 ounces). Three days later, on a Monday, Marie went home. The babies remained in the hospital because all were receiving oxygen, and Colby was on a feeding tube.

The next Saturday, Marie and her husband, Bob, both 36, brought the two girls home. (Colby wasn't off the feeding tube yet.) Everything seemed fine. But that night, Marie awoke just after midnight, unable to breathe. She was rushed to the hospital with blood pressure of 230/140.

The problem: heart failure, brought on by peripartum cardiomyopathy, a rare disorder in which the heart muscle becomes weakened and can't pump blood efficiently. Multiple pregnancy is a risk factor for the life-threatening disorder, which can occur any time between the last month of pregnancy and five months after delivery.

Moms aren't the only ones at risk in multiple pregnancies. Most multiples are born weighing less than 5 1/2 pounds, putting them at increased risk for health complications as newborns and for longer-term disabilities such as mental retardation, cerebral palsy and vision and hearing loss, according to the March of Dimes.

High-tech Multiples

Multiple births have risen dramatically in the United States over the past two decades.

In 2002, 31.1 out of every 1,000 deliveries yielded twins, up from 18.9 in 1980 -- a rise of 65 percent. The number of "higher-order multiples" -- meaning triplets or more -- jumped five-fold over the same period, from 37 per 100,000 to 193.5 per 100,000, according to the CDC.

Two trends explain the surge in multiple births:

* an increasing number both of women in their thirties giving birth (women in their thirties who become pregnant without fertility treatments are more likely than younger women to have multiple births); and

* advances in and greater access to fertility treatments, including in vitro fertilization (IVF), intrauterine insemination and ovulation-inducing drugs.

Of all triplet or higher births in 2000, 43 percent came from advanced reproductive technologies, primarily IVF. (In this process ripened eggs are removed from the woman's ovary, fertilized with semen and allowed to incubate in a laboratory dish. One or more developing embryos are then surgically transferred back into the woman's uterus.) Another 40 percent were likely the result of other fertility treatments such as ovulation-inducing drugs, and only 18 percent occurred naturally, according to a 2003 CDC report.

For a woman who gets pregnant the old-fashioned way, the odds of giving birth to twins are about 1 in 80, says Rockville perinatologist Thomas Pinckert, who specializes in multiple births. The odds of having triplets is 1 in 6,400.

For a woman who became pregnant by IVF in 2001, the odds of having twins were about 1 in 3, according to a study published in April in the New England Journal of Medicine. Her odds of having triplets or more were about 1 in 13. While that's a relatively high likelihood, it's down from 1 in 9 just four years earlier, thanks to concerted efforts by reproductive specialists.

The very high multiples that make the news -- six, seven and even eight babies at a time -- are virtually all the product of fertility drugs plus intrauterine insemination (a procedure in which sperm are injected directly into the uterine cavity, bypassing the cervix), says Michael Levy, a reproductive endocrinologist at Shady Grove Fertility in Rockville.

Applying the Brakes

Many experts attribute the recent downturn in triplets in large part to guidelines issued by SART in 1998. For IVF patients with above-average prognoses for successful IVF (women under 35 who were using fresh -- not frozen -- embryos), SART recommended transferring only three embryos per pregnancy attempt. Four embryos was the recommendation for women with average prognoses, and five for those with below-average chances of getting pregnant. A year later, SART amended the guidelines to recommend only two embryos be transferred in women with a "most favorable" prognosis -- those under 35, with enough good-quality embryos that there would be leftover ones to be frozen.

After its success at reducing the frequency of triplets, SART now wants to take aim at twins, said the group's president, Owen Davis, an associate professor of reproductive medicine at Cornell University's Center for Reproductive Medicine and Infertility in New York. Next month, SART will therefore revise its guidelines again. For most women under 35, SART will recommend that doctors transfer no more than two embryos and will suggest that a single embryo transfer be considered for those with the most favorable prognoses.

IntegraMed, the country's largest network of fertility specialists, announced in May that its Council of Physicians and Scientists has decided to develop a nationwide trial of elective single embryo transfer (eSET). The group expects hundreds of women undergoing IVF treatment to agree to have a single fertilized egg transferred, rather than two or more. What IntegraMed wants to learn is how the transfer of single embryos affects IVF outcome.

The basis for IntegraMed's plan is a recent Belgian study in which 367 women under age 38 with top-quality embryos underwent IVF treatment for the first time. Half had two embryos transferred, half had one. Both groups had a 37 percent birth rate, but 31 percent of the double-embryo-transfer pregnancies resulted in twins, while none of the single embryos transfers did.

Shady Grove Fertility, one of the IntegraMed clinics participating in the study, has collected some preliminary data of its own. In its practice to date, said Levy, it has found that with young healthy women with strong embryos, transferring two embryos has produced a 65 percent chance of pregnancy -- but that comes with a 50-50 chance of twins and a 1 to 2 percent chance of triplets (which results from one of the embryos splitting after being transferred to the mother's womb). With single transfer, the same woman, he said, was found to have a 40 percent chance of pregnancy, with only a 1 to 2 percent chance of twins.

One challenge: persuading clients to accept single implantation. Shady Grove has found, says Levy, that about 45 percent of couples would prefer twins, so they won't have to go through fertility procedures again. "We constantly have to reeducate these couples" about the risks associated with multiple births, he said. With a single baby, the chances of its being born healthy are 97 percent. With twins, that drops to 92 percent, according to Levy.

With other fertility treatments, preventing multiple births is a much less exact science. Using fertility drugs, a woman often produces two, three or four eggs per month instead of one, according to Levy. Doctors can use ultrasound equipment to look at the follicles (fluid-filled spaces within the ovaries that contain eggs) and see how many have grown larger. Usually, only the large ones release an egg -- but not always. One patient at Shady Grove recently showed one big follicle and two small on her ultrasound, but she wound up with triplets.

If the ultrasound shows too many enlarged follicles, Levy explains, he'll recommend a patient cancel the insemination that month, because the chances of multiple gestation are too high. The women are also warned not to have unprotected sex. Of course, not everyone listens. "If you've got someone with 10 follicles, most will see the logic" in not proceeding with the pregnancy attempts that month, says Levy. Smaller numbers take more persuasion.

The Worst Decision

One of the most upsetting scenarios in fertility treatment is when a woman so many embryos actually "take," i.e. implant themselves in the uterine wall, that both the mother and all her babies are at risk of serious health problems. (What's considered risky varies both by the physician and by the woman's health, but triplets seems to be the point where most fertility doctors start worrying.)

In those cases, recommended treatment is often a "reduction" of the pregnancy at 11 weeks. In this procedure, the doctor injects potassium into one or more of the fetuses. The potassium stops the fetal heartbeat, and the fetus is reabsorbed.

"It's a selective abortion, really," said Levy, "but it makes the chances of having a healthy baby far greater."

Not only does such a procedure pose an ethical dilemma for many prospective parents, but it also heightens risks. Reduction carries about a 5 percent chance of losing the pregnancy altogether, according to Levy.

The Owens' first perinatologist urged them to have her pregnancy reduced to twins.

"It was just terrible," Lisa Owen recalled of the meeting, where the doctor was adamant that there was nothing she could do to prevent preterm labor and other complications. Owen and her husband walked out the door and never returned.

Marie and Bob Duncan were also told that reducing their pregnancy from triplets to twins would lower the risk of complications. They declined a reduction as well.

If fertility specialists can prevent the multiple gestations to start with, then parents won't be faced with that decision.

Alternatively, as physician after physician noted in interviews, if insurance would pay for fertility treatments, prospective parents could afford to be cautious -- less likely to push to have more embryos transferred or to insist on going forward with artificial insemination even in a month when it seemed likely that six eggs were going to be released.

The Duncans kept their costs down by going to Canada for IVF treatments -- twice. The first time, Marie Duncan developed a life-threatening condition called ovarian hyperstimulation syndrome. She produced 30 eggs at once, but became so ill the doctors refused to go forward with the embryo transfer. Twenty-two of the eggs were strong enough to be fertilized and frozen -- but none survived to be transferred into Marie's uterus.

When the couple traveled to the Canadian clinic a second time, 10 strong embryos were produced, and the Duncans opted to have three transferred -- the maximum the clinic would allow. All three "took."

The clinic charged the Duncans $6,500 (plus drugs) for up to three IVF cycles using fresh embryos. (A similar three-cycle deal typically runs $20,000 in the United States.) With all drugs, travel, lodging and even sightseeing added in, the family's total costs came to just under $13,000.

Happy Endings

After dropping the first perinatologist who wanted them to reduce their pregnancy to twins, Lisa and Alex Owen found more encouragement with perinatologist Thomas Pinckert in Rockville.

"I do tell patients that statistics suggest that with triplet gestation, there's a 10 percent risk that the babies will be delivered" before they could survive outside the womb, Pinckert said. "There's another 10 to 15 percent risk of delivery at 24 to 28 weeks -- viable, but long-term survival is not as well spelled out. But optimistically, there an 80 percent chance that the babies will do well."

A prospective mother of triplets has an increased chance of pre-eclampsia or gestational diabetes, and any underlying health problems can be expected to worsen exponentially, according to Pinckert. "While most fertility doctors stress that you should reduce" triplets or more, he said, "we try to give an unbiased opinion. We evaluate for a mom's overall health -- does she have a reason she shouldn't carry [triplets]? Most don't."

The Owen triplets will turn 3 on July 23. Children and mother are all doing fine.

The Duncan triplets are also doing well at 10 weeks, reports Marie, except for one having colic.

Marie, on the other hand, is going to cardiac rehab three times a week, and is taking six drugs for her cardiomyopathy. She is taking a seventh for anxiety -- "because when I lie down at night," said Marie, "I start worrying about it. What if it happens again? What if I left four children behind?"

*

Lisa Barrett Mann has written previously for the Health section about IVF issues.

Four human embryos await implanting. The fewer embryos women receive, the lower the risk to them and babies.