The doors to the neonatal intensive care unit at Banner Good Samaritan Medical Center swung open last month to four tiny siblings. Stephanie Mast’s three girls and one boy became the Phoenix hospital’s 69th set of quadruplets.
Another set of quadruplets is expected to arrive before the end of the year.
"Twins certainly are routine at this point. Triplets are becoming more common," said Dr. Deborah Tom, a neonatologist at Banner Good Samaritan. "It’s the higher number that bugs the eyes out sometimes."
Those higher numbers — quadruplets and quintuplets — are now part of the natural flow of multiple babies born at Banner Good Samaritan, which delivers more quadruplets than any other hospital in North America. What is not so natural is the way bunches of wombsharing babies are coming into the world.
Infertility treatment is responsible for the bulk of multiple births, which have skyrocketed as more infertile couples shell out thousands of dollars for today’s advanced drugs and high-tech procedures. From 1980 to 2000, the number of high-order multiples — triplets, quadruplets and higher — has jumped fivefold, according to the National Center for Health Statistics.
The trend is troubling, medical experts say, because of the astronomical costs of caring for women who are pregnant with high-order multiples and their babies after they are born prematurely. There also are the financial and psychological costs to the mother and father.
Meanwhile, the Valley has become a Mecca for infertility clinics, some of which are expanding to serve the many couples starting families here.
Demand for reproductive medical treatment has fueled intense competition for patients among infertility clinics, where the pressure is on to make a baby.
That pressure — driven by couples desperate to get pregnant, doctors who want to succeed and the high dollars at stake — often leads to the kind of risktaking that results in multiple pregnancies. To boost the odds of getting their patients pregnant, doctors are routinely transferring several embryos at once, and in some cases, instantly turning their patients into future parents of multiples.
"Fertility centers attract people based on how successful they are, so the competition to one-up the other guy becomes intense," said Dr. John Elliott, whose medical practice, Phoenix Perinatal Associates, attracts women worldwide who became pregnant with high-order multiples after undergoing infertility treatment. "The increase (in multiple pregnancies) comes from putting back a lot of embryos and not accepting failure."
BEHIND THE NUMBERS
The Tribune reviewed the most recent reports on eight Arizona infertility clinics by the U.S. Centers for Disease Control and Prevention and found that in 2002, clinics putting the most embryos into women at once had some of the highest pregnancy rates. Those clinics, however, also had the highest rates of highorder multiples.
The review focused on assisted reproductive technology — usually in vitro fertilization — using fresh, nondonor embryos produced from sperm and egg in the laboratory and implanted into the uterus of women younger than age 35.
The Tribune found that:
• Five of the eight clinics exceeded the national average of 38.9 percent for multiple births from assisted reproductive technology. Most of those clinics transferred more embryos at once than the nationwide average of 2.7 embryos.
• At all but one clinic, the risk of having a multiple birth was at least 30 percent. At two clinics, at least half of births from assisted reproductive technology were multiples.
• Five of the eight clinics exceeded 1999 guidelines for embryo transfer set by the Society for Assisted Reproductive Technology, the voluntary regulator of infertility treatment providers.
Few of the clinics met more stringent guidelines for embryo transfer set last year by the society, which now recommends that clinics transfer not more than two embryos in patients younger than age 35 with the best prognosis for pregnancy.
Infertility doctors said the numbers do not reflect improvements in the laboratory since 2002 that allow the transfer of fewer embryos for each in vitro cycle.
Physicians are also dealing with unexplained factors behind infertility and a woman’s genetic ability — or inability — to get pregnant.
"There are medical indications for why you would want to transfer more (embryos), and sometimes that backfires on you," said Dr. Jay Nemiro, the medical director of the Arizona Center for Fertility Studies in Scottsdale. "You just don’t know what a woman’s reproductive genetics are going to be."
Nonetheless, medical authorities agree that the more embryos transferred, the greater the risk for multiples — a risk that infertility doctors and their patients continue to take, said Dr. H. Randall Craig.
His Chandler clinic, Fertility Treatment Center, has won awards for low rates of multiples. "It’s a competitive field. People look at your overall success rate," he said.
At some infertility clinics, where success is measured by the number of patients who get pregnant, "the best way to maximize pregnancy rates is to transfer more embryos," Craig said.
Driven to conceive, Tina Nelson and her husband desperately wanted children. The Scottsdale couple had successful careers and married in their early 30s. By the time they realized they were infertile and began their first cycle of in vitro fertilization, Tina was 37.
The cycle did not result in a baby.
The Nelsons tried five more times unsuccessfully, pouring what would have been their retirement savings — nearly $100,000 — into infertility drugs, tests and procedures. After each failed in vitro cycle, Nelson grew more anxious, wanting to put in more embryos. The doctor always held the line at three.
"I just can’t tell you how low I was at certain times," said Nelson. "My husband said, ‘This is changing you.’ I just couldn’t stop. I knew I wanted children."
On the seventh try, after the couple had adopted 6-month-old Shelby, Nelson, 42 at the time, learned she was pregnant. During an ultrasound, she saw three heartbeats.
"I bawled like a baby. That was not the outcome I was looking for," said Nelson, who is 5 feet tall and weighs about 100 pounds. "I didn’t think three healthy babies could come out of me."
Today, Nelson said her 17-month-old triplets — Cooper, Kendall and Katie — are healthy, and that she couldn’t be happier being a mother of multiples.
As president of the Arizona chapter of RESOLVE: The National Infertility Association, Nelson said she wants to help couples in the throes of infertility, a condition that afflicts about 6.1 million Americans, or about 10 percent of people of reproductive age.
"There are so many hurting people out there who need support, who need education," she said.
As men and women wait longer to get married and start families, they are at greater risk for conceiving multiples. They also are at greater risk for infertility. Couples, many in their mid- to late-30s, are increasingly seeking medical help to get pregnant.
The number of assisted reproductive technology procedures increased 78 percent from 1996 to 2002, according to the CDC. The number of children produced from these procedures grew from 20,840 to 45,751 infants, more than half of whom came from multiple-birth deliveries.
Assisted reproductive technology "poses a major risk for multiple births," according to the CDC. "Efforts should be made to limit the number of embryos transferred for patients undergoing (assisted reproductive technology)."
In May 2004, the Society for Assisted Reproductive Technology toughened its guidelines for embryo transfer, recommending that in patients younger than 35 years old "no more than two embryos should be transferred in the absence of extraordinary circumstances."
While doctors from some infertility clinics in Arizona said they are following the guidelines, others said limiting transfers to two embryos is difficult, especially when couples want to increase their odds of getting pregnant and can afford only one cycle of in vitro fertilization. One cycle, including infertility tests and drugs, can cost $10,000 to $30,000.
Transferring one embryo brings the lowest chance of pregnancy, with one clinic estimating a 7 percent chance of success. The probability jumps significantly with the transfer of two embryos, and peaks with three or four.
At the West Valley Fertility Center in Glendale, patients are routinely counseled about the risk of multiples from infertility treatments, said medical director Dr. Vladimir Troche. But the risk often seems small to patients compared with the financial and emotional risk of a failed in vitro cycle, he said.
"In their mind, this is it," said Troche. "It’s a very emotional decision you’re trying to make based on objective facts, but objective facts are fuzzy when you want to get pregnant."
Troche’s clinic had the state’s highest rate of high-order multiples among women younger than 35 receiving in vitro fertilization in 2002. More than 15 percent of patients became pregnant with high-order multiples. Troche said he transfers, on average, three embryos to women in this age group.
"We are really not proud of that 15 percent," he said. "It just reflects how difficult it is to get patients to transfer two embryos."
Patients and doctors said financial constraints force them to take chances they might not otherwise take. Health insurance does not typically cover infertility drugs and services beyond initial diagnostic testing. With one shot at in vitro, doctors and patients are trying to maximize their chances of a pregnancy, often by putting in multiple embryos.
"Somewhere you have to find that balance," said Nemiro. "You definitely don’t want multiples, but you want to balance that with her strong desire to get pregnant."
After five miscarriages and two ectopic pregnancies that required the removal of her fallopian tubes, Jane Crandell of Phoenix had to do in vitro fertilization. She and her husband saved up $12,000 for one cycle, and had six embryos available for transfer.
Given her medical history and age, 36 at the time, Crandell said her doctor, John Couvaras of Phoenix, suggested she have no more than three or four embryos transferred. When the Crandells asked for all six embryos, Couvaras, who declined to be interviewed for this story, had them sign a consent form before transferring all of them. Crandell became pregnant.
"I was so worried about losing this (pregnancy). We had our entire church praying since the time I started my first shot," she said, referring to a standard series of injections to help conception. "My doctor guessed at the most I’d get twins."
On March 25, Julian, Chloe Jane, Sophia and Christian were born.
THE BABY BUSINESS
Some infertility clinics are offering services as a package deal or with a refund offer. At Arizona Reproductive Medicine Specialists in Phoenix, patients who qualify can purchase more than one round of in vitro for less than the cost of buying cycles individually. And some patients can pay for a guarantee that if they fail to get pregnant, they will get their money back.
"What I tell patients is it’s an insurance policy," said Dr. Barbara Faber, co-medical director of Arizona Reproductive Medicine Specialists. "It lowers the anxiety level about the financial impact of a negative result. All we have to do is keep a good pregnancy rate."
But some infertility doctors said such offers are just marketing gimmicks to lure in patients who are most likely to become pregnant from infertility treatment. To qualify, women usually have to be a certain age, have high-quality eggs and lack a history of unexplained miscarriages or poor response to in vitro.
"Personally, I think those kinds of advertising are not ethical," said Dr. Timothy Gelety, medical director of the Arizona Center for Reproductive Endocrinology and Infertility in Tucson. "They’re designed to make money. I can’t help but think it’s not a benefit to the patient. You need to do what’s appropriate for the patient."
Faber said her clinic’s operation of the rebate program is ethical because all patients are treated the same. A woman who has a money-back guarantee, for example, is not going to have more embryos transferred than a woman who is not eligible for a refund, she said.
In 2002, the Phoenix clinic reported to the CDC that it transferred an average of three to four embryos during each in vitro cycle, depending on the woman’s age. Today, Faber said the clinic often transfers two embryos in all age groups.
"It doesn’t change one bit what we do on a clinical basis. We have no idea who’s on refund or not," she said. "It’s just a great way of helping patients deal with their fears and take the stress out of it."
Still, patients at her clinic with the best odds of getting pregnant have about a 40 percent chance their in vitro cycle will fail, a risk that complicates the business of infertility medicine.
"There are very few things like our field of medicine," Faber said. "The outcome is not guaranteed. We don’t know they’re going to be pregnant. There are a lot of unknowns."
BUSTING THE BABY BOOM
Physicians and infertile couples say expanding health care coverage would help deflate the financial and emotional pressures that go with high-tech help making a baby.
If health plans routinely covered advanced reproductive technology treatment, doctors and patients would take less risks because they could go through more than one in vitro cycle, said Elliott of Phoenix Perinatal Associates. Fewer embryos would be transferred during each cycle, and the risk of becoming pregnant with high-order multiples would drop.
"It would allow everybody to drop back and say ‘Let’s do this reasonably,’ " he said.
Fifteen states require that health insurers pay for some degree of reproductive medical treatment. In Connecticut, a law went into effect last month that gives women age 40 or younger coverage for up to two in vitro cycles, three intrauterine insemination cycles and four ovulation induction treatments.
The law is the nation’s first to limit embryo transfers, an effort to reduce multiple births. No more than two embryos can be implanted during each in vitro cycle. In Europe, several countries have a two-embryo limit, as well as insurance coverage for infertility treatment.
The Society for Assisted Reproductive Technology objects to limiting the number of embryos transferred because the limits would take away the discretion doctors need when treating difficult patients.
Health insurers object to mandating coverage for infertility treatment because it would increase costs to employers and their employees, who continue to pay more each year.
And even if insurance coverage reduced the number of embryos transferred during each in vitro cycle, a large source of multiple pregnancies remains. Powerful infertility drugs, which stimulate ovulations, cause at least as many multiple pregnancies as in vitro cycles, and are more difficult to control, infertility specialists said.
Mesa resident Stephanie Mast, her husband and her doctor didn’t expect she would conceive more than triplets after an infertility drug helped her produce five eggs. That’s because two of the eggs were positioned where one of her fallopian tubes had been removed after an ectopic pregnancy.
Somehow, Mast, 29, became pregnant with quadruplets.
"It’s unusual, but my fallopian tube must have moved to gather the egg on the other side," she said.
Mast’s pregnancy illustrates the uncertainties doctors face when putting patients on infertility drugs. Some of the medicines carry a relatively low risk of multiples, while others carry a high risk because they induce superovulation, helping women produce many eggs for fertilization.
Super ovulators are typically used in preparation for in vitro, making many eggs available for the cultivation of embryos in the laboratory. But some physicians have patients use the drugs to help them get pregnant on their own, or for procedures in which the doctor has less control over the number of eggs fertilized.
"The problem comes in when a practitioner is using powerful fertility medication in young women," said Gelety. "You have to be very, very cautious if you’re not sure what a woman’s problem is because the risk is high-order multiples."
But even when patients are monitored while on the drugs and cautioned against having intercourse because they have an abundance of follicles, they do not always heed that advice.
"They want to get pregnant and they’ve been trying for a long time," Troche said. "The risk may not look that big at that point."
To significantly reduce highorder multiple births, competition among clinics to achieve high pregnancy rates would have to be removed. And that is something unlikely to happen, said Elliott.
"It would be very nice if I never had to take another set of quadruplets or quintuplets," he said.