Dr. Robert Stillman is used to a common plea from infertile couples: that he transfer multiple embryos to increase their chances of getting pregnant.
Some women even yell and scream at him, he said, begging for twins.
"The Holy Grail is one embryo, but I have patients every day asking for more, including twice today," said Stillman, a reproductive endocrinologist at Shady Grove Fertility Center in Washington, D.C. "They say they don't want to pay for another cycle or to go through all this again."
An in vitro fertilization (IVF) cycle of only two embryos produces a 60 percent chance of twins, putting babies at risk for premature birth and lifelong health problems.
"Even when you show them the data, they still ask for it," he said. "It's an enormous issue and it keeps the frequency of multiple pregnancies high."
IVF is among the biggest success stories of modern medicine -- its founders just won the Nobel Prize -- but multiple pregnancies put financial strain on an already over-burdened health care system.
Even with new guidelines to transfer one embryo for each in vitro cycle, doctors come under enormous pressure to accommodate couples' demands.
Dr. Michael Kamrava, the Beverly Hills fertility doctor who assisted octomom Nadya Suleman, admitted last week, for instance, that he had made a mistake in 2008 by transferring a dozen embryos against his better judgment.
Kamrava, who helped Suleman conceive six other children before the octuplets, testified in tears before a Medical Board of California hearing last week, according to the Los Angeles Times.
"I'm sorry for what happened," he said. "When I look back at it, I wish I had never done it and it will never happen again."
His attorney, Henry Fenton, asked, "Do you feel that what you did was wrong?"
"At the time that I did it, I thought I did the right thing," said Kamrava, who could lose his medical license. "When I look back at it, even with all those circumstances, I was wrong."
When Kamrava recommended implanting four embryos, or using Suleman's previously frozen embryos, she was adamant he transfer more.
"I had to go with the patient," he testified.
According to the Centers for Disease Control and Prevention, 142,435 assisted reproductive technology cycles were performed at 430 reporting clinics in the United States in 2006, resulting in 43,412 live births (deliveries of one or more living infants) and 57,569 infants.
The incidence of twins has jumped 65 percent in the past two decades. A record 138,961 twin births -- 32.2 per 1,000 live births -- were recorded in 2007, according to the CDC's vital statistics. In addition, there were 5,968 triplet births, 369 quadruplets and 91 quintuplets or higher.
Since then, there has been a reduction in the number of triplets and quadruplets, although the rate of twins has stayed stable, Stillman said.
"Who is to decide how many embryos is enough?" he asked. "If I take a stand and transfer one embryo and they want two, and I talk them into one and they don't get pregnant, it's my fault. There isn't just the blame, but I feel badly."
Shady Grove is the biggest fertility center in the United States, handling 4,200 cycles a year. In certain patient groups, the singleton success rate is about the same as using two embryos. "That's the amazing thing," Stillman said.
He said doctors have to balance patient autonomy with ethical choices. "Beneficence is an important part of it ... doing good for the children," he said. "That's where [Kamrava] failed."
Having twins, not to mention just eight children, carries risks for both mother and her babies.
"For the mother, it's less severe; diabetes and hypertension," Stillman said. "There can be months and months of bed rest with clots and embolisms.
"For the infant, the risks are lifelong: prematurity, cerebral palsy, blindness, months in intensive care. You can go through a litany of things for people who want to have a family. I have this discussion every day."
Indeed, one of Stillman's patients this week lost twins at 20 weeks gestation. "This is the side of twins people don't see," he said.
And it's not just heterosexual couples who are pressuring doctors.
"About 95 to 99 percent of gay couples want twins," said Karen Synesiou, director of the Center for Surrogate Parenting, which has facilities in California and Maryland.
A surrogate mother's eggs are divided in half and fertilized with each of the men's sperm. One from each potential father is then transferred.
"The success rate is so high with egg donors who have had previous pregnancies," she said. "You put a donor in the mix and you only need to get one pregnancy."
Of the 100 couples the center serves each year, 48 percent are gay.
Synesiou said the trend jeopardizes the surrogate industry as a woman can only safely carry one set of twins to term.
"She delivers earlier," Synesiou said. "There are higher medical costs for twins, who are already four weeks early and born under 5 pounds. My job is to help couples be parents and we want them one at a time, the chunky 8-pound babies."
In an effort to reduce multiple births, the American Society for Reproductive Medicine revised its guidelines in 2007, recommending transfer of one embryo for patients with a good prognosis (two for those with a poor prognosis) for each IVF cycle for women younger than 35.
That number can increase up to five for women with failed cycles or those older than 42.
The American Society for Reproductive Medicine says it has a "strong ethical process" and clear guidelines on embryo transfer, but not "where doctors should draw the line with their patients," spokesman Sean Tipton said.
"There can be tensions between patient autonomy and a physician's professional judgment, however a patient's does not have the right to demand the physician practice dangerous medicine," he said.
But Dr. Jamie A. Grifo, program director for the New York University Fertility Center, said there is "a lot of wiggle room in the guidelines."
"The chance of getting octuplets from six implants is one in a billion," he said. "Part of this case is that it's such a statistical fluke. No one measures what it costs to regulate something like this. There's no metrics for that. You're not going to regulate a one in a billion event."
"When given the data, most people make the right decision," Grifo said. "If you don't present it to your patient, you don't have a shot at making the best decisions.
"Every patient is different and that's why you have doctors, to understand the complexities," he said. "If you try to practice medicine by guidelines alone, you will harm more patients than you help."
RESOLVE, the National Infertility Association, worries so much about multiple births that it will soon launch an educational video to urge couples not to seek more than one embryo.
The animated video, which follows the real-life story of a woman with twins born prematurely, will soon be distributed to clinics across the country.
"We are frustrated because we feel responsible for the behavior of the patient," RESOLVE executive director Barbara Collura said. "This is a really big deal and very common. We want to provide the best advice and resources possible to make a better decision."
RESOLVE has been largely responsible for encouraging insurance companies to cover IVF costs.
Shady Grove did a study of patients who were in a financing program and those who didn't have the stresses of finances made better choices.
"Patients may spend $10,000 to $15,000 so they want to hedge their bets and transfer as many embryos as they can," Collura said. "It's a very common sentiment in fertility patients."
In an Aetna insurance program in Washington, D.C., if a patient transfers one embryo, the insurance company will cover a later frozen embryo transfer.
"We hope it will be a trend that will catch on," Shady Grove's Stillman said.
He also urges the CDC to change its reporting so that doctors "don't get credit" for success rates with more than one embryo. "A triplet isn't at all a success," he said. "We need to change the pattern to emphasize singletons."
Cultural attitudes need to change, as well, but Stillman recently saw a hopeful sign.
One patient recently asked for a single transfer.
"She said she actually came in planning for two, but she had stayed at a friend's house and they had twins," he said.
"After staying overnight, she said, 'There is no way we are having two.' I ought to rent her house to other patients."