Multiple Births Persist as Doctors Buck Guidelines
At Some Clinics, Women Get Five or
More Embryos, Raising Risks to Health:
One Cause Is Patient Demand
SYLVIA PAGÁN WESTPHAL / Wall Street Journal 7oct2005
When Teresa Anderson learned she was pregnant with quintuplets she was dumbfounded. She had signed up to be a surrogate mother for an infertile couple and during an in vitro fertilization procedure doctors introduced five embryos into her womb. "They told me there was a one in 30 chance that one would take," she says.
figures are for multiple
Instead, all five took. The 26-year-old mother of two endured a difficult pregnancy and delivered the boys in April at a Phoenix hospital. The multiple births made headlines across the country as a feel-good tale. But they also underscore a reality of the fertility business: Many clinics are implanting more than the recommended number of embryos in their patients, raising the risks for women. The reasons include demand from patients desperate to get pregnant and competition in the field to achieve the highest success rates.
In vitro fertilization has come a long way since the birth of the first test-tube baby in 1978, as ever-improving techniques have helped hundreds of thousands of women get pregnant. In IVF, eggs and sperm are joined in the lab to make an embryo, which is then implanted back into the womb.
One side effect of IVF's popularity is a rise in multiple pregnancies. Studies suggest that 30% to 40% of pregnancies with three or more babies are the result of IVF. Others arise from fertility treatments that increase the number of eggs a woman produces without resorting to IVF. Fewer than one in five are due to natural conception.
Multiple pregnancies are associated with a higher risk of premature birth, low birth weight and complications such as cerebral palsy. For the mother, there is a higher risk of pregnancy-related high blood pressure, postpartum depression and other problems.
Britain, Germany, Sweden, Switzerland and other European countries have banned putting more than three embryos in women undergoing IVF. Doctors who break the rules can lose their licenses, pay fines or face incarceration.
The U.S. has only voluntary guidelines, and the difference shows up in the statistics. About 35% of births following IVF in the U.S. in 2002 were multiple births, with 4% being triplets or higher. The comparable figures in Britain between mid-2002 and mid-2003 were 24% and 0.5%. In Finland and Sweden, where 60% of IVF procedures involve the transfer of only one embryo, multiple pregnancy rates have fallen to under 10% and the rate of triplets is zero, according to a recent study by scientists at Sweden's Göteborg University in the medical journal Minerva Ginecologica.
The risk of multiple births is generally highest when more than two embryos are placed in women under 35. In 1999, based on results from over 35,000 IVF treatments, the Centers for Disease Control and Prevention reported that between 10% and 13% of women under 35 who had three embryos introduced got pregnant with triplets. Moreover, the CDC found that placing three or more embryos in women with healthy eggs made them no more likely to get pregnant than placing two.
In 1999 the American Society for Reproductive Medicine recommended that no more than two embryos should be placed in women under 35 undergoing IVF who produce healthy embryos. Those women who produce poor embryos could get three. Older women could get more. The voluntary guidelines were further tightened in 2004. They now state that women under 35 with a good prognosis should consider only one embryo and that no more than two should be transferred in this age group except under extraordinary circumstances. The new guidelines also say women between 35 and 37 should get only two embryos if they have a good prognosis. If they don't, they should get three but no more.
A study published last year in the New England Journal of Medicine suggests the 1999 guidelines resulted in a slight overall drop in the number of embryos used in IVF treatment in the U.S. The average number of embryos per IVF cycle in the U.S. declined to 3.2 from 3.6 right after the guidelines were issued.
Nonetheless, many fertility doctors say the guidelines continue to be sidestepped. A review by The Wall Street Journal of CDC records for 2002 — the most recent nationwide data available — showed that 130 of 391 clinics, or 33%, still placed on average more than three embryos in women younger than 35. Nineteen clinics introduced an average of four or more embryos.
One of those 19 clinics is the Pacific Reproductive Center in Torrance, Calif. In 2002, the center placed an average of 4.5 embryos in its patients under 35. Among those women, 16% got pregnant with three or more fetuses, and 48% had multiple births.
The clinic's director, Rifaat Salem, says he doesn't always follow the guidelines because he often treats patients who have failed IVF at other clinics. Patients are people, not statistics, he says, and he judges each case on its merits. He says he doesn't hesitate to place "10 or 12" embryos in some women, even if they are under 35, as long as he feels their embryos are of inferior quality and unlikely to yield a pregnancy. Dr. Salem says none of the patients in whom he has introduced 10 or 12 embryos have had more than one baby.
'Good' and 'Bad' Embryos
Several other doctors also cited inferior embryos as a reason they implant more embryos than the guidelines suggest. In IVF, a woman is treated with hormones to ovulate, and several of her eggs are extracted, fertilized and grown. Doctors usually judge whether an embryo is "good" or "bad" by looking at its shape and appearance under a microscope. If embryos look "good," doctors say they usually transfer only two in younger women. If they look "bad," they may transfer more to increase the patient's chance of getting pregnant.
Jonathan Van Blerkom, laboratory director at Colorado Reproductive Endocrinology, says visual inspection is unreliable because some embryos that appear unhealthy are able to develop into healthy babies. He and other specialists say a better way to judge an embryo's quality is by testing for chromosomal abnormalities prior to implantation. But the genetic test is costly and not all clinics offer it.
Heesun Hall of El Segundo, Calif., went to see Dr. Salem for her first round of IVF in 2003, when she was 34. Dr. Salem placed four embryos into her womb. He says in an interview he never would have used that many if the embryos were of good quality. Ms. Hall says she felt uneasy about receiving four, but she and her husband agreed after Dr. Salem reassured them there was a very low chance all four would take. "My husband to this day feels so much guilt over that split-second decision," Ms. Hall says.
Ms. Hall ended up pregnant with quadruplets. Upon advice from her obstetricians, she sacrificed two of her babies in an abortion procedure known as multifetal reduction. Pregnant with the remaining twins, Ms. Hall went into labor early, giving birth to severely premature babies, Zoey and Max, each weighing less than two pounds. At the hospital, Max suffered brain damage from two hemorrhages, but in the end it was Zoey, initially the stronger of the two, who died two months after birth, from a fungal infection. "We held her only twice," Ms. Hall says. Max, now nearly 2, still requires a feeding tube.
Dr. Salem says he feels bad about what happened to Ms. Hall. "Obviously since then we've learned a lot," he says. "She's one of the cases we all should remember." He adds that his clinic now offers the chromosomal test and as a result implants fewer embryos. Ms. Hall says she wishes she had been a more informed patient but she doesn't blame Dr. Salem for what happened because the decision to accept more embryos was ultimately hers.
Ms. Anderson, the surrogate mother of quintuplets, remains resentful of her doctor, Jay Nemiro, who is medical director of the Arizona Center for Fertility Studies in Scottsdale. She says the doctor told her there was a miniscule chance she would get pregnant with multiples, let alone five babies. He knew "how fertile I was. I felt he knew better than to put back five embryos," says Ms. Anderson, who now lives in Leander, Texas. Dr. Nemiro declined to comment.
Doctors say one reason they introduce lots of embryos is that patients demand it. In the U.S., unlike many European countries, most patients pay for a significant portion of, if not the entire, procedure out of pocket. It can cost between $7,000 and $25,000 per treatment, depending on the drugs and tests used.
Desperate patients "put a tremendous amount of pressure" on fertility clinic employees, says Jaime Vasquez, medical director of the Center for Reproductive Health in Nashville, Tenn. His clinic introduced an average of 5.1 embryos in women under 35 in 2002, the highest among all 391 clinics measured by the CDC. Although he says he understands the American Society for Reproductive Medicine's guidelines, he asks, "Are they going to appease the patient when she fails?"
Jodi Figman, an IVF patient from Florida, says she told her doctor at the South Florida Institute for Reproductive Medicine that she and her husband "wanted to be very aggressive" with how many embryos were implanted. She recalls a dinner with a friend, also undergoing IVF, "when we all decided that if the doctor said two, we were going to push for three." She got the three embryos this year at age 36 and ended up pregnant with triplets. She recently underwent a fetal-reduction procedure to remove one fetus. "The risk of me carrying three just isn't worth it," she says.
Matter of Survival
Another reason clinics place more embryos, doctors say, is competition. The CDC's tables show the pregnancy success rates of individual clinics. For some clinics, boasting a good success rate is a matter of survival because patients use the data to comparison-shop. The federal agency says its tables are meant to be merely one factor for patients to consider.
"It's extremely frustrating," says Jacques Cohen of the Tyho-Galileo Research Laboratories in West Orange, N.J., which provides diagnostic services to IVF clinics. Patients look at a small difference in pregnancy rates "as being huge," adds John Schnorr, a fertility doctor at the Southeastern Fertility Center in South Carolina.
Many clinics advertise their CDC scores on Web sites. Dr. Vasquez's Nashville clinic boasts of having one of the highest pregnancy success rates in the nation — 56% in women under 35 — and compares its CDC numbers side-by-side with those of other centers. The Web site doesn't mention that the clinic's rate of triplet pregnancies in this age group was 28% and its rate of multiple births was 52% in 2002.
Michael Alper, founder of Boston IVF, in Waltham, Mass., says some clinics try to boost their pregnancy success rates by rejecting patients who are older or whose medical histories suggest they aren't likely to become pregnant. "To get high success rates you have to treat the best-prognosis couples," he says. "So patients have actually been hurt by the pressure."
Alexander Dlugi, medical director of the Sher Institutes clinic in Bedminster, N.J., says another way to improve pregnancy success rates is to treat a patient initially with hormone shots to see if she produces eggs. If all goes well, the patient is officially enrolled as an IVF patient; if not, she's turned away and never counted in the numbers. "I have seen this firsthand" at other clinics, he says.
The CDC, using a subcontractor, makes announced visits to about 10% of reporting clinics and tells them in advance what records it wants to review for accuracy. "By and large, we believe that [fertility clinics] across the country strive to provide the federal government with accurate data," says Maurizio Macaluso of the CDC's reproductive health division.
Dr. Schnorr in South Carolina isn't sure. He hires independent auditors to examine his own clinic's records. For others, he says, "you don't know how honest the data is."
Meanwhile, Ms. Hall in California recently underwent another IVF procedure in which she received just one embryo. In an email yesterday, she said she is pregnant.