As the case of the so-called Octomom continues to spur outrage and debate over the use of in vitro fertilization (IVF) in the U.S., new research suggests that the most effective and inexpensive IVF method may also be the least likely to result in dangerous multiple births.
A study by Finnish researchers published in the current issue of the journal Human Reproduction finds that transferring a single fresh embryo at a time, followed by subsequent transfers of individual thawed embryos, may be as effective in achieving pregnancy as implanting multiple embryos at once. Using one embryo at a time also cuts medical costs, the study found, saving about $27,000 per live-birth pregnancy.
"Elective single-embryo transfer is the better option under most scenarios," says Dr. Zdravka Veleva, one of the study's authors and a faculty member of the department of obstetrics and gynecology at Finland's University of Oulu. The findings reflect what U.S. fertility doctors say they are increasingly seeing in their own practices. (Read "Building a Better Baby: A New In Vitro Test.")
The study compared outcomes of treatments during two periods at the university's fertility clinic: between 1995 and 1999, when double-embryo transfer was used much more commonly than single-embryo transfer, which was performed for just 4.2% of cases; and between 2000 and 2004, when 46.2% of women opted for elective single-embryo transfer. (The increase in single-embryo transfers reflects, in part, changing attitudes in Europe toward using multiple embryos.) In both time periods, the study found, 90% of women delivered babies within their first four treatment cycles, regardless of how many embryos were implanted. That suggests there is no advantage to multiple-embryo implantation and no delay in creating a successful pregnancy from using one embryo at a time. Additionally, the incidence of multiple births was halved between the two periods.
Unlike many previous studies, which have looked only at the success rates of individual fresh embryo transfers, this study also considered the cumulative success rate for all embryos created and implanted from a single harvesting of eggs including those that had been frozen. Researchers found that the total pregnancy rate per egg retrieval was higher when embryos were implanted individually. For each "ovum pickup," the overall pregnancy rate was 38% among women who had elective single-embryo transfers, and 33% among those who had more than one embryo implanted.
Some of that success can be attributed to improvements in freezing techniques, says Dr. Hannu Martikainen, the study's lead author and the chief physician at the University of Oulu Division of Infertility and Reproductive Endocrinology. "Now we have more and more experience, and we are doing more and more frozen cycles," he says. He points out the importance of not only transferring but also preserving each embryo on its own, which makes it possible to use frozen embryos one at a time rather than in bigger batches. "[If you transfer] three embryos in each cycle, you very soon don't have any good-quality embryos left," he says. (See the top 10 medical breakthroughs of 2008.)
The study's findings may have particular relevance in the U.S., says Veleva, since the cost of IVF is roughly three to four times higher in America (sometimes more than $10,000 per cycle) than in Scandinavia and because many Americans pay for treatments out of pocket. Add to that the high cost and increased risks involved with multiple births: Veleva cites a 2000 study that found that, compared with singleton deliveries, the costs for twins, triplets and higher-order deliveries are approximately four, 11 and 18 times greater, respectively, mostly due to maternal and neonatal complications.
Physicians are increasingly concerned about the hazards of multiple births, which not only increase risks to mother and infant during pregnancy and delivery, but also raise the chances of later developmental problems for babies who are often born prematurely. Although other studies have also shown the benefits of using elective single-embryo transfer to reduce multiple births, and the technique has become standard in several European countries, there is elsewhere a persistent belief that fewer embryo transfers will yield fewer pregnancies. The idea that more is better is difficult to shake.
Indeed, some past studies have shown the benefit of multiple-embryo transfer. "When you're just reporting pregnancy rate per transfer, some studies have shown better results in transferring two versus one," says Dr. Lynn Marie Westphal, a fertility specialist and director of women's health at Stanford University School of Medicine.
But such data may not always account for the specific factors that help determine success rates, such as the age of the patient and the quality of the embryos. At Stanford's fertility clinic, where doctors can carefully select high-quality embryos by growing them in the lab for five days, until the blastocyst stage, instead of the more usual three days, success rates have been on par, if not higher among single transfers, says Westphal. "When I look at our data, in patients with really good blastocysts, the pregnancy rates were comparable," Westphal says. "The singles were just as good if not better in most of the groups." (See the most common hospital mishaps.)
For some patients, however, the chances are slim, despite the best technology. "Some of our patients are in their mid-40s and don't have good embryos," says Westphal. "We know that the implantation rate is so low that even if you transplanted many embryos [for them], they're unlikely to get pregnant."
But even as doctors increasingly consider elective single-embryo transfer the best practice for many IVF candidates, and as more and more fertility clinics report comparable success rates between single- and multiple-embryo transfers, there is still no rule for all women. Even among the best candidates for IVF, says Westphal, there may be much variation. "People don't realize that there's a range," she says. "One 36-year-old is not the same as another 36-year-old, or someone who has done many, many cycles and has terrible embryo quality is not the same as someone who is doing their first cycle and has good embryos."
Despite what the most reliable data may suggest, though, the hope of having a child is not one that most infertile patients and even some doctors would care to quantify or put a price tag on. "Some clinics still have a so-called guarantee that if the patient is not getting pregnant, they get their money back," says Martikainen. "In those cases, of course, the doctor tries to get the patient pregnant at any price."