A new study from Yale University concludes that a good majority of embryos transferred in in-vitro fertilization (IVF) procedures do not result in a live birth.1
"Something in nature has decided that these implanted embryos are not viable," said Pasquale Patrizio, MD, a professor of Obstetrics, Gynecology, and Reproductive Sciences at Yale, who led the study.
Most Embryos Don't Implant: Study
Patrizio and co-researcher George Kovalesky, MD, with the Jones Institute for Reproductive Medicine at Eastern Virginia Medical School, reached that conclusion after combing through information on embryo transfers in IVF from patient databases maintained by the Centers for Disease Control and Prevention (CDC), the Society for Assisted Reproductive Technology (SART), and the American Society for Reproductive Medicine (ASRM).
Patrizio explained that fertility specialists must grapple with a paradox in treating infertile women. They face pressures to limit the numbers of embryos transferred for pregnancy after IVF to reduce the risk of creating a multiple pregnancy with its accompanying health risks to both mother and fetuses.2 At the same time, there's a pressure to transfer higher numbers of embryos in hopes one of them were result in a healthy pregnancy. "It is difficult to strike a balance between these two needs," said Patrizio.
Increasing Trends
For their analysis, Patrizio and Kovalesky analyzed patient information from the years 1995 through 2001. Information on the number of cycles progressing to egg retrieval, the numbers of cycles that resulted in embryo transfer, the average numbers of embryos transferred, the numbers of deliveries, and the numbers of infants born was collected. In some cases, gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) had been performed. In GIFT, both the eggs and sperm are transferred into the fallopian tube for fertilization immediately after eggs are retrieved from the mother.3 ZIFT is a combination of GIFT and IVF, in which an embryo fertilized in a laboratory is then transferred into the fallopian tube to begin pregnancy.4
In every year in the study, the numbers of egg retrievals and embryo transfers increased, the two researchers found. For example, the number of embryo transfers more than doubled, from about 31,000 to more than 65,000 between 1995 and 2001. Despite that rise, the average number of embryos transferred has declined in the past decade, the two physicians noted.
Other Statistics
The number of deliveries and infants born from the embryo transfers studied has consistently increased, as well, leading to fewer non-viable embryos, the study found. However, there were fewer also non-viable embryos when fewer embryos were transferred after IVF, the two researchers found.
In 2001, about one-third of cycles involving embryo transfer resulted in a delivery in 2001, Patrizio and Kovalevsky found. They also found a trend between 1995 and 2001 of fewer numbers of embryos being transferred, which reduced the numbers of embryos that did not result in a pregnancy.
Most Embryos Were Non-Viable
However, the two physicians noted that even though the number of non-viable embryos has decreased, it still is significant. "During 2001, the last year for which data were available, 85% of the embryos transferred did not produce a live birth," they write. "This figure represents the embryo wastage that occurs after transfer of fresh embryos, for which presumably the best embryos have been selected."
Additionally, this is an underestimation, they stressed, since it doesn't include abnormally formed embryos that are discarded, those not deemed suitable for freezing, and those lost during the thaw process afterwards.
Why Don't Embryos Implant?
What are some of the reasons that implanted embryos do not result in a pregnancy? Age is an important factor, Patrizio and Kovalesvsky pointed out. Older women tend to produce more embryos with abnormal chromosomes.5 In some cases, they said, these abnormal embryos have been found in younger women. The cause behind these chromosomally abnormal embryos is still a mystery, they stated.
Two hypotheses are that higher estrogen levels may diminish embryo quality, or some unknown negative influence on embryo development in IVF prior to transfer may reduce its quality. Though, these have yet to be proven, they wrote. In fact, the latter hypothesis "remains highly speculative."
Another possibility, the two researchers wrote, is that only a small fraction of eggs retrieved for use in IVF can actually become viable embryos that result in a healthy pregnancy. As follicles, which release the eggs from the ovaries during ovulation, grow, only one matures to the point at which it can release an egg. But in ovulation induction, more than one egg is retrieved for IVF. Given that, eggs in the follicles that do not mature may be inherently abnormal, which slows follicle growth, the researchers speculated. In assisted reproduction, follicles that naturally would not mature are "rescued" so that eggs can be retrieved from them, as well, but their eggs "may already be abnormal and programmed to form abnormal embryos," they wrote.
Clinical and Other Implications
Whatever the cause, the majority of embryos transferred do not result in the healthy delivery of an infant, and this has both clinical and ethical implications, Patrizio and Kovalevsky wrote. For one, transferring fewer embryos resulted in reduced numbers of non-viable embryos, which ultimately improved the odds of pregnancy success. Yet the reasons for the improved pregnancy rates aren't necessarily tied to this practice. They may instead be linked to improved culture methods and transfer techniques, the two researchers explained.
In addition, the findings have moral implications. The apparent fact that fewer embryos actually result in a healthy baby may ease pressure from those who object to freezing embryos on moral grounds, wrote Patrizio and Kovalevsky.
Finally, they added, the findings should stimulate other experts to investigate the best methods available for identifying the highest quality embryos before transfers are performed. In the meantime, balancing the growing pressure to transfer fewer embryos to reduce multiple births with the need to transfer more embryos in hopes of achieving success remains a difficult dilemma, Patrizio said.
"Some potential methods for screening embryos include using pre-implantation genetic diagnosis [PGD] and biochemical markers of embryo viability," he said. "In addition, this study should also move the field toward perfecting methods of egg production."
1. Kovalesky G, Patrizio P. High rates of embryo wastage with use of assisted reproductive technology: a look at the trends between 1995 and 2001 in the United States. Fertil Steril 2005 Aug;84(2):325-30.
2. American Society for Reproductive Medicine. Complications of Multiple Gestation. Available at: http://www.asrm.org/Patients/FactSheets/complications-multi.pdf. Accessed September 13, 2005.
3. RESOLVE: The National Infertility Association. Gamete Intrafallopian Transfer (GIFT). Available at: http://www.resolve.org/main/national/treatment/options/art/gift.jsp?name=treatment&tag=options. Accessed September 13, 2005.
4. RESOLVE: The National Infertility Association. Zygote Intrafallopian Transfer (ZIFT). Available at: http://www.resolve.org/main/national/treatment/options/art/zift.jsp?name=treatment&tag=options. Accessed September 13, 2005.
5. Munne S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril 1995 Aug;64(2):382-91.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
