A group of doctors from Australia claims couples who use frozen embryos in assisted reproductive techniques (ART) face better odds of having a healthy child with no birth complications than those who use fresh embryos. Their findings are published in the June issue of the journal Fertility and Sterility.¹

What Underlies the Risk?
"The number of births after the use of assisted reproductive technologies has increased steadily around the world, especially in developed countries," wrote Michael Chapman, MD, and his colleagues at the University of New South Wales in Australia. "However, the international literature shows that ART has been associated with an increased number of adverse perinatal outcomes, most notably multiple births, preterm birth, low birth weight, very low birth weight, perinatal death, and increased risk of short and long-term disabilities."

Chapman is a professor of Obstetrics and Gynecology at the university.

Despite published research that has linked ART use with the increased risk of these complications, the effect that certain maternal characteristics and ART procedures on this risk "remains unclear", wrote Chapman and his team.

To learn more answers, the researchers initiated this study, collecting patient records from a database on assisted reproductive technology use in their country. They specifically pulled information on infants born after ART use between 1996 and 2000. Information on types of treatments, numbers of cycles, egg retrieval, embryo transfer, and pregnancy rates was gathered.

As a comparison, Chapman's group also collected information on all Australian births that occurred in 1999, regardless of whether ART was used or not.

Among those couples using ART during the study period, 15,035 viable pregnancies were reported, and most resulted in the delivery of at least one healthy infant. Excluded from the study were cases involving stillborn infants, infants whose birth status was not stated, and infants whose gestational age and/or birthweight were not stated.

Effect of Assisted Reproduction Use
Chapman and his colleagues first set out to determine if ART itself increased the risk of preterm birth and low birthweight. They compared birth complication rates related to ART births and all births in Australia in 1999. They also analyzed any risk factors associated with these birth complications in both groups, such as maternal, infant, and treatment-related factors; cause of infertility; number and type of fresh or frozen embryos transferred; and the type of ART procedure used.

The study team learned that the incidence of birth complications was higher in cases in which assisted reproduction was used. "Almost a third of ART infants were delivered preterm, and a quarter were low birthweight, indicating that ART contributes disproportionately to preterm birth and low birthweight among the general population," they wrote.

Other Factors That Play a Role
Among other findings—more preterm births occurred in older mothers or women who had had at least two children already. Low birth weight was also more common in older mothers. Both preterm birth and low birth weight was associated with higher number of embryos transferred, but were less likely in cases in which intracytoplasmic sperm injection (ICSI) or frozen embryos were used, and in cases in which the infertility was due to a male factor.

In cases in which twins were conceived, birth complications were more commonly associated with mothers who had already had children, a higher number of embryos transferred, and in women aged younger than 29 or older than 45. Female-factor infertility was also a risk factor. By contrast, twins conceived using ICSI or in cases involving frozen embryos were less likely to have these complications.

Theories Postulated
In conclusion, Chapman and his team found that the risk for preterm birth and low birthweight in ART was higher in cases involving older mothers becoming pregnant for the first time, cases in which a female factor is the cause of infertility, and in ART procedures using fresh embryos.

Female-factor infertility may increase the odds of birth complications due to other related factors, such as tubal disease, endometriosis, or a certain hormonal disorder, the study team suggested. "The better outcome of frozen embryos in our study is likely related to the embryo selection process in which those embryos chosen for freezing are of better quality," they wrote.

Couples who choose embryo freezing due to excess embryos also are more likely to better respond to ovulation induction therapy and have good-quality eggs to start with, the researchers speculated.

1. Wang YA, Sullivan EA, Black D, Dean J, Bryant J, Chapman M. Preterm birth and low birth weight after assisted reproductive technology—related pregnancy in Australia between 1996 and 2000. Fertil Steril 2005 Jun;83(6):1650-8.

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.