Fertility study: Frozen embryos yield healthier babies than fresh ones

This month Danish scientists reported results from a 10-year study that showed children born from previously frozen embryos that had been replaced in the womb had higher birth weight than those born when fresh embryos were used.

The mothers had longer pregnancies, and the children did not show increased risk for birth defects, according to Dr. Anja Pinborg of the Copenhagen University Hospital Rigshospitalet who presented the results at the European Society of Human Reproduction and Embryology annual conference in Barcelona July 8.

Since first accomplished successfully 20 years ago, frozen embryo transfer (FER) has become an increasingly used method in assisted reproductive technology, or ART.

But fertility researchers have debated the safety and success rates of FER, with much of the research taking place in Europe where about 42,000 frozen embryo transfers take place annually. A report on ART in the United States published this year by the Centers for Disease Control and Prevention stated that 19% of all 134,260 ART procedures performed in 2005 used frozen embryos (from both the patient’s and donor eggs), and 81% used freshly fertilized embryos from the patient's or a donor’s eggs.

One of the leading concerns with transferring embryos is the risk of developing multiple pregnancies.

Pinborg’s team said their study shows there is less of a risk for multiple pregnancies when frozen embryos are used compared with fresh embryos.

“Up till now the data has been extremely limited,” said Pinborg in a written statement. “There is only one other large birth register study – from Sweden – which shows similar results to ours. Our findings are of particular importance for Scandinavian countries, where single elective embryo transfer is regarded as the gold standard. This has meant that the use of FER has been rising steadily over the past few years. We wanted to be sure that the procedure had no deleterious effect on the offspring,” said Pinborg.

Scientists tracked all 1,267 children born in Denmark between 1995 and 2006 after frozen embryo replacement. Children were divided into three groups: 878 born after cryo-preserved in vitro fertilization (IVF); 310 born after cryo-preserved intracytoplasmic sperm injection (ICSI); and 79 where the method of creation of the embryos was unknown. During the same period 17,857 children were born after IVF/ICSI treatment using fresh embryos, and these children were used as controls.

Study results showed that multiple pregnancies occurred more frequently in the fresh embryo group – 24.8% compared to 27.3% of the fresh embryo group, depending on whether ICSI or IVF was followed. Among the frozen embryo groups, multiple pregnancies occurred in 11.7% and 14.2% in the ICSI and IVF groups, respectively.

Data on the children’s outcomes, including congenital malformations, were obtained from Danish national registries.

Maternal age was significantly higher in the frozen embryo replacement group. Pregnancy duration was also significantly longer for these mothers, and birth weight was also higher by about 200 grams (equal to about 7 ounces) in the FER group. The proportion of low birth weight FER children significantly lower, as was the percentage of pre-term births.

“Additionally there were significantly fewer children admitted to a neonatal intensive care unit in the FER group,” said Pinborg, “although, when limited to single births, this difference disappeared." Pinborg said they found no increased risk of congenital malformations in the FER group. In fact, congenital disorders were higher when fresh embryos were used compared with frozen embryos at rates of 8.8% and 7.1%, respectively.

“Our assumptions about why children born from frozen embryos (FER) had better outcomes than those born from fresh embryos are: one, a positive selection of women and embryos (i.e. only the good prognosis patients have surplus embryos to freeze and only the superior embryos survive the 3-step procedure of freezing-cryostorage-thawing); two, treatment cycles with frozen embryos are generally done in natural cycles without controlled ovarian hyperstimulation (COS) and we do not know whether this COS has a negative influence on endometrial receptivity, implantation and early pregnancy; and three, fewer twin pregnancies after FER, hence less “vanishing twin pregnancies” [a vanishing twin pregnancy is a fetus in a multi-gestation pregnancy which dies in vitro]  and vanishing twin pregnancies have poorer outcomes than single pregnancies,” Pinborg told Flesh and Stone in an email.

Several cycles of in vitro fertilization and intracytoplasmic sperm injection can be performed when frozen embryos are used. Frozen embryos are subsequently thawed and replaced three to five days after ovulation in the same way as fresh embryos are used. The technique helps reduce the number of times ovaries are stimulated and eggs collected, according to the Danish researchers.

Through last year in the United States the procedure was still viewed with some caution. The American Society for Reproductive Medicine issued a statement last fall emphasizing that oocyte cryopreservation, or egg freezing, is “an experimental procedure that should not be offered or marketed as a means to defer reproductive aging.”  According to the ASRM Practice Committee, “Women contemplating the use of egg-freezing technologies need to receive extensive counseling to help them make a fully informed decision.”  

References:
Pinborg A, et al Danish national controlled cohort study on neonatal outcome of 1267 children born after transfer of cryopreserved IVF and ICSI embryos in 1995 to 2006, ESHRE Meeting 2008; Abstract O-122