Frozen IVF embryos lead to 'healthier babies'

“IVF embryos that were frozen may result in healthier babies,” reports The Guardian.

The news is based on a study that combined the results of previously published studies to look at outcomes for the mother and child during pregnancy and just after birth in pregnancies resulting from the transfer of fresh and frozen IVF embryos.

During IVF 'fresh' embryos are usually planted into a woman’s womb once an egg has been successfully fertilised with her partner’s sperm. Some women choose to have one or more embryos frozen and then stored, for a number of reasons, for implantation at a later date.

The research found that single pregnancies after transfer of frozen and then thawed embryos were associated with lower risks of complications such as small birth weight or premature birth.

There was a small increased risk of caesarean section in the 'frozen' group.

It should be stressed that while both the increased and decreased risks found by the researchers were statistically significant (not likely to be due to chance) the absolute risk differences seen were small in all cases.

While the study is certainly valuable it is unlikely to lead to an automatic change in IVF practice (such as the routine freezing of embryos) as further research is required to assess whether other factors, such as maternal age and smoking status, are contributing towards the differences in pregnancy outcomes seen in this study.

Still, the results of this study should provide reassurance to women who have had their embryos frozen as there have been concerns that this could affect the child’s health. This study suggests that this is not the case.

Where did the story come from?

The study was carried out by researchers from the University of Aberdeen and Aberdeen Maternity Hospital. The sources of funding for this study were not disclosed.

The study was published in the peer-reviewed journal Fertility and Sterility.

The study was published in June, but the results of the study have been presented more recently at the British Science Festival by the lead researcher, Dr Abha Maheshwari.

The news was reported accurately by the media..

It is important to remember that this study only looked at the results of successful pregnancies. It cannot be taken as evidence that using either fresh or frozen embryos could increase the chance of having a successful course of IVF treatment.

Women who received fresh or frozen embryos could also be different, and the researchers could not take into account many of the factors that may also explain the differences seen, such as:

the mother’s age
smoking status
whether she had had children before
how long the couple had been infertile
pre-existing medical conditions

What kind of research was this?

This was a systematic review and meta-analysis of published studies that compared outcomes for the mother and child during pregnancy and just after birth in single pregnancies resulting from the transfer of fresh and frozen embryos.

The researchers report that there have been no randomised controlled trials that have compared these two techniques, so only cohort and case-control studies were included.

A systematic review provides the strongest type of evidence, as it combines the results of published studies. However, this systematic review is of observational studies, and therefore has the same limitations as the underlying studies.

A randomised controlled trial would be needed to evaluate the clinical and cost-effectiveness and the acceptability of freezing embryos before implantation.

What did the research involve?

The researchers searched databases of published literature to identify all observational studies (cohort and case-control) that had compared outcomes for the mother and the child during pregnancy and just after birth in pregnancies resulting from the transfer of fresh and frozen embryos. Embryos can be frozen at two different time points and using two different techniques – vitrification (a new method) or slow freezing (an older method). After thawing, frozen embryos can be transferred to women, who may be given additional hormones to prepare the lining of the womb. Studies were included irrespective of the freezing and transfer method used.

The researchers assessed the studies to determine if they were of high quality, and extracted data on the following outcomes:

antepartum haemorrhage (bleeding during pregnancy)
hypertensive disorders of pregnancy, including pregnancy-induced hypertension, pre-eclampsia and eclampsia
gestational diabetes
very preterm birth (defined as delivery before 32 weeks’ gestation)
preterm birth (defined as delivery before 37 weeks)
small size for gestational age
low birth weight (birth weight less than 2,500g)
very low birth weight (birth weight less than 1,500g)
induction of labour
elective and emergency caesarean section
major and minor congenital anomalies (birth defects)
perinatal mortality (defined as the death of a baby from 22 weeks of pregnancy to seven days after birth)
admission to the neonatal intensive care unit

What were the basic results?

The researchers found 11 articles that fulfilled their criteria and were included in the review. Ten of the studies were of high quality. The researchers then combined the results of the studies to give information on a number of outcomes. They found that, compared with immediate transfer of fresh embryos, pregnancies after transfer of frozen thawed embryos reduced the risk of:

Antepartum haemorrhage (relative risk 0.67, 95% confidence interval (CI) 0.55 to 0.81), with an absolute decrease in risk of 2%, based on the results of two studies.
Preterm delivery (relative risk 0.84, 95% CI 0.78 to 0.90), with an absolute decrease in risk of 2%, based on the results of nine studies.
Having a small for gestational age baby (relative risk 0.45, 95% CI 0.30 to 0.66), with an absolute decrease in risk of 2%, based on the results of two studies.
Having a low birth weight baby (relative risk 0.69, 95% CI 0.62 to 0.76), with an absolute decrease in risk of 3%, based on the results of nine studies.
Perinatal mortality (relative risk 0.68, 95% CI 0.48 to 0.96). However, the absolute decrease in risk was less than 1%, based on the results of six studies.

However, pregnancies after transfer of frozen thawed embryos increased the risk of caesarean section (relative risk 1.10, 95% CI 1.05 to 1.15), with an absolute increase in risk of 3%.

There was no difference in the risk of very preterm birth, very low birth weight babies, congenital abnormalities or admission to neonatal intensive care.

How did the researchers interpret the results?

The researchers concluded that “although fresh embryo transfer is the norm in IVF, results of this systematic review of observational studies suggest that pregnancies arising from the transfer of frozen thawed IVF embryos seem to have better obstetric and perinatal outcomes”.

Conclusion

This systematic review has found that single pregnancies after transfer of frozen thawed embryos were associated with a lower risk of perinatal mortality, small for gestational age babies, preterm birth (defined as before 37 weeks’ gestation), low birth weight (defined as less than 2,500g) and antepartum haemorrhage (bleeding during pregnancy). However, the risk of caesarean section was increased. The absolute risk differences seen were small in all cases. The results of this study should provide reassurance to people who have had their embryos frozen, and to cryopreservation programmes.

The study has a number of limitations. Although the study is a systematic review, it is a review of observational studies such as cohort and case-control studies, as no randomised controlled trials have been performed. This means that the freezing of embryos may not be the only cause of the differences seen. It may be that other factors are responsible. The researchers discuss that patients who have had a fresh cycle may be different from those who had frozen replacement cycles, and that they were unable to adjust for the mother’s age, smoking status, the number of children a woman had previously had, pre-existing medical conditions and how long the couple had been infertile. All of these factors could account for the differences seen.

Also, studies were included regardless of the method used to freeze or thaw embryos and how the embryos were implanted, and the researchers state that there was inconsistency in the definition of some outcomes.

Although pregnancy rates were not examined in this study, the researchers also discuss the fact that pregnancy rates are generally better with fresh embryos. This study looked at the outcomes for successful pregnancies, the results may be different if the outcomes per cycle of IVF were investigated.

This study should reassure people who have had embryos frozen, but randomised controlled trials are needed to evaluate the clinical and cost-effectiveness and the acceptability of freezing embryos before implantation.