Perinatal outcomes of singletons born following in-vitro fertilisation: a comparison of different embryo transfer strategies using UK data

Lay summary

Increasing numbers of infertile couples are undergoing in-vitro fertilisation (IVF) treatment in order to conceive. The treatment involves removing eggs from a woman’s ovaries and fertilising them in the laboratory to create embryos which are placed within the womb after either three or five days in the laboratory. Any remaining viable embryos may be frozen for future use. Previous research has shown that babies from frozen embryos are less likely to be premature but are heavier than those resulting from fresh embryos while those born from a five-day old embryo are more likely to be premature than those from a three-day old embryo. The accuracy of these results can be questioned because they are based on data which were unable to take into account women who had more than one IVF baby following different embryo replacement strategies. We analysed detailed HFEA data on all UK IVF records from mothers with one or more single-delivery IVF babies to investigate whether delayed transfer of embryos (five-day replacement or freezing) results in a healthier baby. Our key finding is that single babies born following a frozen embryo transfer are less likely to be small for gestational age than a singleton siblings born following a fresh embryo transfer, but are more likely to be large for gestational age. Single babies born following transfer of a fresh five-day old embryo were more likely to be large for gestational age (although the evidence was not that strong) but were less likely to have a congenital anomaly compared to siblings born following transfer of a fresh three-day old embryo. However, the absolute risks of any of these outcomes occurring are low and there is insufficient evidence to challenge the practice of extended culture of embryos.

Public benefit statement

The absolute risks of perinatal outcomes were low when comparing transfer of a three-day embryo with a five-day embryo between singleton siblings. Therefore we had insufficient evidence to challenge the practice of extended culture of embryos. Although frozen embryo transfers have a number of potential benefits, it has a strong association with large for gestational age babies which is linked to long-term conditions such as diabetes and hypertension. We must be cautious about using this as a default strategy for an initial transfer, particularly when there is no evidence that it increases live birth rate. The research may be used by fertility policy-makers to update clinical guidelines around the risks associated with different embryo transfer strategies.

Scientific publications

• Raja, E.A., Bhattacharya, S., Maheshwari, A., & McLernon, D. J. (2023). A comparison of perinatal outcomes following fresh blastocyst or cleavage stage embryo transfer in singletons and twins and between singleton siblings. Human Reproduction Open, 2023(2):
• Raja, E.A., Bhattacharya, S., Maheshwari, A., & McLernon, D. J. (2022). Comparison of perinatal outcomes after frozen or fresh embryo transfer: separate analyses of singleton, twin, and sibling live births from a linked national in vitro fertilization registry. Fertility and Sterility, 118(2), 323–334.