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PFC moves towards cleavage-stage embryo transfer strategy

PFC moves towards cleavage-stage embryo transfer strategy

Based on the most recent studies, we favor the transfer of cleavage-stage embryos to improve the treatment success with respect to feto-maternal safety.

Traditionally, cleavage-stage embryos were transferred on day 3, but over the past decade advances in cell culture media have led to a shift in in vitro fertilization (IVF) practice from cleavage-stage embryo transfer to blastocyst stage (day 5) transfer.

Embryo transfer at blastocyst stage has become the strategy of choice for most clinics worldwide, with the aim of achieving a healthy singleton live-birth. Nevertheless, the evidence presented in several most recent studies clearly highlights reasons for concern, with the possibility of epigenetic changes resulting from extended culture and potential increased risks to fetal health (Fig. 1). New data on perinatal outcomes suggest that pregnancies after embryo transfer at blastocyst stage are associated with a higher risk of preterm delivery, large for gestational age babies, monozygotic twins and altered sex ratio compared with those following embryo transfers at cleavage stage. A possible explanation could be that extended culture may trigger genetic and epigenetic changes in trophoectodermal cells that can lead to abnormal placentation and implantation, and hence increased risk of preterm delivery. Results from animal studies support this hypothesis.

Figure 1: Balance between blastocyst and cleavage-stage embryo transfer.
Maheshwari et al.: Should we be promoting embryo transfer at blastocyst stage? Reproductive BioMedicine Online (2016) 32, 142–146

There is also low evidence that fresh blastocyst transfer is associated with improved live-birth rates compared with fresh cleavage-stage embryos. In several studies that report cumulative pregnancy rates after fresh and frozen transfers, no significant difference was found. Moreover, it is clear that, pregnancies can arise from non-top quality embryos as well as those which never make it to blastocyst stage. Extended culture in women with very few embryos incurs the risk of either having no embryos for transfer in a fresh cycle or cryopreservation for future use. Hence we do need to consider alternative strategies.

PFC recommends…
…leave the ultimate decision on the length of the embryo culture up to our specialists. In selected good-prognosis patients or/and due to optimal endometrial preparation and identification of the receptive window for embryo transfer (ERA test), or in PGD/PGS cycles, blastocyst culture maybe applicable for single embryo transfer.

Scientific studies:

Maheshwari et al.: Should we be promoting embryo transfer at blastocyst stage? Reproductive BioMedicine Online (2016) 32: 142–146.

Glujovsky et Farquhar: Cleavage-stage or blastocyst transfer: what are the benefits and harms? Fertility Sterility (2016) 106(2): 244–50. Glujovsky et al.: Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Review (2016) (6): CD002118.

Karacan et al.: Comparison of the transfer of equal numbers of blastocysts versus cleavage-stage embryos after repeated failure of in vitro fertilization cycles. J Assist Reprod Genet. (2014) 31(3): 269–274.

American Society for Reproductive Medicine, Birmingham, Alabama: Blastocyst culture and transfer in clinical-assisted reproduction: a committee opinion. Fertility Sterility (2013) 99(3): 667–72.

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