F&S Reports | 2021
Cleavage-stage embryo transfer: we’ll never let it go
Abstract
Improved modern embryo culture techniques such as the use of triple gas incubators and commercially available culture media have helped increase the frequency of culture to the blastocyst stage, use of preimplantation genetic testing for aneuploidy, and single embryo transfer. One could argue that cleavage-stage embryo transfer is unnecessary inmodern practice. In some older patients with poor prognosis, cleavage-stage embryo transfer could even be considered futile. Results from one study indicate that the live birth rate for a single cleavage-stage embryo from a 45-year-old woman at retrieval is less than 1% (1). However, a cleavage-stage transfer is a good option for younger patients who are at risk of having no blastocyst-stage embryos to transfer based on poor embryo progression or failure to make it to the blastocyst stage in a previous cycle. Not having any embryos to transfer after culture to the blastocyst stage can be devastating. Additionally, trying a cleavage-stage transfer may help patients feel that they have tried everything they can to conceive. Some patients maywant to try a transfer with autologous oocytes before moving on to using donor oocytes. The retrospective study by Neblett et al. (2) in this issue evaluated the rates of live birth when patients with six or fewer normally fertilized two pronuclear embryos had either a fresh cleavage or blastocyst-stage transfer. The live birth rates were 25% after cleavage-stage transfers (average female age, 35.8 years) and 40% after day 5 blastocyst-stage transfers (average female age, 34.4 years). The investigators conclude that the success rate for cleavage-stage embryo transfer in patients with poor prognosis is still good enough to offer patients this option. There are some limitations to this study. First, the comparison of the two cohorts (fresh cleavage and blastocyststage transfers) is not directly applicable to a specific clinical decision point. The choice patients have is to transfer at the cleavage stage or culture to the blastocyst stage (or a combination of both). With culture to the blastocyst stage, some patients would have had no blastocyst formation and would not have been included in this study. Although a recent randomized controlled trial (RCT) comparing fresh cleavage-stage transfer with fresh blastocyst-stage transfer in patients with good prognosis found that only 6 of 194 patients allocated to blastocyst transfer had no embryos to transfer (3), the rates of no blastocyst formation would be expected to be higher in patients with poor prognosis included in the study by Neblett et al. (2). Second, there is likely some residual confounding in that even after including only patients with six or fewer normally fertilized embryos, patients with good embryo growth (approximately four cells on day 2 and eight cells on day 3 of culture) were probably more likely to proceed with culture to the blastocyst stage than patients with suboptimal embryo growth. Lastly, this study compared the pregnancy outcomes of only the first (fresh) transfer. The day 5 transfer cohort had an average of 1.4 extra embryos cryopreserved compared with 0.07 embryos cryopreserved in the cleavage-stage