Hum. Reprod. Advance Access originally published online on October 11, 2007
Human Reproduction 2008 23(2):459-460; doi:10.1093/humrep/dem196
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Letters to the Editor |
Reply: On nucleation and implantation: 0% mononucleation or 100% mononucleation in blastomeres is not the whole story
Laboratory Director, Fertility Centers of New England, Reading, MA 01949 USA E-mail: scottl{at}fertilitycenter.com
We wish to thank Drs Sundstrom and Saldeen for their comments and concerns regarding the data that we presented. We agree that it is not the entire story and that an embryo that has only one of four blastomeres with multinucleation may, indeed, be able to implant and form a viable fetus. In contrast, an embryo where no nuclei are visible may have multinucleation, and an embryo with only one or two cells where nuclei are visible may again have multinucleation, that is, not seen. However, in our analysis we did not look at the embryo data for outcome but rather looked at outcome and correlated that with embryo data. This was necessary as the initial series was a prospective data collection, in which Day 2 morphology was not used for embryo selection. The purpose of the prospective data collection was to elucidate the factors in embryo scoring that have the highest impact on delivery. The data was analysed for delivery where all embryos transferred resulted in a live outcome and then half, 1/3 etc. We then also looked at the contribution to fetal heartbeat. In this way we were able to analyse the impact of the different scoring parameters to delivery, the only end point that should be considered. From this, the six most important factors were described that gave the highest delivery outcomes. There were many instances, and we still see them, where there is implantation with what would be described as a poor quality embryo (uneven, multinucleate) but the vast majority do not proceed to delivery. Thus, we agree it is not the whole story, but the analysis was based on clinical outcome, and what types of embryos resulted in a live birth. Further, although some embryos that have no nuclei visible do result in deliveries the percentage is still low (Table 4), which is consistent with the data of Saldeen et al. 
The majority of deliveries are from one nucleus per blastomere (coupled with the other important parameters).
In our original series (Scott et al., 2007) we were scoring embryos as multinucleate even if they had only one cell with multinucleation. Since the publication of this paper, we have continued to gather data on all embryos passing through the laboratory and are noting how many cells in each Day 2 embryo (2 or 4-cell) have mono- or multi- nucleation. Unfortunately, since we now use Day 2 scores as selection criteria it will be hard to analyse this data as we avoid embryos with any amount of multinucleation. When we are unable to do this, it is in poor prognosis patients, and they are not getting pregnant. However, in our preimplantation genetic screening programme there is a high correlation of aneuploidy with multinucleation (unpublished data) even when only one cell is displaying multinucleation on Day 2, and the selection of a cell for biopsy on Day 3 is by the presence of a single nucleus.
If embryos are known to result in lowered implantation potential, and if there is a very low chance of delivery from them, we attempt to not use them at all. Thus, with the gated scoring system we have in place we select embryos by Day 1 and Day 2 morphology, looking for nucleolar precursor bodies equality in numbers and alignment, 4-cell embryos with even cell size on Day 2 with one nucleus per blastomere as best and no nuclei visible as the next best category. Embryos with even one cell as multinucleated are avoided if possible.
References
Saldeen P, Sundstrom P. Nuclear status of four-cell preembryos predicts implantation potential in in vitro fertilization treatment cycles. Fertil Steril (2005) 84(3):584–589.[CrossRef][Web of Science][Medline]
Scott L, Finn A, O'Leary T, McLellan S, Hill J. Morphological parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates. Hum Reprod (2007) 22:230–240.
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