The frequency and developmental capability of human embryos containing multinucleated blastomeres

Abstract

The frequency of multinucleated blastomeres (MNB) in 2- and 4-cell stage human embryos was recorded immediately before embryo transfer using a high-power inverted microscope. About 44% of patients (150/338) possessed embryos exhibiting MNB. The appearance of this nuclear abnormality was not correlated with maternal age. Overall, 15% of the otherwise good quality embryos (274/1885) that developed after monospermic fertilization contained several multinuclei (from two to seven) in at least one cell. Quite often MNB were found within all cells of the embryo (50% in 2-cell embryos). Blastomere multinucleation was significantly higher in 2-cell than 4-cell embryos (P <0.0001). This suggests that a considerable number of human embryos become abnormal during the first embryonic division. The embryos containing MNB were usually excluded for uterine transfers, with the exception of 19 cases when only such embryos could be replaced (6%; 19/338 patients). The results demonstrated that embryos with MNB may implant (4/19 cases; 21%) and they can lead to both spontaneous abortions and the successful birth of healthy infants (two cases). The fact that in the successful cases, 2-cell stage embryos with a mononucleated and a binucleated blastomere were transferred also suggests that due to the cell totipotency, development of a healthy baby is possible from one normal blastomere. Since multinucleation in early embryos may reflect gross chromosomal abnormalities or development of mosaic embryos, it is advisable not to replace embryos with MNB. Occasional transfers, however, can be considered because defective embryos may sometimes develop normally.

Insights on blastomere nuclearity

“…The presence of multinucleated (MN) blastomeres in embryos arising through IVF procedures has been described to range from 14.3% to 74% [1][2][3][4][5][6] and 43% to 87% of the patients to have MN embryos [3,4,7].…”

“…Multinucleation has been associated with developmental arrest [1-4, 7, 12-15], poor embryo morphology [1,2,7], elevated fragmentation [2,3], repeated cycles [3], blastomere asymmetry [16,17] and higher multinucleation rate on 2-cells when compared with more developed embryos [1,3,5,7,13,15,18]. Multinucleation has also been associated with higher blastomere diameter [1,6], decrease in blastocyst formation rate [5,7,15,19], reduced capacity of development on siblings of MN embryos [2,5], high amount of oocytes retrieved and elevated E 2 levels [2,3,20], follicles hypoxia [21], culture media [13,22], the use of GnRH antagonist [23] and apoptosis [6].…”

“…Multinucleation has also been associated with higher blastomere diameter [1,6], decrease in blastocyst formation rate [5,7,15,19], reduced capacity of development on siblings of MN embryos [2,5], high amount of oocytes retrieved and elevated E 2 levels [2,3,20], follicles hypoxia [21], culture media [13,22], the use of GnRH antagonist [23] and apoptosis [6].…”

“…Based on all of the above observations, consensus has been reached: embryos with MN blastomeres are highly unsuitable for replacement and should be excluded for transferring unless non-MN embryos are available [7,8,12].…”

Diagnosis of abnormal human fertilization status based on pronuclear origin and/or centrosome number

“…ART procedures also routinely assess if normal fertilization has occurred by determining whether the embryo has two pronuclei (PN) and if the second polar body (2nd PB) has been extruded. Abnormally fertilized human zygotes with one pronucleus (1PN) or three pronuclei (3PN) have been identified in previous studies [1][2][3][4][5][6][7]. Several hypotheses exist to explain such aneuploidies, but the underlying causes in human ART-derived zygotes remain unknown.…”