Do Multinuclei in IVF Embryos Represent Atypical Morphology or an Abnormality of Cell Division?

Tsvia Frumkin 1 Dalit Ben-Yosef 1 Tamar Shwartz 1 Nava May-Raz 1 Tania Cohen 1 Ariela Carmon 1 Veronica Gold 1 Sagit Peleg 1 Ido Eldar 1 Israel Vagman 1 Benny Almog 1 Fuad Azem 1 Ami Amit 1 Yuval Yaron 2 Adi Reches 1,2 Mira Malcov 1
1Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center
2Prenatal Diagnosis Unit, Tel Aviv Sourasky Medical Center

Introduction: Until recently, IVF embryos demonstrating multinucli blastomeres were considered to be associated with abnormal development. Multinucleated cells may arise by nuclear division with delayed cytokinesis, by multi-lobulated nuclei structure or by the fusion of the plasma membranes of two cells. Lately, morphokinetic analysis has shown that multinuclei can sometimes lead to normal development.

Aim: To attempt to elucidate the etiology for multinuclei embryos and to compare it to their assessment by time lapse microscopy.

Materials & Methods: A total of 105 multinucleated blastomeres were biopsied from embryos subjected to PGD-FISH. Based on FISH results the occurrence leading to multinucleation was hypothesized. Appearance of multinucleate during embryonic development, cell cycle synchronization and timing, PB2 location, fragmentation and scoring were evaluated.

Results: FISH results of the multinuclei balstomeres were divided into 3 groups: 1) Two nucleui demonstrating identical signals (31.5%; 33/105), which may be explained by delayed cytokinesis or fusion of two nuclei. 2) The sum of signals in two nucleuses represents the signals of a single normal nucleus (39%; 41/105), which may be explained by multi-lobulated nuclei structure. 3) Other results which represent abnormal nucleus division. Twenty embryos were assessed by time-lapse microscopy.  In 90% of the assessed embryos from all groups, multinucleation was demonstrated as early as at the 2 cells stage (90%; 18/20).These embryos demonstrated normal dynamic development at day 4-5.

Conclusion: Our results suggest that a significant portion of IVF embryos presenting an atypical morphology of the multinucli, have a normal nucleus and normal cell division. Therefore these embryos are suitable for transfer.









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