Effects of unequal-sized pronuclei and their origin on embryo development and obstetric outcomes: a time-lapse...

Do maternal and paternal pronuclear sizes and their relative differences affect embryonic development, morphokinetics and pregnancy outcomes in human embryos?

A total of 2516 fertilized oocytes with two pronuclei from 1207 patients were assessed using a time-lapse culture system. The associations between the pronuclear area immediately before pronuclear breakdown and its relative ratio (PNR), and embryonic, pregnancy and perinatal outcomes, were retrospectively evaluated. Perinatal outcomes were obtained from a self-reported questionnaire. Zygotes were stratified by PNR and origin of the pronuclei; embryo development, morphokinetics and morphological alterations were compared among the zygotes.

Areas of maternal and paternal pronuclei were not correlated with embryonic, pregnancy and perinatal outcomes. Zygotes with a PNR lower than the median (<0.88, unequal-sized pronuclei) had impaired embryo development (expanded blastocyst; P = 0.0100). Unequal-sized pronuclei resulted in a prolonged time interval between maternal and paternal pronuclear appearance, decreased nucleolus precursor body (NPB) alignment and increased incidence of asynchronous pronuclear breakdown, asymmetric division and multinucleation (P < 0.0001-0.0230). When the paternal pronucleus was smaller than the maternal pronucleus, the decreased NPB alignment, asynchronous pronuclear breakdown and abnormal cleavage were observed more frequently, resulting in significantly decreased blastocyst formation compared with the zygotes with equal-sized pronuclei (P < 0.0001-0.0030).

Zygotes with unequal-sized pronuclei had impairments in preimplantation development, particularly when the paternal pronucleus was smaller than the maternal pronucleus, without any adverse effects on maternal and obstetric outcomes. In addition to the number of pronuclei, evaluating PNR and pronuclear origin would be beneficial when fertilization is verified.