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

Abstract

Research QuestionDo maternal and paternal pronuclear (PN) sizes and their relative differences affect embryonic development, morphokinetics, and pregnancy outcomes in human embryos? DesignTotally, 2,516 fertilised oocytes with two PNs from 1,207 patients were assessed using a time-lapse culture system. The associations between the PN area immediately before PN 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 PNs; embryo development, morphokinetics, and morphological alterations were compared among the zygotes. ResultsAreas of maternal and paternal PN were not correlated with embryonic, pregnancy, and perinatal outcomes. Zygotes with a PNR lower than the median (<0.88, unequal-sized PNs) exhibited impaired embryo development (expanded blastocyst; P = 0.0100). Unequal-sized PNs resulted in a prolonged time interval between maternal and paternal PN appearance, decreased nucleolus precursor body (NPB) alignment, and increased incidence of asynchronous PN breakdown, asymmetric division, and multinucleation (P < 0.0001–0.0230). When the paternal PN was smaller than the maternal PN, the decreased NPB alignment, asynchronous PN breakdown, and abnormal cleavage were observed more frequently, resulting in significantly decreased blastocyst formation compared with the zygotes with equal-sized PNs (P < 0.0001–0.0030). ConclusionsZygotes with unequal-sized PNs exhibited impairments in pre-implantation development, particularly when the paternal PN was smaller than the maternal PN, without any adverse effects on maternal and obstetric outcomes. In addition to the number of PNs, evaluating PNR and PN origin would be beneficial when fertilisation is verified.