Impaired development of zygotes with uneven pronuclear size

Abstract

The correlation between human zygote morphology and chromosomal anomalies after cleavage has not been well characterised. Commonly observed morphological qualities at the zygote stage have provided little insight into further development, and therefore selection for cryopreservation or transfer appears to be less specific than that at later stages of preimplantation development. The purpose of this work was to evaluate the relationship between aberrant pronuclear morphology and chromosomal anomalies after cleavage. Monospermic zygotes exhibiting two pronuclei where diameters differed by at least 4 μm were found to arrest at a significantly higher rate than zygotes with pronuclear diameters differing by less than 4 µm. In addition, a higher incidence of day 2 multinucleation was observed. Embryos deriving from zygotes with dysmorphic pronuclei that were not replaced or cryopreserved by day 3 of development were separated and fixed for fluorescence in situ hybridisation analysis of chromosomes X, Y, 13, 18 and 21. A significantly higher incidence of mosaicism was found in this group compared with others that had developed from zygotes with normal pronuclear morphology. Although the mechanism leading to this form of divergent pronuclear morphology is unclear, results suggest a correlation with oocyte cyto-plasmic immaturity.

Developmental prognosis for zygotes based on pronuclear pattern: Usefulness of pronuclear scoring

“…In our results from group Z4, the association between asymmetric and/or separate PNs and poor prognosis embryos was confirmed [5]. Pronuclear morphology studies have found that differences of more than 4 µm in the diameter of PNs are associated with aneuploidy [6]. The analysis of chromosomal status of embryos from different patterns suggests a lower incidence of chromosomal abnormalities in patients aged < 37 years with zygotes with similar PN size [31].…”

“…Multinucleation is present in the same proportion in embryos for each PN pattern both in our data and in Tesarik's. We find poor prognosis embryos from pattern 4 zygotes, with a higher percentage of blastomere multinucleation compared to the data from Tesarik and Greco [4] and Sadowy et al [6]. It would seem that the presence of a very low number of NPBs (corresponding to p4) in any PN is a poor prognosis factor for embryo development.…”

“…Zygote morphology has been associated with subsequent embryo development as far as fragmentation, arrested cleavage, chromosome dotation and multinucleation is concerned [6]. Survival after cryopreservation has been related to morphological characteristics of cytoplasm maturity, nucleolar aspect and relative location of PN inside the zygote [7].…”

Human Embryonic Behavior Observed with Time-Lapse Cinematography

“…The PN-like body was then absorbed into the ooplasm and migrated toward the mPN, leading to formation of an uneven 2PN embryo ( Figure 5). Although it has been reported that zygotes with uneven 2PN may correlate with ooplasmic immaturity and chromosomal abnormalities [22,23], the etiology and physiological significance of those zygotes are still unknown. The TLC analyses in this study demonstrated for the first time a possible mechanism for the formation of uneven 2PN zygotes.…”

An oocyte score for use in assisted reproduction

“…This is usually achieved either by the extended culture of human embryos to the blastocyst stage [5,6] or by the morphological analysis and selection of the highest quality embryos for transfer [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. More recently, the assessment of zygote quality has been applied [23][24][25][26][27][28][29][30][31][32]. Although these techniques have greatly assisted in achieving an acceptable pregnancy rate with the minimum number of embryos transferred into the uterus, one aspect of these protocols is that non-transferred embryos are discarded or cryopreserved.…”