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Abstract The first embryonic division represents a starting point for the development of a new individual. In many species, tight control over the first embryonic division ensures its accuracy. However, the first division in humans is often erroneous and can impair embryo development. To delineate the spatiotemporal organization of the first mitotic division typical for normal human embryo development, we systematically analyzed a unique timelapse dataset of 300 IVF embryos that developed into healthy newborns. The zygotic division pattern of these best-quality embryos was compared to their siblings that failed to implant or arrested during cleavage stage. We show that division at the right angle to the juxtaposed pronuclei is preferential and supports faithful zygotic division. Alternative configurations of the first mitosis are associated with reduced clustering of nucleoli and multinucleation at the 2-cell stage, which are more common in women of advanced age. Collectively, these data imply that orientation of the first division predisposes human embryos to genetic (in)stability and may contribute to aneuploidy and age-related infertility.

The egg plays a pivotal role in the reproduction of our species. Nevertheless, its fundamental biology remains elusive. Transmission electron microscopy is traditionally used to inspect the ultrastructure of female gametes. However, two-dimensional micrographs contain only fragmentary information about the spatial organization of the complex oocyte cytoplasm. Here, we employed the Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to explore human oocyte intracellular morphology in three dimensions (3D). Volume reconstruction of generated image stacks provided an unprecedented view of ooplasmic architecture. Organelle distribution patterns observed in nine donor oocytes, representing three maturational stages, documented structural changes underlying the process by which the egg acquires developmental competence. 3D image segmentation was performed to extract information about distinct organelle populations, and the following quantitative analysis revealed that the mitochondrion occupies ∼ 4.26% of the maturing oocyte cytoplasm. In summary, this proof-of-concept study demonstrates the potential of large volume electron microscopy to study rare samples of delicate female gametes and paves the way for applying the FIB-SEM technique in human oocyte research.

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Aim: The aim of the study was to evaluate the influence of a specific diagnosis of infertile women and men on their life quality and psychosexual functioning based on internationally validated questionnaires., Materials and Methods: A total of 853 couples seeking treatment for infertility completed the gender-specific batteries comprised of Fertility Quality of Life tool (FertiQoL), Female Sexual Function Index (FSFI) in women, and Brief Sexual Function Inventory (BSFI) in men. Women were followed in the group of primary and secondary infertility and then with specific diagnoses - polycystic ovary syndrome, tubal factor, endometriosis, and idiopathic sterility. Men's categories reflected spermiogram results, i.e., normozoospermia, merged categories of milder disorders of a spermiogram (teratozoospermia, asthenozoospermia, oligozoospermia, and oligoasthenoteratospermia), oligoasthenoteratospermia (OAT) gravis, azoospermia, and when the man was not examined., Results: When evaluating the quality of life in women, we found statistically significant differences between primary and secondary sterility. Primary infertile women scored worse especially in the social area. Worse assessment appeared also in mind-body (area evaluating affliction of the body). Emotional and relational domains included similar results in primary and secondary infertile women. With a specific diagnosis, statistically significant differences were not proved. Using the orientational cut-off score, FertiQoL stated that approximately 10% of women experienced adverse quality of life in relation to fertility. In the domain of sexual functioning, 30% of women demonstrated clinically significant dysfunctions. In men, respondents in the normozoospermic and non-diagnosed categories scored higher than those in the merged category and OAT gravis. Only 2% of men felt their quality of life was poor due to fertility, and clinically significant dysfunctions appeared only in 3% of them., Conclusion: In women, impaired fertility-related quality of life and psychosexual functioning are significantly linked to primary sterility, where specifically the social domain is affected. The impact of a specific diagnosis appears to be minimal. We found high levels of sexual dysfunctions in women. In men, we follow the link of evaluated quality of life in connection with their results of the spermiogram. With spermiogram defects, both areas of functioning can be affected.

The egg plays a pivotal role in the reproduction of our species. Nevertheless, its fundamental biology remains elusive. Transmission electron microscopy is traditionally used to inspect the ultrastructure of female gametes. However, two-dimensional micrographs contain only fragmentary information about the spatial organization of the complex oocyte cytoplasm. Here, we employed the Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to explore human oocyte intracellular morphology in three dimensions (3D). Volume reconstruction of generated image stacks provided an unprecedented view of ooplasmic architecture. Organelle distribution patterns observed in nine donor oocytes, representing three maturational stages, documented structural changes underlying the process by which the egg acquires developmental competence. 3D image segmentation was performed to extract information about distinct organelle populations, and the following quantitative analysis revealed that the mitochondrion occupies ∼ 4.26% of the maturing oocyte cytoplasm. In summary, this proof-of-concept study demonstrates the potential of large volume electron microscopy to study rare samples of delicate female gametes and paves the way for applying the FIB-SEM technique in human oocyte research., Competing Interests: JJ is employed by TESCAN ORSAY HOLDING, the manufacturer of the FIB-SEM microscopes used in this study. However, the study did not receive any funding from the industrial partner. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Trebichalská, Javůrek, Tatíčková, Kyjovská, Kloudová, Otevřel, Hampl and Holubcová.)