Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial.

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%.

Appendix E: Rapid-i: Closed Vitrification Device by Vitrolife.

Cryopreservation of gametes and embryos is a growing technique in numerous reproductive fields including human-assisted reproduction. With improved understanding of embryo physiology and optimized culture conditions, there are now more embryos than ever to vitrify for potential use in subsequent cycles. Many gametes and embryos have been cryopreserved in open systems, but there are concerns with regard to contamination from the liquid nitrogen and also cross-contamination between patients' germplasm.

Cryopreservation in ART and concerns with contamination during cryobanking.

The cryopreservation of gametes and embryos is vital to numerous fields of reproductive biology, including assisted human reproduction. With improved culture conditions, there are an increasing number of embryos to cryopreserve for potential use in subsequent cycles. Many of the gametes and embryos in human IVF are cryopreserved in open systems.

Ultrarapid vitrification of mouse oocytes and embryos.

Cryopreservation facilitates long-term storage of gametes and embryos for numerous purposes. For example, cryobanking of unique mouse strains, particularly transgenic mice, offers important protection of valuable genetics. It also provides a practical solution for facilities trying to house large numbers of research animals or those looking to relocate without the risk of introducing an animal-derived pathogen.

Vitrification of mouse embryos with super-cooled air.

Objective: To develop a closed vitrification device (i.e., one that requires no direct contact with liquid nitrogen) for successful cryostorage of embryos.

Sex-related physiology of the preimplantation embryo.

Male and female preimplantation mammalian embryos differ not only in their chromosomal complement, but in their proteome and subsequent metabolome. This phenomenon is due to a finite period during preimplantation development when both X chromosomes are active, between embryonic genome activation and X chromosome inactivation, around the blastocyst stage. Consequently, prior to implantation male and female embryos exhibit differences in their cellular phenotype.

Exposure of mouse oocytes to 1,2-propanediol during slow freezing alters the proteome.

Objective: To examine the effect of exposure to 1,2-propanediol (PrOH) on the mammalian oocyte proteome.

Design: Experimental study.

Setting: Research laboratory.

Analysis of oocyte physiology to improve cryopreservation procedures.

In contrast to the preimplantation mammalian embryo, it has been notoriously difficult to cryopreserve the metaphase II oocyte. The ability to store oocytes successfully at -196 degrees C has numerous practical and financial advantages, together with ethical considerations, and will positively impact animal breeding programs and assisted conception in the human. Differences in membrane permeability and in physiology are two main reasons why successful oocyte cryopreservation has remained elusive.

Vitrification of mouse pronuclear oocytes with no direct liquid nitrogen contact.

The ability to routinely cryopreserve human oocytes and embryos represents a significant advancement in the field of assisted reproductive technology. Although the method of slow freezing is commonly employed, research on the alternative technique of vitrification is promising. Vitrification involves incubation of the cell in a cryoprotectant rich solution, which permits a glass-like state to occur almost instantaneously in liquid nitrogen.

Calcium-free vitrification reduces cryoprotectant-induced zona pellucida hardening and increases fertilization rates in mouse oocytes.

Despite the success of embryo cyropreservation, routine oocyte freezing has proved elusive with only around 200 children born since the first reported birth in 1986. The reason for the poor efficiency is unclear, but evidence of zona pellucida hardening following oocyte freezing indicates that current protocols affect oocyte physiology. Here we report that two cryoprotectants commonly used in vitrification procedures, dimethyl sulfoxide (DMSO) and ethylene glycol, cause a large transient increase in intracellular calcium concentration in mouse metaphase II (MII) oocytes comparable to the initial increase triggered at fertilization.

Role of phospholipase C-zeta domains in Ca2+-dependent phosphatidylinositol 4,5-bisphosphate hydrolysis and cytoplasmic Ca2+ oscillations.

The sperm-specific phospholipase C-zeta (PLCzeta) elicits fertilization-like Ca2+ oscillations and activation of embryo development when microinjected into mammalian eggs (Saunders, C. M., Larman, M.

Inhibiting MAP kinase activity prevents calcium transients and mitosis entry in early sea urchin embryos.

A transient calcium increase triggers nuclear envelope breakdown (mitosis entry) in sea urchin embryos. Cdk1/cyclin B kinase activation is also known to be required for mitosis entry. More recently, MAP kinase activity has also been shown to increase during mitosis.

Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear targeting of PLCzeta.

During the first cell cycle Ca2+ oscillations are regulated in a cell cycle-dependent manner, such that the oscillations are unique to M phase. How the Ca2+ oscillations are regulated with such cell cycle stage-dependency is unknown, despite their importance for egg activation and embryo development. We recently identified a novel, sperm-specific phospholipase C (PLCzeta; PLCzeta) that triggers Ca2+ oscillations similar to those caused by sperm.

PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development.

Upon fertilisation by sperm, mammalian eggs are activated by a series of intracellular Ca(2+) oscillations that are essential for embryo development. The mechanism by which sperm induces this complex signalling phenomenon is unknown. One proposal is that the sperm introduces an exclusive cytosolic factor into the egg that elicits serial Ca(2+) release.