Age-dependent loss of cohesion protection in human oocytes.

Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis as a common cause. We found that loss of a specific pool of the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon.

The first mitotic division of human embryos is highly error prone.

Human beings are made of ~50 trillion cells which arise from serial mitotic divisions of a single cell - the fertilised egg. Remarkably, the early human embryo is often chromosomally abnormal, and many are mosaic, with the karyotype differing from one cell to another. Mosaicism presumably arises from chromosome segregation errors during the early mitotic divisions, although these events have never been visualised in living human embryos.

Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids.

Decidual remodelling of midluteal endometrium leads to a short implantation window after which the uterine mucosa either breaks down or is transformed into a robust matrix that accommodates the placenta throughout pregnancy. To gain insights into the underlying mechanisms, we established and characterized endometrial assembloids, consisting of gland-like organoids and primary stromal cells. Single-cell transcriptomics revealed that decidualized assembloids closely resemble midluteal endometrium, harbouring differentiated and senescent subpopulations in both glands and stroma.

Regulation and roles of the hyaluronan system in mammalian reproduction.

Hyaluronan (HA) is a non-sulphated glycosaminoglycan polymer naturally occurring in many tissues and fluids of mammals, including the reproductive system. Its biosynthesis by HA synthase (HAS1-3) and catabolism by hyaluronidases (HYALs) are affected by ovarian steroid hormones. Depending upon its molecular size, HA functions both as a structural component of tissues in the form of high-molecular-weight HA or as a signalling molecule in the form of small HA molecules or HA fragments with effects mediated through interaction with its specific cell-membrane receptors.

Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities.

The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed in human pregnancies. A successful meiosis I (MI) division entails separation of homologous chromosome pairs and co-segregation of sister chromatids. For this to happen, sister kinetochores must form attachments to spindle kinetochore-fibres emanating from the same pole.

Semiautomated analysis of embryoscope images: Using localized variance of image intensity to detect embryo developmental stages.

Embryo selection in in vitro fertilization (IVF) treatment has traditionally been done manually using microscopy at intermittent time points during embryo development. Novel technique has made it possible to monitor embryos using time lapse for long periods of time and together with the reduced cost of data storage, this has opened the door to long-term time-lapse monitoring, and large amounts of image material is now routinely gathered. However, the analysis is still to a large extent performed manually, and images are mostly used as qualitative reference.

Uterine selection of human embryos at implantation.

Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embryos elicit an endoplasmic stress response in human decidual cells.

Time to pregnancy: a computational method for using the duration of non-conception for predicting conception.

An important problem in reproductive medicine is deciding when people who have failed to become pregnant without medical assistance should begin investigation and treatment. This study describes a computational approach to determining what can be deduced about a couple's future chances of pregnancy from the number of menstrual cycles over which they have been trying to conceive. The starting point is that a couple's fertility is inherently uncertain.

Consent agreements for cryopreserved embryos: the case for choice.

Under current UK law, an embryo cannot be transferred to a woman's uterus without the consent of both of its genetic parents, that is both of the people from whose gametes the embryo was created. This consent can be withdrawn at any time before the embryo transfer procedure. Withdrawal of consent by one genetic parent can result in the other genetic parent losing the opportunity to have their own genetic children.

Spindle position assessment prior to ICSI does not benefit fertilization or early embryo quality.

Intracytoplasmic sperm injection (ICSI) is traditionally performed with the first polar body at 6 or 12 o'clock, and the injection pipette inserted at 3 or 9 o'clock. This positioning aims to direct the path of the injection pipette at a distance from the presumed metaphase II spindle position. Since spindles can now be imaged directly in living oocytes using computer-assisted polarized light microscopy, the effectiveness of this positioning precaution was studied.

Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one.

Background: The vast majority of oocytes formed in the fetal ovary do not survive beyond birth. Possible reasons for their loss include the elimination of non-viable genetic constitutions arising through meiosis, however, the precise relationship between meiotic stages and prenatal apoptosis of oocytes remains elusive. We studied oocytes in mouse fetal and neonatal ovaries, 14.

Fads and foibles in ART: where is the evidence?

This commentary on the scientific basis of laboratory procedures in assisted conception discusses the origins of widespread discrepancies in 'standard' laboratory techniques experienced by patients and their embryos. The lack of direct evidence from clinical laboratory trials and the reasons for this will be highlighted using some examples drawn mainly from embryo culture. Inconsistencies and grey areas in the governance framework of this unique field could usefully be eliminated and attention focused on the need for a rational approach to procedural trials and pilot studies necessarily conducted in clinical laboratories.

Challenges of the EU 'tissues and cells' directive.

Assisted conception is among many tissue-processing disciplines encompassed by new European legislation on the quality and safety of tissues and cells used therapeutically. These directives have highlighted interdisciplinary differences in some current practices, such as variations in laboratory air quality. This commentary discusses the likely requirements of the EU directives for air quality in tissue-processing laboratories.

Pharmacological manipulation of nitric oxide levels in mouse follicle cultures demonstrates key role of extrafollicular control of ovulation.

Background: Nitric oxide (NO) is involved in ovulation, but it is uncertain whether the mechanisms responsible are systemic or local. In vivo and in perfused ovaries, inhibition of nitric oxide synthase (NOS) reduces ovulation. This study used a well-characterized system of isolated follicle culture to assess which isoforms of NOS might be involved at the follicular level.

Expression of nitric oxide synthase and effect of substrate manipulation of the nitric oxide pathway in mouse ovarian follicles.

Background: Nitric oxide (NO) is a cell messenger with multiple actions in different biological systems, implicated in the control of follicle and oocyte function. NO is formed from L-arginine by isoforms of nitric oxide synthase (NOS) via NG-hydroxy-L-arginine, with L-citrulline as a byproduct. This study aimed to show how modulation of NO by manipulating NOS substrates would affect mouse follicle growth and ovulation in vitro, where vascular effects of NO are attenuated.

Patterns of meiotic recombination in human fetal oocytes.

Abnormal patterns of meiotic recombination (i.e., crossing-over) are believed to increase the risk of chromosome nondisjunction in human oocytes.

Effects of varying gonadotrophin dose and timing on antrum formation and ovulation efficiency of mouse follicles in vitro.

Background: This study tested factors affecting mouse follicle growth in vitro, to determine end-points marking follicle function in vitro.

Methods: Pre-antral follicles (mean 137 microm) from B6CBF1 mice were cultured in a substrate-adherent system for < or = 14 days. FSH (0-1000 mIU/ml) day of HCG (1.