Correction: A secreted proteomic footprint for stem cell pluripotency.

[This corrects the article DOI: 10.1371/journal.pone.

DNA damage in prepared semen is negatively associated with semen quality and fertilisation rate in assisted reproduction technology (ART) treatment.

Sperm DNA contains strand breaks and base damage that can potentially affect reproductive health. This study aims to determine to what extent sperm DNA integrity and alkylation is associated with semen quality and assisted reproduction technology (ART) treatment outcomes, in particular fertilisation and cleavage rates. Male partners of couples attending for infertility treatment were recruited.

Deep learning pipeline reveals key moments in human embryonic development predictive of live birth after in vitro fertilization.

Demand for in vitro fertilization (IVF) treatment is growing; however, success rates remain low partly due to difficulty in selecting the best embryo to be transferred. Current manual assessments are subjective and may not take advantage of the most informative moments in embryo development. Here, we apply convolutional neural networks (CNNs) to identify key windows in pre-implantation human development that can be linked to embryo viability and are therefore suitable for the early grading of IVF embryos.

Glucose influences endometrial receptivity to embryo implantation through O-GlcNAcylation-mediated regulation of the cytoskeleton.

Phenotypic changes to endometrial epithelial cells underpin receptivity to embryo implantation at the onset of pregnancy but the effect of hyperglycemia on these processes remains poorly understood. Here, we show that physiological levels of glucose (5 mM) abolished receptivity in the endometrial epithelial cell line, Ishikawa. However, embryo attachment was supported by 17 mM glucose as a result of glucose flux through the hexosamine biosynthetic pathway (HBP) and modulation of cell function via protein O-GlcNAcylation.

A secreted proteomic footprint for stem cell pluripotency.

With a view to developing a much-needed non-invasive method for monitoring the healthy pluripotent state of human stem cells in culture, we undertook proteomic analysis of the waste medium from cultured embryonic (Man-13) and induced (Rebl.PAT) human pluripotent stem cells (hPSCs). Cells were grown in E8 medium to maintain pluripotency, and then transferred to FGF2 and TGFβ deficient E6 media for 48 hours to replicate an early, undirected dissolution of pluripotency.

A systematic review of transcriptomic studies of the human endometrium reveals inconsistently reported differentially expressed genes.

Genome-wide analysis of gene expression has been widely applied to study the endometrium, although to our knowledge no systematic reviews have been performed. Here, we identified 74 studies that described transcriptomes from whole (unprocessed) endometrium samples and found that these fitted into three broad investigative categories; endometrium across the menstrual cycle, endometrium in pathology, and endometrium during hormone treatment. Notably, key participant information such as menstrual cycle length and body mass index was often not reported.

Does PGT-A improve assisted reproduction treatment success rates: what can the UK Register data tell us?

Purpose: To show how naïve analyses of aggregated UK ART Register data held by the Human Fertilisation and Embryology Authority to estimate the effects of PGT-A can be severely misleading and to indicate how it may be possible to do a more credible analysis. Given the limitations of the Register, we consider the extent to which such an analysis has the potential to answer questions about the real-world effectiveness of PGT-A.

Methods: We utilise the publicly available Register datasets and construct logistic regression models for live birth events (LBE) which adjust for confounding.

General health in a cohort of children conceived after assisted reproductive technology in the United Kingdom: a population-based record-linkage study.

Background: Assisted reproductive technology use is increasing annually; however, data on long-term child health outcomes including hospital admissions are limited.

Objective: This study aimed to examine the potential effects of assisted reproductive technology on any and cause-specific hospital admissions unrelated to perinatal diagnoses.

Study Design: This was a population-based record-linkage study that included a previously established cohort of children born after assisted reproductive technology in the United Kingdom between 1997 and 2009 (n=63,877), their naturally conceived siblings (n=11,343), and matched naturally conceived population controls (n=127,544) linked to their postnatal health outcomes up to March 31, 2016 to provide robust risk estimates of the potential effects of assisted reproductive technology on any and cause-specific hospital admissions unrelated to perinatal diagnoses.

The Quiet Embryo Hypothesis: 20 years on.

This article revisits the hypothesis, proposed in 2002, that the successful development of oocytes and preimplantation mammalian embryos is associated with a metabolism which is "quiet" rather than "active", within limits which had yet to be defined. A distinction was drawn between Functional Quietness, Loss of quietness in response to stress and Inter-individual differences in embryo metabolism and here we document applications of the hypothesis to other areas of reproductive biology. In order to encompass the requirement for "limits" and replace the simple distinction between "quiet" and "active", evidence is presented which led to a re-working of the hypothesis by proposing the existence of an optimal range of metabolic activity, termed a "Goldilocks zone", within which oocytes and embryos with maximum developmental potential will be located.

Transfer of thawed frozen embryo versus fresh embryo to improve the healthy baby rate in women undergoing IVF: the E-Freeze RCT.

Background: Freezing all embryos, followed by thawing and transferring them into the uterine cavity at a later stage (freeze-all), instead of fresh-embryo transfer may lead to improved pregnancy rates and fewer complications during in vitro fertilisation and pregnancies resulting from it.

Objective: We aimed to evaluate if a policy of freeze-all results in a higher healthy baby rate than the current policy of transferring fresh embryos.

Design: This was a pragmatic, multicentre, two-arm, parallel-group, non-blinded, randomised controlled trial.

Trophectoderm differentiation to invasive syncytiotrophoblast is promoted by endometrial epithelial cells during human embryo implantation.

Study Question: How does the human embryo breach the endometrial epithelium at implantation?

Summary Answer: Embryo attachment to the endometrial epithelium promotes the formation of multinuclear syncytiotrophoblast from trophectoderm, which goes on to breach the epithelial layer.

What Is Known Already: A significant proportion of natural conceptions and assisted reproduction treatments fail due to unsuccessful implantation. The trophectoderm lineage of the embryo attaches to the endometrial epithelium before breaching this barrier to implant into the endometrium.

Cohort profile: a national, population-based cohort of children born after assisted conception in the UK (1992-2009): methodology and birthweight analysis.

Purpose: To generate a large cohort of children born after assisted reproductive technology (ART) in the UK between 1992 and 2009, their naturally conceived siblings (NCS) and matched naturally conceived population (NCP) controls and linking this with health outcome data to allow exploration of the effects of ART. The effects of fresh and frozen embryo transfer on birth weight (BW) were analysed to test the validity of the cohort.

Participants: Children recorded on the Human Fertilisation and Embryology Authority (HFEA) register as being born after ART between 1992 and 2009, their NCS and matched NCP controls linked to Office for National Statistics birth registration dataset (HFEA-ONS cohort).

Clinical efficacy of hyaluronate-containing embryo transfer medium in IVF/ICSI treatment cycles: a cohort study.

Study Question: Does the duration of embryo exposure to hyaluronic acid (HA) enriched medium improve the rate of live birth events (LBEs)?

Summary Answer: The use of embryo transfer (ET) medium rich in HA improves LBE (a singleton or twin live birth) regardless of the duration of exposure evaluated in this study, but does not alter gestation or birthweight (BW).

What Is Known Already: HA-enriched medium is routinely used for ET in ART to facilitate implantation, despite inconclusive evidence on safety and efficacy.

Study Design Size Duration: A cohort study was performed evaluating clinical treatment outcomes before and after HA-enriched ET medium was introduced into routine clinical practice.

The marker of alkyl DNA base damage, N7-methylguanine, is associated with semen quality in men.

Sperm DNA contains a range of DNA base damage that can arise, in part, from exposure to methylating agents. However, the effects are not fully characterized and so the aim of this study was to investigate associations between semen quality and the levels of N7-methyldeoxyguanosine (N7-MedG), a marker of exposure to methylating agents, and other markers of DNA damage and DNA methylation. Sperm samples were collected from 105 men attending an assisted reproduction clinic as part of a couple undergoing treatment for infertility and semen quality assessed manually according to WHO guidelines.

Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation.

Embryo implantation begins with blastocyst trophectoderm (TE) attachment to the endometrial epithelium, followed by the breaching of this barrier by TE-derived trophoblast. Dynamic protein modification with O-linked β-N-acetylglucosamine (O-GlcNAcylation) is mediated by O-GlcNAc transferase and O-GlcNAcase (OGA), and couples cellular metabolism to stress adaptation. O-GlcNAcylation is essential for blastocyst formation, but whether there is a role for this system at implantation remains unexplored.

Human spermbots for patient-representative 3D ovarian cancer cell treatment.

Cellular micromotors are attractive for locally delivering high concentrations of drug, and targeting hard-to-reach disease sites such as cervical cancer and early ovarian cancer lesions by non-invasive means. Spermatozoa are highly efficient micromotors perfectly adapted to traveling up the female reproductive system. Indeed, bovine sperm-based micromotors have shown potential to carry drugs toward gynecological cancers.

Chemical signals from eggs facilitate cryptic female choice in humans.

Mate choice can continue after mating via chemical communication between the female reproductive system and sperm. While there is a growing appreciation that females can bias sperm use and paternity by exerting cryptic female choice for preferred males, we know surprisingly little about the mechanisms underlying these post-mating choices. In particular, whether chemical signals released from eggs (chemoattractants) allow females to exert cryptic female choice to favour sperm from specific males remains an open question, particularly in species (including humans) where adults exercise pre-mating mate choice.

The effects of hyaluronate-containing medium on human embryo attachment to endometrial epithelial cells .

Study Question: Does embryo transfer medium containing hyaluronate (HA) promote the attachment phase of human embryo implantation?

Summary Answer: HA-containing medium does not promote human blastocyst attachment to endometrial epithelial cells .

What Is Known Already: Embryo transfer media containing high concentrations of HA are being used to increase implantation and live birth rates in IVF treatment, although the mechanism of action is unknown.

Study Design Size Duration: Expression of HA-interacting genes in frozen-thawed oocytes/embryos was assessed by microarray analysis ( = 21).