The transcriptome of corona radiata cells from individual MII oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

BACKGROUND: Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls. METHODS: All patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays. RESULTS: The transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5). CONCLUSION: The overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-014-0110-6) contains supplementary material, which is available to authorized users

Levels of circulating insulin cell-free DNA in women with Polycystic Ovary Syndrome:a longitudinal cohort study

Correlations between clinical measurements and unmethylated and methylated INScfDNA at baseline and at follow-up. (XLSX 14 kb

Overexploitation, Recovery, and Warming of the Barents Sea Ecosystem During 1950–2013

The Barents Sea (BS) is a high-latitude shelf ecosystem with important fisheries, high and historically variable harvesting pressure, and ongoing high variability in climatic conditions. To quantify carbon flow pathways and assess if changes in harvesting intensity and climate variability have affected the BS ecosystem, we modeled the ecosystem for the period 1950–2013 using a highly trophically resolved mass-balanced food web model (Ecopath with Ecosim). Ecosim models were fitted to time series of biomasses and catches, and were forced by environmental variables and fisheries mortality. The effects on ecosystem dynamics by the drivers fishing mortality, primary production proxies related to open-water area and capelin-larvae mortality proxy, were evaluated. During the period 1970–1990, the ecosystem was in a phase of overexploitation with low top-predators’ biomasses and some trophic cascade effects and increases in prey stocks. Despite heavy exploitation of some groups, the basic ecosystem structure seems to have been preserved. After 1990, when the harvesting pressure was relaxed, most exploited boreal groups recovered with increased biomass, well-captured by the fitted Ecosim model. These biomass increases were likely driven by an increase in primary production resulting from warming and a decrease in ice-coverage. During the warm period that started about 1995, some unexploited Arctic groups decreased whereas krill and jellyfish groups increased. Only the latter trend was successfully predicted by the Ecosim model. The krill flow pathway was identified as especially important as it supplied both medium and high trophic level compartments, and this pathway became even more important after ca. 2000. The modeling results revealed complex interplay between fishery and variability of lower trophic level groups that differs between the boreal and arctic functional groups and has importance for ecosystem management

Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a 'fresh transfer' strategy including hCG trigger in assisted reproductive technology (ART):a study protocol for a randomised controlled trial

Introduction Pregnancy rates after frozen embryo transfer (FET) have improved in recent years and are now approaching or even exceeding those obtained after fresh embryo transfer. This is partly due to improved laboratory techniques, but may also be caused by a more physiological hormonal and endometrial environment in FET cycles. Furthermore, the risk of ovarian hyperstimulation syndrome is practically eliminated in segmentation cycles followed by FET and the use of natural cycles in FETs may be beneficial for the postimplantational conditions of fetal development. However, a freeze-all strategy is not yet implemented as standard care due to limitations of large randomised trials showing a benefit of such a strategy. Thus, there is a need to test the concept against standard care in a randomised controlled design. This study aims to compare ongoing pregnancy and live birth rates between a freeze-all strategy with gonadotropin-releasing hormone (GnRH) agonist triggering versus human chorionic gonadotropin (hCG) trigger and fresh embryo transfer in a multicentre randomised controlled trial. Methods and analysis Multicentre randomised, controlled, double-blinded trial of women undergoing assisted reproductive technology treatment including 424 normo-ovulatory women aged 18-39 years from Denmark and Sweden. Participants will be randomised (1:1) to either (1) GnRH agonist trigger and single vitrified-warmed blastocyst transfer in a subsequent hCG triggered natural menstrual cycle or (2) hCG trigger and single blastocyst transfer in the fresh (stimulated) cycle. The primary endpoint is to compare ongoing pregnancy rates per randomised patient in the two treatment groups after the first single blastocyst transfer. Ethics and dissemination The study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committees in Denmark and Sweden. The results of the study will be publically disseminated. Trial registration number NCT02746562; Pre-results

Live birth rate and number of blastomeres on day 2 transfer

PURPOSE: To investigate whether the presence of large fragment (LF) and abnormal cell divisions (ACDs) has influenced the correlation between live birth rate and number of blastomeres detected on day 2 by conventional scoring. METHODS: This study included 578 embryos cultured in time lapse and selected for transfer by conventional scoring on day 2. By time-lapse recordings, embryos were reassessed to identify ACDs and/or LFs mistaken as blastomeres. The latter identifications were used to recalculate fragmentation rate and the number of blastomeres. Life birth rate according to number of blastomeres was compared in (a) embryos selected by conventional scoring and (b) embryos reassessed by time lapse. RESULTS: After conventional scoring, embryos with four cells had a significantly higher pregnancy rate than embryos with less than four cells and embryos with more than four cells. By time-lapse assessment, ACDs and/or recalculated fragmentation >25 % was recognized in 106/578 (18.3 %) of transferred embryos. None of them resulted in a live birth. After exclusion of these embryos, the number of blastomeres on the day of transfer did not have any impact on life birth rate. CONCLUSION: Conventional scoring on day 2 did not detect ACDs and LFs mistaken as blastomeres. LFs can lead to a recalculated fragmentation rate to >25 %. No significant correlation between live birth rate and number of blastomeres in day 2 embryos was observed when embryos with ACDs and fragmentation >25 % were excluded. Recognition of ACDs and fragmentation >25 % is more predictive of live birth than number of blastomeres. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10815-016-0737-x) contains supplementary material, which is available to authorized users