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

Quality of care for people with multimorbidity:a case series

Abstract Background Multimorbidity is becoming increasingly prevalent and presents challenges for healthcare providers and systems. Studies examining the relationship between multimorbidity and quality of care report mixed findings. The purpose of this study was to investigate quality of care for people with multimorbidity in the publicly funded healthcare system in Denmark. Methods To investigate the quality of care for people with multimorbidity different groups of clinicians from the hospital, general practice and the municipality reviewed records from 23 persons with multimorbidity and discussed them in three focus groups. Before each focus group, clinicians were asked to review patients’ medical records and assess their care by responding to a questionnaire. Medical records from 2013 from hospitals, general practice, and health centers in the local municipality were collected and linked for the 23 patients. Further, two clinical pharmacologists reviewed the appropriateness of medications listed in patient records. Results The review of the patients’ records conducted by three groups of clinicians revealed that around half of the patients received adequate care for the single condition which prompted the episode of care such as a hospitalization, a visit to an outpatient clinic or the general practitioner. Further, the care provided to approximately two-thirds of the patients did not take comorbidities into account and insufficiently addressed more diffuse symptoms or problems. The review of the medication lists revealed that the majority of the medication lists contained inappropriate medications and that there were incongruity in medication listed in the primary and secondary care sector. Several barriers for providing high quality care were identified. These included relative short consultation times in general practice and outpatient clinics, lack of care coordinators, and lack of shared IT-system proving an overview of the treatment. Conclusions Our findings reveal quality of care deficiencies for people with multimorbidity. Suggestions for care improvement for people with multimorbidity includes formally assigned responsibility for care coordination, a change in the financial incentive structure towards a system rewarding high quality care and care focusing on prevention of disease exacerbation, as well as implementing shared medical record systems

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics

The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomic