Impact of exogenous gonadotropin stimulation on circulatory and follicular fluid cytokine profiles.

Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence

Experience of developing and evaluating a fertility preservation patient decision aid for teenage and adult women with cancer for use in oncology settings, UK (The Cancer, Fertility and Me study)

The study was supported in part by the Danish Cancer Society, Grant# R150-A10080Purpose Fear of cancer recurrence (FCR) is a significantly distressing problem that affects a substantial number of patients with and survivors of cancer; however, the overall efficacy of available psychological interventions on FCR remains unknown. We therefore evaluated this in the present systematic review and meta-analysis. Methods We searched key electronic databases to identify trials that evaluated the effect of psychological interventions on FCR among patients with and survivors of cancer. Controlled trials were subjected to meta-analysis, and the moderating influence of study characteristics on the effect were examined. Overall quality of evidence was evaluated using the GRADE system. Open trials were narratively reviewed to explore ongoing developments in the field (PROSPERO registration no.: CRD42017076514). Results A total of 23 controlled trials (21 randomized controlled trials) and nine open trials were included. Small effects (Hedges’s g) were found both at postintervention (g = 0.33; 95% CI, 0.20 to 0.46; P < .001) and at follow-up (g = 0.28; 95% CI, 0.17 to 0.40; P < .001). Effects at postintervention of contemporary cognitive behavioral therapies (CBTs; g = 0.42) were larger than those of traditional CBTs (g = 0.24; β = .22; 95% CI, .04 to .41; P = .018). At follow-up, larger effects were associated with shorter time to follow-up (β = −.01; 95% CI, −.01 to −.00; P = .027) and group-based formats (β = .18; 95% CI, .01 to .36; P = .041). A GRADE evaluation indicated evidence of moderate strength for effects of psychological intervention for FCR. Conclusion Psychological interventions for FCR revealed a small but robust effect at postintervention, which was largely maintained at follow-up. Larger postintervention effects were found for contemporary CBTs that were focused on processes of cognition—for example, worry, rumination, and attentional bias—rather than the content, and aimed to change the way in which the individual relates to his or her inner experiences. Future trials could investigate how to further optimize and tailor interventions to individual patients’ FCR presentation.Publisher PDFPeer reviewe

A novel ASXL1–OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies

ASXL1 plays key roles in epigenetic regulation of gene expression through methylation of histone H3K27, and disruption of ASXL1 drives myeloid malignancies, at least in part, via derepression of posterior HOXA loci. However, little is known about the identity of proteins that interact with ASXL1 and about the functions of ASXL1 in modulation of the active histone mark, such as H3K4 methylation. In this study, we demonstrate that ASXL1 is a part of a protein complex containing HCFC1 and OGT; OGT directly stabilizes ASXL1 by O-GlcNAcylation. Disruption of this novel axis inhibited myeloid differentiation and H3K4 methylation as well as H2B glycosylation and impaired transcription of genes involved in myeloid differentiation, splicing, and ribosomal functions; this has implications for myelodysplastic syndrome (MDS) pathogenesis, as each of these processes are perturbed in the disease. This axis is responsible for tumor suppression in the myeloid compartment, as reactivation of OGT induced myeloid differentiation and reduced leukemogenecity both in vivo and in vitro. Our data also suggest that MLL5, a known HCFC1/OGT-interacting protein, is responsible for gene activation by the ASXL1-OGT axis. These data shed light on the novel roles of the ASXL1-OGT axis in H3K4 methylation and activation of transcription