Transcriptomic signatures in follicular cells associated with failure of in vitro fertilization in humans

ABSTRACT: IVF success rate remains low (usually around 30%) and many cycles are needed to achieve pregnancy, raising issues for patients and society. IVF success or failure mainly depends on quality of the oocytes retrieved and on the patient response to the ovarian stimulation. Hormonal stimulation prior to IVF influences the ovarian environment and therefore impacts oocytes and subsequent embryo quality. We believe that if more information was available to clinicians to analyze why a cycle has failed, they could adapt the next stimulation protocol accordingly and improve success rate. We believe that particular molecular signatures are associated with failure causes and that RNA analysis could be used as a diagnosis tool. The aim of this study was to compare gene expression between failed and successful IVF cycles and to determine how gene expression is affected in follicles from failed cycles. Gene expression in follicular cells obtained from IVF patients (n=32) was analyzed using microarray. Patients that did not become pregnant following the IVF cycle were compared to those that did. Quantitative RT-PCR was used to validate the microarray results and functional analysis was performed using ingenuity pathway analysis. 165 genes were differently expressed between the two groups, including many pro-inflammatory cytokines or other factors related to inflammation. For example, EGR1, IL1B, IL8, CXCL2, CCL3 and CCL4 were all up-regulated in the negative group compared to the positive group. Overexpression of several factors, some of which act upstream from VEGF, indicates increased permeability and vasodilation. Recruitment of immune cells to ovarian tissues also appears more pronounced in the negative group, and might reflect leukocytosis. Our results indicate an impaired balance between pro- and anti- inflammatory mediators in the failed IVF group and also suggest an intermediate state of OHSS that affects oocytes without leading to systemic problems. Some differentially expressed genes appear related to abnormal differentiation and increased apoptosis, which could also result from follicular aging. These findings provide potential biomarkers to identify failure causes, which should lead to improved stimulation protocols and more successful treatment of infertility.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87545 | GEO | 2016/10/03

SECONDARY ACCESSION(S): PRJNA345148

REPOSITORIES: GEO