Serum microRNA profiling for the identification of predictive molecular markers of the response to controlled ovarian stimulation.

Edson Borges Júnior,Maria Gabriela Ferreira Mulato,Amanda Souza Setti,Murilo Vieira Geraldo,Assumpto Iaconelli Júnior,Daniela Paes De Almeida Ferreira Braga

doi:10.5935/1518-0557.20190070

Edson Borges Júnior, Maria Gabriela Ferreira Mulato + Show 4 more

Open Access

https://doi.org/10.5935/1518-0557.20190070

Copy DOI

Abstract

ObjectiveTo identify potential microRNA (miRNA) biomarkers of poor, normal and hyperresponse to controlled ovarian stimulation (COS).MethodsIn the present study, we assessed 40 serum samples from patients undergoing COS. We used ten samples to standardize miRNAs detection in the serum. The remaining 30 samples were split into three groups depending on the patient's response to COS: poor response (PR group, n=10), normal response (NR group, n=10), and hyperresponse (HR group, n=10). Aberrantly expressed miRNAs were identified using a large-scale expression analysis platform. Gene set enrichment analysis was performed to assess the biological processes potentially modulated by the identified miRNAs.ResultsTwenty-two miRNAs were detected only in the PR or HR groups when compared with the NR group. From those, 11 presented poor dissociation curves and were excluded from further analysis. A bioinformatics analysis revealed that the selected 11 miRNAs target several genes involved in GnRH, estrogen and prolactin signaling, oocyte maturation, female pregnancy, and meiosis.ConclusionThe large-scale analysis of miRNA expression identified distinct miRNA profiles for poor and hyperresponse to COS, which potentially modulate key processes for human assisted reproduction. All evidence suggests that the serum microRNA profiling may discriminate patients who will respond in an exacerbated manner from those who will respond insufficiently to COS. Further studies may validate these miRNAs, enabling the individualization of treatment and more successful outcomes.

Highlights

Since the first reported pregnancy following in vitro fertilization (IVF) (Steptoe & Edwards, 1978), assisted reproductive technologies (ART) have quickly progressed
All evidence suggests that the serum microRNA profiling may discriminate patients who will respond in an exacerbated manner from those who will respond insufficiently to controlled ovarian stimulation (COS)
PR=poor response, NR=normal response, HR=hyperresponse, BMI=body mass index. a ≠ b ≠ c

Summary

Introduction

Since the first reported pregnancy following in vitro fertilization (IVF) (Steptoe & Edwards, 1978), assisted reproductive technologies (ART) have quickly progressed. Its efficiency in terms of live births is still low. It has been estimated that 4.45 cycles are needed to achieve one live birth event following IVF (Sunkara et al, 2016). Many variables have been suggested as possible causes for the low efficiency of assisted reproduction. Embryo implantation depends on the acquisition of a receptive endometrium and the presence of a viable embryo (Su & Fazleabas, 2015). The selection of a viable embryo for transfer is a critical step in ART and depends on an adequate number and quality of oocytes. The response to controlled ovarian stimulation (COS) is quite variable among patients, and both poor and hyperresponses may have detrimental effects on the cycle's outcome

Methods

Results

Discussion

Conclusion