Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window

Yuhao Zhao,Jingjing Chen,Raed K Abdullah,Dongmei He,Jiefeng Luo,Shuang Yang,Nenghui Liu,Hong Zeng

doi:10.1186/s12958-021-00820-2

Abstract

BackgroundPoor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window.MethodsEndometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway.ResultsThe presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r2 = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF.ConclusionsMiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure.

Highlights

Poor endometrial receptivity is a major factor that leads to recurrent implantation failure
In some patients with recurrent implantation failure (RIF), endometrial receptivity may be impaired, leading to the window of implantation (WOI) being displaced and asynchrony between the functional embryo and endometrium tissue, which may result in implantation failure [5]
There were no significant differences between the two groups in terms of age, years of infertility, body mass index (BMI), menstrual duration, length of menstrual cycle, and basic serum Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels

Summary

Introduction

Poor endometrial receptivity is a major factor that leads to recurrent implantation failure. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In IVF cycles, many couples with infertility fail to achieve pregnancy repeatedly with no signs of embryo implantation or production of HCG. Recurrent implantation failure (RIF) is defined as failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos (score ≥ 7) in a minimum of three fresh or frozen cycles [4]. In some patients with RIF, endometrial receptivity may be impaired, leading to the window of implantation (WOI) being displaced and asynchrony between the functional embryo and endometrium tissue, which may result in implantation failure [5]. Despite advances in the understanding of implantation failure, the pathogenesis of RIF is complex and requires a multidimensional explanation

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