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

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuhao Zhao ◽  
Dongmei He ◽  
Hong Zeng ◽  
Jiefeng Luo ◽  
Shuang Yang ◽  
...  
Keyword(s):  
Endometrial Biopsy ◽  
Endometrial Receptivity ◽  
Leukaemia Inhibitory Factor ◽  
In Vitro Fertilisation ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Tissue Samples ◽  
Implantation Window

Abstract Background Poor 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. Methods Endometrial 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. Results The 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. Conclusions MiR-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.

scholarly journals Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure

2021 ◽  
Author(s):  
Mi Han ◽  
Yi Cao ◽  
Wenjie Zhou ◽  
Mingjuan Zhou ◽  
Xiaowei Zhou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Underlying Mechanism ◽  
Endometrial Receptivity ◽  
In Vitro Assays ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Tubal Infertility ◽  
Endometrial Stromal Cells

Abstract Impaired endometrial receptivity is the main cause of recurrent implantation failure (RIF), however, its underlying mechanism is unclear. In this study, we found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility who successfully achieved conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to those in the control group (P = 0.001), consistent with the results of genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells cause marked deficiency in supporting blastocysts and human embryonic JAR cell adhesion, mimicking the process of embryo adhesion. However, overexpression of HMGB1 had no effect on cell proliferation and in-vitro decidualization in a human endometrial stromal cell line (T-HESCs) and in primary human endometrial stromal cells (HESCs). These findings indicate that increased HMGB1 levels suppressed the adhesion capability of epithelial cells, contributing to impaired endometrial receptivity in patients with recurrent implantation failure. This characteristic can be used as a target for detecting and treating recurrent implantation failure in clinical practice.

scholarly journals Transcutaneous electrical acupuncture point stimulation improves pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilisation and embryo transfer: a prospective, randomised trial

2019 ◽  
Vol 37 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Zhenhong Shuai ◽  
Xuemei Li ◽  
Xuelian Tang ◽  
Fang Lian ◽  
Zhengao Sun
Keyword(s):  
Embryo Transfer ◽  
Live Birth ◽  
Pregnancy Outcomes ◽  
Clinical Pregnancy ◽  
In Vitro Fertilisation ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Electrical Acupuncture

Objective: To evaluate the effect of transcutaneous electrical acupuncture stimulation (TEAS) on pregnancy outcomes in patients with recurrent implantation failure (RIF) undergoing in vitro fertilisation (IVF). Methods: A total of 122 women with RIF undergoing fresh embryo transfer cycle IVF were randomly allocated to a TEAS or mock TEAS (MTEAS) group. Gonadotrophin therapy using a long protocol was provided in both groups. TEAS consisted of 30 min of stimulation (9–25 mA, 2 Hz) at SP6, CV3, CV4 and Zigong from day 5 of the ovarian stimulation cycle once every other day until the day of embryo transfer. The patients in the control group received MTEAS. Implantation, clinical pregnancy and live birth rates were compared. Results: In the TEAS group, the implantation rate, clinical pregnancy rate and live birth rate (24.3%, 32.8% and 27.9%, respectively) were significantly higher than in the MTEAS group (12.1%, 16.4% and 13.1%, respectively). Conclusions: TEAS significantly improves the clinical outcomes of subsequent IVF cycles among women who have experienced RIF. Trial registration number: ChiCTR-TRC-14004730.

Expression of MSX1, HOXA11 and TP53I3 in the endometrium associated with the onset of pregnancy after repeated failed IVF attempts in patients with tubo-peritoneal factor infertility

GYNECOLOGY ◽  
2020 ◽  
Vol 22 (1) ◽  
pp. 23-28
Author(s):  
Ekaterina A. Knyazeva ◽  
Maria V. Kuznetsova ◽  
Olga V. Burmenskaya ◽  
Andrey E. Donnikov ◽  
Elena A. Kalinina
Keyword(s):  
Gene Expression ◽  
Transcriptome Profiling ◽  
Endometrial Receptivity ◽  
In Vitro Fertilisation ◽  
Ivf Outcome ◽  
Program Outcomes ◽  
Implantation Window ◽  
Genome Wide ◽  
A Genome

Relevance. The success of the in vitro fertilisation (IVF) program, among other factors, depends on the readiness of the endometrium to accept the embryo. It is believed that this is possible during the so-called implantation window, the timing of which can be shifted under the influence of various factors. Evaluation of endometrial receptivity and the implantation window based on analysis of endometrial gene expression before embryo transfer is a promising approach for predicting the likelihood of pregnancy in IVF programs. Aim. To construct a classifier based on the expression of endometrial genes for predicting the outcome of an IVF program in patients with tubal-peritoneal infertility factor and repeated failed IVF attempts in history. Materials and methods. Before the IVF program, a genome-wide transcriptome profiling of endometrial samples of 15 women with tubal-perioneal infertility factor and repeated unsuccessful IVF attempts in history was carried out using Affymetrix arrays. Potential genes capable of classifying IVF program outcomes were selected, after which the expression of these genes was analyzed by qPCR-RT in the endometrium of 47 women to construct IVF outcome classifiers based on the expression of pairs or triples of genes. Results. A classifier based on the expression of the triple of genes MSX1 (HOX7), HOXA11, and TP53I3 made it possible to determine the onset of pregnancy in an IVF program with a sensitivity of 73% and a specificity of 71% with an area under the ROC-curve (AUC) of 0.738 (95% confidence interval 0.5770.898). Earlier, a relationship was found between the expression of these genes and receptivity of the endometrium, which suggests that these genes play a role in the onset of the implantation window. Conclusions. The use of a classifier based on the genes MSX1 (HOX7), HOXA11, and TP53I3 can determine the readiness of the endometrium to accept an embryo and create an individual prognosis of the outcome of an IVF program in women with tubal-peritoneal infertility factor and repeated failed IVF attempts in history.

P–387 Serum progesterone levels on the day of the endometrial receptivity analysis (ERA) biopsy do not correlate with the biopsy results

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Ahuja ◽  
A Taranissi ◽  
M Taranissi
Keyword(s):  
Embryo Transfer ◽  
Essential Element ◽  
Endometrial Biopsy ◽  
Endometrial Receptivity ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Serum Progesterone ◽  
Endometrial Cells ◽  
Live Births ◽  
Negative Results

Abstract Study question Do the serum progesterone levels on the day of the endometrial receptivity analysis (ERA) biopsy correlate with the results of the ERA? Summary answer Serum progesterone levels on the day of the endometrial receptivity analysis biopsy do not correlate with the biopsy results. What is known already Endometrial receptivity is a time sensitive window characterised by maturation of the endometrium, during which the trophectodermal cells attach to the endometrial cells and invade the endometrial stromal vasculature. Progesterone is an essential element for receptivity and pregnancy. There is no consensus regarding the optimal progesterone levels in the luteal phase, for a successful pregnancy. Endometrial receptivity analysis is a diagnostic tool developed by profiling the transcriptome of over 238 genes that are expressed at different stages of the endometrial cycle. The results are reported as receptive, pre-receptive, early receptive, etc and are used to direct a personalised embryo transfer. Study design, size, duration We report a prospective study of 30 patients with a history of recurrent implantation failure (RIF). They underwent ERA testing in a medicated cycle, between early 2018 and late 2020. Participants/materials, setting, methods A large proportion of the patients we treat in our clinic (ARGC) have recurrent implantation failure. Thirty patients with RIF underwent ERA testing in a medicated cycle.They all followed the same protocol with down regulation, followed by estrogenic preparation for about 12–14 days, followed by progesterone for about 120 hours. An endometrial biopsy was taken at about 120 hours after progesterone exposure. Main results and the role of chance An ERA result was available on 28/30 patients. Eighteen were reported to be pre-receptive, seven receptive, 3 early receptive and 2 could not be analysed. The progesterone levels within 24 hours of the biopsy for the pre-receptive group ranged from 21.2–472 nmol/l, for the receptive group ranged from 27.8–152 nmol/l and for the early receptive group ranged from 54.9–162 nmol/l. Though the number of cases is small, we found no co-relation between the serum progesterone levels with the ERA results. Eighteen women underwent an embryo transfer based on the ERA results (pET-personalised embryo transfer). Eleven were positive with four live births, one early ongoing pregnancy, three miscarriages, one ectopic pregnancy, two biochemical pregnancies and seven negative results. Seven women had euploid embryo transfers-three had live births, one is viable at 11 weeks, one had a missed miscarriage and two were negative. There are no studies correlating the serum progesterone levels and the ERA results. In practice, we plan embryo transfers for women in frozen cycles by monitoring the serum progesterone levels alongside the day of the cycle. Hence, we wanted to review if the combination of the progesterone levels along with biopsy results would allow us the improve the results further. Limitations, reasons for caution This is a small study. Larger datasets are required to draw meaningful conclusions. Wider implications of the findings: If the above findings are confirmed by larger studies, we may not need to monitor serum progesterone levels during ERA biopsy cycles. Trial registration number NA

scholarly journals hsa_circ_001946 elevates HOXA10 expression and promotes the development of endometrial receptivity via sponging miR-135b

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fang Zhao ◽  
Yihong Guo ◽  
Zhanrong Shi ◽  
Menglan Wu ◽  
Yuzhen Lv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Western Blotting ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Luciferase Reporter ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Tissue Samples ◽  
Qrt Pcr

Abstract Background Impaired endometrial receptivity is a major reason for embryo implantation failure. There’s a paucity of information regarding the role of circRNAs on endometrial receptivity. Here, we investigated the function of hsa_circ_001946 on endometrial receptivity and its mechanisms. Methods A total of 50 women composing 25 with recurrent implantation failure and 25 who conceived after their implantation were recruited in this study. Expression of hsa_circ_001946, miR-135b, and HOXA10 was evaluated by quantitative RT-PCR (qRT-PCR) in biopsied endometrial tissue samples. The levels of HOXA10, and cell cycle markers (CCNB1, CDK1, and CCND1) were determined by IHC and western blotting assays. Binding relationship among miR-135b, hsa_circ_001946 and HOXA10 were confirmed by dual luciferase reporter assays and western blotting. MTT assays and cell cycle assays by FACS were employed to evaluate the proliferation and cell cycle of cells. T-HESCs were cultured with 1 µM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3’:5’-cyclic monophosphate (8-Br-cAMP) to induce decidualization. The mechanisms and functions of hsa_circ_001946 on decidualization were further assessed by qRT-PCR evaluating the expression of hsa_circ_001946, miR-135b, HOXA10 and decidual markers (PRL and IGFBP1) in T-HESCs. Results Endometrial tissues from patients with recurrent implantation failure had lower hsa_circ_001946 expression, higher miR-135b expression, and lower HOXA10 expression. Hsa_circ_001946 promoted HOXA10 expression by sponging miR-135b in T-HESCs. Overexpression of hsa_circ_001946 restored cell proliferation and cell cycle that were disrupted by miR-135b overexpression in T-HESCs. Decidualized T-HESCs had higher hsa_circ_001946 expression, lower miR-135b expression, and higher HOXA10 expression. Overexpression of hsa_circ_001946 reversed the expression of decidual markers (PRL and IGFBP1) that were suppressed by miR-135b overexpression in T-HESCs. Conclusions In conclusion, our findings suggest that hsa_circ_001946 promotes cell proliferation and cell cycle process and increases expression of decidualization markers to enhance endometrial receptivity progression via sponging miR-135b and elevating HOXA10.

scholarly journals The Expression of miR-31 and its Target Gene FOXP3 in Recurrent Implantation Failure Patients

2020 ◽  
Vol 8 (4) ◽  
pp. 389-395
Author(s):  
Azita Azarpoor ◽  
Abdolreza Ardeshirylajimi ◽  
Samira Mohammadi Yeganeh ◽  
Elham Pour matrood ◽  
Zeinab Dehghan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Tissue Samples ◽  
Significant Difference ◽  
Immunological Disorder ◽  
Recurrent Abortions ◽  
Fertile Women

Objectives: Endometrial receptivity is a complex event that occurs during the midluteal phase of the menstrual cycle known as the "window of implantation". During this period, the endometrium develops characteristics that allow the adhesion and invasion of the embryo to the uterine epithelium. Accordingly, the expressions of miR-31 and its target gene were evaluated to study the effect of miR-31 on FOPX3 gene expression in recurrent implantation failure (RIF) patients and normal fertile women. More precisely, the aim of this study was to understand the expression of miR-31 as one of the important regulators of the FOXP3 gene in the endometrium of RIF patients versus receptive endometria from fertile patients. Materials and Methods: This case-control study was conducted on 20 endometrial tissue samples of normal fertile women and RIF patients in order to evaluate miR-31 and its target gene expression. Results: According to the results of this study, a significant difference existed between RIF patients and normal fertile women (control group). The expression of the FOXP3 gene was more significant in the control group. miR-31 was also significantly expressed, which was due to the endometrial immunological disorder leading to the decreased expression of its target gene (FOXP3). Conclusions: In general, implant abnormalities and recurrent abortions were observed in RIF patients due to the decreased expression of the FOXP3 gene resulting from the inhibitory effects of miR-31.

Vaginal microbiota alterations in women with recurrent implantation failure and the associated metabolome

2019 ◽  
Author(s):  
Min Fu ◽  
Xiaowei Zhang ◽  
Weiping Qian ◽  
Yiheng Liang ◽  
Shouren Lin ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Vaginal Microbiota ◽  
Control Group ◽  
P Value ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Vitro Fertilization ◽  
Α Diversity ◽  
Rdna Sequencing

Abstract In vitro fertilization-embryo transfer (IVF-ET) is now widely applied in treating infertility. As the number of IVF cycles continues to increase, recurrent implantation failure (RIF) has become a big challenge. The cause of RIF is very complex and remains largely unrevealed, especially for those without any pathological features. It has been proved that vaginal microbiota is associated with many female reproductive diseases, such as pregnancy-related diseases, sexually transmitted diseases, tubal factor infertility, and first trimester miscarriage after in vitro fertilization (IVF) and so on. Hence, vaginal microbiota and its metabolome may also relate to RIF. In this study, we characterized the vaginal microbiota and metabolome of patients with unexplained RIF, while patients who achieved clinical pregnancy in the first IVF cycle were used as controls. Results Based on 16S rDNA sequencing of the vaginal microbiota, the RIF group presented higher microbial α-diversity than the control group (0.80±0.50 vs 0.50±0.39, P-value=0.016) and harbored more non-Lactobacillus microorganisms, including 25 significantly increased genera of both aerobic and anaerobic bacteria. The metabolomic profile showed that the relative abundances of 37 metabolites among 2,507 metabolites were significantly different between the two groups. Among them, 2',3-cyclic UMP and phosphoinositide were the top two metabolites significantly upregulated in the RIF group, while glycerophospholipids and benzopyran were important metabolites that were significantly downregulated. Lysobisphosphatidic acid (LPA) and prostaglandin (PG) metabolized from glycerophospholipids are key factors affecting implantation and decidualization. Benzopyran, as a selective estrogen receptor modulator (SERM), may affect the outcome of pregnancy. All of the metabolome outcomes may result in or from the differential microbiota composition in the RIF patients. Conclusions In conclusion, significant differences were presented in the vaginal microbiota and metabolome between RIF patients and women who became pregnant in the first IVF cycle, which are related to embryo implantation. This study not only deeply investigates the relationship between RIF and the vaginal microbial community and its metabolites but also provides a profound understanding of the pathogenesis of RIF.

P–313 Endometrial receptivity analysis for personalized embryo transfer in patients with recurrent implantation failure: a retrospective analysis of a Chinese cohort

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Jia ◽  
Y L Sha ◽  
Z Qiu ◽  
Y H Guo ◽  
A X Tan ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Retrospective Analysis ◽  
Embryo Transfer ◽  
Chinese Women ◽  
Endometrial Receptivity ◽  
Control Group ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Biochemical Pregnancy ◽  
Implantation Rates

Abstract Study question To quantify the effectiveness of endometrial receptivity analysis (ERA)-guided personalized embryo transfer (pET) in Chinese women. Summary answer ERA-guided pET may remarkably improve pregnancy and implantation rates among Chinese women with Recurrent implantation failure (RIF). What is known already RIF is a major cause of infertility, and endometrial receptivity is widely accepted to impact implantation failure. Precision prediction of the WOI, the time when the endometrium is most receptive to the implantation of the embryo, is, therefore, of great significance to improve implantation prospects. Previous studies have shown the effectiveness of ERA for the prediction of the WOI, and how pET, timed by ERA, improves implantation and pregnancy rates; however, the efficacy of ERA-guided pET remains unknown for Chinese women. Study design, size, duration Patients in Chengdu Xi’nan Gynecology Hospital (Chengdu, China) who were undergoing frozen embryo transfer (FET) at the blastocyst stage on day five or day six during the period from November 2019 through September 2020 were recruited for this study. A total of 145 eligible patients were included in the study and assigned to the ERA group (n = 67) or the control group (n = 78). Clinical pregnancy outcomes were compared between the two groups. Participants/materials, setting, methods Endometrial specimens were collected the from ERA group. Total RNA was extracted from endometrial specimens, the transcriptomic sequencing data were processed using RNA-Seq and the endometrial receptivity status was assessed by the ERA predictor. The endometrium was classified as receptive or non-receptive according to the ERA assessment, and pET was done at the time determined by ERA in the ERA group. Subjects in the control group did not receive ERA and underwent blastocyst transfer normally. Main results and the role of chance The demographic and clinical characteristics were comparable between the ERA and control groups (P > 0.05). The ERA test identified 10.45% of samples as receptive and 89.55% of samples as non-receptive in the ERA group, with 70.15% of samples presenting a pre-receptive profile. We observed higher cumulative pregnancy (74.63% vs. 64.10%) and cumulative implantation rate (47.32% vs. 21.68%) rates, and a lower biochemical pregnancy rate (18.00% vs. 34.00%) in the ERA group when compared to the control group (P < 0.05). Additionally, we found higher pregnancy (67.16% vs. 39.74%) and implantation (46.54% vs. 16.94%) rates as well as a lower biochemical pregnancy rate (17.78% vs. 45.16%) after the first ERA test in the ERA group when compared to the control group (P < 0.01). Limitations, reasons for caution First, this is a retrospective analysis, which is relatively more biased than prospective clinical trials. Second, the study sample is considerably small. Third, only 10.45% of the subjects were identified as presenting a receptive profile, which limits the comparisons of clinical outcomes between patients with receptive and non-receptive endometria. Wider implications of the findings: This study demonstrates that the ERA test helps to determine the optimal timing for embryo transfer, improve pregnancy and implantation rates in patients with RIF, and guides the clinical application of the ERA test. Trial registration number approval No. 2020–018

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