scholarly journals The Role of Transcriptomic Biomarkers of Endometrial Receptivity in Personalized Embryo Transfer for Patients with Repeated Implantation Failure

2020 ◽  
Author(s):  
Aihua He ◽  
Yangyun Zou ◽  
Cheng Wan ◽  
Jing Zhao ◽  
Qiong Zhang ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Controlled Trial ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Training Dataset ◽  
Control Group ◽  
Second Phase ◽  
Implantation Failure ◽  
Repeated Implantation Failure ◽  
Experimental Group

Abstract Background: Window of implantation (WOI) displacement was known as one of endometrial origin leading to embryo implantation failure, especially for repeated implantation failure (RIF). A accurately prediction tool of endometrial receptivity (ER) is extraordinary needed to precisely guide the successful embryo implantation. We aimed to establish an RNA-seq based endometrial receptivity test tool (rsERT) using transcriptomic biomarkers, and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with repeated implantation failure (RIF).Methods: Two-phase strategy including tool establishment with retrospective data and benefit evaluation with prospective, nonrandomized controlled trial. In the first phase, the rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 infertile patients with normal window of implantation (WOI) timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n=56; control group, n=86). pET guided by rsERT in the experimental group, and conventional ET in the control group. Results: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using 10-fold cross-validation. IPR of experimental group (50.0%) was significantly improved compared to that (23.7%) of control group (RR, 2.107; 95% CI, 1.159 to 3.830; P = 0.017) when transferring day 3 embryos. Although not statistically different, IPR of experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of control group (RR, 1.562; 95% CI, 0.898 to 2.718; P = 0.111) when transferring blastocyst. Regression analysis can precisely predict the optimal WOI time by using all samples as training dataset (R2= 0.92).Conclusions: The rsERT was developed to accurately predict WOI period and significantly improve pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Optimization of the model made it possible to predict the optimal WOI by one-point sampling.Trial registration: Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx

scholarly journals The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Aihua He ◽  
Yangyun Zou ◽  
Cheng Wan ◽  
Jing Zhao ◽  
Qiong Zhang ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Controlled Trial ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Control Group ◽  
Second Phase ◽  
Implantation Failure ◽  
Clinical Trial Registry ◽  
Repeated Implantation Failure ◽  
Experimental Group

Abstract Background Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. Methods This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. Results The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. Conclusions The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx

The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure

2013 ◽  
Vol 100 (3) ◽  
pp. 818-824 ◽  
Author(s):  
Maria Ruiz-Alonso ◽  
David Blesa ◽  
Patricia Díaz-Gimeno ◽  
Eva Gómez ◽  
Manuel Fernández-Sánchez ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Endometrial Receptivity ◽  
Implantation Failure ◽  
Repeated Implantation Failure

scholarly journals Bioinformatics of Potential Biomarkers in Patients with Repeated Implantation Failure

2020 ◽  
Author(s):  
Mingxia Gao ◽  
Yue Kang ◽  
Bin Li ◽  
Shuang Fan ◽  
Xuehong Zhang
Keyword(s):  
Differential Expression ◽  
Endometrial Receptivity ◽  
Gene Set Enrichment Analysis ◽  
Control Group ◽  
Implantation Failure ◽  
Repeated Implantation Failure ◽  
Gene Screening ◽  
Differential Gene ◽  
Recombination Pathway ◽  
Geo Database

AbstractObjectiveThis study applied the public genetic databases high-throughput gene expression omnibus (GEO) database to compare the difference of gene screening between the repeated implantation failure (RIF) patients and women with normal endometrium. This study aims to provide additional information for the diagnosis and treatment in RIF patients through the gene set enrichment analysis and the construction of protein–protein interactions (PPIs) network.MethodThe human endometrial microarray data of RIF and normal control group were obtained from the GEO database provided by the National Center for Biotechnology Information (NCBI). The analysis and the review of differential gene screening, gene ontology (GO) pathway analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and PPIs network construction were carried out.Result273 genes with differential expression, 87 up-regulated and 186 down-regulated genes, were obtained through differential gene analysis. 50 genes with the most significant differential expression fold change were screened for subsequent analysis. KEGG results indicated that the top three related pathways were cancer pathway, MAPK signaling pathway, and homologous recombination pathway when the relevant pathways were sequenced according to the correlation size. GO analysis showed that differentially expressed genes were involved in protein phosphorylation, complement activation, and other biological processes. PPIs analysis demonstrated that targeted genes show high correlation to the endometrial receptivity, including PAEP, CXCL14, HOXB3, CD55, and VEGFA, all were down-regulated in RIF endometrial tissues compared to the control group, and these genes also influenced and regulated each other.ConclusionThrough public databases and bioinformatics, several factors in endometrial receptivity that affect RIF directly and indirectly were found. In particular, the immune and angiogenesis factors stood out the most. The different genes which regulate the immune response and angiogenesis response may become new targeted treatment for RIF.

scholarly journals Non-invasive intra-uterine administration of Botulinum Toxin A enhances endometrial angiogenesis and improves the rates of embryo implantation

2020 ◽  
Author(s):  
Hwa Seon Koo ◽  
Min-Ji Yoon ◽  
Seon-Hwa Hong ◽  
Jungho Ahn ◽  
Hwijae Cha ◽  
...  
Keyword(s):  
Botulinum Toxin ◽  
Botulinum Toxin A ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Marker Genes ◽  
Implantation Failure ◽  
Toxin A ◽  
Major Barrier ◽  
Repeated Implantation Failure ◽  
Non Invasive

Abstract Background. Endometrial angiogenesis plays crucial roles in determining the endometrial receptivity. Defects in endometrial receptivity often cause repeated implantation failure, which is one of the major unmet needs for infertility and contributes a major barrier to the assisted reproductive technology. Despite the numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition.Method. As a non-invasive treatment strategy, Botulinum toxin A (BoTA) was administered into one side of mouse uterine horns and saline was infused into the other side of horns for the control. Impact of BoTA was assessed in the endometrium at 3 or 8 days after infusion.Results. We demonstrated that BoTA administration enhances the capacity of endothelial cell tube formation and sprouting. The intrauterine BoTA administration significantly induced endometrial angiogenesis displaying increased numbers of vessel formation and expression levels of related-marker genes. Moreover, BoTA intrauterine application promoted the endometrial receptivity and the rates of embryo implantation were improved with BoTA treatment with no morphologically retarded embryos. Conclusion. Intrauterine BoTA treatment has a beneficial effect on vascular reconstruction of functional endometrium prior to embryo implantation by increasing endometrial blood flow near the uterine cavity suggesting BoTA treatment as a potential therapeutic strategy for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.

scholarly journals Customized Frozen Embryo Transfer after Identification of the Receptivity Window with a Transcriptomic Approach Improves the Implantation and Live Birth Rates in Patients with Repeated Implantation Failure

2020 ◽  
Vol 28 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Delphine Haouzi ◽  
Frida Entezami ◽  
Antoine Torre ◽  
Charlène Innocenti ◽  
Yannick Antoine ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Live Birth ◽  
Hormone Replacement ◽  
Control Group ◽  
Implantation Failure ◽  
Test Results ◽  
Birth Rates ◽  
Repeated Implantation Failure ◽  
Live Birth Rates ◽  
Classical Procedure

AbstractThe aim of this prospective study was to evaluate outcome benefits expected in repeated implantation failure (RIF) patients (n = 217) after customized embryo transfer based upon identification of the receptivity window by transcriptomic approach using the Win-Test. In this test, the expression of 11 endometrial genes known to be predictive of endometrial receptivity is assessed by RT-PCR in biopsies collected during the implantation window (6–9 days after the spontaneous luteinizing hormone surge during natural cycles, 5–9 days after progesterone administration during hormone replacement therapy cycles). Then, patients underwent either customized embryo transfer (cET, n = 157 patients) according to the Win-Test results or embryo transfer according to the classical procedure (control group, n = 60). Pregnancy and live birth rates were compared in the two groups. The Win-Test showed that in 78.5% of women, the receptivity window lasted less than 48 h, although it could be shorter (< 24 h, 9.5%) or longer (> 48 h, 12%). This highlighted that only in 20% of patients with RIF the endometrium would have been receptive if the classical embryo transfer protocol was followed. In the other 80% of patients, the receptivity window was delayed by 1–3 days relative to the classical timing. This suggests that implantation failure could be linked to inadequate timing of embryo transfer. In agreement, both implantation (22.7% vs. 7.2%) and live birth rates per patient (31.8% vs. 8.3%) were significantly higher in the cET group than in the control group. cET on the basis of the Win-Test results could be proposed to improve pregnancy and live birth rates.ClinicalTrials.gov ID: NCT04192396; December 5, 2019, retrospectively registered.

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 &gt; 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 &lt; 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 &lt; 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

scholarly journals Effectiveness of Herb-partitioned Moxibustion on the Navel for Pregnancy Outcomes in Patients With Recurrent Implantation Failure Undergoing in Vitro Fertilization and Embryo Transfer: A Study Protocol for a Randomized Controlled Trial

2021 ◽  
Author(s):  
Qingchang Xia ◽  
Shuzhong Gao ◽  
Jingyan Song ◽  
Dongqing Du ◽  
Chunjing Li ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Controlled Trial ◽  
Control Group ◽  
Implantation Failure ◽  
Vitro Fertilization ◽  
Menstrual Cycles ◽  
Randomized Controlled ◽  
Ivf Et

Abstract BackgroundRecurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER) and immunity. The incidence of RIF is usually between 5and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aimed to explore the effectiveness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF. MethodsThis study conducted a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. During the fourth menstrual cycle, will be induced to prepare the endometrium before embryo transfer. No intervention will be used in the control group for 3 menstrual cycles. However, in the fourth menstrual cycle, an artificial cycle will be induced to prepare the endometrium before embryo transfer. The conception outcome will be recorded after a 3-months follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate and clinical pregnancy rate. DiscussionIf the results confirm that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended for application in clinical practice.Trial registration:Chinese clinical trial registry (ChiCTR). Trial registration number: ChiCTR2100043954. Registered on 8 July 2021.

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