Ignite Creation Date:
2024-05-06 @ 10:43 AM
Last Modification Date:
2024-10-26 @ 12:34 PM
Study NCT ID:
NCT03330444
Status:
COMPLETED
Last Update Posted:
2020-10-09
First Post:
2017-10-24
Brief Title:
Development of a Microbiome Non-invasive Diagnosis Tool
Sponsor:
Igenomix
Organization:
Igenomix
Study Overview
Official Title:
Development of a Non-invasive Diagnosis Tool for the Analysis of the Microbiota to Improve Reproductive Outcomes in Infertile Patients
Status:
COMPLETED
Status Verified Date:
2020-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ERA-niMIC
Brief Summary:
Although the endometrium tissue has been traditionally considered free of bacteria recent studies have documented the presence of an endometrial microbiome In a pilot study conducted by our research team the microorganisms present in the endometrium were analysed in samples of endometrial fluid EF using next generation sequencing NGSConsistent with previously published studies in normal conditions the endometrium is mainly composed of different species of the genus Lactobacillus It was further noted that the presence of other pathogenic bacteria such as Streptococcus andor Gardnerella may alter the endometrial microbiome and can disrupt the uterine environment affecting implantation rates and pregnancy success
This project aims to validate the microbiome found in the endometrium of women of reproductive age and try to corroborate the relationship between the endometrial microbiome and the reproductive outcomes in patients undergoing assisted reproduction treatment ART The use of Endometrial Receptivity Analysis ERA tool together with the analysis of the endometrial flora before the embryo transfer will allow to evaluate the impact of the presence of endometrial pathogens on implantation in receptive patients
Therefore the focus of this project is the development and clinical validation of a non-invasive diagnosis tool to analyse the microbiota adding the microbiome study to the ERA analysis
This project aims to validate the microbiome found in the endometrium of women of reproductive age and try to corroborate the relationship between the endometrial microbiome and the reproductive outcomes in patients undergoing assisted reproduction treatment ART The use of Endometrial Receptivity Analysis ERA tool together with the analysis of the endometrial flora before the embryo transfer will allow to evaluate the impact of the presence of endometrial pathogens on implantation in receptive patients
Therefore the focus of this project is the development and clinical validation of a non-invasive diagnosis tool to analyse the microbiota adding the microbiome study to the ERA analysis
Detailed Description:
Embryonic implantation is a critical process to the survival of the species that is relatively inefficient especially in humans Key elements are the embryo the maternal endometrium and the cross-communication between them using different scientific perspectives Endometrial receptivity describes the phenotype that allows embryo adhesion and placentation to occur Due to the need of an accurate and objective molecular diagnostic test for the receptivity status of endometrium the Endometrial Receptivity Analysis ERA was developed ERA test is a customized expression microarray that identifies the transcriptomic expression profile signature of the personalized window of implantation WOI Its clinical usefulness has been demonstrated in patients with implantation failure in whom 25 of them have a displaced WOI becoming pregnant once the embryo transfer is performed at the proper WOI predicted by ERA However this procedure requires an endometrial biopsy EB which is the major drawback of this diagnosis test because embryo transfer has to be delayed to the next cycle and also the possible discomforts caused to the patients For this reason a previous pilot study was conducted in order to confirm whether endometrial receptivity can be predicted through non-invasive methods in endometrial fluid EF samples The gene panel of ERA test was interrogated on epithelial and stromal cells from endometrial biopsies and cells isolated from the EF at the single cell level demonstrating that the major cells on the EF classifies together with the epithelial population
On the other hand to try to better understand the mechanisms that connect endometrial receptivity andor implantation of the embryo with an altered endometrial microbiome another pilot study was conducted to determine the composition of the endometrial microbiome after the analysis of the bacterial 16S ribosomal RNA by NGS Interestingly in patients with receptive endometrium diagnosed by Endometrial Receptivity Array ERA who had endometrial microbiome with pathogens or not dominated by bacteria of the genus Lactobacillus NLD showed significantly lower implantation 231 vs 607 p 002 pregnancy 333 vs 706 p 003 ongoing pregnancy per embryo transfer 133 vs 588 p 003 and live birth 67 vs 588 p 0002 rates than those with a healthy endometrial microbiome dominated by Lactobacillus LD Moreover this relationship was much more significant when pathogenic species found belonged to the genus Gardnerella and Streptococcus This is in line with other published studies that analyze the impact of endometrial pathogens in IVF treatments highlighting the importance of the study of bacterial communities for reproductive health
Given these preliminary results the present study aims to validate in a larger sample set the relationship between the imbalance of endometrial microbiome and the decline in reproductive success in patients undergoing ART To do this the experimental design will be improved in the following areas i a higher sample size will be analysed to validate the previous results obtained in the previous pilot study on endometrial microbiome ii paired samples from endometrial fluid and endometrial biopsy will be analysed for the microbial profile to study whether there is bacterial variability associated to the sample type iii the endometrial microbiota will be simultaneously assessed with ERA as a supplementary diagnosis for this tool and iv the analysis of the endometrial microbiota will be performed using the most advanced technology on bacterial metagenome sequencing to widen the information of the microorganisms identified in each sample
On the other hand to try to better understand the mechanisms that connect endometrial receptivity andor implantation of the embryo with an altered endometrial microbiome another pilot study was conducted to determine the composition of the endometrial microbiome after the analysis of the bacterial 16S ribosomal RNA by NGS Interestingly in patients with receptive endometrium diagnosed by Endometrial Receptivity Array ERA who had endometrial microbiome with pathogens or not dominated by bacteria of the genus Lactobacillus NLD showed significantly lower implantation 231 vs 607 p 002 pregnancy 333 vs 706 p 003 ongoing pregnancy per embryo transfer 133 vs 588 p 003 and live birth 67 vs 588 p 0002 rates than those with a healthy endometrial microbiome dominated by Lactobacillus LD Moreover this relationship was much more significant when pathogenic species found belonged to the genus Gardnerella and Streptococcus This is in line with other published studies that analyze the impact of endometrial pathogens in IVF treatments highlighting the importance of the study of bacterial communities for reproductive health
Given these preliminary results the present study aims to validate in a larger sample set the relationship between the imbalance of endometrial microbiome and the decline in reproductive success in patients undergoing ART To do this the experimental design will be improved in the following areas i a higher sample size will be analysed to validate the previous results obtained in the previous pilot study on endometrial microbiome ii paired samples from endometrial fluid and endometrial biopsy will be analysed for the microbial profile to study whether there is bacterial variability associated to the sample type iii the endometrial microbiota will be simultaneously assessed with ERA as a supplementary diagnosis for this tool and iv the analysis of the endometrial microbiota will be performed using the most advanced technology on bacterial metagenome sequencing to widen the information of the microorganisms identified in each sample
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None