The Embryo-endometrium Multifaceted Interface: Endometrial Cavity Molecular Microbiobial and Transcriptomic Signatures in Predictinf Pregnancy Outcome in Infertile Patients Undergoing Assisted Reproduction Technology Procedures

In reproductive medicine, a fundamental challenge is to evaluate the endometrial health status during the embryo implantation window as a limiting step in predicting the success of treatments of assisted reproduction technology (ART). Some highthroughput tools, recently developed by private genomics companies, are available in the market even if they have not been independently validated and have different limitations. We propose a prospective cohort study with the aim of validating the reliability and increasing efficacy of these tools. Endometrial fluid samples will be collected non-invasively from women undergoing ART cycles and isolated genetic materials will be subjected to 16S rRNA gene sequencing for microbiota profiling and to RNAseq analysis of RNA content of extracellular vesicles previously recognized as a tissue proxy in predicting endometrial receptivity. Clinical pregnancy rate/first cycle will be the target outcome used to assess the resulting predictive models. Ultrasonographic features of the endometrium will also be collected and accounted for in the predictive model.

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Key information

Conditions

Infertility (IVF Patients) Genital Diseases Infertility Urogenital Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Observational

Primary location

OSR Innate Immunity and tissue remodeling Unit and Centro Scienze Natalità OS

Milan, milano, 20133, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

IVF Patients inclusion Criteria:

Indication to ART
Age 18-39 years
First ART cycle
Normal uterine morphology and no hydrosalpinx at ultrasound

IVF Patients exclusion Criteria:

Poor responders according to Bologna criteria
Indications to ART for severe male infertility

Fertile Patients inclusion Criteria:

Subjects will be cycling women with proven fertility undergoing laparoscopy for tubal ligation
BMI < 30
Aged 20 to 40 years

Fertile Patients exclusion Criteria:

Smokers
Not taking any medication

Treatment and study plan

Primary outcomes

Identification of endometrial microbiome diversity

Time frame: through study completion, an average of 1 year

Evaluation of the endometrial microbiome composition and diversity using 16S rRNA sequencing to assess the functional impact of the endometrial microbial community in predicting the clinical pregnancy rate in women undergoing ART cycles.
Extracellular Vesicle (EV) RNA Profiles

Time frame: through study completion, an average of 1 year

Quantification of extracellular vesicle (EV) RNA expression profiles from uterine fluid samples using RNA sequencing (expressed in CPM). Confirmation of the good correlation between expression of genes in tissue samples and in endometrial-derived EVs.
Integrated Predictive Model for Clinical Pregnancy

Time frame: through study completion, an average of 1 year

Development of a multivariable predictive model combining endometrial microbiome diversity, EV RNA profiles, and ultrasound-AI analysis to predict clinical pregnancy rates in ART cycles.

Sponsors and collaborators

Lead sponsor

IRCCS San Raffaele

Other

Collaborators

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Registry information

Important dates

Study start: 2021
Primary completion: 2025
Study completion: 2025
First posted: Jul 25, 2025
Registry last updated: Jul 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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