New Strategies to Evaluate the Reproductive Tract Microbiome (niMICROBIOME)

Evaluation of New Strategies in the Analysis of the Reproductive Tract Microbiome: A Descriptive Pilot Study

The goal of this observational study is to evaluate alternative less invasive sampling methods for the analysis of the endometrial microbiome. For that, vaginal swab and endometrial fluid samples will be assessed in comparison with the standard sampling method (an endometrial biopsy), in women aged 18-50 years on an oocyte donation program and/or who attend the clinic for routine gynecological controls, and whose samples will be collected during the secretory phase of a natural menstrual cycle. The study aims to:

• Evaluate the pontential of the less invasive techniques to assess the endometrial microbiome, compared to the endometrial biopsy, as well as their safety.
• Evaluate the microbiome's stability in a period of 1 to 3 months.

Participants will undergo a sampling round (of the 3 sampling methods), and then a second round 1, 2 or 3 months later, as assigned by the investigator.

Study Overview

• Status: Completed
• Conditions: Infertility; Fertility; Reproductive Health; Microbiome Analysis
• Intervention / Treatment: Diagnostic test: Reproductive tract microbiome analysis

Detailed Description

The endometrium plays a pivotal role in reproductive health, influencing processes such as implantation and pregnancy. Although the endometrium has generally been considered a tissue free of bacteria, numerous studies have documented the presence of an endometrial microbiome mainly composed of different species from the Lactobacillus genus. The presence of pathogenic bacteria has been shown to disrupt the uterine environment, affecting implantation rates and pregnancy success.

Traditional and emerging sampling methods allow for the study of the microbial profile of the endometrium, but the efficiency and representativeness of these techniques vary. Therefore, this study aims to compare the effectiveness, accuracy, and usefulness of three different sampling methods for microbiome analysis: endometrial biopsy, endometrial fluid, and vaginal swab. Additionally, it seeks to compare the endometrial microbial profiles with the vaginal microbiome to assess whether it may provide indirect information about the upper reproductive tract.

Endometrial biopsy is a gynecological procedure routinely performed in the clinical practice to provide the patient with an analysis of their microbiome before embryo transfer, ensuring that it is carried out in a non-pathological endometrium, especially in patients with previous implantation failures. It is considered the standard for uterine lining sampling but is an invasive technique that, due to the discomfort associated with the procedure itself, may not always be feasible. Endometrial fluid is a less invasive method that offers a potential alternative by collecting cells from the endometrial surface. On the other hand, studying the vaginal microbiome, although it may provide insight into reproductive outcomes, may not accurately reflect the microbiome of the uterine cavity, a key location where implantation and pregnancy occur. By using comprehensive microbiome analysis techniques, this study will assess the microbial populations collected by each method and determine the efficiency and usefulness of each sampling technique.

Through direct comparison, this research aims to establish a clearer understanding of how sampling techniques can impact microbiome analysis in the context of reproductive health. The results obtained could have significant implications for clinical practice, potentially offering less invasive and more accurate methods to evaluate the endometrial microbiome. This study aims not only to redirect our approach to sampling the endometrial microbiome but also to improve our understanding of its role in female reproductive health. Furthermore, it would facilitate the assessment of potential correlations between the endometrial and vaginal microbiomes.

• Study Type: Observational
• Enrollment (Actual): 57

Contacts and Locations

Study Locations

• Spain
  • Seville
    • Seville, Seville, Spain, 41092
      • Vida Recoletas Sevilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women, between 18 and 50 years, coming form the donor program and/or patients from the General Gynaecology Unit who attend to routine gynaecological controls to the clinic, and whose samples will be taken during the secretory phase of the natural menstrual cycle.

Description

Inclusion Criteria:

• Women, between 18 and 50 years, coming form the donor program and/or patients from the General Gynaecology Unit who attend to routine gynaecological controls to the clinic and who voluntarily accept to participate and sign the corresponding informed consent approved by the Ethics Committee, once they have been dully informed of the study's nature and knoe the potential risks, benefits and discomforts.

Exclusion Criteria:

• Ongoing pregnancy.
• Samples not obtained during the secretory phase of a natural cycle.
• Intake of any antibiotic, probiotic and/or antifungal in the 7 days prior to the sample collection of the first cycle.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Endometrial and vaginal microbiome description; Participants in this group will undergo two rounds of samples collection, 1, 2 or 3 months apart, as assigned by the investigator.	Diagnostic test: Reproductive tract microbiome analysis; Assessment of the endometrial and vaginal microbiome in three different samples: endometrial biopsy (EB), endometrial fluid (EF) and vaginal swab (VS).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of minimally invasive techniques for the analysis of the endometrial microbiome	Assessment of the viability and technical reliability of the new sampling techniques (endometrial fluid -EF- and vaginal swab -VS-) to evaluate the endometrial microbiome, compared with the standard sampling technique, the endometrial biopsy - EB-. The endometrial microbiome composition will be determined by DNA extraction and bacterial profiling from the three samples (endometrial biopsy -EB-, endometrial fluid -EF- and vaginal swab -VS-). The EB microbiome will serve as reference and it will be compared with the EF's and VS's microbiome to determine whether they are equivalent.	From enrollment to the second sampling round (1 to 3 months, depending on the study assigned group))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the inter-cycle consistency of the microbial profile in a period of 1 to 3 months	Comparison of the endometrial microbiome from each patient at 2 different time points, 1, 2 or 3 months apart. The endometrial microbiome of each patient, determined by DNA extraction and bacterial profiling of the three samples, will be compared at two different time points (1, 2 or 3 months apart) to determine the microbiome's and technique stability and robustness.	From enrollment to the second sampling round (1 to 3 months, depending on the study assigned group))
Safety evaluation of the sampling techniques (EB, EF and VS)	Registration of any relevant adverse events related to the techniques reported by participants	From enrollment to the end of the study (from 1 to 3 months, depending on the assigned group)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of the VS's and EF's pH with the microbiome	Determination of the pH in the VS and EF samples and assessment of the possible correlation with the microbial profile.	From enrollment to the second sampling round (1 to 3 months, depending on the study assigned group))

Collaborators and Investigators

• Sponsor: Igenomix

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2025
• Primary Completion (Actual): February 18, 2026
• Study Completion (Actual): February 18, 2026

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; Dysbiosis; Pathogenic bacteria; endometrial microbiome; Reproductive tract
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Dysbiosis; Infertility
• Other Study ID Numbers: IGX1-MIC-DV-24-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No