Repeated IVF Failureno existNCT07606053
The Role of the Physiological Endometrial Microbiota in Assisted Reproduction Outcomes
An observational study of Repeated IVF Failure and Microbiota, run by Assisting Nature at 1 site in Greece.
Trial summary
The goal of this observational study is to investigate the influence and contribution of the normal composition and balance of the endometrial microbiota on the achievement of embryo implantation and the maintenance of pregnancy in women undergoing IVF, with comparable clinical profiles, including patients with a… Read more about this study
- Who is it for?
- Ages 18 to 54 years, women only
- Conditions the study is for
- Repeated IVF Failure, Microbiota
- How many people
- 80 participants
- Where
- 1 siteGreece
- Study dates
- 2 Jan 2025to 25 Jun 2026
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 54 years
- Women only
- No healthy volunteers
- Adult
Study population: Participants were required to be between 18 and 54 years of age, in accordance with the legally permitted age limits for embryo transfer in Greece
Who may be able to join
- Individuals who are biologically female.
- Age between 18 and 54 years, in accordance with the legally permitted age limits for embryo transfer in Greece.
- Undergoing in vitro fertilization (IVF) treatment.
- Clinical history consistent with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) and comparable IVF treatment profiles.
- Ability to provide informed consent for the use of clinical and microbiome data for research purposes
Who cannot join
- Individuals who are not biologically female.
- Age below 18 or above 54 years.
- Absence of endometrial biopsy samples or incomplete clinical data.
- Presence of significant uterine abnormalities or medical conditions that contraindicate embryo transfer.
- Participation in another interventional clinical study that may interfere with microbiome assessment or IVF outcomes.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
The goal of this observational study is to investigate the influence and contribution of the normal composition and balance of the endometrial microbiota on the achievement of embryo implantation and the maintenance of pregnancy in women undergoing IVF, with comparable clinical profiles, including patients with a history of RIF or RPL, evaluated under identical treatment protocols and hormonal conditions.
The main questions it aims to answer are:
Read more
- Does the normal composition of the endometrial microbiota, particularly the dominance of Lactobacillus species, influence embryo implantation success in women undergoing IVF?
- Does the endometrial microbiota profile affect pregnancy maintenance, ongoing pregnancies, and live birth rates in women with a history of recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL)
Participants will not undergo any additional interventions beyond standard clinical care.They will provide clinical data already collected as part of routine IVF procedures.
Read the detailed description
Endometrial biopsies were collected from patients using a Pipelle catheter during the designated phase of the menstrual cycle. Each sample was immediately placed in a specialized preservative solution and transported to two external laboratories for analysis.
In the first laboratory, bacterial DNA was extracted using a CE-IVD kit, followed by targeted amplification and barcoded sequencing of seven hypervariable regions (V2, V3, V4, V6, V7, V8, V9) of the 16S rRNA gene using the 16STM metagenomic kit and Ion Torrent sequencing system (Ion GeneStudio S5 with Ion Chef Instrument). Data were analyzed with Ion Reporter™ software and MicroSEC ID, using MicroSEC ID and Greengenes databases for taxonomic classification.
In the second laboratory, total DNA was extracted, and targeted amplification of the 16S rRNA gene was performed using the 16S Barcoding Kit 24 V14 (Nanopore), followed by NGS on the MinION Mk1C analyzer. Bioinformatic analysis was conducted using the EPI2ME Labs 16S workflow. Bacterial composition was classified at the genus level, with results expressed as relative abundance percentages. OTU-level data were not disclosed.
Interpretation of microbiota profiles was performed by the treating physician or clinical geneticist. Patients whose samples showed decreased Lactobacillus abundance or the presence of potentially pathogenic microorganisms received individualized interventions. These interventions included a two-week course of antibiotics tailored to the patient's clinical history, followed by probiotics administered orally or via combined oral and vaginal routes for two weeks to two months. Antifungal agents were administered when clinically indicated.
Embryo transfer schedules were adapted based on microbial profiles and clinical assessment. Patients with normal microbial profiles proceeded with IVF in the next cycle. Patients with abnormal profiles, signs of inflammation, or potential pathogenic colonization had embryo transfer postponed for at least one month following completion of the therapeutic regimen.
The study provides a detailed methodological framework for endometrial microbiota analysis, including sample collection, DNA extraction, sequencing strategies, bioinformatic pipelines, and clinical decision-making based on microbial composition, aiming to support personalized management in assisted reproduction.
- Conditions
- Repeated IVF Failure, Microbiota
- Keywords
- Physiological Endometrial Microbiota, Endometrial Microbiota, IVF, In vitro fertilization, Assisted reproduction, Implantation success, Embryo, Endometrial Microbiome, Microbiota, Microbiome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Lactobacillus-dominant microbiota | Participants whose endometrial microbiota is dominated by Lactobacillus species. Data were collected from previously obtained endometrial biopsies, analyzed via 16S rRNA gene sequencing. No interventions were performed beyond standard IVF clinical care. | |
| Non-Lactobacillus-dominant microbiota | Participants whose endometrial microbiota shows depletion of Lactobacillus species or presence of potentially pathogenic microorganisms. Data were collected from previously obtained endometrial biopsies, analyzed via 16S rRNA gene sequencing. In some cases, participants received individualized clinical interventions (e.g., antibiotics or probiotics) based on their microbial profile as part of routine care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Implantation Rate according to microbiome profile
The study formally assesses differences in embryo implantation rates between women with Lactobacillus-dominant and non-Lactobacillus-dominant endometrial microbiota profiles.
Measured: From the day of the embryo transfer to the day of confirmation of implantation (2-4 weeks)
Ongoing Pregnancy/Live Birth Rate according to microbiome profile
Association between endometrial microbiota composition and the likelihood of achieving an ongoing pregnancy or live birth
Measured: From the day of embryo transfer up to the end of the first trimester (up to 12 weeks of gestation) and live birth until delivery (up to 40 weeks of gestation)
Biochemical pregnancy rate and microbiome status
Rate of biochemical pregnancies in relation to endometrial microbiota profile
Measured: From the day of embryo transfer to the day of confirmation of implantation (2-4 weeks)
Secondary outcomes (1)
Endometrial microbiota composition
Relative abundance of Lactobacillus versus non-Lactobacillus genera in endometrial biopsies analyzed by 16S rRNA sequencing.
Measured: At time of biopsy collection (during procedure)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2026
- Study start2 Jan 2025
- Primary completion30 May 2026 (estimated)
- Study completion25 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Repeated IVF FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- Assisting Nature
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07606053
- Sponsor's protocol ID
- Microbiome-AN011
- Other IDs
- Assisting Nature
- Acronym
- no exist
- Status last verified
- May 2026
- First submitted
- 20 Feb 2026
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Physiological Endometrial Microbiota in Assisted Reproduction Outcomes
- ClinicalTrials.gov ID
- NCT07606053
- Acronym / sponsor ID
- no exist / Microbiome-AN011
- Conditions
- Repeated IVF Failure, Microbiota
- Keywords
- Physiological Endometrial Microbiota, Endometrial Microbiota, IVF, In vitro fertilization, Assisted reproduction, Implantation success, Embryo, Endometrial Microbiome
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Assisting NatureUniversity, hospital or other
- Study start
- 2 Jan 2025 (actual)
- Primary completion
- 30 May 2026 (estimated)
- Study completion
- 25 Jun 2026 (estimated)
- First posted
- 26 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to investigate the influence and contribution of the normal composition and balance of the endometrial microbiota on the achievement of embryo implantation and the maintenance of pregnancy in women undergoing IVF, with comparable clinical profiles, including patients with a history of RIF or RPL, evaluated under identical treatment protocols and hormonal conditions.
The main questions it aims to answer are:
- Does the normal composition of the endometrial microbiota, particularly the dominance of Lactobacillus species, influence embryo implantation success in women undergoing IVF?
- Does the endometrial microbiota profile affect pregnancy maintenance, ongoing pregnancies, and live birth rates in women with a history of recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL)
Participants will not undergo any additional interventions beyond standard clinical care.They will provide clinical data already collected as part of routine IVF procedures.
Detailed description
Endometrial biopsies were collected from patients using a Pipelle catheter during the designated phase of the menstrual cycle. Each sample was immediately placed in a specialized preservative solution and transported to two external laboratories for analysis.
In the first laboratory, bacterial DNA was extracted using a CE-IVD kit, followed by targeted amplification and barcoded sequencing of seven hypervariable regions (V2, V3, V4, V6, V7, V8, V9) of the 16S rRNA gene using the 16STM metagenomic kit and Ion Torrent sequencing system (Ion GeneStudio S5 with Ion Chef Instrument). Data were analyzed with Ion Reporter™ software and MicroSEC ID, using MicroSEC ID and Greengenes databases for taxonomic classification.
In the second laboratory, total DNA was extracted, and targeted amplification of the 16S rRNA gene was performed using the 16S Barcoding Kit 24 V14 (Nanopore), followed by NGS on the MinION Mk1C analyzer. Bioinformatic analysis was conducted using the EPI2ME Labs 16S workflow. Bacterial composition was classified at the genus level, with results expressed as relative abundance percentages. OTU-level data were not disclosed.
Interpretation of microbiota profiles was performed by the treating physician or clinical geneticist. Patients whose samples showed decreased Lactobacillus abundance or the presence of potentially pathogenic microorganisms received individualized interventions. These interventions included a two-week course of antibiotics tailored to the patient's clinical history, followed by probiotics administered orally or via combined oral and vaginal routes for two weeks to two months. Antifungal agents were administered when clinically indicated.
Embryo transfer schedules were adapted based on microbial profiles and clinical assessment. Patients with normal microbial profiles proceeded with IVF in the next cycle. Patients with abnormal profiles, signs of inflammation, or potential pathogenic colonization had embryo transfer postponed for at least one month following completion of the therapeutic regimen.
The study provides a detailed methodological framework for endometrial microbiota analysis, including sample collection, DNA extraction, sequencing strategies, bioinformatic pipelines, and clinical decision-making based on microbial composition, aiming to support personalized management in assisted reproduction.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lactobacillus-dominant microbiota | – | –Participants whose endometrial microbiota is dominated by Lactobacillus species. Data were collected from previously obtained endometrial biopsies, analyzed via 16S rRNA gene sequencing. No interventions were performed beyond standard IVF clinical care. |
| Non-Lactobacillus-dominant microbiota | – | –Participants whose endometrial microbiota shows depletion of Lactobacillus species or presence of potentially pathogenic microorganisms. Data were collected from previously obtained endometrial biopsies, analyzed via 16S rRNA gene sequencing. In some cases, participants received individualized clinical interventions (e.g., antibiotics or probiotics) based on their microbial profile as part of routine care. |
Who may qualify
- Ages
- 18 to 54 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Participants were required to be between 18 and 54 years of age, in accordance with the legally permitted age limits for embryo transfer in Greece
Key inclusion criteria (5 listed)
- Individuals who are biologically female.
- Age between 18 and 54 years, in accordance with the legally permitted age limits for embryo transfer in Greece.
- Undergoing in vitro fertilization (IVF) treatment.
- Clinical history consistent with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) and comparable IVF treatment profiles.
- Ability to provide informed consent for the use of clinical and microbiome data for research purposes
Key exclusion criteria (5 listed)
- Individuals who are not biologically female.
- Age below 18 or above 54 years.
- Absence of endometrial biopsy samples or incomplete clinical data.
- Presence of significant uterine abnormalities or medical conditions that contraindicate embryo transfer.
- Participation in another interventional clinical study that may interfere with microbiome assessment or IVF outcomes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Implantation Rate according to microbiome profile
Time frame: From the day of the embryo transfer to the day of confirmation of implantation (2-4 weeks)
The study formally assesses differences in embryo implantation rates between women with Lactobacillus-dominant and non-Lactobacillus-dominant endometrial microbiota profiles.
Ongoing Pregnancy/Live Birth Rate according to microbiome profile
Time frame: From the day of embryo transfer up to the end of the first trimester (up to 12 weeks of gestation) and live birth until delivery (up to 40 weeks of gestation)
Association between endometrial microbiota composition and the likelihood of achieving an ongoing pregnancy or live birth
Biochemical pregnancy rate and microbiome status
Time frame: From the day of embryo transfer to the day of confirmation of implantation (2-4 weeks)
Rate of biochemical pregnancies in relation to endometrial microbiota profile
1 secondary outcome
Endometrial microbiota composition
Time frame: At time of biopsy collection (during procedure)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Repeated IVF Failure
Recruiting
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Repeated Implantation Failure
Recruiting
Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity.
Repeated IVF Failure, Female Infertility
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Repeated IVF Failure and Microbiota, run by Assisting Nature at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Implantation Rate according to microbiome profile (time frame: From the day of the embryo transfer to the day of confirmation of implantation (2-4 weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.