RCT to Assess the Impact of Microbiome Status in Infertile IVF Patients at Their First IVF/ICSI Cycle

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

1018 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-31

Study Completion Date

2023-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Although the endometrium has been traditionally considered free of bacteria, recent studies have documented the presence of an endometrial microbiome. The uterine microbiome can be defined as Lactobacillus-dominated (\<90% Lactobacillus spp.) or non-Lactobacillus-dominated (\<90% Lactobacillus spp. with \>10% of other bacteria). The presence of a pathogenic microbiota in endometrium was associated with significant decrease in implantation, pregnancy, ongoing pregnancy and live birth rates. Some of these pathogens microorganisms can also produce infection and inflammation that may lead to chronic endometritis.

Nowadays, the endometrial microbiome can be investigated with the EMMA test and the most known pathogens related with chronic endometritis can be detected with the ALICE test,both of them developed by Igenomix group. Our goal in this project is to investigate at what extent, if any, the analysis of the endometrial factor, at a microbiome level, in patients at their first IVF cycle improves their clinical outcome.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Effect of Reproductive Tract Microbiota on Pregnancy Outcome in IVF/ICSI

NCT04293068

Infertility Recurrent Implantation Failure Recurrent Miscarriage

UNKNOWN

Whether Vaginal Microbiota Affects Pregnancy Outcomes After Embryo Transfer

NCT06296615

Infertility, Female Microbial Colonization

COMPLETED

The Microbiome of Infertile Couples and Its Effect on Their Reproductive Outcomes

NCT03420859

Abnormal Vaginal Microbiota Infertility

UNKNOWN

Analysis of the Composition of the Vaginal Microbiota During IVF Treatment and Correlation With Serum Progesterone Level on the Day of Embryo Transfer

NCT04820985

IVF

COMPLETED

Postbiotic Intervention on Vaginal Microbiota

NCT07278024

Infertile Women Undergoing IVF or ICSI

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Some authors have reported the existence of an endometrial microbiota present in healthy woman and different from that in the vagina. It is well known that the presence of pathogens (such as Gardnerella and Streptococcus) in the endometrium is related with infertility, pregnancy loss, premature rupture of membranes and preterm birth.

Another factor which has an impact on infertility is Chronic Endometritis (CE). It consists of a persistent inflammation of the endometrial mucosa and its prevalence in infertile patients has been estimated to be between 2.8 and 39%, although this percentage can reach up to 50 and 60% in patients with miscarriages and repeated implantation failure, respectively. The most common cause of CE is bacterial infection, but the traditional methods of diagnosis (histology, hysteroscopy and microbial culture) often give discordant results between them.

Based on all mentioned above, two molecular tests have been respectively developed by Igenomix (an international company that provides leading advanced services in reproductive genetics and infertility) to assess endometrial microbiome: EMMA (Endometrial Microbiome Metagenomic Analysis) and ALICE (Analysis of Infectious Chronic Endometritis). EMMA test analyses and quantifies all the bacteria present in the endometrium, showing the main bacterial genera present in significant amount in an endometrial sample; while ALICE test quantifies the amount of pathogens more often causing CE (Enterococcus spp., Enterobacteriaceae (Escherichia and Klebsiella), Streptococcus spp., Staphylococcus spp., Mycoplasma spp., and Ureaplasma spp.), Chlamydia and Neisseria, also in an endometrial sample.

The current project aims to investigate in a randomized way the potential improvement on the clinical outcome of Chinese infertile patients at their first IVF cycle considering a personalized diagnosis and treatment (when applicable) of their endometrial microbiome status with the EMMA/ALICE. To do that, only the outcomes of the first single embryo transfers performed after the inclusion of each patient will be considered.

Considering a 30% of possible drop-outs, a total of 1018 patients will be recruited (509 randomized in each group). They will be allocated on a balanced way (assigned by chance like the flip of a coin) in one of the two arms described below. Reproductive outcomes (defined following The International Glossary on Infertility and Fertility Care, 2017) will be compared between the two groups.

Data exported from the source documents will be duly codified and treated in order to protect the clinical and personal information of participants in accordance with the current local legislation.

All the statistical analysis performed on the data, as well as the procedures, will be registered in a detailed Statistical Analysis Plan (SAP) that will be developed during the study and before starting data analysis.

An interim analysis of this data is planned once 50% of the recruitment has been achieved. Besides and at that same moment, the study will be overseen by an independent Data Monitoring Committee.

All of the statistical procedures will be done systematically by both, intention to treat analysis (ITT) and per protocol analysis (PP). The ITT analysis will include all randomized patients recruited and assigned to one of the two groups after biopsy collection and before randomization. The PP analysis will be applied to those patients who adequately follow the protocol assigned according to their group and in whom the transfer of the good quality blastocyst is performed.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Infertility, Female IVF

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Intervention group (mET)

Microbiome-driven embryo transfer of a single vitrified blastocyst in an HRT cycle according to the EMMA/ALICE test results.

Group Type EXPERIMENTAL

EMMA/ALICE

Intervention Type DIAGNOSTIC_TEST

Before randomization, an endometrial biopsy (EB) sample will be collected from all participants between day 15 and 25 of a natural cycle or after around 120 hours of progesterone (P) impregnation during a standard HRT cycle. The results of the EMMA/ALICE test will be provided to participants and their gynecologists. Depending on the test results, there are 3 different possibilities:

1. Normal result
2. Ultralow or Dysbiotic result
3. Abnormal result (pathogens) All probiotics and antibiotics that will be used in the study are already authorized by the local health authorities and will be prescribed under their technical data sheet/brochure conditions following the medical indications.

Control group (FET)

Frozen embryo transfer of a single vitrified blastocyst in an HRT cycle according to the clinical standard practice.

Group Type ACTIVE_COMPARATOR

EMMA/ALICE

Intervention Type DIAGNOSTIC_TEST

Before randomization, an endometrial biopsy (EB) sample will be collected from all participants between day 15 and 25 of a natural cycle or after around 120 hours of progesterone (P) impregnation during a standard HRT cycle. The results of the diagnosis will not be disclosed with the patients randomized into this arm nor with their gynecologists.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

EMMA/ALICE

Before randomization, an endometrial biopsy (EB) sample will be collected from all participants between day 15 and 25 of a natural cycle or after around 120 hours of progesterone (P) impregnation during a standard HRT cycle. The results of the EMMA/ALICE test will be provided to participants and their gynecologists. Depending on the test results, there are 3 different possibilities:

1. Normal result
2. Ultralow or Dysbiotic result
3. Abnormal result (pathogens) All probiotics and antibiotics that will be used in the study are already authorized by the local health authorities and will be prescribed under their technical data sheet/brochure conditions following the medical indications.

Intervention Type DIAGNOSTIC_TEST

EMMA/ALICE

Before randomization, an endometrial biopsy (EB) sample will be collected from all participants between day 15 and 25 of a natural cycle or after around 120 hours of progesterone (P) impregnation during a standard HRT cycle. The results of the diagnosis will not be disclosed with the patients randomized into this arm nor with their gynecologists.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients whose written IC approved by the EC has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
* Patients undergoing their first IVF/ICSI cycle (first oocyte pick up, freezing all) with their own oocytes that will receive single embryo transfer of frozen blastocyst stage embryos (day 5/6) on an HRT cycle.
* At least 2 morphologically good quality embryos already vitrified in blastocyst stage (day 5/6).
* Maternal Age: ≤37 years to rule out embryo factor in aging patients.
* BMI: 18.5 - 30.0 kg / m2 (both inclusive).
* Normal ovarian reserve (defined as: AFC ≥ 8; AMH level ≥1.0 ng/ml and/or FSH \< 8 mU/ml) before the controlled ovarian stimulation (COS) initiation.
* Serum P levels ≤ 1.5 ng/ml, measured within 24 hours before the hCG administration in the COS cycle.
* Negative serological tests for HIV, HBV, HCV, RPR.

Exclusion Criteria

* Patients with repeated miscarriages (\> 2 previous biochemical pregnancies or \> 2 spontaneous miscarriages).
* Male partner with severe male factor (spermatozoa \< 2 million/ml). Semen donor is allowed.
* Patients who are intrauterine device (IUD) carriers in the last 3 months before sample collection.
* Adenomyosis or any pathological finding affecting the endometrial cavity such as polyps/sub-mucosal myomas, intramural myomas \> 4 cm, or hydrosalpinx must be previously operated at least 3 months before the endometrial samples are obtained.(Note: Patients are allowed to participate if the pathology is corrected before performing any study procedure).
* Embryos analysed using preimplantation genetic testing for aneuploidies (PGT-A)
* Women who have received antibiotics in the last month previous to sample collection, except for the prophylaxis for the oocyte retrieval. In the control group, antibiotics cannot be provided during the ET cycle
* Illness or unstable medical condition that may put at risk the patient's safety and her compliance in the study

Maximum Eligible Age

37 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes