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

NCT04686357 | Unknown DMC

• 1 other identifier: PUTH EMMA 1.0
• Study Type: interventional
• Target: 1,018
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Infertility, Female; IVF

Keywords

Endometrial microbiota; microbiome treated embryo transfer; frozen embryo transfer; randomized clinical trial; endometrial microbiome metagenomic analysis; analysis of infectious chronic endometritis

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  The number of deliveries that resulted in at least one live birth per ET (transferred patient). Live birth is defined as the complete expulsion or extraction from a woman of a product of conception after 22 weeks of gestation, which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.

  From date of embryo transfer until 40 weeks

Secondary Outcomes (9)

• Implantation rate

  From date of embryo transfer until 5-6 weeks

• Clinical miscarriage rate

  From date of embryo transfer until 20 weeks

• Biochemical pregnancy rate

  From date of embryo transfer until 5-6 weeks

• Ectopic pregnancy rate

  From date of embryo transfer until 8 weeks

• Pregnancy rate

  From date of embryo transfer until 2 weeks

Study Arms (2)

Intervention group (mET)

EXPERIMENTAL

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

Diagnostic Test: EMMA/ALICE

Control group (FET)

ACTIVE COMPARATOR

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

Diagnostic Test: EMMA/ALICE

Interventions

EMMA/ALICE 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.

Intervention group (mET)

Eligibility Criteria

• Age: Up to 37 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University Third Hospital: lead
• Reproductive & Genetic Hospital of CITIC-Xiangya: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator

MeSH Terms

Conditions

Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Study Officials

• Jie Qiao

  Peking university Third Hospital, Beijing

  PRINCIPAL INVESTIGATOR

• QingXue Zhang

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

• Fei Gong

  Reproductive & Genetic Hospital of CITIC-Xiangya

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jie Qiao

CONTACT

+86 010-82266699; Jie.quiao@263.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2020
• First Posted: December 28, 2020
• Study Start: August 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: July 8, 2021

Record last verified: 2021-03