Modulation of Reproductive Microbiota by Ligilactobacillus Salivarius CECT5713

Modulation of the Reproductive Microbiota as a Strategy to Increase Rates of Reproductive Success in Couples With Infertility of Unknown Origin

The objective of the project is to elucidate if the oral administration of Ligilactobacillus salivarius CECT5713 is capable of improving the rates of term pregnancies in couples with infertility problems of unknown cause. On the other hand, the project is aimed to detect microbiological, immunological and hormonal markers that allow the identification of couples in which the administration of the strain could be particularly effective. This is a randomized, double-blind, parallel-group controlled nutritional intervention study. The intervention (Ligilactobacillus salivarius CECT5713 or placebo) will be performed during the 6 months prior to the fertility treatment and during the first IVF cycle (estimated 1-2 months). In case of pregnancy, the woman will continue the treatment until 12 weeks of gestation.

Study Overview

• Status: Completed
• Conditions: Infertility Unexplained
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Ligilactobacillus salivarius CECT5713

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Granada, Spain, 18004
    • Biosearch S.A.U.
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28040
    • Universidad Complutense de Madrid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• legal age
• Intention to achieve a pregnancy, but without achieving it;
• Be willing to undergo in vitro fertilization treatment;
• Be on the waiting list for the IVF cycle with an expected waiting time > 5 months.

Exclusion Criteria:

• Sterility in one of the members of the couple (azoospermia; impermeability of the fallopian tubes...).
• Genitourinary malformations;
• Concurrence of other severe diseases (e.g.: cancer, AIDS, ALS, morbid obesity...) or uncontrolled diseases (inflammatory bowel diseases, diabetes...).
• Treatment/intervention other than the planned IVF after the start date of the intervention.
• Antibiotic treatment at the start date of the intervention.
• Intention to consume another probiotic supplement in the following 3 months.
• Participation in another clinical trial.
• Allergic/intolerant to the excipient.
• Inability to understand the informed consent form and/or to follow the basic instructions of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; All women in the placebo group consume (oral route) a daily capsule with ~50 mg of maltodextrin during the 6 months prior to the fertility treatment and during the first IVF cycle (estimated 1-2 months). In case of pregnancy, the woman will continue the treatment until 12 weeks of gestation.	Dietary supplement: Placebo; Oral administration of a capsule containing maltodextrin.
Experimental: Probiotic group; All women in the probiotic group consume (oral route) a daily capsule with ~50 mg of freeze-dried probiotic (9.5 log10 CFU of L. salivarius CECT5713; excipient: maltodextrin) during the 6 months prior to the fertility treatment and during the first IVF cycle (estimated 1-2 months). In case of pregnancy, the woman will continue the treatment until 12 weeks of gestation.	Dietary supplement: Ligilactobacillus salivarius CECT5713; Oral administration of a capsule containing 9.5 log10 cfu of the strain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful pregnancies	Total number of pregnancies with delivery of a healthy baby	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modification of the vaginal microbiota	Variation in the concentration of lactobacilli and other microbes in vaginal samples (Staph ylococcus, Streptococcus, Enterococcus, Corynebacterium, Rothia, Arthrobacter, Acinetobacter, Actinomyces)	9 months
Vaginal immunomodulation	Variation in the concentration of immune factors in vaginal samples. The presence and concentration of a wide spectrum of cytokines, chemokines and growth factors (IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1β, RANTES, TGF-β1, 2 and 3, VEGF, GRO-alpha and TNF-alpha)	9 months

Collaborators and Investigators

• Sponsor: Biosearch S.A.
• Collaborators: Universidad Complutense de Madrid; Hospital San Carlos, Madrid
• Investigators: Principal Investigator: Juan M. Rodríguez, PhD, Complutense University Madrid

Publications and helpful links

General Publications

• Fernandez L, Castro I, Arroyo R, Alba C, Beltran D, Rodriguez JM. Application of Ligilactobacillus salivarius CECT5713 to Achieve Term Pregnancies in Women with Repetitive Abortion or Infertility of Unknown Origin by Microbiological and Immunological Modulation of the Vaginal Ecosystem. Nutrients. 2021 Jan 6;13(1):162. doi: 10.3390/nu13010162.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): May 3, 2023
• Study Completion (Actual): January 29, 2024

Study Registration Dates

• First Submitted: February 8, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Infertility
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: PROBIFERT P051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Global and individual reproductive rates, microbiological and immunological data will be available to other researchers once the study (including analyses of all the samples) is completed and published.
• IPD Sharing Time Frame: All the raw data will be available to other researchers once the study is published.
• IPD Sharing Access Criteria: Our intention is that all the raw data will be available as a supplementary tables in an open acess journal. They will be also provided on request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No