Application of Lactobacillus Salivarius CECT5713 in Infertility of Unknown Origin

Infertility Unexplained Clinical Trial

Official title:

Application of Lactobacillus 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04446572
• Other study ID #: PREPROBIFERT01
• Status: Completed
• Phase: Phase 2
• Start date: October 16, 2018
• Est. completion date: November 29, 2019

Study information

• Verified date: June 2020
• Source: Universidad Complutense de Madrid
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. The second objective was to evaluate the ability of Lactobacillus salivarius CECT5713 to modulate such parameters and to increase pregnancy rates in women with reproductive failure. The administration of L. salivarius CECT5713 (~9 log10 colony-forming units (CFU)/day) for 6 months or until a diagnosis of pregnancy to women with reproductive failure resulted in an overall successful (term) pregnancy rate of 56%.

Description:

In this study, we aimed to assess the cervicovaginal environment (pH, Nugent score, soluble immune factors and bacterial profile) in women with reproductive failure because of either repetitive abortion or infertility of unknown origin and compare it to that of healthy fertile women. The second objective was to evaluate the ability of Lactobacillus salivarius CECT5713 to modulate such parameters and to increase pregnancy rates in women with reproductive failure. Vaginal pH and Nugent score were higher in women with reproductive failure than in fertile women. Differences were also noted regarding soluble immune factors transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF). Their concentrations in cervicovaginal lavage samples were reduced by about one-half in women with reproductive failure compared to fertile women. Lactobacilli were detected in a higher proportion, and at a higher concentration and having different species profile, in fertile women than in women with repetitive abortion or infertility. The study of the vaginal microbiome revealed that samples from fertile women were characterized by the high abundance of Lactobacillus sequences, while in about one third of samples from women with reproductive failure DNA from this genus was practically absent while there was an abundance of that of Gardnerella and Bifidobacterium. Lactobacillus salivarius CECT5713 seemed to be a suitable candidate to modulate the cervicovaginal microbiota because of its acidifying capacity, adhesion to vaginal cells and co-aggregation with vaginal pathogens. The administration of L. salivarius CECT5713 (~9 log10 CFU/day) for 6 months or until a diagnosis of pregnancy to women with reproductive failure resulted in an overall successful (term) pregnancy rate of 56%. In addition, the probiotic intervention modified significantly key microbiological, biochemical and immunological parameters in women who got pregnant being their post-intervention values similar or close to those of fertile women. The high concentrations of L. salivarius and the detection of L. salivarius DNA in vaginal samples confirmed that the probiotic was able to reach the vaginal mucosa. In conclusion, L. salivarius CECT5713 has proved to be a good candidate to improve reproductive success in women with reproductive failure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: November 29, 2019
• Est. primary completion date: November 29, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 33 Years to 41 Years

Eligibility

Inclusion Criteria:

• Recurrent miscarriage with three or more pregnancy losses during the first 12 weeks of pregnancy (RA group)

• Infertility (inability to conceive) despite being the recipients of ART for at least three times, including two cycles, at least, of in vitro fertilization (IVF) (INF group).

• Fertile women having at least two children after uncomplicated term pregnancies (Control group).

Exclusion Criteria:

• Antiphospholipid syndrome

• Hormonal therapy, antibiotics or probiotics in the 4 weeks previous to sampling.

• Lactose intolerance or cow's milk protein allergy (RA and INF groups)

Related Conditions & MeSH terms

• Abortion in First Trimester
• Abortion, Spontaneous
• Infertility
• Infertility Unexplained

Intervention

Biological:
• Lactobacillus salivarius CECT5713
Starting at day 0, women of the RA and INF groups consumed (oral route) a daily sachet with ~50 mg of freeze-dried probiotic (~9 log10 CFU of L. salivarius CECT5713) for 6 months or until a diagnosis of pregnancy (whatever happened first).

Locations

Country	Name	City	State
Spain	Dpt. Nutricion, Bromatologia y Tecnologia de los Alimentos	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Universidad Complutense de Madrid	Bisearch Life, Centro de Diagnóstico Médico. Ayuntamiento de Madrid.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pregnancies and successful pregnancies	Total number of pregnancies and number of pregnancies with delivery of a healthy baby	6 months
Secondary	Modification of the vaginal microbiota	Variation in the concentration of lactobacilli and other bacteria in cervicovaginal lavage samples	6 months
Secondary	Vaginal immunomodulation	Variation in the concentration of TGF-ß and VEGF in cervicovaginal lavage	6 months