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Application of Lactobacillus Salivarius CECT5713 in Infertility of Unknown Origin

U

Universidad Complutense de Madrid

Status and phase

Completed
Phase 2

Conditions

Infertility Unexplained
Abortion, Spontaneous
Abortion in First Trimester

Treatments

Biological: Lactobacillus salivarius CECT5713

Study type

Interventional

Funder types

Other

Identifiers

NCT04446572
PREPROBIFERT01

Details and patient eligibility

About

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%.

Full 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.

Enrollment

58 patients

Sex

Female

Ages

33 to 41 years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

58 participants in 3 patient groups

Repetitive Abortion (RA) group
Experimental group
Description:
Starting at day 0, women of the RA (n=21) group 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).
Treatment:
Biological: Lactobacillus salivarius CECT5713
Infertility (INF) group
Experimental group
Description:
Starting at day 0, women of the INF group (n=23) 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).
Treatment:
Biological: Lactobacillus salivarius CECT5713
Control group
No Intervention group
Description:
The control group (n = 14) included fertile women having at least two children after uncomplicated term pregnancies.

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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