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临床试验/NCT04446572
NCT04446572已完成2 期

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

Universidad Complutense de Madrid2 个研究点 分布在 1 个国家目标入组 58 人开始时间: 2018年10月16日最近更新:
适应症

试验速览

阶段
2 期
状态
已完成
入组人数
58
试验地点
2
主要终点
Pregnancies and successful pregnancies

研究概览

简要总结

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%.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Parallel
主要目的
Basic Science
盲法
None

入排标准

年龄范围
33 Years 至 41 Years(Adult)
性别
Female
接受健康志愿者

入选标准

  • 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).

排除标准

  • 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)

结局指标

主要结局

Pregnancies and successful pregnancies

时间窗: 6 months

Total number of pregnancies and number of pregnancies with delivery of a healthy baby

次要结局

  • Modification of the vaginal microbiota(6 months)
  • Vaginal immunomodulation(6 months)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Juan M. Rodríguez

Professor

Universidad Complutense de Madrid

研究点 (2)

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