Vaginal Microbiota and In Vitro Fertilization Outcomes: Development of a Simple Diagnostic Tool to Predict Patients at Risk of a Poor Reproductive Outcome

Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease

“…41 Furthermore, women with lower microbial diversity and those with a higher proportion of abnormal vaginal microbiota were more likely to have poor reproductive outcomes following IVF. 42 Nevertheless, the metaanalysis of 12 studies in the IVF setting found that BV did not significantly impact the live birth rate (relative risk [RR], 1.47; 95% confidence interval [CI], 0.96e1.57) or the clinical pregnancy rate (RR, 0.93; 95% CI, 0.75e1.15). 40 Although there is a clear association between BV and infertility, causality has not been conclusively determined; further research that includes large-scale longitudinal and mechanistic studies are needed.…”

Effect of clindamycin and a live biotherapeutic on the reproductive outcomes of IVF patients with abnormal vaginal microbiota: protocol for a double-blind, placebo-controlled multicentre trial

“…Approvals from the Regional Scientific Ethical Committee, Central Denmark Region (M-2017-157-17), the Danish Data Protection Agency [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and Danish Medicines Agency (2016-002385-31) were obtained prior to trial initiation 7 December 2017. Danish law will be complied with regarding the handling of personal information.…”

“…Consistently, publications have reported the Lactobacillus crispatus CST to be associated with optimal genital health and reproductive outcomes. 13 17 31–33 Moreover, abundant in vitro evidence point towards a beneficial production of both D and L lactic acid isomers by L. crispatus that not all other common vaginal lactobacilli produce. 34 35 At the time of planning the present study, only one L. crispatus product, LACTIN-V, existed as an investigational live biotherapeutic product regulated by FDA—at that time in phase II development.…”

Vaginal microbiota and IVF outcomes: poor diagnosis results in flawed conclusions

“…(i) The use of non-validated and arbitrary cut-off levels to stratify normal and abnormal vaginal microbiota based on a pilot study (n=32) investigating low biomass endometrial specimens by next generation sequencing rather than by quantitative polymerase chain reaction (qPCR) as was used in Vergaro et al (Moreno et al, 2016). (ii) This arbitrary cut-off does not sufficiently take into account the alpha diversity within Lactobacillus (L.)-dominated samples (Haahr et al, 2018). For example, L. iners has a 15-fold higher concentration than L. crispatus (Haahr et al, 2018), rendering especially the L. iners group reported by Vergaro et al subject to misclassification due to 'contamination' with large numbers of bacterial vaginosis-associated bacteria (BVAB).…”

“…(ii) This arbitrary cut-off does not sufficiently take into account the alpha diversity within Lactobacillus (L.)-dominated samples (Haahr et al, 2018). For example, L. iners has a 15-fold higher concentration than L. crispatus (Haahr et al, 2018), rendering especially the L. iners group reported by Vergaro et al subject to misclassification due to 'contamination' with large numbers of bacterial vaginosis-associated bacteria (BVAB). (iii) The authors failed to compare using the gold standard for vaginal dysbiosis, the Nugent score, as was done by others (Haahr et al, 2016).…”