In the present narrative review, the probiotic effects of vaginal Lactobacillus spp. are described in detail, covering the importance of the differential production of lactic acid, the lactic acid D/L isoforms, the questionable in vivo effect of hydrogen peroxide, as well as bacteriocins and other core proteins produced by vaginal Lactobacillus spp. Moreover, the microbe–host interaction is explained with emphasis on the vaginal mucosa. To understand the crucial role of Lactobacillus spp. dominance in the vaginal microbiota, different dysbiotic states of the vagina are explained including bacterial vaginosis and aerobic vaginitis. Finally, this review takes on the therapeutic aspect of live lactobacilli in the context of bacterial vaginosis. Until recently, there was very low-quality evidence to suggest that any probiotic might aid in reducing vaginal infections or dysbiosis. Therefore, clinical usage or over the counter usage of probiotics was not recommended. However, recent progress has been made, moving from probiotics that are typically regulated as food supplements to so-called live biotherapeutic products that are regulated as medical drugs. Thus, recently, a phase 2b trial using a Lactobacillus crispatus strain as a therapeutic add-on to standard metronidazole showed significant reduction in the recurrence of bacterial vaginosis by 12 weeks compared to placebo. This may constitute evidence for a brighter future where the therapeutic use of lactobacilli can be harnessed to improve women’s health.

Recent advances in molecular microbiology have enabled refined studies of the genital tract microbiota. This constitutes the basis of the present updated systematic review and meta-analysis which investigate vaginal dysbiosis (VD) as defined by either microscopy (e.g., Nugent score for bacterial vaginosis) or molecular methods (qPCR and Next Generation Sequencing) to evaluate the impact of VD on the reproductive outcomes in women undergoing IVF-treatment. A total of 17 studies were included, comprising 3543 patients and with a VD prevalence of 18% (95%CI 17–19). Across all methods, VD is a significant risk factor for early pregnancy loss in IVF (Relative risk (RR) = 1.71 95%CI 1.29–2.27). Moreover, a predefined sub-analysis of studies using molecular methods for VD diagnosis showed a significant reduction in the clinical pregnancy rate when compared to normal vaginal microbiota patients (RR = 0.55 95%CI 0.32–0.93). However, regardless of diagnostic methodology, VD did not significantly influence live birth rate (LBR). In conclusion, molecular tools have provided a more detailed insight into the vaginal microbiota, which may be the reason for the increased adverse effect estimates in IVF patients with molecularly defined VD. However, the quality of evidence was very low across all outcomes according to GRADE and thus, more studies are warranted to understand the impact of VD in IVF.

The primary aim of the present randomised, double-blind, placebo-controlled trial was to investigate whether clindamycin and live Lactobacillus crispatus CTV-05 (LACTIN-V) would improve clinical pregnancy rates in IVF patients with abnormal vaginal microbiota (AVM) defined by high quantitative PCR loads of Fannyhessea vaginae and Gardnerella spp. IVF patients were randomised prior to embryo transfer into three parallel groups 1:1:1. Group one (CLLA) received clindamycin 300 mg ×2 daily for 7 days followed by vaginal LACTIN-V until the day of pregnancy scan. Group two (CLPL) received clindamycin and placebo LACTIN-V, and finally, group three (PLPL) received an identical placebo of both drugs. A total of 1533 patients were screened, and 338 patients were randomised. The clinical pregnancy rates per embryo transfer were 42% (95%CI 32-52%), 46% (95%CI 36-56%) and 45% (95%CI 35-56%) in the CLLA, CLPL, PLPL groups respectively. Thus, treatment of AVM did not improve reproductive outcome. The EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) clinical trial identifier is 2016-002385-31; first registration day 2016-07-11.

Seal finger (sealer’s finger, spekk finger), an extremely painful hand infection contracted by individuals handling seals, has previously been associated with Mycoplasma phocacerebrale. From 2000 to 2014, six independent strains of a novel Mycoplasma species were isolated at Statens Serum Institut, Denmark, from Scandinavian patients with seal finger (M5725^T, M6447, M6620, M6642 and M6879) or septic arthritis (M6921). Prior to the onset of infection, all patients had reported contact with unspeciated seals. All isolates grew within 2–5 days in Friis’ modified broth and metabolized glucose and arginine but not urea. Strains M5725^T, M6447, M6642 and M6921 also grew in Hayflick-type media. Colonies on agar media were large (0.5–1.0 mm) and had a typical ‘fried egg’ appearance, reduced tetrazolium, and were digitonin sensitive. Growth occurred at 32 °C but not at 42 °C. Strains were susceptible to doxycycline and moxifloxacin but resistant to azithromycin and erythromycin. The genomes of the six strains were sequenced and relatedness to all known Mycoplasma species was inferred. Phylogenetic analyses using 16S rRNA gene sequences and core genome single nucleotide polymorphisms showed that the isolated strains were highly similar and phylogenetically distinct from all other species within the genus Mycoplasma. The sizes of the genome sequences of the strains ranged from 744 321 to 772409 bp, with a G+C content of 25.0–25.2 mol%. Based on these analyses, we propose a novel species of the genus Mycoplasma with the name Mycoplasma phocimorsus sp. nov. with the first isolate M5725^T (NCTC 14922^T=DSM 116188^T) as the proposed type strain and representative strains M6447, M6620, M6642, M6879 and M6921.

Over the last decades, the Chlamydiales order has expanded and a new group of Chlamydia-related bacteria has emerged, covering species such as Waddlia chondrophila associated with bovine abortion. However, it is unknown whether they compromise human reproduction such as Chlamydia trachomatis. We therefore aimed to investigate the association between vaginal colonization of selected species of the Chlamydiales order with spontaneous abortion, preterm birth, and animal exposure. Pregnant women were enrolled at the nuchal translucency scan or when admitted for suspected miscarriage at Aarhus University Hospital, Denmark. Cases were defined as spontaneous abortion <22 weeks and preterm birth <37 weeks. Controls were defined as term birth ≥37 weeks. Vaginal samples from 1203 women were assessed using C. trachomatis, W. chondrophila, and pan-Chlamydiales-specific real-time PCRs targeting the 16S rRNA gene. A total of 1120 women of primarily Caucasian ancestry were enrolled, including 193 spontaneous abortions, 88 preterm births, and 839 term births. After sequencing for verification, the prevalence of Chlamydiales was 3 of 193 (1.6%; 95% CI, 0.5-4.8) in women experiencing spontaneous abortion, 2 of 88 (2.3%; 95% CI, 0.6-8.9) in women with preterm birth, and 20 of 839 (2.4%; 95% CI, 1.6-3.7) in women giving birth at term. Thus, Chlamydiales infection was neither significantly associated with spontaneous abortion (OR, 0.68; 95% CI, 0.15-2.01) nor preterm birth (OR, 1.02; 95% CI, 0.15-3.60) compared with women giving birth at term. Amplicons from the pan-Chlamydiales assay revealed close sequence homology and were primarily identified as uncultured Chlamydiales bacteria. Among Danish pregnant women, the prevalence of Chlamydiales was low and not associated with adverse pregnancy outcomes.