Vaginal matrix metalloproteinase-9 (MMP-9) as a potential early predictor of preterm birth.

OBJECTIVES: To evaluate the differences in vaginal matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs) in pregnant patients with a history of prior preterm birth compared with controls. METHODS: A prospective cohort pilot study recruited patients during prenatal care with history of prior spontaneous preterm birth (high-risk group) or no history of preterm birth (low-risk/controls). Inclusion criteria were singleton gestation at 11-16 weeks and between 18 and 55 years of age. Exclusion criteria were diabetes mellitus, hypertension, diseases affecting the immune response or acute vaginitis. A vaginal wash was performed at time of enrollment, and patients were followed through delivery. Samples were analyzed using semi-quantitative analysis of MMPS and TIMPS. The study was approved by the IRB and a p value <0.05 was considered significant. RESULTS: A total of 48 pregnant patients were recruited: 16 with a history of preterm birth (high-risk group) and 32 with no history of preterm birth (low-risk group/controls). Groups were similar in age, race, BMI, and delivery mode. The high-risk group had more multiparous women (100 vs. 68.8 %; p=0.02), a greater preterm birth rate (31.2 vs. 6.3 %; p=0.02), and a lower birth weight (2,885 ± 898 g vs. 3,480 ± 473 g; p=0.02). Levels of vaginal MMP-9 were greater in high-risk patients than low-risk patients (74.9 % ± 27.0 vs. 49.4 % ± 31.1; p=0.01). When dividing the cohort into patients that had a spontaneous preterm birth (7/48, 14.6 %) vs. those with a term delivery (41/48, 85.4 %), the vaginal MMP-9 remained elevated in the cohort that experienced a preterm birth (85.46 %+19.79 vs. 53.20 %+31.47; p=0.01). There were no differences in the other MMPS and in TIMPs between high and low-risk groups. CONCLUSIONS: There was an increase in vaginal MMP-9 during early pregnancy in those at high risk for preterm birth and in those who delivered preterm, regardless of prior pregnancy outcome. Vaginal MMP-9 may have potential as a marker of increased risk of preterm birth.

Vestibulodynia and the Vaginal Microbiome: A Case-Control Study.

BACKGROUND: Recent studies of the vaginal microbiome have led to a better understanding of the microbiota and interactions with the host environment, however the role of the vaginal microbiome in vestibulodynia remains unclear. AIM: This study aims to investigate and examine differences in the bacterial and fungal microbiome among patients with vestibulodynia and healthy controls. METHODS: A case-control study was conducted examining the vaginal microbiome of 29 patients with vestibulodynia and 26 controls through Stony Brook University Obstetrics and Gynecology ambulatory clinic. Exclusion criteria included a diagnosis of vaginal infection at the time of presentation, a prior diagnosis of vulvodynia or receipt of treatment, immunosuppression, and receipt of steroid or antibiotic therapy. Vaginal swab samples were obtained from participants. DNA was extracted and sent for diversity assay of 16S rRNA for prokaryotic species and internal transcribed spacers (ITS) for fungi. Demographic characteristics for both cases and controls were obtained through a retrospective chart review. OUTCOME MEASURE: Principal component analysis (PCA) and linear discriminant analysis effect size (LefSe) were used to identify differences in relative abundance of operational taxonomic units (OTUs) for the vaginal microbiome between vestibulodynia patients and controls. RESULTS: Lactobacillus species were dominant amongst both cases and controls. PCA of 16S and ITS OTUs did not show significant differences in microbiome composition between vestibulodynia patients and controls. LefSe demonstrated higher abundance of Bifidobacterium longum, the Genus Sneathia, and the Family Leptotrichiaceae, in controls compared to vestibulodynia samples. For ITS, Aspergillus spp. was significantly more prevalent in controls than in vestibulodynia cases. CLINICAL IMPLICATIONS: Additional studies are needed to further assess the clinical significance of these findings. STRENGTHS AND LIMITATIONS: Strengths of this study include ITS amplicon sequence analysis for fungal species diversity. Limitations of this study include small sample size and lack of racial diversity. CONCLUSIONS: Our study did not find significant differences in composition or diversity between the vaginal microbiomes of cases of vestibulodynia and controls; however, the data suggests differences in abundance of biota requiring further research for biological and clinical significance. Panzarella DA, Peresleni T, Collier JL, et al. Vestibulodynia and the Vaginal Microbiome: A Case-Control Study. J Sex Med 2022;19:1451-1462.

Progesterone effects on vaginal cytokines in women with a history of preterm birth.

OBJECTIVE: To determine the effect of intramuscular progesterone on the vaginal immune response of pregnant women with a history of prior preterm birth. METHODS: A prospective, cohort study of women at 11-16 weeks gestation, ≥18 years of age, and carrying a singleton pregnancy was conducted from June 2016 to August 2017 after IRB approval. Women in the progesterone arm had a history of preterm birth and received weekly intramuscular 17-hydroxyprogesterone caproate. Controls comprised of women with healthy, uncomplicated pregnancies. Excluded were women with vaginitis, diabetes mellitus, hypertension, or other chronic diseases affecting the immune response. A vaginal wash was performed at enrollment, at 26-28 weeks, and at 35-36 weeks gestation. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and a P value <0.05 was considered significant. RESULTS: There were 39 women included, 10 with a prior preterm birth and 29 controls. The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, BMI, gestational age at delivery, mode of delivery, and birth weight. Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2±25.1% versus 26.1±13.2%; P = 0.04), IL-1 beta (47.9±26.4% versus 24.9±17%; P<0.01), IL-2 (16.7±9.3% versus 11.3±6.3%; P = 0.03), and IL-13 (16.9±12.4% versus 8.2±7.4%; P = 0.01) were significantly elevated compared to controls. In the third trimester the cytokine densities for IL-1 alpha (26.0±18.2% versus 22.3±12.0%; P = 0.49), IL-1 beta (31.8±15.9% versus 33.1±16.8%; P = 0.84), IL-2 (10.0±8.4% versus 10.9±5.9%; P = 0.71), and IL-13 (9.1±5.9% versus 10.0±6.5%; P = 0.71) were all statistically similar between the progesterone arm and controls, respectively. CONCLUSION: There is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following the administration of 17- hydroxyprogesterone caproate to levels similar to healthy controls.