Lactobacilli Deficiency in Infertile Women Seeking IVF in Arash Hospital: An Imbalance in the Genital Microbiome

Vaginal swab specimens may be preferable to cervical swab or urine specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae because of the ease of specimen collection and transport. The purpose of this study was to evaluate whether vaginal swab specimens are equivalent to cervical swab specimens for the detection of N. gonorrhoeae and C. trachomatis by the Becton Dickinson strand displacement amplification assay (SDA) with the BDProbeTec ET instrument and then to evaluate the use of the amplification control in a clinical research setting. In the first phase, vaginal and cervical swab specimens were obtained from 455 symptomatic women aged 18 to 40 attending primary health care and sexually transmitted disease clinics. Thirty-nine specimens (8.6%) had true-positive results for N. gonorrhoeae and 37 specimens (8.1%) had true-positive results for C. trachomatis. The sensitivity of SDA was superior to that of culture for the detection of N. gonorrhoeae with vaginal swab specimens and equivalent to that of the Roche PCR for the detection of C. trachomatis with cervical swab specimens. In the second phase of the study, 1,411 consecutively collected vaginal swab specimens were evaluated, with 357 (25.3%) specimens giving indeterminate readings on the basis of the result for the amplification control. The prevalences of sexually transmitted pathogens in vaginal swab specimens with and without use of the amplification control were 6.0 and 5.8%, respectively, for C. trachomatis and 3.1 and 3.0%, respectively, for N. gonorrhoeae. Although, vaginal swab specimens were equivalent to cervical swab specimens for the detection of N. gonorrhoeae and C. trachomatis by SDA with respect to sensitivity, one in four vaginal swab specimens yielded an indeterminate result when the amplification control was used. The amplification control has limited value for use with vaginal swab specimens.

Endometritis is a major cause of infertility in many domestic species. However, until now the pathogenesis of the endometritis in the bitch is unclear. The aim of this study was to evaluate the gene transcription pattern of prostaglandin (PG) synthesis enzymes (cyclooxygenase [COX2], PTGES-1 and PGFS) in the endometrium of bitches with or without endometritis. Thirty mixed breed bitches in dioestrus, aged between 1 and 5years, and weighing between 10 and 30kg were used. After ovariohysterectomy (OVX), uterine biopsy samples were collected from the middle part of both horns. Then, endometrial epithelium was collected using the cytobrush method and mRNA analysis was performed by real-time RT-PCR. Data were analysed with Kruskal-Wallis anova using the sas® software. Uterine condition was identified by endometrial biopsies (normal endometria [n=11; NE], acute endometritis [n=10; AE] and chronic endometritis [n=9; CE]). The COX2, PTGES-1 and PGFS/AKR1C3 mRNA expression in bitches with and without endometritis was similar. Except for PGFS/AKR1C3, gene transcription of COX2 and PTGES-1 was significantly increased in AE compared with CE. In addition, COX2 gene transcription was significantly increased in AE compared with NE. In contrast, no differences were found for COX2, PTGES-1 and PGFS/AKR1C3 mRNA expression in the samples of NE compared with CE.

Study question Is there any correlation between the total bacterial load and the lactobacilli quantities in the vaginal and endometrial microbiomes in reproductive-age women? Summary answer There was no correlation between the vaginal and endometrial total bacterial loads and only a weak positive correlation between the quantities of lactobacilli. What is known already The Lactobacilli-dominated microbiota is considered to be the most favorable type of microbiota in the uterine cavity. It is associated with increased reproductive success in women undergoing in vitro fertilization. Whereas the non-Lactobacillus dominated microbial communities are more frequent in women with poor pregnancy outcomes. When analyzing endometrial microbiota, one of the challenges is sampling. Transvaginal sample intake involves the possibility of contaminating the samples with vaginal microbiota. Moreover, it is an invasive procedure leading to the development of infectious inflammatory diseases of the upper genital tract. Thus, researchers are currently searching for predictors of the state of endometrial microbiota. Study design, size, duration It is a cross-sectional study of the vaginal end endometrial micorbiomes from 64 reproductive-age women. Endometrial and vaginal samples were collected simultaneously on days 7–10 of the menstrual cycle. To avoid contamination by vaginal microbiota, Endobrush Standard for Endometrial Cytology (Laboratoire C.C.D.; France) was used for endometrial sampling. Participants/materials, setting, methods The study included women who came to the “Garmonia” Medical Center (Yekaterinburg, Russia) seeking infertility treatment. The average age of the patients was 32.2±5.0. DNA from vaginal and endometrial samples was extracted using PREP-NA-PLUS kit (DNA-Technology, Russia). Vaginal and endometrial microbiota was analyzed using Femoflor real-time PCR kit and DTprime 4M1 thermocycler (DNA-Technology, Russia). Main results and the role of chance Total bacterial load (TBL) in vaginal discharge was 3.8–7.9 lg (median — 7.1, interquartile range — 6.6–7.4). TBL in the endometrial samples was 0–5.1 lg (median — 3.9, interquartile range — 3.6–4.2). There was no correlation between TBL values in vaginal discharge and endometrial samples (Spearman’s rho — 0.247, p = 0.049). Lactobacilli quantities in vaginal discharge were 4.5–8.3 lg (median — 7.2, interquartile range — 6.4–7.6), in endometrial samples — 0–5.1 lg (median — 3.7, interquartile range — 3.1–4.2). There was a weak positive correlation between lactobacilli quantities in vaginal and endometrial samples (Spearman’s rho — 0.362, p = 0.003). The proportion of lactobacilli in vaginal discharge was 1–100% (median — 100%, interquartile range — 95–100%), in the endometrial samples — 0–100% (median — 96%, interquartile range — 25–100%). There was no correlation between lactobacilli proportions in vaginal and endometrial samples (Spearman’s rho — 0.225, p = 0.074). Furthermore, there was no correlation between lactobacilli quantity in the vagina and their proportion in the endometrial microbiota (Spearman’s rho — 0.294, p = 0.018). There was only a weak positive correlation between the quantities of lactobacilli in vaginal and endometrial samples. Vaginal TBL values and lactobacilli proportions did not correlate with lactobacilli quantities and proportions in the endometrial samples. Limitations, reasons for caution The study was conducted on a small sample. Moreover, it is notoriously difficult to interpret the analysis results for endometrial microbiota due to the high risk of contamination and its low microbial biomass. Wider implications of the findxings: Apparently, there is no obvious link between the vaginal and endometrial microbiomes. It is possible that, apart from vaginal microbiota, there are other predictors which could allow us to assume whether lactobacilli are present in the endometrial microbiota. Trial registration number Not applicable

Study question Could vaginal and endometrial microbiome by sequencing 16S rRNA be comparable to classic diagnostic methods or immunohistochemistry CD138 for diagnosis of chronic endometritis? Summary answer A characteristic endometrial and vaginal microbiome is present in patients with chronic endometritis. An abnormal vaginal microbiome correlates with the presence of chronic endometritis. What is known already Chronic endometritis is a disease characterized by persistent inflammation of the endometrial lining. Currently, histopathological evaluation by immunohistochemistry CD138 marker is most common diagnostic method for CE. Microbiome analysis based on subunit 16S rRNA sequencing is a fast tool that can enable the identification of pathogenic microorganisms associated with CE. The main bacteria at vaginal and endometrial level belong to genus Lactobacillus, producers of lactic acid that allows maintaining acidic pH of vagina and acts as barrier against pathogens. Investigations on the effect of an abnormal endometrial and vaginal microbiome could improve assisted reproductive technologies. Study design, size, duration This is a observational pilot study (60 patients and 120 samples). The study population consists of patients attending to our fertility clinic for frozen euploid embryo transfer (FET) from May 2017 to May 2019. Preimplantation Genetic Testing of aneuploidy (PGT-A) was performed at blastocyst stage using Veriseq (Illumina). The inclusion criteria to be meet by patients were: age between 18 and 50 years, own or donated oocytes and use of ICSI. Participants/materials, setting, methods Cohort study with sixty patients undergoing assisted reproductive treatment (TRA) with their own or donated gametes and PGT-A Vaginal and endometrial samples were taken in the cycle prior to embryo transfer. The vaginal and endometrial microbiome was analyzed by mass sequencing of the V3V4 region of 16S rRNA. Bioinformatics analysis was performed using QIIME2 and MicrobiomeAnalyst packages. Alpha, beta diversity and taxonomic characterization were compared with positive and negative CD138 groups for chronic endometritis (CE). Main results and the role of chance Different bacterial communities were detected when vaginal and endometrial samples were analyzed in patients with and without endometritis diagnosed with CD138 immunohistochemistry. In patients with endometritis, a higher alpha diversity index tendency was found in vaginal samples (p = 0.15 for the Shannon index) and significant differences in endometrial samples (p = 0.01 for the Shannon index). In the beta diversity analysis, no significant differences were observed between the groups established as per the diagnosis of endometritis. Vaginal and endometrial samples from women with endometritis showed a microbiome pattern not dominated by Lactobacillus spp. Relative abundance analysis identified the genera Ralstonia and Gardnerella in endometrial sample, and the genera Streptoccoccus and Ureaplasma in vaginal sample of patients diagnosed with CD138 for endometritis. Comparing endometrial and vaginal samples CD138 positive diagnosed for endometritis, alpha diversity (p = 0.06 for the Shannon index and p = 0.08 for the Simpson index) and beta diversity (p < 0.001) showed significant differences. Relative abundance identified the genera Lactobacillus (p = 3.76E-4), Ralstonia (p = 8.19E-4), Delftia (p = 0.004) and Anaerobacillus (p = 0.004) in these sample groups. Limitations, reasons for caution The main limitation of this study is the small sample size. Larger studies including a higher number of samples are needed to confirm the different microbiome pattern observed at the vaginal and endometrial levels in correlation with chronic endometritis. The microbiome pattern has not been analyzed after treatment of CE. Wider implications of the findings Our findings suggest the existence of a characteristic vaginal and endometrial microbiota in patients with chronic endometritis. Different genera and species were identified in patients with and without endometritis depending on whether the sample was endometrial or vaginal. An abnormal vaginal microbiome appears to be strongly correlated with chronic endometritis. Trial registration number Not Applicable

Characterization of the vaginal and endometrial microbiome in patients with chronic endometritis

Introduction/BackgroundHuman papillomavirus (HPV) is well established as the main cause of cervical cancer. Non-invasive self-collected urine and vaginal sampling have the potential advantage of increasing patient compliance with cervical cancer...

Study question Can vaginal microbiome analysis predict endometrial microbiome status in IVF patients? Summary answer Only 38% of paired vaginal and endometrial samples showed correlation, indicating that vaginal microbiome analysis cannot accurately predict endometrial microbiome status. What is known already A healthy vaginal microbiome is predominantly composed by Lactobacillus species and low presence of other bacteria, since Lactobacillus has specific properties (production of lactic acid and bacteriocins) that allow to create a protective environment and prevent colonization by pathogens or the overgrowth of opportunistic bacteria. In recent years, specific endometrial microbiome has also been described. As in vagina, it should be predominantly composed by Lactobacillus to ensure a balanced environment (eubiosis). Certain studies have correlated predominance of Lactobacillus species and the absence of pathogens, to higher rates of reproductive success including increased pregnancy rates and reduced implantation failure and miscarriage. Study design, size, duration This retrospective study analyzed 58 paired endometrial and vaginal sample from 58 patients (average age: 38.8 ± 5.1 years) with a clinical history of implantation failure and/or miscarriage. Microbiome analysis was conducted from March 2022 to November 2024. Participants/materials, setting, methods Each patient underwent endometrial biopsy and vaginal swab procedures on the same day. DNA was extracted from both samples, and bacterial and fungal species were identified using Real-Time qPCR. The ratio of Lactobacillus species, opportunistic bacteria and pathogens (strict and facultative), was calculated. Main results and the role of chance In endometrial samples, 38% were eubiotic (>90% Lactobacillus), compared to 53% in vaginal samples. Comparing paired samples, 67% showed concordance in eubiosis or dysbiosis profiles, while 33% did not. No Pathogens were detected in eubiotic endometrial samples, whereas 22% of dysbiotic samples were pathogenic. In vaginal samples, pathogens were detected in 31% of eubiotic and 34% of dysbiotic samples. Pathogen presence was significantly higher in vaginal than endometrial samples (65% vs 22%, p < 0.0001). Concordance for pathogen presence between vaginal and endometrial samples s was 50% with 45% of the samples showing pathogens in the vagina but not in the endometrium). Among the samples where pathogens were present at both sites, 7 out of 11 showed concordance (at least one matching pathogen). Overall, considering Lactobacillus dominance and pathogen presence, vaginal and endometrial microbiomes correlated in only 38% (22/58) of samples. Limitations, reasons for caution The limited sample size requires, further studies to confirm these findings. Wider implications of the findings This study shows that although there is some concordance in the results of endometrial and vaginal analysis, it is limited. Analyzing both samples could offer a more comprehensive understanding of the overall condition of the reproductive tract, facilitating personalized treatments and potentially enhancing IVF outcomes for patients experiencing implantation failure. Trial registration number No

BackgroundTo reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women’s acceptance of urine collection and preferences towards the different sampling procedures.MethodsOne hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference.ResultsWith the COBAS assay, urine showed good concordance to the vaginal (k = 0.66) self-samples and cervical samples (k = 0.66) for hrHPV detection. The corresponding concordance was moderate (k = 0.59 and k = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure.ConclusionsUrine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.

ObjectivesHuman papillomavirus (HPV) testing in cervical screening offers the potential for self-sampling to improve uptake among non-attenders. High-risk (HR) HPV detection in urine shows promise, but few studies have examined...

To assess the diagnostic accuracy of self-collected urine and vaginal samples for the identification of precancerous cervical lesions in the referral population using high-risk human papillomavirus (hrHPV) assays based on polymerase chain reaction (PCR). It was a prospective study carried out in China from June 2021 to March 2022. The vaginal and urine samples were collected and analyzed by using a newly developed specific hrHPV PCR test, and matched cervical samples were analyzed by using an approved hrHPV DNA test. The primary outcomes were sensitivity for cervical intraepithelial neoplasia 2 or greater (CIN2 +). The secondary outcome was the accuracy of hrHPV findings in urine and vaginal samples compared to cervical samples. A total of 1,701 women were recruited with 113 women excluded. Among 1,588 qualified participants, a total of 203 cases of the CIN2 + group were enrolled in the two centers. The sensitivity and specificity of HPV detection for CIN2 + in urine, vaginal and cervical samples were 86.70% and 36.46%, 90.64% and 30.54%, 93.60% and 26.14%, respectively. The urine sample performed lower sensitivity (p = 0.003) and higher specificity (p < 0.001) than the cervical sample. There was no difference in sensitivity between vaginal and cervical samples (p = 0.146), and the specificity of vaginal samples was higher than that in cervical samples (p < 0.001). The agreement was 78.15% of urine and cervical samples and 85.71% of vaginal and cervical samples. HPV testing on self-collected urine and vaginal samples has acceptable consistency compared with traditional cervical samples. It may be an alternative option for cervical cancer screening. Additional studies are still required to substantiate this issue.

Comparison of urine, self-collected vaginal swab, and cervical swab samples for detecting human papillomavirus (HPV) with Roche Cobas HPV, Anyplex II HPV, and RealTime HR-S HPV assay

The aim of this study was to determine the concentrations of and factors associated with decidual insulin-like growth factor-binding protein-1 (IGFBP-1) in the lower genital tract in early- and mid-gestation in singleton pregnancies. Prospective population-based cohort study. Maternity Clinic, Department of Obstetrics and Gynaecology, University Central Hospital, Helsinki, Finland. A total of 1702 unselected pregnant women undergoing the first- and the second-trimester ultrasound screening between April 2005 and December 2006. The vaginal and cervical swab samples for assay of decidual IGFBP-1 and vaginal pH measurement were taken before transvaginal ultrasonography in the first trimester and in the mid-second trimester. Use of antibiotics, history of vaginal bleeding, and the history of sexual intercourse were questioned on both occasions. The concentration of IGFBP-1 was measured by a quantitative immunoenzymometric assay, which detects the decidual phosphoisoforms of IGFBP-1 (phIGFBP-1). The concentration of 10 micrograms/l was used as a cutoff when factors influencing phIGFBP-1 levels were analysed. The phIGFBP-1 concentrations in the vagina and the cervix and associations between the levels of > or =10 micrograms/l and selected factors. In the first trimester, the median (range) concentrations of phIGFBP-1 in vaginal and cervical samples were <0.3 micrograms/l (<0.3-176 micrograms/l) and 4.8 micrograms/l (<0.3-174 micrograms/l), respectively. During the second trimester, the corresponding values were <0.3 micrograms/l (<0.3-55 micrograms/l) in the vagina and 3.6 micrograms/l (<0.3-126 micrograms/l) in the cervix. In the vaginal samples, the frequency of phIGFBP-1 concentrations > or =10 micrograms/l was 5.8% in the first trimester and 1.5% in the second trimester (P < 0.001). In the cervical samples, the corresponding rates were 34.3 and 28.4%, respectively (P < 0.001). Of the factors studied, nulliparity (P < 0.001) and history of vaginal bleeding (P < 0.001) were independently associated with cervical phIGFBP-1 concentrations > or =10 micrograms/l during both trimesters. In addition, short cervical length (<30 mm) was associated with phIGFBP-1 concentration > or =10 micrograms/l in both vaginal and cervical samples in the second trimester in multivariate analysis. The rate of phIGFBP-1 concentrations > or =10 micrograms/l, both in the vagina and in the cervix, was significantly lower during the second trimester compared with the first trimester. The low rate of levels > or =10 micrograms/l in vaginal samples compared with cervical samples during both trimesters indicates that the exact site of sampling is important when phIGFBP-1 is used as a decidual marker. Nulliparity and history of vaginal bleeding were independently associated with phIGFBP-1 concentrations > or =10 micrograms/l in cervical samples during both trimesters.

Is there any change in the distribution of microvilli and microtubules in the apical endometria of women with adenomyosis? We observed microvilli damage in the apical endometria and an axonemal alteration characterized by abnormal distribution of longitudinal bundles of microtubules within microvilli in women with adenomyosis. Human adenomyosis has a negative impact on female fertility. Abnormal utero-tubal sperm transport, tissue inflammation and toxic effect of chemical mediators have been proposed as contributing factors. Inflammation-induced damage of mucosal cilia in the Fallopian tube has been reported. However, information on inflammation-induced damage of microvilli on the apical endometrial cells and its core bundles of microtubules in adenomyosis remains unknown. This is a prospective cohort study with subjects undergoing laparoscopic surgery or hysterectomy for clinical indication and evaluations of endometrial biopsy samples in two academic university hospitals. During the period between March 2015 and December 2018, endometrial biopsy samples were prospectively collected from 15 control women and 45 women with adenomyosis for immunohistochemical analysis and a separate cohort of 10 control women with cervical intraepithelial neoplasia Grade 3 (CIN3) and 20 women with adenomyosis for analysis by immunohistochemistry and transmission electron microscopy (TEM). For immunohistochemical study, endometrial biopsy samples were prospectively collected from 15 control women with fibroids, 25 women with focal adenomyosis and 20 women with diffuse adenomyosis after surgery. The diagnosis of fibroid and adenomyosis was made clinically by transvaginal ultrasonography and magnetic resonance imaging and confirmed by histology. Immunohistochemical analysis was performed retrospectively using antibody against CD68 (marker of macrophages) in endometrial biopsy specimens of women with and without adenomyosis. TEM was performed with the apical endometria collected from a separate cohort of 10 control women with CIN3 and 20 women with focal and diffuse adenomyosis for the identification of any change in the distribution of microvilli and longitudinal bundles of microtubules within microvilli. Comparing to control endometria and contralateral side, tissue infiltration of macrophages (Mφ) in the endometria was significantly higher on the ipsilateral side of focal adenomyosis (P = 0.02 and P = 0.03, respectively) and anterior/posterior walls of diffuse adenomyosis (P = 0.01 for both). In a subgroup analysis of patients with focal adenomyosis with and without symptoms, the endometria of symptomatic women displayed a tendency of higher Mφ infiltration on the ipsilateral side than in asymptomatic women (P = 0.07). Comparing to contralateral side endometria of symptomatic women, Mφ infiltration was significantly higher in the endometria of symptomatic women collected from the ipsilateral side of focal adenomyosis (P = 0.03). We found a significantly less tissue infiltration of Mφ in the endometria of women with CIN3 than that in endometria of women with focal adenomyosis. TEM analysis showed that number of microvilli in the endometria was significantly decreased on the ipsilateral side (P = 0.003) comparing to that on the contralateral side of focal adenomyosis. The Chi-squared test indicated that cases with abnormal (disruption in the normal arrangement of 9 peripheral pairs + 1 central pair) microtubules (MT) were significantly higher in women with adenomyosis than in cases with normal patterns (P = 0.0016). While contralateral side displayed significantly less abnormal MT (P = 0.0002), ipsilateral side of focal adenomyosis showed significantly higher abnormal MT (P = 0.0164) comparing to normal patterns. Cases with symptomatic adenomyosis showed significantly higher abnormal MT than normal MT (P = 0.0004). An axonemal alteration characterized by abnormal structural distribution of microtubules within microvilli in the apical endometria in response to endometrial inflammation may be involved in adverse reproductive outcome in women with adenomyosis. The average age of women in this study was high that may be associated with overall decline in fertility regardless of the presence or absence of adenomyosis or endometriosis. We collected endometrial biopsy samples from two completely separate cohorts of women for analysis by immunohiostochemistry and TEM. We need future follow-up study with increased sample size and from the same patients to precisely clarify the mechanistic link between axonemal alteration and negative fertility outcome. Our current findings may have some biological implication to better understand the endometrial epithelial biology and pathology in women with adenomyosis and may open the avenue for future study in other reproductive diseases. The ultra-structural abnormalities of microvilli and microtubules in the apical endometria in response to tissue inflammatory reaction may clarify the possible association between negative fertility outcome and adenomyosis. Our findings may be clinically useful during counseling with symptomatic patients with adenomyosis desiring pregnancy. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study. N/A.

Cervical ripening during pregnancy resembles an inflammatory process. Matrix metalloproteinases (MMPs), particularly MMP-8, have been linked to inflammatory processes. We studied the concentrations of, and factors associated with, MMP-8 in the lower genital tract fluids in the first and second trimesters. In a prospective population-based cohort study, vaginal and cervical swab samples were obtained from 2130 unselected pregnant women undergoing their first and second trimester ultrasound screening. MMP-8 was determined by immunofluorometric assay. Use of antibiotics, history of vaginal bleeding, and history of sexual intercourse were recorded on both occasions. Vaginal smears were obtained for Gram-staining and leukocyte counting. Cervical length was measured by ultrasonography. The main outcome measures were MMP-8 concentrations in the vagina and cervix. The median (range) MMP-8 concentrations in vaginal and cervical samples were 107.4 microg/l (undetectable-2406.6 microg/l) and 318.3 microg/l (0.1-2074.6 microg/l), respectively, in the first trimester, and 112.5 microg/l (undetectable-2093.4 microg/l) and 344.8 microg/l (0.4-1783.5 microg/l), respectively, in the second trimester. Multiparity and vaginal leukocytosis were both associated with increased MMP-8 concentrations in vaginal and cervical samples in both trimesters. Bacterial vaginosis (BV) was associated with increased vaginal and cervical MMP-8 in the first trimester, but only with increased vaginal MMP-8 in the second trimester. A history of sexual intercourse (in the previous 48 h) was associated with lower MMP-8 concentrations in cervical samples in both trimesters. MMP-8 concentrations were lower in vaginal samples than in cervical samples, and no difference was found between the first and second trimesters. Multiparity, BV and an elevated leukocyte count in the vagina were associated with increased MMP-8 concentrations. Sexual intercourse had an opposite effect. The study suggests that MMP-8 is a physiologic constituent in lower genital tract fluids, where it may be involved in host response to inflammatory and infectious processes.

Vaginal microbiome changes with levonorgestrel intrauterine system placement