Cervical Secretions Research Articles

Helping Patients to Predict and Confirm Ovulation with the Use of Combined Urinary Hormonal and Smartphone Technology: A Proof-of-Concept Retrospective Descriptive Case Series.

Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment (n = 95) or family planning advice (n = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing (n = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation.

Early menstrual cycle impacts of oestrogen and progesterone on the timing of the fertile window.

What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. Oestrogen enhances cervical mucus secretion while progesterone inhibits it. Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva. Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle. This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings. This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction. The authors declare no conflicts of interest. No funding was provided for this secondary data analysis. N/A.

O-028 DNA methylation testing with cervical secretion can serve as a non-invasive biomarker for predicting successful implantation in frozen-thawed embryo transfer

Abstract Study question Is cervical secretion gene methylation profile associated with embryo implantation outcome, and can be used as a non-invasive biomarker for pregnancy prediction in FET cycles? Summary answer Cervical secretion gene methylation profiles show significant associations with implantation outcomes, and can serve as a non-invasive predictor of successful pregnancy in FET cycles. What is known already Cause of implantation failure remains a black box in reproductive medicine, and the exact mechanism of how endometrial receptivity is still behind the curtain. Epigenetic modifications including DNA methylation regulate gene expression and may alter endometrium receptivity. Endometrial DNA methylation changes vigorously only during the reconstruction of a new endometrium throughout each menstrual cycle, suggesting a unique methylation landscape in each regenerated endometrium. Cervical secretions contain implantation-related cytokines and genetic material from endometrium, and the DNA methylation profiles of cervical secretions is highly correlated with endometrium. Therefore, cervical secretions can be used as non-invasive surrogates for investigating endometrial condition. Study design, size, duration This multi-centered, case-control study enrolled 72 infertile females who entered the FET cycle with at least one high-quality blastocyst available between Aug 2017 and Dec 2022. Embryos assessed by Gardner scoring system with grade 3BB or above were defined as high-quality. Cervical secretions were collected on the day right before embryo transfer, and then DNA methylation profile were assessed. Participants/materials, setting, methods These females aged between 20-45 years-old with regular menstruation cycle (24-35 days) and normal BMI (17.5–32.0 kg/m2). Uterine cavity lesions and hydrosalpinx without treatment, adenomyosis, large uterine myoma that distorted endometrium, and thin endometrium (<7mm) were excluded. The association between the cervical secretion gene methylation profile and pregnancy outcome was evaluated via quantitative methylation-specific PCR (qMSP), methylation array, and genome-wide analysis. Different machine learning algorithms were utilized for differential methylation analysis and implantation prediction. Main results and the role of chance Cervical secretion DNA methylome differed between receptive (pregnant) and non-receptive (non-pregnant) FET cycle with genome-wide methylation array. The accuracy of pregnancy outcome prediction using top 2000 differential methylation probes (DMPs) in promoter region can be as high as 86% in all tested sample and 96.4% in pregnant samples. Bioinformatic analysis of six selected candidate genes related to implantation from literature review showed significant differences in DNA methylation between receptive and non-receptive endometrium. The methylation level of the six candidate genes with eight regions were measured by the qMSP platform and showed varying degrees of differential methylation status between the pregnancy and non-pregnancy groups. The AUCs for a single gene/region ranged from 0.53–0.67 for implantation prediction. Ten different machine learning models were applied and the results showed that the combination of candidate genes’ DNA methylation profiles could differentiate pregnant from non-pregnant samples with an accuracy as high as 86.67% and an AUC of 0.81 by logistic regression model. The best model from different machine learning algorithms using selected DMPs of genes related to window of implantation (WOI) can predict ongoing pregnancy with accuracy rates as high as 86.78% and AUC values up to 0.91. Limitations, reasons for caution The results obtained from a relatively small cohort size, and the timing of sample collection is on the day right before embryo transfer. Further investigation of methylation profiles in late follicular phase along with large sample size with euploid embryo transfer are mandatory for validation and clinical applications. Wider implications of the findings We firstly demonstrated the feasibility of cervical secretion methylation profile as a non-invasive testing for pregnancy prediction. The promising result may contribute to predicting endometrial receptivity for cycles with a favorable endometrium and maximize the successful pregnancy rate of embryo transfer. Trial registration number not applicable

Analysis of Reproductive Tract Microecological Changes During the Frozen-Thawed Embryo Transfer Cycle and Clinical Pregnancy Outcomes

This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy, which will be a breakthrough point for improving outcomes. A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study. Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation, day 7 after estrogen replacement therapy started, the day when progesterone was added, and the day of transplantation. The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods. 1) The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation (P<0.01), but did not differ significantly on day 7 after oral estrogen replacement therapy started, the day of progesterone administration, and the day of transplantation (P≥0.1). 2) Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points. 3) Microbial analysis at different time points showed that there were significant differences in vaginal flora, including Peptoniphilus, Enterocloster, Finegoldia, Klebsiella, Anaerobutyricum, Agathobaculum, Sporanaerobacter, Bilophila, Prevotella, and Anaerococcus in the pregnant group (P<0.05). 4) Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid, linatine, (R)-amphetamine, hydroxychloroquine, and L-altarate in the vaginal secretions of the pregnant group (P<0.05), and that there were significant differences in isocitric acid, quassin, citrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 5) Metabolite analysis at different time points showed that, in the non-pregnant group, there were significant differences in linatine, decanoyl-L-carnitine, aspartame, sphingosine, and hydroxychloroquine in the vaginal secretions (P<0.05), and the isocitric acid, quassin, ctrinin, and 12(R)-HETE in the cervical secretions (P<0.05). 6) Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities, especially Klebsiella. Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy, which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.

Isolation and Identification of Morganella morganii from Rhesus Monkey (Macaca mulatta) in China

A bacterium was isolated and identified from the secretion of a rhesus monkey with endometritis. The morphological results showed that the strain exhibited round, convex, gray-white colonies with smooth surfaces and diameters ranging from 1 to 2 mm when cultured on Columbia blood agar at 37 °C for 24 h; on salmonella–shigella agar (S.S.) at 37 °C for 24 h, the colonies appeared round, flat, and translucent. Gram staining showed negative results with blunt ends and non-spore-forming characteristics. Molecular biology results showed that the 16S rRNA sequence of the strain revealed over 96.9% similarity with published sequences of M. morganii from different sources in the NCBI GenBank database. Morphological and molecular biology analysis confirmed that the strain (RM2023) isolated from cervical secretions of rhesus monkey was M. morganii. Drug sensitivity testing demonstrated that the isolated strain (RM2023) was sensitive to ceftriaxone, amikacin, gentamicin, cefazolin, cefuroxime, ceftazidime, levofloxacin, cotrimoxazole, norfloxacin, and tetracycline; moderately sensitive to ampicillin; and resistant to penicillin, vancomycin, ciprofloxacin, and clindamycin. The research findings provide valuable insights for disease prevention in rhesus monkeys and contribute to molecular epidemiological studies.

Performance verification and clinical evaluation of the NAP-Fluo Cycler system for detecting five genital tract pathogens based on microfluidic technology

IntroductionSexually transmitted infections (STIs) are among the most common infectious diseases worldwide, often leading to coinfections. Timely detection of genital tract pathogens in at-risk populations is crucial for preventing STIs. We evaluated the NAP-Fluo Cycler System, an innovative microfluidic nucleic acid detection platform, for its ability to simultaneously identify Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), and Mycoplasma hominis (MH) in urethral or cervical secretions. Materials and methodsThe limits of detection (LODs), repeatability, specificity, and interference resistance of the system were evaluated using standard strains, a panel of 24 pathogens, and seven interferents. We used the system to analyze 302 clinical samples and compared the results with those of five approved commercial reference kits. ResultsThe system achieved LODs of 500 IFU/mL, 500 CFU/mL, and 500 CCU/mL for CT, NG, and UU/MG/MH, respectively, demonstrating high stability (coefficient of variation <1.1 %), specificity, and resistance to interference. Among 302 clinical samples, 237 tested positive with single, dual, and triple infection rates of 35.6 %, 16.2 %, and 3.0 %, respectively. The reference kits detected 138 positive samples. The concordance rates with commercial reference kits were 100 % for UU, NG, and MH; 94.85 % for CT; and 80.00 % for MG. ConclusionsThis system offers a streamlined, rapid, and multiplex detection method that reduces testing time and complexity. Although it performs well with pure strains, it has limitations when using clinical samples of CT and MG, suggesting the need for further refinement before its widespread use in the clinic.

Effect of Ureaplasma/Mycoplasma genital tract infection on preterm labor.

Genitourinary tract infections in pregnant women are one of the causes of abnormal pregnancy development including miscarriages, premature labor or premature rupture of membranes (PPROM). Atypical bacteria responsible for reproductive tract infections include Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum. Identification of pathogens and appropriately selected therapy can improve obstetric outcomes in patients with symptoms of threatened miscarriage or threatened preterm labor. The purpose of our study is to analyze the impact of reproductive tract infections with ureaplasma and mycoplasma bacteria during pregnancy. In the presented study, we retrospectively analyzed the cases of 201 pregnant patients hospitalized in the Obstetrics and Gynecology Department of Poznan Regional Hospital in 2019-2022, who had a swab taken from external os area of the cervix for atypical bacteria - Ureaplasma and Mycoplasma. Only patients with symptoms of threatened miscarriage or threatened preterm labor were included in the study group. Microbiological tests were performed in the hospital laboratory with the Mycoplasma IST 3 test from Biomerieux. We found a higher incidence of preterm labor in patients with symptoms of threatened preterm labor and a genital tract infection with Ureaplasma/Mycoplasma bacteria, compared to patients not infected with Mycoplasma/Ureaplasma - 31.1% vs 20% (p = 0.098). This observation in the case of Ureaplasma/Mycoplasma monoinfection group applied to 6 patients. - 75% of the group. Pregnant patients who had co-infection with other types of bacteria (48 patients in total) gave birth before 37 weeks of pregnancy in 27.1% of cases. We obtained a significant difference (p = 0.007) when comparing groups with positive and negative cultures for Ureaplasma/Mycoplasma by the presence of monoinfection/coinfection and the week of pregnancy in which delivery occurred. We also noted the effect of atypical bacterial infection for PPROM - this complication preceded preterm delivery in 40% of ureaplasma-positive patients, compared to 20% of PPROM without infection. We found a similar rate of preterm labor and pregnancy loss in Ureaplasma/Mycoplasma-positive patients who received antibiotic therapy (35.7%) compared to a group of pregnant women who did not receive treatment (31.6%). Infection of the genital tract with atypical bacteria Ureaplasma and Mycoplasma has a negative impact on the course of pregnancy. Identification of the type of microorganisms in cervical canal secretions of pregnant patients with symptoms of threatened miscarriage or preterm labor seems crucial. The impact of antibiotic therapy though, requires further analysis.

A randomized, double-blind, positive-controlled, Phase-II clinical trial to evaluate efficacy and safety of Fuke Qianjin capsule in Pakistani patients with pelvic inflammatory disease.

Ethnopharmacological relevance: Pelvic inflammatory disease (PID) is a frequently occurring gynecological disorder mainly caused by the inflammation of a woman's upper genital tract. Generally, antibiotics are used for treating PID, but prolonged use poses potential risks of gut bacterial imbalance, bacterial resistance, super bacteria production, and associated adverse reactions. Traditional Chinese medicine (TCM) has shown unique advantages in various ailments and has received widespread clinical research attention. Fuke Qianjin (FUKE) capsule is an approved National Medical Products Administration (NMPA License No. Z20020024) Chinese herbal prescription that has been widely used individually or in combination with other Western medicines for the treatment of various gynecological inflammatory diseases, including chronic cervicitis, endometritis, and chronic PID. Aim: This clinical trial was designed to assess the safety and efficacy of FUKE capsule in mild-to-moderate symptomatic PID patients. Materials and methods: This phase 2, randomized, double-blind, positive controlled clinical trial was conducted in mild-to-moderate symptomatic PID patients at a single center in Pakistan from 21 September 2021 to 11 March 2022. Eligible female participants were randomly assigned to a test and a control group with a ratio of 1:1. The test group subjects received two metronidazole (METRO) tablets and one doxycycline hyclate (DOXY) simulant at a time, twice daily for 14 days, and two Fuke Qianjin (FUKE) capsules, three times a day after a meal for 28 days. Subjects in the control group received two METRO tablets and one DOXY tablet at a time, twice daily for 14 days, and two FUKE simulant capsules, three times a day after meal for 28 days. The primary efficacy outcome was an improvement in pelvic pain symptoms assessed through a visual analog scale (VAS). The secondary outcomes were the improvement in secondary efficacy symptoms like local physical signs, clinical assessment of leucorrhea and cervical secretions through laboratory examination, and improvement in the maximum area of pelvic effusion assessed through gynecological ultrasound after the treatment. The safety outcomes were assessed through vital signs, laboratory tests, electrocardiogram findings, and adverse events/serious adverse events. Results: A total of 198 subjects with active PID were randomly assigned to a test group (n = 99) and a control group (n = 99). The baseline characteristics of the subjects in the two groups were similar. In the intention-to-treat analysis, the primary efficacy was 84.9% for the test group and 71.6% for the control group, with a statistically significant difference (p = 0.0370; 95% CI -0.2568 to -0.0088). The secondary clinical efficacy was 88.4% for the test group and 82.7% for the control group, with no significant difference (p = 0.2977; 95% CI -0.1632 to 0.0501). The improvement in local physical signs was 95.8% for the test group and 76.9% for the control group, with no significant difference (p = 0.0542; 95% CI -0.3697 to -0.0085). The inter-group non-inferiority comparison showed that the upper limit of the 95% CI was less than 0.15 and thus met the non-inferiority requirements of the test group to the control group. The results of clinical signs of leucorrhea and cervical secretions showed that there was no difference in the rate of improvement between the test and control groups, indicating that FUKE was non-inferior to DOXY. A total of 14 adverse events in eight subjects were observed in the trial, with an incidence rate of 4.7%. Four subjects in each group experienced seven adverse events with 4.5% and 4.8% incidence rates of adverse reactions in the test and control groups, with no statistically significant differences (p = 0.2001). No serious adverse events occurred in the trial. Conclusion: The results of this trial indicate that the test drug (Fuke Qianjin capsule) is non-inferior to the control drug (doxycycline hyclate tablet) in treating mild-to-moderate PID patients with comparable efficacy, safety, and tolerability to the control drug. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT04723069.

Clinical and Demographic Factors Associated With Kaposi Sarcoma-Associated Herpesvirus Shedding in Saliva or Cervical Secretions in a Cohort of Tanzanian Women.

Reasons for the high prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P = .009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6.

Overcoming poor ovarian response in assisted reproductive technology programs in patients of late reproductive age

Objective: to increase the effectiveness of in vitro fertilization in patients of late reproductive age by optimizing prepregnancy preparation for the IVF program.Materials and methods: The study included 67 patients of late reproductive age with a history of unsuccessful IVF attempts, divided into two groups at the second stage of the study, depending on the volume of prepregnancy preparation: group 1 (33 patients), group 2 (34 patients). The control group (50 patients) were healthy women of reproductive age. Immunohistochemical examination of the endometrium and microbiological examination of the uterine cavity, hormonal status of peripheral blood, study of the concentration of melatonin in peripheral blood and follicular fluid, antioxidant status of follicular fluid, expression of leukemia inhibitory factor (LIF) in the cervical secretion were performed.Results: in patients with age-related dysregulation of the hypothalamic-pituitary-ovarian axis and impaired fertile function, a systemic and local (in follicles) decrease in melatonin levels was revealed. The studied effects of melatonin suggested that its use in patients of late reproductive age with reduced follicular reserve and a "poor" response to ovarian stimulation may increase the effectiveness of in vitro fertilization (IVF).Conclusions: The inclusion in the pre-gravidar preparation of a complex of water-soluble polypeptide fractions of the epiphysis, stimulating the production of endogenous melatonin, made it possible to increase the effectiveness of IVF in patients by an average of 3.1 times according to the criterion of "clinical pregnancy" and 4.1 times according to the criterion of "live birth".

Association Between Cervical Inflammatory Mediators and Prevalent Cervical Human Papillomavirus Infection.

Inflammatory mediators are important regulators of immune response and can modulate the inflammation caused by viral infections, including human papillomavirus (HPV). In this study, we evaluated the association between cervical immune mediators, including chemokines, cytokines, and growth factors with HPV infections. We used a nonmagnetic bead-based multiplex assay to determine 27 immune mediators in cervical secretions collected from 275 women in a prospective longitudinal cohort design. All the study participants were age 18 years or older, had a history of vaginal sexual intercourse, were not currently pregnant, and had no history of cervical disease or hysterectomy. The mean (±standard deviation) age of the participants was 41 (±8) years, and about half (51% [141/275]) were HPV-positive, of whom 7% (10/141) had low-risk HPV (lrHPV), 61% (86/141) had high-risk HPV (hrHPV), and 32% (45/141) had both lrHPV and hrHPV infections. Higher concentrations of some immune mediators were associated with HPV infections, including eotaxin, interferon-gamma, interleukin (IL)-1β, IL-2, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated upon activation normal T-cell expressed and secreted (RANTES), and tumor necrosis factor (TNF)-α and any HPV; IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70, and IL-13 and lrHPV; and eotaxin, interferon, IL-1B, IL-4, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1α, MIP-1β, RANTES, TNF-α concentrations, and hrHPV infections. Higher concentrations of granulocyte macrophage colony-stimulating factor, IL-1 receptor antagonist (IL-1Ra), and monocyte chemotactic protein-1 (MCP-1) were associated with reduced odds of any HPV, while IL-1Ra and MCP-1 were associated with reduced odds of hrHPV infections. Several chemokines, cytokines, and growth factors are associated with group-specific HPV infections in this population of women. These important findings contribute to the understanding of the immune response to HPV, cytokine profiles and their potential implications for cervical pathogenesis, and can guide future research in this field.

Safety testing of Ovaprene: An investigational nonhormonal monthly vaginal contraceptive

ObjectiveEvaluate safety of Ovaprene, an investigational non-hormonal vaginal contraceptive designed for monthly use. Study designOpen-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment emergent adverse events (TEAEs), systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids. ResultsWe enrolled 38 participants. Of these, 33 used Ovaprene and completed 77 Ovaprene cycles. The most common product-related urogenital TEAEs were bacterial vaginosis (BV) and vaginal odor. The frequency of transitioning from Lactobacillus-dominated community state type to community state type IV (not Lactobacillus-dominated) was similar before Ovaprene use and afterwards. Mean Nugent scores were <4 at each visit without a discernable upward trend. Inflammatory markers showed wide variation but no upward trend, and E. coli inhibitory activity of cervical secretions did not change. We found no Staphylococcus aureus, the causative agent in Toxic Shock Syndrome, on used Ovaprenes or in vaginal samples. No clinically important changes in systemic laboratory findings, pelvic examinations, or colposcopies occurred during Ovaprene use. ConclusionOvaprene use did not result in cervicovaginal irritation or adverse effects on resident vaginal microbiota, and did not impact transitions from a Lactobacillus-dominated community state type to community state type IV. ImplicationsThe finding that use of Ovaprene, an investigational monthly user-controlled nonhormonal vaginal contraceptive, does not appear to result in adverse changes in vaginal health during short term use supports further evaluation of the contraceptive potential of the device.

Feasibility study of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester

Objective: To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester. Methods: A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes. Results: (1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups (P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks (RR=2.521, 95%CI: 1.314-4.838; P=0.002), amniotic infection (RR=2.473, 95%CI: 1.061-5.764; P=0.025), perinatal survival (RR=1.880, 95%CI: 1.104-3.199; P=0.014). Conclusion: Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

Significance of cervical secretion culture in predicting maternal and fetal outcome in pregnant women with premature rupture of membranes: a retrospective cohort study.

Background: To investigate the clinical value of cervical secretion culture in pregnant women with premature rupture of membranes (PROM) in predicting maternal and fetal outcomes. Methods: We retrospectively reviewed clinical records of pregnant women who underwent obstetric examination and delivered in Fujian Maternal and Child Healthcare from December 2013 to December 2016. Pregnant women with a clear diagnosis of PROM, who underwent cervical secretion culture immediately after hospital admission were selected for the study. The primary outcome was the occurrence of chorioamnionitis. The secondary outcome was neonatal admission to the neonatal intensive care unit (NICU). Correlation between maternal and fetal outcomes and the results of the cervical secretion culture was analyzed by one-way analysis and multifactorial analysis, respectively. The predictive efficacy of cervical secretion culture was evaluated using receiver operating characteristic curve (ROC), area under the curve (AUC) and the integrated discrimination improvement (IDI). Results: A total of 7,727 pregnant women with PROM were included in the study. Of them, 1812 had positive cervical secretion cultures (635 positive for mycoplasma infection, 475 for bacterial, 637 for fungal, and 65 for chlamydial infections). Pregnant women with positive mycoplasma and bacterial cultures had higher rates of developing chorioamnionitis compared to women with negative cervical secretion cultures (9%, 12% vs. 1%, respectively). Similarly, positive mycoplasma and bacterial cultures were associated with higher rate of the preterm (before 34 weeks) labor (3%, 3% vs. 1% in women with negative cultures, respectively), and neonatal admission to the NICU (9%, 11% vs. 7%, respectively). After adjusting for various confounding factors, our analysis demonstrated that a positive cervical secretion culture for mycoplasma or bacterial pathogens remained an independent risk factor for chorioamnionitis. Cervical secretion culture outcome was less effective in predicting chorioamnionitis (AUC 0.569) compared to white blood count (WBC) (AUC 0.626) and C-reactive protein (CRP) levels (AUC 0.605). The IDI of the combined predictive model incorporating WBC, CRP, maternal fever and cervical secretion culture results was 0.0029. Conclusion: Positive cervical secretion cultures, especially for mycoplasma and bacteria, are associated with higher incidence of adverse maternal and fetal outcomes. However, the predictive value of this test is poor, and cannot be efficiently used for predicting chorioamnionitis.

DIFFERENCES OF FIBRONECTIN LEVELS IN FIRST TRIMESTER NORMAL PREGNANCY AND MISCARRIAGE

Introduction: Miscarriage is a reflection of the low quality of health in pregnant women. The incidence of miscarriage in the world accounts for 23 million (15%) of the 130 million births per year and up to 80% of miscarriages occur in the first trimester of pregnancy. Miscarriage will affect a woman's social, physical, and psychological. The complexity of the negative impact of miscarriage makes it necessary to pay special attention. Biomarker examination is needed to more accurately identify pregnancies at risk of miscarriage before the appearance of clinical symptoms. The use of fetal fibronectin (fFN) levels have been used as a marker of unexpected labor and as evidence of premature rupture of the fetal membranes. Normally fFN can be detected in cervical and vaginal secretions at &lt;20 weeks gestation. The presence of fFN at &gt;22 weeks gestation indicates disruption of the uteroplacental surface. Therefore, if screening for fibronectin levels using the Enzyme-Linked Immunosorbent Assay (ELISA) test can be carried out in the first trimester of pregnancy, there is a high possibility that miscarriage can be prevented.Method: The type of research is analytical observational research with a cross-sectional research design. The stored samples were examined for fibronectin levels using the ELISA test, which included 21 blood serum samples from normal pregnancy patients in the first trimester and 21 miscarriage samples.Results: The results of the ELISA test produced an average first-trimester normal pregnancy fibronectin level of 118.8 ± 18.4 ng/mL while the miscarriage fibronectin level was 208.2 ± 152.0 ng/mL. Data analysis using the Mann-Whitney test obtained a p-value = 0.138, which means there was no significant difference in fibronectin levels between normal pregnancy in the first trimester and miscarriage.Conclusion: This study concludes that fibronectin levels are not specific biomarkers in detecting miscarriage in the first trimester of pregnancy.

Gambaran Karakteristik Penderita Gonore yang Melakukan Pemeriksaan Pewarnaan Gram di RS PKU Muhammadiyah Yogyakarta

Gonorrhea is a sexually transmitted disease caused by the bacterium Neisseria gonorrhoeae. This bacterium infects the urethra, cervix, anus, and throat, depending on the type of sexual contact involved. This research aimed to provide an overview of the characteristics of respondents suffering from gonorrhea who underwent examination using the Gram staining method at PKU Muhammadiyah Yogyakarta Hospital. This research employed cross-sectional method and was conducted at PKU Muhammadiyah Yogyakarta Hospital, and collected data from 24 samples between May 2022 and May 2023. The results showed that 19 patients (79,2%) tested positive. Among them, the majority of male patients showed positive results, with 18 respondents (75,0%), while only 1 female respondent (4.2%) tested positive. On the other hand, 2 male respondents (8,3%) and 3 female respondents (12,5%) tested negative. Individuals infected with gonorrhea were found to produce anti- gonococcal antibodies in their serum, semen, and cervical secretions. Specific antibody responses to gonococcal antigens were reported in various gonococcal polysaccharides and protein antigens. This research clearly shows that males are more frequently affected by gonorrhea infections. In addition, the Gram staining method provides faster results and employs a straightforward technique, which makes it the preferred choice for diagnosing gonorrhea.

Prevalence and circulant genotypes of Chlamydia trachomatis in university women from cities in the Brazilian Amazon.

Approximately 80% of infected women infected by Chlamydia trachomatis are asymptomatic, although this infection can lead to serious complications in the female reproductive tract. Few data on Chlamydia infection and genotypes are available in Amazonian communities. To describe the prevalence of and associated factors and to identify the genotypes of sexual C. trachomatis infection in female university students in different urban centers (capital and interiors) in the Brazilian state of Pará, in the eastern Amazon region. A cross-sectional study was performed among young women attending public universities in four different urban centers in the eastern Amazon region. They were invited to participate in the studt and cervical secretions were collected for molecular diagnosis of C. trachomatis. We utilized amplification of the ompA gene by nested PCR. Positive samples were genotyped by nucleotide sequencing. Study participants completed a questionnaire on social, epidemiological, and reproductive health variables. A Qui-square and Binominal regression test were used to evaluate the degree of association of these variables with the infection. A total of 686 female students was included in the study. The overall prevalence of C. trachomatis was 11.2% (77/686). The prevalence of this infection was higher in interiors (15.2% vs 9.5%/ p: 0.0443). Female university students who do not have a sexual partner (11.8%/p <0.008), who do not use a condom in their sexual relations (17.8%/p <0.0001) and who reported having suffered a miscarriage (32%/p <0.0001) have high chances of acquiring this sexual infection. The ompA gene was sequenced in only 33 (42.8%) samples, revealing the genotype J was the most frequent (27.2% [9/33]), followed by genotypes D (24.2% [8/33]), and then genotypes F (18.2% [6/33]), E (15.1% [5/33]) K (6.1% [2/33]), Ia (6.1% [2/33]), and G (3.1% [1/33]). The high prevalence of sexual infection by C. trachomatis in the female university students from the interior of the state of Pará, individuals with no fixed sexual partner, those that had had a miscarriage, the students that do not use condoms in their sexual relations. The genotype J of C. trachomatis genotypes was the most frequent. These data are important to help defining the epidemiological effects of chlamydial infections in Amazonian populations.

Analysis of the difference in metabolites and gene expressions between pre-receptive and receptive endometria

To analyze the difference in the gene expression, amino acid and carnitine levels in the cervical secretions between the endometria of pre-receptive and receptive stages, with an aim to provide clues for identifying new molecular markers for endometrial receptivity. Fifty nine infertile women treated at the Department of Reproductive Medicine of Linyi People's Hospital from January 6, 2020 to January 31, 2022 were selected as as the study subjects, which were matched with 3 pairs (6 cases) of infertile women preparing for embryo transfer based on factors such as age, body mass index, and length of infertility. Endometrial tissue samples were collected for gene transcription and expression analysis. Twenty five women who had become pregnant through assisted reproductive technology were selected as the control group, and 28 non-pregnant women receiving ovulation monitoring at the Outpatient Department were enrolled as the case group. Status of endometrial receptivity was determined by ultrasonography. In the former group, endometrial tissues were sampled for sequencing, and GO and KEGG database enrichment analysis of differentially expressed genes was carried out. In the latter group, cervical secretions were collected, and amino acid and carnitine levels were measured by mass spectrometry. Statistical analysis was carried out using rank sum test, t test and chi-square test with SPSS v25.0 software. No difference was found in the clinical data of the patients with regard to age, body mass index, infertility years, AMH, FSH, LH, E2, and type of infertility. Compared with the receptive endometrial tissues, there were 100 significantly up-regulated genes and 191 significantly down-regulated genes in the pre-receptive endometrial tissue, with the most significantly altered ones being HLA-DRB5 and MMP10. The biological processes, molecular functions and pathways enriched by more differentially expressed genes in GO and KEGG were mainly immune regulation, cell adhesion and tryptophan metabolism. Analysis of secretion metabolism also revealed a significant difference in the levels of amino acids and carnitine metabolites between the two groups (P < 0.05), in particular those of Alanine, Valine, 3-hydroxybutyrylcarnitine (C4OH) + malonylcarnitine (C3DC)/captoylcarnitine (C10). A significant difference has been discovered in the levels of gene transcription and protein expression in the endometrial tissues from the pre-receptive and receptive stages. The levels of amino acids and carnitine, such as Alanine, Valine, 3-hydroxybutyryl carnitine (C4OH)+malonyl carnitine (C3DC)/caproyl carnitine (C10), may be associated with the receptive status of the endometrium, though this need to be verified with larger samples.

Analysis of the current status and related factors of human papillomavirus infection among community-dwelling women aged 18-24 years without a history of vaccination in Shanghai City

Objective: To understand the status of human papillomavirus (HPV) infection among young women without a history of vaccination in Shanghai, and analyze the related factors of HPV infection in this population. Methods: A total of 2 660 women aged 18-24 years old who had made an appointment for HPV vaccine at 36 community health service centers in Shanghai from July 2022 to February 2023 were selected as the study subjects. Basic information (including demographic characteristics, previous disease history, female menstrual and reproductive history, sexual life history, etc.) was collected by a self-filling electronic questionnaire. Cervical secretions were detected by HPV nucleic acid typing. The multivariate logistic regression model was used to analyze the factors related to high-risk HPV (HR-HPV) infection in the target population. Results: The age of the subjects was (23±1) years old, and the infection rate of HPV was 14.51% (386 cases), among which the infection rates of HR-HPV and low-risk HPV were 13.53% (360 cases) and 1.84% (49 cases), respectively. The main subtypes of HR-HPV infection were HPV52, 16, 58, 39 and 66. The multivariate logistic regression model analysis showed that compared with the control group, the OR (95%CI) values for HR-HPV infection in the group of married, earned less than 2 000 yuan/month, drank alcohol occasionally, gynecological disease history, had two or more sexual partners in the past year, and did not know whether the partners had other sexual partners were 0.41 (0.25-0.66), 0.39 (0.21-0.70), 1.45 (1.13-1.86), 1.29 (1.00-1.66), 2.18-5.18 (1.02-16.05), and 1.82 (1.31-2.54), respectively. Conclusion: The infection rate of HPV among women aged 18-24 years old in Shanghai remains at a high level. The main subtypes of HR-HPV infection are HPV52, 16, 58, 39 and 66. The marital status, economic income level, drinking status, gynecological disease history and sexual life history are related to HR-HPV infection.

Distribution of human papillomaviruses (HPV) by geographical area and affected organ in Greece

Introduction: Even today we do not have a comprehensive picture of the impact of the virus in Greece and its location at various anatomical sites. Aim: The aim of the study was to investigate and record the impact of HPV infection in the Greek population with emphasis on the affected organ/system. Methodology: The data of the tissue bank of the histology and embryology laboratory of the Medical School of Athens was utilized. It includes cases with the following characteristics: a) they are fully characterized in terms of HPV infection (complete subtyping of the virus), b) they belong to benign and malignant neoplasms of various organs with complete histopathological assessment, c) have been collected in at least the last decade d) have accompanying clinical and demographic data and e) their origin covers the entire Prefecture of Attica and a wide age range. Results: In 60% of the samples no type of HPV was detected, while in 12%, low-risk types were detected and in 28% high-risk types. Women had a higher rate of infection with different types of HPV and were at higher risk, with HPV types 16 &amp; 18 being more common than men, who were more likely to have HPV 6 &amp; HPV 11 types. Infection with a high-risk type occurred in 23.4% of women versus 0.3% of men. The most common type in cervical secretions was HPV 16 (14% and 10.3% respectively), followed by HPV 18 with rates of 7.4% and 10.3% respectively. Regarding skin, HPV types 16 &amp; 18 were found with the same frequency (11.1%). In the perineum-rectum, the types of HPV6 &amp; 11 predominated (20.7%), followed by HPV 16 &amp; 18. Conclusion: The present study contributes to the further investigation of the prevalence of HPV in Greece, with emphasis on more types of HPV and more anatomical sites, providing information on the male population. It will help update public health planning, detect and prevent HPV-related cancers in both sexes in Greece