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ObjectiveTo evaluate the cervical mucus effects of a norgestrel 0.075 mg progestin-only contraceptive pill over a 28-day cycle.Study designWe recruited persons ages 18 to 35 with normal cycles at 2 US academic medical centers. Participants took norgestrel 0.075 mg daily for 28 days at the same time (within a 3 hour window) daily, recorded through a text-message based e-diary. We extracted cervical mucus using a standardized aspiration technique on the day of pill initiation and then at least every 3 to 4 days over the cycle. We monitored subjects for follicular activity with transvaginal ultrasound examination and blood sampling for ovarian hormones and gonadotropins at each visit. We assessed cervical mucus scoring using a 4-category/12-point modified Insler scale (score ≥9 [favoring fertility], 5-8 [intermediate], and ≤4 [unfavorable to fertility]). We stratified cervical mucus scores by serum estradiol levels and ovulatory status based on a modified Hoogland score.ResultsExcluding enrollment, we collected and evaluated 413 mucus samples from 51 participants. Participants had a median mucus score of 0 (Interquartile Range 0, 2); most had scores ≤4 (samples = 385, 93%) and none had a score ≥9 favoring fertility. Seventeen (33%) participants ovulated, of which 14 (82%) had unfavorable mucus scores (≤4) at the time of ovulation and 3 (18%) had intermediate scores (5-8).ConclusionsNorgestrel 0.075 mg daily prevents mucus changes that favor fertility, even during ovulatory cycles.ImplicationsDaily administration of norgestrel 0.075 mg over an initial 28-day cycle did not result in fertile cervical mucus. Although approximately one-third of users ovulated in this first cycle of pill use, contraceptive efficacy may be maintained by mucus effects.

A study was conducted in the rural area of Bihar from October to November 2020 with a sample size of 40 animals on the day of oestrus to evaluate the nutritional and reproductive management followed by the farmers. The experimental animals ranged from zero to fifth parity and overall breeding and feeding management were recorded, oestrus sign pattern was listed out, time of insemination relative to oestrus was recorded and cervical mucus was scored to correlate with the conception rate. From this study, it was clear that nutritional factor was still an area of concern to target improvement of the livestock. This study also highlights the cervical mucus pattern using a crystoscope as an easy, simple and cost-effective oestrus detection aid. [ABSTRACT FROM AUTHOR]

ObjectiveTo understand glycosylation of endocervical proteins at different times throughout the menstrual cycle in naturally cycling women and in women using hormonal or non-hormonal contraceptive methods, in order to characterize biochemical fingerprints of favorable and unfavorable cervical mucus.DesignLectin/antibody-probed protein blot analysis of endocervical mucus samples collected onto ophthalmologic sponges (wicks) from two groups: a longitudinal cohort of naturally cycling women at three time points in their menstrual cycles (discovery cohort), and a cross-sectional cohort of women on hormonal or non-hormonal contraceptive methods (validation cohort).SettingParticipants were recruited from the San Francisco Bay Area from 2010 to 2016.Patient(s)Women with regular cycles not using hormonal or intrauterine device (IUD) contraceptives were recruited for the longitudinal cohort (n = 8). Samples from women using levonorgestrel-containing combined oral contraceptives (n = 16), levonorgestrel containing IUDs (n = 14), copper IUDs (n = 17), depo-medroxyprogesterone acetate (DMPA) (n = 15), and controls (n = 13) were used for validation.Intervention(s)None.Main outcome measure(s)Detection of specific glycosylation patterns on lectin/antibody probed protein blots.Result(s)Two lectins (Lens culinaris agglutinin and Lycopersicon esculentum [tomato lectin]), and the antibody MECA-79 demonstrated consistent cycle-dependent changes in protein binding. The glycan-binding patterns of the levonorgestrel-containing contraceptives were generally similar to each other and to those from women in the luteal phase. The DMPA samples showed slightly different binding patterns.Conclusion(s)We identified molecular signatures of unfavorable mucus from women in the luteal phase and on hormonal contraceptives. Further characterization of these biomarkers may be useful in contraceptive development and in evaluation of infertility.

Accurate determination of estrus status in an animal based on an appropriate estrus detection method can guarantee the cows' pregnancy after mating. This study aims to determine the estrus status of Aceh cows using the van Eerdenburg estrus behavior scoring method. This study was conducted from 22 January to 12 February 2021, at the Technical Implementation Unit for Animals of the Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia. The sample used was eleven Aceh cows aged 4-6 years old. Parameters observed were the number of cows exhibiting signs of estrus using the estrus behavior scoring method. The accuracy of estrus detection was confirmed by palpation per rectum to detect the presence of uterine tone. By observing signs of estrus using the method studied, 90.9% (10/11) of the cows were determined to be in estrus. Confirmation by the presence of uterine tone showed a 100% accuracy rate. The most effective sign of estrus was the passivity of the cow when being ridden by another cow or bull. This study concluded that estrus status in local cows could be determined using the estrus behavior scoring of the van Eerdenburg method. [ABSTRACT FROM AUTHOR]

This work analyzes the electrical impedance (EI) measurement of cervical mucus (CM) using a device to determine the fertile window. In this prospective and longitudinal study, fourteen healthy women aged 18 to 44 were enrolled to evaluate three menstrual cycles. EI was measured through a medical device inserted into the vagina for two minutes daily. Patients were monitored by urine luteinizing hormone (LH) strip, blood collection, and vaginal ultrasound to visualize the dominant follicle. Finally, the predictive EI capacity was validated by the receiver operating characteristic (ROC) of anovulatory vs. ovulatory impedances. The peak of LH was 35.7 (±4.5) mUI/ml and the dominant follicle size was 15.45 mm (±0.559). There were statistical differences in EI measurements between the follicular and luteal phases vs. the ovulation phase (p<0.0361 and p<0.0160). After data normalization, an area under the ROC curve (AUC) of 0.713 (P value= 0.0253), a Youden J index of 0.4545O, a sensitivity of 63.6%, and a specificity of 81.8% were found. Low EI in the ovulatory period belongs to the LH ovulatory peak and follicular release. EI can be used for ovulation monitoring, birth control, or promoting pregnancy as a safe and innocuous method. [ABSTRACT FROM AUTHOR]

This study aimed to determine the length of the estrus period in Aceh cows based on changes in the characteristics of cervical mucus observed using a camera-equipped artificial insemination (AI) endoscope. This study used twelve healthy and reproductively sound cows aged 4-6 years. All cows were synchronized using prostaglandin F2a (PGF2a) injected intramuscularly twice, 11 days apart. Estrus detection was conducted 24 hours following the second injection of PGF2a three times daily for 30 minutes, respectively. Estrous cows were then subjected to the examination of their cervical mucus at 0, 6, 12, and 18 hours after the beginning of estrus. This study showed that out of 12 samples, only eight cows exhibited estrus signs. Characteristics of cervical mucus of cows at 0 and 6 hours of estrus were transparent. At 12 hours of estrus, five cows showed transparency, and the remaining three cows showed cloudy cervical mucus. Meanwhile, at 18 hours of estrus, all sampled cows showed cloudy cervical mucus then regarded as the end of the estrus. That means the estrus length of Aceh cows in this study was 15.75 ± 3.11 hours. It can be concluded that the determination of the duration of estrus in Aceh cows based on changes in the characteristics of the cervical mucus can be carried out using an AI endoscope with a camera. For further research, it is suggested to apply this estrus detection technique in the implementation of AI and determine the pregnancy rate. [ABSTRACT FROM AUTHOR]

Currently, human papillomavirus tests and cytology are used to screen for cervical cancer. However, more accurate ancillary screening tests are needed. MicroRNAs (miRNAs) and cytokines are promising biomarkers that are aberrantly expressed in cervical cancer. Therefore, the potential of developing new screening markers based on the levels of miRNAs and cytokines in serum and local mucus samples from the same patients with cervical neoplasia was investigated. miRNA screening was performed by microarray and measurement using real-time reverse-transcriptase PCR. Cytokine were measured using multiplex bead assay, and changes in expressions were analyzed based on disease severity. As lesions progressed, miR-20b-5p, -155-5p, -144-3p, -451a, and -126-3p expression levels were increased in mucus, and miR-16-5p, -223-3p, and -451a expression levels were decreased in serum. Regarding cytokines, IL-6, IL-8, monocyte chemoattractant protein-1, Eotaxin, interferon-γ, and RANTES were increased, whereas granulocyte-colony-stimulating factor (G-CSF) was significantly decreased in mucus. miRNAs and cytokines in serum did not have high diagnostic accuracy. However, a combination of miR-20b-5p, -451a, -126-3p, Eotaxin, as well as G-CSF in mucus samples, had high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.989 (0.979-0.999). Our results suggest that using mucus for this ancillary test is more beneficial than serum., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This study aimed to compare the ferning score based on the pH of the cervical mucus and its relation with gestation and the calf gender of cows. Ten Holstein Friesian crossbreed cows which were detected in estrus and about to be artificially inseminated, were used for this study. Sample of cervical mucus was collected using Metricheck for pH and ferning observations. Pregnancy diagnosis was conducted two months after insemination, and the gender of the calves was recorded at parturition. This study indicated that cervical mucus pH did not affect the ferning characteristics, ferning score, and pregnancy of cows. However, higher ferning scores tended to result in the pregnancy of cows. Also, alkaline pH tended to result in male calves and vice versa. Further study is needed with a more significant number of samples related to the application of ferning display as an indicator of estrus to obtain a higher pregnancy rate. [ABSTRACT FROM AUTHOR]

Persistent HPV infection associated with immune modulation may result in high-grade squamous intraepithelial lesions (CIN)2/3. Currently, there is little information on the cervicovaginal microbiome, local cytokine levels and HPV infection related to CIN. Follow-up of patients after local surgery provides an opportunity to monitor changes in the cervicovaginal environment. Accordingly, we undertook this longitudinal retrospective study to determine associations between HPV genotypes, cervicovaginal microbiome and local cytokine profiles in 41 Japanese patients with CIN. Cervicovaginal microbiota were identified using universal 16S rRNA gene (rDNA) bacterial primers for the V3/4 region by PCR of genomic DNA, followed by MiSeq sequencing. We found that Atopobium vaginae was significantly decreased (p < 0.047), whereas A. ureaplasma (p < 0.022) increased after surgery. Cytokine levels in cervical mucus were measured by multiplexed bead-based immunoassays, revealing that IL-1β (p < 0.006), TNF-α (p < 0.004), MIP-1α (p < 0.045) and eotaxin (p < 0.003) were significantly decreased after surgery. Notably, the level of eotaxin decreased in parallel with HPV clearance after surgery (p < 0.028). Thus, local surgery affected the cervicovaginal microbiome, status of HPV infection and immune response. Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia may be important for understanding the pathogenesis of CIN in future. [ABSTRACT FROM AUTHOR]

Background: The cervical mucus is a heterogeneous secretion regulated by steroid hormones that are normally produced by the ovary (estrogen and progesterone), in general, estrogen stimulates the secretion of large amounts of watery mucus (Atrio et al. 2015). The cervical mucus is important for conception, it is needed to help sperm survive and swim from the cervix into the uterus and eventually the fallopian tubes (Kar, 2012). Aim of the study: The study aims to determine the correlation between the mid-cycle estradiol and the total cervical mucus score of clomiphene citrate and letrozole treated infertile females. Materials and Method: 50 infertile female patients were included in this study, they were recruited from private infertility clinic patients. The patients were divided equally into two groups, the first group treated with Clomiphene Citrate (100 mg/day) and the second group treated with letrozole (5mg/ day), both groups started the dose from day 3 to 7 of the menstrual cycle i.e 5 tor days. The serum level of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin were measured at day 2 of the cycle (pretreatment). Transvaginal ultrasound was monitored follicular growth at mid-cycle day (when the dominant follicle size was 17 - 20 mm), At the same time, the cervical mucus (CM) score and serum E2 measurements were done. Result: The results revealed no significant differences in demographic data and basal hormonal levels between the clomiphene citrate and letrozole treated groups. There was a significant difference in the mid-cycle E2 level (p < 0.001) with higher levels in the clomiphene citrate group. There was also a significant difference in the total cervical mucus score (p<0.001) between the two groups. In the clomiphene citrate group, there was a significant negative correlation between total cervical mucus score and the mid-cycle E2 (r= -0.517, p=0.008), while in the letrozole group there was an insignificant correlation between mid-cycle E2 and total cervical mucous score (r= -0.07, p=0.74). Regarding the pregnancy outcome, there was no significant difference in pregnancy rate between the two groups (p=0.258), and in the clomiphene citrate group, there was no significant difference in the total cervical mucus score (p=0.165), while in the letrozole group there was a significant difference in total cervical mucus score (CM) between pregnant and non-pregnant female (p < 0.001 ) with higher scores in pregnant patients in both groups. Conclusions: Letrozole treated group showed higher cervical mucus score while the clomiphene citrate treated group demonstrated a significant correlation between mid-cycle E2 and total cervical mucus score. [ABSTRACT FROM AUTHOR]

Background: There is variability between women for days of menstrual bleeding, cycle lengths, follicular phase lengths, and luteal phase lengths, related to age and parity.Objective: To describe total cycle length; anovulatory cycles; follicular and luteal phase lengths; and days and intensity of menstrual and non-menstrual bleeding in women without known subfertility over the course of 1 year.Methods: 581 women (3,324 cycles) with no known subfertility (18-40 years of age) were followed for up to 1 year. Women recorded vaginal bleeding and mucus discharge daily. We used the peak day of cervical mucus as the estimated day of ovulation and the last day of the follicular phase. We used generalised linear mixed models stratified by age and parity to describe menstrual cycle parameters.Results: The majority of women were <30 years of age (74.5%), non-Hispanic White (88.6%), and nulliparous (70.4%). The mean menses length was 6.2 (1.5) days, median 6; cycle length 30.3 (6.7) days, median 29; follicular phase length 18.5 (6.5) days, median 17; and luteal phase length 11.7 (2.8) days, median 12. Nulliparous women aged ≥30 years vs nulliparous women aged <30 had shorter cycles (29.2 days, 95% confidence interval (CI) 27.8, 30.7 vs 31.5 days, 95% CI 30.8, 32.2) and shorter follicular phases (17.6 days, 95% CI 16.2, 18.9 vs 19.6 days, 95% CI 18.9, 20.2). Among all women, within-woman differences between the longest and shortest menses length >3 days, total cycle length >7 days, follicular phase >7 days, and luteal phase >3 days were found in 11.6%, 43.0%, 41.7%, and 58.8% of women, respectively.Conclusions: Our findings confirm variability between women of menstrual cycle parameters related to age and parity, and also highlight within-woman variability in the follicular and luteal phases. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated that women instructed in fertility awareness methods can identify the Peak Day of cervical mucus discharge for each menstrual cycle, and the Peak Day has high agreement with other indicators of the day of ovulation. However, previous studies enrolled experienced users of fertility awareness methods or were not fully blinded.Objective: To assess the agreement between cervical mucus Peak Day identified by fertile women without prior experience on assessing cervical mucus discharge with the estimated day of ovulation (1 day after urine luteinising hormone surge).Methods: This study is a secondary analysis of data from a randomised trial of the Creighton Model FertilityCareTM System (CrM), conducted 2003-2006, for women trying to conceive. Women who had no prior experience tracking cervical mucus recorded vulvar observations daily using a standardised assessment of mucus characteristics for up to seven menstrual cycles. Four approaches were used to identify the Peak Day. The referent day was defined as one day after the first identified day of luteinising hormone (LH) surge in the urine, assessed blindly. The percentage of agreement between the Peak Day and the referent day of ovulation was calculated.Results: Fifty-seven women with 187 complete cycles were included. A Peak Day was identified in 117 (63%) cycles by women, 185 (99%) cycles by experts, and 187 (100%) by computer algorithm. The woman-picked Peak Day was the same as the referent day in 25% of 117 cycles, within ±1 day in 58% of cycles, ±2 days in 84%, ±3 days in 87%, and ±4 days in 92%. The ±1 day and ± 4 days' agreement was 50% and 90% for the expert-picked and 47% and 87% for the computer-picked Peak Day, respectively.Conclusions: Women's daily tracking of cervical mucus is a low-cost alternative for identifying the estimated day of ovulation. [ABSTRACT FROM AUTHOR]

Background: The 2014 Bethesda System for Reporting Cervical Cytology classifies squamous intraepithelial lesions (SILs) of cervix into two main categories: low‐grade SIL (LSIL) and high‐grade SIL (HSIL). In some clinical practices, the LSIL cannot rule out high‐grade lesion (LROH) interpretive category is used in cases with LSIL and findings that may raise the possibility of HSIL. Our purpose is to assess follow‐up histopathology and high‐risk human papillomavirus (hrHPV) results in patients with LROH, in comparison with LSIL, atypical squamous cells, cannot rule out HSIL (ASC‐H), and HSIL in our institution. Design: Cervical Papanicolaou tests with LROH, LSIL, ASC‐H and HSIL interpretation, surgical follow‐up, and hrHPV status were retrieved from the computer database from May 2014 to December 2016. Results: Of 109 963 total Papanicolaou tests, LROH comprised 0.3%, LSIL 3.1%, ASC‐H 0.2% and HSIL 0.4%. Only 3272 cases with surgical diagnoses were included in the study. The most common histological outcome for ASC‐H was cervical intraepithelial neoplasia (CIN)2/3 (32.6%); LSIL was CIN 1 (45.7%); LROH was CIN 1 (46.7%) and HSIL was CIN 2/3 (64.4%). For LROH and LSIL, 31.1% and 7.5% respectively, had CIN 2/3. Approximately 79% of cases were hrHPV positive. Of LROH cases with surgical follow‐up, 86.9% tested hrHPV positive, accounting for the second most common positive group after HSIL (92.6%). Conclusion: In our study cohort, LROH interpretation is associated with a higher number of CIN 2 or higher lesions on follow‐up compared to patients with LSIL (P < 0.0001), and is associated with a significant percentage of positive other hrHPV, supporting LROH as a useful diagnostic category that triggers appropriate follow‐up in affected women. In our article, we assess the histopathology follow‐up and available high‐risk human papillomavirus (hrHPV) results in patients with low‐grade squamous intraepithelial lesion, cannot rule out high grade lesion (LROH), in comparison with LSIL, ASC‐H, and HSIL using a single institution's experience. Our purpose is to reiterate the LROH value as an interpretative category. [ABSTRACT FROM AUTHOR]

The research aimed to identify the bacteria present in the reproductive tract of dairy cattle at follicular and luteal phases of the estrus cycle. Seven samples of cervical mucus were each obtained from the reproductive tract, at follicular and luteal phase, of fourteen healthy cattle, 2-3 years of age, with body condition scores of 2.0-8.3. Sporet, motility, triple sugar iron agar, mannitol and glucose tests were done to obtain gram characteristics and bacterial morphology, which enabled identification at the genus level. Non-specific bacteria isolated at follicular phase were Staphylococcus (50%), Corynebacterium (25%) and Escherichia (25%). At luteal phase, Staphylococcus (45.5%), Escherichia (45.5%) and Corynebacterium (9%) were isolated. The results suggest that a number of bacteria can be found in the reproductive tract of dairy cattle, both at follicular phase and luteal phase. [ABSTRACT FROM AUTHOR]

Abstract SHetA2 is a novel compound with strong potential to treat cervical dysplasia, but its low aqueous solubility limits its oral bioavailability. A vaginal suppository achieved SHetA2 cervix concentrations that were severalfold above the predicted therapeutic levels. Thus, we aimed at determining the minimum dose that would achieve SHetA2 therapeutic levels while reducing cyclin D1 levels, the pharmacodynamic end point. The disposition of SHetA2 after vaginal administration of escalating SHetA2 doses and the corresponding reduction in cyclin D1 levels was compared to that after the conventional oral treatment. Vaginal administration of a 15-mg/kg dose achieved an area under the cervix concentration versus time curve (AUC cervix) that was ∼120 times larger than that after a 60 mg/kg administered orally. AUC cervix and C max-cervix did not increase proportionally with respect to the dose, with the 30-mg/kg dose resulting in higher AUC cervix and C max-cervix (1368.53 μg.mL/h and 155.38 μg/g, respectively) compared to the 15 mg/kg (334.98 μg.mL/h and 121.78 μg/g, respectively) or 60 mg/kg (1178.55 μg.mL/h and 410.38 μg/g, respectively). Likewise, the 30-mg/kg dose caused a larger reduction in cyclin D1 levels than the other doses. Thus, the 30-mg/kg dose was selected for future efficacy studies in a mouse model of cervical neoplasia. [ABSTRACT FROM AUTHOR]

Aim To establish a correlation between positive values of IGFBP-1 (>10 mg/L, Actim Partus Test, APT) and premature cervical ripening in imminent preterm labor. Methods A prospective study was conducted in primary health care centers in Tuzla, Gynecology and Obstetrics Clinic of the University Clinical Centre in Tuzla and General Hospital Tešanj. The study included 50 women (singleton pregnancy, 28-37 week) with imminent preterm labor diagnosed by cervical biometry and modified Bishop score) (examinees) and 30 healthy pregnant women (control group). The presence of IGFBP-1 was tested in cervical secretion several times in weeks 28-37 until a positive test was shown. Results IGFBP-1 was positive in 43 (86%) examinees and in six (20%) patients from the control group (p=0.001). In 31 (62%) examinees APT was positive in weeks 28-30, and in nine (18%) in weeks 31- 33, while three (6%) examinees had positive test in 34-37 week; in the control group, three (10%) were tested positive in weeks 31-33 and three (10%) in weeks 34-37. At first testing (28-30 weeks) APT was statistically significantly more frequently positive in the examined group (p

The female lower reproductive tract microbiota is a complex ecosystem comprising various microorganisms that play a pivotal role in maintaining women's reproductive well-being. During pregnancy, the vaginal microbiota undergoes dynamic changes that are important for a successful gestation. This review summarizes the implications of the cervical mucus plug microenvironment and its profound impact on reproductive health. Further, the symbiotic relationship between the vaginal microbiome and the cervical mucus plug is highlighted, with a special emphasis on how this natural barrier serves as a guardian against ascending infections. Understanding this complex host-microbes interplay could pave the way for innovative approaches to improve women's reproductive health and fertility., Competing Interests: None declared., (Thieme. All rights reserved.)

This work presents a semianalytical solution based on Laplace transform to study the behaviour of poroelastic materials in the context of the Extended Nonequilibrium Thermodynamics. In this framework, the fluid phase incorporates a relaxation time and, consequently, a frequency-dependence appears. This rheological behaviour could explain the frequency-dependence experimentally observed in biological tissues, which has traditionally attributed to the solid phase of tissues. In particular, the analytical solution is applied to two cases, heaviside and sinusoidal inputs, of a semi-infinite domain, which is filled with a material such as the human cervix. From the results, it is observed that the frequency-dependence of the fluid phase could be relevant to high relaxation times while for null relaxation times the classical poroelastic theory is recovered. Finally, the present analytical solution could be used to validate future computational codes and experimental settings. [ABSTRACT FROM AUTHOR]

Cervical mucus modulates fertility by cyclical changes of its biophysical and functional properties. Based on an analogy with bronchial goblet cells we set out to investigate the possible role of the gamma-aminobutyric acid (GABA) signalling pathway in the mediation of oestrogen-induced mucus secretion from endocervical secretory cells. The aim of the study was to examine the existence of GABAA receptor (GABAAR), glutamic acid decarboxylase 65/67 (GAD65/67) and vesicular GABA transporter (VGAT) in human and mouse cervical tissue. The mouse cervical tissue expressed GabaAR mRNA transcripts throughout the oestrous cycle. GABAAR-positive immunolabelling was present in the superficial layer of the mouse cervico-vaginal epithelium in pro-oestrus. Human cervical tissue showed the presence of GABAAR, GAD67 and VGAT mRNA transcripts and clear immunofluorescent signals of all three molecules were detected in the endocervical secretory epithelium. The results of this study confirmed that elements of the GABA signalling pathway are present in the secretory epithelium of mouse and human cervical tissue and that GABA signalling pathway could be considered a possible mediator in oestrogen regulation of mucus secretion in the endocervical glands. [ABSTRACT FROM AUTHOR]

Objective: To detect if removing the cervical mucus before performing intrauterine insemination (IUI) could improve pregnancy outcomes in patients with unexplained infertility.Design: Prospective randomized study.Setting: An Egyptian University Hospital.Population: Seven hundred and fourteen couples with unexplained infertility who underwent intrauterine insemination (IUI) with or without cervical mucus removal.Methods: Using computer-generated numbers, patients were randomly allocated to cervical-mucus-removal (removed from both internal and external os) or non-mucus-removal groups. Only participants were blinded as to group assignment.Main Outcome Measures: The clinical pregnancy rate.Results: Of 714 IUI patients between November 2014 and March 2017, 361 were in the mucus removal group, and 353 in the non-mucus-removal group. Difficult catheterization was encountered in 17 cases out of 666 (2.6%) 12 in the cervical-mucus-removal group and five in the non-mucus-removal group). A total of 666 IUI cycles were completed while 48 were either cancelled or lost in their follow-up. The clinical pregnancy rate was significantly higher in the mucus-removal group [31.0% (n = 112)] than in the non-mucus-removal group [21.8% (n = 77); P = 0.005]. Ovarian hyperstimulation developed in 33 (4.6%) cases: 18 cervical mucus-removal and 15 non-mucus-removal. All except one were mild and managed with outpatient care.Conclusions: Cervical mucus removal before IUI could improve pregnancy outcomes in women with unexplained infertility.Tweetable Abstract: Cervical mucus removal before IUI can improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Spontaneous preterm birth has enormous consequences for newborns, children, and families. Intra-amniotic inflammation (IAI) is the leading cause of spontaneous preterm delivery, mainly at earlier gestational ages. Amniocentesis is the only method used to identify IAI in clinical practice. Although it is an invasive procedure with a very low risk of complications, many women and physicians are hesitant about amniocentesis on this indication. This has been an incentive to explore IAI and the intra-amniotic environment through noninvasive techniques, such as sampling cervical mucus, vaginal fluid, or maternal blood. With this overview, we aim to provide a concise update on the state of the art of the noninvasive sampling of the intrauterine environment in women with preterm labor and intact membranes. So far, it is unknown whether this screening helps improve our knowledge about the impact of IAI on the neonatal and long-term outcome, but we believe it merits this review. [ABSTRACT FROM AUTHOR]

Mammalian spermatozoa in organisms with internal fertilization are required to swim in the cervical and oviductal mucus, whose rheological properties differ substantially from those of water. Moreover, on the way to the oviduct, a change in sperm motility called hyperactivation may occur. In the present study, we focused on the motion characteristics of hyperactivated bovine sperm and investigated the effect of the surrounding fluid on motility. We prepared two kinds of polyacrylamide with high-viscosity non-Newtonian fluid properties, similar to the actual cervical and oviductal mucus. Using semen from Japanese cattle, we evaluated curvilinear velocity (VCL), straight-line velocity (VSL), and average path velocity (VAP). Additionally, we estimated linearity (LIN), straightness (STR), and wobble (WOB) as sperm motility parameters for several surrounding fluids. We successfully induced hyperactivation of bovine sperm in high-viscosity non-Newtonian fluid. Hyperactivation resulted in an increase in VCL and a decrease in VSL. In the high-viscosity non-Newtonian fluid, the hyperactivated sperm moved in a zig-zag pattern with regularity, different from the movement observed in a diluted solution. The increase in WOB in the non-Newtonian fluid suggests that hyperactivated sperm efficiently progress along the groove that exists on the oviductal mucus wall. These results improve our understanding of the motility of bovine sperm when they undergo hyperactivation in the actual cervical and oviductal mucus. [ABSTRACT FROM AUTHOR]

The present study was conducted on repeat breeder (RB, n=40) crossbred cows under field conditions to evaluate their endometrial cytology and cervico-vaginal mucus (CVM) characteristics in relation to post-treatment fertility. The endometrial cytology was obtained using cytobrush technique and CVM by aspiration technique from vaginal fornix using sterile pipette and syringe. The cows yielding bacterial growth in CVM were treated with sensitive antibiotics (i/m) for 3-5 days (Gr I, RBT: 28) and cows not yielding bacterial growth (control, Gr II, RBC: 12) were given 10 ml of normal saline (i/m). The cows were inseminated at subsequent estrus and followed for repeating to estrus and/or pregnancy. The subclinical endometritis was diagnosed using endometrial cytology (PMN%: ≥ 4%) in cows yielding bacterial isolates (n=28) with mean PMN% of 21.80±8.39, 32.18±3.26 and 29.25±6.63 for those having clear stringy consistency, turbid viscous, and watery white flaky CVM, respectively. The mean PMN% in RB cows with no bacterial isolates (n=12) and having clear stringy CVM was 1.50±0.23. The mean values of spinnbarkeit (cm), pH and Whiteside test scores of CVM were 14.60±0.51, 5.82±0.85 and 3.00±0.17; 7.41±0.15, 7.44±0.21 and 7.08±0.19; and 1.40±0.60, 1.91±0.28, and 1.75±0.25, respectively, for culturally positive cows having CVM of clear stringy, turbid viscous and watery with white flakes, respectively (Group I). The mean spinnbarkeit (cm), pH and Whiteside test scores in control cows not yielding any bacterial isolates and having clear stringy CVM (Group II) were 13.08±0.99, 7.37±0.10 and 0.33±0.19. The RB cows with clear stringy, turbid viscous and white flaky CVM and yielding bacterial isolates had mean inter-estrus intervals of 18.80 ±0.51, 15.91±0.48 and 13.83±0.41 days, respectively, the differences being significant (P<0.05), with respective post-treatment pregnancy rates of 80.00, 63.63 and 41.66 %, with an overall pregnancy rate of 57.15%. This interval was 19.42±0.45 days in RB control cows, wherein the pregnancy rate was 66.66% without any treatment. The cytobrush technique (PMN%) for endometrial cytology and Whiteside test of CVM were good tools for ruling out the subclinical genital infections in repeat breeding cows. [ABSTRACT FROM AUTHOR]

Purpose: Timing of sample collection represents a major source of variability in studies evaluating the effects of administered agents on cervical mucus in naturally-cycling women. We sought to create and validate an artificial model of the cervical mucus cycle using exogenous E2 and P4 replacement in ovarian suppressed women.Materials and Methods: We conducted a prospective experiment (clinicaltrials.gov, NCT02969590) examining cervical mucus changes in six women during natural and artificial menstrual cycles [leuprolide acetate, estradiol transdermal patch (0.05-0.3 mg/day) and progesterone 200 mg/day]. We collected serum and mucus samples at each visit corresponding to early, mid and late follicular, ovulation and mid-luteal time points in the natural and artificial cycles. We evaluated mucus according to the modified Insler score described in the WHO laboratory Manual for the Examination and Processing of Human Semen.Results: We enrolled healthy women between 27 and 40 years of age. All of the subjects achieved a mucus score of ≥10 both in the natural cycle and during peak estradiol replacement levels (0.3 mg/day) in the artificial cycle. During the simulated luteal phase, all mucus scores were ≤5 (median 3.5; range 1-5), similar to scores seen in the luteal phase of natural cycles (median 1; range 1-3).Conclusions: Our artificial cycle model (leuprolide acetate suppression) and dose escalation with estradiol patches produced favourable cervical mucus with mucus scores similar to those in the periovulatory phase of natural menstrual cycles. Additional studies are needed to validate the model for evaluation of mucus effects of contraceptive agents. [ABSTRACT FROM AUTHOR]

Endometritis significantly impacts fertility and milk yield, thus reducing profitability of the dairy production. In cows that develop endometritis, normal postpartum endometrial inflammation is dysregulated. Here, we propose that endometrial inflammation is reflected in cervico-vaginal mucus (CVM) which could therefore be used as a prognostic tool. CVM was collected from 20 dairy cows (10 with clinical endometritis and 10 healthy) 7 and 21 days postpartum (DPP). Polymorphonuclear (PMN), mononuclear leukocyte and epithelial cells were counted, total protein levels were estimated and levels of IL-1β, IL-6, IL-8, serum amyloid A (SAA), haptoglobin (Hp) and C5b were analyzed by ELISA in CVM. PMN were consistently high in CVM from 7 to 21 DPP, but were higher in CVM from cows with clinical endometritis 21 DPP compared with healthy cows. In contrast, there were more epithelial cells in healthy cows 21 DPP than in clinical endometritis animals. Total protein levels decreased significantly in CVM from healthy cows between days 7 and 21 postpartum. All inflammatory biomarkers except C5b, remained high in cows with clinical endometritis from 7 to 21 DPP, indicating sustained and chronic endometrial inflammation. IL1, IL-6, IL-8 and Hp levels were higher in CVM from cows with clinical endometritis compared to healthy cows 21 DPP. Interestingly IL-1β levels were raised in CVM from clinical endometritis but not in healthy cows 7 DPP suggesting that early measurement of IL-1β levels might provide a useful predictive marker of clinical endometritis. In contrast, SAA and C5b levels were increased in healthy cows 21 DPP, compared to cows with clinical endometritis suggesting that these acute phase proteins might have an anti-inflammatory role. Our results show that CVM is convenient for profiling disease-associated changes in key inflammatory molecules postpartum and reaffirms that sustained inflammation is a key feature of clinical endometritis in the dairy cow. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the influence of antisperm Ig G and Ig A antibodies (ASA) from the sera and cervical mucus of cows on bulls sperm motility. A total of 64 cows was included in the study and samples of sera and cervical mucus were collected on the day of artificial insemination. Cows were of Busha breed or mix breed with Simmental. The presence of antisperm Ig G and Ig A antibodies was determined by indirect immunofluorescence method and according to these results, cows were dIvided in groups as follows: cows with high or low ASA titer in their sera and cows with high or low ASA titer in the cervical mucus. Influence of antisperm antibodies on sperm motility was further estimated by Computer Assisted Semen Analysis (CASA). Results demonstrated a significant difference in the influence of antisperm antibodies depending on their origin and titer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the tolerability of cervical insulin-like growth factor binding protein 1 (IGFBP-1) and its value as a predictor of successful labour induction, compared with Bishop score and transvaginal ultrasound (TVUS) cervical length.Design: A prospective study.Setting: A tertiary hospital in Malaysia.Population: A cohort of 193 term nulliparous women with intact membranes.Methods: Prior to labour induction, cervical fluid was obtained via a vaginal speculum and tested for IGFBP-1, followed by TVUS and finally Bishop score. After each assessment the procedure-related pain was scored from 0 to 10. Cut-off values for Bishop score and cervical length were obtained from the receiver operating characteristic (ROC) curve. Multivariable logistic regression analysis was performed.Main Outcomes Measures: Vaginal delivery and vaginal delivery within 24 hours of starting induction.Results: Bedside IGFBP-1 testing is better tolerated than Bishop score, but is less well tolerated than TVUS [median (interquartile range) of pain scores: 5 (4-5) versus 6 (5-7) versus 3 (2-3), respectively; P < 0.001]. IGFBP-1 independently predicted vaginal delivery (adjusted odds ratio, AOR 5.5; 95% confidence interval, 95% CI 2.3-12.9) and vaginal delivery within 24 hours of induction (AOR 4.9; 95% CI 2.1-11.6) after controlling for Bishop score (≥4 or ≥5), cervical length (≤29 or ≤27 mm), and other significant characteristics for which the Bishop score and TVUS were not predictive of vaginal delivery after adjustment. IGFBP-1 has 81% sensitivity, 59% specificity, positive and negative predictive values of 82 and 58%, respectively, and positive and negative likelihood ratios of 2.0 and 0.3 for vaginal delivery, respectively.Conclusion: IGFBP-1 better predicted vaginal delivery than BS or TVUS, and may help guide decision making regarding labour induction in nulliparous women.Tweetable Abstract: IGFBP-1: a stronger independent predictor of labour induction success than Bishop score or cervical sonography. [ABSTRACT FROM AUTHOR]

Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. [ABSTRACT FROM AUTHOR]

Poor water solubility and adverse side effects pose a challenge for clinical application of paclitaxel (PTX). In this work, a series of PTX dimers are synthesized by coupling two PTX molecules with dicarboxylic acids. As-synthesized PTX dimers form stable nanoparticles in aqueous solution without using any surfactants or adjuvants, and the solubility of PTX in water increases by 2500-fold compared to that of free PTX. These nanoparticles with high content of PTX are internalized by cancer cells and exhibit comparable cytotoxicity with Taxol. Furthermore, when the PTX dimers are incorporated into methoxypoly(ethylene glycol) 2 K – block -poly( d , l -lactide) 2 K (PEG-PDLLA) micelles, the loading content of PTX dimers is as high as 85 wt%. The formed nanoparticles possess the high stability in biological conditions. Both in vitro and in vivo experiments show that these (PTX dimer)/PEG-PDLLA formulations possess effective cellular uptake and potent cytotoxicity, and exhibit reduced systemic toxicity and enhanced antitumor efficacy towards human cervical tumor. We believe these PTX dimers-based nanoparticles would be an alternative formulation for PTX, and such drug dimer assembling behaviors could be extended to other therapeutic agents. [ABSTRACT FROM AUTHOR]

Although essential for artificial insemination (AI) and MOET (multiple ovulation and embryo transfer), oestrus synchronisation and superovulation are associated with increased female reproductive tract mucus production and altered sperm transport. The effects of such breeding practices on the ovine cervicovaginal (CV) mucus proteome have not been detailed. The aim of this study was to qualitatively and quantitatively investigate the Merino CV mucus proteome in naturally cycling (NAT) ewes at oestrus and mid-luteal phase, and quantitatively compare CV oestrus mucus proteomes of NAT, progesterone synchronised (P4) and superovulated (SOV) ewes. Quantitative analysis revealed 60 proteins were more abundant during oestrus and 127 were more abundant during the luteal phase, with 27 oestrus specific and 40 luteal specific proteins identified. The oestrus proteins most disparate in abundance compared to mid-luteal phase were ceruloplasmin (CP), chitinase-3-like protein 1 (CHI3L1), clusterin (CLU), alkaline phosphatase (ALPL) and mucin-16 (MUC16). Exogenous hormones greatly altered the proteome with 51 and 32 proteins more abundant and 98 and 53 proteins less abundant, in P4 and SOV mucus, respectively when compared to NAT mucus. Investigation of the impact of these proteomic changes on sperm motility and longevity within mucus may help improve sperm transport and fertility following cervical AI. Significance This manuscript is the first to detail the proteome of ovine cervicovaginal mucus using qualitative and quantitative proteomic methods over the oestrous cycle in naturally cycling ewes, and also after application of common oestrus synchronisation and superovulation practices. The investigation of the mucus proteome throughout both the follicular and luteal periods of the oestrous cycle, and also after oestrous synchronisation and superovulation provides information about the endocrine control and the effects that exogenous hormones have on protein expression in the female reproductive tract. This information contributes to the field by providing important information on the changes that occur to the cervicovaginal mucus proteome after use of exogenous hormones in controlled breeding programs, which are commonly used on farm and also in a research setting. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic gynecological inflammatory disease characterized by the presence of functional endometrial glands and stroma outside of the uterine cavity. It affects 7-10% of women of reproductive age and up to 50% of women with infertility. The current gold standard for the diagnosis combines laparoscopic evaluation and biopsy of the visualized lesions. However, laparoscopy requires general anesthesia and developed surgical skills and it has a high procedural cost. In addition, it is associated with the risk, although rare, of potential intraoperative or postoperative complications. To date, several noninvasive biomarkers have been proposed; however, no definite diagnostic biomarker is yet available. The aim of this study was to characterize the CM proteome in patients with endometriosis using high resolution mass spectrometry--based proteomics, implemented by bioinformatic tools for quantitative analysis, in order to investigate the pathophysiological mechanisms of endometriosis. Methods: Cervical mucus samples were collected from patients affected by endometriosis and fertile controls. An aliquot of the soluble acidic fraction of each cervical mucus sample, corresponding to 0.5 mg of total protein, was left to digest with sequencing grade modified porcine trypsin. The peptides were analyzed by LC-MS/MS on a high resolution Orbitrap Elite mass spectrometer and data were evaluated using bioinformatic tools. Results: We aimed at the first total profiling of the cervical mucus proteome in endometriosis. From the list of identified proteins, we detected a number of differentially expressed proteins, including some functionally significant proteins. Six proteins were quantitatively increased in endometriosis, almost all being involved in the inflammatory pattern. Nine proteins were quantitatively reduced in endometriosis, including some proteins related with local innate immunity (CRISP-3 and Pglyrp1) and protection against oxidative stress (HSPB1). Fifteen proteins were not detected in endometriosis samples including certain proteins involved in antimicrobial activity (SLURP1 and KLK13) and related to seminal plasma liquefaction and male fertility (KLK13). Conclusions: This is the first application of high resolution mass spectrometry--based proteomics aimed in detecting an array of proteins in CM to be proposed for the noninvasive diagnosis of endometriosis. This chronic disease presents in CM an inflammatory protein pattern. [ABSTRACT FROM AUTHOR]

Contents Accurate detection of oestrus is important for artificial insemination. The aim of this study was to identify oestrous-specific bovine cervical mucus proteins that could be used to determine the optimal time for artificial insemination. Non-oestrous and controlled internal drug release ( CIDR)-induced oestrous-stage mucus proteins were purified and subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulphate polyacrylamide gel electrophoresis and MALDI- TOF/ TOF. Among differentially expressed proteins, lactoferrin ( LF) and glutamate receptor-interacting protein 1 ( GRIP1) showed a twofold increase during the CIDR-induced oestrous stage compared to the levels in non-oestrous stage in bovine cervical mucus. The RT- PCR, Western blotting and immunohistochemistry results showed that LF and GRIP1 expression was significantly increased during the oestrous stage in the uterus. This study demonstrated that bovine LF and GRIP1 exist during the oestrous stage, but not during the non-oestrous stage, suggesting that cervical mucus LF and GRIP1 are useful oestrous detection markers in cattle. [ABSTRACT FROM AUTHOR]

The cervical mucus plug (CMP) is believed to play an integral role in the maintenance of pregnancy in the mare, primarily by inhibiting microbial entry. Unfortunately, very little is known about its composition or origin. To determine the proteomic composition of the CMP, we collected CMPs from mares (n = 4) at 9 months of gestation, and proteins were subsequently analyzed by nano-LC-MS/MS. Results were searched against EquCab2.0, and proteomic pathways were predicted by Ingenuity Pathway Analysis. Histologic sections of the CMP were stained with H&E and PAS. To identify the origin of highly abundant proteins in the CMP, we performed qPCR on endometrial and cervical mucosal mRNA from mares in estrus, diestrus as well as mares at 4 and 10 m gestation on transcripts for lactotransferrin, uterine serpin 14, uteroglobin, uteroferrin, deleted in malignant brain tumors 1 and mucins 4, 5b and 6. Overall, we demonstrated that the CMP is composed of a complex milieu of proteins during late gestation, many of which play an important role in immune function. Proteins traditionally considered to be endometrial proteins were found to be produced by the cervical mucosa suggesting that the primary source of the CMP is the cervical mucosa itself. In summary, composition of the equine CMP is specifically regulated not only during pregnancy but also throughout the estrous cycle. The structural and compositional changes serve to provide both a structural barrier as well as a physiological barrier during pregnancy to prevent infection of the fetus and fetal membranes. [ABSTRACT FROM AUTHOR]

Introduction: The viscoelastic properties of the cervical mucus plug are considered essential for the occlusion of the cervical canal and thereby for protection against ascending infections during pregnancy. Factors controlling this property are virtually unknown. This study explores a possible role of trefoil factor peptides 1, 2 and 3 (TFF1-3); peptides believed to influence mucus viscosity. Material and Methods: The study is based on spontaneously shed cervical mucus plugs from 14 women in active labor. The viscoelastic properties; the elastic modulus (G') and the viscous modulus (G") were determined by an oscillatory rheometer. The concentrations of TFF1-3 were measured by an in-house enzyme-linked immunosorbent assay. Associations were analyzed by random-effects generalized least-squares regression analyses. Results: Median (range) concentrations of TFF1, TFF2 and TFF3 were 3.1 (1.2-8.6), 1.1 (<0.006-3.7) and 1000 (170-5300) nmol/g cervical mucus plug, respectively. The TFF3 concentration was associated with G' (regression coefficient 11.7 Pa/Log nm; 95% CI 3.0-20.4, p = 0.009) and G" (regression coefficient 3.2 Pa/Log nm; 95% CI 1.5-5.0, p < 0.001). Conclusion: We suggest that TFF3 plays a role in the viscoelastic properties of the cervical mucus plug. [ABSTRACT FROM AUTHOR]

Introduction: Cervical artificial insemination (AI) with frozen-thawed semen in sheep has yielded unacceptably low pregnancy rates. The exception is in Norway where vaginal AI yields non-return rates in excess of 60%, which has been attributed to the ewe breed used., Objectives and Methods: This study aimed to characterise, for the first time, the ovine follicular phase cervical mucus metabolome, with a focus on the amino acid profile. Cervical mucus was collected from four European ewe breeds with known differences in pregnancy rates following cervical AI with frozen-thawed semen. These were Suffolk (low fertility), Belclare (medium fertility), Norwegian White Sheep (NWS) and Fur (both high fertility)., Results: A total of 689 metabolites were identified in the cervical mucus of all the four ewe breeds. Of these, 458 metabolites were altered by ewe breed, which had the greatest effect in the dataset (P < 0.05). We detected 194 metabolites involved in the amino acid pathway, of which 133, 56 and 63 were affected by ewe breed, type of cycle and their interaction, respectively (P < 0.05). N-methylhydantoin and N-carbamoylsarcosine (degradation products of creatinine pathway) exhibited the greatest fold change decrease in the Suffolk breed compared to Fur and NWS (P < 0.001). Oxidized metabolites were also decreased in Suffolk compared to high fertility breeds (P < 0.05). In contrast, other metabolites such as 3-indoxyl-sulfate, putrescine, cadaverine were significantly increased in Suffolk at the synchronised cycle., Conclusion: The suboptimal amino acid profile in the cervical mucus of the low fertility Suffolk breed may have negative consequences for sperm transport., (© 2023. The Author(s).)