Evaluation of cervical mucus and reproductive efficiency of seasonally anovular dairy goats after short-term progestagen-based estrous induction protocols with different gonadotropins.

The use of three different gonadotropins was tested for estrous induction in dairy goats during the non-breeding season. All does received an injection of 30 µg of d-cloprostenol and intravaginal sponges containing 60mg of medroxyprogesterone acetate (MAP) for 6 d plus 20 IU of porcine FSH (pFSH), 200 IU of eCG or 250 IU of hCG 24h before sponge removal. In Experiment 1 (n=24), ovarian ultrasound parameters were recorded and cervical mucus was evaluated daily for 5 d after sponge removal or until ovulation. In Experiment 2 (n=80), reproductive efficiency of artificially inseminated or naturally mated does was assessed. The mean interval from sponge removal to ovulation (73.5±23.7 h), number of ovulations (1.6±0.7) and ovulatory follicle diameter (7.2±0.8 mm) did not vary (P >0.05) among the three groups. At ovulation, cervical mucus had crystalline-striated to striated (22.2%), striated to striated-caseous (72.2%) and striated-caseous to caseous (5.6%) appearance. The largest follicle diameter was greater (P <0.05) in does with crystalline (6.7±1.4 mm), crystalline-striated (7.2±1.1 mm) or striated (7.3±1.3 mm) mucus than in those with striated-caseous (5.3±1.4 mm) or caseous (4.5±1.1 mm) mucus. Percentage of animals exhibiting estrus (92.5%) and conception rate (60.8%) were similar (P >0.05) among the three gonadotropins groups. Results of this study support the use of eCG (200 IU), hCG (250 IU) and pFSH (20 IU) for the estrous induction protocols in dairy goats during the non-breeding season. Cervical mucus evaluation can be used as an additional method to determine the optimal time for artificial insemination in goats.

Insights into the role of cervical mucus and vaginal pH in unexplained infertility / Sobre o papel do muco cervical e do PH vaginal na gênese da infertilidade inexplicada

Unexplained infertility diagnosis is made in the presence of a normal semen analysis when tubal patency and normal ovulatory function are established. Among several potential causes, unexplained infertility could be attributed to vaginal pH and cervical mucus abnormalities. Although the vaginal canal and the cervix generally function as effective barriers to sperm, and although the production of mucus is essential to transport them from the vagina to the uterine cavity, these factors receive little attention in the investigation of couples with unexplained infertility. A substantial reduction in sperm number occurs as they transverse the cervix. From an average of 200 to 300 million sperm deposited in the vagina, only a few hundred achieve proximity to the oocyte. Given this expected high spermatozoa loss, a slight modification in cervical mucus may rapidly transform the cervix into a "hostile" environment, which, together with changes in vaginal environment and cervix structure, may prevent natural conception and be a cause of infertility. In this review, we discuss the physiological role of the vaginal pH and cervical mucus in fertility, and describe several conditions that can render the cervical mucus hostile to sperm and therefore be implicated in the pathophysiology of unexplained infertility.

RESUMO O diagnóstico de infertilidade inexplicada baseia-se na presença de espermograma normal, constatadas também permeabilidade tubária e função ovulatória normais. Entre as várias causas potenciais de infertilidade inexplicada, a presença de muco cervical e pH vaginal anormais devem ser consideradas. Embora a produção adequada de muco cervical seja essencial para o transporte dos espermatozóides da vagina para a cavidade uterina, e tanto o canal vaginal quanto o colo do útero desempenham função importante como barreira à passagem dos espermatozóides, estes fatores recebem pouca atenção na investigação de casais com infertilidade inexplicada. Uma redução substancial do número de espermatozoides ocorre à medida que estes percorrem o trato reprodutivo feminino. Partindo de cerca de 200 a 300 milhões de espermatozoides depositados na vagina, apenas algumas centenas alcançam a proximidade do oócito. Alteracões do muco cervical podem rapidamente transformar o colo do útero num ambiente hostil, que em conjunto com alterações no ambiente vaginal e da estrutura de colo do útero, podem apresentar-se condicões impedientes para a concepção natural; desse modo, convertem-se em causa de infertilidade. Nesta revisão, discutimos o papel fisiológico do pH vaginal e do muco cervical na fertilidade, descrever várias condicões que podem tornar o muco cervical hostil aos espermatozoides e, por fim analisamos como estes fatores interferem na fisiopatologia da infertilidade inexplicada.

Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI).

Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging ("theranostics"). Here, we describe liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, e.g., the diaCEST MRI contrast agent barbituric acid (BA). We observed that polyethylene glycol (PEG)-coated liposomes containing ≥7 mol% PEG diffused only ~10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol%-PEG liposomes contained sufficient BA loading for diaCEST contrast, and provided improved vaginal distribution compared to 0 and 3mol%-PEG liposomes. However, increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution, suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol%-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces. FROM THE CLINICAL EDITOR: This team of authors characterized liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents, such as barbituric acid (a diaCEST MRI contrast agent) and concluded that liposomal MPP with optimized PEG coating enables drug delivery and imaging at mucosal surfaces.

Prominent cervical mucous and its impact on cervical length measurement: findings of a national survey.

INTRODUCTION: Cervical length measurement by transvaginal scanning (TVS) has been proposed by some as a universal screening test for preterm labour. The presence of prominent cervical mucous may affect assessment of the cervix; however, the exact technique to measure the cervix when there is prominent mucous or funnelling has not been described. We evaluated the level of agreement in cervical length measurements amongst Australian specialists and sonographers reporting on cervical assessment using an online survey. METHODS: We conducted an online survey with 11 images of the cervix to assess how obstetric sonographers and sonologists report on the cervix when there is prominent mucous or funnelling. They were asked five questions about the image of the cervix. A kappa coefficient was calculated from the responses. RESULTS: We had 151 complete responses to the online survey. For the images which showed funnelling or prominent cervical mucous, there was little agreement regarding the cervix being open or closed and regards the location of the internal os. The Kappa coefficient was 0.22 indicating a low level of agreement for the location of the internal os. CONCLUSION: There is lack of agreement amongst Australian specialists and sonographers reporting on cervical assessment when there is prominent mucous or funnelling seen in the cervix. We propose a method to standardise reporting on the cervix incorporating the chorioamniotic membrane for the identification of the inner cervical os when there is prominent mucous or funnelling.

Cervical mucus status can be accurately estimated by transvaginal ultrasound during fertility evaluation.

Examinations of the cervical mucus for determining its quantity and physical characteristics are used to provide a clinical marker for the timing of ovulation. We propose that transvaginal ultrasound, which is routinely used as a tool for monitoring follicular growth in patients undergoing ovulation induction, might also be used simultaneously for estimating cervical mucus measurements. With no additional effort or expense, these data may help to optimize individual patient management.

Qualitative glandular cervical score as a potential new sonomorphological parameter in screening for preterm delivery.

This study compared diagnostic accuracy of sonographic assessment of cervical length (CL) and qualitative glandular cervical score (QGCS), in the second trimester regarding the prediction of preterm delivery (PTD) in the low-risk population. Cervical length < or = fifth percentile for our population was defined as shortened. The parameters evaluated in QGCS were: cervical mucus area and deepest invasion of cervical glands, and score < or = fifth percentile for our population was defined as low. Shortened CL was found in 6.1% whereas the low QGCS was found in 5.5%. The incidence of PTD < 34 completed wk was 2.1%, and between 34 to 37 wk it was 3%. Low QGCS in comparison with shortened CL had twofold higher likelihood ratio (LR) (23; 95% CI [12 to 43] versus 11; 95% CI [5 to 25]) for PTD < 34 completed wk and fourfold higher LR (12; 95%CI [5 to 28] versus 3; 95% CI [1 to 13]) for PTD between 34 to 37 wk. Low QGCS has the same if not better accuracy in comparison with shortened CL regarding the prediction of PTD in the low-risk population.

Matrix metalloproteinases and their inhibitors in the cervical mucus plug at term of pregnancy.

OBJECTIVE: This study was undertaken to evaluate the presence of matrix metalloproteinases (MMPs) and their inhibitors in the cervical mucus plug obtained during active labor at term. STUDY DESIGN: Cervical mucus plugs from 17 healthy women in normal active labor were homogenized, extracted, and analyzed by 4 different assays. RESULTS: Gelatin zymography revealed large amounts of MMP-2 and MMP-9, and triple-helical collagen degradation demonstrated collagenase activity (MMP-8). Reverse zymography showed that tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2 are detectable in the cervical mucus plug. Quantification by enzyme-linked immunosorbent assay confirmed the presence of MMP-2, MMP-8, MMP-9, and TIMP-1. CONCLUSION: Our results suggest that proteolytic or nonproteolytic effects of MMP and TIMP may play a part in the function of the cervical mucus plug of pregnancy.

Radioactivity in cervical mucus after intraperitoneal deposition of Tc-99m labelled albumin particles before and after sterilisation.

OBJECTIVE: To study the transport of radiolabelled albumin particles from the pouch of Douglas to cervical mucus. STUDY DESIGN: A prospective randomised study, including 10 healthy women, undergoing laparoscopic sterilization. A solution of human serum albumin particles, labelled with Technetium 99(m) (Tc-99(m)) was injected into the pouch of Douglas, either before or after sterilisation. RESULTS: Gamma camera images showed gradual spread to the entire peritoneal cavity. Blood samples, showed increasing levels of radioactivity. Measurement of radioactivity in cervical mucus showed significant activity both in women sterilized before and after the deposition. CONCLUSION: The study showed evidence of transport of radioactivity from the pouch of Douglas to cervical mucus. The transport seemed to consist of free activity since no radionuclide labelled particles could be detected in cervical mucus. The transport was probably haematogenous or lymphatic and not intraluminal through the fallopian tube. Further studies utilizing particles comparable in size to fertilized ova are required to design methods for evaluating the transport from the fallopian tube to the uterine cavity.

Ultrasonographic assessment of endocervix and cervical mucus in ovulatory menstrual cycles.

OBJECTIVE: In addition to the routinely used methods to evaluate the menstrual cycle, a new method will be described, assessing the aspect of the endocervix and the presence of cervical mucus by transvaginal ultrasonography. STUDY DESIGN: 36 healthy female volunteers with regular menstrual cycles participated in the study. Transvaginal ultrasonography was performed every other day until ovulation was observed, assessing the diameter of the largest ovarian follicle, endometrial thickness, the aspect of the endocervix, and the presence of cervical mucus. On the same days serum hormone concentrations were determined. RESULTS: Changes in the echodensity of the endocervix were observed in 35 volunteers, from 7 (1-19) (median and range) days before ovulation onwards. The presence of cervical mucus could clearly be observed in the preovulatory phase in 25 volunteers, from 3 (1-7) days before ovulation onwards. CONCLUSION: Preovulatory changes in the aspect of the endocervix and cervical mucus can be observed by transvaginal ultrasonography. Ultrasonography of the cervix may offer an additive diagnostic tool in fertility disorders and will, in many cases, make visual inspection of the cervix unnecessary.

Efficacy of methods for determining ovulation in a natural family planning program.

OBJECTIVE: To evaluate the efficacy in ovulation detection of methods used in natural family planning in comparison with pelvic ultrasonography. DESIGN: Prospective analysis of ovulation detection by natural family planning methods and ultrasonography. SETTING: Natural family planning clinic, Department of Obstetrics and Gynecology, University of Naples "Federico II". PATIENT(S): Forty healthy women who were highly motivated to use natural family planning. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Transvaginal ultrasonographic findings, urinary LH levels, salivary beta-glucuronidase activity, salivary ferning levels and characteristics of cervical mucus, and BBT. RESULT(S): Urinary LH level determination yielded a 100% correlation with the simultaneous ultrasonographic diagnosis of ovulation. Mucus sensations and characteristics yielded a 48.3% correlation when simultaneously evaluated with ovulation. Beta-glucuronidase levels yielded a 27.7% correlation. The salivary ferning test had a 36.8% ovulation-detection rate the day of ovulation, but 58.7% of results were uninterpretable. Body temperature measurements yielded a 30.4% correlation with the simultaneous ultrasonographic diagnosis of ovulation. CONCLUSION(S): Measuring urinary LH levels is an excellent method for determining ovulation. Although variations in mucus characteristics and basal body temperature correlate somewhat with ovulation, the length of the fertile period is overestimated with these methods. The salivary ferning test and measurement of beta-glucuronidase levels are not good methods for home ovulation testing.

PIP: This methodological study aims to evaluate the efficacy of methods used for determining ovulation in a natural family planning in comparison with pelvic ultrasonography. Prospective analysis of ovulation detection methods was conducted with 40 women. Ovulation-detection methods employed in the study include transvaginal ultrasonography, daily morning urinary luteinizing hormone (LH) determinations, determination of salivary beta-glucuronidase activity, salivary ferning test, determination of cervical mucus levels and characteristics, and measurement of rectal or oral basal body temperature. Results revealed a 100% correlation between urinary LH level and ovulation diagnosis obtained from ultrasonographic examination. Other ovulation-detection methods contain the following correlation results: mucus sensations and characteristics, 48.3%; alpha-glucuronidase, 27.7%; and salivary ferning test, 36.8%. These findings draw the researchers to conclude that self-determination of LH levels could be an excellent method in ovulation determination.

Uterine endometrial cavity movement and cervical mucus.

Uterine endometrial movements were observed by transvaginal ultrasound during mid- and late follicular phase and luteal phase in 273 cycles (180 spontaneous cycles in 72 patients; 75 clomiphene citrate cycles in 18 patients; 18 gonadotrophin cycles in 11 patients). The percentage of scans with endometrial movements was 74% in the mid-follicular phase, 96% in the late follicular phase and 72% in the luteal phase. Movements of endometrial cavity echo-free space were observed only in the late follicular phase when the cervical mucus was abundant. The direction of these endometrial cavity movements was objective and therefore distinct. The movements were either vertical (cervix-fundus) or horizontal at the fundus, often to and fro, not unidirectional. The endometrial cavity echo-free space content showed a fern-leaf pattern similar to that of cervical mucus. Thus the content might be cervical mucus plus endometrial secretion, and these fluids might be circulating, flushing or communicating via the cervical canal and the Fallopian tubes through these endometrial cavity movements.