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PubMed2005

Development and characterization of bioadhesive vaginal films of sodium polystyrene sulfonate (PSS), a novel contraceptive antimicrobial agent.

PURPOSE: Polystyrene sulfonate (PSS) is a novel noncytotoxic antimicrobial contraceptive agent. A gel formulation of PSS was found safe for vaginal administration in phase I clinical trials. The purpose of the current study was to develop and evaluate novel bioadhesive vaginal film formulations of PSS. METHODS: PSS films were prepared by solvent evaporation and optimized for various physical, mechanical, and aesthetic properties. Further, films were evaluated for various biological activities and safety. RESULTS: Vaginal films containing 300 mg PSS per unit have been developed, using generally regarded as safe (GRAS) listed excipients. The films are colorless, transparent, thin, soft, and tough, dissolve rapidly in physiologic fluid to form a smooth, viscous and bioadhesive solution that could be retained in the vagina for prolonged intervals. Sperm function inhibition (hyaluronidase and cervical mucus penetration) and antimicrobial activities against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) by PSS films were found comparable to PSS. Also, films did not inhibit normal vaginal microflora (Lactobacillus) and were noncytotoxic as indicated by negligible sperm immobilization and cytotoxicity to host cell assays. CONCLUSIONS: Rapidly dissolving bioadhesive vaginal film formulation of PSS with desired physical, mechanical, aesthetic, and biological properties is a suitable candidate vaginal microbicide for prevention of sexually transmitted disease (STDs) and is ready for toxicological and clinical evaluation.

Animals↗
PubMed1994

The effect of a surgical lubricant on in vivo sperm penetration of cervical mucus.

The implications of these data is that coital lubricants may impair fertility of some couples. Unfortunately, conception was not an end point on this study, and our conclusions must be considered inferential. Nevertheless, the results from this study lead us to recommend avoidance of surgical lubricants by couples attempting pregnancy.

Adult↗
PubMed2003

Immune profiling of plasma and cervical secretions using recycling immunoaffinity chromatography.

Small volumes of cervical secretions have limited measurements of immunity at the cervix, which may be important to studies of human papillomavirus (HPV). We report the use of recycling immunoaffinity chromatography to efficiently study immune profiles in cervical secretions. Frozen pairs of plasma and cervical secretions (collected on ophthalmic sponges) were selected randomly from women with normal cervical cytology (n = 50) participating in a natural history study of HPV in Guanacaste, Costa Rica. Single 25- micro l aliquots of plasma and (diluted) cervical secretions were assayed for interleukin (IL) -1 beta, -2, -4, -6, -8, -10, -12, -13, -15, IFN-alpha, -beta, -gamma, tumor necrosis factor-alpha, -beta, RANTES (regulated on activation normal T-cell express and secreted), MCP-1 (monocyte chemoattractant protein), -2, -3, macrophage inflammatory protein-1 alpha, -1 beta (regulated on activation normal T-cell express and secreted), macrophage colony-stimulating factor, IgG, IgA, and cyclooxygenase 2. All of the specimens were tested as blind replicates, and refrozen plasma was retested 4 months later. To evaluate the reproducibility of the repeat measurements and to examine the correlation between plasma and cervical secretions, we calculated kappa values with 95% confidence intervals among categorized analyte values and Spearman correlation coefficients (rho) among detectable, continuous analyte values. Measurements of all of the analytes in either plasma or cervical secretions were highly reproducible, with all of the kappa > or = 0.78 (70% above 0.90), and all of the rho > or = 0.88 (96% above 0.90). Only IL-1 beta (kappa = 0.60 and rho = 0.82) and IL-6 (kappa = 0.50 and rho = 0.78) levels were strongly correlated between plasma and cervical secretions. IFN-gamma, tumor necrosis factor-beta, RANTES, MCP-1, MCP -2, macrophage inflammatory protein-1 alpha, and macrophage colony-stimulating factor levels were especially poorly correlated between plasma and cervical secretions (kappa < or = 0.25 and rho < or = 0.25). We conclude that recycling immunoaffinity chromatography is a reproducible method of measuring immune profiles from biological specimens, and immune profiles are not well correlated between plasma and cervical secretions, perhaps necessitating cervical collections to study cervix-specific immunity in HPV natural history studies.

Adult↗
PubMed1982

Ultrasound timing of human chorionic gonadotropin administration in clomiphene-stimulated cycle.

Seventeen patients treated with clomiphene citrate were examined using real-time ultrasound timing 28 ovulatory cycles to determine the pattern of follicular development under clomiphene stimulation. The rate of growth was faster, but the follicular diameter range at ovulation was similar to that during spontaneous cycles. This information was used to time midcycle human chorionic gonadotropin (hCG) administration in over 97 cycles in 21 patients responsive to clomiphene who had not conceived. When hCG was given when the mean follicular diameter reached 18 mm, 92% of these cycles were ovulatory. Fourteen patients (67%) conceived within 6 ovulatory treatment cycles. Five of 7 patients (71%) who did not conceive were found to have endometriosis at laparoscopy. Midcycle cervical scores were significantly lower in clomiphene-treated as compared with spontaneous ovulatory cycles, and additional treatment with ethinyl estradiol did not effect a significant improvement. Timing of midcycle hCG using ultrasound is an effective method of inducing ovulation in patients in whom an estrogenic follicular response without ovulation is obtained with clomiphene treatment.

Cervix Mucus↗
PubMed2005

Intra-uterine insemination versus timed intercourse for cervical hostility in subfertile couples.

BACKGROUND: The postcoital test has poor diagnostic and prognostic characteristics. Nevertheless, some physicians believe it can identify scanty or abnormal mucus that might impair fertility. One way to avoid 'hostile' cervical mucus is intrauterine insemination. With this technique, the physician injects sperm directly into the uterine cavity through a small catheter passed through the cervix; the theory is to bypass the "hostile" cervical mucus. Although most gynaecological societies do not endorse use of intrauterine insemination for hostile cervical mucus, some physicians consider it an effective treatment for women with infertility thought due to cervical mucus problems. OBJECTIVES: The aim of this review was to determine the effectiveness of intrauterine insemination with or without ovarian stimulation in women with cervical hostility who failed to conceive. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), POPLINE (to June 2005) and LILACS (to June 2005). In addition, we contacted experts and searched the reference list of relevant articles and book chapters. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing intrauterine insemination with intercourse timed at the presumed fertile period. Participants were women with cervical hostility who failed to conceive for at least one year. DATA COLLECTION AND ANALYSIS: We assessed the titles and abstracts of 386 publications and two reviewers independently abstracted data on methods and results from five studies identified for inclusion. The main outcome is pregnancy rate per couple. MAIN RESULTS: We did not pool the outcomes of the included five studies in a meta-analysis due to the methodological quality of the trials and variations in the patient characteristics and interventions. Narrative summaries of the outcomes are provided. Each study was too small for a clinically relevant conclusion. None of the studies provided information on important outcomes such as spontaneous abortion, multiple pregnancies, and ovarian hyperstimulation syndrome. AUTHORS' CONCLUSIONS: There is no evidence from the published studies that intrauterine insemination is an effective treatment for cervical hostility. Given the poor diagnostic and prognostic properties of the postcoital test and the observation that the test has no benefit on pregnancy rates, intrauterine insemination (with or without ovarian stimulation) is unlikely to be a useful treatment for putative problems identified by postcoital testing.

Biomarkers↗
PubMed2001

Acupuncture for cervical ripening and induction of labor at term--a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate whether acupuncture at term can influence cervical ripening, induce labor and thus reduce the need for postdates induction. METHODS: On the estimated date of confinement (EDC) women were prospectively randomized to an acupuncture group (AG) or a control group (CG). Data of 45 women were evaluated (AG, n = 25; CG, n = 20). Inclusion criteria were as follows: confirmed EDC, uncomplicated course of pregnancy, singleton pregnancy in cephalic presentation. Exclusion criteria were as follows: cervical dilation > 3 cm, active labor, premature rupture of membranes, previous cesarean section, pathologies in mother or fetus. Women were examined at 2-day intervals. The cervical length was measured with vaginal ultrasonography, cervical mucus was obtained for a fetal Fibronectin test and the cervical status was assessed according to the Bishop score. In the AG, the points Hegu (Large Intestine 4) and Sanyinjiao (Spleen 6) were pierced on both sides every second day. If women were not delivered 10 days after EDC, labor was induced by administering vaginal prostaglandin tablets. RESULTS: The cervical length in the AG was shorter than that in the CG on day 6 and day 8 after EDC (P = 0.04 for both). In the AG the time period from the first positive Fibronectin test to delivery was 2.3 days, while that in the CG was 4.2 days (P = 0.08). The time period from EDC to delivery was on average 5.0 days in the AG and 7.9 days in the CG (P = 0.03). Labor was induced in 20% of women in the AG (n = 5) and in 35% in the CG (n = 7) (P = 0.3). Overall duration of labor, and first and second stage of labor were not different in the two groups. In 56% of women who underwent acupuncture (n = 14) and in 65% of controls (n = 13), Oxytocin was used to augment labor. (P = 0.54). CONCLUSION: Acupuncture at points LI4 and SP 6 supports cervical ripening at term and can shorten the time interval between the EDC and the actual time of delivery.

Acupuncture Points↗
PubMed1982

Initial evaluation of a convection counter streaming galvanization technique of sex separation of human spermatozoa.

A new method for separating X and Y human spermatozoa called convection counter streaming galvanization was evaluated. The method was independently performed by this semenology laboratory with the use of the special separation equipment and extending media provided by its developer, Dr. Bhairab C. Bhattacharya. The mean number of Y spermatozoa increased from 48% to 77% in the separated fraction predicted to be Y-enriched. The fraction predicted to be X-enriched increased from a mean of 52% to 77%. The one separation process allowed accumulation of both enriched fractions simultaneously. The separated portions of spermatozoa maintained good motility and penetration of cervical mucus but produced a mean recovery concentration in the X- and Y-enriched fractions of only 15% to 16% of the preseparation concentration.

Cell Separation↗
PubMed1989

Clinical evaluation of the Capronor contraceptive implant: preliminary report.

Capronor, a single-capsule, biodegradable, subdermal contraceptive that releases levonorgestrel over a 12- to 18-month period, has been evaluated in 48 healthy women, ages 18 to 40 years. Sixteen participants received a 2.5 cm capsule (12 mg of levonorgestrel), and 32 received a 4.0 cm capsule (21.6 mg of levonorgestrel). Serum levonorgestrel levels were significantly lower in the 2.5 cm group. Ovulation occurred in all cycles in the 2.5 cm group and in 26.3% of cycles in the 4.0 cm group. Levonorgestrel levels with the shorter capsule were too low for reliable contraception in all users, and 4 cm may be a minimal functional length. Bleeding patterns were regular in most women who ovulated and irregular in most remaining subjects. It is assumed that changes in cervical mucus and the endometrium contributed to effective contraception despite the frequency of ovulation.

Administration, Cutaneous↗
PubMed1993

[Male infertility of immunologic origin and its treatment].

Antibodies against sperm surface antigens may be responsible for 3 to 20% of idiopathic male infertility cases. Antisperm immunisation may be suspected in view of a clinical suggestive history, a spontaneous sperm-agglutination and an inability of spermatozoa to penetrate a normal cervical mucus. The responsibility of antisperm antibodies in the infertility state could be demonstrated in vitro by their effects on several sperm functions. An inverse correlation between antibodies titres and conception rates has been demonstrated and it justifies a therapeutical approach in the presence of high levels of antibodies. Corticosteroids must not be used as the results obtained did not justify the side effects observed. Intra-uterine insemination as well as in vitro fecundation can help some of these couples but results must be improved by better methods of selection of motile sperm populations devoid of antibodies.

Antibodies↗
PubMedDate not supplied

[Diagnosis of urogenital chlamydiosis using rapid immunoenzyme method: Abbott TestPack Chlamydia].

Twenty women suffering from chronic genital inflammations were screened for urogenital chlamydiosis using Abbott Testpack Chlamydia kit for enzyme immunoassay (EIA) and NIARmedik Chlamoscan kit for immunofluorescent method. The cells were scraped off from the cervical canal during the second phase of the cycle. In addition, smears were taken from the vagina and cervical canal to be screened for microflora using Romanowsky-Giemsa staining. EIA detected C. trachomatis antigens in 3 (15%) out of 20 examinees, whereas direct immunofluorescence revealed these antigens in only 2 (10%) patients. The results differed in a patient with urogenital candidiasis. Evidently, the system of special filters in the Testpack Chlamydia releases the cell suspension from concomitant cell dendrites, blood, mucus, and thus increases the sensitivity of the test.

Adolescent↗
PubMed1989

Polymerase chain reaction for fast, nonradioactive detection of high- and low-risk papillomavirus types in routine cervical specimens and in biopsies.

A polymerase chain reaction (PCR) procedure capable of amplifying specific DNA sequences by up to a millionfold was developed for detection of infection by human papillomaviruses (HPVs) of low (HPV6, HPV11) or high (HPV16, HPV18, HPV33) oncogenic potential. For high-risk HPVs the region chosen was within the E6 open reading frame, which can become integrated into genomic DNA. A region corresponding to this was chosen for low-risk HPVs. After repeated cycles of specific oligonucleotide-primed extension of viral DNA with Klenow or thermophilic DNA polymerase, the type of HPV present was then determined on the basis of the size of the ethidium-bromide-stained band visible after polyacrylamide gel electrophoresis: for HPV6 or 11 the band was approximately 120 bp, for HPV 16 or 33 it was approximately 200 bp, and for HPV18 it was approximately 100 bp. Specific hybridization to the relevant band was seen using radioactive or nonradioactive (alkaline-phosphatase-linked) target oligonucleotide probes. Using the PCR method, we have determined, within as little as a few hours, the infection status of a variety of clinical specimens, including cervical scrapes and lavages, anal scrapes, and anogenital biopsies. The PCR steps can be automated, adding to the potential of PCR for widespread use in the detection of HPV, which is becoming increasingly popular in cervical screening.

Biopsy↗
PubMed1984

ELISA for quantitative measurement of low-molecular-weight bronchial protease inhibitor in human sputum.

A double-antibody sandwich enzyme-linked immunosorbent assay is described to quantify the low-molecular-weight bronchial protease inhibitor in sputum and other body fluids. Relatively large amounts of this inhibitor were found in sputum, saliva, nasal secretions, seminal plasma, cervical mucus, and tear fluid. The inhibitor concentration in sputum varied from 4 to 405 micrograms/ml (mean, 66 micrograms/ml). With this assay, it was shown that in sputum the inhibitor is concentrated in the mucin-containing gel phase.

Body Fluids↗
PubMed2003

[Chlamydial heat shock protein (hsp 60) and fertility disorders].

OBJECTIVE: Summarization of recent knowledge on heat shock proteins (HSPs) of human and bacterial (chlamydial) origin and their participation in fertility disturbances. DESIGN: Review article for training of physicians (gynecologists and obstetricians). SETTING: Veterinary Research Institute, Brno. METHOD AND RESULTS: The subject of the study is heat shock protein--hsp60 as a significant epitope Chlamydia trachomatis. Heat shock proteins are induced as a response to various stress insults from external environment (hyperthermy, UV radiation, free oxygen radicals, heavy metals, ethanol etc.) and certain processes related to the cell cycle. Sensitization with the heat shock protein Chlamydia trachomatis and subsequent excretion of highly homologous human heat shock protein are co-operating factors in the development of fertility disturbances. Significant levels of IgA antibodies to hsp60 occur in cervical mucus of women and in seminal plasma of men with fertility disturbances. CONCLUSION: Preceding infection C. trachomatis and resulting sensitization with chlamydial heat shock protein indicate an unfavourable prognosis of the reproductive outcome and impairs the perspective of a successful in vitro fertilization.

Antibodies, Bacterial↗
PubMed1986

A standardized approach for evaluating the penetration of human spermatozoa into cervical mucus in vitro.

Carefully timed and quantitated Kremer-type tests were performed for assessment of sperm-mucus interaction in 100 couples who underwent an infertility workup. A novel scoring system for these in vitro tests was elaborated and validated. The success of penetration of seminal spermatozoa into the mucus, and their migration within the mucus column, was related to both the sperm concentration and their motility, especially their progressivity. A calculated index of sperm motility quality gave a 70% accuracy rate in predicting the test result (normal versus abnormal), but this success rate was not significantly improved by incorporation of the sperm concentration into the index. No clear biologic relationship was found between this method for assessing Kremer-type tests (which correlated closely with accepted clinical reporting practices) and Katz's "percentage of successful collisions." This apparent discrepancy is considered to reflect basic differences in the approaches of the two scoring systems.

Cervix Mucus↗
PubMed1981

A study to determine the effect of Betadine Vaginal Cleansing Kit on cervical flora after insertion of an intra-uterine contraceptive device.

Twenty-four women with negative high vaginal swabs, who attended for insertion of an intra-uterine contraceptive device, were randomly allocated to two groups. One group used the Betadine Vaginal Cleansing Kit before and after insertion of the intra-uterine device; the other group did not use any cleansing agent. After 4 to 6 weeks, the patients were re-examined and a cervical swab was taken. The bacteriological findings were of interest and significance. In the study group there was bacterial in only one patient out of the twelve, whereas in the control group there was bacterial growth in ten out of the twelve. The bacteria grown were of doubtful clinical significance, but in certain circumstances they could take a pathogenic role. The marked absence of bacterial growth in the study group is significant because, during a 4 to 6 week period, the cervical mucus remained sterile thus minimizing the risk of pelvic infection during and immediately after insertion. Whether is has any significant effect in the long-term reduction of the incidence of pelvic infection remains to be seen, and further studies are needed.

Adolescent↗
PubMed2005

Delimitation of squamous cell cervical carcinoma using infrared microspectroscopic imaging.

Infrared (IR) spectroscopic imaging coupled with microscopy has been used to investigate thin sections of cervix uteri encompassing normal tissue, precancerous structures, and squamous cell carcinoma. Methods for unsupervised distinction of tissue types based on IR spectroscopy were developed. One-hundred and twenty-two images of cervical tissue were recorded by an FTIR spectrometer with a 64x64 focal plane array detector. The 499,712 IR spectra obtained were grouped by an approach which used fuzzy C-means clustering followed by hierarchical cluster analysis. The resulting false color maps were correlated with the morphological characteristics of an adjacent section of hematoxylin and eosin-stained tissue. In the first step, cervical stroma, epithelium, inflammation, blood vessels, and mucus could be distinguished in IR images by analysis of the spectral fingerprint region (950-1480 cm(-1)). In the second step, analysis in the spectral window 1420-1480 cm(-1) enables, for the first time, IR spectroscopic distinction between the basal layer, dysplastic lesions and squamous cell carcinoma within a particular sample. The joint application of IR microspectroscopic imaging and multivariate spectral processing combines diffraction-limited lateral optical resolution on the single cell level with highly specific and sensitive spectral classification on the molecular level. Compared with previous reports our approach constitutes a significant progress in the development of optical molecular spectroscopic techniques toward an additional diagnostic tool for the early histopathological characterization of cervical cancer.

Carcinoma, Squamous Cell↗
PubMed1994

Differential apomucin expression in normal and neoplastic human gastrointestinal tissues.

BACKGROUND/AIMS: The cloning of genes encoding human mucins is the basis for the study of their normal tissue distribution and the alterations associated with cancer. The aim of this study was to determine the normal and tumor tissue expression of MUC1, MUC2, MUC5B, and MUC5C. METHODS: The reactivity of apomucin-specific antibodies with fresh normal and tumor tissues was analyzed using immunohistochemical techniques. RESULTS: Anti-MUC1 antibodies reacted with most glandular epithelia. Anti-MUC2 antibody was mainly reactive with intestinal goblet cells and cervical mucous cells. Anti-MUC5B was reactive with a wide range of epithelial tissues whereas anti-MUC5C was reactive with stomach, trachea, and endocervix. Double-labeling experiments showed coexpression of MUC1/MUC2 and MUC2/MUC5C in colonic tissue. Multiple apomucins were detected in colon cancers, but no relationship to histochemical mucus stains was observed. CONCLUSIONS: It is concluded that (1) each apomucin shows a distinct tissue expression pattern; (2) multiple apomucins are present in a single tissue and at the single cell level; and (3) altered apomucin expression takes place in pathological colonic tissue.

Amino Acid Sequence↗
PubMed1997

Evaluation of the postcoital test in cycles involving exogenous gonadotropins.

OBJECTIVE: To evaluate the hypothesis that a postcoital test, optimally performed in the periovulatory period of cycles in which gonadotropin-induced superovulation was used, correlates with cycle fecundity. METHODS: Of 1135 total consecutive cycles, 367 first cycles were analyzed from the reproductive endocrinology and infertility service of a university medical center. This referral population had a mean age of 34.6 years for the female partner, a nulliparity rate of 81%, and a mean length of infertility of 4.8 years. Postcoital tests were performed 36-40 hours after hCG administration in gonadotropin-stimulated cycles. Clinical pregnancy was defined as fetal cardiac activity as seen on transvaginal ultrasound examination. RESULTS: Couples with no sperm observed per high-power field in the cervical mucus achieved a 16% fecundity rate (21 pregnancies in 129 cycles), one to ten sperm a 18% fecundity rate (28 pregnancies in 154 cycles), and more than ten sperm a 15% fecundity rate (13 pregnancies in 84 cycles). There was no significant difference between groups (n = 367, P = .85); the power to detect a statistically significant difference was .82. As validation of optimal cervical mucus, fecundity rates were compared with these postcoital test values across the entire range of peak periovulatory serum estrogen levels, and no correlation was seen (P = .61, .86, and .96 for estrogen levels of 201-500, 501-1500, and 1501-3433 pg/mL, respectively). CONCLUSION: With precise periovulatory timing and supraphysiologic estrogen levels optimizing qualitative cervical mucus characteristics in gonadotropin-induced cycles, the number of sperm observed per high-power field does not correlate with cycle fecundity.

Adult↗