Probable mode of action of oral contraceptives.
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This is a report of the variations of cervical mucus of women wearing different kinds of IUDs, before and after the insertion. We could not find significant variations of the clinical patterns in women wearing copper IUDs, but noticeable variations were found in progesterone releasing device users.
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Previous studies from this center have indicated that the cynomolgus macaque (Macaca fascicularis) may serve as a model for human sperm interaction with the cervix and uterus. In some macaque species, transcervical aspiration of the uterine contents carries a significant risk of disturbing the cervical milieu due to the serpentine nature of the cervix. The only alternatives have been surgical procedures such as laparotomy or laparoscopy. In this paper, we report our experience with a new technique for ultrasound-guided sampling of spermatozoa in the macaque uterus. Twenty adult female cynomolgus macaques were monitored for menses (first day of menses = day 1), and one mating per cycle was allowed on day 10, 11, or 12. In one group of ten animals, cervical mucus was sampled at 3 or 18 hr postcoitus (pc) and ultrasound-guided uterine aspiration was performed at 24 hours pc. In a second group of ten monkeys, uterine aspiration was at six hr pc and sperm numbers and motility were counted in the uterine fluid. Uterine fluid was obtained from fourteen of twenty monkeys. Pregnancy occurred in ten of the twenty experimental cycles. Ultrasound-guided uterine aspiration appears to be a reliable method for the evaluation of sperm transport in female macaques. The correlations between uterine sperm recovery and cervical mucus sperm populations are discussed. The high conception rate in treatment cycles indicates that this procedure can be performed without apparent risk to pregnancy.
An in vitro penetration test employing bovine cervical mucosa to evaluate vaginal contraceptives is presented. Its usefulness for the evaluation of the potency of a formulation in preventing sperm penetration was assessed by comparison of five commercially available preparations, with the use of both human and primate spermatozoa. The results were compared with those obtained with a spermicidal test (Sander-Cramer method) and in vivo with the use of the primate Macaca arctoides. Analysis of the two in vitro tests and the one in vivo test showed a significant degree of concurrence. The cervical mucus test much more closely reflected in vivo results than the Sander-Cramer test. A recommendation is made regarding the type and order of in vitro and in vivo methods to be used for the development and/or testing of new formulations.
The effect of relaxin, a peptide hormone present in seminal plasma, on the penetration of cervical mucus by washed human sperm in vitro was studied. Penetration was analyzed by two methods. The total number of sperm per 100 X field at the 10-mm, 20-mm, and 30-mm points along a mucus-filled capillary tube was counted and the farthest distance 100 sperm and 5 sperm/100 X field penetrated the capillary tube was measured. These measurements were made at 30, 60, and 90 minutes. Treating washed sperm with physiologic concentrations of relaxin resulted in significantly increased sperm penetration as compared with sperm treated with albumin or buffer. Replacing seminal plasma to washed sperm resulted in equivalently increased penetration. The findings strongly suggest that relaxin is necessary for proper penetration of cervical mucus by human sperm.
The postcoital test determines the adequacy of sperm and the receptivity of cervical mucus. It is the only test which evaluates the interaction between sperm and the female genital tract fluids. The Sims-Huhner test should be an integral part of an infertility investigation, but it must not be used as a substitute for semen analysis. Since cervical mucus accurately reflects the ovarian cycle, the PC test is a useful indicator of the endocrine preparation of the female reproductive system. It is also an important method for the evaluation of a variety of contraceptive steroids which may act directly or indirectly upon cervical secretion. For best results the test should be properly timed, meticulously performed, and knowledgeably interpreted.
OBJECTIVE: To improve prediction of ovulation in normal cycles. DESIGN: Collection of women's characteristics and their menstrual cycles. Monitoring and analysis of time relationships between several indicators of ovulation: transvaginal ultrasonography, cervical mucus, basal body temperature, urinary luteinising hormone, and ratio of urinary oestrogen to progesterone metabolites. SETTING: Each of eight natural family planning clinics was to study 12 women for at least three cycles. POPULATION: One hundred and seven normally fertile and cycling women aged 18 to 45. METHODS: Daily measurements of urinary luteinising hormone, follicle stimulating hormone, oestrone-3-glucuronide and pregnanediol-3alpha-glucuronide. Basal body temperature recording and cervical mucus checking. Transvaginal ultrasound examination of the ovaries. MAIN OUTCOME MEASURES: Delays between the expected day of ovulation according to the luteinising hormone peak or to ultrasound evidence and the expected days according to the other indices of ovulation. RESULTS: Ultrasonography was able to show evidence of ovulation in 283 out of 326 cycles. The average time lag between luteinising hormone peak and ultrasound evidence was less than one day (+0.46) but premature and late luteinising hormone-expected date of ovulation were observed in nearly 10% and 23% of cycles, respectively. Basal body temperature rise was observed in 98% of cycles. Cervical mucus peak symptom, rapid drop in the ratio of urinary metabolites, and luteinising hormone initial rise were all close to ultrasonographic evidence in more than 72% of cycles. CONCLUSIONS: For accuracy and practical reasons, the cervical mucus peak symptom, the ratio of urinary metabolites and luteinising hormone initial rise might be better indices of ovulation than the luteinising hormone peak.
BACKGROUND: To verify the expression of neutrophil gelatinase associated lipocalin (NGAL), molecule now arising great interest because of its proposed involvement in cell-cycle regulation, acute phase response and immunomodulation, into extracellular fluids of female reproductive tract, in order to provide useful data to understand its biological functions. The data collected are purely qualitative, just meant to reveal the presence of lipocalin into the assayed fluids, and they have to be considered as preliminary for a quantitative study (in progress at the moment) based on a double antibody radioimmunoassay. METHODS: Three kinds of extracellular fluid were randomly sampled: amniotic fluid (13 samples), cervical mucus (10 samples), coloster (20 samples). The inclusion criteria concerning the selection of the donor women were: age (fertile period), healthy state and pregnancy state. All the samples underwent protein assay, electrophoresis and western blot. RESULTS: All the samples examined revealed NGAL's presence. CONCLUSIONS: The positive results of this study seem to strengthen the hypothesis related to NGAL biological functions, specifically the ones that suggest its role into cell differentiation, embryonic development and inflammation. Therefore the female reproductive tract is suggested as a new promising study object in this research field.
Evaluation of luteal phase function is an important part of fertility evaluation in the female. Among fifty clinically identified patients with primary infertility certain well-established laboratory methods were used to identify the luteal phase defect. These methods included serum progesterone assays, endometrial biopsy, vaginal cytology, basal body temperatures and cervical mucus scoring, with appropriate controls. Based on both endometrial biopsy which was two or more days out of phase and the serum progesterone level of less than 2.5 ng/ml, luteal phase defect was found in five patients among the 50 patients (10 percent). It was found that an endometrial biopsy which was well dated showed a definite correlation with the progesterone assays and could be considered as the most easily performed and reliable indicator, useful in detecting a luteal phase defect.
OBJECTIVE: To determine the clinical significance of endocervical mucus pH on sperm-mucus interaction during infertility investigation. PATIENTS AND MATERIAL: Two hundred sixteen couples with a median duration of infertility of 4 years (range, 1 to 19 years) presenting at the infertility unit of the Women's University Hospital of Heidelberg, Germany. MAIN OUTCOME MEASURES: Determination of endocervical pH by colorimetric and electrometric measurement and correlation of results with the outcome of postcoital testing (PCT) and other parameters of infertility investigation (semen and cervical mucus [CM] quality, microbial colonization of cervix and ejaculates, medical history, hormonal status, and specific medication) and the subsequent fertility in a prospective study. In vitro experiments with the sperm-cervical mucus penetration test (SCMPT) used as biological model. RESULTS: The colorimetric determination of endocervical mucus pH is an easy method, suitable for routine clinical use, correlating significantly with electrometric measurement of pH. Median pH was 7.0 (range, 5.4 to 8.2). The mucus pH was significantly related with the results of PCT, even when mucus and semen variables were taken into account. No significant relationship was seen between the cervical index and mucus pH and the microbial colonization of cervix and ejaculates. The pH of endocervical secretions correlated with the peripheral hormonal status: low pH levels were significantly more frequent in patients with hyperandrogenemia, indicated by high testosterone and/or dehydroepiandrosterone sulfate levels before medication was started, and in hyperandrogenemic patients treated with dexamethasone than in the other women. Oral administration of estrogens led to a subtle alkalinization of the CM. With regard to subsequent fertility 6 months after pH testing, the pregnancy rate was significantly lower in women offering reduced mucus pH on occasion of the PCT in the group of couples with primary infertility and in couples with oligozoospermia of the male partner. The significant influence of pH on sperm-mucus interaction was confirmed in vitro with the SCMPT. CONCLUSIONS: The results indicate that the pH of the CM, easily determined with pH indicator paper, is an important parameter of mucus quality with significant influence on spermatozoal viability in CM, which correlates with peripheral hormonal status and can be affected by oral medication with estrogens. Therefore the routine determination of pH on occasion of the PCT is recommended during infertility investigation.
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PROBLEM: During 1987-1996, cervical mucus spermagglutinating antibodies of secretory immunoglobulin A (sIgA) or IgG detected by the tray agglutination test (TAT) and the indirect mixed antiglobulin reaction (MAR) test were found in 234 women aged 23-29 years with previously unexplained infertility. METHOD OF STUDY: Hydrocortisone was applied to the ectocervix. RESULTS: Spermagglutinating antibodies of sIgA disappeared totally in 102 patients (91 resulting in deliveries of healthy babies, 3 in ectopic pregnancies, and 8 in spontaneous miscarriages). A decrease of spermagglutinating antibodies in ovulatory mucus during hydrocortisone application without pregnancy was registered in 60 infertile women. This group was referred to treatment by in vitro fertilization. No hydrocortisone effect on immunocompetent cells producing antispermatozoal IgG alone or combined with sIgA was seen in 72 patients. CONCLUSIONS: Vaginal mycosis, a side effect of hydrocortisone treatment, was seen in seven cases. Hydrocortisone for local immunosuppression becomes a valuable method of therapy in cervical immunologic infertility caused predominantly by antispermatozoal sIgA.
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BACKGROUND: The aim of this study was to investigate the influence of the solid phase of the mucus hydrogel in facilitating the upward movement of spermatozoa during the menstrual cycle. METHODS: A total of 171 sperm migration experiments using 47 selected ovulatory mucus samples were performed in vitro in tubes of various shape and diameter. Physical constraints applied to cervical mucus combined with scanning electron microscopy (SEM) techniques permitted analysis of the mechanism of sperm orientation within cervical mucus submitted to capillary constraints simulating the various conditions of sperm orientation in vivo. RESULTS: The results support the theory according to which spermatozoa entering the cervical canal are constrained to follow the oriented micellar lines of strain. Stretched ovulatory mucus exhibits noticeable prevalent orientation of most filaments aligned in a manner roughly parallel to the traction axis. By contrast, even after strong stretching applied to luteal-type mucus and longer contact periods, the alignment of glycoproteic meshes was not sufficiently marked to allow spermatozoa to orient themselves and to move rapidly. The results are discussed as a function of the variations occurring in the three-dimensional macromolecular arrangement of the glycoproteic framework subjected to flow constraints. CONCLUSIONS: The study confirms that there is a close relationship between the three-dimensional arrangement of the mucus framework and the ability of spermatozoa to move rapidly in a given direction. The high resolution and three-dimensional aspect of SEM micrographs support the correlation of sperm orientation with current data on rheologic properties of biologic hydrogels.