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Identification of the complement regulatory proteins CD46, CD55, and CD59 in human fallopian tube, endometrium, and cervical mucosa and secretion.

PROBLEM: Complement lytic activity has been demonstrated, and a potential for its activation is present in human cervical and tubal secretions and in the endometrium. This necessitates the presence of regulatory mechanisms for protection of the sperm and the implanting allogeneic conceptus in the female genital tract. Complement regulatory proteins demonstrated on sperm and in seminal fluid have been attributed such a role. It is however likely that additional protection is required for a successful conception and implantation to take place. This lead us to investigate the distribution of the complement regulatory factors in cervical mucus and mucosa, uterine endometrium, and fallopian tube. METHOD: Endometrium and cervical mucosa were obtained from patients undergoing hysterectomy for benign conditions, and specimens were selected from different stages of the menstrual cycle. Fallopian tubes were obtained from patients submitted for sterilization, while cervical mucus was aspirated from volunteers undergoing gynecological examination. Immunohistochemistry was performed on all tissue samples, using monoclonal antibodies to membrane cofactor protein (MCP), decay accelerating factor (DAF), CD59 and complement receptor 1 (CR1). Western blot analysis was performed on cervical mucus under nonreducing conditions. RESULTS: MCP, DAF, and CD59 were found to be expressed in human endometrium and fallopian tube. No variation in expression was detected throughout the menstrual cycle. CR1 was not expressed. Soluble forms of DAF and CD59 were found to be present in cervical mucus. CONCLUSION: The complement regulatory proteins MCP, DAF, and CD59 are expressed throughout the female genital tract, and may thus play an important role in protecting the traversing sperm and implanting blastocyst from complement mediated damage.

Antibodies, Monoclonal↗

A phase I study of Femcap used with and without spermicide. Postcoital testing.

The objectives of the study were to assess the ability of the Femcap, a new vaginal contraceptive device made of silicone and designed to fit snugly around the cervix to prevent the penetration of sperm into midcycle cervical mucus when used with and without spermicide; and to compare it with the standard contraceptive diaphragm used with spermicide. Eight women underwent two baseline cycles of postcoital testing in which no device was used, followed by three test cycles in which Femcap with spermicide, Femcap with nonspermicidal lubricant (K'Y gel) or the Ortho All-Flex diaphragm with spermicide was used. The sequence of testing cycles was randomized. In each cycle, condoms were used prior to midcycle, then a midcycle cervical mucus specimen was examined to ensure midcycle characteristics and the absence of sperm. Each woman then had intercourse using either no device (baseline cycles) or the prescribed device (test cycles) and returned 2-3 h afterwards. Cervical mucus was again assessed for adequacy and the presence of spermatozoa. The average number of progressively motile sperm seen per high power field was as follows: first baseline cycle, 18.0; second baseline cycle, 17.8; test cycle with Femcap used with nonspermicidal lubricant, 0.1; test cycle with Femcap used with spermicide, 0.2; and test cycle with the diaphragm used with spermicide, 0.0. There was no significant difference between baseline cycles or among test cycles in the average number of progressively motile sperm seen (p > 0.05). The average number of progressively motile sperm seen in each test cycle did, however, differ significantly from the average number seen in either baseline cycle (p < 0.05). Femcap, used with either a spermicidal lubricant or a nonspermicidal lubricant, appears to be comparable with the diaphragm used with spermicide in preventing sperm from entering midcycle cervical mucus.

Cervix Mucus↗

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.

Adolescent↗

A prospective multicentre trial of the ovulation method of natural family planning. I. The teaching phase.

The percentage of 869 women in five countries capable of being taught to recognize the periovulatory cervical mucus symptom of the fertile period was determined in a prospective multicentre trial of the ovulation method of natural family planning. The women were ovulating, of proven fertility, represented a spectrum of cultures and socioeconomic levels, and ranged from illiteracy to having postgraduate education. In the first of three standard teaching cycles, 93% recorded on interpretable ovulatory mucus pattern. Eighty-eight per cent of subjects successfully completed the teaching phase; 7% discontinued for reasons other than pregnancy, including 1.3% who failed to learn the method. Forty-five subjects (5%) became pregnant during the average 3.1-cycle teaching phase. The average number of days of abstinence required by the rules of the method was 17 in the third teaching cycle (58.2% of the average cycle length). To what extent the findings of this study can be extended to other couples remains to be demonstrated.

Adult↗

Field trial of billings ovulation method of natural family planning.

There are couples with unmet family planning needs and couples who do not use any modern method, yet they desire to space or avoid pregnancies. Many of them look for safe and effective options like the natural family planning methods. The Billings Ovulation Method based on single index cervical mucus parameter is one such option. The present multicentre trial conducted in India has shown an encouraging use-effectiveness of the method, indicating method failure as low as 1.5 +/- 0.3 and use-failure 15.9 +/- 0.8 per 100 users at 21 months. The method continuation rates have also been as high as 88.3/100 users at 6 months and 52.0/100 users at 21 months.

Adult↗

Identifying the fertile phase of the human menstrual cycle.

The identification of the human fertile phase as the time during which a woman or a couple may conceive is elusive. The fertile time depends on many factors in each individual menstrual cycle and may be said to be more of a statistical than a physiological entity. This paper reviews the application of statistical methods to three areas related to conception and the fertile phase. The first is the prediction and detection of ovulation from serial measurements, such as hormones, basal body temperature and cervical mucus, throughout the menstrual cycle. Typically, such variables increase from some baseline level to a peak around ovulation (the most fertile time), then subside to low levels in the postovulatory phase. The statistical challenge is to detect the rise (signalling the onset of potential fertility) and subsequent fall. Analytic methods considered include thresholds, Bayesian change-point models and particularly the cumulative sum (cusum) technique which is both simple to apply and understand, and effective. The second area comprises appropriate methods of analysing and interpreting data from clinical studies of the fertile phase, especially in so-called natural family planning (NFP) where it is usual for women to observe several indices of potential fertility. Such studies usually try to establish the temporal relationships between markers of the fertile phase and examine the success of different combinations of markers in delineating the fertile time in comparison with a standard 'defined' phase, for example, the interval from three days before to two days after the peak of luteinizing hormone. The third area is the assessment of the probability of conception on certain days of the cycle, which is vital to the understanding of the fertile phase and its application to NFP. Direct estimation of such probabilities is impractical; instead, resort must be made to estimation by maximum likelihood of the parameters of specially constructed models. Suitable models are described. Finally, the need for a new prospective study of the probability of conception in relation to the markers of the fertile phase used in the symptothermal method of NFP is discussed.

Female↗

Reduced fertilization rates in older men when cervical mucus is suboptimal.

OBJECTIVE: Cervical mucus is vital in the regulation of sperm survival and transport through the reproductive tract. The goal of this study is to assess whether the lowered fertility for men in their late 30s and early 40s is related to the nature of cervical mucus on the day of intercourse. METHODS: In a prospective study of 7 European family planning centers, 782 couples not using birth control recorded daily observations of intercourse and the nature of cervical mucus. Using data from 1,459 menstrual cycles, 342 ending in pregnancy, we estimate day-specific conception probabilities in relation to mucus and male and female age. RESULTS: On days where cervical mucus was not evident, intercourse for men in their late 30s and early 40s was 50% less likely to result in a clinical pregnancy, adjusting for intercourse timing and female age. As secretions become more conducive to sperm transport, the effect of male age diminishes steadily from 21% on days with damp secretions, to 11% on days with thick mucus, to only 4% on days with most fertile-type mucus. CONCLUSION: The effect of male age on fecundability can be minimized by timing intercourse on days with optimal secretions. LEVEL OF EVIDENCE: II-2.

Adult↗

The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices.

Modern hormonal contraceptives and intrauterine contraceptive devices have multiple biologic effects. Some of them may be the primary mechanism of contraceptive action, whereas others are secondary. For combined oral contraceptives and progestin-only methods, the main mechanisms are ovulation inhibition and changes in the cervical mucus that inhibit sperm penetration. The hormonal methods, particularly the low-dose progestin-only products and emergency contraceptive pills, have effects on the endometrium that, theoretically, could affect implantation. However, no scientific evidence indicates that prevention of implantation actually results from the use of these methods. Once pregnancy begins, none of these methods has an abortifacient action. The precise mechanism of intrauterine contraceptive devices is unclear. Current evidence indicates they exert their primary effect before fertilization, reducing the opportunity of sperm to fertilize an ovum.

Abortifacient Agents↗

A new quantitative test for sperm penetration into cervical mucus.

A new experimental and theoretical procedure is described for characterizing the penetration of spermatozoa into cervical mucus in vitro. Semen is introduced to a prescribed volume of mucus contained in a flat capillary tube. Use of the tube enables the surface area of semen-mucus contact to be fixed, and provides excellent visualization of sperm movement in the mucus. The time interval of semen-mucus contact is also controlled. The number of motile sperm and their swimming speeds are determined in both the semen and mucus by hemocytometer counts and simple time-exposure photomicrography. The assay provides two new measures of the sperm-mucus interaction. The number of successful sperm entries into the mucus is compared with the number of original collisions between seminal sperm and the semen-mucus interface. The comparison is expressed as a ratio of the numbers of sperm in these two groups, viz., PSC = percentage of successful collisions. The vitality of spermatozoa that do succeed in entering the mucus is assessed by comparing their swimming speeds with those of sperm in the semen. This second comparison is also expressed as a ratio, viz., VR = velocity ratio = mean swimming speed in mucus/mean swimming speed in semen. The clinical application of the method to human semen and cervical mucus is described, and sample results are presented.

Cervix Mucus↗

A comparison of methods to interpret the basal body temperature graph.

Specific criteria are given for several methods of determining the basal body temperature shift. The specific criteria selected have been coded for a uniform interpretation by computer, and interpretations have been compared for 8496 charts. Our results indicate that the method that defines the temperature shift as 0.3 degrees F or more above the running low average for at least 3 consecutive days provides the best concurrent chart interpretation method. A method that creates a smoothed curve that transects the average of all temperatures on a completed graph provides a good retrospective method for identifying the temperature shift. Both the temperature averaging technique and curve smoothing technique identified a temperature shift in more than 95% of the charts with complete temperature readings.

Adolescent↗

Diagnosis and treatment of cervical mucus abnormalities.

PURPOSE: To present causes of cervical mucus problems leading to poor postcoital tests and options for treatment. METHODS: Presentation of mostly original research dealing with diagnosis and treatment of cervical mucus abnormalities. RESULTS: The simplest but least effective therapy was guaifenesin. Short-term use of ethinyl estradiol can be effective. Sometimes the ethinyl estradiol must be used for a longer time period which suppresses follicular maturation, so exogenous gonadotropin must be used to counteract suppression. CONCLUSIONS: In contrast to the conclusions of a meta-analysis by Griffith and Grimes the author believes that performing a postcoital test is a very valuable tool in investigating infertility as long as it is performed at the appropriate time as determined by serum estradiol, progesterone, luteinizing hormone and ultrasound. Clomiphene citrate therapy is the most common etiology for abnormal postcoital tests in the modern era.

Cervix Mucus↗

Cervical mucus changes and ovulation prediction and detection.

Cervical mucus can be used to predict ovulation if a woman has received adequate education in the method and is committed to careful observation of her cervical mucus changes. Many different tests have been based on the quantity, physical properties or biochemical constituents of cervical mucus. However, routine use of cervical mucus for ovulation monitoring by patients requires that the tests be more practical for accurate sample collection and more objective for the detection of cervical mucus changes.

Cervix Mucus↗

A review of cervical mucus and sperm interactions in humans.

Cervical mucus is an aqueous or gel mixture of fluids, ions and compounds, and cells, primarily produced by the endocervical epithelium. The amount secreted varies with menstrual phase and compositions changes under hormonal influence. Sodium shows the greatest concentration change at ovulation but does not change early enough to be of value in natural family planning practice. Dried mucus has a fern appearance due to NaCl crystals at ovulation. Other substances, less clearly related, are too difficult to analyze or in too low concentration. Soluble proteins, amino acids, and simple sugars show wide fluctuation and probably influence sperm penetration and nutrition. One function of mucus is antimicrobial activity of leukocytes, which decreases at midcycle. Another, sperm transport, is a function of estrogen's effect on mucus rather than ovulation. Sperm concentration in the mucus column is maximal from 15 minutes to 2 hours after vaginal deposition. Rapid penetration into cervical mucus favors sperm survival because of its optimal pH. Infertility may be caused by immunoglobulins or spermagglutinins in cervical mucus. To date, no constituent of cervical mucus has been identified which undergoes an easily detectable change 4 days before ovulation. Several potential methods for use in natural family planning are suggested.

Cervix Mucus↗

[Problem in the partial separation of X- and Y-carrying human spermatozoa].

The introduction of a fluorescent staining technique for identification of Y chromosome made possible the distinction of X- and Y-bearing human spermatozoa. Using this fluorescence analysis the isolation of Y- and X-bearing human spermatozoa were investigated employing two different methods for separation of spermatozoa. 1. The migration of human spermatozoa in cervical mucus obtained from women shortly before mid-cycle was studied, using an in-vitro method for horizontal sperm penetration. Basing on the progressive sperm motility in cervical mucus, a fraction rich in Y-bearing spermatozoa in the frontal zone of sperm migration was found. 2. Gradient centrifugation at different rotor speeds using a discontinous sucrose gradient has been employed for separation of human spermatozoa. A significant trend for separation of Y- and X-bearing spermatozoa was demonstrated. The results were shortly discussed.

Centrifugation, Density Gradient↗

[Immunoglobulin content of cervical secretion].

The content of immunoglobulins in the cervical mucus has been determined quantitatively by the method of radial immunodiffusion. IgG and IgA has been ascertained in all samples, whereas IgM was not measurable. The concentrations of IgG and IgA in the cervical mucus was compared with those of mucous--membrane and of blood-serum. It was discussed the importance of periodical changes of cervical mucus for the penetration of spermatozoa.

Cervix Mucus↗