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PubMed1975

Luteinizing hormone-releasing hormone in the treatment of anovultory infertility.

Fifteen infertile, anovulatory women, ages 20 to 37, were treated with synthetic luteinizing hormone-releasing hormone (LH-RH) to stimulate follicular maturation and/or ovulation. Thirteen of the patients had been treated unsuccessfully with other therapeutic regimens. To obtain follicular maturation, LH-RH was given intramuscularly in daily doses of 25 mu-g for 7 days and 50 mu-g for the next 7 days, or 100 mu-g for 3 days and 150 mu-g for the next 3 days. Both regimens were begun on the 4th day of a spontaneous or induced cycle. Follicular maturation (evaluated by the cervical mucus scale) occurred in three of seven cycles treated withe the first regimen and three of five treated with the second regimen. To induce ovulation, LH-RH was given in intravenous infusion (50 to 500 mu-g), intramuscularly (100 mu-g), or in a combination of both methods. The drug was administered after follicular maturation with LH-RH, clomiphene citrate, or human menopausal gonadotropin had been achieved; it was also given during four cycles in which spontaneous follicular maturation had occurred. Ovulation occurred in 10 of 25 treated cycles. Five pregnancies resulted, three in the first post-treatment cycle.

Adult↗
PubMed1992

Actions of platelet activating factor (PAF) on gametes and embryos: clinical aspects.

Platelet activating factor (PAF) is a phospholipid widespread in body tissues. Previous reviews have discussed its production by preimplantation embryos and the evidence implicating it as an autocrine mediator in aspects of gamete and embryo physiology. Human spermatozoa contain variable amounts of PAF, the amount contained depending on the source and method of preparation of the sperm. Incubation of human sperm with PAF tends to increase their forward velocity, especially in samples with slow motility. PAF treatment causes an increase in the proportion of acrosome-reacted sperm and in their ability to penetrate both zona-free hamster ova and cervical mucus. PAF has been found in human follicular fluid at ovulation. A role for PAF in ovulation has been suggested, because PAF antagonists reduce the rate of ovulation in rats. In some studies, modest improvements to mouse in vitro fertilization (IVF) rates have been achieved with PAF supplementation of media under specific conditions. Furthermore, in the rabbit and mouse, PAF antagonists have been reported to inhibit fertilization in vivo and in vitro respectively. However, addition of PAF to human IVF medium, but only at the time of insemination and fertilization, had no effect on either fertilization or pregnancy rates. Sensitive bio- and immuno-assays have shown that PAF is secreted by human embryos into their fluid milieu. PAF secretion by these zygotes during culture, although markedly variable, has been correlated with the achievement of pregnancy and pregnancy outcome. Although the secretion of PAF by the mouse embryo decreases during culture in vitro, exogenous PAF enhances embryo viability during culture. Similarly, culture of human zygotes in PAF-supplemented medium prior to embryo transfer significantly increases the chance of achieving pregnancy. Both the implantation and live-birth rates are increased in human IVF by addition of PAF to the medium.

Embryo, Mammalian↗
PubMed1977

Decrease of sperm antibody titer in males, and conception after treatment of chronic prostatitis.

Although autoimmunization to spermatozoa is a cause of male infertility, the cause of antibody formation is unknown in most cases. It has been shown that the titer is usually unchanged for as much as 16 years in the same individual. Trials to reduce the titer with varying methods have not been successful. A new possibility of treatment was indicated by the finding of a higher incidence of prostatitis in men with sperm antibodies than in a control group. Following treatment of prostatitis we observed a reduction of the antibody titer in eight cases. In five cases the cervical mucus penetrating capacity of the spermatozoa improved, and conception occurred.

Autoantibodies↗
PubMed1998

Sperm acrosome status and sperm antibodies in infertility.

PURPOSE: We studied whether the spermatozoa from sperm autoimmune infertile men undergo premature acrosomal loss and whether this relates to the presence of sperm antibodies in wives. MATERIALS AND METHODS: We evaluated acrosome status of live washed native and overnight capacitated spermatozoa from 17 sperm nonautoimmune fertile and 23 sperm autoimmune infertile men using an immunofluorescent peanut lectin binding assay. We used cytotoxic and immunobead binding assays to prescreen the serum and seminal plasma of these men, and serum and cervical mucus of the wives for immunological infertility. We performed immunofluorescent sperm antibody assays on all study samples to ascertain sperm antibody isotype levels in each sample. Levels of acrosomal loss in husband native and capacitated spermatozoa were correlated with levels of IgG, IgA and IgM sperm antibodies in the study samples. RESULTS: Sperm autoimmune infertile men had a significantly larger percentage of sperm (p <0.0001) that had lost the acrosome and a lower percentage of sperm with intact acrosome (p <0.0001) in native and capacitated preparations in contrast to those of fertile controls. Levels of cytotoxic and IgA antibodies, especially in seminal plasma and cervical mucus, correlated significantly with percentages of sperm with a total loss of acrosome in native and capacitated sperm preparations (p < or = 0.01). CONCLUSION: Infertile men with sperm antibodies in serum and seminal plasma undergo premature acrosome loss. This loss may expose the reproductive tract immune system, especially that involving IgA, in autoimmune infertile men and the wives to high immunogenic levels of sperm acrosome membrane antigens, thereby rendering them immunologically infertile.

Acrosome↗
PubMed1989

[New diagnostic procedures in assessing male fertility].

In 160 patients with normal and pathological semen samples, we studied the penetration of human spermatozoa in standardized bovine cervical mucus (assay Penetrak). Our results indicate that Penetrak can detect those dysfunctions of sperm motility which cannot be diagnosed by conventional semen analysis - The toluidine blue-pyronine staining is an easy way to differentiate between spermatozoa within an hour. The reliability of this technique is comparable to that of conventional methods and therefore appropriate for routine diagnostics. - As case studies on 140 patients proved, the level of carnitine in the seminal plasm can be regarded as a parameter of epididymal function. In combination with the examination of FSH serum levels, this method may be helpful in the differential diagnosis of azoospermia due to obstruction, Sertoli-cell-only syndrome, or spermatogenic arrest. - In severe oligozoospermia, testicular biopsy using semithin sections may be of high diagnostic and prognostic value. In contrast to paraffin sections, this technique is particularly appropriate for the detection of cytological characteristics of germ cells. The type and number of pathological germ cells are decisive regarding the prognosis. Furthermore, a carcinoma in situ (CIS) can be definitely identified by means of semithin sections. - In a study on 2047 patients, we found seminoma cells in 15 cases (0.73%); 5 of these patients already had a solid seminoma in the testicular rete. Risk-patients are those showing oligozoospermia of less than 10 million spermatozoa per ml or azoospermia associated with unilaterally or bilaterally subnormal testicular volume. In these cases, the testicles are inconspicuous, both palpatorically and sonographifically.

Biopsy↗
PubMed1989

New tests for the prediction of ovulation.

With improvements in basic science understanding and technology, it is predictable that within the next decade, more reliable and accurate methods of ovulation prediction will be available. The former may result from the exploration of gonadal peptides and their measurement whereas the latter may result from the ever-increasing resolution of ultrasonographic imaging. The current state of the art in predicting ovulation involves the combination of several of the described techniques (cervical mucus, urinary LH, ultrasonography). Used skillfully together they serve the infertility specialist well.

Body Temperature↗
PubMed1975

Antibacterial activity of human cervical mucus.

The antimicrobial property of human uterine cervical mucus was tested in three groups of women. Healthy women, using no contraception, women using an intrauterine device and women receiving hormonal treatment for contraception. Cervical mucus was taken on the 10th, 14th, 18th and 22nd day of the menstrual cycle. Cervical mucus had a strong inhibitory effect on the growth of Micrococcus lysodeicticus in all three groups. The strength of the inhibitory effect on the other microorganisms were in the following order: Staphylococcus albus, Staphylococcus aureus, Proteus mirabilis, Escherichia coli, Candida albicans, Streptococcus haemolyticus, Streptococcus faecalis. Use of an intrauterine device did not affect the antimicrobial effect of cervical mucus. The use of hormonal contraceptive canceled the antimicrobial effect on the series of microorganisms, with the exception of M. lysodeicticus. The maximum inhibitory effect occurred on the 14th day and declined toward the end of the menstrual cycle.

Adult↗
PubMed1988

Intrauterine insemination: a European collaborative report.

This report summarizes the data collected in the European Collaborative Report on intrauterine insemination (IUI) with pretreated sperm. A questionnaire concerning methods and results of IUI was sent to European infertility clinics and evaluable data were obtained from 29 of these clinics. A total of 196 pregnancies was reported from a total of 20 clinics. Pregnancy rates per treatment cycle were on average 7.4% of all male infertility, 10.8% for infertility due to hostile cervical mucus and 12.9% for idiopathic infertility, giving an overall pregnancy rate per treatment cycle of 8.4%. The clinical abortion rate was on average 12.2%. The mean number of years of primary infertility in the patient group of the clinics reporting pregnancies was 4.8 years and the mean number of years of primary infertility in the patient group conceiving was 5.2 years. A total of 127 births was reported with a sex ratio (male/female) of 0.512. One congenital malformation was reported. In many clinics, treatment of male infertility with IVF or IUI gave comparable results per treatment cycle. No single factor in the procedure for performing IUI was identified accounting for the different pregnancy rates obtained in the clinics included in this study.

Adult↗
PubMed1983

The phasic approach to oral contraception: the triphasic concept and its clinical application.

The phasic approach to oral contraception is described with a historical review of the evolution of new administration regimens aimed at lowering total steroid content from monophasic to biphasic to the new triphasic approach. The phasic regimen designs which support the intended mechanism of action of each of the phasic approaches are discussed. Emphasis is placed on the discussion of the rationale for the new triphasic oral contraceptive and the clinical demonstration of the triphasic's inhibition of ovulation and maintenance of functional integrity of the pituitary-ovarian axis. A new theoretical formula and practical concept are presented that incorporate a progestogen potency factor, and consequently provide a common denominator enabling a comparison of the magnitude of the effects of various oral contraceptive products on pituitary responsiveness. Widespread clinical studies are described which reinforce the suggestion that the triphasic is the state of the art and represents an important contribution to contraceptive technology.

Contraceptives, Oral↗
PubMed2000

Detection of Neisseria gonorrhoeae and Chlamydia trachomatis colonization of the gravid cervix.

OBJECTIVES: The aims of the study were to determine whether a Gram stain of cervical mucus can accurately rule out infection with Neisseria gonorrhoeae or Chlamydia trachomatis and to compare a diagnostic test that is based on the polymerase chain reaction with a deoxyribonucleic acid probe in the detection of these organisms. STUDY DESIGN: Gravid patients were screened for N gonorrhoeae and C trachomatis with a deoxyribonucleic acid probe, Gram stain, and analysis with the polymerase chain reaction. A normal, noninfected sample was defined by <10 polymorphonuclear leukocytes per high-power field on the Gram stain. Standard statistical methods were used to compare results of the Gram stain and the deoxyribonucleic acid probe, as well as to compare results of deoxyribonucleic acid probe hybridization and polymerase chain reaction analysis. A P value of <.05 was considered statistically significant. RESULTS: Patient enrollment totaled 519. The prevalence of infection as determined by deoxyribonucleic acid probe hybridization was 1.4% for N gonorrhoeae (7/518) and 6.8% for C trachomatis (35/518). The cervical Gram stain predicted the absence of infection in 17% (90/518) of patients, with a negative predictive value of 99% for N gonorrhoeae and 97% for C trachomatis. African American race, age <20 years, and unmarried status were all predictors of the presence of C trachomatis or N gonorrhoeae cervicitis. For the patients who lacked these risk factors (n = 74), the Gram stain had 100% negative predictive value. Analysis with the polymerase chain reaction detected 8 additional patients with C trachomatis and 105 additional patients with N gonorrhoeae, in comparison with deoxyribonucleic acid probe hybridization. CONCLUSION: The cervical Gram stain can accurately predict the absence of N gonorrhoeae and C trachomatis in gravid women. Analysis with the polymerase chain reaction indicates that N gonorrhoeae and C trachomatis are significantly more prevalent in this population than previously reported.

Cervix Uteri↗
PubMed1987

Evidence for a possible cytosol estrogen receptor deficiency in endocervical glands of infertile women with poor cervical mucus.

Endocervical gland estrogen receptor (ER) deficiency has been proposed as a possible cause for the poor cervical mucus (CM) in some infertile women with cervical factor. Cytosol ERs were measured in endocervical tissue obtained by biopsy within 3 days of ovulation (determined by the endogenous luteinizing hormone [LH] surge) in five infertile women with persistent poor preovulatory CM (group 1) and in endocervical tissue obtained in the late follicular phase in eight ovulatory women with excellent CM (group 2). ER concentrations were measured in Fmol/mg protein by the dextran-coated charcoal separation method (New England Nuclear Kit, Boston, MA). CM score evaluation and measurement of serum estradiol (E2) and progesterone (P) levels were performed concomitantly. Serum E2 levels of 123.4 +/- 29.3 pg/ml (mean +/- standard error of the mean [SEM]) in group 1 were comparable to E2 levels of 123.3 +/- 15.0 pg/ml in group 2. Serum P concentrations of 0.9 +/- 0.27 ng/ml in group 1 were comparable to 0.79 +/- 0.29 in group 2. A CM score of 4.6 +/- 0.69 in group 1 was significantly lower than 11.6 +/- 0.53 in group 2 (P less than 0.01). The cytosol ER was negative in four of five women in group 1, whereas in group 2, ER was positive in six, borderline in one, and negative in one subject. This study suggests that cytosol ER may be deficient in some women with cervical factor.

Adult↗
PubMed1998

RETRACTED: The pharmacodynamics and efficacy of Implanon. An overview of the data.

Implanon is a long-acting reversible contraceptive method, consisting of a single rod that is applied subdermally. Ovulation inhibition was determined by serum progesterone (P) levels and ultrasound scanning (USS) of the ovaries. Ovarian function was further assessed by serum estradiol (E2) levels. The effects of Implanon on serum gonadotropin levels (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) and on cervical mucus were also investigated, by means of Insler scores and sperm penetration tests. The effect of the endometrium was assessed by endometrial biopsies and USS. The Pearl index was calculated over 13 studies performed according to Good Clinical Practice (GCP), including 1716 women using Implanon. Return of ovulation after implant removal was determined by P levels and USS of the ovaries. The contraceptive efficacy of Implanon was high, with zero pregnancies during 53,530 cycles (4103 woman-years), resulting in a Pearl index of 0.0 (95% confidence interval, 0.00-0.09). This was achieved by inhibition of ovulation, which was reflected by suppressed P levels, as the primary mode of action. Ovulation was inhibited, but otherwise ovarian activity was still present (follicle growth, E2 synthesis). The FSH serum concentrations were only slightly lower than preinsertion levels and LH surges were prevented. The viscosity of the cervical mucus was increased. The endometrium was thin but not atrophic; it showed primarily inactive or weak proliferation. Return of ovulation after removal of Implanon was rapid.

Adolescent↗
PubMed1997

A prospective, randomized, cross-over comparison of two methods of artificial insemination by donor on the incidence of conception: intracervical insemination by straw versus cervical cap.

In a prospective, randomized study of insemination with donor semen, intracervical insemination by straw was compared with insemination using a cervical cap with an intracervical reservoir. A total of 91 patients completed 486 treatment cycles. There were no significant differences in age, parity, indication for insemination by donor, or method of cycle monitoring between women who became pregnant and those who did not conceive with either insemination method. In 236 standard intracervical insemination cycles, 14 patients became pregnant (5.9% per cycle), whereas 38 patients conceived in 250 cervical cap cycles (15.2% per cycle). Both the crude pregnancy rates and the cumulative pregnancy rates calculated by the Kaplan-Meier life-table method were significantly different (chi(2)-test, P < 0.001, and log-rank test, P < 0.005 respectively). Pregnancy rates in artificial insemination with cryopreserved donor semen may be improved by the use of a cervical cap when compared to cervical insemination by straw. The use of the cervical cap may prolong the exposure of the spermatozoa to the cervical mucus and prevent the backflow of semen into the vagina.

Body Temperature↗
PubMed2000

Sperm function tests after vasovasostomy.

AIM: To evaluate the sperm function after vasovasostomy. METHODS: Semen samples from 42 subjects after vasovasostomy (Group A: 1-6 months, Group B: 6-12 months; Group C: 12-18 months after vasectomy reversal) were investigated. Semen from 34 normal fertile men was used as controls. Sperm function tests, including hypoosmotic swelling test (HOST), acridine orange (AO) fluorescence, acrosome reaction (triple-stain), cervical mucus penetration test (CMPT), etc were done. RESULTS: After vasectomy reversal, the percentage of HOST was significantly lower than that of the normal fertile men. In regard to AO, there were no significant differences between the three vasovasostomy groups and between these 3 groups and the controls. With triple-stain, the percentage of normal acrosome reaction was significantly lower in Group A as compared with the controls, but not in Groups B and C. There were no significant differences in the results of CMPT between the vasovasostomy groups and the controls. However, the number of "poor" type was significantly higher in Groups A and C than in the controls; the percentage of "negative" type were higher in Groups A and B than in the controls. CONCLUSION: After vasovasostomy a lower level of HOST remained for one year and gradually recovered after one year. Six months after vasectomy reversal, the percentage of acrosome reaction could be changed from lower level to normal range. The data of AO indicated that the genetic material (double-stranded DNA) in spermatozoa was not affected by vasovasostomy. To evaluate the result of CMPT after vasectomy reversal, not only the normal results but also the abnormal results ("poor" and "negative" types) should also be considered.

Adult↗
PubMed1982

Penetration of human ejaculated spermatozoa into human and bovine cervical mucus. II. Pattern and velocity of penetration.

The pattern of penetration of human ejaculated spermatozoa into human cervical mucus (HCM) and bovine cervical mucus (BCM) was studied in an in vitro penetration system by means of plate capillary tubes. Sperm penetrate the HCM in a unique pattern making their way progressively forwards in a one-way direction in between the filaments. In contrast, sperm move preferably forward in BCM. The different patterns are probably due to different organizations of the glycoproteins. The penetration values (PV) were also different in the two systems when studied after short periods of incubation (15 and 30 min), but incubation for 1 h brought both systems to the same rate of PV. Thus, this period is enough to overcome the differences between the patterns of penetration. Sperm velocity in semen, in HCM, and in BCM were the same. Cervical mucus (CM) did not affect sperm velocity. A strong correlation (r = 0.8) was found between sperm velocity in the semen and its PV rate either in HCM or in BCM. The results of this study recommend the use of BCM as a reference CM in cross penetration tests and suggest its establishment as a routine method for assessment of sperm quality.

Animals↗
PubMedDate not supplied

Traditional and new molecular methods for early detection of cervical cancer.

Disadvantages of the traditional Papanicolaou-method for the cytological detection of cervical carcinomas and their precursors can be overcome by the use of specific molecular markers for nuclear attypicality. High grade HR-HPV induced cervical dysplasia is initiated by deregulated expression of viral oncogenes in replicating epithelial stem cells. Here, the E6-E7 gene products gain control of cell cycle and mitotic activity first and induce multistep mutagenesis with severe genomic instability in successin. The detailed molecular analysis of these activities has allowed the development of biomarkers for dysplastic cervical cells. The marked over-expression of the cyclin dependent kinase inhibitor p16INK4a is regularly observed in HR-HPV induced malignant lesions and indicates an active expression of the viral oncogene E7 in dysplastic cells. Morphologically, these molecular deregulations are reflected mainly in an altered nuclear-cytoplasmic ratio, anisonucleosis, and hyperchromasia. With p16INK4a immunostaining--as reported in the literature--dysplastic and atypical cells can be easily detected even under low magnification and differentiated by higher magnification from occasional positive atrophic or metaplastic cells by their atypical nuclear structure. In questionable cases the additional use of proliferation markers could eliminate false interpretation. The results with these new molecular techniques can by further optimized by applying the ThinPrep-method for the preparation of the cytological slides to ensure overlying blood, mucus or inflammatory cells do not mask atypical cells. With these new methods we can expect to lower the rate of false-positive and false-negative cytology tests as experienced with the traditional Papanicolaou-method, of not eliminate them completely, gaining thereby great advantages for patients and for cost-efficiency.

Biomarkers, Tumor↗
PubMed1998

Silent premature rupture of membranes, detected and monitored serially by an AFP kit.

A 24-year-old woman underwent conization and cervical cerclage during pregnancy. After she later complained of fluid leakage, a premature rupture of the membranes (PROM) was suspected, because of positive results on a test for nitrazine, the intra-amniotic dye injection method (PSP test), and an AFP-kit test at 22 weeks of gestation. The nitrazine and PSP tests later turned negative. However, during the period from the 22nd through 26th weeks of gestation, the results of AFP-kit tests fluctuated, with repeated positive indications for bacterial cultures and elevated granulocyte elastase activity in the cervical mucus. The pregnancy was well maintained with administration of antibiotics and ritodrine hydrochloride until 34 weeks of gestation. The presence of chorioamnionitis, local inflammation of the fetal membranes, was found by pathological examination after the delivery. We propose a new clinical entity--to be referred to as silent PROM--the premature chemical rupture of the membranes.

Adult↗