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B Runnebaum

Publications and source records attributed to B Runnebaum.

At least 91 records · Page 5Linked to original sources

The pH as an important determinant of sperm-mucus interaction.

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.

Adult↗

[The effect of heavy metals on the in vitro interaction between human sperm and cervical mucus].

The sperm-cervical mucus-penetration test (SCMPT) was used in vitro to examine the influence of heavy metals (mercury, cadmium and copper) on sperm function. 30 each of freshly obtained different sperm samples with varying starting sperm motility and oestrogen-stimulated cervical mucosa from women of known fertility were used. Mercury chloride (HgCl2; 0.005-0.5 mmol/l), cadmium chloride (CdCl2; 0.05-10 mmol/l) and copper sulphate (CuSO4; 0.0001-10 mmol/l) were added to the in-vitro system. After incubation, at 37 degrees C for 6 hours, linear progression, penetration depth and motility index of the sperm (cumulative SCMPT score) were analysed. An untreated control was run in parallel with each test. The added substances, especially CdCl2 and HgCl2, significantly reduced the quantitative and qualitative penetrability of sperm (P = 0.001), in step with the concentration. The concentrations which were used, especially those of mercury, were in the range of in-vivo. measured levels. These results make clear that heavy metals can influence human sperm function.

Cadmium↗

The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women.

The efficacy and tolerability of a new oral contraceptive, norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol; Cilag GmbH Research, Sulzbach, Germany) were examined in an open-label study of 59,701 women who were evaluated during 342,348 menstrual cycles; 42,022 women completed the planned treatment regimen of six cycles. A use-efficacy (overall) Pearl index of 0.25 pregnancies per 100 woman-years was calculated based on 342,348 cycles. Tolerability was assessed for all women who completed six treatment cycles. Reductions in mean cycle length and duration of bleeding were noted; 32% of the women experienced reductions in the intensity of bleeding by the end of cycle 6. After six cycles of use, amenorrhea occurred in 1%, spotting in 4%, and breakthrough bleeding in 3% of the participating women. Treatment with norgestimate/ethinyl estradiol had minimal effects on weight, blood pressure, pulse, lipid metabolism, and blood glucose. Adverse effects (acne, nausea, or headaches) occurred at low frequencies and in many cases, were reduced compared with pretreatment levels. The results of this large-scale open trial were comparable with results from two other multicenter trials of the same formulation.

Adolescent↗

Lipid metabolism in Norplant-2 users--a two-year follow-up study. Total cholesterol, triglycerides, lipoproteins and apolipoproteins.

Changes in lipid metabolism in 25 healthy female volunteers during a 24-month application of Norplant-2 were evaluated in an open clinical trial. Total serum cholesterol decreased significantly (p less than 0.05/p less than 0.05) by 10%/9% after 12 months and by 3%/7% (n.s./n.s.) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). Serum triglycerides decreased by 34%/28% (n.s./p less than 0.05) after 12 months and by 29%/25% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). HDL-cholesterol decreased significantly by 18%/12% (p less than 0.01/p less than 0.05) after 12 months and by 12%/12% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). No statistically significant difference between serum levels of LDL-cholesterol prior to and after 12 and 24 months of Norplant-2 use could be found. VLDL-cholesterol levels decreased significantly by 38%/38% (p less than 0.05) after 12 and by 25%/25% after 24 months of Norplant-2 application (p less than 0.01) (all subjects/subjects completing 24 cycles). Apolipoprotein Al decreased significantly by 23%/23% (p less than 0.001/p less than 0.01) after 12 and by 21%/22% after 24 months of Norplant-2 application (p less than 0.01/p less than 0.01) (all subjects/subjects completing 24 cycles). No statistically significant difference between apolipoprotein All levels prior to and after 12 and 24 months of Norplant-2 implantation could be found. Apolipoprotein B decreased significantly by 27%/17% (p less than 0.05/p less than 0.05) after 12 months of Norplant-2 application (all subjects/subjects completing 24 cycles). The decline after 24 months of Norplant-2 use was not significant. Changes in lipid metabolism caused by oral hormonal contraceptives differ in the various clinical trials; however, most investigators found that serum levels of total cholesterol and triglycerides increase under the application of OCs. Contrary to this, a decrease of total cholesterol and triglycerides under Norplant-2 use was noted. Furthermore, we found a significant decrease of lipoproteins and apolipoproteins--with the exception of LDL-cholesterol and apolipoprotein All, which did not show any significant modifications. Thus, Norplant-2 seems to be non-contributory to cardiovascular risk and might even provide protection against such risks.

Adult↗

Differentiation of round cells in semen by means of monoclonal antibodies and relationship with male fertility.

OBJECTIVE: To differentiate round cells in semen samples of subfertile men and evaluate the clinical significance during infertility investigation. PATIENTS: One hundred and eight randomly chosen couples with a median duration of infertility of 4 (range, 1 to 20) years presenting at the outpatient infertility clinic of the University of Heidelberg, Germany. MAIN OUTCOME MEASURES: Differentiation of round cells in semen by means of monoclonal antibodies (mABs) and a streptavidin-biotin system for staining. Correlation of results with medical history, outcome of clinical examination, sperm analysis, microbial screening of both partners, evaluation of sperm functional capacity in vivo by means of the postcoital test (PCT) and in vitro with the standardized crossed sperm-cervical mucus penetration test (SCMPT) and the subsequent fertility in a prospective study. RESULTS: The method used for differentiation of round cells proved to be practical and suitable for routine use. The percentage of leukocytes ranged from 0% to 58% with a median of 3%. Number of round cells and percentage of leukocytes did not differ markedly with regard to andrologic history, clinical findings, for example, varicocele, results of standard sperm analysis, and microbial colonization of semen samples. However, high rates of leukocytes of the round cells correlated with reduced sperm count and morphology and results of PCT. Leukocyte-positive (> 15% leukocytes) specimens were also significantly more frequent in case of inadequate SCMPT and reduced sperm penetration ability in vitro. CONCLUSIONS: In asymptomatic patients (in terms of genital tract infection), the majority of round cells consist of immature germ cells and < 5% are white blood cells. The streptavidin-biotin system and the mABs used in this study proved to be useful to identify patients with elevated rates of leukocytes in semen possibly reflecting subclinical genital tract infection with influence on sperm functional capacity and subsequent fertility. Thus the procedure can be recommended to be included in a comprehensive evaluation of male fertility.

Adult↗

[Harmful substances and infertility. Substances of abuse].

Contaminants exercise an influence on different levels of reproduction, resulting in disturbances of the cycle, abortion and diverse complications during pregnancy among women, whereas, in the case of men, alterations of the spermiogram have been observed. Numerous unfavourable influences on reproduction are known from toxins such as alcohol, cigarettes and caffeine. By means of a survey of references and own results, these secondary effects are demonstrated in order to warn couples of the serious consequences with regard to the abuse of toxins, e.g. coffee, tobacco etc., when seeking advice in questions of infertility and pregnancy.

Alcohol Drinking↗

[Environmental pollutants and fertility disorders. Heavy metals and minerals].

So far, the influence of lead, cadmium and mercury on human fertility has hardly been considered. First experiences by the authors with the chelating agent 2,3 dimercaptopropane-1-sulfonate (DMPS), which mobilizes heavy metals deposited in the body, seem to favour an association between the body load of heavy metals and complications during the menstrual cycle and during pregnancy. By means of an extensive survey of references, the importance of heavy metals for reproduction is demonstrated. In addition, the deficiency of particular minerals and their interaction with heavy metals are considered. Indications are given for diagnosis and therapy of the exposure to heavy metals. The practical procedure is demonstrated by means of three case studies.

Abnormalities, Drug-Induced↗

Microbial colonization and sperm--mucus interaction: results in 1000 infertile couples.

After screening a large series of infertile patients (n = 1000 couples), potentially pathogenic microorganisms were identified in genital secretions of the majority of couples. None of the patients displayed signs or symptoms of infection of the lower genital tract. In semen specimens and cervical swabs, mycoplasmas were found in 18 and 12%, potentially pathogenic aerobic bacteria in 50 and 31%, additionally commensal aerobes in 38% and 25%, respectively. The microbial pattern showed great variability with polymicrobial growth most common. The rate of cultures positive for potentially pathogenic anaerobes was markedly influenced by the transport conditions. In endocervical material, Herpes simplex virus (HSV) was identified in 4.5%. Yeasts were found in the posterior vaginal fornix in 10%. Concerning both partners, there were only 10 couples (1%) from whom microorganisms in genital secretions could not be isolated, not including lactobacilli in females. This high prevalence of microbes and the low number of leukocytes indicate colonization rather than infection. When the microbial findings from both partners were analysed with regard to the outcome of sperm-cervical mucus penetration testing in vitro, which was performed simultaneously, no significant correlation was found. Furthermore, microbial prevalence did not differ between couples with 'explained' and 'unexplained' infertility. The results of this study demonstrate that in patients without symptoms of genital tract infection, microbial colonization is of minor importance for sperm--mucus interaction and that extensive microbial screening should be preferentially performed in cases of poor sperm and/or mucus function.

Adult↗

Clinical data which influence semen parameters in infertile men.

Spermiograms, Sims-Huhner postcoital tests, in-vitro sperm penetration tests and hormone stimulation tests, including gonadotrophin-releasing hormone, thyrotrophin-releasing hormone and the adrenocorticotrophic hormone (ACTH) test, were obtained in 225 infertile men. The present paper deals with the influence which anamnestic factors have on the spermiogram and on hormone levels. Adrenocortical function decreased with age. Blue-collar workers had poorer sperm parameters than white-collar workers. Smokers exhibited hormone alterations without significant changes in the spermiogram. Regular alcohol consumption was associated with elevated dehydroepiandrosterone-sulphate and oestradiol concentrations and poor postcoital test results. Emotional stress had a negative influence on sperm parameters. Environmental influences warrant additional attention in the evaluation of men with abnormal spermiograms.

Adrenal Cortex↗

Biochemical analysis of cervical mucus by nuclear magnetic resonance spectroscopy.

Biochemical evaluation of cervical mucus is difficult due to the characteristic rheological properties of this hydrogel. The application of high resolution nuclear magnetic resonance spectroscopy proved to be a valuable new method for differentiated biochemical analyses of human cervical mucus. A particular advantage is that it is non-destructive, that it can be applied to specimens of small volume and that no sample preparation, such as solubilization, is necessary.

Cervix Mucus↗

Serum inhibin levels in gonadotrophin stimulated in-vitro fertilization/gamete intra-fallopian transfer cycles.

Serum inhibin concentrations of 64 cycles of in-vitro fertilization--embryo transfer (IVF-ET) or gamete intra-Fallopian transfer (GIFT) have been analysed retrospectively. No significant difference was observed in serum inhibin levels of cycles stimulated with buserelin and human menopausal gonadotrophin (HMG) or HMG alone. During the late follicular phase, serum inhibin was higher in cycles resulting in pregnancy than in cycles without a pregnancy (peak values on day +1: 8.3 versus 6.4 IU/ml, respectively). The same difference was found between stimulation cycles resulting in a viable or a non-viable pregnancy (peak values on day +1: 8.3 versus 7.5 IU/ml). However, these differences were not significant. During the early luteal phase, serum inhibin values were similar in these groups of patients. Our results indicate that the use of the gonadotrophin-releasing hormone (GnRH) analogue buserelin, in combination with HMG, for ovarian stimulation does not affect inhibin production by granulosa cells in vivo. The late follicular and early luteal concentrations of serum inhibin have to be considered unsuitable as predictors in IVF/GIFT cycles with respect to pregnancy and pregnancy outcome.

Adult↗

[Gonadotropin releasing hormone and analogs. Physiology and pharmacology].

The natural gonadotropin-releasing hormone (GnRH) is secreted by hypothalamic neurons and acts at the level of anterior pituitary gonadotrophs releasing the peptides luteinizing hormone and follicle-stimulating hormone. GnRH is a decapeptide sensitive to peptidases, resulting in a short half-life. The synthesis of highly potent analogues of GnRH provides peptides with a longer half-life and a higher affinity to the GnRH-receptor. The presently available GnRH analogues for clinical use act initially as agonists by upregulating GnRH receptors in the pituitary. A few days after continuous application of GnRH analogues down-regulation of receptors and desensitization of the pituitary occur. In addition to receptor mechanisms, a number of postreceptor actions at the level of second messengers (protein kinase C, leukotriene and inositol phosphates) are responsible for the inhibition of adequate gonadotropin secretion. This paradoxical entire fertility action of the analogues is the basic principle for its clinical use, resulting in a reversible suppression of pituitary and thereby ovarian function.

Animals↗

[The limits of hormone substitution in pollutant exposure and fertility disorders].

Heavy metals and chloro-organic compounds can influence female fertility at every phase of reproduction. They may induce hormonal disorders, preventing ovulations and pregnancies. They can also result in abortions and fetal malformations. For this reason, the urinary excretion of heavy metals was measured after oral load with the chelating agent dimercaptopropanesulfonate (Dimaval) in women with hormonal irregularities. In addition, blood was examined for various polychlorinated compounds (polychlorinated biphenyls - PCB -, hexachlorocyclohexane - HCH -, pentachlorophenole - PCP -, hexachlorobenzol - HCB -, dichlordiphenyltrichloroethane - DDT -, dichlorodiphenylethane - DDE -, tetrachlorodiphenylethane - DDD -). Mercury contaminations were seen most commonly and correlated significantly with the number of amalgam fillings and with the release of mercury while chewing. The latter was demonstrated with the so-called chewing-gum test. Women with hormonal disorders or alopecia had, on the average, the highest mercury excretion during the wash-out test. Cadmium excretion was pronounced for the following groups of women: those with technical professions, those suffering from thyroid dysfunctions, and those with habitual abortions and uterine fibroids. With increasing age, pesticide concentrations of the blood rose significantly. Women with endometriosis and with antihyroidal antibodies had significantly higher PCB values. Despite therapeutic intervention, fewer women with elevated DDT/DDE/DDD values conceived when compared to those with lower values. alpha-HCH concentrations were often elevated in women with uterine fibroids. With increasing PCP levels pregnancies often ended in abortion. Results of this investigation indicate that women with hormonal irregularities or specific fertility disorders should be examined for heavy metal and pesticide contamination prior to hormone treatment.

Adult↗

The androgenicity of oral contraceptives: the young patient's concerns.

Sexual activity is quite common among women aged 14 to 20 in developed countries, averaging perhaps 10% at age 15 to about 70% at 19. Thus, the need for contraception may begin quite early in life and will continue for as long as 30 years. One of the best candidates for long-term contraception for young sexually active females is the oral contraceptive (OC), which provides health benefits besides contraception. Long-term benefits include lowered rates of ovarian and endometrial cancer, as well as of benign breast disease and ovarian cysts. Another benefit is protection against upper-tract sequelae of sexually transmitted diseases. Short-term benefits are correction of menstrual irregularity, reduction in menstrual flow, and diminished premenstrual syndrome and dysmenorrhea. Recent OC formulations contain only one-third the estrogenic potency of older OCs and therefore are associated with dramatic decreases in what were always the major side effects of OCs: heart attack, stroke, and pulmonary embolism. Other side effects of OCs have been most closely associated with the progestogenic component, and are related to the androgenic effects of progestins, particularly some synthetic progestins. However, some new synthetic progestins have been found to have minimal androgen receptor activity in preclinical testing and to cause minimal or no androgen-related side effects in clinical trials. One of these new progestins having a favorable androgenic profile is norgestimate. Its efficacy and safety in combination with low doses of ethinyl estradiol have been documented in the European and the American literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

[Value of the metoclopramide test in diagnosis of hormonal causes of female sterility].

A retrospective study was used to assess the diagnostic value of the metoclopramide (MCP)-stimulation test for diagnosing hormonal infertility in women. 1326 couples sought help at the hormone-counselling laboratories at the University Gynaecological Hospital in Heidelberg during a six year period and were evaluated with a standardized diagnostic program. The patients were grouped as manifestly hyperprolactinaemic, normoprolactinaemic or functionally hyperprolactinaemic, according to their basal serum prolactin (Pr)-level, and the results of the MCP-stimulation test. The number of patients in the normoprolactinaemic group varied from 894 to 1188 and functionally hyperprolactinaemic varied from 263 to 19 patients, depending on the cut-off value selected. We used cut-off values of 200, 250, 300 or 400 ng/ml in evaluating the MCP response. During a two year follow-up, 40% of the women conceived. Increasing Pr-levels, at stimulation, were associated with significantly more spontaneous pregnancies. Thus more women conceived in the functional hyperprolactinaemic group than in the normoprolactinaemic group. 281 women had used a dopamine agonist (21%). Women in the bromocriptine group (except manifestly hyperprolactinaemic patients) had significantly higher pregnancy rates than those not treated with bromocriptine. This results was particularly significant for women with normoprolactinaemic. It was caused by higher bromocriptine induced conception rate. 60% of the therapeutic pregnancies occurred in normoprolactinaemic women receiving the dopamine agonist therapy. Our results suggest that MCP-stimulation induced functional hyperprolactinaemia is not required for a successful approach. In sterility of unknown origin with normal basal Pr serum levels, a three month trial with low-dose dopamine agonist can be tried.

Adult↗

Production of leukotrienes in gonadotropin-releasing hormone-stimulated pituitary cells: potential role in luteinizing hormone release.

Gonadotropin-releasing hormone (GnRH) stimulated the formation of two major metabolites of the 5-lipoxygenase pathway, leukotriene (LT) B4 and LTC4, as well as luteinizing hormone (LH) release in primary cultures of rat anterior pituitary cells. Several lines of evidence suggested the presence of a GnRH-dependent pituitary endocrine system in which LTs act as second messengers for LH release: (i) GnRH-dependent LT formation was observed within 1 min and immediately preceded GnRH-induced LH release, whereas exogenous LTs stimulated LH release at low concentrations; (ii) the dose responses of GnRH-induced LT production and LH release were similar and both effects required the presence of extracellular Ca2+ ions; (iii) GnRH-induced LH release was blocked by up to 45% following the administration of several LT receptor antagonists; (iv) LTE4 action on LH secretion was entirely abolished by LT receptor antagonists; and (v) an activator of protein kinase C acted synergistically with LTE4 to induce LH release. The major source of LT formation in the pituitary cell cultures appeared to be the gonadotrophs, as shown by GnRH receptor desensitization experiments. The results demonstrate the presence of a GnRH-activatable 5-lipoxygenase pathway in anterior pituitary cells and provide strong support for the hypothesis that LTs play a role in LH release in the GnRH signaling pathway.

Animals↗

Dosage frequency and drug-compliance behaviour--a comparative study on compliance with a medication to be taken twice or four times daily.

The objective of the study was to investigate patient compliance with two different dosage regimens. Ethinyloestradiol 80 micrograms daily was prescribed to 35 female outpatients to be taken as 20 micrograms four times daily or 40 micrograms twice daily for 7 days. It was given to standardise cervical mucus before a sperm cervical mucus penetration-test (SCMPT) was performed. Sixty-five patients with primary infertility (mean age 29.9 y) completed the study. Compliance was assessed by microprocessor-based compliance monitoring. Besides compliance (percentage of prescribed doses taken), the adherence of the patients to the dosage schedule was evaluated--'regimen compliance'. The latter parameter of drug intake behaviour was calculated by the number of days in which 2 (BID) or 4 openings (QID) were recorded by the electronic monitor. As a third parameter, the deviation from the prescribed dosing intervals, i.e. 12 or 6 h, was also determined. Partial compliance was the predominant finding and only 9 patients (13.8%) were over-compliant. Mean compliance was 75.7% in all 65 patients as a group, range 7.1 to 143%. The mean compliance with the QID regimen was 67% compared to 85% with the BID regimen. 'Regimen compliance', the percentage of doses taken on schedule, was 36% and 63% for the QID and BID regimens, respectively. Drug-intake behaviour was more erratic with the QID than the BID regimen, as indicated by the 55% of opening intervals recorded which exceeded the range of 3-9 h (mean: 6 h), compared to only 19% exceeding 6-18 h intervals (mean: 12 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗