Biomedical subjects
Publications and source records attributed to I Gerhard.
The underlying causes and rationale for treatment of recurrent abortion are not entirely clear. The Euro-Team early pregnancy protocol was developed as a diagnostic work-up based on the evaluation of risk factors. Possibilities for therapy can be based only on the expectancy that elimination of some risk factors may improve the prognosis.
In an open, non-randomized prospective phase-III-study the clinical and endocrine efficacy as well as the safety of leuprorelin acetate depot (Enantone-Gyn Monats-Depot) were investigated. The therapeutic results of 198 patients, gathered from 5 university institutions and two city hospitals, are reported. Endometriosis was classified by the revised American Fertility Society score (r-AFS) before and at the end of treatment. Serum levels of LH, FSH, prolactin, estradiol, progesterone, androstenedione, testosterone and leuprorelin acetate were determined by radioimmunoassay. The mean total r-AFS score changed as follows: before surgical intervention during first-look laparoscopy 21 +/- 24 at the end of first-look laparoscopy 15 +/- 19 at the end of the GnRH-treatment 8 +/- 14 During leuprorelin acetate treatment the r-AFS stages changed as follows: [table; see text] Using the scoring system 85.2% of the patients improved. Relief of dysmenorrhoea could be achieved in 95.4%, relief of dyspareunia in 64% and of pelvic pain in 69.4% of patients. Baseline hormone levels dropped sharply during treatment. [table; see text] Androstenedione, testosterone, blood pressure, body weight, haematological parameters, liver enzymes, creatinine, electrolytes and HDL-/LDL-cholesterin remained more or less unchanged. Side effects being hot flushes, sweating, sleeplessness, headache, nausea, depression and vaginal dryness were due to estradiol deprivation. In 135 patients resumption of menstruation occurred in 95.6% within the first three months post-treatment. 23 patients of whom 21 were judged as infertile, became pregnant immediately after treatment was finished. The study results confirm the efficacy of leuprorelin acetate depot in the treatment of even advanced stages of endometriosis.
It is demonstrated by means of extensive reference studies, as well as own results, that organic solvents and pesticides can be accountable for intoxications and various complications during pregnancy (e.g. abortion, stillbirth, intrauterine growth retardation). An initial stimulation of the adrenal cortex (hyperandrogenaemia) can result in partial insufficiency of the adrenal cortex with symptoms like alopecia and feeling of sickness. Consequences can be hypo- and hyperthyroidism. The immunological system is affected (e.g. abortion, susceptibility to infections). Neurovegetative and neuropsychological concomitant symptoms are numerous. Toxic contaminants affect men at different levels of the semen producing organs (e.g. oligospermia, azoospermia). Indications regarding diagnosis of toxic substances related illnesses as well as therapeutic and prophylactic potentialities are presented.
The hypothalamic-pituitary axis of 22 hyperandrogenic infertile women had suppression with either the gonadotrophin-releasing hormone (GnRH)-analogue buserelin (n = 12) or with an oestrogen-gestagen compound (Diane; n = 12). This was followed by pulsatile GnRH application for inducing ovulation (Zyklomat). In terms of ovulation and pregnancy rates the buserelin pre-treatment was more effective than the steroid pre-treatment, especially in hyperandrogenic non-polycystic ovaries (PCO).
During the research period from January 1984 through June 1991 649 patients between the age of 0 and 16 were examined. Divided into 13 diagnostic groups the vulvovaginitis occurred most frequently with 30.6%. The predominant causal agents were E. coli (18.1%) and streptococci B (11.5%). Almost 24% did not show any agents. Aside from malformations of the genitals (6%), the genital bleedings (8.3%), genital tumours (2.7%), the search for anticonceptives (7.5%), examinations by specialists (8.1%) and borderline surgical problems, cycle disorders (14.7%) were most frequent. Among the cycle disorders dysmenorrhea and oligomenorrhea were predominant. The hormonal inhibition of growth was also checked very carefully. Thus the necessity of well-aimed training of children's gynaecology becomes dear. Our results stress the importance of an intensive disciplinary contact between gynaecologists who are interested in pediatrics and pediatricians.
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.
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.
In a primigravida with a fundal/anterior wall placenta, a successful cephalic version was noted at 39 weeks after repeated moxibustion of the point Zhiyin (bl 67). Since routine foetal heart rate monitoring showed a sinusoidal pattern with severe decelerations, immediate Caesarean section was performed. Foetomaternal macrotransfusion of about 300 ml of blood was found. In view of this complication, possible risks of the method are discussed. Moxibustion does not seem to be suitable as self-therapy without close medical follow-up.
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.
Following a complete gynecologic--endocrinologic workup, 45 infertile women suffering from oligoamenorrhea (n = 27) or luteal insufficiency (n = 18) were treated with auricular acupuncture. Results were compared to those of 45 women who received hormone treatment. Both groups were matched for age, duration of infertility, body mass index, previous pregnancies, menstrual cycle and tubal patency. Women treated with acupuncture had 22 pregnancies, 11 after acupuncture, four spontaneously, and seven after appropriate medication. Women treated with hormones had 20 pregnancies, five spontaneously, and 15 in response to therapy. Four women of each group had abortions. Endometriosis (normal menstrual cycles) was seen in 35% (38%) of the women of each group who failed to respond to therapy with pregnancy. Only 4% of the women who responded to acupuncture or hormone treatment with a pregnancy had endometriosis, and 7% had normal cycles. In addition, women who continued to be infertile after hormone therapy had higher body mass indices and testosterone values than the therapy responders from this group. Women who became pregnant after acupuncture suffered more often from menstrual abnormalities and luteal insufficiency with lower estrogen, thyrotropin (TSH) and dehydroepiandrosterone sulfate (DHEAS) concentrations than the women who achieved pregnancy after hormone treatment. Although the pregnancy rate was similar for both groups, eumenorrheic women treated with acupuncture had adnexitis, endometriosis, out-of-phase endometria and reduced postcoital tests more often than those receiving hormones. Twelve of the 27 women (44%) with menstrual irregularities remained infertile after therapy with acupuncture compared to 15 of the 27 (56%) controls treated with hormones, even though hormone disorders were more pronounced in the acupuncture group. Side-effects were observed only during hormone treatment. Various disorders of the autonomic nervous system normalized during acupuncture. Based on our data, auricular acupuncture seems to offer a valuable alternative therapy for female infertility due to hormone 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.
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.
During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.
Knowledge of the immune response to natural infection with Neisseria gonorrhoeae is presupposition for the development of a gonococcal vaccine. Pili and protein I have gained importance for a subunite vaccine. A pilus vaccine proved to be ineffective in a field trial due to extensive pilus variability. According to an alternative strategy protein I may represent an important vaccine candidate for a gonococcal vaccine. To study the local and systemic, humoral immune response to N. gonorrhoeae cervical secretion, vaginal fluid and serum from prostitutes and family planning patients were compared by the use of a protein I ELISA. In local secretions and in serum patients in the study group showed significantly higher anti-protein-I-IgA-levels than patients in the control group. In cervical secretion immune response to an acute gonococcal infection consisted of a short lived, significant increase of anti-protein-I-IgA, while anti-protein-I-IgG showed a lower, but longer lasting significant increase. The course of the immune response in vaginal fluid reflected the immune response of cervical secretion at a lower level. In serum antigenic stimulus of a local gonococcal infection resulted in a significant but short lived protein I specific IgG immune response. In local infection with N. gonorrhoeae protein I represents a target antigen of the local and systemic immune response. Clear differences exist between local and systemic humoral immune response in the protein I reactive immunoglobulin class and in the course of reactivity. In the future it may be possible to define epitopes on protein I which induce protective immunity.
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Sperm-mucus interaction under in-vitro or in-vivo conditions can be affected by local anti-sperm antibodies (ASA). In a prospective study, a mixed antiglobulin reaction (MAR) test, using immunoglobulin-coated red cells and spermatozoa, was used to detect the presence of IgG and/or IgA on the spermatozoal surface in 209 males of infertile partnerships. The results of direct MAR tests range from 0 to 100% and a significant correlation between MAR % IgG and MAR % IgA (r = 0.74) was found. MAR positive semen samples were significantly more frequent in the group of patients with an inadequate outcome of postcoital testing (PCT). The sperm-mucus interaction in vitro, evaluated by means of the in-vitro sperm-cervical mucus penetration test (SCMPT) with cervical mucus (CM) of patients' partners, was particularly related to spermatozoal surface antibodies of the IgA class: MAR IgA positive ejaculates were seen in 13.9% of males with inadequate SCMPT versus 4.4% when SCMPT was adequate. The significant correlation between MAR IgA and the sperm penetration ability in vitro could also be proven when donors' CM was taken for the SCMPT, but not when a non-human material was used for in-vitro penetration testing. Microbial colonization of semen specimens did not interfere with the outcome of MAR testing. The pregnancy rate after 12 months was 23% (48/209) and was significantly lower when greater than 30% of spermatozoa were covered with surface ASA of the IgG or IgA class.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to examine more closely the interaction between thyroid function and pituitary--ovarian axis in infertile women. In 185 infertile women without clinical signs of thyroid dysfunction, TRH-tests (TSH basal and 30 min after 200 micrograms TRH i.v.) were performed in the early follicular phase in addition to routine hormonal checks (gonadotrophins, oestradiol, DHEAS, testosterone, prolactin). The women were classified as euthyroid (n = 74; TSH stim 5-20 mU/l), latent hyperthyroid (n = 31; TSH stim less than 5 mU/l), and preclinical hypothyroid (n = 80; TSH stim greater than 20 mU/l). From frozen serum, the following determinations were performed: TSH IRMA, laevothyroxine (T4), thyroxine binding globulin (TBG), microsomal (Mab) and thyroglobulin (Tab) antibodies. Various correlations between the thyroid parameters and the pituitary--ovarian axis were demonstrated. With increasing TBG concentrations, the interval between menses decreased. Overall and spontaneous pregnancy rates were highest in women with normal (less than 75th perc.) basal and stimulated TSH, high (greater than 75th perc.) T4 and low (less than 25th perc.) Mab. Women with normal Tab or high TBG experienced the highest delivery rate (77 versus 30%), while in women with low Tab or high Mab abortion and tubal pregnancies were most frequent. As only 25 women exhibited elevated Mab (greater than 500 U/ml) or Tab (greater than 200 U/ml) which correlated with elevated TSH and normal T4, the routine determination of thyroid antibodies was not necessary. The TRH-test, however, should be included in infertility work-up.
Thyroid stimulating hormone (TSH) determinations before and after thyrotropin-releasing hormone (TRH) stimulation were obtained in 834 infertile women, from 1982 until 1985. Thyroid function disturbances were seen in 20% of the women, in accordance with the prevalence in South Germany. Postcoital tests were significantly poorer in women with subclinical hypothyroidism than in euthyroid patients. Spontaneous conception was more frequent in euthyroid (16%) than in hypothyroid (6%) women. During the same period, prolactin was determined after TRH stimulation in the early follicular phase and after metoclopramide stimulation in the luteal phase, in 759 women. The pregnancy rate was not improved by administration of dopamine agonists in women with an exaggerated response to TRH or metoclopramide. Our results suggest that subclinical hypothyroidism as well as disorders of prolactin secretion may play a role in infertility. The TRH test is proposed to rule out thyroid dysfunction. Neither the TRH nor the metoclopramide test was useful for the prognostic differentiation of prolactin secretion disorders.