[Intentions and effects of the embryo protection regulation from the physician's viewpoint].
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Biomedical subjects
Publications and source records attributed to D Krebs.
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Multiple factors influence the outcome of in vitro fertilisation and embryo transfer (IVF-ET). In our prospective study different factors have been subject of examination concerning their effect on the outcome of in vitro fertilisation and embryo transfer. 1237 couples undergoing 1675 consecutive treatment cycles between 1.1.1990-31.12.1991 were included in this study. Prior to treatment, couples were divided into "good" and "poor" prognosis groups. Cycles were prospectively labelled as carrying a potentially "poor prognosis", if one or more of the following factors were noted: 1) female age > 35; 2) an existence of male factor; 3) couples with more than 3 previous unsuccessful treatment cycles. Couples with none of these factors were assigned to the "good" prognosis group. The pregnancy rate per cycle in the "poor" prognosis group was 5.96%, compared with 17.92% per cycle in the "good" prognosis group (p < 0.001). The most important factors determining pregnancy rates were female age and male factor, and we observed that the rate of pregnancy declined after the third treatment cycle. An explanation may be seen in lower fertilisation rates after the age of 35 and cases of poor semen quality. Both will result in poor embryo quality.
A diagnosis of breast cancer as early as possible is most important for a good prognosis. Among previous imaging modalities (mammography, sonography, DSA, thermography, CT) only mammography was able to prove a significant reduction of mortality, but unfortunately only for women above 50 years of age. Magnetic resonance mammography (MRM) is under technical and clinical evaluation for more than 8 years. Special surface coils and a variety of measurement sequences have been tested. By using "dynamic MRM", i.e., the repetitive imaging of the same slices before and at short time intervals after the injection of contrast medium, a high sensitivity (97.3%) and specificity (96.9%) was found in detecting breast cancers of different histology. In this study especially clinically or mammographically difficult cases were included in order to test the efficacy of dynamic MRM. Breast cancer can be proven or excluded with a very high degree of confidence. Conventional mammography had been yielding a vast number of false positive findings. With MRM, therefore, the number of biopsies can be substantially reduced. The remarkable uniformity of the maximum rate of signal enhancement in carcinomas may be explained by the changed vascularisation of malignant tumours based on early tumour angiogenesis. This change in vascularisation can be detected by combining the use of contrast medium with a high contrast sensitive measurement technique. This method seems to be much more reliable than mammographic or sonographic procedures. MRM needs further technical improvements. Since breast cancer is still the most frequent cause of cancer in women in the Western hemisphere, MRM should be used in all cases where is a discrepancy among radiographic, sonographic or clinical findings. However, MRM examinations should be performed only by experienced examiners, since a variety of pitfalls must be avoided.
After discussing the problem of folic acid requirements and supply during pregnancy, the results of a longitudinal study on 162 pregnant women are presented. By measuring biochemical and morphological changes in two subgroups (non-substituted vs unspecifically substituted), the necessity of a substitution with folic acid is discussed, as there might be additional requirements for the pregnant and the foetal organism. Concentrations of folic acid in the maternal plasma and in the erythrocytes as well as the segmentation rate and hypersegmentation of the granulocytes show a clear decrease in pregnancy. At the same time there was a significant difference between the subjects substituted and not substituted; the foetus and newborn levels were much higher than their mothers' concentrations. Moreover, there was a correlation between red cells folic acid levels in the last trimester and duration and outcome of pregnancy. These results indicate a substitution with folic acid for certain populations in pregnancy, which are highlighted.
For the therapy of severe forms of male sterility, we introduced all three methods of assisted fertilisation by micromanipulation in our hospital: partial zonal dissection (PZD), subzonal sperm injection (SUZI) and intracytoplasmatic sperm injection (ICSI). We report on our first pregnancy and birth.
Visual noise subjectively contains more meaningful patterns (1) when tachistoscopically presented to the left visual field, and (2) for persons who believe in extrasensory perception (ESP). These results indicate a possible right hemisphere mediation of delusional perception and suggest some delusional component in the belief in ESP.
By immunization of mice with the anti-CA 125 monoclonal antibody OC125, we tried to induce antibodies directed against the tumour-associated antigen CA125, via activation of the idiotypic network. Mice immunized by repeated administrations of F(ab')2-fragments of the OC125 antibody produced anti-idiotypic antibodies, imitating the original target antigen of the OC125. After induction of these anti-idiotypic antibodies (Ab2 beta) a murine IgG-anti-CA125 (Ab3) response was detected. The induction of idiotypic cascades offers the possibility of immunization against tumour-associated antigens, without using the original antigen and breaking antitumour tolerance.
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We evaluated the effect of repeated administration of OC125 F(ab')2 fragments on cancer antigen (CA) 125 determination in 210 serum samples from 30 patients. We found falsely high CA 125 concentrations in 142 (68%) samples, using a homologous CA 125 enzyme immunoassay (EIA) with OC125 antibodies. The Truquant OV2 method, which involves two other murine antibodies, and the IMx CA 125 method, which uses sheep antibodies as capture antibodies, resulted in only slightly increased (false-positive) values in some samples with exceptionally high CA 125 EIA values. We measured falsely low CA 125 values in 37 (18%) samples with the Truquant OV2 method. Interferences could be eliminated by removal of serum IgG. Our results suggest that interferences are to some extent caused by anti-idiotypic IgG induced by OC125 administration. Assays involving nonmurine anti-CA 125 antibodies as capture antibodies seem to be most suited for CA 125 determination after OC125 treatment, but in every case an apparent increase of CA 125 after OC125 infusion should be validated.
In the present paper, a new therapeutic concept of photodynamic laser therapy using antibody-linked dyes for the treatment of gynecological malignancies is described. So far, HPD (hematoporphyrin derivative) has been employed in this area, but is associated with toxic systemic reactions. We see a solution to this problem in the linking of a systemically non-toxic dye--known to induce photodynamic reactions while not itself being selectively accumulated within tumor cells--to an antibody directed against a selective tumor-associated antigen. The results of our study demonstrate the efficacy of this therapeutic concept as exemplified by the selective destruction of dye-labeled ovarian carcinoma cells by laser light of a defined wavelength (675 nm). The potential of this form of photodynamic therapy extends far beyond its use in ovarian carcinoma.
A prospective and randomized study was performed to investigate the effect of supportive hormones on the development and outcome of early pregnancies following in vitro fertilization and embryo transfer. Immediately after pregnancies were confirmed endocrinologically on day 15 after oocyte collection, 17 alpha-hydroxyprogesterone caproate and oestradiol valerate (PC/EV) was administered to half of the patients in a randomly controlled trial. One group received supportive treatment until the twelfth week of gestation, whereas the other group received no treatment at all. Both groups were followed up by measurements of serum levels of human chorionic gonadotrophin (HCG), oestradiol and progesterone every three days until day 35, when a first ultrasound examination was carried out to confirm fetal vitality. Subsequently, pregnancies were monitored sonographically at regular intervals. In cases of miscarriage, dilatation and curettage was performed and histology analysed. A total of 120 pregnant patients entered the study: 55 of them received hormone treatment and 65 patients were controls. Within the treatment group 48 (89%) clinically ongoing pregnancies were observed, five (9%) miscarriages occurred after the seventh week of gestation and one preclinical pregnancy was noted. In the control group, 38 (59%) ongoing pregnancies were observed, nine (14%) miscarriages occurred and 17 (27%) preclinical pregnancies were recorded. Two ectopic pregnancies, one in each group, were excluded from evaluation. A significantly higher percentage of pregnancies were intact at 7 weeks of gestation after treatment with PC/EV (p less than or equal to 0.01).
During the last few years, many healthy children have been born after in vitro fertilization and embryo transfer, fulfilling the wish for a child for many couples who had often nearly given up hope. Because of in vitro fertilization and other related methods developed subsequently (gamete intra-Fallopian transfer, intratubal embryo transfer), progress in the diagnosis and treatment of involuntary childlessness took place and has helped many patients. Furthermore, by dealing with these methods, new knowledge about ovarian function, fertilization and early embryonic development could be gained. This has also led to better treatment of childless couples. Despite the broad diagnostic and therapeutic possibilities of reproductive medicine, its limits must also be taken into account. These limitations have been recognized early by physicians and scientists dealing with this subject and also by society. Guidelines and laws have been drawn up which now give a clear framework.
A study was performed to evaluate a new transcervical, Fallopian tube access system for use in falloposcopy procedures without the need for conventional hysteroscopy or uterine distension. Visualization was accomplished by the use of a 0.5 mm falloposcope which was delivered to the Fallopian tube by a new linear everting catheter. The linear everting catheter allows access to the Fallopian tube by means of a flexible, tubular rolling membrane which can safely negotiate the tortuous anatomy from the ostium to the ampulla. Concurrent laparoscopy was performed solely for supervision purposes and not for tubal manipulations in 13 Fallopian tube access procedures in 10 patients. The ostia were visualized in 12 cases and the Fallopian tube was accessed in all 12 without complications. As a precursor for future gamete and embryo transfer procedures, intra-tubal insemination was performed by visualizing the ostia, accessing the Fallopian tubes, and obtaining successful isthmic-ampullary, intra-luminal images.
Rabbit embryos at the pronuclear stage (n = 480) were frozen using a mixture of propanediol and sucrose. The survival rate was 71% according to their morphological features shortly after thawing. The viability rate after 5 days of culture was 10% according to the number of embryos that reached the blastocyst stage, while the rate of formation of blastocysts from freshly collected and cultured pronuclear embryos was higher (59%). The implantation rate was higher (24%) if the frozen/thawed zygotes were directly transferred to foster mothers after 2-4 hours of culture, whereas with zygotes cultured for 24 hours (4 to 8-cell stages) the implantation rate was poor (4%). Both rates were low compared with the implantation rate (52%) achieved with freshly collected and directly transferred pronucleate embryos.
Chlorinated hydrocarbons are distributed worldwide and due to their lipophilic properties and chemical stability they accumulate in the foodchain. The concentrations of 19 different chlorinated hydrocarbons (hexachlorohexane (HCH), DDT and various metabolites and nine different polychlorinated phenyl (PCB) congeners were detected in various body tissues and fluids (maternal and fetal serum, adipose tissue, placenta, amniotic fluid) of full term pregnant women from Germany and Tanzania. Great variation of total toxin burden and toxin distribution within the different body compartments was found. This was in part due to local differences of exposure to some of the chlorinated hydrocarbons. Comparing samples from Germany and Tanzania, typical distribution patterns reflected the specific economic situation of the two countries with a high burden of insecticides (DDT and Dieldrin) in the agricultural country and high levels of constituents of industrial products (hexachlorobenzene (HCB) and PCBs) in Germany. Different chlorinated hydrocarbons seem to show different distribution patterns in body tissues, probably due to their chemical structure, the lipid content of the compartment and the overall toxin burden of the individual. A 10 to 100 fold accumulation of chlorinated hydrocarbons was observed in maternal adipose tissue compared with the other compartments. The concentrations of certain toxins in fetal cord serum and placenta were higher than in maternal serum.
The positive effect of an immunotherapy using tumor-associated antigens or tumor cells of ovarian carcinomas has not yet been proven. Although many unique tumor-associated antigens have been described and a tumor rejection could be seen in occasional cases, the failure of the immune system to destroy tumor cells is not clearly understood. An alternative approach is to initiate the idiotypic network utilizing antibodies (Ab1 or 2) against a tumor-associated antigen, which induces the production of anti-idiotypic-antibodies (Ab2 beta), mimicking the "internal image" of the tumor-associated antigen. These antibodies are able to induce a specific antitumor immunity in two ways: (1) the Ab2 can present the critical epitope in a different way and so modulates the immune system, or (2) it can induce the production of an Ab3, which by itself binds to the tumor antigen. Our first results on 22 patients with advanced ovarian carcinomas show that the induction of an anti-idiotypic antibody (Ab2 beta) against OC 125 mimicking the TAA Class III CA 125 leads to a prolongation of the survival rate also for extended stages. We see a beneficial role of the induction of the idiotypic network against a tumor-associated antigen showing delayed clinical courses of the disease after vaccination of the patients with antibody fragments of the OC 125.
In 26 patients with severe factor infertility (total spermatozoa per ejaculate 0.8-6.3 million) in vitro fertilisation was performed using a capillary tube culture system. Spermatozoa were concentrated and incubated with oocytes in a very small volume (10-20 microliters) within capillary tubes. In seven out of 26 patients (27%) at least one oocyte could be successfully fertilised (overall fertilisation rate 11.6%, 22/190 oocytes) and in two patients a pregnancy with the birth of a healthy child could be observed. If sperm progression was only of grade 2 or less no fertilisation could be observed in 10 patients with a total of 75 oocytes. The described capillary technique for in vitro fertilisation using very small volumes for sperm-oocyte culture may be useful in cases of severe oligozoospermia or before considering extreme therapies such as donor insemination of sperm microinjection.
From 1979-1988, 134 inpatients (m:f = 80:54) were treated because of an intracranial angioma (AVM). The male/female ratio was 3/2 in general as well as during the "reproductive age" (15-45 yrs). In 6 patients (20-27 yrs; grav 2/para 1: n = 3; grav 1/para 0: n = 3) the AVM became symptomatic during pregnancy (n = 4: 23-33 gestational week) or at birth (n = 2). In the group of the presently non-pregnant women (n = 40) 47 uncomplicated deliveries had occurred years before. We conclude that the available data neither allow us to reject nor to confirm the hypothesis that pregnancy and/or delivery influence the manifestation of cerebral AVMs. The reasons for this dilemma of epidemiology are discussed.