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K Diedrich

Publications and source records attributed to K Diedrich.

At least 91 records · Page 5Linked to original sources

Safety aspects of gonadotrophin-releasing hormone antagonists in ovarian stimulation procedures: ovarian hyperstimulation syndrome and health of children born.

The safety of ovarian stimulation procedures or the procedure of assisted reproduction in general can be estimated by various parameters. Two of the most important are the health of children born after the procedure and the incidence of ovarian hyperstimulation syndrome (OHSS). The latter is important because it is the most severe, potentially life-threatening complication of any stimulation procedure. The use of gonadotrophin-releasing hormone (GnRH) antagonists in ovarian stimulation protocols has had no impact on the health of children born. This was proven in 227 children born after the use of cetrorelix and in 73 children born after the use of ganirelix. To analyse the incidence of OHSS and the impact of GnRH antagonists on clinical pregnancy rates compared with the long protocol, a meta-analysis was done. This showed a reduction of OHSS with the use of cetrorelix. Furthermore, when compared with the long protocol, clinical and ongoing pregnancy rates were not significantly reduced with the use of cetrorelix. Taken together, the use of GnRH antagonists are safe with regard to children's health. The incidence of OHSS does not increase with ganirelix, and a reduction can be expected with cetrorelix.

Female↗

Application of a 1.48-microm diode laser for bisecting oocytes into two identical hemizonae for the hemizona assay.

Laser systems are very promising new technical tools in assisted reproduction. It was investigated if laser radiation can replace the mechanical cutting procedure via micromanipulator in the hemizona assay (HZA), a commonly used bioassay to determine the sperm-zona pellucida binding capacity. An oocyte was bisected precisely into two identical hemizonae with approximately 20 laser pulses (pulse length 30 msec) using a 1.48-microm diode laser. Compared with the conventional method using microscalpels for zona bisection, laser treated hemizonae showed equivalent sperm-binding and within the two groups there was no detectable difference between matching hemizonae in their capacity for tight sperm-binding. To evaluate whether laser radiation affects the outcome of the HZA when effects of certain substances are investigated, the spermatozoa were preincubated with human follicular fluid (hFF), which inhibits the binding of spermatozoa to zona pellucida in vitro. Supplementation with follicular fluid exerted an inhibitory effect in both groups. The hemizona index (HZI) showed no statistical differences between the two methods. Therefore, the 1.48-microm diode laser is a suitable new instrument for generating equally sized hemizonae. There is no use for holding pipettes and microscalpels, on the contrary, for performing the HZA the laser is a precise, very quick and easy to use new working tool.

Female↗

Strong impact of estrogen environment on Doppler variables used for differentiation between benign and malignant breast lesions.

OBJECTIVES: To analyze the impact of an estrogen environment on the Doppler variables usually used for differentiation between benign and malignant lesions. METHODS: A total of 142 malignant and 107 benign breast lesions was demonstrated (in 91 premenopausal and 152 postmenopausal patients) by B-mode ultrasound. Intratumoral vessels were visualized by color Doppler and blood flow velocity waveforms were analyzed by pulsed Doppler. The number of intratumoral vessels and the Doppler variables, peak systolic velocity, resistance and pulsatility indices and the peak systolic/diastolic ratio were evaluated in different endocrine milieus represented by menopausal status, phase of the menstrual cycle, intake of oral contraceptives or hormone replacement therapy. RESULTS: In malignant tumors the Doppler variables resistance and pulsatility indices and the systolic/diastolic ratio were significantly higher in postmenopausal women than in premenopausal women. In benign tumors significantly higher values of resistance and pulsatility indices were also detected in post- compared to premenopausal women (P < or = 0.05). In premenopausal patients with benign tumors taking oral contraceptives the number of intratumoral vessels was significantly higher, while resistance index and systolic/diastolic ratio values were decreased compared to patients with spontaneous menstrual cycles. In postmenopausal patients hormone replacement therapy did not influence Doppler variables in the benign or the malignant groups. CONCLUSION: Our results demonstrate a robust influence of menopausal status and oral contraceptives on Doppler variables of breast lesions. We believe it is likely that some of the differences in the Doppler variables found in reports comparing benign and malignant breast lesions were caused by their association with a pre- or postmenopausal status.

Adolescent↗

Tailoring the GnRH antagonist cetrorelix acetate to individual patients' needs in ovarian stimulation for IVF: results of a prospective, randomized study.

INTRODUCTION: This study was performed to evaluate whether a tailored approach to the administration of the GnRH antagonist cetrorelix acetate according to follicular size leads to a reduction in the amount of Cetrotide vials used and/or an increased number of monitoring visits. METHODS: Sixty patients were prospectively randomized (using sealed envelopes) to receive either the fixed multiple dose antagonist protocol starting on day 6 of stimulation (group 1), or an individualized protocol with the time of antagonist start according to follicle size (14 mm, group 2), or an individualized single dose protocol (group 3). Recombinant human (rh)FSH was used. The primary endpoints were the number of Cetrotide vials and number of monitoring visits. Statistical power for the parameter Cetrotide vials was 80%. RESULTS: Patients in group 1 needed significantly more Cetrotide vials (6.81 +/- 1.61) than patients of group 2 (4.59 +/- 1.65; P < 0.01). The number of monitoring visits was similar between the three groups. Surprisingly, the number of retrieved oocytes was significantly higher in the individualized groups as compared with group 1. Despite a significantly lower total amount of rhFSH used, estradiol levels were significantly higher in group 2 as compared with group 1. CONCLUSION: Tailoring of GnRH antagonist protocols leads to an optimization of ovarian stimulation with more oocytes retrieved despite less rhFSH used, and the same number of monitoring visits.

Adult↗

Use of cetrorelix in combination with clomiphene citrate and gonadotrophins: a suitable approach to 'friendly IVF'?

BACKGROUND: With the recently introduced GnRH antagonists, soft stimulation protocols on the basis of clomiphene pretreatment should be possible as the pituitary remains fully sensitive at the beginning of the cycle. METHODS: A prospective trial was carried out on 107 patients undergoing IVF treatment using the multiple dose GnRH antagonist protocol (cetrorelix), clomiphene citrate, and either HMG (n = 54) or recombinant FSH (rFSH) (n = 53). Different stimulation protocols were used to find the most appropriate one for clinical application. RESULTS: Both treatment groups, HMG and rFSH, yielded comparable results concerning gonadotrophin dose, stimulation days and pregnancy rate. A mean number of 6.34 +/- 4.4 metaphase II oocytes was retrieved and a mean number of 2.45 +/- 0.65 embryos was transferred. However, the overall rate of premature LH surges was 21.5% (defined as measurement of LH >10 IU/l and progesterone >1 ng/ml) which is unacceptable for clinical practice. CONCLUSIONS: Increasing the daily cetrorelix dose from 0.25 to 0.5 mg might decrease the number of premature LH surges. Soft stimulation protocols with clomiphene should be used cautiously.

Adult↗

Increased frequency of X-bearing sperm in males from an infertility clinic: analysis by two-color fluorescence in situ hybridization.

Semen samples from 34 men visiting the Lübeck infertility clinic were investigated using a two-color FISH method to determine the ratio of X- and Y-bearing sperm. The overall ratio was significantly shifted to a preponderance of X-containing sperm. A statistical comparison with seven reports from the literature which included 53 normal probands demonstrated in our patients a significant tendency of a preponderance of X-bearing sperm and significantly less Y-bearing sperm. Furthermore, the Lübeck sperm samples are remarkably more heterogeneous in respect to their variability of X- and Y-bearing spermatozoa than in the other mentioned studies with normal probands. These phenomena have to be evaluated in further studies on groups of infertile males showing similar infertility histories.

Adult↗

Outcome of anticipated ICSI cycles using intentionally frozen-thawed testicular spermatozoa according to the spouse's response to ovarian stimulation.

PURPOSE: To investigate the outcome of ICSI cycles, using frozen-thawed testicular spermatozoa from patients suffering from non-obstructive azoospermia, in relation to the spouse's response to ovarian stimulation. METHODS: A retrospective study with two groups of couples where males suffered from non-obstructive azoospermia. In group 1 (n = 14), the female partners responded poorly to ovarian stimulation (< or = 4 oocytes retrieved). In group 2 (n=14), the female partners responded well (> or = 10 oocytes retrieved). Both groups underwent 14 cycles of ICSI using frozen-thawed spermatozoa obtained by TESE. RESULTS: The total amount of gonadotropin, the duration of stimulation, the peak estradiol concentrations and the number of oocytes were significantly different between the two groups. Despite the satisfactory fertilisation rates, the outcome in poor responders was disappointing due to a low number of oocytes. There was only one pregnancy in the poor responder group whereas there were four in the group that responded well. The pregnancy rates per oocyte collection were 7.14% in group 1 versus 28.57% in group 2. The implantation rates were 60.60% versus 55.33%, respectively. CONCLUSION: It is possible to achieve satisfactory fertilisation rates using frozen-thawed, surgically-retrieved testicular spermatozoa, but the poor ovarian response to stimulation induction is the limiting factor in reaching implantation and pregnancy. It is preferable that poorly stimulated cycles be canceled, in the hope of a better subsequent response.

Adult↗

Comparison of poor responders with good responders using intentionally frozen-thawed epididymal spermatozoa in subsequent ICSI cycles.

PURPOSE: To compare the outcome of intracytoplasmic sperm injection (ICSI) cycles performed with frozen-thawed epididymal spermatozoa between patients who respond poorly and patients who respond well to ovarian stimulation. METHODS: 17 patients suffering from obstructive azoospermia underwent microsurgical retrieval of epididymal spermatozoa (MESA) and the spermatozoa were frozen. The frozen-thawed spermatozoa were used in subsequent ICSI cycles. In six patients, the female partners responded poorly to ovarian stimulation. They accomplished nine ICSI cycles. In 11 patients, the female partners responded well to ovarian stimulation and they accomplished 16 cycles. RESULTS: Poor responders were older than those who reponded well. The mean number of metaphase II oocytes collected was lower in the poor responder group. In the poor responders, two couples failed to fertilise the oocytes in two ICSI cycles. In the good responders, one couple failed to fertilise the oocytes in an ICSI cycle. There were no significant differences in fertilization rates between the two groups. The estradiol concentrations on the day of hCG administration were significantly higher in the good responders. There was no pregnancy in the poor responder group, while three patients who responded well conceived. Eight good responders had 34 supernumerary 2PN oocytes which were cryopreserved. CONCLUSION: Frozen-thawed epididymal spermatozoa from men with obstructive azoospermia are potent to achieve satisfactory fertilization rates. Poor ovarian response to stimulation induction appears to be the main limiting factor in reaching the stage of embryo transfer. It is preferable in older women to cancel cycles with poor response in the hope that a better response might be obtained in a subsequent cycle. Thus, the frozen-thawed epididymal sperm can be preserved and the most stressful and expensive phase of IVF-ICSI treatment can be avoided.

Adult↗

Selection pressure for the factor-V-Leiden mutation and embryo implantation.

The factor-V-Leiden mutation is seen in high frequencies in white people, despite its contribution to second-trimester abortion, preterm birth, and deep-vein thrombosis. The reason for its high frequency is not known. We investigated 102 mother-child pairs who had had successful in-vitro fertilisation by intracytoplasmic sperm injection as a model for human implantation. In 90% (9 of 10) of mother-child pairs who carried factor-V-Leiden mutation, the first embryo transfer was successful, compared with 49% (45 of 92) in factor-V-Leiden negative pairs (p=0.018, Fisher's exact test). Furthermore, the median number of unsuccessful transfers was lower in pairs who were positive for the mutation (0, range 0-2) than those who were negative (1, 0-8) (p=0.02, Mann Whitney U test) suggesting that improved implantation rate is an important genetic advantage of the factor-V-Leiden mutation.

Adult↗

Towards environmental toxicogenomics -- development of a flow-through, high-density DNA hybridization array and its application to ecotoxicity assessment.

Assessment of the environmental hazard posed by soils/sediments containing low to moderate levels of contaminants using standard analytical chemical methods is uncertain due (in part) to a lack of information on contaminant bioavailability, the unknown interactive effects of contaminant mixtures, our inability to determine the species of a metal in an environmental matrix, and the relative sensitivity of bioassay species. Regulatory agencies compensate for this uncertainty by lowering cleanup goals, but in this process they effectively exclude otherwise attractive cleanup options (i.e. bioremediation). Direct evaluations of soil and sediment toxicity preclude uncertainty from most of these sources. However, the time and cost of chronic toxicity tests limits their general application to higher levels of tiered toxicity assessments. Transcriptional level (mRNA) toxicity assessments offer great advantages in terms of speed, cost and sample throughput. These advantages are currently offset by questions about the environmental relevance of molecular level responses. To this end a flow-through, high-density DNA hybridization array (genosensor) system specifically designed for environmental risk assessment was developed. The genosensor is based on highly regular microchannel glass wafers to which gene probes are covalently bound at discrete (200-microm diameter spot) and addressable (250-microm spot pitch) locations. The flow-through design enables hybridization and washing times to be reduced from approximately 18 h to 20 min. The genosensor was configured so that DNA from 28 environmental samples can be simultaneously hybridized with up to 64 different gene probes. The standard microscopic slide format facilitates data capture with most automated array readers and, thus high sample throughput (> 350 sample/h). In conclusion, hardware development for molecular analysis is enabling very tractable means for analyzing RNA and DNA. These developments have underscored the need for further developmental work in probe design software, and the need to relate transcriptional level data to whole-organism toxicity indicators.

Animals↗

Prospective evaluation of the systemic immune response following abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy.

BACKGROUND: Alterations in serum levels of cytokine interleukin-6 (IL-6) and acute-phase protein C-reactive protein (CRP) correlate directly with extent of tissue damage and inflammatory reaction. We therefore prospectively compared the postoperative levels of IL-6 and CRP following abdominal (AH), vaginal (VH), and laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: A total of 29 patients were included in the study (10 VH, 10 LAVH, 9 AH). Nine blood samples were taken from each patient at various time points before, during, and after surgery. CRP and IL-6 were measured under standardized conditions using ELISA and turbidometry. RESULTS: Preoperative levels of IL-6 and CRP were low in all three patient groups. There was a significant increase in the IL-6 level in patients undergoing AH at the time of peritoneal closure that reached a maximum 2 h postoperatively and remained significantly elevated for 12 h postoperatively when compared to the IL-6 levels of patients undergoing VH or LAVH (p < 0.05). The levels of the IL-6 time courses differed significantly among the three operative procedures (p = 0.013). In contrast, the levels of the CRP time courses did not differ significantly (p = 0.066); however, CRP expression was elevated 36 h postoperatively in patients undergoing AH, as compared with those undergoing VH. CONCLUSION: Elevated IL-6 levels subsequent to AH may reflect significantly greater tissue damage in these patients than in patients who undergo VH or LAVH. LAVH should therefore be considered in cases that cannot be managed by the vaginal route alone.

Acute-Phase Reaction↗

Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Meta-analysis.

The use of GnRH antagonists has revolutionized ovarian stimulation for assisted reproduction. Two GnRH antagonists are clinically available, namely, cetrorelix and ganirelix. Several studies have directly compared these new stimulation protocols against the long GnRH agonist protocol. To evaluate whether there is a reduction in cases of ovarian hyperstimulation syndrome (OHSS) and/or a reduction in pregnancy rates, a meta-analysis was performed. There was a significant reduction of OHSS cases in the cetrorelix studies (odds ratio, OR, 0.23; 95% confidence interval, CI, 0.10-0.54), but no reduction for ganirelix (OR 1.13; 95% CI 0.24-5.31). The incidence of OHSS degree III cases was reduced in the cetrorelix protocols as compared to the long protocol to a nearly significant degree (OR 0.26; 95% CI 0.07-1.01). Ganirelix did not reduce the incidence of OHSS degree III at all (OR 1.08; 95% CI 0.27-4.38). The pregnancy rate per cycle was significantly lower in the ganirelix protocols than in the long protocol (OR 0.76; 95% CI 0.59-0.98). The studies using cetrorelix showed quite similar, not significantly different results for the antagonist and the long protocol groups for the pregnancy rate per cycle (OR 0.91; 95% Cl 0.68-1.22). From the data one can conclude that cetrorelix but not ganirelix will reduce the incidence of cases of OHSS and that cetrorelix but not ganirelix will result in the same pregnancy rates as the long protocol. Several possibilities to explain this phenomenon are discussed.

Chorionic Gonadotropin↗

Ureteric and pulmonary endometriosis.

Pulmonary lesions and ureter involvement are rare complications of endometriosis. We describe the first case with an involvement of both sites in this condition. The radiographs showed "pulmonary metastases" together with clinical findings of a hydronephrosis, mimicing a malignant metastatic gynecologic tumor of unknown primary. A laparoscopy showed severe endometriotic lesions; therefore the findings were most likely related to the condition of endometriosis. The patient was treated with gosereline acetate for six months (Zoladex). Control radiographs showed complete regression of the pulmonary lesions and the patient is symptom free at 36 months after diagnosis.

Adult↗

Coping with male infertility. Gender differences.

Infertility is a stressor that affects the infertile couple. Coping of infertile couples with the unfulfilled desire for a child is affected by numerous variables. Depending on the diagnose is the patients were assigned to four groups: Group 1: female infertility (infertile women of fertile men), Group 2: infertility of the men, Group 3: infertility of both partners, Group 4: idiopathic sterility). One hundred and ten infertile couples were investigated with the Freiburg questionnaire of Coping with Illness. Compared to their partners, the women of infertile couples report a higher feature rating in the cales "depressional coping" and "self-distraction and self-stabilisation". Women of infertile couples show lower feature ratings compared to the standardised collective of patients with chronic somatic disease only on the scale "religiousness and search for meaning". Involuntarily childless men activate all coping strategies to a smaller extent than the reference sample. The experience of infertility is greatly affected by gender and the associated role expectations.

Adaptation, Psychological↗

Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing hormone-releasing hormone antagonist cetrorelix.

OBJECTIVE: To summarize data from completed phase II and III clinical trials on children born after controlled ovarian stimulation using the luteinizing hormone-releasing hormone antagonist cetrorelix. DESIGN: All children born after ovarian stimulation in patients treated for infertility who were in prospective studies until March 23, 1999. SETTING: Academic research center. PATIENT(S): Children born after IVF or IVF plus ICSI. INTERVENTION(S): Controlled ovarian stimulation with cetrorelix in a multiple-dose or single/dual-dose protocol. MAIN OUTCOME MEASURE(S): Outcome of pregnancy and, in deliveries, the date of birth, number and sex of children born, birth weight, body length, and abnormalities were recorded. At approximately 1 year of age and 2 years of age, body weight and length and abnormalities in physical and mental development were recorded. RESULT(S): Two hundred nine and 18 children were born after fresh and frozen embryo transfers, respectively. Of the pregnancies, 76.2% (179 of 234) resulted in live birth and ectopic pregnancy occurred in 3.4% (8 of 231); one heterotopic pregnancy and four induced abortions were recorded. The malformation rate among all live births, stillbirths, and aborted fetuses was 3.1%. CONCLUSION(S): Use of cetrorelix in controlled ovarian stimulation does not harm the subsequently born children.

Adult↗

Vascular endothelial growth factor mRNA in eutopic and ectopic endometrium.

OBJECTIVE: To evaluate changes in expression levels of vascular endothelial growth factor (VEGF) mRNA in human endometrial explants in a chicken chorioallantoic membrane model of endometriosis. DESIGN: Experimental prospective study. SETTING: University hospital. PATIENT(S): Endometrial biopsy samples were obtained from healthy, ovulating women undergoing elective surgery. INTERVENTION(S): Endometrial fragments were placed on the chicken chorioallantoic membrane and removed for analysis after 0, 24, 48, and 72 hours. MAIN OUTCOME MEASURE(S): Expression of different VEGF mRNA splice variants was tested. Expression of VEGF(165) mRNA was assessed by using competitive polymerase chain reaction and normalized to expression of the housekeeping gene human glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. RESULT(S): After 0, 24, 48, and 72 hours of incubation, all grafts expressed VEGF(121), VEGF(145), VEGF(165), and VEGF(189) mRNA. Expression of VEGF(165) mRNA increased up to 10-fold at 24 to 72 hours compared with precultivation values. CONCLUSION(S): Levels of VEGF(165) mRNA in endometrial grafts increase after implantation on chicken chorioallantoic membrane. Hypoxic induction of VEGF mRNA expression in endometrial cell cultures has been reported previously. Induction of VEGF expression might indicate relative hypoxia of the specimen due to insufficient vascularization. Expression of VEGF may assist in vascularization of endometrial explants after retrograde menstruation.

Animals↗

Preimplantation genetic diagnosis: the German situation.

Preimplantation genetic diagnosis makes it possible to detect some genetic disorders in embryos in vitro before they are transferred to the uterus. Using this technique, there is an opportunity for couples who have an increased risk of transmitting severe genetic disorders to their offspring to reduce this risk by >95%. By doing PGD, abortions at a later stage can be avoided.

Ethics, Medical↗

Gonadotropin-releasing hormone antagonist protocol: a novel method of ovarian stimulation in poor responders.

OBJECTIVE: To estimate the efficacy of gonadotropin-releasing hormone (GnRH) antagonist 'Cetrorelix' in poor responders comparing with the standard long protocol. DESIGN: The study population consisted of 21 poor responders who underwent ICSI and treated with Cetrorelix according to the multiple-dose protocol and who were compared with 21 poor responders treated according to the long protocol and who also underwent ICSI. Patients in both groups were matched for chronological age, the number of follicles found by ultrasound at the retrieval day and cause of infertility. Fifteen patients of GnRH antagonist group were treated with the combination of GnRH antagonist with clomiphene citrate (CC) plus gonadotropins, while six patients were treated with the combination of GnRH antagonist plus gonadotropins, but without CC. RESULTS: The use of GnRH antagonist in a multiple dose protocol gave a pregnancy rate of 14.28% which was in the range expected for patient with poor response, but with shorter treatment duration and with fewer ampoules of gonadotropins as compared with the use of a GnRH agonist protocol in a depot formulation. Within Cetrorelix group patients who received CC had a significant shorter duration of stimulation and needed fewer ampoules as compared with patients in the same group who did not receive CC. CONCLUSIONS: A GnRH antagonist multiple dose protocol may be the protocol of choice for the treatment of poor responders. The use of GnRH antagonist Cetrorelix ended with significantly less ampoules of gonadotropins and a shorter duration of stimulation.

Adult↗