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Biomedical subjects

K Diedrich

Publications and source records attributed to K Diedrich.

At least 109 records · Page 6Linked to original sources
PubMed2001

Preoperative reduction of uterine fibroids in only 16 days by administration of a gonadotrophin-releasing hormone antagonist (Cetrotide).

Ten premenopausal women with symptomatic uterine fibroids confirmed by magnetic resonance imaging (MRI) were treated with four injections (s.c.) of 3 mg of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix every 4 days, starting on the first day of cycle. On every fourth day, blood samples were drawn for the measurement of gonadotrophins and sex steroids. On the 17th day of treatment after a final MRI control, myomectomy was performed laparotomically, laparoscopically or hysteroscopically. All patients showed a deep and sustained suppression of gonadotrophins and sex steroids over the treatment time. In three patients, no change or even an increase in uterine fibroids volume was observed according to MRI, and in one patient MRI did not allow a reliable interpretation. However, six patients showed a mean reduction of 31% in fibroid size after only 16 days of hormonal treatment. In nine patients laparoscopic or hysteroscopic myomectomy could be performed, while laparotomy was necessary only in one non-responder. Preparation of the cleavage plane during surgery was easy and blood loss was minimal. Patient compliance was excellent. No side-effects occurred. The GnRH antagonist Cetrotide(R), acting as an intermediate depot preparation at a dose of 3 mg, opens up a new avenue for preoperative short term treatment in a subgroup of patients with uterine fibroids, minimizing treatment time and patient discomfort.

Journal Article↗
PubMed2001

Preimplantation genetic diagnosis in Germany - ethical responsibility and law.

Preimplantation diagnosis (PGD) can be judged as early or brought forward prenatal diagnosis and brings up the ethical question in Germany whether potential selection of embryos and intentional killing of a human conceptus, showing a defect not or almost not compatible with life, is reconcilable with human dignity. Whereas prenatal diagnosis and its consequences are socially accepted in Germany, PGD is not compatible with the Embryo Protection Law and is still under debate since >5 years. On the other hand abortion is not subject to prosecution because the legal status of the mother outweighs that of the embryo or fetus. Here the conflict of two legally protected rights - the embryo's worth of protection and the woman's family planning - are accepted and form the basis of the potential decision of the prospective mother to carry the fetus to term or not. An obvious and deep contradiction of assessment is present between the legal requirements for the regulation of abortions in its amendment of 1995 and the Embryo Protection Law which exists unchanged since 1991. The killing of an embryo or fetus in vivo is not subject to prosecution although it is illegal, whereas the discard of an embryo in vitro after PGD was performed, also illegal, is subject to prosecution.

Journal Article↗
PubMed2001

Evaluation of an optimal luteal phase support protocol in IVF.

SUBJECT: Luteal phase support has been shown in the past to be an essential part of ovarian stimulation protocols, especially the long protocol. It could be shown that hCG is as effective as is progesterone for luteal phase support but hCG is accompanied by a higher rate of complications. METHODS: Progesterone can be administered in several routes. The oral, intramuscular (i.m.) and vaginal routes have been chosen frequently in the past. The oral route is ineffective, since progesterone has a low oral bioavailability (<10%), and a high rate of metabolites, which may result in side effects such as somnolence etc. Intramuscular administration provides very high serum levels of progesterone and this route is effective with regard to pregnancy rates. Injection of progesterone, however, is painful and cannot be done by the patient herself. The vaginal route is also effective, progesterone can be administered by the patient herself and progesterone is delivered directly to the uterus, where high levels are achieved (first uterine pass effect). RESULTS: Several studies could show, in the past, that the vaginal administration of progesterone is effective also with regard to the downregulation of uterine contractions. Crinone 8% Vaginal Gel is especially designed for vaginal use with a special applicator and has to be administered once daily in the morning. It adheres to the vaginal epithelium, and leakage of the gel is substantially reduced as compared to other drugs like capsules or suppositories. CONCLUSIONS: Since progesterone is as effective as hCG for luteal phase support but provides a higher safety with regard to ovarian hyperstimulation syndromes, and vaginal progesterone is as effective as intramuscular progesterone, vaginal progesterone should be the standard choice for luteal phase support. Crinone 8% seems to be the most comfortable way of vaginal administration of progesterone for luteal phase support in IVF cycles.

Administration, Intravaginal↗
PubMed2001

Predictive value of chromatin decondensation in vitro on fertilization rate after intracytoplasmic sperm injection (ICSI).

This study was undertaken to identify the relationship between sperm chromatin decondensation after incubation with sodium dodecyl sulphate (SDS) and ethylene diamine tetra acetic acid (EDTA), or heparin at various points of time. Likewise, this study will determine chromatin stability within definite time intervals, chromatin decondensation after intracytoplasmic sperm injection (ICSI), and whether chromatin decondensation in vitro could be used as a predictive test for fertilization capability after ICSI. Sixty-five infertile couples undergoing ICSI therapy were included in this prospective study. Male factor infertility was the main indication for inclusion. One millilitre from each semen sample after washing was mixed with SDS-EDTA (group 1) or SDS/heparin (group 2) and incubated for 120 min. Many smears were made within 10 min of mixing the spermatozoa with detergent and the reducing agents and at the following points of time 30, 60 and 120 min and after 24 h. Chromatin decondensation was evaluated after staining with acridine orange (AO). The mean percentage of uncondensed chromatin of spermatozoa in the semen sample in the first group before addition of SDS/EDTA was 26.1 +/- 19.0 and 22.3 +/- 18.9% in the second one. After incubation of spermatozoa for 30, 60 and 120 min and 24 h, the chromatin decondensation increased in the first group to 64.0 +/- 28.6, 83.0 +/- 21.1, 87.9 +/- 14.6, 92.1 +/- 16.2 and 98.0 +/- 6.75%, respectively. The corresponding values in the second group were 69.5 +/- 29.9, 78.6 +/- 22.4, 86.9 +/- 17.1, 95.13 +/- 6.5 and 98.3 +/- 5.6%. On the other hand, no correlations were found between the chromatin decondensation or chromatin decondensation rate in vitro and the fertilization rates in all investigated groups. In conclusion, neither the chromatin decondensation ability in vitro nor the rate of chromatin decondensation between various points of time after using SDS/EDTA, SDS/heparin could predict the chromatin decondensation of spermatozoa (fertilization capability) after ICSI.

Adult↗
PubMed2001

The role of gonadotropin-releasing hormone antagonists in in vitro fertilization.

Gonadotropin-releasing hormone (GnRH)-antagonists can suppress the pituitary hormone secretion completely within a few hours, allowing the avoidance of premature luteinization within controlled ovarian hyperstimulation (COH) for assisted reproductive technologies (ART) by midcycle administration. Two different protocols were described, which were widely used in COH in several phase II and III studies as well as in clinical practice since the GnRH-antagonists Cetrorelix (Cetrotidesound recording copyright sign; Serono International S.A., Geneva, Switzerland) and Ganirelix (Orgalutansound recording copyright sign, Antagonsound recording copyright sign; Organon, Oss, The Netherlands) are available on the market. Cetrorelix was applied in single- and multiple-dose protocols; Ganirelix was used until now only according to the multiple-dose protocol. Fertilization rates of >60% as well as clinical pregnancy rates of about 30% per transfer sound most promising. Estradiol secretion is not compromised by the GnRH-antagonists using recombinant follicle-stimulating hormone (FSH) for COH. The incidence of a premature leutinizing hormone (LH) surge is far below 2% while the pituitary response remains preserved, allowing the induction of ovulation by GnRH or GnRH-agonists. However, luteal phase support remains mandatory. The incidence of severe ovarian hyperstimulation syndrome (OHSS) seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened. Without any doubt GnRH-antagonists have the potential to become the new standard for controlled ovarian hyperstimulation.

Embryo Transfer↗
PubMed2001

Embryo implantation and GnRH antagonists: ovarian actions of GnRH antagonists.

The gonadotrophin-releasing hormone (GnRH) antagonists, cetrorelix and ganirelix, have both been approved for ovarian stimulation to prevent a premature LH surge. Since GnRH receptors and their gene expression have been detected in human ovary, concern has risen over whether GnRH antagonists might affect ovarian function. Three large trials which compared GnRH agonists (used in the standard protocol worldwide), with the new antagonist treatment found no significant differences concerning the most important goals, e.g. pregnancy rate, fertilization and quality of oocytes. However, the concentration of oestradiol, and the pregnancy and implantation rates were lower in GnRH antagonist-treated patients. These findings again fuelled the debate about the possible extrapituitary effects of GnRH antagonists. Here, we review the conflicting data in the literature on the ovarian effects of GnRH antagonists and discuss our own results. In our view, it is unlikely that GnRH antagonists have a relevant impact on ovarian steroidogenesis and function; however, GnRH antagonists may exert other effects on the ovary.

Animals↗
PubMed2001

Uterine artery Doppler velocimetry and the outcome of pregnancies resulting from ICSI.

BACKGROUND: An increased incidence of pregnancy complications following assisted reproduction has been reported. The use of uterine artery Doppler ultrasound may aid the prediction of such complications. METHODS: Doppler was performed at 18-24 weeks gestation in 114 singleton and 32 twin pregnancies after intracytoplasmic sperm injection (ICSI) and compared with a control group matched for age, parity and plurality. Outcome variables included gestational age at delivery, prematurity, preterm premature rupture of membrane (PPROM), birth weight, birth weight discordance of >20% in twins, small for gestational age (SGA), mode of delivery, development of pre-eclampsia and placental abruption. RESULTS: Compared with the controls, there were no significant differences concerning uterine Doppler parameters, pregnancy complications and the neonatal outcome, either in singleton or in twin pregnancies. According to Doppler results and/or risk factors by medical history, 42% of singleton ICSI and 39% of spontaneous singleton pregnancies were considered as high risk. In singletons, abnormal Doppler findings were associated with pre-eclampsia in 22% and SGA in 26% of ICSI patients, compared with 33 and 21% in controls; in contrast, 0 and 10% in ICSI and 3 and 6% in controls showed these complications but no risk factors respectively. No correlation was found between PPROM, prematurity, the rate of Caesarean section and pathological Doppler results. CONCLUSIONS: Uterine Doppler examination holds the potential to identify patients with an increased risk for developing pregnancy complications. According to our results, this risk is not elevated after ICSI treatment, therefore the decision of offering an intensified antenatal care should be based on the results of Doppler examination or risks by medical history rather than the mode of conception.

Abruptio Placentae↗
PubMed2001

Interactions of insulin-like growth factor-I, insulin and estradiol with GnRH-stimulated luteinizing hormone release from female rat gonadotrophs.

BACKGROUND: It is well established that ovarian steroids modulate gonadotropin secretion from anterior pituitary cells. It has been speculated that insulin and IGF-I might influence gonadotropin secretion. OBJECTIVE: To investigate the effects of IGF-I and estradiol alone, or combinations of IGF-I with insulin and estradiol on GnRH-stimulated LH release from female rat pituitary cells in serum-supplemented and serum-free culture conditions. METHODS: Pituitary cells were incubated for 24 h or 48 h with a series of increasing concentrations of IGF-I or estradiol and stimulated with 1 nmol/l GnRH for 3 h. To determine the interaction of IGF-I and estradiol on GnRH-stimulated LH secretion, cells were exposed to increasing concentrations of IGF-I and 100 pmol/l estradiol for 24 h. We also investigated the effects of combined treatment with IGF-I and insulin on GnRH-stimulated LH secretion. RESULTS: Our findings indicate that long-term IGF-I treatment (24 h) alone has a significant augmenting effect on GnRH-stimulated LH release in serum-free medium only, with a maximum at low concentrations (10 and 100 pmol/l). Estradiol significantly increased GnRH-induced LH release in a dose-dependent manner. The extent of GnRH-stimulated LH secretion by long-term estradiol treatment (24 h) was significantly greater in serum-supplemented (+42%) medium than in serum-free medium. Estradiol facilitated IGF-I-primed LH responses to GnRH in serum-free medium. In contrast, in serum-supplemented medium, the facilitating potential of estradiol was lower. We also found that, in GnRH-stimulated cells, LH release was augmented by insulin treatment, in contrast to quiescent cells that had been pretreated with 100 pmol/l IGF-I alone and 1 nmol/l insulin alone. CONCLUSIONS: IGF-I and to a lesser extent insulin stimulate GnRH-induced LH secretion from pituitary gonadotrophs. This action is enhanced by estradiol treatment of the cells. However, the well known stimulatory action of estradiol on LH secretion is dependent on the presence of growth factors.

Animals↗
PubMed2001

Actions of gonadotropin-releasing hormone antagonists on steroidogenesis in human granulosa lutein cells.

OBJECTIVE: GnRH antagonists have recently been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). We have here investigated whether the GnRH antagonists cetrorelix and ganirelix exert effects on ovarian steroidogenesis. Since there is some controversy about the action of GnRH agonists in the human ovary we also tested the effect of triptorelin on steroid production in cultured human granulosa lutein cells. METHODS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue. RESULTS: Such in vivo treatment did not result in significant effects of triptorelin or the two GnRH antagonists on spontaneous or human chorionic gonadotropin (hCG)-stimulated steroidogenesis. To exclude the possibility that the in vivo treatment might not affect in vitro steroid production because of low or absent peptide activity, we performed in vitro treatments with triptorelin, cetrorelix and ganirelix for up to 96 h. However, these treatment paradigms did not influence basal or hCG-stimulated steroid production. CONCLUSIONS: We conclude that GnRH antagonists do not exert any significant effects on ovarian steroidogenesis in vitro and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Cells, Cultured↗
PubMed2001

Subjective well-being in infertile couples.

The subjective well-being of infertile couples is affected by numerous variables. One hundred and ten infertile couples were investigated using the von Zerssen symptom checklist. With the exception of sterile women of fertile men (group 1: female infertility), women and men in the overall randomized sample and the diagnostic groups (group 2: subfertility of the man; group 3: sterility of both partners; group 4: idiopathic sterility) report fewer general symptoms than the overall population of patients with somatic and psychiatric diseases. Subfertile men show lower rating in the symptom checklist than the norm. Involuntarily childless women express more symptoms than their partners.

Adaptation, Psychological↗
PubMed2001

Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support.

BACKGROUND: A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70). METHOD: All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was > or = 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n=83) or progesterone only (group V, n=121). For vaginal progesterone Utrogest was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). RESULTS: Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p<0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. CONCLUSION: Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient.

Administration, Intravaginal↗
PubMed2000

Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer.

Breast cancer is a major cause of cancer-related death in women. BRCA1 tumour-suppressor function is abolished in sporadic breast cancer by down-regulation of the protein level. This down-regulation inversely correlates with tumour grading. BRCA1 is part of a multiprotein complex, which also contains the recombination factor Rad51. Here we describe that in contrast to BRCA1, histological grading of sporadic invasive ductal breast cancer significantly correlates with over-expression of wild-type Rad51. These data suggest that in addition to the absence of the tumour-suppressor protein BRCA1, over-expression of wild-type Rad51 also contributes to the pathogenesis of a significant percentage of sporadic breast cancers and that other mechanisms than mutations must be responsible for this altered expression.

BRCA1 Protein↗
PubMed2000

Clinical application of GnRH-antagonists.

Due to the different pharmacological mode of action, GnRH-antagonists seem to open up new avenues to hormonal treatment in several indications. Although it may be still too early to speculate about the possible end of the era of GnRH-agonists, from what is known today, the advantages of GnRH-antagonists are most evident in our opinion. When the development of sustained delivery systems may continue and be completed, the antagonists will have a major potential within benign gynecological conditions and also in the treatment of malignancies such as prostatic, mammary, endometrial or ovarian cancer. Suitable sustained delivery systems and the development of GnRH-antagonists with sufficient oral bioavailability, represent the present and future challenge for these efforts.

Clinical Trials, Phase III as Topic↗
PubMed2000

The situation of preimplantation genetic diagnosis in Germany: legal and ethical problems.

Preimplantation genetic diagnosis (PGD) has not been performed in Germany. Existing German laws do not explicitly permit or prohibit PGD. German law does forbid the wasting of totipotent embryonic cells, fertilizing oocyctes without transferring them in the same cycle, and the use of micromanipulations that later may harm embryonic development. German law also limits the number of oocytes allowed to be fertilized in each in vitro fertilization (IVF) cycle to three and prohibits research on embryos. The existence of these laws may impede but not prevent the development of PGD programmes in Germany. In contrast, the liberal regulation of pregnancy termination coupled with the development of ethical guidelines specific to PGD may facilitate the introduction of PGD in Germany. Because of these contradictions, legislation is required to clarify the legal status of PGD in Germany.

Abortion, Legal↗
PubMed2000

Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction.

A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO degrees II and degrees III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation.

Buserelin↗
PubMed2000

Serum leptin concentrations throughout the menstrual cycle.

Leptin is a cytokine involved in the regulation of food intake and fertility in rodents and in humans. No data exist about serum leptin serum levels during the spontaneous menstrual cycle. In this study 16 ovulatory cycles of endocrinologically normal volunteers were analyzed. Blood samples were taken on alternate days throughout the menstrual cycle for measurement of serum estradiol, progesterone, LH, FSH and leptin serum levels. No correlation of leptin values with estradiol values (r = 0.07) or progesterone values (r = 0.14) were seen. Mean leptin values during the luteal phase were significantly higher (16.67 +/- 9.45 ng/mL) compared to the follicular phase (13.50 +/- 8.75 ng/mL) (P < 0.02). A strongly positive correlation with the progression of the menstrual cycle could be seen (r = 0.91). The physiological significance of higher luteal phase leptin levels is unknown.

Adult↗