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Biomedical subjects

Klaus Diedrich

Publications and source records attributed to Klaus Diedrich.

72 records · Page 4Linked to original sources
PubMed2002

Comparison of cryopreservation outcome with gonadotropin-releasing hormone agonists or antagonists in the collecting cycle.

OBJECTIVE: To compare the pregnancy rates of frozen-thawed 2-pronucleate (2PN) oocytes obtained either in a long protocol or in an antagonist protocol and ovarian stimulation with either human menopausal gonadotropin (hMG) or recombinant follicular stimulating hormone (recFSH). DESIGN: Retrospective data analysis. SETTING: Academic infertility center. PATIENT(S): Three hundred forty-two infertile couples who underwent a transfer of cryopreserved 2PN oocytes. INTERVENTION(S): hMG (n = 194) or recFSH (n = 92) in a long protocol or hMG (n = 16) or recFSH (n = 40) stimulation under pituitary suppression with the GnRH antagonist Cetrotide was used. The 2PN oocytes were transferred after endometrial preparation using E(2) valerate and vaginal progesterone (Crinone 8% vaginal gel). MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and abortion rates. RESULT(S): Implantation rates in the freeze-thaw cycles were 5.6% (hMG) and 3.8% (recFSH) with 2PN oocytes from the long protocol and 7% from the antagonist cycles, irrespective of whether hMG or recFSH was used. Pregnancy rates were similar independent of whether they resulted from the long-protocol cycles with hMG (15.4%) and recFSH (13.1%) or from the antagonist protocol cycles with hMG (25.0%) and recFSH (17.5%). CONCLUSION(S): The potential to implant is independent of the gonadotropin-releasing hormone analogue and gonadotropin chosen for the collection cycle when previously cryopreserved 2PN oocytes were replaced after thawing in the cleavage stage.

Adult↗
PubMed2002

Detection of increased icb-1 transcript levels in maturing HL-60 cells: a novel marker for granulocytic and monocytic in vitro differentiation.

Human gene icb-1 was initially described as a gene with increased expression in endometrial tumor cells differentiated in vitro by culture on a reconstituted basement membrane. We provide evidence for a more general involvement of icb-1 gene function in cellular differentiation processes. We report the up-regulation of icb-1 transcript levels in HL-60 promyelocytic leukemia cells during their in vitro differentiation induced by all-trans retinoic acid, vitamin D(3) or DMSO. Increased icb-1 mRNA levels could be observed both in monocytic and granulocytic differentiation. We also report the identification of the novel icb-1 splice variants icb-1beta and gamma, and the spleen-specific isoform icb-1delta. Expression of icb-1 can be used as a novel marker for in vitro differentiation processes of HL-60 cells.

Alternative Splicing↗
PubMed2002

Will GnRH antagonists assist in the treatment of benign gynaecological diseases?

While GnRH agonists have become well-established tools for preoperative treatment of uterine fibroids or postoperative treatment in endometriosis for 3-6 months, GnRH antagonists seem to offer important advantages due to their specific pharmacological mode of action. Avoiding any flare-up effect, it seems to be possible to reduce treatment time to about only 2-4 weeks in the case of fibroids to obtain a clinically relevant reduction in size. Furthermore, due to the classic competitive receptor blockade induced by GnRH antagonists, it is feasible to preserve residual oestradiol secretion for a period of 8 weeks in patients with endometriosis. Endometriosis patients undergoing this treatment reported a symptom-free period, with no signs of mood changes, hot flushes, loss of libido, vaginal dryness or other symptoms. Serum oestradiol oscillated around a mean level of 50 pg/ml during therapy. Sequential administration of the GnRH antagonist cetrorelix (Cetrotide), in a 3 mg dosage once weekly over 8 weeks in the case of endometriosis or administration every 4th day for a time span of 2-4 weeks for fibroids, creates a new opportunity for medical treatment. Although 3 mg of cetrorelix acetate obviously acts as an intermediate depot preparation, results obtained so far are very preliminary.

Endometriosis↗
PubMed2002

Ovarian stimulation: from basic science to clinical application.

Treatment for infertility, including ovarian stimulation, was first introduced almost 100 years ago. At this time, radiation therapy became an established treatment, and it was only some decades later that the problem of radiation-induced cancer emerged. Non-human gonadotrophins, such as pregnant mare serum gonadotrophin (PMSG), and human pituitary gonadotrophins (HPG), were commonly used for hormonal stimulation procedures. However, use of PMSG led to antibody formation, and it was therefore only useful for the first treatment cycle. HPG produced good results, but its use came to an end in the late 1980s when it was linked to the development of Creutzfeldt-Jakob disease. The first hormonal product from human menopausal urine to be used was human menopausal gonadotrophin (HMG), followed later by purified preparations of this product. All of these preparations contained a high percentage of unknown urinary proteins, which interfered with batch-to-batch consistency. This changed with the introduction of recombinant gonadotrophins, produced from an immortalized/standardized mammalian cell line (CHO). More recent developments include the introduction of long-acting gonadotrophin formulations. The development of gonadotrophin-releasing hormone (GnRH) analogues and more recently the use of GnRH antagonists has helped to improve ovarian stimulation protocols by optimizing their efficacy, and making them easier to administer.

Animals↗
PubMed2002

The use of cryopreserved mature and immature testicular spermatozoa for intracytoplasmic sperm injection: risks and limitations.

Treatment of severe male subfertility has become available since the intracytoplasmic injection of a single sperm into an oocyte was successfully applied for the first time in 1992. Moreover, with the use of fresh and cryopreserved epididymal and testicular spermatozoa for this procedure, fertilization and pregnancies could be accomplished. This review addresses the development and performance of these techniques and discusses achievements and problems as well as future aspects of the feasibility of early spermatid injection. Furthermore, limitations of these procedures and concerns with regard to genetic and epigenetic risks of using immature gametes are stressed.

Cryopreservation↗
PubMed2002

Gonadotropin-releasing hormone antagonists: pharmacology and clinical use in women.

Gonadotropin-releasing hormone (GnRH) antagonists are now widely used in protocols of patients with controlled ovarian hyperstimulation to treat infertility. By competitively binding to the pituitary GnRH receptor, they lead to a rapid suppression of gonadotropins and consecutively sex hormones. In the past, GnRH agonists have been exclusively used for these patients, with the disadvantage of an initial rise of gonadotropins--the flare-up effect. Several trials comparing the agonistic and antagonistic analogs of GnRH found no significant differences in oocyte quality, fertilization and pregnancy rates. Slightly lower implantation and pregnancy rates, and estradiol levels, in patients treated with GnRH antagonists has raised concern about eventual extrapituitary adverse effects. However, no convincing evidence has yet been found for any detrimental ovarian effects of GnRH antagonists. The lower rate of ovarian hyperstimulation syndrome, a potentially severe disadvantage of infertility treatment, is a positive feature of GnRH antagonists. The key point is that GnRH antagonists have been proven to be as effective and safe as GnRH agonists. This broadens the spectrum of indications for GnRH antagonists to sex hormone-dependent disorders like endometriosis, uterine fibroids, and gynecological cancers such as breast and ovarian cancer.

Female↗
PubMed2002

Progesterone and estradiol enhance lipid mediated transfection of Sk-Br-3 mammalian cancer cells.

Cyclodextrin encapsulated beta-estradiol and progesterone were used for enhancement of gene delivery using the breast cancer cell line Sk-Br-3. A non-toxic concentration of cyclodextrin encapsulated sex steroids (50 microM) added to lipid or liposomal transfection led to a 12-fold increase of reporter gene expression (luciferase) with progesterone and an 8-fold increase with estradiol using Lipofectamine Plus mediated transfection. Using the lipid formulation Fugene-6 the results were a 5.5-fold and a 4.5-fold increase respectively. This enhancement could only be observed if the sex steroids were added to the cells before application of the DNA-Fugene complex supporting the evidence that intracellular processes are responsible for the activity of the steroids. The strong differences between progesterone and estradiol in modifying Lipofectamine Plus transfection in Sk-Br-3 cells may to be explained by differences in the distribution of these receptors in the cellular compartments. These results seem to add evidence on the possibility of using sex steroids to increase the efficiency of non-viral vectors for transfection, and may ultimately prove to be relevant to gene therapy in the treatment of breast cancer as well as other solid tumors.

Cells, Cultured↗
PubMed2001

Inhibin A/B in HMG or recombinant FSH ovarian stimulation with cetrorelix medication.

The inhibins are valuable factors in the assessment of the quality of an ovarian stimulation cycle. In spite of good clinical results with recombinant FSH and multiple dose LHRH- antagonist (Cetrotide((R))) administration, there remains a theoretical concern that in cycles stimulated with recombinant FSH, devoid of any LH activity, not enough endogenous LH is available to guarantee good follicle maturation. A total of 287 serum samples from 41 patients was assessed: 20 patients received ovarian stimulation with recombinant FSH, 21 patients with HMG and multiple dose Cetrotide administration. Inhibin A and B were measured on cycle days 2 and 6, the day of HCG administration, the day of embryo transfer as well as 7 and 14 days after the transfer. The two patient groups were similar with regard to age, amount of gonadotrophins required and number of follicles >18 mm and 15-18 mm. Inhibin A and B concentrations were comparable throughout the stimulation, thus indicating the equality of ovarian stimulation with recombinant FSH/HMG and midcyclic antagonist administration. Higher inhibin B concentrations throughout the stimulation were correlated with a higher oocyte yield. The small number of pregnancies prevented assessment of the relationship between inhibin B values and pregnancy rate.

Journal Article↗
PubMed2001

Impact of intracytoplasmic sperm injection on the activation and fertilization process of oocytes.

Intracytoplasmic sperm injection (ICSI) is used worldwide to treat preferentially severe cases of male factor infertility. In this review, data regarding the processes of oocyte activation and fertilization in non-assisted conception, conventional IVF and ICSI are discussed. The second messenger calcium shows a typical pattern after ICSI, which is different from that after subzonal insemination (SUZI), which is closer to the conditions of normal fertilization. The onset of calcium spikes is delayed. Sometimes a monophasic calcium pattern, in animals typical for parthenogenetic activation, is observed despite normal subsequent oocyte activation. Furthermore, the frequency of spikes is higher after SUZI, and only one phase instead of two is observed after ICSI for the second onset of calcium release. These alterations may be explained by the differences in oocyte activation after ICSI, since no oolemma-sperm contact is present. Sperm decondensation also follows another pattern after ICSI: as long as residuals of the acrosome are present on the sperm head, no sperm decondensation takes place at that site. Therefore, decondensation is delayed and pronucleus formation, especially that of the male pronucleus, takes longer after ICSI as compared with conventional IVF. Since studies have shown that gonosomes are located preferentially in the apical part of the sperm nucleus, this was proposed to be an explanation for a higher incidence of gonosomal aberrations in offspring after ICSI. However, other explanations, taking clinical data like the background risk of the parents into account, can also be offered for this phenomenon. These alternative theories are more likely to be associated with a slight instead of a frank increase in gonosomal aberrations. The inheritance of paternal mitochondrial DNA seems not to be a problem after ICSI, as shown by different studies. Mitochondrial DNA can be demonstrated in embryos after conventional IVF as after ICSI up to the blastocyst stage but not in children born after ICSI. Finally, lesion of the meiotic spindle by the ICSI procedure seems not to be a problem when data from different studies are taken into account. As assumed also at the beginning of the ICSI era, the meiotic spindle is almost always located in an area of < 90 degrees deviation from the polar body axis. Therefore, intrusion of the microinjection needle at the 90 degrees position might not endanger the spindle apparatus. To conclude, several studies using different approaches might show differences in the oocyte activation pattern, the 'choreography of fertilization' and pronucleus formation after ICSI. However, this different pattern does not necessarily mean that ICSI per se is a problem for embryonal development. The different pattern can be explained by the fact that ICSI uses another means of oocyte entry than the normal fertilization process. The clinical data of a high fertilization, cleavage and implantation rate, and especially the data from newborn babies, show that ICSI is a reliable procedure.

Journal Article↗
PubMed2001

Fertilization rate and preimplantation development after intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is the treatment of choice in cases of male factor infertility. In the present review, all data from the literature regarding early fertlilization and preimplantation embryo development are analysed. ICSI seems to offer better fertilization rates than conventional IVF, even in the absence of a male factor and in prospective, randomized studies on sibling oocytes. Blastocyst formation is lower in ICSI than in IVF. This may be due to sublethal disturbances in oocyte architecture and function. Implantation and pregnancy rates, however, are similiar in ICSI and conventional IVF. Therefore, it can be concluded that ICSI offers a safe approach, as far as is known to date, for the treatment of male factor infertility. Embryo selection in cases of sublethal damage to oocytes seems to take place in the early preimplantation stages. Nor does the risk of monozygotic twinning, which was also proposed to be higher in ICSI compared with conventional IVF, seem to increase with this procedure.

Journal Article↗
PubMedDate not supplied

Clomiphene-induced LH surges and cetrorelix.

The following rat pituitary cell culture experiments were carried out to find an explanation for the increased premature LH surges in stimulation protocols using clomiphene citrate (CC) and subsequent gonadotrophin with mid-cycle administration of the GnRH antagonist cetrorelix (Cetrotide(R)) in IVF cycles. Rat pituitary cells were pretreated with CC, then stimulated with GnRH with and without co-administration of different concentrations of GnRH antagonist and compared with non-CC-pretreated controls. While lower concentrations of cetrorelix suppressed LH in CC-non-pretreated cells, but not in CC-pretreated cells, higher concentrations of cetrorelix suppressed LH in both groups. CC pretreatment increased the sensitivity of the pituitary for GnRH and reduced the efficacy of subsequent GnRH antagonist. Thus, the elevated risk of premature LH surges in clinical protocols using CC, gonadotrophin and GnRH antagonist could be overcome by increasing the antagonist dose.

Animals↗
PubMedDate not supplied

Follow-up of children born after assisted reproductive technologies.

The course of pregnancies and the health of children born after assisted reproductive technologies are two of the most important outcome parameters of the quality of the techniques. There is an ongoing discussion as to whether these parameters may show poorer results as compared with spontaneous conception. Recent studies have shown increased risks for the pregnancy course following conventional IVF (e.g. premature birth, low birthweight), and a higher rate of major malformations after conventional IVF as well as after intracytoplasmic sperm injection. Molecular biological studies may support the idea that these risks are not related to the techniques used, but to parental background factors. Data from surrogate motherhood also demonstrate that here the risk is lower as compared with pregnancies from IVF mothers, who carry their own child to birth. Therefore, there are more infertility related problems than those related to technique. Finally, however, a risk related to the technique itself cannot be excluded completely by currently available data.

Congenital Abnormalities↗
PubMedDate not supplied

Gonadotrophin-releasing hormone antagonists: will they replace the agonists?

Modern gonadotrophin-releasing hormone (GnRH) antagonists such as cetrorelix and ganirelix reliably prevent premature LH surges in controlled ovarian hyperstimulation for assisted reproductive technologies. Cetrorelix and ganirelix are safe and effective compounds. Because of their distinct pharmacological mode of action, it has been possible to achieve a significant reduction of treatment time. Fertilization and pregnancy rates are comparable to those obtained in agonist protocols for ovarian stimulation. No allergic or hyperergic reactions have been reported, and patient compliance is excellent. The fact that GnRH antagonists allow an immediate suppression of gonadotrophin concentrations while preserving pituitary responsiveness to endogenous GnRH provides enormous flexibility in treatment. GnRH antagonists have helped to overcome some major disadvantages of GnRH agonists, especially of the long protocol, which is currently the standard protocol for ovarian stimulation. The mistaken administration of antagonists during early pregnancy is not possible, since they are only administered during ovarian stimulation when a premature LH surge may be imminent. They are used in the spontaneous cycle or after pretreatment with oral contraceptives. Pregnancy can easily be ruled out by testing for human gonadotrophic hormone before onset of gonadotrophin stimulation on the second or third day of the cycle. Since flare-up effects are absent, there is no risk of cyst formation. Hormonal withdrawal symptoms are eliminated, since no period of pituitary suppression occurs, and therefore exogenous gonadotrophins are not required. Overall, the duration of the stimulation cycle is as short as a normal menstrual cycle. The procedure seems to be safer than the long protocol, since the most serious complication, the occurrence of severe cases of OHSS, is reduced. It is also safe with respect to the course of pregnancies and the health of offspring. Both protocols developed so far, the single dose and multiple dose antagonist protocol, are comparable, utilizing data from the large prospective phase IIIb studies. Although several studies have indicated a slight reduction in pregnancy rate with GnRH antagonists as compared with agonists, this problem may be rectified by developing flexible antagonist regimens designed for individual patients. Introducing flexible GnRH antagonist regimens should be the area of research in the near future.

Female↗
PubMedDate not supplied

An evaluation of the multiple dose protocol of cetrorelix in single ovary women.

BACKGROUND: The ovarian response and the pregnancy outcome of women with one ovary have been investigated under various IVF stimulation protocols. Cetrorelix is a novel agent offering important advantages in ovarian stimulation. In this study, the multiple protocol of cetrorelix is evaluated in single ovary women, for the first time. MATERIALS AND METHODS: Retrospective comparison of the ovarian response and ICSI/ET outcome between 12 cycles of single ovary women and 39 cycles of women with two ovaries. RESULTS: Between the two groups, there were no statistically significant differences in any of the analysed parameters. In the group of single ovary, 2 pregnancies were achieved and 4 children were born. In the group of two ovaries, 10 pregnancies were achieved and nine children were born. CONCLUSION: Single ovary women have the same response to ovarian stimulation with cetrorelix/hMG/rFSH as women having both ovaries, but they present a lower, although not statistically significant, pregnancy rate.

Adult↗
PubMedDate not supplied

In vivo and in vitro decondensation of human sperm and assisted reproduction technologies.

For a successful fertilization and pronucleus formation to occur, not only a properly condensed sperm nucleus, but also decondensation ability in the oocyte is important. The sperm abnormalities causing failure of sperm decondensation in the oocyte are unrecognizable by conventional semen analysis and different methods are used. The chromatin decondensation ability of the human spermatozoa in vivo and in vitro and its association with infertility and assisted reproduction techniques (ART) are clearly discussed in this paper. The factors affecting the decondensation ability of the human sperm are also mentioned. It is suggested that the methods currently used to assess sperm chromatin decondensation are of limited value in assessing fertilization and pregnancy rates after ART.

Female↗
PubMedDate not supplied

Vitamin D analogs in cancer prevention and therapy.

The Second International Symposium on "Vitamin D Analogs in Cancer Prevention and Therapy", was held in Lübeck, Germany, May 7-8, 2005. This meeting was specifically designed to summarize the latest developments in the epidemiology, molecular biology, metabolism, biological effects and clinical use of vitamin D analogs, leading to new concepts for their application in cancer prevention and therapy. Forty keynote lectures were presented at the Symposium and the following conclusions were summarized at a round-table discussion. Cancer Prevention: Evidence from epidemiological and laboratory investigations now convincingly demonstrate that vitamin D deficiency and insufficiency are underrecognized worldwide problems that are associated with several health problems, including the higher prevalence and unfavorable course of cancer. There is an urgent need for additional well-designed studies to define the optimal vitamin D status (25-hydroxyvitamin D serum level) and for campaigns to better inform the public and medical profession alike about the health risks related to vitamin D deficiency and insufficiency. Cancer Therapy: Knowledge of the underlying molecular mechanisms that mediate the antitumor effects of vitamin D analogs has expanded greatly during recent years and results from the first clinical trials indicate that such analogs hold promise for cancer therapy, most probably in combination with other agents. However, the era of vitamin D analogs in cancer therapy has just begun and efforts to perform well-designed clinical studies and to develop new analogs with fewer systemic side-effects have to continue.

Humans↗
PubMedDate not supplied

Vitamin D--metabolism in the human breast cancer cell line MCF-7.

BACKGROUND: The three main vitamin D metabolizing enzymes, vitamin D3-25-hydroxylase (25-OHase, 25-hydroxylase), 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-OHase, 1alpha-hydroxylase) and 25-hydroxyvitamin D3-24-hydroxylase (24-OHase, 24-hydroxylase), have been described in malignant breast tissue. This in vitro study aimed to obtain more information regarding the regulation of these enzymes in the human breast cancer cell line MCF-7. MATERIALS AND METHODS: Vitamin D receptor (VDR)- positive MCF-7 cells in culture were stimulated with the vitamin D metabolites vitamin D3, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 for 24, 48; 72 and 96 hours in physiological and supraphysiological concentrations. The expressions of 25-hydroxylase, 1alpha-hydroxylase and 24-hydroxylase and their changes after stimulation were assessed by real-time PCR. RESULTS: The expression of 25-hydroxylase was slightly influenced by vitamin D3. The expression of 1alpha-hydroxylase was induced after stimulation with vitamin D3 and 25-hydroxyvitamin D3. Stimulation with 1,25-dihydroxyvitamin D3 markedly increased the expression of 24-hydroxylase time- and dose-dependently. CONCLUSION: Our results demonstrated that MCF-7 cells are able to regulate the expression of 24-hydroxylase. This might be a mechanism for these tumor cells to protect themselves against the antiproliferative and apoptosis-inducing effects of calcitriol.

Breast Neoplasms↗