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Biomedical subjects

C Keck

Publications and source records attributed to C Keck.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Limitations of reproductive medicine from an andrological/urological point of view].

Since the first child was born after in-vitro fertilization in 1978, different techniques of ovarian stimulation, oocyte retrieval and embryo culture have improved significantly. The development of microinjection techniques was a mile stone in reproductive medicine. Even in cases of severe impairment of semen quality, using the Intracytoplasmic Sperm Injection (ICSI), pregnancy rates of approximately 20 % per treatment cycle can be achieved. However for using artificial reproductive techniques (ART) the female age is a major limiting factor as well as the development of premature ovarian failure (POF). Crucial for the male is the question whether or not sperm cells can be retrieved. Today an interdisciplinary approach is recommended to take care of the afflicted couple in order to address the complex problem of infertility. There is evidence that children born after microinjection techniques bare a higher risk for chromosomal aberrations compared to the normal population. However rates of major malformations seem to be identical in both groups. An evaluation of the potential risks and efforts and an extensive counseling of the infertile couple has to be taken before initiating invasive ART.

Chromosome Aberrations↗
PubMed1999

Elevated serum progesterone concentrations during the early follicular phase of the menstrual cycle: clinical significance and therapeutic implications.

This study describes the incidence and clinical significance of hyperprogesteronemia in the early follicular phase of the menstrual cycle and the effects of prednisolone treatment in patients with this condition. Progesterone, testosterone and dehydroepiandrosterone sulfate (DHEAS) serum concentrations were determined in 316 consecutive patients admitted for infertility treatment. Elevated concentrations of progesterone in the early follicular phase could be detected in 36 cases (11.4%). In these patients, elevated testosterone and DHEAS concentrations could be detected in eight and ten cases, respectively. Serum concentrations of 17 alpha-hydroxyprogesterone and cortisol were normal in all patients. Treatment with 2.5-7.5 mg prednisolone/day normalized progesterone serum concentrations within 4-8 weeks. Twenty-four patients achieved a pregnancy either by timed intercourse or by intrauterine insemination (IUI) over the following 12 months.

Adult↗
PubMed1998

Intrauterine insemination as first line treatment of unexplained and male factor infertility.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of intrauterine inseminations (IUI) as first line treatment of unexplained or male factor infertility. STUDY DESIGN: Retrospective analysis of 414 consecutive IUI treatment cycles in 124 couples with unexplained or male factor infertility. RESULTS: In 414 cycles 25 pregnancies were achieved (6% pregnancy rate per cycle and 20% per couple respectively). 24 healthy babies were born (20 singletons and 2 twins) as a result of our treatment. There was no significant difference in ejaculate parameters of patients who achieved a pregnancy compared with patients who failed to do so. Lowest values at which pregnancies were achieved were 0.8 mill sperm/ml and 11% progressive motility after sperm processing and 8% normal morphology before semen preparation. CONCLUSION: There is still a place for IUI as first line treatment for couples with unexplained or male factor infertility. Even in patients with moderate impairment of semen quality pregnancy rates up to 20% per couple can be achieved.

Adult↗
PubMed1998

Effects of 17beta-estradiol and progesterone on interleukin-6 production and proliferation of human umbilical vein endothelial cells.

The present investigation was performed to study the effects of steroids on interleukin-6 (IL-6) production and on proliferation of human umbilical vein endothelial cells (HUVEC). HUVEC were isolated and cultured in 24-well dishes until confluency was achieved. Afterwards cells were stimulated with either 17beta-estradiol or progesterone at concentrations of 10(-12)-10(-6) mol/l. IL-6 concentrations in cell supernatants were measured by ELISA and cell proliferation was determined by flow-cytometric assessment of S-phase-cells. 17Beta-estradiol significantly inhibited basal IL-6 secretion at doses of 10(-12)-10(-6) mol/l whereas progesterone had no measurable effects. Neither 17beta-estradiol nor progesterone affected the proliferation rate of endothelial cells. The results of our study suggest that 17beta-estradiol at non-proliferative doses regulates IL-6 secretion of endothelial cells and thereby modulates processes of vascular physiology.

Cell Division↗
PubMed1998

Expression of interleukin-6 and interleukin-6 receptors in human granulosa lutein cells.

Cytokines are important regulators of reproductive functions. Significant amounts of interleukin-6 (IL-6) have been detected in the serum and ascites of patients with ovarian hyperstimulation syndrome (OHSS). These findings suggest the involvement of IL-6 as a mediator in the pathogenesis of OHSS. This study was performed to analyse IL-6 and IL-6 receptor (IL-6-R) expression in human granulosa lutein cells (GC). GC were cultured after isolation from follicular fluid. IL-6 concentrations in follicular fluid and serum from individual patients and GC supernatants were measured by enzyme-linked immunosorbent assay. We found detectable concentrations of IL-6 in serum and follicular fluid of all patients. Expression of IL-6 in GC was shown immunocytochemically. IL-6 mRNA was detected in GC by in-situ hybridization. Gene expression for IL-6 and IL-6-R in GC was demonstrated using reverse transcription-polymerase chain reaction. IL-6 significantly inhibited human chorionic gonadotrophin (HCG)-induced progesterone secretion of GC. The results of our study suggest that IL-6 is expressed in HGC and that this cytokine is able to modulate GC function via its specific receptor. This is the first report that describes the precence of IL-6-R in human granulosa lutein cells.

Cells, Cultured↗
PubMed1998

Fetal cerebral AV-malformation and cardiomegaly, diagnostic and therapeutic problems.

Intracerebral aneurysms are rare. However they are potentially life-threatening. Today by means of ultrasound investigations these malformations can occasionally be identified prenatally. In these cases questions of intrauterine therapy, mode and time of delivery and postnatal treatment have to be discussed with the parents. We describe two cases with prenatal diagnosis of intracerebral arteriovenous malformations, diagnostic workup, therapeutic options and fetal outcome.

Adult↗
PubMed1998

Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) production by luteinized human granulosa cells in vitro; a paracrine signal in corpus luteum formation.

Vascularization is a prerequisite for corpus luteum formation. Angiogenesis is thought to be regulated by vascular growth factors. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) specifically induces endothelial cell proliferation as well as angiogenesis and increases capillary permeability. Recently, VEGF/VPF-mRNA expression was demonstrated in luteinized human granulosa cells (GC) in vitro. In addition, the production of VEGF/VPF by human granulosa can be demonstrated immunocytochemically. VEGF/VPF is thought to mediate its effects through specific cell surface receptors. So far, two VEGF/VPF-receptors (VEGF/VPF-R) have been identified (KDR, and flt-1). A third receptor (flt-4) is highly correlated to KDR and flt-1, but the true ligand for this receptor is still unknown. The appearance of all three receptors is more or less restricted to endothelial cells. To clarify whether VEGF/VPF acts in an auto- or paracrine fashion in human luteinized GC, mRNA was scrutinized for specific expression of the three receptors by Northern blot technique. No specific VEGF/VPF-R or flt-4 transcripts were detectable, indicating that VEGF/VPF is a genuine paracrine growth factor from human luteinized GC directed to endothelial cells.

Adult↗
PubMed1997

Intrauterine insemination for treatment of male infertility.

Intrauterine inseminations (IUI) have been performed since the beginning of this century for treatment of infertility. Despite its widespread use the clinical value of this technique remains unclear. Today, indications for IUI include male factor, cervical factor, immunological and unexplained infertility and infertility due to ejaculatory disorders. IUI is superior to intravaginal (IVI) or intracervical insemination (ICI). Before insemination, semen has to be processed using one of the established sperm preparation techniques. Different techniques seem to be equally effective in preparing a highly concentrated sperm fraction with progressively motile, morphologically normal sperm. Ovarian stimulation further improves pregnancy rates achieved by insemination. Human menopausal gonadotropin (HMG) stimulation seems to be superior to clomiphene citrate stimulation. Among other factors, timing and number of inseminations are crucial when influencing the outcome of IUI treatment.

Female↗
PubMed1995

Benefits and risks of hormone replacement therapy (HRT).

In western countries more than 30% of the female population are postmenopausal. Approximately 30% of postmenopausal women suffer from clinical symptoms of the climacteric such as vasomotor symptoms, associated with hot flushes, night sweat, insomnia and depressive mood. Sufficient hormonal replacement therapy (HRT) will abolish specific menopausal symptoms in over 90% of patients, unspecific symptoms such as headache respond to placebo and HRT equally well. The question of cancer risk related to HRT will be addressed in this review. In combination with progestins, estrogens are obviously protective regarding ovarian and endometrial cancer. The association between HRT and breast cancer risk is presently unclear. Epidemiological data available so far do not provide compelling evidence as to a cause and effect relationship between HRT and breast cancer risk. There seems to be an overall trend towards a slightly increased risk with increasing duration of HRT use. Guidelines for HRT use in women with a history of endometrial and breast cancer are provided in this article.

Breast Neoplasms↗
PubMed1995

Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulosa cells: importance in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled ovarian stimulation treatment. This iatrogenic condition is potentially lethal and occurs in 0.3-5% of stimulated ovarian cycles. hCG exacerbates OHSS. The pathophysiology of OHSS is still unknown; therefore, treatment regimens are aimed at ameliorating symptoms. Prominent features of OHSS are an elevated risk of thromboembolism due to enhanced production of von Willebrand factor by endothelial cells and ascites, or pulmonary edema due to increased vascular permeability followed by third space fluid accumulation. Both of these sequelae can be evoked by vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF). High concentrations of VEGF/VPF have been demonstrated in ascitic fluid from patients with OHSS, but the source of VEGF/VPF in these patients remained unidentified. Here we report that the messenger ribonucleic acid expression of VEGF/VPF in human luteinized granulosa cells (GCs) is dose and time dependently enhanced by hCG in vitro. Furthermore, VEGF/VPF proteins are produced by GCs. Our results suggest that the effects of hCG on the development and course of OHSS may be mediated by the production of VEGF/VPF by GCs.

Adult↗
PubMed1995

Potential of testosterone buciclate for male contraception: endocrine differences between responders and nonresponders.

Suppression of serum LH and FSH, by testosterone (T) alone or in combination with other agents, has proved to be the most promising approach to male contraception. T enanthate, the only androgen preparation tested in male contraceptive efficacy trials so far, must be injected every week due to its short terminal elimination half-life of 4.5 days and leads to supraphysiological T serum levels. A new T ester synthesized under WHO and NIH auspices, testosterone buciclate (TB), showed a favorable pharmacokinetic profile, with a terminal half-life of 29.5 days when tested in hypogonadal men. Here we describe the results of the first clinical trial with TB for male contraception. After two control examinations, normal healthy male volunteers were given a single im injection of 600 mg TB (group I; n = 4) and 1200 mg TB (group II; n = 8) on day 0. Follow-up examinations were performed every 2 weeks up to week 32. In both groups mean serum T levels remained in the normal physiological range throughout the study course. Serum levels of dihydrotestosterone (DHT) showed a dose- and time-dependent increase, with serum levels slightly above the normal range in group II for several weeks and a maximal concentration of 3.8 +/- 0.5 nmol/L (mean +/- SE) in week 6. No suppression of spermatogenesis to oligozoospermia was observed in group I. However, in group II, spermatogenesis was suppressed to azoospermia in three of eight volunteers in week 10 that persisted up to weeks 14, 20, and 22, respectively. In these three men, LH and FSH were suppressed by TB injections to the respective assay detection limits, whereas in the other five subjects, mean serum levels were only decreased to values near the lower normal limit for LH and FSH, respectively. In addition, throughout the study course, a significant difference in serum sex hormone-binding globulin was detected between the responders (mean values, 21.2-26.4 nmol/L) and nonresponders (mean values, 36.2-46.3 nmol/L). Serum levels of LH as well as total and free T at baseline and after TB injection were lower in the responders than in the nonresponders. Both subgroups showed similar increases in serum LH and FSH after GnRH stimulation. In a newly introduced GnRH antagonist suppression test, serum LH and T were decreased to significantly lower levels in the responders. These results indicate a different hormonal equilibrium and probably different susceptibility to feedback regulation of the responders compared to the nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1994

[Ovarian hyperstimulation syndrome].

Techniques of assisted fertilization are usually preceded by ovarian stimulation therapies. This implies the risk of development of an ovarian hyperstimulation syndrome (OHS). With this article, clinical relevance, possible pathogenetic mechanisms, diagnosis, therapy and prevention of OHS are discussed. In addition, three patients with severe OHS are presented. Valid parameters for OHS risk assessment are peripheral E2 values as well as number and diameter of follicles. Until now, the mechanisms which lead to severe OHS are unknown, but hCG seems to trigger the development of symptoms, as OHS very rarely occurs without prior hCG application. Symptoms of severe OHS comprise ovarian enlargement, fluid- and electrolyte imbalance, third space fluid accumulation, haemoconcentration and hypercoagulation. Only symptomatic therapy is available. The significance of vascular mediators for the development of OHS is discussed.

Chorionic Gonadotropin↗
PubMed1994

Ineffectiveness of kallikrein in treatment of idiopathic male infertility: a double-blind, randomized, placebo-controlled trial.

In order to clarify the potential of kallikrein for treatment of idiopathic male infertility, a double-blind, randomized, placebo-controlled study was performed. A total of 44 patients were treated with 600 IU/day kallikrein and 47 patients with placebo for 12 weeks. Following two basal investigations, control examinations were performed at 6 and 12 weeks and included conventional and computer-aided semen analysis, hormone measurements and evaluation of drug safety. No significant changes in sperm concentration, normal sperm morphology and sperm motility evaluated by conventional analysis were detected. Computer-aided semen analysis revealed a significant increase in average path velocity and lateral head displacement of spermatozoa only in the placebo group. Within the observation period of 6 months four pregnancies occurred in each group. In conclusion, kallikrein treatment at a dose of 600 IU/day leads neither to an improvement of semen variables nor does it increase the pregnancy rate of the female partners, and is therefore not suited for therapy of idiopathic male infertility.

Adolescent↗
PubMed1993

[Mutation in the cystic fibrosis transmembrane-regulator gene in bilateral congenital ductus deferens aplasia].

A 28-year-old man and his 27-year-old wife were investigated for infertility of 3 1/2 years' duration. There was azoospermia caused by bilateral aplasia of the vas deferens, and therefore it was planned to aspirate spermatozoa from the epididymis for the purpose of in-vitro fertilisation. As part of the diagnostic workup the man was investigated for those mutations of the cystic fibrosis transmembrane regulator (CFTR) gene which occur with undue frequency in association with aplasia of the vas deferens. Deoxyribonucleic acid (DNA) analysis revealed a typical three base deletion (delta F 508). In the wife, CFTR gene mutations were excluded with 80% probability. The likelihood of cystic fibrosis in this couple's children was accordingly estimated to be about 0.2%--an acceptable risk. Assisted fertilization in patients with bilateral aplasia of the vas deferens should not be undertaken until they have been thoroughly investigated and informed of the risks.

Adult↗
PubMed1993

The stimulation of rat Leydig cell steroidogenesis by human ovarian steroidogenesis-inducing protein (SIP) may not require endogenous cAMP.

Recently a protein from ovarian follicular fluid was isolated which stimulates steroid production in different cells (Khan et al., 1990). The present study was performed to further characterize the short term effects of this steroidogensis-inducing protein (SIP) on steroid production in isolated rat Leydig cells and to compare the effects with LH/hCG and LHRH. SIP stimulated testosterone production in a dose-dependent manner. In Leydig cells isolated from adult rats the degree of stimulation was much higher than that obtained with hCG, dibutyryl cAMP (db cAMP) or LHRH. Moreover, the stimulated steroid production in the presence of hCG or db cAMP was further enhanced by SIP. The time courses of hCG and SIP action on testosterone production were comparable and maximal stimulation of steroid production was obtained within one hour. In contrast to hCG, SIP did not stimulate cAMP production. An antagonist of LHRH action was unable to block the effects of SIP on Leydig cells indicating that SIP does not act via LHRH receptors. Neither SIP nor LH could further stimulate the steroid production in the presence of 22-R-OH-cholesterol, illustrating that both stimulators control the availability of cholesterol as substrate. An inhibitor of mitochondrial cholesterol side chain cleavage (CSCC), aminoglutethemide, completely blocked the stimulatory effects of SIP and LH/hCG. Thus the effects of SIP on steroid production are not the result of conversion of contaminating steroids in the SIP-preparation. SIP and LH/hCG actions were also blocked when the cells were incubated in the presence of cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of multiple ejaculations after extended periods of sexual abstinence on total, motile and normal sperm numbers, as well as accessory gland secretions, from healthy normal and oligozoospermic men.

Four healthy donors provided three ejaculates on one day to deplete their sperm reserves and also after abstention periods of 1, 2, 4, 7, 10 and 14 days. The percentage of spermatozoa that were normally formed, progressively motile and which swelled in hypotonic medium remained unchanged throughout this period and the increase in total numbers of viable spermatozoa for 10 days prompted a comparison of seven donors and six oligozoospermic men. Multiple ejaculations after 10 days of abstinence for the patients with low normal, motile sperm numbers increased the total number, number of normal and number of motile spermatozoa by a mean of 230, 370 and 520%, respectively.

Adult↗