Biomedical subjects

Georg Griesinger

Publications and source records attributed to Georg Griesinger.

14 recordsLinked to original sources

PubMed2006

Vascular endothelial growth factor response to exogenous chorionic gonadotropic hormone in the luteal phase of women with a history of severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of ovarian stimulation. No reliable test exists to predict the syndrome. The objective of the present prospective observational study was to examine vascular endothelial growth factor (VEGF) secretion after human chorionic gonadotropin (hCG) administration in the luteal phase of a spontaneous cycle of women with a history of severe OHSS. Five women with a history of severe OHSS were administered 250 mug recombinant hCG intravenously on day 21 of a spontaneous menstrual cycle. Plasma samples were collected at regular intervals from 15 min before hCG to 6 h thereafter and the free VEGF plasma concentrations were determined. Plasma levels of free VEGF remained at the lower detection limit of the assay throughout the observational period. Women with previous severe OHSS do not show a significant short-time response of VEGF secretion upon hCG administration. No evidence was found to support the notion that women inclined to develop a severe form of the syndrome after ovarian stimulation could possibly be identified by the VEGF short-time secretory response to exogenous hCG in the luteal phase of a spontaneous cycle.

Adult↗

PubMed2006

Assessment of luteinizing hormone level in the gonadotropin-releasing hormone antagonist protocol.

In the GnRH-antagonist multiple-dose protocol, the LH level retrieved from a single measurement during ovarian stimulation and concomitant GnRH-antagonist administration can vary according to [1] the time point of sampling with respect to the GnRH-antagonist injection and [2] episodic changes in circulating LH concentration due to the pulsatile release of LH from the pituitary gland. To exemplify the size of pharmacodynamic effect of a single 0.25-mg cetrorelix administration on LH concentration profile and pulsatility, we measured endogenous LH levels every 15 minutes from 8 hours before the first cetrorelix administration until 24 hours thereafter on ovarian stimulation day 6 and 7 in a single patient.

Adult↗

PubMed2006

First pregnancy and life after preimplantation genetic diagnosis by polar body analysis for mucopolysaccharidosis type I.

Preimplantation genetic diagnosis (PGD) may help couples at risk to avoid pregnancies with known genetic diseases. In Germany, the only option to perform PGD is the analysis of polar bodies (PB). Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder. Q70X is one of the frequent diseases causing mutations of alpha-L-iduronidase (IDUA), leading to a severe phenotype with mental retardation and various somatic abnormalities, and making a request for PGD is understandable. Using five polymorphic DNA markers from the vicinity of IDUA, PGD on first PB was performed for a consanguineous couple, both heterozygotes of the Q70X mutation of IDUA. Sixteen first PB were obtained by laser assisted hatching of the zona pellucida. Genotyping led to the conclusion that 3/16 oocytes carried wild-type IDUA alleles. Only one of these oocytes showed pronucleus formation after intracytoplasmic sperm injection and was transferred on day 2 after oocyte retrieval. A singleton pregnancy was established. Prenatal diagnosis showed a fetus heterozygous for Q70X. For MPS I, PB analysis is a feasible way to perform PGD and it may be an acceptable alternative for couples with moral objections to embryo selection, or for countries in which genetic testing of the embryo is prohibited.

Base Sequence↗

PubMed2006

Role of LH in ovarian stimulation: considerations.

The role of LH in ovarian stimulation continues to be controversial. Most observational studies on both gonadotrophin-releasing hormone (GnRH) agonist and GnRH antagonist protocols failed to show an effect on ongoing pregnancy likelihood of punctually measured 'low' or 'high' endogenous LH concentrations during ovarian stimulation. As yet, it is still unknown whether individual patients with strongly suppressed levels of immunoreactive LH would actually benefit from additional LH administration. This can only be explored by means of interventional trials. Most trials on LH supplementation in general populations in both GnRH agonist and GnRH antagonist protocols have not found a benefit of LH supplementation, although it has been indicated that some subgroups, such as older age patients, or patients with a low ovarian response might benefit from LH. These concepts need to be explored further before recommendations can be given as to in who, in what protocol, at what time point and in what doses LH should be supplemented.

Female↗

PubMed2005

GnRH-antagonists in reproductive medicine.

Suppression of sex steroid production based on desensitisation and down-regulation of pituitary gonadotropin-releasing hormone (GnRH)-receptors by agonistic GnRH-analogues resulting in the blockage of gonadotropin release from the anterior pituitary gland is a well-established approach in a variety of clinical conditions. Antagonistic analogues of GnRH exert their effect by competing with endogenous GnRH for pituitary binding sites. Because of the lack of any intrinsic activity of these compounds, the characteristic initial 'flare-up' effect of GnRH-agonist administration is absent. A more rapid suppression of gonadotropin release from the pituitary gland can be achieved, enabling shorter treatment regimes in ovarian hyperstimulation for assisted reproduction. As yet, GnRH-antagonists have attained market approval only for the indication of premature luteinizing hormone (LH) surge prevention in controlled ovarian hyperstimulation and palliative treatment of advanced prostatic cancer. However, GnRH-antagonists may be useful in a variety of other malignant and non-malignant indications where rapid sex steroid suppression is desired, such as uterine leiomyomas, endometriosis, gynaecological cancers or benign prostatic hyperplasia. In the context of infertility treatment, available data on the application of GnRH-antagonists in the treatment of endometriosis and uterine leiomyomas are reviewed.

Endometriosis↗

PubMed2005

GnRH antagonists in ovarian stimulation: a treatment regimen of clinicians' second choice? Data from the German national IVF registry.

The place of GnRH antagonists in ovarian stimulation is controversial. Meta-analyses on studies comparing GnRH agonist and GnRH antagonist treatment regimens have suggested a comparatively lower efficacy of GnRH antagonists, which is likely to have influenced clinicians' attitudes. This report describes GnRH antagonist utilization for ovarian stimulation in Germany from 2000-2003. Data from the national IVF registry were analysed. The majority of ovarian stimulation cycles are still performed in long GnRH agonist protocols, although a significant increase in GnRH antagonist usage has been noted (P < 0.0001). Two observations support the notion that GnRH antagonists are often utilized as a treatment option in cycles with an unfavourable a priori prognosis: (i) the proportion of GnRH antagonist cycles increases with cycle rank (P < 0.0001, chi(2) for linear trend); and (ii) GnRH antagonist cycles are more often conducted in older patients as compared to GnRH agonist cycles (P < 0.0001). This has important implications for interpreting clinical performance of GnRH antagonists outside a research context.

Female↗

PubMed2005

Mayer-Rokitansky-Küster-Hauser syndrome associated with thrombocytopenia-absent radius syndrome.

OBJECTIVE: To describe the association of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and thrombocytopenia-absent radius (TAR) syndrome. DESIGN: Descriptive case report. SETTING: Tertiary university-affiliated care and referral facility. PATIENT(S): A 22-year-old woman with TAR syndrome referred to our department with primary amenorrhea. INTERVENTION(S): Patient history, physical and laboratory examination, diagnostic laparoscopy, and karyotyping. MAIN OUTCOME MEASURE(S): Physical features in the combination of syndromes presented. RESULT(S): Laparoscopy revealed absent uterus and complete vaginal agenesis. CONCLUSION(S): This extremely rare case might provide further evidence of a link between the development of the skeletal system and the genitourinary tract.

Abnormalities, Multiple↗

PubMed2005

Factors affecting outcome after ICSI with spermatozoa retrieved from cryopreserved testicular tissue in non-obstructive azoospermia.

There is a lack of data regarding variables affecting the treatment outcome for non-obstructive azoospermia when spermatozoa from cryopreserved testicular specimens are utilized for ICSI. The objective of the present retrospective analysis was to investigate the effect of various parameters on treatment outcome in such cases. One hundred and sixty-five couples with non-obstructive azoospermic males undergoing a total of 297 cycles were included. In all cases the testicular tissue retrieved by multiple open-biopsy testicular sperm extraction was stored in liquid nitrogen and, after thawing, only mature spermatozoa were used for ICSI. When no motile spermatozoa were recovered, immotile spermatozoa were used. In 159 cycles, motile spermatozoa were utilized for ICSI, while in 138 cycles immotile spermatozoa were utilized. Higher normal fertilization rate (60.4 +/- 3.1 versus 51.3 +/- 1.6%, P < 0.05), number of embryos transferred (2.8 +/- 0.06 versus 2.6 +/- 0.04, P < 0.05), modified cumulative embryo score (31.2 +/- 1.6 versus 23.9 +/- 0.8, P < 0.001), and proportion of motile spermatozoa injected (67.8 versus 49.8%, P < 0.05) were observed in cycles that resulted in clinical pregnancies. Binary logistic regression analysis showed that sperm motility (odds ratio 2.06, 95% CI 1.1-3.9, P < 0.05), but not woman's age, number of treatment cycle, type of GnRH-analogue used for pituitary suppression, number of oocytes retrieved or number of embryos transferred was a significant determinant of the likelihood of clinical pregnancy. In conclusion, sperm motility after freeze/thawing of testicular tissue is the major determinant of the success of ICSI in non-obstructive azoospermia.

Adult↗

PubMed2005

Cumulative pregnancy rate after ICSI with cryopreserved testicular tissue in non-obstructive azoospermia.

The aim of the present study was to describe a simplified and inexpensive method of testicular tissue freezing, to assess the cumulative clinical pregnancy rate (CPR) by this technique, and to provide useful information for counselling couples with non-obstructive azoospermia. One hundred and sixty-five couples with non-obstructive azoospermic males pursuing assisted conception, from December 1995 to December 2002, were included. In all cases, the testicular tissue retrieved by open multiple-biopsy (both sides, by testicular sperm extraction) was frozen using a simple liquid nitrogen vapour freezing technique and was stored in liquid nitrogen thereafter. Only mature spermatozoa were used for intracytoplasmic sperm injection (ICSI) after thawing. Expected CPR were calculated using the Kaplan-Meier survival analysis. A total of 281 cycles were performed resulting in 53 clinical pregnancies. Crude and expected CPR (95% confidence intervals) after three cycles were 32.1 (25.7-40.1) and 55.7% (37.0-74.4) respectively. In conclusion, this simplified method for freezing testicular tissue resulted in a satisfactory outcome after ICSI in cases of non-obstructive azoospermia.

Adult↗

PubMed2005

Polar body diagnosis for hemophilia a using multiplex PCR for linked polymorphic markers.

Preimplantation genetic diagnosis (PGD) is usually performed on blastomeres. In Germany, the only possibility to perform PGD is by analysis of polar bodies. We performed PGD using polar bodies in a woman who is a carrier of hemophilia A. Multiplex PCR followed by nested fluorescent PCR for five linked polymorphic markers was established. From 11 analyzed polar bodies, only 1 showed alleles linked to the mutation. The corresponding oocyte was transferred and no pregnancy was established. As seen in other investigations, the rate of heterozygous first polar bodies is surprisingly high.

Adult↗

PubMed2005

New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists.

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer.

Animals↗

PubMed2004

What is the most relevant standard of success in assisted reproduction? Is BESST (birth emphasizing a successful singleton at term) truly the best?

There is much variability and no consensus on the definition of the most relevant outcome parameter after assisted reproduction technology (ART). Descriptive reports, such as annual statistics from national registries on the success of ART programmes, should present treatment success in terms of live birth per ovarian stimulation started, as this is the most relevant information for patients and doctors alike. Addressing concerns about the high rate of multiple pregnancies, rescaling the outcome of ART in large programmes and national audits to the singleton, live birth, might trigger a global change of attitude towards elective single embryo transfer in addition to any legal restrictions imposed. For clinical studies, the outcome measure will depend on the hypothesis tested, and investigators should remain free to choose the appropriate primary outcome measure.

Embryo Transfer↗

PubMed2004

Gonadotropin-releasing hormone antagonists for assisted reproductive techniques: are there clinical differences between agents?

Gonadotropin-releasing hormone (GnRH) antagonists have been tested extensively in ovarian stimulation protocols for assisted reproductive techniques (ART). GnRH antagonists immediately and rapidly inhibit gonadotropin release by the anterior pituitary gland by competitive blockage of the GnRH receptor, preventing and interrupting luteinising hormone surges in controlled ovarian hyperstimulation for infertility treatment. A review of the available literature on GnRH antagonists for ART is presented, focusing on the pharmacological and clinical properties of the two compounds available on the market, cetrorelix and ganirelix. Both cetrorelix and ganirelix are well tolerated and effective drugs for controlled ovarian hyperstimulation and are of comparable value for infertility treatment. Cetrorelix is available as a 0.25mg preparation for daily injections and as a 3mg intermediate depot preparation. Ganirelix is available as a 0.25mg preparation for daily injections.Currently, two treatment protocols are used in clinical practice: the GnRH antagonist multiple-dose protocol and the GnRH antagonist single-dose protocol. Both protocols are effective and well tolerated. Cetrorelix and ganirelix have not yet been directly compared in a clinical trial; nor have the single-dose and the multiple-dose approaches been compared in a randomised, controlled trial. Data to compare these compounds in clinical terms can be extrapolated only from results of phase II dose-finding studies and phase III studies comparing GnRH agonist cycles with GnRH antagonists in single- and multiple-dose protocols. Therefore, all conclusions on clinical differences between cetrorelix and ganirelix should remain tentative, as they are based on a limited amount of available data.Randomised, controlled trials comparing cetrorelix and ganirelix are warranted to further evaluate benefits and drawbacks of individual GnRH antagonists. Furthermore, more data are needed to determine the efficacy and safety of cetrorelix and ganirelix in established treatment protocols in patients other than those included in clinical trials investigating new drugs, such as "poor responders", patients with polycystic ovaries, patients with a history of allergy or overweight patients.

Clinical Trials as Topic↗

PubMed2002

Ascorbic acid supplement during luteal phase in IVF.

PURPOSE: To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospective, randomized, placebo-controlled, group comparative, double-blind study. METHODS: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age <40 years, undergoing first IVF-embryo transfer cycles in two private outpatient infertility clinics. All women were stimulated by the same protocol. The mean age was 31.73 (+/- 4.4 SD) years. RESULTS: No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups. CONCLUSIONS: There was no clinical evidence of any beneficial effect, as defined by main outcome measures, of ascorbic acid on IVF-ET. Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment.

Adult↗