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Biomedical subjects

R Felberbaum

Publications and source records attributed to R Felberbaum.

At least 19 recordsLinked to original sources
PubMed2006

Cytokine and hormonal profile in blood serum and follicular fluids during ovarian stimulation with the multidose antagonist or the long agonist protocol.

BACKGROUND: The aim of our study was to explore cytokine and hormonal profiles in blood and follicular fluids from normal women stimulated with either the multidose antagonist or the long agonist protocol. METHODS: Fifty-six patients were stimulated with the multidose antagonist protocol and 12 with the long agonist protocol. Interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha), leptin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), estradiol (E(2)), progesterone and testosterone levels were measured in serum and follicular fluids by immunoassays. RESULTS: The two treatment groups had similar cytokine concentrations in serum. The intrafollicular concentrations of IL-1beta, IL-6, VEGF and leptin were also similar in the two groups. The concentrations of bFGF in follicular fluids from the antagonist group (169.5 +/- 113.2 ng/ml) were lower than those from the agonist group (249.7 +/- 119.8 ng/ml). bFGF concentrations were correlated with the amount of administered gonadotrophins (R = 0.364, P < 0.01) which was significantly lower in the antagonist group (antagonist group: 2037.7 +/- 725.8 IU; agonist group: 2836.4 +/- 1163.5 IU). CONCLUSIONS: Normal women stimulated with either the multidose antagonist or the long agonist protocol generally have similar cytokine profiles in serum and follicular fluids. The intrafollicular levels of bFGF tend to be lower in antagonist cycles because of the lower amount of administered gonadotrophins.

Adult↗
PubMed2006

Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques (ART) from treatments initiated during 2002 are presented in this sixth report. Data was mainly collected from already existing national registers. From 25 countries, 631 clinics reported 324,238 treatment cycles with: IVF 122,634, ICSI 135,048, frozen embryo replacement (FER) 57 162, egg donation (ED) 7677, preimplantation genetic diagnosis/screening (PGD/PGS) 1563 and in vitro maturation (IVM) 154. Overall this represents a 12% increase since year 2001. For the second time, results on European data on intrauterine inseminations were reported from 17 countries. A total of 93,284 cycles [IUI-husband/partner (H), 78 505 and IUI-donor (D), 14,779] were included. In 13 countries where all clinics reported to the register, a total of 177,429 cycles were performed in a population of 193.7 million, corresponding to 916 cycles per million inhabitants. For IVF the clinical pregnancy rate per aspiration and per transfer was 26.0 and 29.5%, respectively. For ICSI the corresponding rates were 27.2 and 29.4%. These figures are marginally better than in 2001. After IUI-H the clinical pregnancy rate was 11.6% in women below 40 and 7.8% in women>or=40 years of age. After IVF and ICSI the distribution of transfer of 1, 2, 3 and 4 or more embryos was 13.7, 54.8, 26.9 and 4.7%, respectively. Compared with year 2001, less embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 75.5, 23.2 and 1.3%, respectively. This gives a total multiple delivery rate of 24.5%, compared with 25.5% in year 2001. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 5.2% between countries. After IUI-H in women below 40 years of age, 10.2% were twin and 1.3% triplet gestations.

Adult↗
PubMed2006

GnRH agonists and antagonists in assisted reproduction: pregnancy rate.

Although gonadotrophin-releasing hormone (GnRH) antagonists offer many advantages when used in ovarian stimulation, their popularity is lower than expected. GnRH protocols are suspected to yield lower pregnancy rates compared with the long agonist protocol. In the current study, subgroup analyses from the German IVF registry (DIR) were performed to evaluate the hypothesis that GnRH antagonists are often used as second-line medication in patients with difficult medical conditions, and thus pregnancy rates may be biased. Consequently, pregnancy rates in the first six stimulation cycles (low rank cycles) were more favourable in the group treated according to the long protocol, while in the patient group requiring more stimulation cycles (high rank cycles; 7, 9 and 10), numerically higher pregnancy rates were achieved with GnRH antagonist protocols. On the other hand, in a patient collective with equal demographic and clinical features (<35 years, tubal infertility), the long and the GnRH antagonist protocols resulted in similar pregnancy rates, supporting the hypothesis that both stimulation protocols lead to equal results.

Adult↗
PubMed2005

Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol.

BACKGROUND: Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol. METHODS: 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG. RESULTS: Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively). CONCLUSIONS: Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.

Adult↗
PubMed2005

Assisted reproductive technology in Europe, 2001. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques from treatments initiated during 2001 are presented in this fifth report. Data were collected mainly from already existing national registers. From 23 countries, 579 clinics reported 289 690 cycles with: IVF 120 946, ICSI 114 378, frozen embryo transfer (FER) 47 195 and egg donation (ED) 7171. Overall this represents a 4% increase since the year 2000. For the first time, results on European data on intra-uterine inseminations (IUIs) were reported from 15 countries. A total of 67 124 cycles [IUI husband'sperm (IUI-H) 52 949 and IUI donor sperm (IUI-D) 14 185] were included. In 12 countries where all clinics reported to the register, a total of 108 910 cycles were performed in a population of 131.4 million, corresponding to 829 cycles per million inhabitants. For IVF, the clinical pregnancy rate per aspiration and per transfer was 25.1 and 29.0%, respectively. For ICSI, the corresponding rates were 26.2 and 28.3%. These figures are similar to the results from 2000. After IUI-H, the clinical pregnancy rate was 12.8% in women <40 and 9.7% in women > or =40 years of age. After IVF and ICSI, the distribution of transfer of one, two, three and > or =4 embryos was 12.0, 51.7, 30.8 and 5.5%, respectively. Compared with the year 2000, fewer embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 74.5, 24.0 and 1.5%, respectively. This gives a total multiple delivery rate of 25.5%, compared with 26.9% in the year 2000. The range of triplet deliveries after IVF and ICSI differed from 0.0 to 8.2% between countries. After IUI-H in women <40 years of age, 10.2% were twin and 1.1% were triplet gestations.

Age Distribution↗
PubMed2004

FSH time-concentration profiles before and after administration of 0.25 mg cetrorelix in the gnRH-antagonist multiple-dose protocol for ovarian hyperstimulation.

PURPOSE: To determine FSH concentration behavior before and after cetrorelix 0.25 mg administration in the GnRH-antagonist multiple-dose protocol on day 6 of ovarian stimulation with 150-300 IU daily recombinant FSH. METHODS: Blood samples for FSH measurements were drawn from seven women every 15 min from 8 h prior to the first cetrorelix administration in the GnRH-antagonist multiple-dose protocol until 15-32 h thereafter. RESULTS: No significant change of FSH concentration was observed. CONCLUSIONS: This observation indicates that no rationale exists of increasing the daily FSH dosage concomitantly to the GnRH-antagonist administration to compensate for a drop of endogenous FSH.

Biomarkers↗
PubMed2004

Taxanes in the first-line chemotherapy of metastatic breast cancer: review.

Taxanes belong to the most effective agents in the treatment of advanced and non-hormone responsive breast cancer. Several recently published phase III studies have examined the role of taxane-anthracycline combinations in the first line treatment of metastatic breast cancer. Especially, patients with symptomatic visceral spread seem to benefit from taxanes containing polychemotherapy that is adequately dosed. Polychemotherapy with taxanes appears to be more effective than monotherapy. But at present, there are no adequate data concerning the comparison of taxane-monotherapy and anthracycline-containing polychemotherapy. New hopeful results with respect to efficacy and toxicity are reported from the docetaxel-capecitabine polychemotherapy. Thus, the combination of anthracyclines (adriamycin, doxorubicin) and taxanes (docetaxel, paclitaxel) is a promising tool in the treatment of metastatic breast cancer. New interesting combinations are under investigation.

Anthracyclines↗
PubMed2003

[Enhanced liposomal transfection through the application of sex steroids in gynecological cancer cells].

OBJECTIVE: Liposomal transfection in gene therapeutic application against gynecological malignoma does not reach satisfying efficacy. A desirable goal would be the specific intensification of transfection in these kind of cells. Steroids have successfully been used in other systems to increase liposomal transfection and hopefully there might be a specific impact of sexual steroids in cells from high sex steroid receptor expressing malignoma, like some mamma- and endometrium cancer. MATERIAL AND METHODS: The mamma carcinoma cell line T-47D was transfected with the transfection agent DOTAP and cyclodextrin solubilized steroids and cholesterol were co-applied. The efficiency of transfection was followed by luciferase activity resulting from the transfected reporter gene. RESULTS: Like cholesterol, which is already established as transfection co-agent, also the steroids progesterone, estrogen, testosterone and hydrocortisone provoked a clear increase in transfection efficiency shown in a dose dependent manner. CONCLUSIONS: These results indicate the usefulness of steroids as additives for liposomal transfection procedures in gene therapeutic application. As sexual steroid receptors migrate into the nucleus of a cell after binding its specific ligand a targeted enhancement of transfection is supposable in malignoma overexpressing steroid receptors. There is evidence that plasmid DNA can be co-transported with nuclear proteins into the nucleus.

Breast Neoplasms↗
PubMed2003

[Cumulus cell apoptosis as a predictor for oocyte quality in artificial reproduction technique].

OBJECTIVE: To be able to predict the success of ART reliable tests for determining the quality of the oocytes are necessary. Apart from a vague morphologic assessment via microscopy a direct analysis of the oocyte quality is not possible. Because of the very close relation between the oocyte and the cumulus cells the analysis of the cumulus cells might give sufficient information on the oocyte quality. In this study we correlate the apoptotic activity of cumulus cells to the outcome of fertilized oocytes after Intracytoplasmic Sperm Injection (ICSI). MATERIAL AND METHODS: 246 cumulus-oocyte-complexes from patients undergoing infertility treatment with the ICSI procedure were individually collected. The comet assay was used to determine the proportion of apoptotic cells within the cumulus population of each oocyte and correlated with oocyte fertilization and oocyte quality as well as with pregnancy outcome in 86 patients. RESULTS: We were able to show that high quality embryos correlate to a low rate of apoptotic cells in their corresponding cumuli. Differences regarding the pregnancy outcome were statistically not significant. CONCLUSIONS: Our results on cumulus cell apoptosis and embryo quality confirm other publications. To arrive at statistically proven criteria for the further development of single oocytes an increase in the number of analyzed patients is necessary.

Apoptosis↗
PubMed2003

Ductal carcinoma in situ of the breast: diagnosis and management.

Currently, no precise morphologic or biologic prognostic factors reliably identify patients with ductal carcinoma in situ (DCIS) who are at high risk of disease progression. DCIS is a disease with an extremely favorable prognosis and a small likelihood of dying from breast cancer, regardless of what type of treatment is received. No retrospective or prospective study to date has demonstrated a significant difference in breast cancer specific mortality regardless of treatment. The similarities between DCIS and invasive cancer suggest that an important area for future research should be elucidating the processes that can either unleash or contain the invasive potential of DCIS cells. Thus, an understanding of the biology of DCIS can assist in the prevention, the assessment, and the diagnosis of invasive breast cancer.

Breast↗
PubMed2002

Luteal phase support using either Crinone 8% or Utrogest: results of a prospective, randomized study.

The Crinone 8% preparation makes it possible to administer natural progesterone (90 mg) vaginally once daily for luteal phase support (LPS). Until now, no prospective, randomized studies have directly compared this new preparation with widely used Utrogest capsules, which were originally designed for oral administration but are used routinely as a vaginal preparation. A prospective, randomized study investigated 126 patients undergoing cycles of in vitro fertilization (IVF) and IVF/intracytoplasmic sperm injection (ICSI). Patients received either Crinone 8% (n = 73) vaginally once daily or two Utrogest capsules (n=53) vaginally three times daily (600 mg). Clinical pregnancy rates were comparable (28.8 versus 18.9%), as were clinical abortion rates until 12 weeks of gestation (14.3 versus 10.0%) and clinical ongoing pregnancy rates (24.7 versus 17.0%) in the Crinone 8% and Utrogest groups, respectively. Forty-seven non-pregnant patients were randomly selected to answer questions regarding comfort during LPS. Crinone 8% had a clear advantage over Utrogest as it resulted in less vaginal discharge (P < 0.01) and fewer application difficulties (P<0.05). Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone 8% was easier to apply (P < 0.01) and less time consuming (P < 0.05) to use than Utrogest.

Abortion, Spontaneous↗
PubMed2002

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↗
PubMed2001

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↗
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

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

No significant leukocytosis under controlled ovarian stimulation using the LHRH antagonist Cetrorelix and recFSH.

OBJECTIVE: To study the influence of an LHRH (luteinizing hormone releasing hormone) antagonist protocol (Cetrorelix) and the use of recombinant follicle-stimulating hormone (FSH) on the development of leukocytosis, compared to the use of urinary HMG (human menopausal gonadotrophin). DESIGN: Prospective, randomized phase III clinical trial. SETTING: Infertility day clinic, Department of Gynecology and Obstetrics. PATIENTS: Thirty patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment following controlled ovarian stimulation using a multiple dose protocol and the LHRH antagonist Cetrorelix. MAIN OUTCOME MEASURE: Differences in white blood cell (WBC) count before stimulation, during the follicular phase and in the midluteal phase. RESULTS: Statistically significant increase in WBC count in the HMG group from the start of stimulation to the midluteal phase. No statistically significant increase in the recFSH group, but only a trend towards higher values was observed. CONCLUSION: The development of a leukocytosis in controlled ovarian stimulation does not depend on the protocol used. Urinary gonadotrophins seem to have a greater potential to increase WBC count compared to recombinant gonadotrophins.

Estradiol↗