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Biomedical subjects

J A Garcia-Velasco

Publications and source records attributed to J A Garcia-Velasco.

17 recordsLinked to original sources
PubMed2006

Vascular endothelial cadherin regulates vascular permeability: Implications for ovarian hyperstimulation syndrome.

CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of treatment with fertility drugs. It is characterized by increased vascular permeability and simultaneous overexpression of vascular endothelial growth factor (VEGF) in ovarian cells. OBJECTIVE: We tested the hypothesis that the endothelium and endothelial cell-to-cell junctions are downstream targets of VEGF during OHSS pathogenesis. We investigated the potential involvement of vascular endothelial (VE)-cadherin, an interendothelial adhesion molecule, in the capillary hyperpermeability in OHSS. DESIGN: Human endothelial cells from umbilical veins (HUVEC) were used as an in vitro model of OHSS. INTERVENTION: Cell cultures were treated with varying doses of estradiol (E2), human chorionic gonadotropin (hCG), VEGF, and antihuman VEGF antibodies, either alone or in combination, and the effect on VE-cadherin release was evaluated at different time points. Permeability assays were performed using fluoresceinisothiocyanate-labeled albumin, and actin filaments rearrangement was evaluated by fluorescent microscopy. RESULTS: Culturing of HUVEC with high doses of E2 produced no significant changes in VE-cadherin concentration, but hCG and VEGF produced a significant increase in VE-cadherin release. Time-course experiments showed that VE-cadherin was secreted 12 h after VEGF addition. Antihuman VEGF antibodies prevented these changes. Permeability assays demonstrated that, although E2 did not alter the arrangement of HUVEC in vitro, hCG and VEGF caused changes in the actin fibers indicative of increased capillary permeability. VEGF also induced an increase in paracellular permeability of HUVEC at the same doses used in the previous experiments. CONCLUSIONS: Adhesion molecules like VE-cadherin may play a role in the development and progression of increased capillary permeability in severe OHSS.

Antigens, CD↗
PubMed2006

Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis.

BACKGROUND: Women with endometriosis who are treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have a lower pregnancy rate compared to women with tubal factor infertility. It has been suggested that the administration of gonadotrophin releasing hormone (GnRH) agonists for a few months prior to IVF or ICSI increases the pregnancy rate. OBJECTIVES: To determine the effectiveness of administering GnRH agonists for three to six months prior to IVF or ICSI in women with endometriosis. SEARCH STRATEGY: We used computer searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register (NRR) and the MDSG Specialised Register of controlled trials. We handsearched proceedings of annual meetings of the American Society for Reproductive Medicine (ASRM) and the European Society for Human Reproduction and Embryology (ESHRE). We reviewed lists of references in original research and review articles. We contacted experts in various countries to identify unpublished trials. SELECTION CRITERIA: We included randomised controlled trials using any GnRH agonist prior to IVF or ICSI to treat women with any degree of endometriosis diagnosed by laparoscopy or laparotomy DATA COLLECTION AND ANALYSIS: Two independent review authors abstracted data (HNS and JGV). We sent e-mails to investigators to seek additional information. We assessed the validity of each study using the methods suggested in the Cochrane Handbook. The data were checked by the third review author (SD) and any disagreement was resolved by arbitration with the fourth review author (AA). We generated 2 x 2 tables for principal outcome measures. The Peto-modified Mantel-Haenszel technique was used to calculate odds ratios (OR) and assess statistical heterogeneity between studies. MAIN RESULTS: Three randomised controlled trials (with 165 women) were included. The live birth rate per woman was significantly higher in women receiving the GnRH agonist compared to the control group (OR 9.19, 95% CI 1.08 to 78.22). However, this was based on one trial reporting "viable pregnancy" only. The clinical pregnancy rate per woman was also significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15). The information on miscarriage rates came from two trials with high heterogeneity and, therefore, results of the meta-analysis were doubtful. The included studies provided insufficient data to investigate the effects of administration of GnRH agonists on multiple or ectopic pregnancies, fetal abnormalities or other complications. AUTHORS' CONCLUSIONS: The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

Drug Administration Schedule↗
PubMed2005

Medical treatment of endometriosis.

The medical treatment of endometriosis is a critical aspect of the therapeutic approach to this disease. This review will present an overview of current literature about the medical treatment of endometriosis, without referring to the surgical treatment or a combination of both. The main purpose of the current medical treatment of endometriosis is to create an amenorrheic state, in other words, to create a hypoestrogenic environment by suppressing estrogen secretion of the ovary. Current research has focused upon medications designed to attack specific aspects of the development and maintenance of endometriosis. This includes progesterone receptor modulators, gonadotropin releasing hormone (GnRH) analogs, aromatase inhibitors and, tumor necrosis factor alpha (TNFalpha) inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors and estrogen receptor beta agonists like inmunomodulators. These drugs show decreased spreading of lesions and reduced disease related symptoms. Medical treatment is moderately effective in reducing pain but ineffective in improving fertility; a combination of medical treatment with assisted reproductive technology may be beneficial in improving fertility.

Danazol↗
PubMed2004

Extended coasting duration exerts a negative impact on IVF cycle outcome due to premature luteinization.

Coasting, or withholding gonadotrophin administration while maintaining gonadotrophin-releasing hormone analogue until oestradiol drops to a safe concentration, is an alternative approach to prevent ovarian hyperstimulation syndrome (OHSS) in high responder patients. However, the length of this procedure has not been precisely studied. This paper is a retrospective study of 132 patients who showed a high response (oestradiol > 4500 pg/ml and/or more than 20 follicles > 17 mm) to ovarian stimulation and were coasted due to their high risk of developing OHSS, and evaluated the impact of the duration of coasting on IVF cycle outcome. Additionally, serum LH and progesterone concentrations were studied to investigate whether premature luteinization was present in these cycles and whether it might be related to coasting duration. A significant decrease in implantation rate was found when coasting was required for more than 4 days, together with a trend towards a higher cancellation rate. Premature luteinization was significantly elevated in women undergoing coasting compared with control women (34 versus 15.6%, P < 0.05). In the majority of patients who showed premature luteinization, coasting lasted >/=3 days. To conclude, prolonged coasting may affect the endometrium, anticipating the implantation window. These data may explain why some women undergoing extended coasting show a lower implantation rate compared with controls.

Adult↗
PubMed2001

Endometrial receptivity in terms of pinopode expression is not impaired in women with endometriosis in artificially prepared cycles.

OBJECTIVE: To assess endometrial receptivity in terms of pinopode expression in women with endometriosis. DESIGN: Prospective, observational study. SETTING: Oocyte donation program at the Instituto Valenciano de Infertilidad. PATIENT(S): Twelve women with endometriosis as the only cause of infertility. INTERVENTION(S): Pinopode expression pattern analysis by scanning electron microscopy in two sequential endometrial biopsies obtained in the same cycle of each patient. MAIN OUTCOME MEASURE(S): Pinopode pattern and pregnancy rates. RESULT(S): Pinopode expression in women with endometriosis did not differ from that of patients without endometriosis undergoing artificial cycles. Similarly, the clinical outcome in these women was comparable to that of the general population included in the oocyte donation program. The pregnancy rate per transfer was 46.7%. CONCLUSION(S): These results show that in women with endometriosis undergoing oocyte donation under hormone replacement therapy, pinopode expression is not altered, suggesting that endometrial receptivity in women with this disease remains unaltered.

Biopsy↗
PubMed2001

Human ovarian steroid secretion in vivo: effects of GnRH agonist versus antagonist (cetrorelix).

BACKGROUND: In order to investigate whether gonadotrophin-releasing hormone (GnRH) antagonists exert a significant effect on steroid secretion in vivo compared with GnRH agonists, concentrations of sex steroid hormones (oestradiol, progesterone and testosterone) were studied in follicular fluid from women undergoing ovarian stimulation and treated with either GnRH agonist or antagonist. In addition, the correlation between follicular fluid steroid hormone concentrations and variables of follicular and oocyte development was evaluated. METHODS: Microparticle enzyme immunoassay and radioimmunoassays were used. RESULTS: The mean (SEM) follicular fluid oestradiol concentration was significantly lower in patients treated with GnRH antagonist than in those treated with GnRH agonist (542.0 +/- 76.9 versus 873.0 +/- 105.1 pg/ml, P = 0.02), which correlates with the mean serum oestradiol concentrations found in these two groups. No significant differences were found between groups in follicular fluid progesterone concentrations. Women undergoing GnRH antagonist treatment showed similar concentrations of follicular fluid testosterone compared with GnRH agonist-treated women (14.8 +/- 1.1 versus 13.3 +/- 2.7 ng/ml). The oestradiol:testosterone ratio was markedly reduced in women treated with GnRH antagonist (49.1 +/- 2.3 versus 60.1 +/- 4.4, P = 0.04). In contrast, no differences were found either in the progesterone:testosterone ratio, or in the oestradiol:progesterone ratio. CONCLUSIONS: GnRH antagonist therapy in women undergoing ovarian stimulation had a significant effect on ovarian follicular steroidogenesis.

Adult↗
PubMed2001

Blastocyst transfer: does it really affect the outcome?

Blastocyst transfer is of great interest to most assisted reproductive technology clinics. The ability to select the best embryos to transfer in order to increase pregnancy rates, and to replace lower numbers of embryos to reduce the likelihood of an unwanted multiple pregnancy have both been realized. The optimal method to prolong embryo culture up to day 5 or 6 is still to be identified, although present techniques offer acceptable blastocyst development rates. Freezing of supernumerary blastocysts is still a matter of discussion, as adequate results are still awaited.

Cell Culture Techniques↗
PubMed2001

Endometrial quality in infertile women with endometriosis.

Several analyses in our infertility (IVF) and oocyte donation programs were carried out to gain clinical knowledge of the factors involved in the etiology of endometriosis-associated infertility. We first compared the IVF outcomes in women with tubal infertility and endometriosis. The results indicated that patients with endometriosis had a poorer IVF outcome in terms of reduced pregnancy rate per cycle, per transfer, and reduced implantation rate per embryo replaced. We then evaluated embryo development in vitro in women with and without endometriosis who underwent IVF and embryo replacement 72 hours after oocyte retrieval. We observed that compared to controls, patients with endometriosis had a significantly reduced number of blastomeres per embryo as well as an increased incidence of arrested embryos in vitro. In subsequent studies we compared fertility parameters in patients receiving donor oocytes. We noted that when donor oocytes came from patients without known endometriosis, embryo development and implantation rates were similar in patients with and without endometriosis. However, when the results of oocyte donation were classified according to the nature of the oocytes donated, patients who received embryos derived from oocytes from women with endometriotic ovaries showed a significantly reduced implantation rate compared to the controls. Taken together, these observations suggest that IVF in patients with endometriosis may be related to alterations within the oocyte, which, in turn, result in embryos of lower quality with a reduced ability to implant.

Endometriosis↗
PubMed2000

High doses of gonadotrophins combined with stop versus non-stop protocol of GnRH analogue administration in low responder IVF patients: a prospective, randomized, controlled trial.

Recent evidence suggests that early cessation of gonadotrophin releasing hormone analogue (GnRHa) administration may offer some benefit to low responder patients undergoing IVF. A prospective, randomized controlled trial was designed to evaluate whether early cessation of GnRHa in an ovarian stimulation regimen is more beneficial than just increasing the doses of gonadotrophins. Seventy low responder patients (less than three mature follicles in a previous cycle) with normal basal follicle stimulating hormone concentrations and a previous cancelled IVF cycle were randomly allocated into two protocols: (i) non-stop protocol: long GnRHa suppression with high doses of gonadotrophins, and (ii) stop protocol, in which GnRHa administration is stopped with the onset of menses, while gonadotrophin doses remained similar to the non-stop protocol. A significantly higher number of mature oocytes were obtained in the study group (stop protocol) compared to the control group (non-stop protocol) (8.7 +/- 0.9 versus 6.2 +/- 0.7, P: = 0. 027). The stop protocol reduced the number of ampoules of gonadotrophins required (56.6 +/- 2.7 versus 68.0 +/- 3.5, P: = 0. 013). Both protocols resulted in a similar cancellation rate (2.7 versus 5.8%) (with no cycles cancelled due to ovulation), pregnancy rate (14.3 versus 18.7%), and implantation rate (12.1 versus 8.8%). The early cessation of GnRHa combined with high doses of gonadotrophins permitted the retrieval of a significantly higher number of oocytes.

Adult↗
PubMed2000

Empty follicle syndrome: evidence for recurrence.

The empty follicle syndrome (EFS) is a frustrating condition in which no oocytes are retrieved in an IVF cycle. Although this is an infrequent event in IVF patients, the economic consequences as well as the emotional frustration of a cancelled cycle due to the inability to obtain oocytes are enormous. The mechanisms responsible for EFS remain obscure, though many hypotheses have been put forward ranging from dysfunctional folliculogenesis to a drug-related problem. We found that the EFS is a rare event (1.8% of oocyte retrievals) but with profound implications for counselling the couple about their future reproductive performance. The chances of recurrence of EFS increase with the age of the patient (24% recurrence rate for the 35-39 year age group, and 57% for those over 40 years). We postulate that ovarian ageing, through altered folliculogenesis, may be implicated in the aetiology of EFS and its recurrence.

Adult↗
PubMed1999

Interleukin-8 stimulates the adhesion of endometrial stromal cells to fibronectin.

OBJECTIVE: To study the effect of interleukin-8 (IL-8) and mouse anti-human IL-8 monoclonal antibody on endometrial stromal cell adhesion to fibronectin. DESIGN: Prospective, controlled in vitro study. SETTING: Academic research laboratory. PATIENT(S): Women undergoing benign gynecologic surgery for indications other than endometrial disease. INTERVENTION(S): Endometrial stromal cells were treated with IL-8 and mouse anti-human IL-8 monoclonal antibody at different concentrations and adhesion assays were performed by labeling the cells with calcein. MAIN OUTCOME MEASURE(S): Fluorescence in calcein-labeled endometrial stromal cells. RESULT(S): IL-8 induced a concentration-dependent increase of cell adhesion to fibronectin matrix (twofold at 10 ng/mL; P = .006). Treatment of endometrial stromal cells with anti-IL-8 neutralizing antibody inhibited partially the cell adhesion. CONCLUSION(S): IL-8 stimulates the adhesion of endometrial stromal cells to fibronectin in a concentration-dependent manner. IL-8 may thus be relevant for the attachment of endometrial implants in the pathogenesis of endometriosis.

Animals↗
PubMed1999

A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation.

A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU. In subjects of the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (10.6 versus 6.2 oocytes, P < 0.001). The total dose needed to develop at least three follicles with a diameter of > or = 17 mm was significantly lower in the 100 IU treatment group (1114 IU versus 1931 IU, P < 0.001). In the low-dose group, significantly lower serum concentrations of oestradiol, progesterone and FSH were observed at the day of human chorionic gonadotrophin administration. Although more cycle cancellations due to low response were seen in the 100 IU group (n = 24 versus n = 3), the clinical pregnancy rate per started cycle was similar (24.7% in the 100 IU group versus 23.3% in the 200 IU group). In the high-dose group, more side-effects, in particular more cases of ovarian hyperstimulation syndrome, were noted. It is concluded that compared to 200 IU, the use of a 100 IU fixed dose is less efficacious in terms of the number of oocytes retrieved, but more efficient as indicated by a lower total dose.

Buserelin↗
PubMed1999

Is the endometrium or oocyte/embryo affected in endometriosis?

One of the most puzzling problems of endometriosis is determining which mechanisms link this spectrum of conditions to infertility. There is conflicting evidence about the effect of endometriosis on the endometrium and on oocyte/embryo quality. Clinical studies reveal that implantation rates seem to be lower in women with endometriosis, while spontaneous abortion rates show variable results which are difficult to interpret due to the design of the studies. Biochemical markers (integrins and other cell adhesion molecules), morphological markers (pinopodes), apoptosis and ultrasound studies confirm that not only does the endometrium from women with endometriosis behave differently from the endometrium of women without endometriosis, but ectopic endometrium also behaves differently from eutopic endometrium. Data from oocyte donation programmes suggest that oocyte quality may be hampered in women with endometriosis. Recent reports have focused on the molecular mechanisms that may be altered, such as ovarian steroid production, or inadequate luteal function. In this review, we analyse the most recent literature dealing with the different mechanisms which affect the endometrium and oocyte/embryo quality and which thereby might cause infertility.

Abortion, Spontaneous↗
PubMed1999

Interleukin-8 expression in endometrial stromal cells is regulated by integrin-dependent cell adhesion.

Concentrations of interleukin (IL)-8, a potent chemotactic factor produced by many cell types, are elevated in the peritoneal fluid of women with endometriosis. We investigated whether endometrial stromal cell (ESC) adhesion induces the expression of IL-8 and if this process is integrin-mediated. ESCs were plated onto culture dishes coated with various extracellular matrix (ECM) substrates, such as fibronectin, laminin, collagen IV, and poly-L-lysine, or mouse anti-human integrin beta(1,) and beta(2) monoclonal antibodies. IL-8 expression was induced by adherence of ESCs to fibronectin or collagen IV, but not to poly-L-lysine, a non-integrin-dependent adhesion matrix. Engagement of beta(1)-containing integrins was associated with ESC adhesion and resulted in up-regulation of IL-8 mRNA expression and protein secretion. Disruption of the actin cytoskeleton by treating ESC with cytochalasin D completely blocked the increase of IL-8 that was induced in response to integrin activation. These findings indicate a novel mechanism of IL-8 regulation; cell adhesion to ECM is an important event that leads to stimulation of IL-8 expression, and this process is mediated by integrins.

Animals↗
PubMed1999

Macrophage derived growth factors modulate Fas ligand expression in cultured endometrial stromal cells: a role in endometriosis.

Fas-Fas ligand (FasL) interactions play a significant role in the immune privilege status of certain cell populations, and several cytokines and growth factors can modulate their expression. When a FasL-expressing cell binds a Fas-bearing immune cell, it triggers its death by apoptosis. In this study, we demonstrate that normal human endometrial epithelial but not stromal cells express FasL. Moreover, we showed that macrophage-conditioned media induced FasL expression by endometrial stromal cells in a dose-dependent manner. To elucidate which macrophage product was responsible for the up-regulation of FasL, endometrial stromal cell cultures were treated with the macrophage products platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta1, and basic fibroblast growth factor (bFGF). The first two (which are known to be elevated in the peritoneal fluid of women with endometriosis) induced a dose-dependent up-regulation of FasL expression, which was specifically inhibited by the antibody. Interestingly, bFGF (which is not elevated in peritoneal fluid of women with endometriosis) did not induce any response. These results suggest that the pro-inflammatory nature of the peritoneal fluid of women with endometriosis induces the FasL expression by regurgitated endometrial cells, and signals Fas-mediated cell death of activated immune cells. This could be a mechanism for endometrial cells to escape immune surveillance, implant and grow.

Cell Differentiation↗
PubMed1999

Regulation of monocyte chemotactic protein-1 expression in human endometrial stromal cells by integrin-dependent cell adhesion.

Shed menstrual endometrium is viable and has the ability to implant and grow in women, who eventually develop endometriosis. Many of the cell-to-cell or cell-to-extracellular matrix (ECM) connections are mediated by integrins. Monocyte chemotactic protein (MCP)-1, a potent chemotactic factor produced in many cell types, is elevated in the peritoneal fluid of women with endometriosis. In this study, we investigated whether endometrial stromal cell (ESC) adhesion itself induces the expression of MCP-1 and whether this process is integrin mediated. ESC were plated on Petri dishes and 24-well plates coated with fibronectin, laminin, collagen IV, poly-L-lysine, or mouse anti-human integrin beta(1) and beta(2) monoclonal antibodies. Adherence of ESC to various ECM substrates, except for poly-L-lysine, a non-integrin-dependent adhesion matrix, induced the expression of MCP-1 at both mRNA and protein levels. Engagement of beta(1)-containing integrins was associated with ESC adhesion and resulted in up-regulation of MCP-1 gene expression and protein secretion. Disruption of the actin cytoskeleton by treating ESC with cytochalasin D completely blocked the increase of MCP-1 induced in response to integrin activation. These findings indicate a novel mechanism of MCP-1 regulation. Cell adhesion to ECM is an important event that leads to stimulation of MCP-1 expression, and this process is mediated by integrins.

Animals↗