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Carlos Simón

Publications and source records attributed to Carlos Simón.

At least 55 records · Page 3Linked to original sources
PubMed2003

Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study.

OBJECTIVE: To evaluate the reproductive and neonatal outcome of blastocyst transfer after coculture with human endometrial epithelial cells in IVF and oocyte donation. DESIGN: Retrospective study. Private assisted reproductive center. PATIENTS(S): Two hundred sixty women undergoing IVF and 469 oocyte recipients. INTERVENTION(S): IVF or intracytoplasmic sperm injection (ICSI) and transfer of at least one blastocyst after coculture with human endometrial epithelial cells. MAIN OUTCOME MEASURE(S): Blastocyst formation rate, implantation and pregnancy rates, neonatal outcome, and congenital birth defects. RESULT(S): Among patients who had transfer with their own oocytes, 1193 of 2349 cocultured embryos developed up to the blastocyst stage (50.8%), and pregnancy and implantation rates of 33.9% and 19.2%, respectively, were achieved. In the oocyte donation program, 1819 blastocysts were obtained from 3127 embryos (58.2%), with subsequent pregnancy and implantation rates of 57.0% and 31.0%, respectively. The blastocyst rate remained stable throughout the 5 years of the study, but the pregnancy and implantation rates increased dramatically. Of 139 deliveries, 57 (41.0%) were multiple pregnancies and 1 (0.7%) was a multifetal birth (four live born infants). Out of 200 children born, 59% were male, and congenital birth defects were observed in 2.5%. CONCLUSION(S): Coculture of human embryos with endometrial epithelial cells yields a blastocyst formation rate of 50.8% to 58.2% and encouraging implantation and pregnancy rates. This technique reduces the mean number of embryos transferred in each patient. The number of embryos implanted is more relevant to neonatal outcome than is the coculture system and blastocyst transfer used. The risk of congenital birth defects associated with this program is similar to that recorded in early ET in IVF or ICSI.

Adult↗
PubMed2003

Preimplantation genetic diagnosis by fluorescence in situ hybridization: clinical possibilities and pitfalls.

Preimplantation genetic diagnosis using the fluorescence in situ hybridization technique (FISH) is being used widely to prevent the transmission of sex-linked diseases, to screen for translocations, and for aneuploidy screening in specific in vitro fertilization (IVF) patient groups, along with FISH analysis of spermatozoa in infertile men. In this study, we aim to critically analyze our clinical results in patients at risk of transmitting sex-linked diseases (n = 55), in carriers of translocations (n = 43), in women who have recurrent miscarriage (two or more miscarriages) (n = 128), recurrent IVF failure (three or more failed IVF attempts) (n = 47), and patients of advanced maternal age (37 years old or older) (n = 79). The use of the FISH technique in carriers of sex-linked diseases and translocation patients prevents transmission of these conditions and provides good IVF outcome. In patients with recurrent miscarriage, implantation failure, and advanced maternal age, a high incidence of embryos with abnormal chromosomes 13,16,18,21,22, X, and Y was observed (range 69-75%), as expected. In those three groups of patients, the selection of euploid embryos for transfer resulted in good pregnancy rates with a low incidence of miscarriage. Limitations and pitfalls of this technique are also discussed.

Abortion, Spontaneous↗
PubMed2003

Uterine and ovarian function in endometriosis.

Although numerous studies have attempted to elucidate the implication of endometriosis for infertility, this matter still remains unexplained. Diverse clinical approaches based on assisted reproduction techniques have produced conflicting results on this issue. Nevertheless, impairment of implantation and pregnancy rates seems to affect women who suffer from endometriosis. Whether this effect is due to alteration of the oocyte/embryo or the endometrium still remains to be elucidated, although actual data allude to deficiencies in both. Infertility due to poor quality embryos derived from impaired oocytes obtained from malfunctioning ovaries have been described by some groups. Endometrial defects have been argued by others. Adding more confusion to this topic, the influence of peritoneal fluid in women with endometriosis and/or mixed causes also needs to be considered. The aim of this review is to describe the current situation in the endometriosis-related infertility literature.

Ascitic Fluid↗
PubMed2003

Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation syndrome in high-risk IVF patients: a randomized controlled study.

BACKGROUND: Intravenous albumin administration has been described for many years as a debatable, but probably useful preventive measure in ovarian hyperstimulation syndrome (OHSS). The present study details the largest randomized controlled trial to date of albumin infusion versus no treatment in IVF patients with a high risk of developing moderate to severe OHSS. METHODS: Between March 1999 and February 2002, women undergoing IVF at the IVI Valencia with >20 retrieved oocytes were included. A total of 988 patients was initially enrolled. Immediately after oocyte retrieval, patients were allocated to two groups based on a computer randomization: the first group received 40 g human albumin; the second group received no treatment. Subjects were weighed and a blood analysis performed immediately after oocyte retrieval and again 7 days later. Women were monitored on an outpatient basis until menstruation, or until fetal heart activity was detected. Twelve subjects were excluded due to follow-up loss, leaving 976 women (377 of them oocyte donors), with 488 in each group. RESULTS: No difference was found between the two groups in terms of patient characteristics and outcome. Moderate-severe and severe-only OHSS rates were similar. The incidence of haemoconcentration and liver and renal dysfunction at 7 days after oocyte retrieval was similar in the two groups. In women who developed moderate/severe (n = 66) or only severe (n = 46) OHSS, there was no difference based on prior albumin administration between blood parameters or body weight on the day of oocyte retrieval, 7 days later, and even when comparing variation between both measurements. Moreover, the number of patients with paracentesis, hospital admissions, complications and days of OHSS until resolution did not differ. CONCLUSIONS: Albumin infusion on the day of oocyte retrieval is not a useful means of preventing the development of moderate-severe OHSS.

Adult↗
PubMed2003

The effect of pronuclear morphology on early development and chromosomal abnormalities in cleavage-stage embryos.

BACKGROUND: Pronuclear (PN) zygote morphology has been proposed as a useful tool for selecting the best embryos for transfer. METHODS: PN morphology was recorded in 888 zygotes and classified according to similar/different PN size [groups A (n = 816) and B (n = 72)] and to the number, distribution and synchrony of nucleolar precursor bodies (NPB): subgroup I, pronuclei with 3-4 polarized NPB; subgroup II, 5-7 synchronic polarized NPB or 7-10 NPB distributed randomly; and subgroup III, morphologies other than those of groups I or II. Embryo development and chromosomal abnormalities were evaluated for each PN pattern. RESULTS: In patients aged </=37 years, the number of zygotes reaching morula and blastocyst stage was significantly (P = 0.0003) higher in group A than in group B. In group A, the incidence of chromosomal abnormalities was significantly (P = 0.0247) lower than in group B, and significant differences were observed when pattern AI was compared with pattern AII (P = 0.0280), AIII (P = 0.0024), BIII (P = 0.0077) and total B (P = 0.0247). In patients aged >37 years, statistical differences among groups were not observed. CONCLUSIONS: In patients aged </=37 years, zygotes with similar PN size and with polarized NPB present the best prognosis based on embryo development and the incidence of chromosomal abnormalities, whereas in patients aged >37 years, this correlation does not exist.

Adult↗
PubMed2003

Hormonal and embryonic regulation of chemokine receptors CXCR1, CXCR4, CCR5 and CCR2B in the human endometrium and the human blastocyst.

Chemokines are implicated in the implantation process. The aim of this study was to investigate mRNA expression and protein levels of chemokine receptors CXCR1, CXCR4, CCR5 and CCR2B in human endometrium throughout the menstrual cycle, during HRT and in the human blastocyst. The regulation of chemokine receptors in the endometrial epithelium was also studied using an in-vitro model for the apposition phase of human implantation. We found up-regulation of endometrial CXCR1 mRNA (419-fold increase), CCR5 mRNA (612-fold increase) and CCR2B mRNA (657 fold-increase) during the luteal phase peaking in the pre-menstrual endometrium. CXCR4 mRNA levels presented a specific although modest (18-fold increase) up-regulation during the implantation window. These findings were corroborated at the protein level in natural and HRT cycles. Immunoreactive CCR5 and CCR2B receptors were detected in human blastocysts whereas CXCR4 and CXCR1 were not present. Chemokine receptors in cultured endometrial epithelial cells showed an up-regulation and polarization of CXCR1, CXCR4 and CCR5 receptors when a human blastocyst was present. The specific distribution and regulation of chemokine receptors in the endometrial epithelium and the human blastocyst suggest a possible implication of these receptors in the apposition and adhesion phases of human implantation.

Adult↗
PubMed2003

Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology.

In humans, embryonic implantation and reproduction depends on the interaction of the embryo with the receptive endometrium. To gain a global molecular understanding of human endometrial receptivity, we compared gene expression profiles of pre-receptive (day LH+2) versus receptive (LH+7) endometria obtained from the same fertile woman (n = 5) in the same menstrual cycle in five independent experiments. Biopsies were analysed using the Affymetrix HG-U95A array, a DNA chip containing approximately 12,000 genes. Using the pre-defined criteria of a fold change >/=3 in at least four out of five women, we identified 211 regulated genes. Of these, 153 were up-regulated at LH+7 versus LH+2, whereas 58 were down-regulated. Amongst these 211 regulated genes, we identified genes that were known to play a role in the development of a receptive endometrium, and genes for which a role in endometrial receptivity, or even endometrial expression, has not been previously described. Validation of array data was accomplished by mRNA quantification by real time quantitative fluorescent PCR (Q-PCR) of three up-regulated [glutathione peroxidase 3 (GPx-3), claudin 4 (claudin-4) and solute carrier family 1 member 1 (SLC1A1)] genes in independent LH+2 versus LH+7 endometrial samples from fertile women (n = 3) and the three up-regulated genes throughout the menstrual cycle (n = 15). Human claudin-4 peaks specifically during the implantation window, whereas GPx-3 and SLC1A1 showed highest expression in the late secretory phase. In-situ hybridization (ISH) experiments showed that GPx-3 and SLC1A1 expression was restricted to glandular and luminal epithelial cells during the mid- and late luteal phase. The present work adds new and important data in this field, and highlights the complexity of studying endometrial receptivity even using global gene-expression analysis.

Adult↗
PubMed2003

A combined approach for gene discovery identifies insulin-like growth factor-binding protein-related protein 1 as a new gene implicated in human endometrial receptivity.

In the past, human endometrial receptivity has been investigated by chasing specific molecules throughout the menstrual cycle. Now the genomic approach allows us to investigate the hierarchical contribution of a high number of genes to a specific function. In this study, we analyzed differentially the gene expression pattern of 375 human cytokines, chemokines, and related factors, plus that of their receptors, in endometrial receptivity. To do this, we used a combined approach of human endometrium and cell lines. We have compared the gene expression pattern in receptive vs. prereceptive human endometria and contrasted the results with gene expression in the highly adhesive cell line (to JAR cells and mouse blastocysts) RL95-2 vs. HEC-1A, a cell line with markedly less adhesiveness. IGF-binding protein-related protein 1 (IGFBP-rP1), also known as IGFBP-7/mac 25, was the second most up-regulated gene in both of the investigated models. These results were corroborated by performing RT-PCR on the same RNA samples and validated by quantitative fluorescent RT-PCR and in situ hybridization in endometrium throughout the menstrual cycle. Interestingly, a 35-fold increase in expression during the receptive phase was compared with the prereceptive phase followed by a sharp increase in the late luteal. Further quantitative fluorescent RT-PCR experiments using the epithelial and stromal endometrial fraction throughout the menstrual cycle confirmed that IGFBP-rP1 expression was localized in the epithelial and stromal compartments and up-regulated mainly in the latter. In situ experiments confirmed the endometrial localization and regulation of IGFBP-rP1 mRNA. At the protein level, IGFBP-rP1 was localized by immunohistochemistry at the apical part of the luminal and glandular epithelium, stromal, and endothelial cells. In conclusion, using a genomic approach with a combined experimental design of receptivity in vivo and in vitro, we have discovered the implication of IGFBP-rP1 in endometrial physiology, which seems related to endometrial receptivity.

Animals↗
PubMed2003

Recombinant vs. urinary follicle-stimulating hormone in couples undergoing intrauterine insemination. A randomized study.

OBJECTIVE: To compare the results of ovulation induction in couples undergoing intrauterine insemination (IUI) with a standard daily dose of 100 IU of recombinant follicle-stimulating hormone (rFSH) vs. 150 IU of urinary follicle-stimulating hormone (uFSH). STUDY DESIGN: Prospectively, 118 cycles were randomized to rFSH and 106 cycles to uFSH. Ovarian response was compared on the human chorionic gonadotropin administration day by serum estradiol (E2) levels and number of ovarian follicles produced. RESULTS: In the rFSH group a significantly lower dose of FSH was administered (799.1 vs. 1,293.0 IU, P < .001), and a lower number of follicles > or = 12 mm (2.9 vs. 3.7, P < .001) and lower number of midsized follicles (12-16 mm) were observed (0.7 vs. 1.7, P < .001) as compared to the uFSH group. No difference was found between groups in the number of follicles > or = 17 mm or in serum E2 levels obtained. The E2/FSH dose ratio was significantly higher in the rFSH group (0.9 vs. 0.6, P < .001), and the ratio of E2/follicles > or = 17 mm was significantly lower in the rFSH group (308.9 vs. 406.5, P < .001). CONCLUSION: A standard daily dose of 100 IU of rFSH is more effective than uFSH in women undergoing IUI treatment since a more symmetric response is obtained.

Adult↗
PubMed2002

Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients.

OBJECTIVE: To determine whether transabdominal ultrasound guidance during embryo transfer (ET) is a useful tool for increasing pregnancy rates in patients undergoing oocyte donation. DESIGN: Prospective, randomized, controlled trial. SETTING: In vitro fertilization academic center. PATIENT(S): Three hundred seventy-four infertile patients undergoing oocyte donation. INTERVENTION(S): Transabdominal ultrasound-guided ET. MAIN OUTCOME MEASURE(S): We measured the pregnancy rate and implantation rate after transabdominal ultrasound-guided ET versus the rates in a control group who did not receive transabdominal ultrasound-guided ET. RESULT(S): Clear visualization at ultrasound during ET was achieved in 90.8% of the patients who had ultrasound-guided ET. A similar number of easy transfers were performed in both the ultrasound-guided and the control groups (84.5% vs. 86.6%). The pregnancy rate was comparable between the groups (59.9% ultrasound vs. 55.1% control), as was the implantation rate (30.6% ultrasound vs. 26.3% control). No differences were found in the miscarriage rate (10.7% ultrasound vs. 9.1% control) or in the multiple pregnancy rate (21.4% ultrasound vs. 22.5% control). Although all ectopic pregnancies occurred in the group that did not receive ultrasound guidance, the differences were not statistically significant (0 vs. 2.7%). CONCLUSION(S): We could not show any benefit in terms of pregnancy rate in oocyte recipients for whom ET was performed under direct transabdominal ultrasound visualization of the endometrial cavity. There was a lower ectopic pregnancy rate when ultrasound guidance was used, but this rate was not statistically significant in comparison with the pregnancy rate without ultrasound guidance.

Abdomen↗
PubMed2002

Comparison of polymerase chain reaction-dependent methods for determining the presence of human immunodeficiency virus and hepatitis C virus in washed sperm.

OBJECTIVE(S): To evaluate the effectiveness of sperm washes by double capacitation in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and to compare between polymerase chain reaction (PCR)-dependent methods to determine viral presence after the procedure. DESIGN: Controlled prospective clinical trial. SETTING: Private and university-affiliated setting. PATIENT(S): Thirty-four HIV-positive men attending our center for assisted reproduction with their partners. INTERVENTION(S): Forty-one semen samples from seropositive males were obtained and washed through density gradients and swim-up and analyzed for the presence of HIV and HCV with either nested or one-round PCR. Qualitative and quantitative detection of DNA and RNA of HIV and RNA of HCV. RESULT(S): Of all the semen samples that were analyzed after washing, seven out of 41 samples tested positive for one or both viruses by nested PCR. The confirmation of these results with the currently used commercial methods of quantitative PCR (one-round PCR) resulted in all negatives. CONCLUSION(S): Sperm wash with nested PCR is the appropriate method to use in the assisted reproduction techniques that are offered to serodiscordant couples. The detection limits exhibited by one-round PCR do not offer a sufficient guarantee that transmission of all viral particles will be avoided since both viruses can be present in amounts lower than the detection threshold of this technique.

Adult↗
PubMed2002

Expression and function of 3beta hydroxisteroid dehydrogenase (3beta HSD) type II and corticosteroid binding globulin (CBG) in granulosa cells from ovaries of women with and without endometriosis.

PURPOSE: To investigate the secretion of progesterone (P4) and corticosteroid binding globulin (CBG) by granulosa luteal cells (GC) as well as the mRNA levels of CBG and 3beta hydroxisteroid dehydrogenase (3beta HSD), in women with and without endometriosis in vivo and in vitro. METHODS: Prospective study in a private, university-affiliated assisted reproduction unit, including women with severe endometriosis (n = 14) or without the disease (n = 20) undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer. GC were obtained from each follicle aspirated, pooled for each patient, and follicular and blood contaminating leukocytes depleted through immunomagnetic purification. Secreted P4 and CBG, and mRNA for both 3beta HSD and CBG were determined in vivo and in vitro using RIA and reverse transcription followed by competitive polymerase chain reaction (cRT-PCR). RESULTS: The pattern of expression of 3beta HSD and CBG mRNAs in vivo and in vitro was similar in both groups. Also, GC from patients with endometriosis produced equal amounts of P4 and CBG than controls without the disease, either in freshly isolated cells or in 24-h cultures. CONCLUSIONS: The GC function in terms of 3beta HSD and CBG mRNA expression and P4/CBG secretion does not seem to be altered in patients with endometriosis in comparison with those without this condition.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

Gender selection: ethical, scientific, legal, and practical issues.

PURPOSE: This work offers an overview of the technology available and assisted reproductive technology (ART) practitioner attitudes to human reproductive sex preselection in either sperm with the use of flow cytometry (FC) or in embryos by means of preimplantational genetic diagnose (PGD) together with an analysis of Spanish legal environment. METHODS: A review of the legal, ethical and technical literature of the methods to select the sex in the offspring is performed. RESULTS: Sex selection in humans has different utilities to be employed depending on each country's law. Moreover, different ethical concerns are raised depending on the type of sex selection, in sperm or embryos. Both methodologies to pre-select the sex are trustworthy, with a high predictive power in the determination of the sex, but nevertheless, PGD is better than FC selection in this aspect. CONCLUSIONS: After a careful analysis of ethical, legal, and scientific features of gender selection, FC combined with PGD appears to be the most acceptable way to select the sex of the progeny whatever the circumstances are.

Female↗
PubMed2002

Hormonal and embryonic regulation of chemokines IL-8, MCP-1 and RANTES in the human endometrium during the window of implantation.

Chemokines are a family of small polypeptides which specialize in the attraction of leukocytes. The presence of specific leukocyte subsets at the implantation site is an important element of the complex, and not completely understood, process of embryonic implantation. This report includes the investigation of the in-vivo immunolocalization and hormonal regulation of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and RANTES (regulated upon activation normal T-cell expressed and secreted) in the human endometrium during hormone replacement therapy cycles for oocyte recipients in an IVF programme. In addition, we have analysed the embryonic regulation of these endometrial epithelial chemokines (IL-8 and MCP-1) using an in-vitro model for the apposition phase of human implantation by co-culturing single human embryos until the blastocyst stage with human endometrial epithelial cells (EEC). IL-8 and MCP-1 were immunolocalized in the human endometrium to the glandular and lumenal epithelium as well as to the endothelial cells. RANTES was mainly localized to the stromal compartment and endothelial cells. The immunoreactive levels of endometrial IL-8 and MCP-1 were up-regulated by the administration of progesterone during the receptive phase of the cycle. Furthermore, it was demonstrated that, in vitro, the human blastocyst does not produce measurable amounts of IL-8, MCP-1 or RANTES; however, it does up-regulate EEC IL-8 mRNA expression (P < 0.05) and protein production (P < 0.05), but not IL-8 secretion. The human embryo did not regulate EEC MCP-1 expression. These results provide evidence of hormonal and embryonic regulation of specific endometrial chemokines, suggesting two different but related mechanisms to induce the production of chemokines by the EEC, thus contributing to the attraction of specific leukocyte populations during the peri-implantation phase.

Blastocyst↗
PubMed2002

Vascular endothelial growth factor receptor-2 activation induces vascular permeability in hyperstimulated rats, and this effect is prevented by receptor blockade.

The existence of a vasoactive molecule released in response to hCG is believed to be the main feature in the development of ovarian hyperstimulation syndrome (OHSS) in women, and vascular endothelial growth factor (VEGF) is the main candidate as the human chorionic gonadotropin (hCG) mediator. This study was conducted to investigate the role of VEGF in increasing vascular permeability (VP) in vivo, a characteristic of OHSS. We analyzed the source and specific isoforms of VEGF involved and developed strategies to reverse increased VP in hyperstimulated rats targeting the VEGF system. Ovarian hyperstimulation was induced with pregnant mare's serum gonadotropin, or pregnant mare's serum gonadotropin plus hCG. Time-course experiments analyzed VP and the expression of whole VEGF mRNA in the mesentery and the ovaries. VP and ovarian mRNA VEGF expression increased to peak values after 48 h. No significant change in expression was observed in the mesentery. To further prove the ovarian origin of VEGF, we showed that VP was not altered when ovariectomized rats were treated with gonadotropins. The ovary expressed VEGF(120) and VEGF(164) isoforms. Immunohistochemistry showed VEGF in granulosa and zona pellucida of preovulatory and atretic follicles and in granulosa-lutein and endothelial cells of whole corpus luteum. A specific VEGF receptor-2 inhibitor (SU5416) was administered in three different protocols: on a daily basis, every 48 h, or two injections after hCG. Increased VP was reversed when SU5416 was administered every 48 h or two injections after hCG. These results show that the ovary is the main source of VEGF(120) and VEGF(164), which act through the VEGF receptor-2 to increase VP, and provide new insights into the prevention of OHSS.

Animals↗