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C Simón

Publications and source records attributed to C Simón.

At least 19 recordsLinked to original sources
PubMed2006

Fresh human orthotopic ovarian cortex transplantation: long-term results.

BACKGROUND: Ovarian orthotopic transplantation in patients with premature ovarian failure is reported to result in full-term pregnancies. Ischaemia and freezing/thawing are potentially injurious for tissues. This study was designed to analyse the effect of ischaemia on long-term ovarian function in humans. METHODS: Prospective case-control study. Subjects were 12 premenopausal women undergoing hysterectomy and fresh orthotopic transplantation of the entire ovarian cortex plus a control group of five patients undergoing hysterectomy only. Follow-up lasted 2 years. Serum FSH and anti-Müllerian hormone (AMH) were recorded, and ovulatory cycles were determined by vaginal ultrasound and serum progesterone levels. RESULTS: Follow-up showed that ovulation was restored in 11 of the 12 patients who received grafts over the duration of the study (9.3 +/- 1.73 ovulations versus 12.0 +/- 0.86 in controls, NS), and 9 of 12 patients remained ovulatory after 2 years. We identified four patterns of FSH secretion during the study, 5 of 12 (41.7%) women having the same pattern as controls. There was a trend for serum AMH levels 7 days after surgery (0.16 +/- 0.02 microg/l) to be lower than pre-surgery levels (0.38 +/- 0.09 microg/l, P = 0.07) and higher in women whose FSH patterns suggested normal ovarian function, but the results did not reach significance. After transplantation, FSH correlated more closely (r = -0.639, P = 0.02) with normal ovarian function than AMH (r = 0.465, P = 0.12). CONCLUSIONS: Fresh orthotopic ovarian cortex transplantation is a viable procedure. It maintains normal ovarian function after 2 years in 75% of cases and preserves ovarian function against ischaemia in 41.7% of patients.

Adult↗
PubMed2006

Serum interleukin-6 levels are elevated in women with minimal-mild endometriosis.

BACKGROUND: There is a need for a reliable marker of endometriosis, especially in early stages of peritoneal disease during which imaging is not effective. The use of serum interleukin (IL)-6 as a marker is controversial. To readdress the matter, patients undergoing laparoscopy were prospectively evaluated for serum IL-6 levels. MATERIALS AND METHODS: A total of 119 women 31 years old who underwent laparoscopy were divided into groups: control patients (n = 38) with no pathologic findings; endometriosis sufferers (n = 47) with minimal-mild (MM, n = 11) or moderate-severe (MS, n = 36) endometriosis; uterine myomas (n = 13) and benign ovarian pathologies (n = 21). Blood was drawn on cycles days 5-12 and stored for subsequent analysis of IL-6 and carbohydrate antigen (CA)-125 levels. RESULTS: Serum IL-6 levels were significantly (P = 0.002) higher in women with MM endometriosis (29.4 9.0 pg/ml) than in controls (15.7 9.3 pg/ml). When all the non-endometriosis patients were grouped together (n = 72) and serum IL-6 (17.8 12.1 pg/ml) compared with MS (n = 36; 17.6 10.3 pg/ml) and MM (n = 11; 29.4 9.0 pg/ml) endometriosis significantly (P < 0.01) higher levels in MM endometriosis were observed as compared to the other two groups. Serum Ca-125 levels were significantly (P < 0.01) elevated in MS endometriosis. A serum IL-6 threshold of 25.75 pg/ml afforded a sensitivity of 75% and specificity of 83% in the diagnosis of MM endometriosis. Sensitivity and specificity for CA-125 in the diagnosis of MS endometriosis, using 35 IU/ml as the cut-off value, were 47% and 97%, respectively. CONCLUSIONS: IL-6 is a reliable non-invasive marker of MM endometriosis, whereas Ca-125 is of use as a marker of severe cases.

Adult↗
PubMed2006

Wide genomic analysis of human endometrial receptivity: new times, new opportunities.

Microarray technology has broadened the insight into many research fields allowing scientists to analyse the expression of many genes in quick and efficient experiments aimed at translating these findings into clinical applications. In reproductive medicine, researchers have exploited microarrays to increase understanding of the molecular mechanisms involved in endometrial receptivity and how a possible therapeutic translation can be feasible. In the last 4 years, several studies have focused on the genomics of the human endometrium in different physiological and pathological conditions, and these studies have generated a large amount of information about the regulation and dysregulation of the window of implantation (WOI) genes in fertile, subfertile and refractory conditions. However, the key molecules/mechanisms in endometrial receptivity remain to be elucidated. In this comprehensive review, we have analysed the available results obtained in our own and other laboratories, defining the genomic profile of the receptive endometrium in different situations and its possible clinical application.

Animals↗
PubMed2006

Identification, characterization and co-localization of label-retaining cell population in mouse endometrium with typical undifferentiated markers.

BACKGROUND: The endometrium, lining of the uterus, is a highly active organ that is remodelled periodically during the lifespan. Different studies suggest the presence of an adult or progenitor stem cell (PSC) population in this tissue because of its cyclic regenerative capacity. METHODS: In this study, we aim at identifying and localizing the putative PSC population in the murine uterus using the 5-bromo-2'-deoxyuridine (BrdU) labelling method to detect label-retaining cells (LRCs) that cycle slowly. Uteri from BrdU-treated mice were analysed via single and double immunohistochemistry to co-localize them with the markers of undifferentiation already described such as c-KIT and POU5F1 (also known as OCT-4). Finally, we confirmed the presence of the indicated markers at mRNA level. RESULTS: We observed the presence and gradual decrease of LRCs in the endometrium during the lifespan of the mice. In adulthood, the LRC population decreased notably and remained in the lower region of the stroma in the murine endometrium. Some of the endometrial LRCs co-localized with c-KIT and POU5F1. PCR and nested-PCR confirmed the presence of these undifferentiated markers. CONCLUSIONS: We demonstrated that the murine endometrium possesses LRCs with the features of a putative PSC population localized at the lower region of the stroma.

Animals↗
PubMed2006

Effect of an intrauterine device on the gene expression profile of the endometrium.

CONTEXT: The human endometrium acquires the ability to allow embryo attachment just for a specific period of time during each menstrual cycle. Understanding of the opposite functional status, referred to as refractoriness, can potentially be used to improve receptivity in infertile patients or as an interceptive approach to prevent gestation. OBJECTIVE: The objective of the study was to analyze the endometrial gene expression profile induced by an inert intrauterine device (IUD) at the time of implantation. DESIGN: We used a microarray containing more than 16,000 cDNAs to investigate the gene expression profile of receptive vs. refractory endometrium in the same women induced by the presence of an IUD. We compared the gene expression profile of endometrium obtained at LH+7 (window of receptivity) from the same women (n = 5) at the following time points: month 1, corresponding to the natural cycle before IUD insertion; month 3, just before IUD removal; and months 5 and 15. Data were validated by quantitative RT-PCR for IGF binding protein-3, peroxisome proliferative activated receptor-gamma, glycodelin, and leukemia inhibitory factor and immunohistochemistry for glycodelin. RESULTS: We identified 147 genes significantly dysregulated in the refractory endometrium (78 up- and 69 down-regulated). Interestingly, 52 of these genes have previously been reported to be regulated during window of implantation. Surprisingly, the majority of genes (96.6%) remained dysregulated 2 months after IUD removal, but 1 yr later most of them (80%) returned to normal. CONCLUSIONS: Our results reveal that a refractory endometrium in a fertile woman produced by an IUD is induced by preventing the normal transition to a receptive gene expression profile through effects on a specific subset or cluster of genes that impact on endometrial receptivity.

Adult↗
PubMed2005

Leptin system in embryo development and implantation: a protein in search of a function.

Implantation is a crucial moment in the reproduction process that requires perfect synchronization between the embryo and the maternal endometrium. The embryo must reach the blastocyst stage and the endometrium must be prepared to receive it. An appropriate and specific molecular dialogue must also take place between them. There is ample evidence to show that the leptin system is implicated in this cross-talk. Examples are described. Although there is some controversy surrounding the data, they are supported by the presence of leptin receptor mRNA in mouse and human oocytes and embryos throughout preimplantation development. Otherwise, the leptin mRNA is only detected at the blastocyst stage in both human and mouse. Furthermore, leptin is found at higher concentrations in the conditioned media from competent human blastocysts than in those from arrested embryos, suggesting that this molecule is a marker for blastocyst viability. Given that expression of the leptin receptor increases in the human endometrium during the luteal phase, the secreted leptin could trigger its activation. Finally, leptin and the leptin receptor have been detected in implantation sites. All these findings point to the involvement of the leptin system in the molecular mechanism of the implantation process and embryo development.

Embryo Implantation↗
PubMed2005

Embryonic implantation and leukocyte transendothelial migration: different processes with similar players?

A clear parallelism between the different steps in human embryo-endometrial apposition/adhesion/invasion and leukocyte-endothelium rolling/adhesion/extravasation can be established. During human implantation and leukocyte trafficking, a first wave of soluble mediators regulates the expression and functional activity of adhesion molecules such as L-selectin and integrins, which mediate both processes. Apical surfaces of human endometrial epithelium and endothelium are key elements for the initiation of molecular interactions to capture the blastocyst or leukocyte, respectively. Subsequently, the blastocyst and the leukocyte migrate through the epithelium and endothelium toward their final destination, the endometrial stroma, to initiate placentation or the inflammatory foci as part of the immune response. Similarities between the intermediate molecular mechanisms of these two physiologically unrelated processes are discussed.

Animals↗
PubMed2004

Endometrial leptin and leptin receptor expression in women with severe/moderate endometriosis.

The leptin system has been implicated in reproductive function, acting at endocrine and paracrine levels. Recently, deregulation of this gene family has been linked to endometrial changes caused by endometriosis. In the present study, we compare the expression of leptin receptor mRNA during the pre-receptive (LH+2) and receptive (LH+9) phases in the eutopic endometrium from patients with severe/moderate endometriosis (n = 30) versus fertile controls (n = 12). In each patient, two endometrial samples were obtained at LH+2 and LH+9 in their natural cycles. When real-time quantitative fluorescent PCR was performed, an up-regulation of OB-RL and all the isoforms investigated was observed at LH+9 versus LH+2 in patients with and without endometriosis. However, no difference was found in the expression pattern of the total leptin receptor OB-RT, or in its long OB-RL and soluble HuB219.3 forms when the eutopic endometria of patients with severe/moderate endometriosis and fertile controls were compared. By means of in situ hybridization, total leptin receptor mRNA was localized in the luminal epithelium and the glands of the endometrium. The immunohistochemical analysis of the long form of leptin receptor was also performed in order to confirm these findings at the protein level. Finally, we have also shown similar leptin mRNA expression in both the control group and patients with endometriosis. In conclusion, we have not identified differences in the endometrial expression and localization of leptin and the leptin receptor when comparing the eutopic endometrium of women with severe/moderate endometriosis and fertile controls.

Adult↗
PubMed2004

Coasting acts through downregulation of VEGF gene expression and protein secretion.

BACKGROUND: This study was conducted to investigate the mechanisms by which coasting may be effective in decreasing the incidence of ovarian hyperstimulation syndrome (OHSS). METHODS: A total of 160 women (patients and oocyte donors) undergoing coasting and 116 controls were included in the study. Serum, follicular fluid and granulosa cells were collected on the day of oocyte retrieval. Vascular endothelial growth factor (VEGF) concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to evaluate VEGF gene expression in granulosa cells. Cell death was studied by flow cytometry using annexin V-fluorescein isothiocyanate (FITC) and counterstaining by propidium iodide, and double staining with CD45 monoclonal antibody was performed to distinguish the contamination of apoptotic leukocytes. RESULTS: Follicular cells aspirated from coasted patients showed a ratio in favour of apoptosis, especially in smaller follicles (48 versus 26%, P < 0.05). Follicular fluid determinations confirmed that coasting reduces VEGF protein secretion (1413 versus 3538 pg/ml, P < 0.001) and gene expression (2-fold decrease) in granulosa cells. Follicular fluid VEGF protein levels positively correlated with follicular size (r = 0.594, P = 0.001) and estradiol production (r = 0.558, P = 0.038). Women who underwent coasting showed a comparable IVF cycle outcome; however, a higher cancellation rate was found in cycles that were coasted. CONCLUSIONS: Coasting affects all follicles through apoptosis, especially immature follicles, without affecting oocyte/endometrial quality. The significant decrease found in VEGF expression and secretion explains why coasting is clinically effective in reducing the incidence and severity of OHSS.

Down-Regulation↗
PubMed2004

Parameters affecting the results in a program of artificial insemination with donor sperm. A 12-year retrospective review of more than 1800 cycles.

PURPOSE: We aimed to establish the influence of the parameters affecting artificial insemination (AI) results in order to describe the ideal situations to achieve the best results as well as to adequately counsel the patients undergoing these treatments about their pregnancy chances. METHODS: We performed a controlled retrospective clinical study over more than one decade in a total of 1858 cycles in 710 patients. Clinical histories and computer registers were systematically reviewed between January 1990 and June 2002. We analyzed the influence of diverse factors affecting AI results such as patient's age, ovarian stimulation, and seminal characteristics to offer a detailed description of the technique. RESULTS: Less than 35-years-old, smooth ovarian stimulation and 5 million of progressive motile sperm inseminated two consecutive days are the optimum conditions for achieving good results. Also, period of time that sperm remained frozen do not affect the result. Furthermore, we present the likely or expected outcomes of these treatments depending on the male and female etiologies. CONCLUSIONS: We discourage AI in aged patients, and strongly recommend undergoing ovarian stimulation. Nonetheless, we must reach an adequate amount of sperm with good motility in order to inseminate with maximum guaranties of success.

Age Factors↗
PubMed2004

Analysis of chromosomal abnormalities in testicular and epididymal spermatozoa from azoospermic ICSI patients by fluorescence in-situ hybridization.

BACKGROUND: An increased incidence of numerical chromosomal abnormalities has been reported in the ejaculated spermatozoa of infertile patients. However, there are few cytogenetic studies of testicular and epididymal spermatozoa, and their results are still controversial. METHODS: Fluorescence in-situ hybridization (FISH) analysis of chromosomes 13, 18, 21, X and Y was performed on seven testicular samples and two epididymal samples from patients with obstructive azoospermia (OA), and on 13 testicular samples from patients with non-obstructive azoospermia (NOA). Five ejaculated sperm samples from normozoospermic fertile donors were evaluated as a control group. RESULTS: Both epididymal sperm samples showed normal FISH results for the parameters analysed when compared with those of the control group. FISH results were abnormal in 29% (two of seven) of testicular samples from OA patients and in 54% (seven of 13) of those from NOA patients, although this difference was not statistically significant. Testicular samples from OA patients showed a significant increase of disomy for sex chromosomes (P<0.01), whereas NOA patients displayed significantly higher rates of diploidy (P<0.0001) and disomy for chromosomes 13 (P<0.0001), 21 (P<0.001) and sex chromosomes (P<0.0001) than the control group. CONCLUSIONS: Testicular spermatozoa from azoospermic patients present increased rates of chromosomal abnormalities, mainly of the sex chromosomes, which are particularly high in NOA patients.

Adult↗
PubMed2004

Administration of low-dose LH induces ovulation and prevents vascular hyperpermeability and vascular endothelial growth factor expression in superovulated rats.

The administration, to rats, of a combination of pregnant mares serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) in high doses induces the ovarian hyperstimulation syndrome (OHSS) which is characterized by increased vascular permeability (VP) and simultaneous overexpression of vascular endothelial growth factor (VEGF) in ovarian cells. hCG has a longer half-life than LH and a greater biological activity, expressed in a higher incidence of complications such as OHSS. Similarly, FSH may also be related to the ovulatory changes within the follicle as there is a simultaneous surge in spontaneous cycles. The aim of this study was to compare the capacity of hCG, FSH and LH to induce ovulation and simultaneously prevent OHSS in the animal model. Immature female rats were treated with 10 IU PMSG for 4 days, and ovulation was triggered with saline, 10 IU hCG, 10 IU FSH, 10 IU LH or 60 IU LH. The number of oocytes ovulated into the tubes, VP and mRNA VEGF expression were evaluated and compared. All the hormones employed were as effective at triggering ovulation, with similar significant P values when compared with the control for which saline was used. The use of 10 IU LH resulted in significantly lower VP and VEGF expression than that seen in the groups treated with 10 IU hCG, 10 IU FSH or 60 IU LH. In conclusion, FSH and hCG, as well as a sixfold increase in LH, displayed similar biological activities, including increased VP due to excessive VEGF expression. The use of lower doses of LH produced similar rates of ovulation, while preventing the undesired changes in permeability. These experiments should therefore encourage clinicians to determine the optimal dose of LH to be employed in women in order to trigger ovulation and, at the same time, avoid the risk of OHSS.

Animals↗
PubMed2003

Administration of moderate and high doses of gonadotropins to female rats increases ovarian vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression that is associated to vascular hyperpermeability.

Convincing evidence supports the role of ovarian-origin vascular endothelial growth factor (VEGF) in inducing vascular permeability (VP) and ascites associated with ovarian hyperstimulation syndrome (OHSS) in mammals, including humans. A circulatory dysfunction has been described in every woman treated with gonadotropins for in vitro fertilization. It is not known, however, whether the action of gonadotropins also includes up-regulation of the VEGF receptor-2 (VEGFR-2) and whether increased VP is also found when milder stimulation is used. Thus, we applied an OHSS animal model to answer these questions. Immature female rats were stimulated with saline (control group) or with high (10 IU of eCG x 4 days + 30 IU hCG, OHSS group) or mild (10 IU of eCG + 10 IU of hCG, mild-stimulation group) doses of gonadotropins. The VP and the expression of whole-VEGF and VEGFR-2 mRNAs were analyzed through time-course experiments (0, 24, 48, and 96 h after hCG). Although eCG increased VP and the expression of VEGF and VEGFR-2 mRNAs in the ovaries of both mild- and OHSS-stimulated animals, hCG further augmented these parameters and produced the highest values after 48 h. A linear correlation was found between increased expression of VEGF and VEGFR-2 mRNAs and enhanced VP in both mild and OHSS groups. Immunohistochemistry showed the presence of VEGF and VEGFR-2 in the granulosa-lutein and endothelial cells of the entire corpus luteum. These studies confirm that in hyperstimulated animals as well as in mildly treated rats, VEGF and VEGFR-2 are overexpressed and associated with an increase in VP, which may be responsible for the accumulation of ascitic fluid in the syndrome.

Animals↗
PubMed2003

Impact of preimplantation genetic diagnosis on IVF outcome in implantation failure patients.

Implantation failure (IF) is defined as three or more failed IVF attempts, and preimplantation genetic diagnosis (PGD) is being used in these patients to improve IVF outcome. PGD was performed in 49 implantation failure patients with a mean number of 4.2 +/- 1.6 previous IVF failures, and in nine fertile controls. Fluorescence in-situ hybridization (FISH) on blastomeres from biopsied day 3 embryos was performed for chromosomes 13, 16, 18, 21, 22, X and Y. There was a significantly higher rate of chromosomal abnormalities (67.4%) compared with controls (36.3%). In 57 cycles, a pregnancy rate of 34.0% and an implantation rate of 19.8% was observed in implantation failure patients compared with controls (33.3 and 24.1% respectively), with all the pregnancies in the implantation failure group coming from the transfer of at least one chromosomally normal blastocyst on day 5. It is concluded that in IVF patients, use of PGD along with blastocyst transfer improves IVF outcome.

Adult↗
PubMed2003

Chromosomal abnormalities and embryo development in recurrent miscarriage couples.

BACKGROUND: Chromosomal abnormalities are an important cause of spontaneous abortion and recurrent miscarriage (RM). Therefore, we have analysed the incidence of chromosomal abnormalities and embryo development in patients with RM. METHODS: Preimplantation genetic diagnosis (PGD) was performed on 71 couples with RM and 28 couples undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in-situ hybridization. RESULTS: The implantation rate in RM patients was 28% and three patients (13%) miscarried. The percentage of abnormal embryos was significantly increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%). All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for chromosomes 16 and 22 were significantly higher (P < 0.01) in RM cases. In the RM population, euploid embryos reached the blastocyst stage more frequently than abnormal embryos (61.7 versus 24.9%; P < 0.0001). CONCLUSIONS: RM is associated with a higher incidence of chromosomally abnormal embryos, of which some are able to develop to the blastocyst stage. IVF plus PGD is an important step in the management of these couples, but the technique has to move towards a full chromosome analysis.

Abortion, Habitual↗
PubMed2003

Testicular sperm extraction (TESE) and ICSI in patients with permanent azoospermia after chemotherapy.

BACKGROUND: Patients persistently azoospermic after chemotherapy have been considered traditionally as sterile unless sperm was frozen before therapy. Recent advances during the last decade combining testicular sperm extraction (TESE) and ICSI in patients with non-obstructive azoospermia allow these males to father their own genetic offspring. METHODS: A retrospective study was conducted of 12 patients with non-obstructive azoospermia after chemotherapy undergoing TESE between 1995 and 2002. Cancer type and anti-neoplastic treatments were recorded, together with maximum testicular volume, serum FSH levels and testicular histopathology. When TESE was successful, spermatozoa were cryopreserved for performing ICSI later. RESULTS: In five patients (41.6%) motile spermatozoa for cryopreservation and ICSI were retrieved. Four of them had received chemotherapy for testicular cancer, and one had been treated by chemotherapy/radiotherapy for Hodgkin's disease. Clinical and histological parameters were unable to predict with certainty TESE outcome in an individual patient. Eight ICSI cycles were performed on five couples and one pregnancy was obtained which resulted in the delivery of a healthy girl. CONCLUSION: Some patients with permanent azoospermia after chemotherapy can be successfully treated by TESE-ICSI. This procedure, however, may have potential genetic risks. Therefore, freezing semen before starting gonadotoxic therapy is the strategy of choice, and patients should be counselled accordingly.

Adult↗