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Biomedical subjects

Carlos Simón

Publications and source records attributed to Carlos Simón.

At least 37 records · Page 2Linked to original sources
PubMed2004

Mifepristone is an effective oral alternative for the prevention of premature luteinizing hormone surges and/or premature luteinization in women undergoing controlled ovarian hyperstimulation for in vitro fertilization.

The present clinical study was conducted to investigate the effectiveness of a daily dose of 40 mg mifepristone in preventing premature LH surges in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and to study the effect of this antiprogestin cotreatment on endometrial receptivity. This was a prospective, open-label, randomized, exploratory study in 15 healthy volunteer oocyte donors who were randomly allocated to the experimental COH group, including mifepristone (group 1), or the control group, using a long protocol with GnRH agonists (group 2), in a ratio of 2:1, i.e. 10 and five subjects, respectively. In group 1, human chorionic gonadotropin (hCG) was randomly administered (group 1A) or was withheld (group 1B) at the end of stimulation, so that two subgroups of five subjects each were formed, differing in the final oocyte maturation trigger. In all patients receiving mifepristone, 50 mg progesterone were administered im at the time of hCG administration to counteract residual antiprogestogenic activity of mifepristone. Serum estradiol, progesterone (P), LH, and FSH levels were monitored in each patient on d 3 and 6 and every 48 h thereafter. Endometrial biopsies were taken 2 and 7 d after hCG or P administration. Endometrial tissue was processed and evaluated in a blinded fashion for endometrial dating and quantitative PCR of at least four genes known to be up-regulated in receptive endometrium. The total FSH dose and duration of treatment in the two arms of the study were similar. The mean LH levels on d 6 of stimulation and the day of hCG/P treatment in the mifepristone group were 0.8 +/- 0.7 and 0.5 +/- 0.6 mIU/ml, and those in control subjects were 2.4 +/- 3.8 and 2.0 +/- 1.7 mIU/ml, respectively. No LH surges were observed in any subject treated with mifepristone. Serum P levels on the day of hCG/P were below the cut-off level (1.2 ng/ml) in all subjects of the mifepristone group (range, <0.5 to 1.05 ng/ml). The mean numbers of cumulus-oocyte complexes retrieved were 11.6 +/- 6.6 and 19.6 +/- 11.8 in the subgroup treated with mifepristone and hCG and in the control group, respectively. The mean percentages of metaphase II, metaphase I, and germinal vesicle stage oocytes were 86.2, 6.9, and 3.4% in the mifepristone group and 68.4, 6.1, and 11.2% in the control group. In the mifepristone group that did not receive hCG and received P only at the end of stimulation, an endogenous LH surge was not observed nor were oocytes obtained. Histological evaluation of endometrial samples in patients treated with mifepristone and hCG (group 1A) confirmed normal development, whereas in patients treated with mifepristone only (group 1B), there was a complete arrest of the endometrial maturation. The expression patterns of glycodelin, IGF-binding protein-7, glutathione peroxidase-3, and solute carrier family 1 member 1 show a striking absence of up-regulation in patients treated with mifepristone (groups 1A and 1B) compared with controls (group 2). The results of this exploratory study provide evidence that mifepristone is effective for the prevention of premature LH surges and/or premature luteinization in women undergoing COH for in vitro fertilization. However, endometrial receptivity status requires additional evaluation after decreasing RU-486 doses before this strategy can be considered as a new alternative to GnRH agonist/antagonist treatment.

Administration, Oral↗
PubMed2004

Report of the results of a 2 year programme of sperm wash and ICSI treatment for human immunodeficiency virus and hepatitis C virus serodiscordant couples.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) serodiscordant couples with the male infected can be helped to have children minimizing the transmission risk. Our aim was to evaluate the results of our assisted reproduction programme for these couples and to develop adequate strategies for their management. METHODS: Members of serodiscordant couples: (i) HIV positive males attending our centre for sperm wash and assisted reproduction and (ii) HCV positive males needing assisted reproduction for infertility provided 134 semen samples for sperm wash. Before ICSI treatment, semen was confirmed to be negative for viral presence by reverse transcription and nested PCR after the sperm wash. RESULTS: Sperm washes were effective in 90% of the samples. Regardless of the type of infection, no differences were found in semen quality, embryos obtained and pregnancy rates (40-48% per cycle). To date, 41 pregnancies and 23 newborns were obtained. Fertilization rates were lower in HCV than in HIV serodiscordant couples (59.3+/-5.3% versus 72.0+/-8.1%), probably because they were infertile couples for whom we recommended sperm wash and PCR. No seroconversion was detected in the patients' follow-up. CONCLUSIONS: To date, sperm wash, nested PCR and ICSI is a safe and effective procedure that avoids HIV and HCV transmission with reasonable pregnancy rates, and is cost-effective.

Adult↗
PubMed2004

Relationship between standard semen parameters, calcium, cholesterol contents, and mitochondrial activity in ejaculated spermatozoa from fertile and infertile males.

PURPOSE: To correlate levels of cholesterol (CH), calcium (Ca2+), and mitochondrial activity (MA) with the standard semen parameters and to compare them between fertile and infertile men. METHODS: We studied 151 semen samples from infertile (n = 60) or fertile (n = 91) males. Basic sperm parameters were analyzed. Ca2+ and CH concentrations on seminal plasma were determined by enzymoimmunoanalysis. Intracellular Ca2+ and CH concentrations in the sperm plasma membrane and mitochondrial activity by fluorometry. RESULTS: There was a significant positive correlation between sperm membrane CH and sperm morphology. Intracellular Ca2+ was lower in infertile patients compared to fertile. No differences were found regarding Ca2+ and CH concentrations in seminal plasma. MA is directly and strongly related with sperm motility. CONCLUSIONS: Intracellular concentrations of Ca2+ and the proportion of CH in the sperm membrane are two important markers of the sperm quality due to its direct relationship with sperm morphology and fertility potential.

Calcium↗
PubMed2004

Comparison of two different starting multiple dose gonadotropin-releasing hormone antagonist protocols in a selected group of in vitro fertilization-embryo transfer patients.

OBJECTIVE: To compare the efficacy of two starting protocols of multiple dose GnRH antagonists (GnRH-a). DESIGN: Prospective randomized controlled study. SETTING: In vitro fertilization-embryo transfer program at the Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S): One hundred nine patients undergoing controlled ovarian hyperstimulation (COH) with recombinant gonadotropins and GnRH-a (0.25 mg/d). INTERVENTION(S): Patients started GnRH-a administration on stimulation day 6 (group 1) or when the leading follicle reached a mean diameter of 14 mm (group 2). MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates; serum E(2) and LH levels during ovarian stimulation; days of stimulation and GnRH-a administration. RESULT(S): Days needed for ovarian stimulation were similar in both groups but there was a significant difference when comparing days of GnRH-a administration. Serum E(2) and LH followed similar curves in both groups. Implantation and pregnancy rates were 23.7% and 44.4 % in group 1 and 28.6% and 50.9 % in group 2 (P=not significant [NS]). CONCLUSION(S): The efficacy of the two starting protocols of the multiple dose GnRH-a evaluated in this study is similar; however, this remark can only be drawn for a selected group of patients.

Adult↗
PubMed2004

Role of cholesterol, calcium, and mitochondrial activity in the susceptibility for cryodamage after a cycle of freezing and thawing.

OBJECTIVE: To correlate the levels of two concrete sperm markers, cholesterol and Ca(+2), together with mitochondrial activity on raw semen samples with the post-thaw recovery of spermatozoa with progressive motility on human sperm samples as the first step to improve sperm cryostorage protocols. DESIGN: Controlled prospective research project. SETTING: Private and university-affiliated setting. PATIENT(S): Semen samples from 122 males attending our center for infertility (n = 47) or semen donation (n = 75) were studied. INTERVENTION(S): The mean basic semen parameters of the 122 semen samples studied before and after the freezing and thawing process. MAIN OUTCOME MEASURE(S): We determined Ca(+2) and cholesterol concentrations on seminal plasma by enzymoimmunoanalysis techniques, intracellular Ca(+2) concentrations, cholesterol concentrations in the sperm plasma membrane and mitochondrial activity by fluorometry. RESULT(S): Cholesterol concentration in seminal plasma and cholesterol contents in the sperm membrane and mitochondrial activity were studied. No correlations were initially found to be of statistical significance. Regarding seminal plasma and intracellular sperm Ca(+2) concentrations, a statistically significant negative correlation was found (P=.036 and P=.016). CONCLUSION(S): Higher cholesterol contents do not appear to protect sperm against cryodamage. Conversely, Ca(+2) equilibrium appears to be essential for a good post-thaw recovery. Mitochondrial activity is not reflecting the possibilities of sperm survival and is probably not a good indicator of the sperm metabolism.

Calcium↗
PubMed2004

Relationship among standard semen parameters, glutathione peroxidase/glutathione reductase activity, and mRNA expression and reduced glutathione content in ejaculated spermatozoa from fertile and infertile men.

OBJECTIVE: To determine the expression and enzymatic activity of glutathione peroxidase (GPX)-1, GPX-4, and glutathione reductase together with glutathione (GSH) concentrations in spermatozoa from fertile and infertile men. DESIGN: Prospective study. SETTING: University-affiliated private center. PATIENT(S): Fifty-four infertile men undergoing assisted reproduction techniques and 55 fertile sperm donors with pregnancies and newborns by artificial insemination. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Analysis of gene expression by fluorescent quantitative polymerase chain reaction and an analysis of enzymatic activity and GSH concentration by controlled biochemical reactions and spectrophotometry. RESULT(S): GPX-4 activity but not mRNA expression is directly related to sperm morphology (strict criteria) and is more compromised with a low percentage of normal sperm. These differences are also demonstrated when fertile and infertile men were compared. In addition, intracellular GSH concentrations are lower when sperm morphology is severely impaired, but no differences were found between fertile and infertile men. CONCLUSION(S): Intracellular sperm GSH system components GPX-4 and GSH are altered in infertile men, and these alterations seem to be linked to sperm morphology.

Case-Control Studies↗
PubMed2004

Global gene expression profiling of human endometrial receptivity.

Scientific knowledge on the molecular changes that occur during the window of implantation is fundamental for the understanding of human reproduction. To gain a global molecular understanding of human endometrial receptivity, we have compared gene expression profiles of pre-receptive (day LH + 2) versus receptive (LH + 7) in well characterized human endometrial biopsies. The samples were analyzed using the Affymetrix HG-95A array, a high density oligonucleotide microarray comprising more than 12,000 genes. In this work, we present part of our results and a comparison with similar works published in the literature. Identified genes include not only genes previously documented to be involved in implantation but also genes for which a role in endometrial receptivity, or even endometrial expression, has not been previously described. Collectively, these studies identify new candidate markers that may be used to diagnose unequivocally the receptive endometrium.

Endometrium↗
PubMed2004

Embryonic chromosomal abnormalities obtained after rescue intracytoplasmic sperm injection of 1-day-old unfertilized oocytes.

PURPOSE: To study if second day intracytoplasmic sperm injection (ICSI) results in chromosomal abnormalities in the embryos. METHODS: Rescue ICSI was performed on 14 metaphase II (MII) oocytes after unsuccessful conventional IVF, four were fertilized. Fluorescent in situ hybridization (FISH) was performed on these four embryos and was informative for three. RESULTS: There were two tetraploid embryos, one mosaic embryo with trisomy 21, tetrasomy 18, and tetrasomy for sex chromosomes in one cell and trisomy 22 in another cell. CONCLUSIONS: We discourage the use of second day ICSI due to the observed increase in chromosomal abnormalities in these embryos.

Adult↗
PubMed2004

Gene expression pattern and immunoreactive protein localization of LGR7 receptor in human endometrium throughout the menstrual cycle.

Relaxin (RLX) is a pregnancy-associated polypeptide hormone. In non-pregnant women, the peak of circulating relaxin coincides with the window of endometrial receptivity and both in vivo and in vitro experiments showed that it plays a role in the decidualization process. Recently, two receptors, LGR7 and LGR8, have been identified as high affinity receptors for relaxin. Here we describe LGR7 mRNA and protein expression in human endometrium using semi-quantitative and quantitative fluorescent PCR (Q-PCR) and immunohistochemical analyses. Three different experimental designs were used. First, endometrial biopsies from five different phases of the menstrual cycle were analysed. Secondly, we assessed the early luteal phase in more detail. Finally we analysed the expression at LH+2 (2 days after the natural LH surge, pre-receptive endometrium) versus LH+7 (receptive endometrium) within the same menstrual cycle from the same patient to avoid inter-cycle or inter-person variations in gene expression. Our results indicate that there is no consistent regulation of LGR7 mRNA expression, neither during the menstrual cycle nor during the early-mid-luteal phase. In general, we observed a large degree of variation in LGR7 mRNA expression levels between patients. LGR7 immunoreactive protein was identified in all stages of the menstrual cycle. LGR7 protein was localized in both the epithelial and the stromal compartments, except for the mid-luteal phase when the expression was restricted to the endometrial epithelium. We conclude that no consistent regulation of LGR7 mRNA expression can be detected in human endometrium during the menstrual cycle.

Cell Line↗
PubMed2004

Determinants of endometrial receptivity.

Understanding the molecular changes that occur during the window of implantation is fundamental to our knowledge of human reproduction. Lately, the development of microarray technology has allowed this process to be studied from a global molecular perspective. In the last 2 years, researchers have focused their efforts on throwing light on the gene expression profile of the receptive endometrium. The genes hold the key to the development of the endometrium at any stage, and we have focused our work on the window of implantation. The four most recently published works in this field have revealed a long list of genes that are up- or downregulated at the time of implantation. Although these studies have been conducted using varying approaches, collectively these studies identify new candidate markers that can be used to accurately diagnose the receptive state of the endometrium. The next step is to perform functional analysis for confirming the importance of these genes. In this article, we gather together these recent findings to provide an overview of the current knowledge regarding the genetic functioning of human endometrial receptivity and related processes.

Embryo Implantation↗
PubMed2004

The leptin system during human endometrial receptivity and preimplantation development.

The leptin system is implicated in the regulation of body weight and reproductive function, acting at endocrine and paracrine levels. This ligand-receptor system is mandatory for embryonic implantation in rodents. Here, we investigate the expression pattern of total leptin receptor (OB-R(T)), the long form (OB-R(L)) and short isoforms HuB219.1 and HuB219.3 in the human endometrium. Furthermore, we studied leptin and OB-R(T) mRNA during human embryonic preimplantation development and the embryonic regulation of the endometrial OB-R(L). Leptin receptor expression and its isoforms increase in the luteal phase and peak in the late part. Leptin receptor was localized at the epithelial and glandular epithelium using in situ hybridization. Reverse transcription-nested PCR showed the presence of OB-R(T) mRNA at all the embryonic stages, whereas leptin mRNA was only detected at the blastocyst stage. The embryonic regulation of endometrial epithelial OB-R(L) and HuB219.3 was studied, and no impact was found. Finally, OB-R(L) was immunohistochemically localized in the human cytotrophoblast and maternal decidua. These findings suggest that secretory endometrium is a target tissue for leptin action, and oocytes and preimplantation embryos possess OB-R mRNA, indicating that leptin may be necessary for embryonic development. Furthermore, leptin mRNA is specifically expressed at the blastocysts stage, suggesting a function in the blastocyst-endometrial dialogue.

Adult↗
PubMed2003

Regulation of embryonic implantation.

The preimplantation embryo produces several factors during its development to signal its presence to the maternal organism. This paper will focus on the role of two distinctive cytokine and growth factor systems (interleukin-1 (IL-1) system and the vascular endothelial growth factor (VEGF) system) during early embryonic development and implantation. IL-1 receptor is expressed in the endometrium of various species and antagonising the biological effects of IL-1 leads to implantation failure in mice. We could show that this is due to an endometrial, not an embryonic effect. Furthermore, we could detect the expression of all components of the IL-1 system in preimplantation embryos from mice and humans. We could show a possible influence of IL-1 on other systems involved in embryonic implantation, including invasion (MMPs/TIMPs) and angiogenesis (VEGF), therefore suggesting a role of this cytokine family during early embryonic development. Immediately after contact to the endometrium, the embryo must induce angiogenesis to ensure its survival, VEGF is a potent angiogenetic growth factor. We have shown a cyclic regulation of the soluble VEGF-receptor, sflt, in human endometrium and have detected the expression of the transmembraneous VEGF-receptors, Flt-1 and kinase insert domain containing receptor (KDR) throughout the menstrual cycle. Furthermore, we have shown that the VEGF gene is one of the earliest genes activated during human preimplantation embryo development, giving rise to the assumption that VEGF is crucial for embryonic development.

Animals↗
PubMed2003

Transmembrane and truncated (SEC) isoforms of MUC1 in the human endometrium and Fallopian tube.

The cell surface mucin MUC1 is expressed by endometrial epithelial cells with increased abundance in the secretory phase of the menstrual cycle, when it is found both at the apical cell surface and in secretions. This suggests the presence of a maternal cell surface glycoprotein barrier to embryo implantation, arising from the anti-adhesive property of MUC1. In previous work, we demonstrated alternatively spliced MUC1 variant forms in tumour cells. The variant MUC1/SEC lacks the transmembrane and cytoplasmic sequences found in the full-length variant. We now show that MUC1/SEC mRNA is present in endometrial carcinoma cell lines, endometrial tissue and primary cultured endometrial epithelial cells. The protein can be detected using isoform-specific antibodies in uterine flushings, suggesting release from endometrium in vivo. However, on the basis of immunolocalisation studies, MUC1/SEC also remains associated with the apical epithelial surface both in tissue and in cultured cells. Transmembrane MUC1 and MUC1/SEC are both strikingly localised to the apical surface of tubal epithelium. Thus MUC1 may contribute to the anti-adhesive character of the tubal surface, inhibiting ectopic implantation. The mechanism by which this barrier is overcome in endometrium at implantation is the subject of ongoing investigation.

Carcinoma↗
PubMed2003

Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome.

OBJECTIVE: To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. DESIGN: Prospective observational study. SETTING: In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. PATIENT(S): Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. INTERVENTION(S): Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. MAIN OUTCOME MEASURE(S): Cycles were grouped according to serum P level on the day of hCG administration (<1.2 ng/mL or > or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. RESULT(S): The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. CONCLUSION(S): Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.

Adolescent↗
PubMed2003

Obesity and the risk of spontaneous abortion after oocyte donation.

OBJECTIVE: To determine whether obesity increases the risk of spontaneous abortion. DESIGN: Retrospective study. SETTING: Oocyte donation program at the Instituto Valenciano de Infertilidad in Spain. PATIENT(S): Seven hundred twelve cycles of recipients of ovum donation with known body mass index (BMI), good-quality embryo transfer, and absence of uterine pathology or clinical history of antiphospholipid antibodies or recurrent abortion. INTERVENTION(S): Recipients were divided in four BMI (kg/m(2)) groups: lean, with BMI <20 (n = 92; 12.9%); normal, with BMI = 20-24.9 (n = 398; 55.9%); overweight, with BMI = 25-29.9 (n = 172; 24.2%); and obese, with BMI >/=30 (n = 50; 7%). Clinical parameters were compared among the groups. MAIN OUTCOME MEASURE(S): Spontaneous abortion rates according to BMI. RESULT(S): No difference was found among the four BMI groups in any of the parameters of the cycle analyzed. The overall abortion rate was 15.8% (57 of 360). There were significant differences in abortion rates between the obese (38.1%), and the normal (13.3%) and overweight (15.5%) groups. When several cutoff BMI values were established (20, 25, and 30), only the obese women demonstrated a greater risk of abortion. Compared with the normal population, the obese group showed a significant fourfold increase in the risk of spontaneous abortion. CONCLUSION(S): Our findings confirm that obesity (BMI >/=30) is an independent risk factor for spontaneous abortion. Therefore, it would be advisable for obese patients to reduce weight before becoming pregnant.

Abortion, Spontaneous↗
PubMed2003

Factors that determine discordant outcome from shared oocytes.

OBJECTIVE: To investigate the factors that may be related to pregnancy in oocyte recipients who shared oocytes from the same donor and showed discordant pregnancy outcome. DESIGN: Matched pair analysis. SETTING: IVF academic center. PATIENT(S): Five hundred forty-two oocyte donation cycles that shared oocytes from 197 donors with discordant outcome. INTERVENTION(S): Egg donation and embryo transfer. MAIN OUTCOME MEASURE(S): Pregnancy rate and implantation rate. RESULT(S): Three hundred sixty-five matched-paired discordant outcome oocyte recipients were analyzed. Pregnant and nonpregnant recipients were similar in terms of age, serum E(2) levels, endometrial thickness, indications for oocyte donation, and abnormal sperm parameters. No differences were found in the number of oocytes received per patient, fertilization rate, IVF/intracytoplasmic sperm injection (ICSI) distribution, embryo quality, or on embryo transfer difficulty. CONCLUSION(S): Discordant pregnancy outcome could not be explained by the different egg recipients and cycle factors studied. In addition to chance, other factors must be investigated that could explain discordant outcome in egg recipients sharing oocytes from single donors.

Adult↗