Biomedical subjects

C Simón

Publications and source records attributed to C Simón.

At least 91 records · Page 5Linked to original sources

PubMed1998

FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy wastage.

PURPOSE: Our purpose was to detect aneuploidy for chromosomes 13, 16, 18, 21, 22, X, and Y in preimplantation embryos from patients with a history of unexplained recurrent miscarriage. METHODS: Three patients with a history of unexplained recurrent spontaneous abortion were included in this study. Embryos were biopsied at the eight-cell stage, individually fixed on slides, and processed for fluorescent in situ hybridization (FISH). A multiple FISH protocol for seven chromosomes pairs (13, 16, 18, 21, 22, X, and Y) has been developed. RESULTS: A total of 39 embryos was studied with the multiple FISH protocol developed. Successful analysis of the biopsied embryos was achieved within the time limits usually allowed in a preimplantation diagnosis program. Analysis of the blastomeres showed that 17 embryos were chromosomally normal for the probes used, 16 embryos were aneuploid, and in 6 embryos no informative results were obtained. CONCLUSIONS: In the patients studied, a large proportion of embryos (41%) exhibited chromosomal abnormalities for the probes used. Preimplantation diagnosis to screen for chromosome abnormalities could be a feasible approach to improve the possibility of successful pregnancy in these couples.

Abortion, Habitual↗

PubMed1998

Increased chromosome abnormalities in human preimplantation embryos after in-vitro fertilization in patients with recurrent miscarriage.

Recurrent miscarriage is a pathological condition induced by maternal and embryonic causes. This paper describes a prospective study to determine the real incidence of aneuploidy for autosomes 13, 16, 18, 21, 22, and gonosomes in preimplantation human embryos obtained from patients with recurrent pregnancy loss after ovarian stimulation in an IVF-ET programme. Our results indicate that aneuploidy for the chromosomes analysed are abnormally higher in embryos obtained after IVF from recurrent abortion patients (58%) compared to non-recurrent abortion patients undergoing IVF. Furthermore, monosomies are six times more frequent than trisomies (47:8) in preimplantation embryos from recurrent abortion patients. Based on the present study, preimplantation genetic diagnosis (PGD) of embryos obtained from patients with recurrent miscarriage could prove advantageous in diagnosing abnormal embryos and selecting normal embryos for transfer.

Abortion, Habitual↗

PubMed1998

The use of long- and short-acting forms of gonadotrophin-releasing hormone analogues in women undergoing oocyte donation.

Evidence accumulated in in-vitro fertilization (IVF) cycles suggests that the use of long-acting forms of gonadotrophin-releasing hormone analogues (GnRHa) for pituitary desensitization may impair the outcome of IVF as compared to classical short-acting formulations. Whether the negative effects are directed against the corpus luteum, the endometrium, or both is unknown. However, the presence of high affinity binding sites for gonadotrophin-releasing hormone (GnRH) in the human endometrium suggests a possible role of these analogues on this target organ, affecting embryo implantation. In the present study, we tested direct effects of two different forms of GnRHa on implantation using the ovum donation model. Patients were prospectively allocated to one of the three study groups: the short-acting form of the analogue leuprolide acetate (group I; n=64), the long-acting form of the same analogue (group II; n=58), and the long-acting preparation of the analogue tryptorelin (group III; n=61). A total of 68 cycles of embryo transfer was carried out in group I, whereas 67 were performed in group II and 65 in group III. Cancellation rates were respectively 18.1, 17.3 and 18.8% because of bleeding while being on the waiting list for anonymous oocyte donation. The number of oocytes donated, fertilization rates and embryos replaced in each group were similar. As a result, pregnancy rate per transfer was 38.2, 49.3 and 44.6% respectively. Implantation rates per embryo replaced were respectively 13.4, 19.1 and 17.0%. These data suggest that the use of a long-acting form of GnRHa provides success rates similar to the short-acting preparations, resulting in more convenient medication for patients with ovarian function included in ovum donation programmes.

Adult↗

PubMed1998

Luteal leukocytes are modulators of the steroidogenic process of human mid-luteal cells.

Flow cytometry analysis of luteal cells revealed that an important proportion of these cells are leukocytes. The percentage of leukocytes was higher in the early (42 +/- 4) and late (35 +/- 3) luteal phases than in the mid-luteal (24 +/- 2) phase. However, the proportion of macrophages did not differ between the luteal stages. The flow cytometric properties correlated with cellular size and granularity were not reliable as discriminators of luteal cell subpopulations. Therefore, to assess the contribution of luteal leukocytes, these cells were completely removed from luteal cell suspensions (total cells), by a negative selection procedure (immunomagnetic separation). The functional role of leukocytes in mid-luteal steroidogenesis was assessed, in total as well as leukocyte-depleted cells. Progesterone production was found to have increased 2.2-fold in leukocyte-depleted cell cultures, in comparison with total cells under basal conditions. However, the response to human chorionic gonadotrophin (HCG) was 36% lower under the latter conditions. Oestradiol production was not significantly modified under basal or HCG-treated conditions. In leukocyte-depleted cells, the concentration of interleukin (IL)-1beta decreased 5-fold in comparison with total cell cultures, suggesting that leukocytes are the principal source of IL-1beta. In summary, the results of the present investigation suggest functional interactions between the immune system and steroidogenic cells of the human corpus luteum.

Adult↗

PubMed1998

Intracytoplasmic sperm injection as a routine indication in low responder patients.

The aim of this study was to determine if a low response to gonadotrophin stimulation could be considered as an indication for intracytoplasmic sperm injection (ICSI). This prospective study included a total of 96 non-male infertile couples with six or fewer retrieved oocytes, who underwent 104 in-vitro fertilization (IVF) cycles between January 1996 and April 1997. They were randomly divided into two groups for fertilization, one by IVF and the other by ICSI. Groups were compared in terms of fertilization rates, fertilization failure, embryo quality, embryos transferred and reproductive outcome. ICSI provided similar fertilization rates per inseminated oocyte (77.7 versus 70.2%) and per obtained oocyte (56.5 versus 58.8%) as IVF. Furthermore, equal numbers (2.2 versus 2.5) and quality of embryos were obtained and comparable pregnancy (21.1 versus 17.3%) and implantation (14.0 versus 11.1%) rates. Neither the number of retrieved oocytes, nor patient age was relevant for the fertilization rates obtained with both techniques. The number of cases with complete fertilization failure was similar in both procedures. We conclude that the technique of fertilization is not related to the reproductive outcome of low responders, and the routine use of ICSI is not indicated.

Adult↗

PubMed1998

Expression of interleukin-1 system mRNA in single blastomeres from human preimplantation embryos.

Gathering knowledge about the molecular events during preimplantation development is one of the most important challenges in in-vitro fertilization (IVF). The interleukin-1 (IL-1) system has been shown to be intimately involved in embryonic implantation. The aim of our study was to detect the major components of the IL-1 system in single blastomeres from human preimplantation embryos and to relate our findings to the further development of the biopsied embryos in vitro. Single blastomeres were removed from morphologically normal embryos obtained from dipronuclear zygotes and examined by reverse transcription (RT)-nested polymerase chain reaction (PCR). Expression of beta-actin (external standard), IL-1beta, IL-1 receptor antagonist (IL-1ra) and IL-1 receptor (IL-1R) type I mRNA were related to embryonic development and IVF outcome. Blastomeres from 12 embryos were examined: beta-actin and IL-1R type I mRNA were detected in all blastomeres (100%) whereas IL-1beta could be detected in only nine of the blastomeres (75%). IL-1ra was expressed in only two (17%) of the blastomeres and those were simultaneously positive for IL-1beta. Both IL-1ra positive embryos were arrested in development before reaching blastocyst stage. Five embryos (three of them IL-1beta mRNA positive and two IL-1beta mRNA negative) were transferred as blastocysts; none of the transfers resulted in a pregnancy. We postulate that embryos expressing IL-1ra mRNA in a detectable amount appear more likely to be arrested in early developmental stages.

Base Sequence↗

PubMed1998

Molecular interactions between embryo and uterus in the adhesion phase of human implantation.

Molecular interactions at the embryo-maternal interface at the time of implantation is an exciting field demanding a wide effort in order to understand the crucial process of embryonic implantation. The objective of the present work is to demonstrate the existence of a specific communication pathway (at the molecular level) between embryo and endometrium in the adhesion phase of human embryonic implantation. This pathway of molecular interactions is apparently initiated by the endometrium in the presence of an implanting blastocyst. It is mediated through the embryonic interleukin 0(IL)-1-alpha + IL-1-beta, and the target is the endometrial epithelial beta-3 integrin subunit. If the relevance of beta-3 is accepted as a marker of uterine receptively, these observations may imply that the normal hormonally-regulated human endometrium is the trigger of molecular events preparing the blastocyst to efficiently communicate and regulate endometrial adhesion molecules in order to implant.

Antigens, CD↗

PubMed1998

MUC1 and endometrial receptivity.

Mucins, best known as the major constituent of mucus, are a family of highly glycosylated, high molecular weight (> or = 200 kDa) glycoproteins present on the surface of human epithelial cells. MUC1 has the features of an integral membrane protein. It has an extracellular tandem repeat domain that forms the major part of the core protein, and results in a highly repetitive structure, which is extremely immunogenic. In the protein there is also a proteolytic cleavage site reported in the proximal extracellular domain. The secreted form of MUC1 lacks the cytoplasmic tail, but it is not clear whether this results from alternative splicing or proteolysis and release of the free extracellular domain. The locus of the MUC1 gene is on band 21 of the long arm of chromosome 1 (1q21). Anti-adhesion properties of this mucin are probably the result of the unique structure of the molecule. In mouse uterine epithelium, the homologue MUC1 is regulated with reduced expression in the implantation period, but in humans, expression is high during the peri-implantation period. MUC1 may inhibit the interaction between trophoblast and apical epithelium adhesion molecules at the time of implantation, giving the possibility of forming a uterine barrier for implantation.

Animals↗

PubMed1998

Expression of interleukin-1 system genes in human gametes.

There is considerable evidence that the interleukin-1 (IL-1) system plays an important role in ovarian and testicular physiology, implantation, and other reproductive events. Human embryos express IL-1beta, IL-1 receptor type I (IL-1RtI), and IL-1 receptor antagonist (IL-1RA) at both the mRNA and protein levels. The presence of IL-1alpha and IL-1beta in oocyte-conditioned media and on the surface of human oocytes suggests that these cells may also produce this cytokine; however, whether the IL-1 system gene products are present as stable mRNAs in human gametes (oocytes and spermatozoa) has not yet been demonstrated. We used stringent cell separation techniques combined with reverse transcription-polymerase chain reaction to investigate the expression of various IL-1 system genes (IL-1alpha, IL-1beta, IL-1RtI, and IL-1RA) in human gametes and cumulus cells. Our results indicate that freshly isolated cumulus cells express all these IL-1 system components. On the other hand, IL-1alpha, IL-1beta, and IL-1RtI mRNAs were not found in either unfertilized or fertilized human oocytes, and a very few metaphase II human oocytes had transcripts for either secreted (10%) or intracellular (17%) IL-1RA. Mature spermatozoa did not contain mRNA for any of the of the IL-1 system components. The absence of informational RNA for the IL-1 system components in human unfertilized and polyploid oocytes and fresh immature oocytes suggests that maternal transcripts for these genes do not contribute to early embryo development. The presence of IL-1 components at the protein level in human oocytes may be due to binding of IL-1 produced by cumulus cells or other cell types, or to prior intrafollicle transcription and translation. Likewise, IL-1 system components do not appear to have a physiological role in mature spermatozoa since none of these components are present at the mRNA or protein levels, and important functional parameters such as motility and acrosome reaction appear not to be affected by IL-1beta in vitro. However, the abundant expression of IL-1alpha, IL-1beta, the IL-1RtI, and its antagonist IL-1RA by human cumulus cells provides further evidence that the IL-1 system plays a role in human ovarian physiology.

Female↗

PubMed1998

Single blastomeres within human preimplantation embryos express different amounts of messenger ribonucleic acid for beta-actin and interleukin-1 receptor type I.

Gaining knowledge about the physiological timetable of gene expression during preimplantation embryo development is crucial, and a better understanding of cytokine and growth factor expression in early embryonic development could lead to improved in vitro culture conditions and enhance in vitro fertilization implantation rates. Our aim was to detect the patterns and levels of two messenger ribonucleic acids [mRNAs; beta-actin and interleukin-1 receptor type I (IL-1R tI)] in single human blastomeres by RT-nested PCR and to compare possible variations in the gene expression both between different embryos and in multiple blastomeres within the same embryo. Single blastomeres from nine human tripronucleic preimplantation embryos were examined by one round of RT and two rounds of nested competitive PCR. Beta-actin mRNA was detected in each blastomere, and IL-1R tI mRNA was found in 72% of the blastomeres examined. Beta-actin was expressed at a level of 511-12185 molecules of complementary DNA/blastomere, and IL-1R tI was expressed at a level of 2-290 molecules of complementary DNA/blastomere. Our results suggest that the mRNA pattern of an embryo cannot be reliably quantitated from the mRNA pattern of a single blastomere and therefore imply limitations for the use of this method for preimplantation diagnosis.

Actins↗

PubMed1997

Oocyte quality in polycystic ovaries revisited: identification of a particular subgroup of women.

PURPOSE: Our purpose was to assess the endocrine status of women with polycystic ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine markers of the syndrome, in an attempt to define a subpopulation with poor quality oocytes. METHODS: This was a retrospective study. Patients were first endocrinologically analyzed: serum levels of androgens (T, androstenedione, DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose tolerance test (OGTT) were recorded and are expressed as absolute values and area under the curve (AUC). Subsequently, they were followed over a 2-year period in which patients underwent several attempts of IVF as well as serving as oocyte donors. Patients were divided into three groups: group I (n = 4) was women who displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles in which they served as donors; group II (n = 16) was PCO patients in whom IVF (n = 38) and/or oocyte donation cycles (n = 42) resulted in pregnancies; and group III (n = 13) was IVF patients with normal appearance of the ovaries by ultrasound. The endocrine status was compared with the IVF results. RESULTS: There was no difference among groups in the endocrinological parameters tested, except for the OGTT which identified women in group I as having higher serum glucose and insulin levels than patients in groups II and III. Similarly, the OGTT showed higher serum glucose values in group II compared to group III. Women in group I were also obese. Patients in group III were older than PCO patients and needed more gonadotropins to reach an ovarian response which resulted in a reduced number of oocytes retrieved. Fertilization was also impaired in group I, in which no pregnancy was recorded. CONCLUSIONS: This study shows that there is a particular subgroup of PCO patients with lower fertilization rates and embryos unable to implant. These patients are obese and nonhyperandrogenic and show derangements of insulin secretion.

Adult↗

PubMed1997

Pregnancy and birth rates after oocyte donation.

OBJECTIVE: To determine accumulated conception and live birth rates in ovum donation. DESIGN: Retrospective study from a computer database. Pregnancies with one gestational sac observed by ultrasound have been included as conceptional cycles and pregnancies that resulted in one live child were recorded for the analysis of the live birth rates. Life table analysis was applied. SETTING: Oocyte donation program at the Instituto Valenciano de Infertilidad. PATIENT(S): Three hundred ninety-seven recipients undergoing a total of 627 ETs were analyzed. INTERVENTION(S): Ovarian stimulation and ovum pick-up in donors. Uterine ET in recipients after appropriate exogenous steroid replacement. MAIN OUTCOME MEASUREMENT(S): Accumulated and estimated (95% confidence intervals [CI]) conception and live birth rates in the oocyte donation program as well as considering age and cause of infertility of the recipients. RESULT(S): Pregnancy rate after one cycle was 53.4% (CI 50.9% to 55.9%), with a delivery rate of 42.6% (CI 40.1% to 45.1%). Accumulated pregnancy rate increased up to 94.8% (CI 90.6% to 99.0%) after four transfers. Similarly, live birth rates reached 88.7% (CI 88.1% to 89.3%) after four attempts of ET by ovum donation. Cycle fecundity rates were maintained at approximately 50% after each attempt. Implantation rate was 18.3% (430/2,340 replaced embryos). Age and cause of entering the program did not influence the overall results of ovum donation. CONCLUSION(S): Oocyte donation is a successful treatment modality for infertile couples that offers even higher success rates than natural conception. No difference in cumulative pregnancy rate was observed regardless of recipient age, indication for oocyte donation, or number of cycles attempted.

Adult↗

PubMed1997

The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.

OBJECTIVE: To determine an optimal insemination technique in patients undergoing IVF after failed IUI and the role of intracytoplasmic sperm injection (ICSI) in such cases. DESIGN: Prospective, randomized study in couples with unexplained infertility (n = 63) and mild endometriosis (n = 7) undergoing IVF after four IUI cycles. Sibling oocytes were randomized into standard IVF or ICSI insemination according to the order of retrieval. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Italy. PATIENT(S): Seventy couples with unexplained infertility undergoing IVF after failing to conceive with controlled ovarian stimulation and IUI. INTERVENTION(S): In vitro fertilization and ICSI. MAIN OUTCOME MEASURE(S): Fertilization, cleavage, and embryo quality were compared in IVF- and ICSI-inseminated oocytes. RESULT(S): There was no significant difference in fertilization rates between ICSI (60.4%) and conventional IVF (54.0%). Similarly, there was no difference in embryo quality between both groups. There was no total fertilization failure in ICSI-inseminated oocytes, whereas 8 (11.4%) of 70 cases showed absence of fertilization when conventional IVF was used. CONCLUSION(S): Couples with unexplained infertility and mild endometriosis failing to conceive with IUI and undergoing IVF have an 11.4% chance of fertilization failure that can be overcome easily by using ICSI in at least some oocytes. ICSI, however, is not superior to IVF as an insemination technique in most cases. These data should be used in counseling patients.

Adult↗

PubMed1997

Effect of disruption versus continuation of gonadotrophin-releasing agonist after human chorionic gonadotrophin administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization.

Previous studies have described the luteolytic effect of gonadotrophin-releasing hormone agonist (GnRHa) administered in the early luteal phase. The present work was undertaken to compare in a prospective and randomized design the effect of disruption versus continuation of daily GnRHa after human chorionic gonadotrophin (HCG) administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization (IVF). Two different studies were designed and a total of 38 ovum donors, aged 23-30 years, were included. In the first study, the effect of GnRHa on the early luteal phase of IVF-stimulated cycles was investigated (n = 27); the patients were divided into two groups, according to whether they stopped (n = 13) or continued with daily GnRHa injections (n = 14) for an additional period of 15 days after HCG administration. Blood was drawn from luteal phase days 2 to 6 (day 0 = day of HCG administration) and oestradiol and progesterone concentrations were analysed. The second study focused on the effects of continuation versus disruption of GnRHa administration in the mid-late luteal phase. A similar design was employed including six patients who stopped GnRH on day 0 and five other women who continued GnRHa for 15 days after HCG administration. In this second study, blood was drawn from days 5 to 11 and oestradiol, progesterone and luteinizing hormone (LH) concentrations were analysed. IVF parameters were similar in both groups. The results indicate that continuous GnRHa administration, after HCG injection, does not produce changes in oestradiol, progesterone and LH concentrations in the early, mid- and late luteal phases compared to those patients in whom GnRHa is discontinued at the day of HCG administration. The present work demonstrates that, when ovulation induction is performed, the corpus luteum is driven primarily by the HCG, regardless of the administration or disruption of GnRHa in the luteal phase. This suggests that the lack of differences between continuation versus disruption of GnRHa may be due to the accumulation of the product over the previous 2-3 weeks of treatment.

Adult↗

PubMed1997

Endometrial thickness and serum oestradiol concentrations as predictors of outcome in oocyte donation.

Adequate endometrial preparation with exogenous steroids is mandatory for successful ovum donation. This study was undertaken to assess the value of endometrial thickness by ultrasound and serum oestradiol as predictors of ovum donation outcome and to analyse the correlation between serum oestradiol concentrations and the endometrial thickness. Endometrial thickness and serum oestradiol concentrations on the day of oocyte donation were recorded and compared to several in-vitro fertilization parameters. The cycles (n = 465) were classified according to serum oestradiol values and endometrial thickness. Comparison of the groups showed that endometrial thickness was significantly (P = 0.002) higher when serum oestradiol was >400 pg/ml as compared to <100 pg/ml. Pregnancy and implantation rates did not differ among the groups, women with serum oestradiol <50 pg/ml having similar outcome to the remaining cases. Endometrial thickness showed a similar picture in terms of pregnancy and implantation. Also, women with an endometrium <4 mm in size had normal pregnancy and implantation rates. There was a positive correlation (P = 0.0044) between endometrial thickness and implantation, as well as between endometrial thickness and serum oestradiol (P = 0.0184). None of the parameters examined was able to predict ovum donation outcome. It is concluded that endometrial thickness is preferred to serum oestradiol for the monitoring of endometrial development, although neither is able to predict success in oocyte donation.

Adult↗

PubMed1997

Reproductive impact of congenital Müllerian anomalies.

This retrospective longitudinal study was undertaken in order to determine the incidence and reproductive impact of uterine malformations on women desiring to conceive during their reproductive years. A total of 3181 patients in whom the morphology of the uterus was ascertained by hysterosalpingography (HSG) and laparoscopy/laparotomy during the years 1980-1995 was included in the study. The population analysed included fertile, infertile and sterile patients. The overall frequency of uterine malformations was 4.0%. Infertile patients (6.3%) had a significantly (P < 0.05) higher incidence of Müllerian anomalies, in comparison with fertile (3.8%) and sterile (2.4%) women. Septate (33.6%) and arcuate (32.8%) uteri were the most common malformations observed. Each malformation was individually analysed in fertile and infertile patients, in order to ascertain its actual reproductive impact. The performance of the unicornuate and didelphys uteri was similar with a chance of having a living child of 37-40%. The reproductive potential of the bicornuate uterus showed a live birth rate of 62.5% and the septate uterus showed a live birth rate of 62%. In all these abnormalities, early miscarriages (25-38%) and preterm deliveries (25-47%) were quite common. The arcuate uterus presented a live birth rate of 82.7%. It is concluded that uterine anomalies are relatively frequent in fertile women, and more frequent in infertile patients. Nevertheless, fertile patients with normal reproductive performance do exist, and Müllerian defects can permit an absolutely normal obstetric outcome. The reproductive performance of the unicornuate and didelphys uteri was poor, while that of the septate and bicornuate uteri was better than expected. The arcuate uterus had no impact on reproduction.

Abortion, Spontaneous↗

PubMed1997

The impact of endometriosis in couples undergoing intracytoplasmic sperm injection because of male infertility.

To assess the impact of endometriosis on intracytoplasmic sperm injection (ICSI) outcome, we have retrospectively evaluated 980 ICSI cycles, comparing the results of women with and without endometriosis. A total of 101 cycles was identified in which various degrees of endometriosis were involved, and in the remaining 879 cycles, male infertility was the only cause of infertility. Ejaculated spermatozoa were microinjected in all cycles. There was a significant reduction (P = 0.004) in the number of oocytes retrieved from women with endometriosis as compared to those without endometriosis. However, there were no significant differences in either fertilization or pregnancy and implantation rates between women with or without endometriosis. We conclude that the presence of endometriosis in patients undergoing ICSI because of severe male infertility does not affect fertilization, pregnancy and implantation rates, although significantly fewer oocytes are retrieved from patients with endometriosis.

Adult↗

PubMed1997

Accidental exposure to daily long-acting gonadotrophin-releasing hormone analogue administration and pregnancy in an in-vitro fertilization cycle.

A case of successful pregnancy in an in-vitro fertilization cycle, in spite of an accidental exposure to daily long-acting gonadotrophin-releasing hormone analogue administration, is reported. The patient underwent two intracytoplasmic sperm injection cycles with thawed epididymal spermatozoa, in which, due to a pharmacist's mistake, ovarian stimulation was carried out by a combination of long-acting gonadotrophin-releasing hormone agonist (leuprolide depot) and gonadotrophins. A successful singleton pregnancy was achieved after intrauterine embryo transfer with the birth of a healthy boy after 38 weeks. We describe the circumstances and results of this clinical case, as well as reviewing the literature.

Adult↗