Instituto Bernabeu of Fertility and Gynecology

Alicante, Spain

Instituto Bernabeu of Fertility and Gynecology

Alicante, Spain
SEARCH FILTERS
Time filter
Source Type

Lledo B.,IB Biotech. | Ortiz J.A.,IB Biotech. | Morales R.,IB Biotech. | Manchon I.,Instituto Bernabeu of Fertility and Gynecology | And 3 more authors.
Human Fertility | Year: 2013

Complex chromosomal rearrangements (CCRs) are structural aberrations involving more than two chromosomes which rarely appear in individuals with normal phenotypes. These individuals report fertility problems, recurrent miscarriages, or congenital anomalies in newborn offspring as a consequence of either meiotic failure or imbalanced chromosome segregation. A CCR involving chromosomes 5, 15, and 18 was discovered in a phenotypically normal man through a fetus with congenital malformations and partial trisomy of chromosome 15 and monosomy of chromosome 5. Ultrasound examination at 20 weeks of gestation showed severe oligoamnios and hydrothorax. Prenatal cytogenetic analysis and array comparative genomic hybridization (array-CGH) revealed a female fetus with dup15q26.3 and del5p15.33. We diagnosed the CCR using three-color fluorescence in situ hybridization (three-color FISH), and a balanced CCR using array-CGH and FISH was diagnosed in the paternal karyotype. The father is a carrier of a balanced translocation 46,XY,t(5;15;18)(p15.31;q26.3;p11.2). Due to the complexity of these rearrangements the diagnosis is difficult and the reproductive outcome uncertain. Reporting such rare cases is important to enable such information to be used for genetic counseling in similar situations and help estimate the risk of miscarriage or of newborns with congenital abnormalities. © 2013 The British Fertility Society.


Gomez-Torres M.J.,University of Alicante | Garcia E.M.,University of Alicante | Garcia E.M.,Instituto Bernabeu of Fertility and Gynecology | Guerrero J.,Instituto Bernabeu of Fertility and Gynecology | And 10 more authors.
Reproductive Biology and Endocrinology | Year: 2015

Background: Fertilization is a key physiological process for the preservation of the species. Consequently, different mechanisms affecting the sperm and the oocyte have been developed to ensure a successful fertilization. Thus, sperm acrosome reaction is necessary for the egg coat penetration and sperm-oolema fusion. Several molecules are able to induce the sperm acrosome reaction; however, this process should be produced coordinately in time and in the space to allow the success of fertilization between gametes. The goal of this study was to analyze the metabolites secreted by cumulus-oocyte-complex (COC) to find out new components that could contribute to the induction of the human sperm acrosome reaction and other physiological processes at the time of gamete interaction and fertilization. Methods: For the metabolomic analysis, eighteen aliquots of medium were used in each group, containing: a) only COC before insemination and after 3 h of incubation; b) COC and capacitated spermatozoa after insemination and incubated for 16-20 hours; c) only capacitated sperm after 16-20 h in culture and d) only fertilization medium as control. Six patients undergoing assisted reproduction whose male partners provided normozoospermic samples were included in the study. Seventy-two COC were inseminated. Results: The metabolites identified were monoacylglycerol (MAG), lysophosphatidylcholine (LPC) and phytosphingosine (PHS). Analysis by PCR and in silico of the gene expression strongly suggests that the cumulus cells contribute to the formation of the PHS and LPC. Conclusions: LPC and PHS are secreted by cumulus cells during in vitro fertilization and they could be involved in the induction of human acrosome reaction (AR). The identification of new molecules with a paracrine effect on oocytes, cumulus cells and spermatozoa will provide a better understanding of gamete interaction. © 2015 Gómez-Torres et al.


PubMed | University of Alicante, University of Zaragoza, Instituto Bernabeu of Fertility and Gynecology, University of Murcia and CSIC - Center of Edafology and Applied Biology of the Segura
Type: | Journal: Reproductive biology and endocrinology : RB&E | Year: 2015

Fertilization is a key physiological process for the preservation of the species. Consequently, different mechanisms affecting the sperm and the oocyte have been developed to ensure a successful fertilization. Thus, sperm acrosome reaction is necessary for the egg coat penetration and sperm-oolema fusion. Several molecules are able to induce the sperm acrosome reaction; however, this process should be produced coordinately in time and in the space to allow the success of fertilization between gametes. The goal of this study was to analyze the metabolites secreted by cumulus-oocyte-complex (COC) to find out new components that could contribute to the induction of the human sperm acrosome reaction and other physiological processes at the time of gamete interaction and fertilization.For the metabolomic analysis, eighteen aliquots of medium were used in each group, containing: a) only COC before insemination and after 3 h of incubation; b) COC and capacitated spermatozoa after insemination and incubated for 16-20 hours; c) only capacitated sperm after 16-20 h in culture and d) only fertilization medium as control. Six patients undergoing assisted reproduction whose male partners provided normozoospermic samples were included in the study. Seventy-two COC were inseminated.The metabolites identified were monoacylglycerol (MAG), lysophosphatidylcholine (LPC) and phytosphingosine (PHS). Analysis by PCR and in silico of the gene expression strongly suggests that the cumulus cells contribute to the formation of the PHS and LPC.LPC and PHS are secreted by cumulus cells during in vitro fertilization and they could be involved in the induction of human acrosome reaction (AR). The identification of new molecules with a paracrine effect on oocytes, cumulus cells and spermatozoa will provide a better understanding of gamete interaction.


Lledo B.,IB Biotech. | Guerrero J.,Instituto Bernabeu of Fertility and Gynecology | Ortiz J.A.,IB Biotech. | Morales R.,IB Biotech. | And 5 more authors.
Human Reproduction | Year: 2012

BACKGROUND: Fragile X syndrome is associated with low ovarian reserve and poor ovarian response. The aim of this study was to investigate whether CGG repeats on the fragile X mental retardation 1 (FMR1) gene have predictive value for ovarian response to stimulation with gonadotrophins and for clinical outcome in our oocyte donation program. METHODS: Oocyte donor candidates were selected according to Instituto Bernabeu oocyte donation program requirements. Fragile X genetic screening was performed in 204 oocyte donors, defining 141 controls and 63 cases: 35-39 repeats (n = 34), 40-45 (n = 12) and >45 (n = 17). All the patients underwent ovarian stimulation using a GnRH antagonist protocol and received a GnRH agonist trigger. The main factors used to measure outcome were oocyte yields, days of stimulation, gonadotrophin dosages, biochemical pregnancy, ongoing pregnancy and miscarriage rates. RESULTS: No differences between the study group and controls were reported in oocyte yields (17.5 versus 18.9) or days of stimulation (11.40 versus 9.82). The control group used significantly more gonadotrophin (2212 versus1850 IU) than the study group. Clinical outcome was not affected by the CGG repeats on the FMR1 gene in oocyte donors. CONCLUSIONS: No negative effect was observed for intermediate-sized CGG repeats on ovarian stimulation and clinical outcome using a non-confounding model of oocyte donation. These results disagree with previous studies performed on infertility patients. Owing to the present study, fragile X genetic screening should not be considered for prediction of response to ovarian stimulation. © The Author 2011. Published by Oxford University Press. All rights reserved.


Lledo B.,Instituto Bernabeu Biotech | Ortiz J.A.,Instituto Bernabeu Biotech | Llacer J.,Instituto Bernabeu of Fertility and Gynecology | Bernabeu R.,Instituto Bernabeu Biotech | Bernabeu R.,Instituto Bernabeu of Fertility and Gynecology
Pharmacogenomics | Year: 2014

Effective controlled ovarian stimulation (COS) is crucial for IVF outcome. Ovarian response to follicle-stimulating hormone, however, varies widely among women undergoing ovarian stimulation. Advance identification of patients who will elicit a poor or high response to standard treatment would be of great clinical benefit for such patients. Application of pharmacogenetics to ovarian response may predict stimulation success but also help in the adjustment and design of doses prior to treatment. Different studies have examined the impact of variations in follicle-stimulating hormone receptor, biochemical pathways involved in estrogen production and action, folliculogenesis and other aspects. Recently, gene-association studies have tried to identify a number of genetic variations affecting interindividual variability in COS. © 2014 Future Medicine Ltd.


Lledo B.,Instituto Bernabeu Biotech | Turienzo A.,Instituto Bernabeu Biotech | Ortiz J.A.,Instituto Bernabeu Biotech | Morales R.,Instituto Bernabeu Biotech | And 4 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2014

Purpose: Investigate whether R72P on p53 gene polymorphism has a higher prevalence among women with a history of recurrent implantation failure (RIF) and pregnancy loss (RPL) and its influence in their IVF cycle outcome. Material and methods: tjhep53 polymorphism R72P has been studied in 181 women. The control group included 83 oocyte donors. In the study group 98 women were included: 44 with RIF and 54 with RPL. From the study group, 76 patients underwent IVF-cycles (55 RPL and 21 RIF). Results: The frequency of PP genotypes on p53 among RIF was 11.4 % compared with 18.5 % for RPL and 6 % in controls (p<0.01). There were no significant differences with respect to patient characteristics. Significant differences were reported in pregnancy rate (69.4 % for RR/RP and 33.3 % for PP; p<0.05), embryo implantation rate (33.3 % for RR/RP and 7.3 % for PP; p<0.05) and ongoing pregnancy rate (53.1 % for RR/RP and 14.3 % for PP; p<0.05) among RIF and RPL. Conclusions: This investigation reveals that in RIF and RPL patients R72P on p53 gene is more prevalent than fertile population. Moreover, patients carrying a PP genotype on p53 codon 72 will have less chance to achieve an ongoing pregnancy. This information together with some additional markers will allow development of diagnostic tests for detects risk for RIF and RPL before infertility treatment is initiated. © 2013 Springer Science+Business Media.


Lledo B.,Instituto Bernabeu Biotech | Guerrero J.,Instituto Bernabeu of Fertility and Gynecology | Turienzo A.,Instituto Bernabeu Biotech | Ortiz J.A.,Instituto Bernabeu Biotech | And 5 more authors.
Pharmacogenetics and Genomics | Year: 2013

Objective: The aim of this study was to investigate whether N680S FSHR polymorphism has a predictive value for the ovarian response to stimulation with gonadotropins and cycle outcome in our egg donor program. Methods: The oocyte donor candidates were selected according to the Instituto Bernabeu egg donation program requirements and ASRM and ESHRE guidelines for oocyte donation. The FSHR polymorphism N680S was studied in 145 oocyte donors. All donors underwent controlled ovarian hyperstimulation (COH) (n=355) using urinary follicle-stimulating hormone in a GnRH antagonist protocol and receiving a GnRH agonist triggering. The main outcome measures were oocyte yield, days of stimulation, gonadotropin doses, biochemical pregnancy, ongoing pregnancy, and miscarriage rates. Results: Significant differences were reported in the antral follicle count (16.5±5.0 for NN, 14.5±4.7 for NS, and 14.1±3.8 for SS), number of eggs retrieved (21.5±9.2 for NN, 18.5±8.2 for NS, and 19.8±8.9 for SS), and gonadotropin doses (2098.5±639.4 IU for NN, 2023 ±490.1 IU for NS, and 2149.5±552.3 IU for SS) between the genotypes. The clinical outcome was not affected by the N680S polymorphism of the FSHR gene in the egg donors. Conclusion: In a population of fertile egg donors, the FSHR gene polymorphism at position 680 is associated with different ovarian responses to COH. The genotype of the FSHR gene is an important factor for determining the prognosis of the COH cycles in normo-ovulatory fertile women. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Morales R.,IB Biotech | Lledo B.,IB Biotech | Ortiz J.A.,IB Biotech | Ten J.,Instituto Bernabeu of Fertility and Gynecology | And 2 more authors.
Systems Biology in Reproductive Medicine | Year: 2016

Chromosomal polymorphisms involve heterochromatic regions and occur in the general population. However, previous studies have reported a higher incidence of these variants in infertile patients. The aim of this study was to examine the relationship between polymorphic variants and infertility and their association with aneuploidies in male gametes and embryos. We retrospectively considered 1,551 cytogenetic studies involving infertile patients (study group; n=866) and oocyte/sperm donors as the control group (n=685). We had detected 168 polymorphisms in the study group and 92 in the control group. An increase in the frequency of polymorphic variants was observed among infertile patients (19.4% study group vs. 13.4% control group; P < 0.01). Sperm aneuploidies among 145 infertile men were evaluated by fluorescent in situ hybridization (FISH). The frequency of infertile men with increased rates of sperm aneuploidy was higher among polymorphism carriers. Twenty men showed an abnormal rate of sperm aneuploidy in the carrier group (n=53) vs. 15 in the non-carrier group (n=92) (37.7% vs. 16.3%, respectively; P < 0.01). Finally, aneuploidies in blastocysts (n=301) resulting from donated oocytes were also examined by array comparative genomic hybridization (array-CGH). Significant differences were reported in the embryo aneuploidy rate between female carriers and non-carriers in oocyte donation cycles (50.0% vs. 27.6%; P < 0.001). This study suggests that polymorphic variants have an impact on fertility. Moreover, our results show a relationship between polymorphisms and aneuploidy in spermatozoa and embryos. Abbreviations: FISH: fluorescent in situ hybridization; CGH: comparative genomic hybridization; ESHRE: European Society of Human Reproduction and Embryology; ASRM: American Society for Reproductive Medicine; RPL: recurrent pregnancy loss; WHO: World Health Organization; ISCN: International System for Human Cytogenetic Nomenclature guidelines; WGA: whole genome amplification; SPSS: Statistical Package for Social Sciences © 2016 Taylor & Francis.


Lledo B.,IB Biotech | Llacer J.,Instituto Bernabeu of Fertility and Gynecology | Turienzo A.,IB Biotech | Ortiz J.A.,IB Biotech | And 5 more authors.
Reproductive BioMedicine Online | Year: 2014

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat sequence within exon 1. In-vitro studies have shown a relationship between CAG repeats in the AR gene and its transactivation potential. This variation in length may play a role in anovulatory infertility. The objective of this study was to investigate whether CAG polymorphism of the AR gene has a predictive value for ovarian reserve, response and cycle outcome in an egg donor programme. CAG length of the AR gene was determined in 147 oocyte donors. All donors underwent ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol (n = 355). No differences were reported in days of stimulation, gonadotrophin doses, and number of oocytes retrieved. Clinical outcomes were not affected by the CAG repeat length of the AR gene; the primary end-point, antral follicle count, was significantly affected (P < 0.05). In conclusion, in a population of fertile egg donors AR gene CAG polymorphism does not affect ovarian response to gonadotrophins. Antral follicle count was associated with the CAG polymorphism genotype. This suggests that genetic factors may increase susceptibility to poor ovarian reserve, and that AR gene genotype could play a role in the natural ovarian ageing process. © 2014 Reproductive Healthcare Ltd. All rights reserved.


PubMed | IB Biotech and Instituto Bernabeu of Fertility and Gynecology
Type: Journal Article | Journal: Reproductive biomedicine online | Year: 2014

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat sequence within exon 1. In-vitro studies have shown a relationship between CAG repeats in the AR gene and its transactivation potential. This variation in length may play a role in anovulatory infertility. The objective of this study was to investigate whether CAG polymorphism of the AR gene has a predictive value for ovarian reserve, response and cycle outcome in an egg donor programme. CAG length of the AR gene was determined in 147 oocyte donors. All donors underwent ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol (n = 355). No differences were reported in days of stimulation, gonadotrophin doses, and number of oocytes retrieved. Clinical outcomes were not affected by the CAG repeat length of the AR gene; the primary end-point, antral follicle count, was significantly affected (P < 0.05). In conclusion, in a population of fertile egg donors AR gene CAG polymorphism does not affect ovarian response to gonadotrophins. Antral follicle count was associated with the CAG polymorphism genotype. This suggests that genetic factors may increase susceptibility to poor ovarian reserve, and that AR gene genotype could play a role in the natural ovarian ageing process.

Loading Instituto Bernabeu of Fertility and Gynecology collaborators
Loading Instituto Bernabeu of Fertility and Gynecology collaborators