T. Anahory

Centre Hospitalier Universitaire de Montpellier, Montpelhièr, Languedoc-Roussillon, France

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Publications (71)124.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: This study provides an overview of 10 years of experience of preimplantation genetic diagnosis (PGD) for cystic fibrosis (CF) in our centre. Due to the high allelic heterogeneity of CFTR mutations in south of France, we have set up a powerful universal test based on haplotyping 8 STR markers together with the major mutation p.Phe508del. Of 142 couples requesting PGD for CF, 76 have been so far enrolled in the genetic work-up, and 53 had 114 PGD cycles performed. Twenty-nine cycles were cancelled upon IVF treatment due to hyper- or hypostimulation. Of the remaining 85 cycles, a total of 493 embryos were biopsied and a genetic diagnosis was obtained in 463 (93.9%), of which 262 (without or with a single CF-causing mutation) were transferable. Twenty-eight clinical pregnancies were established, yielding a pregnancy rate per transfer of 30.8% in the group of 7 couples with one member affected with CF, and 38.3% in the group of couples whose both members are carriers of a CF-causing mutation (including 6 couples with CBAVD). So far, 25 children were born free of CF and no misdiagnosis was recorded. Our test is applicable to 98% of couples at risk of transmitting CF.
    Clinical Genetics 04/2014; · 4.25 Impact Factor
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    ABSTRACT: The majority of fluorescence in situ hybridization (FISH) studies on the meiotic segregation of Robertsonian translocations focus on the most common types, rob(13; 14) and rob(14; 21). Here we report the first study for carriers of rare Robertsonian translocations rob(13; 21) and rob(15; 22) combining analysis of meiotic segregation in sperm and blastomeres following pre-implantation genetic diagnosis (PGD). Dual-colour FISH was applied to nuclei from spermatozoa and blastomeres from PGD embryos using two subterminal contig probes for each translocation, and a second round with probes for chromosomes 16 and 18. Patient 1 had a rob(13; 21) and patient 2 had a rob(15; 22), and 86.3% and 87.5% of gametes respectively were consistent with meiotic segregation resulting in a normal or balanced chromosome complement. Analysis of embryos showed that for patient 1 and 2 respectively, 25% and 46% were balanced, and of the unbalanced embryos, 50% and 31% were mosaic or chaotic. Our patients with a rob(13; 21) and rob(15; 22) were found to have a similar meiotic segregation pattern to that for male carriers of the common Robertsonian translocations. The observed rate in unbalanced embryos being mosaic or chaotic may result in an increased risk of chromosomal abnormalities. Our results may help to improve the genetic counseling for carriers of rare Robertsonian translocations.
    European journal of medical genetics 02/2012; 55(4):245-51. · 1.57 Impact Factor
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    ABSTRACT: Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was first to focus on the knowledge of the effects of cigarette smoking on reproductive stages and particularly on implantation process and early placentation. Human clinical and experimental studies were analysed in order to find hypothesis and explanations for the effects observed. Then, our second aim was to analyse which factors could influence smoke effects. We observed that smoke compounds induce impairment of endometrial maturation, disturb angiogenesis and trophoblastic invasion. Cigarette compounds also impair uterine and endometrial vascularisation and myometrial relaxation. These effects lead to implantation failure in IVF and higher risk of miscarriage. Many factors influence the effects of cigarette smoke, as smoke behaviour, dose and duration of exposition. Sidestream is also damaging on reproductive function. Prenatal exposure leads to irreversible and deleterious effects on ovarian reserve. These observations need to be confirmed in order to improve health care in women of reproductive age.
    Gynécologie Obstétrique & Fertilité 09/2011; 39(10):567-74. · 0.55 Impact Factor
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    ABSTRACT: Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was to focus on the knowledge of the effects of cigarette smoking on all reproductive stages, from oocyte to embryo. For each reproductive functions human clinical and experimental studies were analysed in order to find hypothesis and explanations for effects observed. All reproductive functions are targets of smoke compounds and cigarette smoking impairs ovarian reserve, sexual steroids synthesis, Fallopian tubes functions and embryo development, leading to reduced fecundity. Some of smoke compounds were identified in ovarian tissue, in uterine fluid and in the embryo, suggesting direct toxicity.
    Gynécologie Obstétrique & Fertilité 09/2011; 39(10):559-66. · 0.55 Impact Factor
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    ABSTRACT: To directly study the meiotic segregation of a complex reciprocal translocation (CCR) as well as the occurrence of an interchromosomal effect. In situ sperm fluorescence in situ hybridization (FISH) analysis. Department of Cytogenetics and INSERM research center. A male carrier of a balanced complex reciprocal translocation t(5;13;14)(q23;q21;q31). Sperm samples from the carrier and direct FISH analysis on sperm slide preparations. Meiotic segregation pattern determined on sperm nuclei and estimation of the incidence of unbalanced spermatozoa and an interchromosomal effect (ICE). Only 27% of spermatozoa displayed a normal or balanced chromosome complement. The rate of unbalanced sperm was 69.4%, including different types of 3:3, 4:2, and 5:1 segregations. There was no evidence for the occurrence of an interchromosomal effect in autosomal chromosomes, but the gonosomes displayed a statistically significant increase in disomy rates. These results are consistent with the formation of a hexavalent configuration at the pachytene stage of meiosis and a high prevalence of imbalance production. The mechanisms of formation of CCRs must be examined with regard to these direct results and new molecular data on the formation of genomic rearrangements.
    Fertility and sterility 03/2011; 95(7):2433.e17-22. · 3.97 Impact Factor
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    ABSTRACT: Ovarian response in female translocation carriers is not well understood. We aimed to evaluate the impact of chromosomal autosomal balanced translocations on the ovarian response to controlled ovarian stimulation (COS) in female carriers undergoing IVF and PGD. In a retrospective study, we included all female translocation carriers who underwent PGD at our centre. We compared these patients to female patients from couples with male translocation carriers who underwent PGD. Results from 79 cycles of PGD from 33 female translocation carriers were compared with 116 cycles from 55 male translocation carriers. No difference was observed for patient characteristics: female age, anti-Müllerian hormone or antral follicle count. No difference in COS parameters was observed for the total dose of recombinant FSH, the number of retrieved oocytes and embryos on Day 3, for unaffected and transferred embryos. For the two groups, pregnancy rate was similar per cycle (12.7 versus 20.7%, P = 0.208). Multivariate analysis demonstrated that female translocation carriers had a significantly higher estradiol level on the day of hCG administration (+540 pg/ml, P = 0.05). This paper is the largest to report ovarian response of female translocation carriers. This study showed that the ovarian response to COS was not impaired by balanced translocation status, suggesting that female chromosomal structural abnormalities did not influence the results of COS in PGD. Thus, female carriers of balanced translocations could be considered normal responders and standard doses of gonadotrophins used for ovarian stimulation.
    Human Reproduction 02/2011; 26(5):1232-40. · 4.67 Impact Factor
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    ABSTRACT: Complex chromosomal rearrangements (CCRs) describe structural rearrangements, essentially translocations, involving at least three breakpoints on two or more chromosomes. Although they are rare in humans, their clinical identification is important since CCR carriers can display various phenotypes which include phenotypically normal subjects, infertile males and patients with mental retardation and/or congenital abnormalities. The rearrangement can be de novo or familial. The use of fluorescent in situ hybridization assays and molecular techniques for the characterization of CCRs have indicated that the rearrangements could be more complex than initially assumed. Accumulating data have revealed that the mechanisms underlying the genesis of CCRs remain elusive. We performed a large PubMed search in order to summarize the current knowledge in this field and address important aspects of CCR formation and meiotic behavior, highlighting the complexity of these rearrangements at the chromosomal and genomic level. The review of published data indicates that the complexity of CCRs is becoming increasingly known, thanks to the application of more and more efficient molecular techniques. These approaches have allowed the precise sequence analysis of breakpoints and the identification of insertions, deletions, inversions and recombination events. New models have been proposed for the formation of CCRs, based on replication-based mechanisms and specific sequence elements. Their meiotic behavior has been discussed in the light of these new molecular data. Despite the increasing understanding of the mechanisms involved in their genesis, CCRs arise as unique, complex events for which the genetic and reproductive counseling of carriers remains a challenge.
    Human Reproduction Update 01/2011; 17(4):476-94. · 9.23 Impact Factor
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    ABSTRACT: Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was to focus on the knowledge of the effects of cigarette smoking on all reproductive stages, from oocyte to embryo. For each reproductive functions human clinical and experimental studies were analysed in order to find hypothesis and explanations for effects observed. All reproductive functions are targets of smoke compounds and cigarette smoking impairs ovarian reserve, sexual steroids synthesis, Fallopian tubes functions and embryo development, leading to reduced fecundity. Some of smoke compounds were identified in ovarian tissue, in uterine fluid and in the embryo, suggesting direct toxicity.
    Gynecologie Obstetrique & Fertilite - GYNECOL OBSTET FERTIL. 01/2011; 39(10):559-566.
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    ABSTRACT: Pericentric inversions (PIs) are structural chromosomal abnormalities, potentially associated with infertility or multiple miscarriages. More rarely, at meiosis, odd numbers of genetic recombinations within the inversion loop produce recombinant gametes which may lead to aneusomy of recombination in the offspring. We report a FISH segregation analysis of an inv5(p15.3q11.2) carrier, both in sperm and blastomeres. In sperm, we directly evaluated the proportion of recombinant gametes and compared the results with chromosomal abnormalities found in blastomeres collected from embryos obtained following a preimplantation genetic diagnosis (PGD) procedure. A total of 7006 sperm nuclei were analyzed. The size of the inverted segment represented 27% of the total length of chromosome 5. The frequencies of balanced chromosomes (normal or inverted), recombinant chromosomes and unbalanced combinations were 97.1, 0.17 and 2.73%, respectively. Of six embryos, PGD FISH analysis revealed that one was a balanced embryo, whereas five were unbalanced and there were no recombinants. This study demonstrated the value of sperm-FISH analysis in providing reproductive genetic counseling for PI carriers. Our study also highlights the clinical relevance of performing PGD instead of prenatal diagnosis.
    Human Reproduction 07/2010; 25(7):1818-23. · 4.67 Impact Factor
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    ABSTRACT: The impact of gonadotropin-releasing hormone (GnRH) agonist long compared with GnRH antagonist protocols, under in vitro fertilization conditions on endometrial receptivity, is still debated. Therefore, we compared the effect of both GnRH antagonist and agonist long protocols on the endometrial receptivity by analyzing, to our knowledge for the first time, the global gene expression profile shift during the prereceptive and receptive stages of stimulated cycles under the two GnRH analogue protocols compared with natural cycles in the same patients. For the same normal-responder patients, endometrial biopsies were collected on the day of oocyte retrieval and on the day of embryo transfer after human chorionic gonadotropin administration of a stimulated cycle with either GnRH agonist long or GnRH antagonist protocols and compared with the prereceptive and receptive stages of a natural cycle. Samples were analyzed using DNA microarrays. Gene expression profiles and biological pathways involved during the prereceptive stage to the receptive endometrial transition of stimulated and natural cycles were analyzed and compared for each patient. Both protocols affect endometrial receptivity in comparison with their natural cycle in the same patients. Major differences in endometrial chemokines and growth factors under stimulated cycles in comparison with natural cycles were observed. Such an effect has been associated with gene expression alterations of endometrial receptivity. However, the endometrial receptivity under the GnRH antagonist protocol was more similar to the natural cycle receptivity than that under the GnRH agonist protocol.
    Biology of Reproduction 04/2010; 82(4):679-86. · 4.03 Impact Factor
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    ABSTRACT: This study aimed at evaluating parameters and results of ovarian stimulation for myotonic dystrophy type 1 (DM1) female patients undergoing preimplantation genetic diagnosis (PGD) and to assess an eventual association between genotype and ovarian reserve. A retrospective study involved all 17 DM1 patients treated in the study centre's PGD programme. The control group consisted of 22 patients treated for X-linked disorders in the same period. Comparative analysis of ovarian stimulation parameters and results was performed with bivariate and multivariate analysis. Then, among DM1 patients, a correlation between genotype (number of CTG repeats) and ovarian reserve, assessed by antral follicle count, was investigated. Comparative study showed no difference concerning the number of oocytes, embryos and pregnancy rate between the two groups. Multivariate analysis demonstrated that DM1 patients needed a significantly higher dose of gonadotrophins (+544IU, P<0.001) than X-linked disorders patients and suggests a decreased ovarian sensitivity. However, with higher dose of gonadotrophins, PGD for DM1 offers good reproductive outcomes with a clinical pregnancy rate of 35.7%. Genotype was not correlated to ovarian reserve and appeared not to be helpful for the choice of the dose of gonadotrophins.
    Reproductive biomedicine online 02/2010; 20(5):610-8. · 2.68 Impact Factor
  • Fertility and Sterility - FERT STERIL. 01/2010; 94(4).
  • Reproductive Biomedicine Online - REPROD BIOMED ONLINE. 01/2010; 20.
  • Fertility and Sterility - FERT STERIL. 01/2010; 94(4).
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    ABSTRACT: BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.
    Human Reproduction Update 01/2010; 17(1):76-95. · 9.23 Impact Factor
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    ABSTRACT: The first week of human embryonic development comprises a series of events that change highly specialized germ cells into undifferentiated human embryonic stem cells (hESCs) that display an extraordinarily broad developmental potential. The understanding of these events is crucial to the improvement of the success rate of in vitro fertilization. With the emergence of new technologies such as Omics, the gene expression profiling of human oocytes, embryos and hESCs has been performed and generated a flood of data related to the molecular signature of early embryo development. In order to understand the complex genetic network that controls the first week of embryo development, we performed a systematic review and study of this issue. We performed a literature search using PubMed and EMBASE to identify all relevant studies published as original articles in English up to March 2010 (n = 165). We also analyzed the transcriptome of human oocytes, embryos and hESCs. Distinct sets of genes were revealed by comparing the expression profiles of oocytes, embryos on Day 3 and hESCs, which are associated with totipotency, pluripotency and reprogramming properties, respectively. Known components of two signaling pathways (WNT and transforming growth factor-β) were linked to oocyte maturation and early embryonic development. Omics analysis provides tools for understanding the molecular mechanisms and signaling pathways controlling early embryonic development. Furthermore, we discuss the clinical relevance of using a non-invasive molecular approach to embryo selection for the single-embryo transfer program.
    Human Reproduction Update 01/2010; 17(2):272-90. · 9.23 Impact Factor
  • Reproductive Biomedicine Online - REPROD BIOMED ONLINE. 01/2010; 20.
  • Reproductive Biomedicine Online - REPROD BIOMED ONLINE. 01/2010; 20.
  • Fertility and Sterility - FERT STERIL. 01/2010; 94(4).
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    ABSTRACT: Complex chromosome rearrangements (CCRs) are structural aberrations involving three or more breakpoints on two or more chromosomes. These CCRs result in a high rate of chromosome imbalances potentially leading to subfertility and congenital abnormality. In this study, we analysed meiotic segregation in the sperm of a patient with a familial CCR 46, XY,t(1;19;13)(p31;q13.2;q31)mat included in an intracytoplasmic sperm injection program because of oligoasthenozoospermia. The rearrangement was first identified using conventional and molecular cytogenetic methods. Primed in situ labelling (PRINS) and fluorescence in situ hybridization (FISH) techniques were then combined allowing the simultaneous use of five fluorochromes on the same sperm preparation, for the segregation analysis and the evaluation of the reproductive options for this patient. Segregation analysis was performed in a total of 1822 sperm nuclei from the translocation carrier. The percentage of unbalanced sperm was 75.9%, including 34.1% from 3:3 segregation, 38.2% from 4:2 segregation, 3.5% from 5:1 segregation and 0.05% from 6:0 segregation. Only 14.8% of sperm nuclei were consistent with a normal or balanced chromosome complement. In conclusion, chromosome segregation analysis combining FISH and PRINS was performed in sperm from a CCR carrier using five fluorochromes. These results advance our understanding of the mechanisms of meiotic segregation, and facilitate the assessment of the usefulness of preimplantation genetic diagnosis procedures in CCR couples.
    Molecular Human Reproduction 12/2009; 16(2):111-6. · 4.54 Impact Factor

Publication Stats

620 Citations
124.47 Total Impact Points

Institutions

  • 2007–2010
    • Centre Hospitalier Universitaire de Montpellier
      • Département de biologie de la reproduction
      Montpelhièr, Languedoc-Roussillon, France
    • Institut de Recherche en Cancerologie de Montpellier
      Montpelhièr, Languedoc-Roussillon, France
  • 2002–2006
    • French National Centre for Scientific Research
      • Institut de Génétique Humaine
      Lutetia Parisorum, Île-de-France, France
  • 2005
    • Institut de Génétique Humaine
      Montpelhièr, Languedoc-Roussillon, France
  • 2003
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France