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Jacques Cohen

Publications and source records attributed to Jacques Cohen.

At least 19 recordsLinked to original sources
PubMed2025

Guidelines From the French-Speaking Society for Histocompatibility and Immunogenetics (SFHI) for Harmonisation of HLA Genotyping in Autoimmune Diseases, Drug Hypersensitivity and Pharmacogenetics.

HLA molecules play a central role in the adaptive immune response. Their high polymorphism influences individual susceptibility to various autoimmune diseases and certain drug-induced hypersensitivities. In France, HLA genotyping is classified as a medical genetics procedure and is strictly regulated. The Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) has established national guidelines outlining clinically validated indications, required resolution levels and interpretation criteria based on robust data. These guidelines are particularly relevant for common clinical contexts, including autoimmune diseases and pharmacogenetic testing. Well-established associations include HLA-DQB1*02/DQA1*05 (DQ2) and HLA-DQB1*03:02/DQA1*05 (DQ8) with celiac disease, HLA-B*27 with spondyloarthritis, HLA-DQB1*06:02 with type 1 narcolepsy, HLA-A*29 with Birdshot chorioretinopathy and several pharmacogenetic risk alleles such as HLA-B*57:01 (abacavir), HLA-B*15:02 and HLA-A*31:01 (carbamazepine) and HLA-B*58:01 (allopurinol). In immunotherapy, the efficacy of tebentafusp has been shown to depend on HLA-A*02:01 positivity. HLA alleles must be interpreted as relative risk factors, not absolute predictors. Critical analysis of HLA-related scientific literature requires consideration of the genotyping technique, typing resolution, allele frequencies within the studied population and environmental factors. High-resolution typing is essential in pharmacogenetics and recommended in selected autoimmune disorders. Interpretation should be conducted by qualified medical biologists, integrating clinical context, allelic diversity and recent technological advances, particularly next-generation sequencing. HLA genotyping represents a valuable tool in diagnosis and risk assessment, with increasing importance in the era of personalised medicine.

Humans↗
PubMed2006

Removal of 2 cells from cleavage stage embryos is likely to reduce the efficacy of chromosomal tests that are used to enhance implantation rates.

OBJECTIVE: To evaluate whether differences in results between studies that involve preimplantation genetic diagnosis for chromosome testing are affected by technology, such as the number of cells to be biopsied or by differences in study design. DESIGN: Evaluation of studies of aneuploidy testing according to the use of probes, fixation technology, error determination, and number of cells per embryo analyzed. SETTING: Preimplantation genetic diagnosis laboratories. PATIENT(S): Patients in published studies who underwent preimplantation genetic diagnosis for infertility or repeated pregnancy loss. INTERVENTION(S): As determined by each evaluated study, the number of biopsied cells and its effect on further development was evaluated by a comparison of models of embryo freezing and partial cell loss. MAIN OUTCOME MEASURE(S): Use of probes, fixation strategy, number of biopsied cells, and error rate determination of different published studies. RESULT(S): Differences in results between studies can be explained by the technology used and are not affected necessarily by differences in design and patient allocation. CONCLUSION(S): Studies that contradict the finding that aneuploidy screening improves implantation and lowers miscarriage rates all have > or =1 of the following aspects in common: (I) an excess of cells having been removed; (II) inadequate choice of probes; and (III) suboptimal fixation technology.

Abortion, Spontaneous↗
PubMed2006

The limited importance of pronuclear scoring of human zygotes.

BACKGROUND: Several studies have shown a correlation between the pronuclear morphology score (PNMS) and subsequent embryo development and implantation. Embryos with poor pronuclear score, elsewhere referred to as Z3 and Z4, are often not transferred or cryopreserved because it is believed that they have poor pregnancy potential. The objective of this study is to report our data on the use of the pronuclear score and its effect on pregnancy outcome. METHODS: Retrospective analysis of IVF/ICSI-embryo transfer cycles completed over the course of 1 year (n = 334). Comparisons were made only in those groups of patients in whom cohorts of similarly scored PNMS embryos were transferred. The proportion of such homologous cohorts was 104/334 (31%). All other replacements were excluded from final analysis as they were dissimilar as far as PNMS is concerned. Pregnancy outcomes were evaluated. RESULTS: The incidence of live birth resulting from the transfer of single pronuclear score homologous embryo types was 56 (14/25), 41 (13/32), 54 (23/43) and 0% (0/4) for PNMS scores 1, 2, 3 and 4, respectively. There was no correlation between PNMS category of the embryos transferred and live birth rates (P = 0.139). CONCLUSIONS: PNMSs of 1, 2 or 3 do not correlate with live birth rates when assessing unique PNMS embryo transfers. In particular, previously considered poor (type 3) embryos can result in pregnancy with normal live birth rates. Whether type 4 embryos are compatible with normal development remains to be shown.

Adult↗
PubMed2006

Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study.

OBJECTIVE: The inicidence of miscarriage is correlated with maternal age. The majority of miscarriages are chromosomally abnormal. The purpose of this study was to determine in a large population of infertility patients (>2000 cycles) if preimplantation genetic diagnosis (PGD) reduced the rate of spontaneous abortions. DESIGN: Multicenter retrospective controlled study. SETTING: One hundred IVF centers referring samples to a reference PGD laboratory. PATIENT(S): Infertile women. INTERVENTION(S): The spontaneous abortion rate after PGD was retrospectively compared to non-PGD cycles from the 2002 American Society for Reproductive Medicine-Society for Assisted Reproduction Technology report on IVF cycles. MAIN OUTCOME MEASURE(S): Spontaneous abortions and trisomic offspring rates. RESULT(S): The study included 2,279 cycles of PGD. The pregnancy rate per retrieval was 26.7% (average age 39.6). The mean pregnancy loss for the PGD group (0.167) was significantly lower than for the general IVF group (0.215) (P<.001). After PGD, the spontaneous abortion rate was 14.1% for ages 35-40, and 22.2% for women over 40, compared to 19.4% (P=.03) and 40.6% (P<.001), respectively, in controls. The clinical error rate of PGD (1.2%) was significantly lower than expected (4.7%) (P<.001). CONCLUSION(S): The data suggests that PGD significantly reduces the risk of spontaneous abortions in women undergoing IVF and PGD, particularly in women over 40. In addition, PGD may also reduce the risk of trisomic offspring.

Abortion, Spontaneous↗
PubMed2006

Cryopreservation of unfertilized human oocytes.

Previous investigations revealed that choline-based freezing media developed in our laboratory were superior to conventional sodium-based media for storing mouse oocytes. This paper examines the ability of the choline-based medium CJ2 and a modified form of this medium, CJ3, to cryopreserve unfertilized human oocytes. Oocytes that were consented for research and matured overnight, as well as freshly collected, donor, mature metaphase II (MII) oocytes, were cryopreserved using choline-based media and an optimized slow-cooling protocol. The results showed higher survival and fertilization rates when CJ3 supplemented with 0.2 mmol/l sucrose was used as compared with CJ2 supplemented with either 0.1 mmol/l or 0.2 mmol/l sucrose. Freshly collected oocytes were more difficult to cryopreserve than those matured in vitro. Modification of the base medium proved to be one of the key factors in obtaining survival rates over 90%. Fertilization rates, embryo development, and genetic analysis of embryos resulting from control and frozen-thawed oocytes are provided. There appears to be a high correlation between chromosomal anomalies and abnormal morphology in embryos from thawed oocytes.

Choline↗
PubMed2006

Inhibition of human spermatozoa-zona pellucida binding by a combinatorially derived peptide from a synthetic target.

Intact zona-free human oocytes were screened using a combinatorial peptide library selection protocol. Pieczenik Peptide Sequence 1 (PPS1) HEHRKRG binds human spermatozoa. A complementary and unique binding sequence HNSSLSPLATPA (PPS2) was developed from the first PPS1 ligand that binds to the human zona pellucida or oolemma. Cytoplasm-free zonae from unfertilized eggs were obtained and used as an assay system to test the effects of exposure to these two ligands. Spermatozoa were inserted into evacuated zonae and their behaviour and binding activity were assessed at regular intervals. The behaviour of spermatozoa exposed to PPS1 and unlabelled spermatozoa injected into unexposed zonae was similar as far as binding was concerned (50 and 54% binding), but PPS1 exposed spermatozoa had higher motility and displacement, marked by their escape from the zona pellucida. Zonae exposed to PPS2 inhibited the interaction between injected spermatozoa and the inside of the zona when compared with controls (8.3 and 53.8% attached respectively, P < 0.001). The sperm-zona pellucida interaction described in this paper is applied as a functional assay for molecular interactions of sperm binding and can be used to assess function for potential surface markers on gametes. It is shown here that a unique binding ligand (PPS2) can be synthesized from another complimentary ligand (PPS1) without the need for a known intermediate substrate. PPS1 and PPS2 may have properties that can be used to target processes involved in conception and assisted reproduction. A movie sequence taken approximately 30 min after injection of spermatozoa into empty human zonae pellucidae shows behaviour of non-manipulated spermatozoa into zonae not exposed or exposed to ligand. This may be purchased for viewing on the Internet at www.rbmonline.com/Article/2159 (free to web subscribers).

Amino Acid Sequence↗
PubMed2005

Association of abnormal morphology and altered gene expression in human preimplantation embryos.

OBJECTIVE: We set out to characterize the expression of nine genes in human preimplantation embryos and determine whether abnormal morphology is associated with altered gene activity. DESIGN: Reverse transcription and real-time polymerase chain reaction were used to quantify the expression of multiple genes in each embryo. The genes studied have various important cellular roles (e.g., cell cycle regulation, DNA repair, and apoptosis). SETTING: Research laboratory working closely with a clinical IVF practice. PATIENT(S): Over 50 embryos were donated by infertile patients (various etiologies). Among these, all major stages of preimplantation development and a variety of common morphologic abnormalities were represented. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quantification of mRNA transcripts. RESULT(S): We detected an association between certain forms of abnormal morphology and disturbances of gene activity. Cellular fragmentation was associated with altered expression of several genes, including TP53, suggesting that fragmenting blastomeres are suffering stress of a type monitored by p53, possibly as a consequence of suboptimal culture conditions. CONCLUSION(S): Appropriate gene expression is vital for the regulation of metabolic pathways and key developmental events. Our data indicates a possible causal relationship between changes in gene expression and the formation of clinically relevant abnormal embryo morphologies. We hypothesize that embryos with expression profiles characteristic of good morphology and appropriate for their developmental stage have the greatest potential for implantation. If confirmed, this could lead to a new generation of preimplantation genetic diagnosis (PGD) tests for assessing embryo viability and predicting implantation potential.

Blastocyst↗
PubMed2005

Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages.

OBJECTIVE: To determine whether preimplantation genetic diagnosis (PGD) and transfer of euploid embryos would decrease spontaneous abortion rates in recurrent miscarriage (RM) patients. DESIGN: Controlled clinical study. SETTING: In vitro fertilization centers and PGD reference laboratory. PATIENT(S): Recurrent-miscarriage patients with three or more prior lost pregnancies with no known etiology. INTERVENTION(S): Biopsy of a single blastomere from each day 3 embryo, followed by fluorescence in situ hybridization analysis. MAIN OUTCOME MEASURE(S): The rate of spontaneous abortions in RM subjects undergoing PGD were compared with [1] their own a priori expectations and [2] a comparison group of women undergoing PGD for advanced maternal age (> or =35 years). RESULT(S): Before PGD, RM patients had lost 87% (262/301) of their pregnancies, with an expected loss rate of 36.5%. After, they only lost 16.7% pregnancies. This difference was mostly due to reduction in pregnancy loss in the > or =35-years age subgroup, to 12% from an expected 44.5%. CONCLUSION(S): Preimplantation genetic diagnosis aneuploidy screening has a beneficial effect on pregnancy outcome in RM couples, especially those in which the woman is aged > or =35 years. Our data indicate that PGD reduces the risk of miscarriage in RM patients to baseline levels.

Abortion, Habitual↗
PubMed2005

Self-correction of chromosomally abnormal embryos in culture and implications for stem cell production.

OBJECTIVE: To ascertain whether embryos classified by preimplantation genetic diagnosis (PGD) for infertility as abnormal and then plated to obtain stem cells would self-correct partially or totally in culture, producing disomic stem cells. DESIGN: Prospective study to determine the chromosome status of embryos on day 3 and 6, as well as cultured cells derived from inner cell masses from the same embryos when cultured up to day 12. SETTING: Research laboratory. PATIENT(S): Patients undergoing PGD of aneuploidy. INTERVENTION(S): Of 142 embryos classified by PGD for aneuploidy as abnormal, 50 were cultured to the blastocyst stage. At that stage a fraction of the embryos underwent trophectoderm biopsy to reconfirm the PGD diagnosis. After further co-culture with feeders up to day 12, 34 embryos attached to the feeder cells. Of those, 24 were analyzed by fluorescence in situ hybridization (FISH) and the rest for the expression of Oct-4, SSEA-3, SSEA-4, TRA1-60, and TRA1-80. MAIN OUTCOME MEASURE(S): Disomic cells obtained from trisomic embryos. RESULT(S): Analysis by FISH of day-12 cultures showed that 7 were totally normal, 6 were mostly abnormal, and 11 had experienced some chromosome normalization, having between 21% and 88% normal cells. Day-12 culture was positive for Oct-4 expression by reverse transcriptase polymerase chain reaction analysis and for SSEA-3, SSEA-4, TRA1-60, and TRA1-80 by immunocytochemistry. CONCLUSION(S): Chromosome self-normalization occurs in a significant proportion of chromosomally abnormal embryos, possibly because of the loss of a chromosome in trisomic cells after blastocyst stage. Thus chromosomally abnormal embryos are a potential source of disomic stem cells. Not all chromosomally abnormal embryos self-corrected. Abnormal stem cells that might be derived could be used as models to study the effect of chromosomal abnormalities on human development.

Chromosome Aberrations↗
PubMed2005

Genetic testing of embryos: a critical need for data.

Preimplantation genetic diagnosis (PGD), the genetic testing of embryos developed through IVF is one of the fastest growing techniques in reproductive medicine and IVF. Some suggest that PGD will become part of every IVF cycle in the future. The growing popularity of PGD has highlighted the fact that there are no comprehensive data available about the use of PGD, its accuracy, or the health outcomes of babies born following PGD. For patients, practitioners, and policymakers alike, such information is critical. To address the gaps in knowledge, a working group of the leading experts in the development and practice of PGD and IVF has begun to design a database to collect information about PGD as practised in the United States.

Databases, Factual↗
PubMed2005

Cryopreservation of biopsied cleavage stage human embryos.

The aim was to develop a method to optimize cryopreservation of biopsied multi-celled human embryos. Human day 3 embryos that were donated to research, along with those found to be chromosomally abnormal after blastomere biopsy and fluorescence in-situ hyridization (FISH), were cryopreserved using a slow-freezing protocol in either standard embryo cryopreservation solution [embryo transfer freezing medium (ETFM), a conventional sodium-based medium] or CJ3 (a choline-based, sodium-free medium). After thawing, the number of intact cells was recorded and the previously biopsied embryos were re-analysed using FISH. Biopsied embryos had a lower proportion of intact blastomeres after cryopreservation as compared with intact embryos. However, a significantly (P < 0.05) higher proportion of blastomeres from intact and biopsied embryos cryopreserved in CJ3 (84.1 and 80.1% respectively) survived after thaw than those in ETFM (73.6 and 50.5% respectively). The proportion of aneuploid and mosaic embryos was not statistically different between the two groups. In addition, the frequency of lost cells by aneuploid and mosaic embryos was similar. This study describes a new method that improves the survival of cryopreserved biopsied embryos, and shows that it may also be beneficial for the storage of intact human multi-celled embryos.

Biopsy↗
PubMed2005

Combinatorial peptide library binding of mammalian spermatozoa identifies a ligand (HIPRT) in the axin protein: putative identification of a sperm surface axin binding protein and intriguing developmental implications.

The identification of components in cell-cell interactions is an important research goal in reproductive and developmental biology. Such interactions are critical to gamete development, fertilization, implantation and basic development. Several proteins involved with sperm-oocyte interaction and other developmentally important phenomena have been identified. However, these are obviously only a subset of the molecular components involved in such complex cell-cell interactions. One method that has been used to identify binding partners for particular molecular targets is the use of combinatorial libraries accessible on phage surfaces. For the most part, this technique has mainly been applied to screen specific target moieties. However, in some cases whole-cell screening has been attempted. This study describes the first report of screening intact, living mammalian gametes using a proprietary whole-cell combinatorial library binding and analysis protocol. Results from the first screening protocol of mouse spermatozoa strongly identified a putative sperm-binding ligand using proprietary bioinformatic analysis. This amino acid sequence (HIPRT) precisely corresponds with a previously characterized highly conserved protein-protein interaction site in the axin protein. This sequence is found within the binding site for a known sperm surface protein, glycogen synthase kinase-3. This result not only provides proof of the utility of this technique to identify cell surface ligands in mammalian gametes, but it also suggests a potential role for spermatozoa in facilitating developmental axis formation in mammalian embryos.

Amino Acid Sequence↗
PubMed2004

Increased rate of aneuploid embryos in young women with previous aneuploid conceptions.

OBJECTIVES: To determine whether a history of a previous aneuploid conception increases the rate of aneuploidy among women having preimplantation diagnosis (PGD). METHODS: Preimplantation embryos were tested for aneuploidy using FISH probes specific for chromosomes 13,15,16,17,18,21,22,X and Y. Using logistic regression to control for maternal age, we compared the rates of aneuploidy and other chromosome errors in 344 embryos from women having PGD because of a history of a previous aneuploid conception, 363 embryos from 42 women having PGD because of X-linked disorders and 1158 embryos from 135 women having PGD because of repeated in vitro fertilization failure. RESULTS: The frequency of aneuploidy differed significantly among patient groups for women younger than 35 (p = 0.003) but not for women older than 35. In women < 35, the rate of detected aneuploidy was 37.4% in the Aneuploid group, 20.9% in the X-linked group and 27.0% in the RIF group. (p = 0.0003 when the control groups are combined). The frequency of other chromosome abnormalities, as well as pregnancy and implantation rates, did not differ significantly among patient groups. CONCLUSIONS: This study suggests that a history of a trisomic pregnancy, whether or not it was a viable trisomy, is associated with an increased risk of another aneuploid conception at conception.

Adult↗
PubMed2004

Over a decade of experience with preimplantation genetic diagnosis: a multicenter report.

OBJECTIVE: To review a 12-year experience of the world's three largest preimplantation genetic diagnosis (PGD) centers. DESIGN: Multicenter analysis of the clinical outcome of PGD. SETTING: In vitro fertilization programs at the Reproductive Genetics Institute, Chicago, Illinois; Saint Barnabas Medical Center, West Orange, New Jersey; and SISMER, Bologna, Italy. PATIENT(S): Poor-prognosis IVF patients, patients carrying balanced chromosomal translocations, and couples at risk for producing children with Mendelian disorders. INTERVENTION(S): In vitro fertilization, intracytoplasmic sperm injection, polar body removal, blastomere biopsy, and ET. MAIN OUTCOME MEASURE(S): DNA or chromosomal analysis of biopsied polar bodies or blastomeres, implantation and clinical pregnancy rates, and live-born pregnancy outcome. RESULT(S): A total of 754 babies have been born as a result of 4,748 PGD attempts, which shows the expanded application and the practical relevance of PGD for single-gene disorders, chromosomal aneuploidies and translocations, late-onset diseases with genetic predisposition, and nondisease testing in couples at need for human leukocyte antigens-matched offspring for treatment of affected siblings. CONCLUSION(S): Preimplantation genetic diagnosis is evolving to become a clinical option for couples at risk for producing offspring with Mendelian diseases, has a positive numerical impact in standard assisted reproduction practices through aneuploidy testing, and reduces by at least fourfold the spontaneous abortion rate in couples carrying translocations.

Blastula↗
PubMed2004

Over a decade of experience with preimplantation genetic diagnosis.

The three respondents provide additional support for preimplantation genetic diagnosis (PGD) having the pivotal place it now has in prenatal genetic diagnosis: chromosomal abnormalities (e.g., unbalanced translocations), Mendelian disorders, and HLA typing for transfer of compatible, genetically normal, embryos. Transferring euploid embryos has decreased the clinical abortion rate and increased the implantation rate in assisted reproductive technologies (ART), but it has not necessarily improved the live-birth rate. Safer embryo biopsy, more extensive diagnostic efforts (i.e., microarray analysis), and more refined patient selection may be required before shifting from preselection of embryos based solely on morphological parameters to transfer of only aneuploidy-free embryos.

Abortion, Spontaneous↗