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Biomedical subjects

Jacques Cohen

Publications and source records attributed to Jacques Cohen.

34 records · Page 2Linked to original sources
PubMed2004

Differences in chromosome susceptibility to aneuploidy and survival to first trimester.

The purpose of this study was to find specific rates of aneuploidy in cleavage-stage embryos compared with first trimester data and to evaluate post-zygotic selection against aneuploidy. A total of 2058 embryos were analysed by flurorescence in-situ hybridization (FISH), and specific aneuploidy rates were obtained for 14 chromosomes. Data from morphologically abnormal embryos could be pooled with data from preimplantation genetic diagnosis (PGD) cycles because it was observed that they had similar rates of aneuploidy; thus, for the purpose of studying aneuploidy they could be, and were, pooled. Specific chromosome aneuploidy rates were not related to morphology or development of the embryos. The average maternal age of patients with aneuploid embryos was significantly higher than the overall analysed population. Monosomy appeared more commonly than trisomy. The chromosomes most frequently involved in aneuploidy were (in order) 22, 16, 21 and 15. When compared with first trimester pregnancy data, aneuploidies detected at cleavage stage seem to die in excess of 90% before reaching first trimester, with the exception of chromosome 16 and gonosomes (76% and 14% respectively). Differences in chromosome-specific aneuploidy rates at first trimester conceptions are probably produced by different chromosome-specific aneuploidy rates at cleavage stage and different survival rates to first trimester.

Aneuploidy↗
PubMed2004

Expression profiles of individual human oocytes using microarray technology.

Microarray technology is a relatively new technique that provides the investigator with the ability to monitor and quantify the expression of thousands of genes simultaneously. This technological breakthrough has the potential to provide detailed insight into cellular processes involved in the regulation of gene expression. In this study, microarray methods were used to examine the expression of linearly amplified RNA from individual and pooled (n = 5) human oocytes. The amplification strategy consistently produced a complex representative cDNA population. A catalogue of 1361 transcripts expressed in human oocytes was identified, of which 406 have been independently confirmed using other methods.

DNA, Complementary↗
PubMed2004

Spindle organization after cryopreservation of mouse, human, and bovine oocytes.

Oocyte cryopreservation would alleviate a number of ethical, social, and religious problems associated with human embryo storage. One potential problem is the effect of cryopreservation on the metaphase II spindle and chromosomes. The microtubules that make up the spindle tend to depolymerize at sub-physiological temperatures. Although there are numerous reports in the literature on this topic, discrepancies as to whether the spindle can or cannot reform persist. One of the confounding factors may be the low cryosurvival rates (around 50%) for mammalian oocytes. In recent years, a cryopreservation medium and protocol have been developed that allow oocytes of several species to be cryopreserved with high survival rates (>85%). Bovine, mouse, and human oocytes consistently reformed a morphologically normal spindle with chromosomes aligned along the metaphase plate (70% or higher) after first surviving cryopreservation (>87% survival for all species tested). Normal chromosome numbers were found in every second polar body tested by FISH (second polar bodies n = 4). It is concluded that the mammalian spindle, although depolymerized during cryopreservation, has the ability to reform, and in the mouse has been shown to function normally. Therefore, spindle reformation may not be a major cause for concern when storing mammalian MII oocytes.

Animals↗
PubMed2004

An overview of oocyte cryopreservation.

The ability to cryopreserve human oocytes and store them indefinitely would be beneficial for cancer patients at risk of becoming sterile after therapy, allow women to delay reproduction, and alleviate religious concerns associated with embryo storage. In 1986, Chen was the first to report a pregnancy originating from a frozen-thawed human oocyte. Although over 100 babies have been born from oocyte storage since then, pregnancy rates remain unacceptably low. Adapting embryo cryopreservation techniques to oocyte storage has had limited success and new reproducible methods are needed. Problem areas other than intracellular ice formation and osmotic effects need to be identified. A broad approach of critical analysis should be conducted regarding the entire cryopreservation process from pre-equilibration and cooling, to thawing and stepout. All established facets deserve reanalysis in order to assess which aspects can be optimized or changed so that cellular demise can be avoided and cellular viability enhanced. New methods, including the use of choline-based media and vitrification have proven useful in increasing survival and pregnancy rates in some clinics. Other methods yet untested, such as injection of complex carbohydrates into the oocyte, deserve further studies. Vitrification research has led to the formulation of new ideas and has demonstrated the flexibility of cells to survive cryopreservation. Although successful, vitrification protocols are potentially harmful and technically challenging, due to elevated cryoprotectant concentrations and rapid cooling rates. Bovine embryo vitrification methods have been used to store human oocytes and embryos, particularly blastocysts with some success. Vitrification solutions containing high molecular weight polymers have also proved beneficial by reducing solution toxicity. In general, further advances are needed to improve human oocyte storage before widespread routine clinical use.

Animals↗
PubMed2004

The status of preimplantation genetic diagnosis in Japan: a criticism.

Advances in preimplantation genetic diagnosis (PGD) are occurring worldwide. New clinics specializing in this approach to the control of disease genes or imbalanced chromosome numbers in human preimplantation embryos continue to increase. One exception is Japan, where the Japanese Society of Obstetrics and Gynecology disapproves of this practice because it discriminates against people with genetic abnormalities. Yet, some doctors there wish to introduce this method to help their couples to improved forms of IVF. This paper stresses the rights of patients to have a healthy baby, if necessary by the use of PGD. It argues against prohibition, since it complements the current nature of prenatal diagnosis and avoids the need for abortions in case of afflicted embryos. Consideration is also given to other attempts at restriction that have failed.

Female↗
PubMed2003

Monozygotic twinning following assisted conception: an analysis of 81 consecutive cases.

BACKGROUND: This study attempts to identify risk factors for monozygotic (MZ) twinning following assisted conception. METHODS: Eighty-one MZ twinning pregnancies that occurred over a 7-year period in our IVF/embryo transfer programme were evaluated. These were compared with 4224 non-MZ pregnancies from the same period. RESULTS: The overall incidence of MZ twinning was 1.88% (81/4305) of all clinical pregnancies. A total of 63% (51/81) of the MZ pregnancies included one or more other implantations as well. MZ twinning was unrelated to maternal age, paternal age, gonadotrophin dosage, peak estradiol and progesterone levels, number of oocytes collected, and number of embryos replaced. Patients with MZ twinning had significantly more attempts at assisted reproduction than those with non-MZ multiple pregnancy. A logistic regression analysis suggested a role, albeit not emphatic, for the zona pellucida in MZ twinning. Twenty-four of the 65 MZ cases with known placentation were monoamniotic. This incidence far exceeds that seen following spontaneous conception (P < 0.0001). CONCLUSIONS: The risk of monoamniotic twinning is increased following IVF/embryo transfer. Zona pellucida disruption appears to increase the incidence of MZ twinning. However, the overall micromanipulation data together with the unexpected placentation data suggest that zona-mediated embryo splitting is not the only mechanism of twinning under artificial conditions.

Embryo Transfer↗
PubMed2002

Fetal development of mouse oocytes and zygotes cryopreserved in a nonconventional freezing medium.

This study (1) analyzed fetal development of mouse embryos after oocyte cryopreservation in CJ2, a choline-based medium, (2) examined the effect of culture duration in vitro on subsequent fetal development, and (3) compared survival and fetal development of zygotes frozen in embryo transfer freeze medium (ETFM; sodium-based medium) or CJ2. Unfertilized oocytes and zygotes were cryopreserved using a slow-cooling protocol. After thawing, oocytes were inseminated after drilling a hole in their zona, cultured in vitro either to the two-cell or blastocyst stage, and transferred to the oviducts or uterine horns of recipient mice. In parallel experiments, frozen-thawed zygotes were similarly cultured and transferred. Implantation rates for transferred embryos were high (range 66-88%), regardless of whether they had been frozen as oocytes or zygotes and whether they had been transferred to the oviduct or uterus. However, fetal development was significantly higher when two-cell embryos were transferred. With blastocyst transfer, control embryos implanted and produced a greater proportion of fetuses than did oocytes frozen in CJ2, whereas transfer at the two-cell stage resulted in similar proportions of implantation sites and fetuses. Blastocyst transfer of zygotes cryopreserved in ETFM or CJ2 produced similar fetal development rates (23.6% vs 20.0%), but when frozen-thawed zygotes were transferred at the two-cell stage the fetal development rates were higher in the ETFM group (53.3%) than in the CJ2 group (32.0%). A high proportion (46.7%) of oocytes frozen in CJ2 in a nonprogrammable freezer and plunged at -20 degrees C developed into live offspring. This study shows that in the mouse (1) oocytes frozen in CJ2 can develop into viable fetuses, (2) prolonging culture in vitro has a detrimental effect on embryo transfer outcome, and (3) CJ2 offers no advantage for zygote cryopreservation.

Animals↗
PubMed2001

Zona dissection by infrared laser: developmental consequences in the mouse, technical considerations, and controlled clinical trial.

Infrared laser systems are currently being marketed for application in clinical zona pellucida dissection. However, these systems have undergone only limited animal testing and minor clinical trials that lacked proper controls. Two of these systems have been evaluated in protocols that addressed potential detrimental effects on embryonic development in the mouse. Exaggerated large openings were made in the zona pellucida of 8-16 cell mouse embryos. Embryonic development and subsequent implantation and viability were assessed. A definite negative effect on these parameters was observed following the use of one of these systems. Following this animal trial, the second system was evaluated in a clinical trial for assisted hatching and embryo biopsy. Laser dissection was directly compared with the standard zona drilling using acidified Tyrode's solution. While no significant difference was evident between the two protocols, it was felt that laser dissection presented some problems in both consistency between operators and in the efficacy of subsequent manipulations such as blastomere biopsy and fragment removal. These results argue that laser zona dissection is far from a simple technique and should be carefully evaluated before any clinical application is made.

Journal Article↗
PubMed1994

The science, fiction, and reality of embryo cloning.

Although many scientists view cloning as a useful procedure for scientific research into early embryo development -- one that cannot currently be used to produce multiple copies of humans -- the popular literature has led some individuals to view it as sinister. To address the concerns of the public, various conceptions of cloning are distinguished and their basis in fact analyzed. The possible uses, benefits, and detriments of both embryo splitting and nuclear transplantation are explained. Once the nature and purposes of cloning are understood, and the distinctive ethical dilemmas created by embryo splitting and nuclear transplantation are sorted out, these procedures should be clinically implemented to assist in vitro fertilization treatment for those who are infertile and to further other therapeutic and investigational efforts in medicine.

Animal Experimentation↗
PubMedDate not supplied

Ooplasmic transfer: animal models assist human studies.

Ooplasmic transplantation is based on the premise that ooplasmic components are compromised in some individuals. In theory, the transfer of small amounts of healthy ooplasm can correct such deficits, allowing for improved development and implantation. The technique is based on a well-established background of experimental embryology demonstrating that cytoplasmic manipulation in oocytes and early embryos can be entirely compatible with normal development. Cytoplasm has been manipulated via karyoplast and cytoplast transfer and by cytoplasmic injection. Term development has been obtained following such manipulations in a variety of mammalian species. While some manipulative scenarios have exhibited compromised development, others have exhibited improved development. Developmental problems involving specific epigenetic and mitochondrial incompatibilities have been observed in a very limited subset of animal studies. These studies are based on genetic and physical models that have little relation to the actual substance of ooplasmic transplantation in the human. In fact, the majority of animal studies suggest that ooplasmic transplantation is well-founded and unlikely to result in negative developmental consequences. Furthermore, there are considerable physical, physiological and developmental differences between human and rodent eggs and embryos. These differences suggest that potentially negative issues raised by rodent results may not be relevant in the human.

Animals↗
PubMedDate not supplied

Improved implantation after preimplantation genetic diagnosis of aneuploidy.

The objective of this study was to assess the improvement in implantation rates after preimplantation genetic diagnosis (PGD) of numerical abnormalities for the sole indication of advanced maternal age when compared with a control group. Each PGD patient was matched to a control patient according to several parameters prior to obtaining pregnancy results. The diagnosis was based on the analysis of chromosomes X, Y, 13, 15, 16, 18, 21 and 22 plus a ninth probe (1, 7, 14 or 17) on a single cell per embryo. The results were also analysed in relation to the previous number of IVF cycles and the number of dipronucleated zygotes obtained, when replacing presumptively chromosomally normal embryos on day 4 of development. It was found that women of advanced reproductive age (average age 40 years) had a higher implantation rate (18%) than their matched controls treated with standard IVF (11%) (P < 0.05). This increase was not observed in patients with two or more previous IVF cycles or patients with fewer than eight zygotes. Patients with eight or more 2PN zygotes and one or no previous cycles showed the greatest improvement in implantation rate, from 8.8% in controls to 19.2% in the PGD group (average age 40 years) (P < 0.025).

Abortion, Habitual↗
PubMedDate not supplied

Chromosome mosaicism in cleavage-stage human embryos: evidence of a maternal age effect.

The present study evaluated mosaicism in a large series of cleavage-stage human embryos analysed by fluorescence in-situ hybridization. Only embryos with at least three cells analysed were included (n = 1235), of which 556 were mosaics. The most common types of mosaicism were chaotic (48%), diploid/polyploid (26%), and those caused by mitotic non-disjunction (25%). The number of abnormal cells per embryo ranged from 44% in diploid/polyploid to 84% in chaotic mosaics. Chromosome 16 was most commonly involved in mitotic non-disjunction mosaics. While overall mosaicism did not increase with maternal age, the average maternal age of the embryos that had mosaics caused by mitotic non-disjunction was significantly higher than that for normal or other mosaic embryos (P < 0.001). During the cleavage stage, the embryonic genome is not yet fully activated and consequently the mRNA and protein pools are still similar to those found in the oocyte. We therefore propose that the malfunctioning of the meiosis apparatus, which is similar to the mitotic one, may cause either meiotic errors or mitotic non-disjunction at cleavage-stage embryo development.

Analysis of Variance↗
PubMedDate not supplied

Genotyping: the HLA system and embryo development.

The human major histocompatibility complex (MHC), in addition to its role in the regulation of cell-cell interactions in the immune response, also influences reproductive success. Human leukocyte antigen-G (HLA-G) is an MHC class I gene of particular interest in reproductive biology because of its specific expression on fetal cytotrophoblast cells, and its reported involvement both in protection of the developing fetus from destruction by the maternal immune response and in the prevention of maternal pre-eclampsia. HLA-G has 15 known alleles at the DNA level, and allelic frequency varies among ethnic groups. This study describes the results of an inaugural attempt to correlate an HLA-G genetic polymorphism with pregnancy outcome in a patient population undergoing IVF. The study group was composed of 102 Caucasian women. A maternal HLA-G genetic polymorphism was investigated by polymerase chain reaction (PCR) analysis of DNA collected from granulosa cells surrounding oocytes harvested for the IVF procedure. While no statistically significant correlation was identified in this initial study, larger studies examining DNA from trios of mother, father and offspring are planned.

Adult↗