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Query: UMLS:C0013080 (Down syndrome)
 14,180 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 42-year-old female patient with history of secondary infertility was referred to our assisted conception unit for in vitro fertilization (IVF). Before her referral, she had two cycles of IVF at another centre; the first was unsuccessful and, after conceiving at the second attempt, the pregnancy was terminated at 14 weeks' gestation following a positive nuchal translucency scan and a diagnosis of trisomy 21 (Down syndrome) by a chorionic villous biopsy performed in the first trimester. The screening tests for trisomy 21 were offered to the patient in view of her advanced age. Subsequent karyotyping revealed that both partners had a normal chromosomal complement. Following genetic counselling, the couple were offered IVF treatment along with preimplantation genetic screening for trisomy 21. Four of the five embryos were suitable for biopsy, and one blastomere from each embryo was analyzed using fluorescent in situ hybridization for chromosome 21. The analysis revealed that two embryos had trisomy 21, one had monosomy 21, and only one embryo was diploid for chromosome 21. The single diploid embryo was transferred to the uterus on day 3, and resulted in an uneventful pregnancy and delivery of a healthy live-born male.
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PMID:Live birth following preimplantation genetic screening for trisomy 21. Should aneuploidy screening be offered to all older patients undergoing IVF? 1832 Apr 37

Aneuploidy, which leads to unpaired chromosomal axes during meiosis, is frequently accompanied by infertility. We previously showed, using three mouse models of Down syndrome, that it is an extra chromosome, but not extra gene dose, that is associated with male infertility and virtual absence of post-meiotic gem cells. Here, we test the hypothesis that aneuploid segments are differentially modified and expressed during meiosis, depending on whether they are present as an extra chromosome or not. In all three models examined, the trisomic region lacks a pairing partner, but in one case, spermatocytes have an extra (and unpaired) chromosome, while the two other models involve translocation of the trisomic region rather than an extra chromosome. An extra unpaired chromosome was always modified by phosphorylation of histone H2AX and lacked RNA PolII. But in the case of trisomic regions attached to a paired chromosome, assembly of these protein modifications was affected by the position of a trisomic region relative to a centromere and the physical extent of the unpaired chromatin. Analysis of gene expression in testes revealed that extra copy number alone was not sufficient for meiotic upregulation of genes in the trisomic interval. Additionally and unexpectedly, presence of meiotic gene silencing chromatin modifications was not sufficient for downregulation of genes in unpaired trisomic chromatin. Thus, the meiotic chromatin modifications that are cytologically visible are unlikely to be directly involved in sterility versus fertility of DS models. Finally, the presence of an extra unpaired chromosome, but not the presence of extra (trisomic) genes, caused global deregulation of transcription in spermatocytes. These results reveal mechanisms by which an extra chromosome, but not trisomic gene dose, impact on meiotic progress and infertility.
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PMID:Meiotic behavior of aneuploid chromatin in mouse models of Down syndrome. 1963 31

In Lebanon, assisted reproductive techniques (ART) are widely used to overcome infertility, but the genetic risk associated with these techniques is still ignored. In this study, in order to estimate the transmission risk of paternal chromosomal anomalies to ART offspring, the meiotic segregation of chromosomes X, Y, 18, and 21 was analyzed by fluorescent in situ hybridization on the spermatozoa of 19 Lebanese infertile men. Our results show significantly higher frequencies of sex chromosome disomies in the group of patients with oligozoospermia compared with a control group of fertile males. Interestingly, the sex chromosome aneuploidy rates were highly variable between oligozoospermic patients, and ranged between 0.9% and 12.87%. No significant increase in aneuploidy rates was found for the group of nonoligozoospermic patients with asthenozoospermia and/or teratozoospermia. In addition, the disomy rate for chromosome 21 was analyzed in 8 patients, in whom higher disomy rates were shown as compared with the controls. Altogether, the results suggest that Lebanese oligozoospermic men undergoing ART may have an increased risk of transmitting sex chromosome anomalies to their offspring, as well as, in some cases, trisomy 21. Based on this work, genetic counseling programs for Lebanese infertile couples undergoing ART procedures should be developed, in order to improve the investigation and selection of Lebanese infertile couple candidates for ART procedures and optimize the choice of ART techniques.
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PMID:High frequency of sex chromosomal disomy in spermatozoa of Lebanese infertile men. 2116 47

Apart from a personal tragedy, could Down syndrome, cancer and infertility possibly have something in common? Are there links between a syndrome with physical and mental problems, a tumor growing out of control and the incapability to reproduce? These questions can be answered if we look at the biological functions of a protein complex, named cohesin, which is the main protagonist in the regulation of sister chromatid cohesion during chromosome segregation in cell division. The establishment, maintenance and removal of sister chromatid cohesion is one of the most fascinating and dangerous processes in the life of a cell. Errors in the control of sister chromatid cohesion frequently lead to cell death or aneuploidy. Recent results showed that cohesins also have important functions in non-dividing cells, revealing new, unexplored roles for these proteins in human syndromes, currently known as cohesinopathies. In the last 10 years, we have improved our understanding of the molecular mechanisms of the cohesin and cohesin-interacting proteins regulating the different events of sister chromatid cohesion during cell division in mitosis and meiosis.
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PMID:Sister chromatid cohesion control and aneuploidy. 2125 90

Family history as a screening technique has received little attention from epidemiologists as a means of early detection of disorders. In this paper, we present several every-day family cases that will prepare the family physician to make use, at will, of this special investigative tool. We deal primarily with Down's syndrome, defects of the central nervous system, infertility, metabolic disorders and, finally, marriage of close relations. For each case, the role to be played by the physician dealing with a positive family history involving a problem is detailed in terms of risks of occurrence and recurrence of the condition; particular aspects of the counselling process are presented, especially the logistic, psychological, ethical and social aspects. We conclude that the family physician should routinely take a complete, detailed and accurate family history of the patients whom he/she sees, both in the course of obsterical care and during routine check-ups, in order to help identify cases of family-related chronic diseases.
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PMID:[Not Available]. 2126 71

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.
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PMID:Causes of infertility in men with Down syndrome. 2180 50

Mistakes in chromosome segregation lead to aneuploid cells. In somatic cells, aneuploidy is associated with cancer but in gametes, aneuploidy leads to infertility, miscarriages or developmental disorders like Down syndrome. Haploid gametes form through species-specific developmental programs that are coupled to meiosis. The first meiotic division (MI) is unique to meiosis because sister chromatids remain attached while homologous chromosomes are segregated. For reasons not fully understood, this reductional division is prone to errors and is more commonly the source of aneuploidy than errors in meiosis II (MII) or than errors in male meiosis. In mammals, oocytes arrest at prophase of MI with a large, intact germinal vesicle (GV; nucleus) and only resume meiosis when they receive ovulatory cues. Once meiosis resumes, oocytes complete MI and undergo an asymmetric cell division, arresting again at metaphase of MII. Eggs will not complete MII until they are fertilized by sperm. Oocytes also can undergo meiotic maturation using established in vitro culture conditions. Because generation of transgenic and gene-targeted mouse mutants is costly and can take long periods of time, manipulation of female gametes in vitro is a more economical and time-saving strategy. Here, we describe methods to isolate prophase-arrested oocytes from mice and for microinjection. Any material of choice may be introduced into the oocyte, but because meiotically-competent oocytes are transcriptionally silent cRNA, and not DNA, must be injected for ectopic expression studies. To assess ploidy, we describe our conditions for in vitro maturation of oocytes to MII eggs. Historically, chromosome-spreading techniques are used for counting chromosome number. This method is technically challenging and is limited to only identifying hyperploidies. Here, we describe a method to determine hypo-and hyperploidies using intact eggs. This method uses monastrol, a kinesin-5 inhibitor, that collapses the bipolar spindle into a monopolar spindle thus separating chromosomes such that individual kinetochores can readily be detected and counted by using an anti-CREST autoimmune serum. Because this method is performed in intact eggs, chromosomes are not lost due to operator error.
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PMID:Mouse oocyte microinjection, maturation and ploidy assessment. 2180 28

BACKGROUND Across the developed world couples are postponing parenthood. This review assesses the consequences of delayed family formation from a demographic and medical perspective. One main focus is on the quantitative importance of pregnancy postponement. METHODS Medical and social science databases were searched for publications on relevant subjects such as delayed parenthood, female and male age, fertility, infertility, time to pregnancy (TTP), fetal death, outcome of medically assisted reproduction (MAR) and mental well-being. RESULTS Postponement of parenthood is linked to a higher rate of involuntary childlessness and smaller families than desired due to increased infertility and fetal death with higher female and male age. For women, the increased risk of prolonged TTP, infertility, spontaneous abortions, ectopic pregnancies and trisomy 21 starts at around 30 years of age with a more pronounced effects >35 years, whereas the increasing risk of preterm births and stillbirths starts at around 35 years with a more pronounced effect >40 years. Advanced male age has an important but less pronounced effect on infertility and adverse outcomes. MAR treatment cannot overcome the age-related decline in fecundity. CONCLUSIONS In general, women have partners who are several years older than themselves and it is important to focus more on the combined effect of higher female and male age on infertility and reproductive outcome. Increasing public awareness of the impact of advanced female and male age on the reproductive outcome is essential for people to make well-informed decisions on when to start family formation.
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PMID:Demographic and medical consequences of the postponement of parenthood. 2198 71

The most frequent defect of the male urogenital tract at birth is cryptorchidism. Cryptorchidism causes primitive testicular pathology responsible for infertility. Men with Down's syndrome (DS) have an increased risk of cryptorchidism. The spermatid perinuclear RNA-binding protein (STRBP) gene codifies a microtubule-associated RNA-binding protein and it is highly expressed in the testis as well as in the brain. At both levels, this gene seems to play a relevant role in the regular development of these organs. These observations prompted us to evaluate the expression of STRBP mRNA in 5 DS men with cryptorchidism and 5 normal healthy men (controls) by quantitative Real Time PCR in peripheral blood leukocytes. We found a decreased expression of the STRBP gene in men with DS and cryptorchidism compared with controls. This finding suggests that the impaired expression of this gene in DS may play a pathogenetic role in the altered brain and testicular development in subjects with DS and cryptorchidism.
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PMID:Expression of STRBP mRNA in patients with cryptorchidism and Down's syndrome. 2239 Nov 37

Chromosome abnormalities are extremely common in human oocytes and embryos and are associated with a variety of negative outcomes for both natural cycles and those using assisted conception techniques. Embryos containing the wrong number of chromosomes (aneuploidy) may fail to implant in the uterus, miscarry, or lead to children with serious medical problems (e.g., Down syndrome). Preimplantation genetic screening (PGS) is a method that seeks to improve the outcomes of assisted reproductive treatments, such as in vitro fertilization (IVF), by ensuring that the embryos chosen for transfer to the uterus are chromosomally normal. Here we summarize published and novel data concerning the frequency and variety of chromosomal abnormalities seen in oocytes and embryos at the cleavage and blastocyst stages of development. Clinical outcomes of studies using PGS are presented, and the controversy over the use of chromosome screening as a tool for embryo selection is discussed. We describe validation and preliminary clinical data from the new generation of methods being used for PGS, including comparative genomic hybridization (CGH), microarrays (aCGH and single nucleotide polymorphism arrays), and quantitative polymerase chain reaction. These methodologies allow comprehensive chromosomal analysis, provide high accuracy, and have yielded encouraging preliminary clinical data. The combination of advances in genetics and embryology seems poised to usher in a new era in the treatment of infertility.
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PMID:Aneuploidy screening for embryo selection. 2272 10


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