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Microsimulation models may assist in making individual fLife expectancy should be estimated. Clinical assessment should be per and the choice requires careful analysis of additional factors. Yearly expectancy is lower than the presumed durability of the bio echocardiographic examination is recommended after the fth prosthesis, particularly if comorbidities may necessitate further year in patients with a bioprosthesis and earlier in young patients. Indications for antithrombotic therapy after valve repair or Although bioprosthetic recipients can avoid long-term use of replacement are summarized in Table 19. Oral anticoagulation is the rst postoperative month is a high-risk period for thrombo recommended lifelong for all I B 213 embolism and anticoagulation should not be lower than the target patients with a mechanical prosthesis. In addition, during this period, anticoagula recommended lifelong for tion is subject to increased variability and should be monitored patients with bioprostheses I C more frequently. Monitoring by following intracoronary stenting, but increases the risk of bleeding. The oral route should be favoured over the 203,227 management, based on risk assessment. Besides prosthesis intravenous route, which may carry a higher risk of anaphylaxis. Intravenous prothrombin complex ract removal) and those procedures where bleeding is easily con concentrate has a short half-life and, if used, should therefore be trolled (recommendation class I, level of evidence C). The prognosis is favourable with medical If required, after a careful risk-benet assessment, combined therapy in most cases of small thrombus (,10 mm). A good aspirin therapy should be discontinued 1 week before a non response with gradual resolution of the thrombus obviates the cardiac procedure.

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Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: Identification of the categories for which it should be proposed. Preimplantation genetic diagnosis for aneuploidy screening in women older than 37 years. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages. Substandard application of preimplantation genetic screening may interfere with its clinical success. Multicentre trial of preimplantation genetic screening reported in the New England Journal of Medicine: An in-depth look at the findings. Technology requirements for preimplantation genetic diagnosis to improve assisted reproduction outcomes. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Chromosomal mosaicism in cleavage-stage human embryos and the accuracy of single-cell genetic analysis. Impact of blastomere biopsy and cryopreservation techniques on human embryo viability. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. The cytogenetics of polar bodies: Insights into female meiosis and the diagnosis of aneuploidy. First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy. Comparative genomic hybridization of oocytes and first polar bodies from young donors. Comprehensive chromosome screening of polar bodies and blastocysts from couples experiencing repeated implantation failure. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Detection of aneuploidy by array comparative genomic hybridization using cell lines to mimic a mosaic trophectoderm biopsy. Clinical validation for mosaicism detected in trophectoderm biopsy samples analyzed by chromosomal microarrays. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Live birth outcome with trophectoderm biopsy, blastocyst vitrification, and single-nucleotide polymorphism microarray-based comprehensive chromosome screening in infertile patients. Development and validation of an accurate quantitative real-time polymerase chain reaction-based assay for human blastocyst comprehensive chromosomal aneuploidy screening. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: A prospective, blinded, nonselection study.

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Of the 135 potential articles, 10 Chromosome Microarray Testing (Non-Oncology Conditions) Page 8 of 21 UnitedHealthcare Commercial Medical Policy Effective 07/01/2019 Proprietary Information of UnitedHealthcare. Combined data of the reviewed studies (n = 18) indicated that fetuses with an ultrasound anomaly restricted to one anatomical system (n = 2220) had a 3. The authors concluded that microarray has considerable diagnostic and prognostic value in these pregnancies. Out of the 125 cases with abnormal findings, 110 were also detected by conventional karyotype analysis. In contrast, the incremental yield was marginal in patients with fetus with increased nuchal translucency (0. In the subset with normal karyotype, clinically significant abnormalities were identified in 6. This detection rate did not vary significantly with gestational age, suggesting that, unlike aneuploidy, the contribution of submicroscopic chromosomal abnormalities to fetal demise does not vary with gestational age. The authors concluded that both the provision of results in cases in which karyotype fails and the detection of abnormalities in the presence of a normal karyotype demonstrate the increased diagnostic utility of microarray in pregnancy loss. Other well-known microdeletion or microduplication syndromes were also identified in six cases. The authors concluded that microarray analysis identified clinically significant genomic alterations in 6. A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. The array correctly identified all 10 (100%) anomalies and identified additional complex rearrangements in 2 (20%) of the cases. A total of 46,298 postnatal patients were tested by chromosomal microarray analysis for a variety of indications, most commonly intellectual disability/developmental delay, congenital anomalies, dysmorphic features, and neurobehavioral problems. The frequency of detection of abnormalities associated with actionable clinical features was tallied, and the Chromosome Microarray Testing (Non-Oncology Conditions) Page 11 of 21 UnitedHealthcare Commercial Medical Policy Effective 07/01/2019 Proprietary Information of UnitedHealthcare. A total of 2088 diagnoses were made of more than 100 different disorders that have specific clinical features that warrant follow-up. In a subset of cases monitored for physician response, appropriate clinical action was taken more than 90% of the time as a direct result of the microarray finding. The authors concluded that the disorders diagnosed by chromosomal microarray analysis frequently have clinical features that need medical attention, and physicians respond to the diagnoses with specific clinical actions, thus arguing that microarray testing provides clinical utility for a significant number of patients tested. The study included 349 individuals; 223 males, 126 females, aged 5 months-19 years.

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Some have estimated that it would take two to six hours of in-person genetic counseling over several sessions. Even with an adequate number of genetic counselors and sufcient time, most individuals would have difculty absorbing so much complex, largely prob abilistic, and varied information. Scholarsarealreadyaddressingthedecision-makingchallengesofmov ing from targeted genetic testing to genome sequencing in the general population, see eg Sarah Bowdin et al. Deciding what kind of genomic information one wants to receive is not unique to the reproductive context. For example, while most individu als would want information about medically actionable health risks in the adult genetic testing context,53 they may be uncertain about the value of learning information related to health risks for which there are limited or no interventions. People are ofen not good predictors, ex ante, about the kind of information they will want when they actually con front the option to obtain such information. Tese challenges are potentially even greater in the reproductive context where the interest in and desire for genetic information is not simply a medical decision, but a choice based on personal values and circumstances. Certainly such factors come into play with many medical decisions to varying degrees. As a result, decision making is complex even in the current environment where prenatal testing focuses on a single or limited number of conditions. In other words, information that might not infuence deci sions about whether to continue a pregnancy, such as lesser medical risks, could poten tially infuence decisions about which embryos to implant. As researchers discover more meaningful associations between genetic variants and non-medical traits, comprehensive genomic analysis will force us to consider the relevance of information about non-medical traits in this context. Certain non medical traits, such as sex, infuence decisions to terminate pregnancies in some coun tries. Parents might, for example, decidethattheywouldliketoknowaboutinbornerrorsofmetabolismtomakedietaryadjustmentsimmedi ately in the newborn period. While some parents might implant an embryo that would develop an inborn error of metabolism and plan to treat with diet, many or most would likely chose a diferent embryo that did not have such a risk. For example, genomic analysis could reveal an increased propensity for certain characteristics the parents might not prefer (eg shorter stature65) in combination with an increased propensity for traits the parents particularly value (eg musicality66). The more compre hensive and complex the genomic profle of the fetus, the beter the odds it would only satisfy curiosity and not assist with decisions about whether to continue a pregnancy.

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