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Genes Mar 2024Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature... (Review)
Review
BACKGROUND
Among aneuploidies compatible with life, trisomy 22 mosaicism is extremely rare, and only about 25 postnatal and 18 prenatal cases have been described in the literature so far. The condition is mainly characterized by facial and body asymmetry, cardiac heart defects, facial dysmorphisms, growth failure, delayed puberty, and variable degrees of neurodevelopmental delay.
PROBLEM
The scattered information regarding the condition and the dearth of data on its natural history and developmental outcomes restrict genetic counseling, particularly in prenatal settings. Moreover, a prompt diagnosis is frequently delayed by the negative selection of trisomic cells in blood, with mosaicism percentage varying among tissues, which often entails the need for further testing. Purpose/topic: The aim of our work is to provide assistance in prenatal and postnatal genetic counseling by systematically delineating the current knowledge of the condition. This entails defining the prenatal and postnatal characteristics of the condition and presenting novel data from three cases, both prenatally and postnatally. Additionally, we report the developmental outcomes observed in two new patients.
Topics: Pregnancy; Female; Humans; Mosaicism; Prenatal Diagnosis; Trisomy; Chromosomes, Human, Pair 22; Uniparental Disomy; Chromosome Disorders
PubMed: 38540405
DOI: 10.3390/genes15030346 -
World Journal of Gastrointestinal... Dec 2023Colorectal cancer (CRC) is a prevalent malignant tumor involving adenomas that develop into malignant lesions. Carcinoembryonic antigen (CEA) is a non-specific serum...
BACKGROUND
Colorectal cancer (CRC) is a prevalent malignant tumor involving adenomas that develop into malignant lesions. Carcinoembryonic antigen (CEA) is a non-specific serum biomarker upregulated in CRC. The concentration of CEA is modulated by tumor stage and grade, tumor site in the colon, ploidy status, and patient smoking status. This study aimed to evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.
AIM
To evaluate current evidence regarding the diagnostic power of CEA levels in the early detection of CRC recurrence in adults.
METHODS
A systematic search was performed using four databases: MEDLINE, Cochrane Trials, EMBASE, and the Web of Science. The inclusion criteria were as follows: Adult patients aged ≥ 18 years who had completed CRC curative treatment and were followed up postoperatively; reporting the number of CRC recurrences as an outcome; and randomized, clinical, cohort, and case-control study designs. Studies that were not published in English and animal studies were excluded. The following data were extracted by three independent reviewers: Study design, index tests, follow-up, patient characteristics, and primary outcomes. All statistical analyses were performed using the RevMan 5.4.1.
RESULTS
A total of 3232 studies were identified, with 73 remaining following the elimination of duplicates. After screening on predetermined criteria, 12 studies were included in the final analysis. At a reference standard of 5 mg/L, CEA detected only approximately half of recurrent CRCs, with a pooled sensitivity of 59% (range, 33%-83%) and sensitivity of 89% (range, 58%-97%).
CONCLUSION
CEA is a significant marker for CRC diagnosis. However, it has insufficient sensitivity and specificity to be used as a single biomarker of early CRC recurrence, with an essential proportion of false negatives.
PubMed: 38222002
DOI: 10.4240/wjgs.v15.i12.2907 -
Frontiers in Endocrinology 2023Preimplantation genetic testing for aneuploidy (PGT-A) is an emerging technology that aims to identify euploid embryos for transfer, reducing the risk of embryonic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preimplantation genetic testing for aneuploidy (PGT-A) is an emerging technology that aims to identify euploid embryos for transfer, reducing the risk of embryonic chromosomal abnormalities. However, the clinical benefits of PGT-A in recurrent pregnancy failure (RPF) patients, particularly in young RPF patients, remains uncertain.
OBJECTIVE AND RATIONALE
This meta-analysis aimed to determine whether RPF patients undergoing PGT-A had better clinical outcomes compared to those not undergoing PGT-A, thus assessing the value of PGT-A in clinical practice.
SEARCH METHODS
We systematically searched PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database for Chinese Technical Periodicals (VIP) from 2002 to 2022. Thirteen published studies involving 930 RPF patients screened using PGT-A and over 1,434 RPF patients screened without PGT-A were included in this meta-analysis. Clinical outcomes were evaluated based on embryo transfers after PGT-A (n=1,015) and without PGT-A (n=1,799).
CLINICAL OUTCOMES
The PGT-A group demonstrated superior clinical outcomes compared to the fertilization (IVF)/intracytoplasmic sperm injection (ICSI) group. The PGT-A group had a significantly higher implantation rate (IR) (RR=2.01, 95% CI: [1.73; 2.34]), clinical pregnancy rate (CPR) (RR=1.53, 95% CI: [1.36; 1.71]), ongoing pregnancy rate (OPR) (RR=1.76, 95% CI: [1.35; 2.29]), live birth rate (LBR) (RR=1.75, 95% CI: [1.51; 2.03]), and significantly lower clinical miscarriage rate (CMR) (RR=0.74, 95% CI: [0.54; 0.99]). Subgroup analysis based on patient age (under 35 years and 35 years or older) showed that both PGT-A subgroups had significantly better CPR (P<0.01) and LBR (P<0.05) values compared to the IVF/ICSI groups.
SUMMARY
This meta-analysis demonstrates that PGT-A in RPF patients, is associated with improved clinical outcomes, including higher IR, CPR, OPR, and LBR values, and lower CMR compared to the IVF/ICSI group. These findings support the positive clinical application of PGT-A in RPF patients.
SYSTEMATIC REVIEW REGISTRATION
http://INPLASY.com, identifier INPLASY 202320118.
Topics: Pregnancy; Female; Humans; Male; Adult; Preimplantation Diagnosis; Semen; Genetic Testing; Fertilization in Vitro; Abortion, Spontaneous; Aneuploidy
PubMed: 37850092
DOI: 10.3389/fendo.2023.1178294 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of...
Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy.
PubMed: 37654386
DOI: 10.4103/jpbs.jpbs_547_22 -
Human Reproduction (Oxford, England) Oct 2023Is spontaneous collapse (SC) by human blastocysts a prognostic factor in IVF treatment? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Is spontaneous collapse (SC) by human blastocysts a prognostic factor in IVF treatment?
SUMMARY ANSWER
SC in human blastocyst is associated with reduced euploid embryo and pregnancy rates.
WHAT IS KNOWN ALREADY
SC of the human blastocyst is a phenomenon that was revealed relatively recently following the clinical application of time-lapse monitoring in IVF laboratories. The ploidy and clinical prognosis of affected blastocysts are still poorly understood, with inconsistent reports. Systematic reviews and meta-analyses on this topic are currently absent in the literature but its potential as a marker of embryo viability holds great clinical value. In this study, we aimed to comprehensively evaluate the potential of SC as a prognostic factor in regard to ploidy status, and pregnancy, live birth and miscarriage rates.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis were performed according to PRISMA guidelines, with a protocol registered with PROSPERO (CRD42022373749). A search of MEDLINE, EMBASE, and the Cochrane Library for relevant studies was carried out on 10 October 2022, using key words relevant to 'blastocyst collapse' and 'time-lapse imaging'.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Two independent reviewers systematically screened and evaluated each study in terms of participants, exposure, comparator, and outcomes (PECO). The Quality In Prognosis Studies tool was used for quality assessment. Data were extracted according to Cochrane methods. Pregnancy, live birth, ploidy, or miscarriage data were summarized by risk ratios (RRs) or odds ratios and their 95% CIs. All meta-analyses were performed with random-effects models.
MAIN RESULTS AND THE ROLE OF CHANCE
Following removal of duplicates, a total of 196 records were identified by the initial search. After screening according to PECO, 19 articles were included for further eligibility assessment. For meta-analysis, seven retrospective cohort studies were eventually included. After data pooling, the incidence of blastocyst SC was 37.0% (2516/6801) among seven studies (ranging from 17.4% to 56.2%). SC was associated with significantly lower clinical pregnancy rates (two studies, n = 736; RR = 0.77, 95% CI = 0.62-0.95; I2 = 30%), ongoing pregnancy rates (five studies, n = 2503; RR = 0.66, 95% CI = 0.53-0.83; I2 = 60%), and reduced euploidy rates (three studies, n = 3569; RR = 0.70, 95% CI = 0.59-0.83; I2 = 69%). Nevertheless, live birth rates (two studies, n = 816; RR = 0.76, 95% CI = 0.55-1.04; I2 = 56%) and miscarriage rate (four studies, n = 1358; RR = 1.31, 95% CI = 0.95-1.80; I2 = 0%) did not differ between blastocysts with or without SC. There was, however, significant heterogeneity between the studies included for evaluation of ongoing pregnancy rates (I2 = 60%, P = 0.04), live birth rates (I2 = 56%, P = 0.13), and ploidy rates (I2 = 69%, P = 0.04). Subgroup analyses were conducted according to different definitions of SC, number of collapse events, and whether the transferred blastocyst had undergone preimplantation genetic testing for aneuploidy; with inconclusive findings across subgroups.
LIMITATIONS, REASONS FOR CAUTION
All studies in the meta-analysis were retrospective with varying levels of heterogeneity for different outcomes. Not all studies had accounted for potential confounding factors, therefore only unadjusted data could be used in the main meta-analysis. Studies employed slightly different strategies when defining blastocyst SC. Standardization in the definition for SC is needed to improve comparability between future studies.
WIDER IMPLICATIONS OF THE FINDINGS
Our results indicate that blastocyst SC has negative implications for a pregnancy. Such blastocysts should be given a low ranking when selecting from a cohort for intrauterine transfer. Blastocyst SC should be considered as a contributing variable when building blastocyst algorithms to predict pregnancy or live birth.
STUDY FUNDING/COMPETING INTEREST(S)
There is no external funding to report. All authors report no conflict of interest.
REGISTRATION NUMBER
PROSPERO 2022 CRD42022373749.
Topics: Pregnancy; Female; Humans; Retrospective Studies; Abortion, Spontaneous; Prognosis; Pregnancy Rate; Live Birth; Blastocyst
PubMed: 37581900
DOI: 10.1093/humrep/dead166 -
Journal of Assisted Reproduction and... Oct 2023To establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy... (Meta-Analysis)
Meta-Analysis
PURPOSE
To establish if preimplantation genetic testing for aneuploidy (PGT-A) at the blastocyst stage improves the composite outcome of live birth rate and ongoing pregnancy rate per embryo transfer compared to conventional morphological assessment.
METHODS
A systematic literature search was conducted using PubMed, EMBASE and Cochrane database from 1st March 2000 until 1st March 2022. Studies comparing reproductive outcomes following in vitro fertilisation using comprehensive chromosome screening (CCS) at the blastocyst stage with traditional morphological methods were evaluated.
RESULTS
Of the 1307 citations identified, six randomised control trials (RCTs) and ten cohort studies fulfilled the inclusion criteria. The pooled data identified a benefit between PGT-A and control groups in the composite outcome of live birth rate and ongoing pregnancy per embryo transfer in both the RCT (RR 1.09, 95% CI 1.02-1.16) and cohort studies (RR 1.50, 95% CI 1.28-1.76). Euploid embryos identified by CCS were more likely to be successfully implanted amongst the RCT (RR 1.20, 95% CI 1.10-1.31) and cohort (RR 1.69, 95% CI 1.29-2.21) studies. The rate of miscarriage per clinical pregnancy is also significantly lower when CCS is implemented (RCT: RR 0.73, 95% CI 0.56-0.96 and cohort: RR 0.48, 95% CI 0.32-0.72).
CONCLUSIONS
CCS-based PGT-A at the blastocyst biopsy stage increases the composite outcome of live births and ongoing pregnancies per embryo transfer and reduces the rate of miscarriage compared to morphological assessment alone. In view of the limited number of studies included and the variation in methodology between studies, future reviews and analyses are required to confirm these findings.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Aneuploidy; Birth Rate; Blastocyst; Genetic Testing
PubMed: 37479946
DOI: 10.1007/s10815-023-02866-0 -
Fertility and Sterility Aug 2023Noninvasive and minimally invasive preimplantation genetic testing for aneuploidy (PGT-A) is a tool that may one day become the gold standard for embryonic chromosomal...
Noninvasive and minimally invasive preimplantation genetic testing for aneuploidy (PGT-A) is a tool that may one day become the gold standard for embryonic chromosomal screening. Investigations on this topic have ranged from studying the culture media of embryos to the fluid inside the blastocoel, all in an attempt to find a reliable source of DNA without the need to biopsy the embryo. There is great interest across the board, both from those for and against biopsy, in a reliable test process that would give the patient and provider the same information possible from a biopsy without the risk. We aim to explore the current available research to better understand the utility and accuracy of PGT-A with these new sampling techniques. General concordance rates in comparison with biopsy-based PGT-A are promising, but it is clear that additional research and understanding are needed before adopting noninvasive and minimally invasive PGT-A as a widely used tool with strong clinical utility.
Topics: Pregnancy; Female; Humans; Preimplantation Diagnosis; Genetic Testing; Aneuploidy; Blastocyst; Culture Media; Fertilization in Vitro
PubMed: 37356468
DOI: 10.1016/j.fertnstert.2023.06.013 -
Fertility and Sterility Jul 2023To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat... (Review)
Review
IMPORTANCE
To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment.
OBJECTIVE
International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management.
EVIDENCE REVIEW
A systematic review without meta-analysis of studies published in English from January 2015 to May 2022.
FINDINGS
Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence.
CONCLUSION
True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age).
RELEVANCE
Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement.
Topics: Humans; Female; Embryo Implantation; Embryo Transfer; Infertility; Reproductive Techniques, Assisted; Aneuploidy; Retrospective Studies
PubMed: 36822566
DOI: 10.1016/j.fertnstert.2023.02.014 -
Prenatal Diagnosis Feb 2023The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The aim was to determine the accuracy of cell-free DNA testing (cfDNA) for detecting sex chromosome aneuploidies (SCA) in singleton pregnancies.
METHODS
A systematic review and meta-analysis was performed to assess cfDNA accuracy for prenatal detection of 45,X, 47,XXY, 47,XXX and 47,XYY. Inclusion was restricted to studies published between January 2010 and December 2021 reporting both cfDNA and confirmatory diagnostic test results.
RESULTS
For 45,X, the sensitivity was 98.8% (95%CI 94.6%-100%), specificity 99.4% (95%CI 98.7%-99.9%) and positive predictive value (PPV) 14.5% (95%CI 7.0%-43.8%). For 47,XXY, the sensitivity was 100% (95%CI 99.6%-100%), specificity 100% (95%CI 99.9%-100%) and PPV 97.7% (95%CI 78.6%-100%). For 47,XXX, the sensitivity was 100% (95%CI 96.9%-100%), specificity 99.9% (95%CI 99.7%-100%) and PPV 61.6% (95%CI 37.6%-95.4%). For 47,XYY, the sensitivity was 100% (95%CI 91.3%-100%), specificity 100% (95% CI 100%-100%) and PPV 100% (95%CI 76.5%-100%). All four SCAs had estimated negative predictive values (NPV) exceeding 99.99%, though false negatives were reported.
CONCLUSIONS
This analysis suggests that cfDNA is a reliable screening test for SCA, though both false negatives and false positives were reported. These estimates of test performance are derived from pregnancies at high pretest risk for aneuploidy, limiting the generalisability to average risk pregnancies.
Topics: Pregnancy; Female; Humans; Cell-Free Nucleic Acids; Sex Chromosome Aberrations; Aneuploidy; Chromosomes, Human, X; Prenatal Diagnosis
PubMed: 36588186
DOI: 10.1002/pd.6298 -
Andrology Oct 2022The environment plays a key role in male infertility, changing the incidence in various populations, and pesticides are one of the most studied hazards. The use of the... (Review)
Review
BACKGROUND
The environment plays a key role in male infertility, changing the incidence in various populations, and pesticides are one of the most studied hazards. The use of the latter has never decreased, jeopardizing the safety of workers and the general population.
OBJECTIVE
Our purpose was to summarize the results of studies discussing the association between pesticides and male fertility.
METHODS
A comprehensive literature search was performed through MEDLINE via PubMed, Scopus, and Web of Science. Only human studies were considered. Semen parameters and DNA integrity were considered to evaluate the effect of pesticides on men.
RESULTS
A total of 64 studies that investigated their impact in terms of semen parameters (51 studies) and chromatin and DNA integrity (25 studies) were included. The most frequently affected parameters were total sperm count, sperm motility, and sperm morphology, although a reduction in ejaculate volume and concentration occur in several cases. A tangible worsening of semen quality was associated with organochlorines and organophosphates. Furthermore, pesticide exposure, especially pyrethroids, was related to a higher DNA fragmentation index and chromosome aneuploidy in most articles.
CONCLUSION
The epidemiological evidence supports the association between pesticides and male fertility for workers and the exposed population in terms of semen quality, DNA fragmentation, and chromosome aneuploidy.
Topics: Aneuploidy; Chromatin; DNA; Fertility; Humans; Infertility, Male; Male; Occupational Exposure; Organophosphates; Pesticides; Pyrethrins; Semen; Semen Analysis; Sperm Count; Sperm Motility; Spermatozoa
PubMed: 35793270
DOI: 10.1111/andr.13228