Prenatal Genetic Diagnostic Testing Research Articles

P-233 Embryo transfer timing and clinical pregnancy success: a retrospective study

Abstract Study question The aim of this study is to compare the clinical outcome of day5 versus day6 genetically normal blastocyst transfers. Summary answer 1000 oocytes were analyzed showing a highly significant difference in the number of normal embryos and clinical pregnancy rates in day5 versus day6 blastocysts What is known already studies have shown that day 5 embryos have a higher pregnancy rate compared to day 6 embryos, some studies had only euploid embryos transferred and others did not have any genetic testing done on embryos. No study had a sample size as large as 1760 and the number of embryos studied was a limiting factor in their results. Study design, size, duration The study is a retrospective cross-sectional chart review with multivariate analysis, data from January 2019 up to February 2023 were extracted. 1760 patients were recruited, 1000 in the day5 group and 760 in the day6 group. The data recorded for each patient included maternal age, body mass index (BMI), anti-Müllerian hormone (AMH) level, number, prenatal genetic diagnostic testing, frozen embryo transfer, sperm parameters, and pregnancy status. Participants/materials, setting, methods All embryos were genetically tested for aneuploidy before transfer, using next-generation sequencing technology to rule out 24-chromosome aneuploidies (1-22, X, Y). All patients who have single embryo transfer, frozen embryos and pre-implantation genetic diagnosis (PGD) were included in the study. Continuous variables were expressed as mean with standard deviation and categorical variables as numbers and frequencies (percentages). Statistical differences between groups were estimated using the chi-square or Fisher’s test. All analyses were performed using SAS studio. Main results and the role of chance 1,000 cycles were analyzed for Day 5 and 760 for Day 6 embryo. The number of blastocysts formed, and genetically diagnosed embryos significantly favor the Day 5 group. There’s a significant difference in the number of normal embryos, with the Day 5 group having more. There is a highly significant difference in clinical pregnancy rates. On the other hand, the differences in biochemical pregnancies are not statistically significant. The occurrence of ectopic pregnancies shows no significant difference. Additionally, there is no statistically significant difference in the rates of miscarriage. There is a highly significant difference in blastocyst formation rates, with Day 5 embryos. This indicates that Day 5 embryos have a significantly higher likelihood of forming blastocysts compared to Day 6 embryos. Implantation: Day 5 embryos have an implantation rate of 62.0% compared to 49.7% for Day 6 embryos. Day 5 embryos exhibit a significantly higher likelihood of successful implantation. Euploid: The difference in euploid rates is statistically significant, albeit with a lower p-value of 0.0236. Day 5 embryos have a rate of 59.6%, while Day 6 embryos have a rate of 56.0%. Day 5 embryos are associated with a lower likelihood of being aneuploid Limitations, reasons for caution Limitation of this study is that we do not have data available regarding complications during pregnancy in the day 5 versus day 6 groups and we had no data regarding the the live birth rate between the two groups. Wider implications of the findings This study has the potential to revolutionize worldwide discussions during IVF consultations. With the large sample size we can provide for the first time a statistically significant difference in the percentage of success when transferring a day5 (61%) versus day6 (49%) euploid embryo. Trial registration number not applicable

Failure to diagnose hypochondroplasia by prenatal diagnosis: a case report

BackgroundHypochondroplasia (HCH) is a common nonlethal skeletal dysplasia caused by pathogenic variations in the fibroblast growth factor receptor 3 (FGFR3) gene, and HCH has similar clinical manifestations with achondroplasia (ACH), which can be screened during the fetal period by prenatal ultrasound testing and diagnosed by genetic testing.Case presentationwe report the special case of a patient with obvious growth retardation and rhizomelic disproportionate short stature, accompanied by other manifestations, including an enlarged head and short hands at 1 year old. However, several multiple color ultrasound exams identified shortened limbs (< 3rd percentile), an increased biparietal diameter (> 95th percentile) and a low nasal bridge in the fetal period. Due to the high incidence rate of ACH, genetic testing for the hotspot FGFR3 gene c.1138 g > A pathogenic variations was performed immediately in the third trimester. Unfortunately, the definitive diagnosis could not be made before birth due to the negative result of hotspot gene exam. Whole exome sequencing (WES) was performed at 1 year identified FGFR3 gene c.1620C > A variations positivity, and the patient was finally diagnosed as HCH.ConclusionOur report extends the understanding of the limitations of prenatal genetic diagnostic testing, especially the hot spot pathogenic variations test should be not the only clinical diagnostic basis. Moreover, this case also emphasizes that further gene analysis for patients with significant conflict between the clinical manifestation and the prenatal genetic panel examination findings should be reconducted timely to spare the family from a delayed diagnosis or a misdiagnosis.

Disparities in the acceptance of chromosomal microarray at the time of prenatal genetic diagnosis.

Chromosomal microarray (CMA) increases the diagnostic yield of prenatal genetic diagnostic testing but is not universally performed. Our objective was to identify provider and patient characteristics associated with the acceptance of CMA at the time of prenatal genetic diagnostic testing. Retrospective cohort study of patients undergoing prenatal genetic diagnostic testing (chorionic villus sampling or amniocentesis) at a single institution between 2014 and 2020. Primary outcome was the acceptance of CMA based on the genetic counselor ,GC who saw the patient. Secondary analyses assessed patient characteristics associated with the acceptance of CMA. 2372 participants were included. Fifty-eight percent of participants accepted CMA. Acceptance of CMA varied significantly by GC, ranging from 31% to 90%. Patients with public insurance and those who identified as Black or Hispanic/Latina were less likely to have CMA performed (aOR 0.24, 95% CI 0.20-0.30, and 0.68, 95% CI 0.50-0.92). Even among those with a structural anomaly present, public insurance was associated with significantly lower odds of CMA being performed (aOR 0.39, 95% CI 0.25-0.61). Acceptance of CMA at the time of prenatal genetic diagnostic testing varied based on the GC performing the counseling. Public insurance was associated with lower frequency of accepting CMA.

Indications, Results and Complications of Prenatal Genetic Diagnostic Testing at a Single Healthcare Center

Indications, Results and Complications of Prenatal Genetic Diagnostic Testing at a Single Healthcare Center

904 Prenatal genetic diagnostic testing during the COVID-19 pandemic

904 Prenatal genetic diagnostic testing during the COVID-19 pandemic

Psychological measures of patient’s decision-making for prenatal genetic testing

Objective To use a questionnaire to determine the levels of maternal decision-related distress, clarity of the pros and cons, and certainty when considering prenatal genetic diagnostic testing; and to assess the relationship between these constructs and patient characteristics. Method Cross-sectional study. Voluntary, anonymous questionnaires distributed 2017–2019 to women referred for invasive prenatal genetic testing. Excluded: English or Spanish illiterate. Maternal characteristics were collected. Questions evaluated distress, decisional certainty, and decisional clarity on a 5-point Likert scale (range: 0 = low/uncertain/unclear to 4 = high/certain/clear). Analysis: non-parametric Kruskal–Wallis, correlation statistics, and ANOVA. Results Forty-four female patients completed it. Most were married, white, Catholic, and multiparous. 58% had already made a testing decision. Patients expressed low distress levels (mean 1.18 ± 0.80) and expressed high decisional certainty (mean 3.28 ± 0.76) and clarity (mean 3.30 ± 0.99). Decisional certainty and clarity were positively correlated (r = 0.47, p < .01), whereas distress was negatively correlated with decisional certainty (r = −0.8136, p < .0005) and decisional clarity (r = −0.49, p = .007). No significant differences by religion or parity. Greater distress (p < .05) and less decisional clarity (p = .07) occurred between those still debating testing vs those who had decided. Conclusions Higher maternal distress scores were associated with lower decisional certainty and decisional clarity in women considering prenatal genetic testing.

877: The association between patient characteristics and psychological experiences when deciding about prenatal genetic diagnostic testing

The decision to pursue prenatal genetic diagnostic testing (PGDT) can be psychologically challenging, with influence from family or cultural constructs. Our objective was to determine if selected patient characteristics are associated with the degree of distress, certainty, and decisional clarity when considering PGDT. Cross-sectional design. Patients were given a voluntary, anonymous questionnaire (Q) assessing the decision-making process in regards to invasive (CVS and/or amniocentesis) PGDT. Qs were distributed from 2017-2019 to those referred for genetic testing. Questions (44 total, 5-point Likert scale with 0-4 range) were structured to evaluate patient decisional certainty, distress, and clarity on the pros/cons, and were partly adapted from published validated Q’s. Exclusion criteria: English or Spanish illiterate. Means, variances (SD), and ranges were tabulated. 3 variables were examined a priori for potential influence on the Q responses. 44 patients completed the Q (77% white, 45% Catholic, 35% less than college degree). 25% were nulliparous and 25% were undecided as whether to pursue PGDT. See Table 1. There was no significant difference in regards to distress (p=0.37), decisional clarity (p=0.16) or certainty (p=0.50) between Catholics and non-Catholics. There was no significant difference in regards to distress (p=0.37), decisional clarity (p=0.40) or certainty (p=0.82) between nulliparous vs. multiparous patients. Greater distress (1.6±0.75 v 1.1±0.78, p< 0.05) and less decisional clarity (2.7±1.36 v 3.5±0.64, p=0.07) were noted between those who were still debating PGDT testing vs those who had decided. In this group, there was no statistically significant difference in decisional certainty scores (p=0.17). Women who are in the midst of the decision reported greater distress and less clarity. This information suggests that provider counseling and follow up of patients in proximity to the PGDT recommendation may be beneficial. Future studies can investigate other patient characteristics that may influence decision making for PGDT.

How Uncertain Are Patients in Regards to Invasive Prenatal Genetic Diagnostic Testing? [25K

INTRODUCTION: The purpose of this project is to determine patients' decisional certainty regarding the use of invasive prenatal genetic diagnostic testing (PGDT). METHODS: Cross-sectional design, IRB-approved study. Voluntary, anonymous questionnaire (Q) assessing patient decision making process in regards to invasive (CVS and/or amniocentesis) PGDT. Q (paper and online options) were distributed from 2017-2018 to those undergoing genetic testing in a university academic practice. Questions (7 items on certainty, 5-point Likert scale) were structured to evaluate patient decisional certainty, and were partly adapted from published validated Q's. Exclusion criteria: English or Spanish illiterate. Means, variances (SD), and ranges were tabulated. RESULTS: 50 female patients returned the study; 38 (76%) completed it entirely. Patients mean age was 31.76±6.07 years and 79% were Caucasian. 75% had equal PGDT decision making with their partner. Most were referred due to a positive carrier screen, or a positive cell free DNA result. 71% of patients had already made a decision at the time of the Q. Participants expressed high certainty of their decision to do PGDT (mean 3.18 on a 1=uncertain to 5=certain scale, SD 0.79). Non-white women appeared to have greater decisional certainty than white patients (3.54 (SD 0.6) v 3.08 (SD 0.8), respectively). CONCLUSION: Patients are very certain in their decision-making regarding PGNT; however this may be a reflection of when they completed the survey as most did so after deciding on PGDT.

How Well Do Patients Clearly Understand Invasive Prenatal Genetic Diagnostic Testing? [38L

INTRODUCTION: To determine patient clarity of the perceived benefits/drawbacks about invasive prenatal genetic diagnostic testing (PGDT). METHODS: Cross-sectional design. Voluntary, anonymous questionnaire (Q) assessing patient's decision making process in regards to invasive (CVS and/or amniocentesis) PGDT. Qs (paper and online options) were distributed between 2017 and 2018 to those recommended for PGDT in a university academic practice. Questions (5 items on clarity, 5-point Likert scale) were structured to evaluate patient decisional clarity, and were partly adapted from published validated Q's. Exclusion criteria: English or Spanish illiterate. Means, variances (SD), and ranges were tabulated. RESULTS: 50 female patients returned the study; 38 (76%) completed it in entirety. 75% had equal PGDT decision making with their partner. Most were referred due to a positive carrier screen followed by positive cell free DNA result. Participants expressed high clarity of understanding advantages and disadvantages of PGDT (mean 3.28 on a 1=no clarity to 5=high clarity scale, SD 0.94). CONCLUSION: Patients have a clear understanding of PGDT; this may be attributable to in office counseling (MD and/or genetic counselors) done prior to decision making.

Prenatal Genetic Diagnostic Testing in the Era of Cell Free Fetal DNA For Aneuploidy Screening [10D

INTRODUCTION: Prenatal screening for fetal aneuploidy has improved tremendously since the incorporation of cell-free DNA (cfDNA) in to the genetic screening armamentarium. Despite its improved detection rate of aneuploidy, this remains a screening tool and not designed to provide diagnostic information. This study aimed to assess whether initiation of cfDNA screening at the University of Illinois at Chicago (UIC) in January 2012 influenced the acceptance of prenatal diagnostic testing in at-risk women. METHODS: Retrospective study of two cohorts of women who received prenatal genetic counseling at UIC: pre-cfDNA era from January 2010 to December 2011 and cfDNA era from January 2012 to December 2016. Charts of eligible patients were reviewed; demographics, indications for genetic counseling and acceptance of diagnostic testing were analyzed. Statistical tests: Chi-square, Fisher exact test, Student t-test, bivariate and multivariate analysis were utilized. RESULTS: A total of 2371 women had genetic counseling at UIC from 2010 to 2016; 629 prior to cfDNA and 1741 after. There were 319 women who had diagnostic testing, 168 (26.7%) during pre-cfDNA era vs. 151 (8.7%) in the cfDNA era, RR 4.0 (95% CI 3.1-5.0), p&lt;0.001. Multivariate analysis using Mantel-Haenszel test revealed that pregnant women prior to availability of cfDNA were more likely to pursue prenatal genetic diagnostic testing, and it remained statistically significant even after controlling for confounders, RR 1.20 (1.18-1.23), p&lt;0.001. CONCLUSION: Advent of cfDNA as prenatal screening was associated with decreased utilization of diagnostic prenatal testing in women whose offspring were at risk of chromosomal abnormalities.

Practice Bulletin No. 162: Prenatal Diagnostic Testing for Genetic Disorders.

Prenatal genetic diagnostic testing is intended to determine, with as much certainty as possible, whether a specific genetic disorder or condition is present in the fetus. In contrast, prenatal genetic screening is designed to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder. Originally, prenatal genetic testing focused primarily on Down syndrome (trisomy 21), but now it is able to detect a broad range of genetic disorders. Although it is necessary to perform amniocentesis or chorionic villus sampling (CVS) to definitively diagnose most genetic disorders, in some circumstances, fetal imaging with ultrasonography, echocardiography, or magnetic resonance imaging may be diagnostic of a particular structural fetal abnormality that is suggestive of an underlying genetic condition.The objective of prenatal genetic testing is to detect health problems that could affect the woman, fetus, or newborn and provide the patient and her obstetrician-gynecologist or other obstetric care provider with enough information to allow a fully informed decision about pregnancy management. Prenatal genetic testing cannot identify all abnormalities or problems in a fetus, and any testing should be focused on the individual patient's risks, reproductive goals, and preferences. It is important that patients understand the benefits and limitations of all prenatal screening and diagnostic testing, including the conditions for which tests are available and the conditions that will not be detected by testing. It also is important that patients realize that there is a broad range of clinical presentations, or phenotypes, for many genetic disorders and that results of genetic testing cannot predict all outcomes. Prenatal genetic testing has many benefits, including reassuring patients when results are normal, identifying disorders for which prenatal treatment may provide benefit, optimizing neonatal outcomes by ensuring the appropriate location for delivery and the necessary personnel to care for affected infants, and allowing the opportunity for pregnancy termination.The purpose of this Practice Bulletin is to review the current status of prenatal genetic diagnostic testing and the evidence supporting its use. For information regarding screening for fetal aneuploidy, refer to Practice Bulletin No. 163, Screening for Fetal Aneuploidy.

Practice Bulletin No. 163

Prenatal genetic screening is designed to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder. In contrast, prenatal genetic diagnostic testing is intended to determine, with as much certainty as possible, whether a specific genetic disorder or condition is present in the fetus. The purpose of prenatal screening for aneuploidy is to provide an assessment of the woman's risk of carrying a fetus with one of the more common fetal aneuploidies. This is in contrast to prenatal diagnostic testing for genetic disorders, in which the fetal chromosomes are evaluated for the presence or absence of abnormalities in chromosome number, deletions, and duplications, or the fetal DNA is evaluated for specific genetic disorders. The wide variety of screening test options, each offering varying levels of information and accuracy, has resulted in the need for complex counseling by the health care provider and complex decision making by the patient. No one screening test is superior to other screening tests in all test characteristics. Each test has relative advantages and disadvantages. It is important that obstetrician-gynecologists and other obstetric care providers be prepared to discuss not only the risk of aneuploidy but also the benefits, risks, and limitations of available screening tests. Screening for aneuploidy should be an informed patient choice, with an underlying foundation of shared decision making that fits the patient's clinical circumstances, values, interests, and goals.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options for fetal aneuploidy and to review their benefits, accuracy, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders.

Practice Bulletin No. 162 Summary: Prenatal Diagnostic Testing for Genetic Disorders.

Prenatal genetic diagnostic testing is intended to determine, with as much certainty as possible, whether a specific genetic disorder or condition is present in the fetus. In contrast, prenatal genetic screening is designed to assess whether a patient is at increased risk of having a fetus affected by a genetic disorder. Originally, prenatal genetic testing focused primarily on Down syndrome (trisomy 21), but now it is able to detect a broad range of genetic disorders. Although it is necessary to perform amniocentesis or chorionic villus sampling (CVS) to definitively diagnose most genetic disorders, in some circumstances, fetal imaging with ultrasonography, echocardiography, or magnetic resonance imaging may be diagnostic of a particular structural fetal abnormality that is suggestive of an underlying genetic condition.The objective of prenatal genetic testing is to detect health problems that could affect the woman, fetus, or newborn and provide the patient and her obstetrician-gynecologist or other obstetric care provider with enough information to allow a fully informed decision about pregnancy management. Prenatal genetic testing cannot identify all abnormalities or problems in a fetus, and any testing should be focused on the individual patient's risks, reproductive goals, and preferences. It is important that patients understand the benefits and limitations of all prenatal screening and diagnostic testing, including the conditions for which tests are available and the conditions that will not be detected by testing. It also is important that patients realize that there is a broad range of clinical presentations, or phenotypes, for many genetic disorders and that results of genetic testing cannot predict all outcomes. Prenatal genetic testing has many benefits, including reassuring patients when results are normal, identifying disorders for which prenatal treatment may provide benefit, optimizing neonatal outcomes by ensuring the appropriate location for delivery and the necessary personnel to care for affected infants, and allowing the opportunity for pregnancy termination.The purpose of this Practice Bulletin is to review the current status of prenatal genetic diagnostic testing and the evidence supporting its use. For information regarding screening for fetal aneuploidy, refer to Practice Bulletin No. 163, Screening for Fetal Aneuploidy.

최신 비침습적 산전 유전 검사(NIPT)의 임상 적용과 간호학적 의미

Purpose: Nineteen articles were analyzed to gather opinions and nursing implications about NIPT recently launched. Methods: Nineteen articles were selected from EBSCO (eBook business collection), Google Scholar, and two Korean academic d-bases with key words `prenatal screening testing`, `prenatal genetic diagnostic testing`, NIPT or `cell free DNA (cfDNA)`. Authors developed a framework for analyzing the 19 articles including opinions and suggestions for future implications. Results: Eleven articles written by the first author affiliated with medicine or genetics, viewed NIPT as promising because of safety, accuracy, early detectability and cost effectiveness. Articles written by journalists or authors affiliated with history and ethics were concerned with the possible risk of ELSI (ethical, legal, social issues), erratic interpretation of test results, and lack of genetic counseling service. Conclusion: With consideration of Korean clinical, and legal circumstances, not only pregnant women and families but also health professionals must prepare for clinical NIPT implications including updating prenatal genetic testing, counseling services, protecting ELSI and amulticultural team approach.

Laminin-5 in diseases of the oral cavity

The basement membrane molecule laminin forms a family of proteins. Laminin-5 was identified as key protein in the anchoring filaments of the basement membrane. The anchoring filaments connect the basement membrane to the epithelial cells and together form the epithelial adhesion complex. Disturbances in the epithelial adhesion complex result in subepithelial blistering dermatosis. Autoantibodies against laminin-5 are found in cicatricial pemphigoid. Mutations in genes of laminin-5 with loss of the protein cause epidermolysis bullosa Herlitz. It can be determined during prenatal genetic diagnostic testing. Laminin-5 supports migration of keratinocytes and forms the basis for migrating keratinocytes in oral wound healing. Positive re-epithelialization via laminin-5 has been the subject of experimental studies. Oral squamous cell carcinomas are found to have a focal loss of laminin-5 in conjunction with a loss of the cellular receptor, and increased synthesis of laminin-5 by budding tumor cells has been observed along with deposition of the protein in the stroma. As a result of these observations laminin-5 has been suggested as a route of invasion. Quantitative assessment of this phenomenon and the modulation of laminin-5-tumor cell interaction offer new and hopeful means of describing and affecting the invasive behaviour of oral squamous carcinoma.