UNASSIGNED: Preimplantation genetic testing (PGT) can reduce the risk of familial genetic diseases, chromosome abnormalities, and recurrent abortions. It is unclear whether genetic counselees with PGT indications understand and accept the implications of PGT. A well-developed and validated tool is needed to evaluate the knowledge, attitude, and practice (KAP) levels of genetic counselees with PGT indications. The purpose of this study was to develop and validate a PGT KAP questionnaire (PGT-KAP-Q) for genetic counselees with PGT indications.
UNASSIGNED: First, we established an item pool based on a literature review and qualitative interviews. Second, we developed the PGT-KAP-Q using the Delphi method. Third, we evaluated the quality of the questionnaire using item analysis and psychometric evaluation. The item analysis included extreme value comparison, application of the correlation and Cronbach\'s alpha (α) coefficient methods, and factor analysis. We also evaluated the content and structural validity of the questionnaire, as well as the internal consistency, test-retest reliability, and split-half reliability.
UNASSIGNED: After the literature review and interviews, and based on three rounds of expert consultations, we formed a 43-item questionnaire. In the validity analysis, the item\'s content validity index (I-CVI) and the average scale level CVI (S-CVI/Ave) values (>0.78 and >0.95, respectively) confirmed the questionnaire\'s content validity. Exploratory factor analysis showed that all 43 items had strong factor loadings (>0.4), and the three factors of the PGT-KAP-Q explained 51.97 % of the total variance. The Cronbach\'s α coefficient for the questionnaire was 0.95 (p < 0.05), the split-half reliability was 0.76 (p < 0.05) and the test-retest reliability coefficient was 0.78 (p < 0.05).
UNASSIGNED: The 43-item PGT-KAP-Q for genetic counselees with PGT indications is reliable and valid. It contains a moderate number of items, is easy for patients to understand and accept, and can be used for clinical research and applications.

OBJECTIVE: PGT-A to deselect aneuploid embryos in ART cycles may hold promise by augmenting pregnancy rates per transfer and reducing pregnancy loss rates for patients with unexplained recurrent pregnancy loss.
OBJECTIVE: To explore effectiveness of PGT-A in managing unexplained recurrent pregnancy loss by evaluating several key aspects: (i) the likelihood of a live birth in a subsequent spontaneous pregnancy, (ii) whether women with unexplained recurrent pregnancy loss have higher rate of aneuploidy, (iii) whether euploid blastocysts offer comparable live birth rate in patients with unexplained recurrent pregnancy loss, (iv) whether the endometrium is less selective in unexplained recurrent pregnancy loss, and (v) whether PGT-A increases live birth rate or reduces pregnancy losses until delivery.
METHODS: PubMed and Cochrane Library databases were searched from inception until June 2024.
UNASSIGNED: Studies involving patients with ≥2 unexplained recurrent pregnancy loss, who underwent ART with or without PGT-A, or expectant management were included.
METHODS: The primary outcome measure was the live birth rate. Secondary outcome measures were aneuploidy rate, clinical pregnancy rate, and clinical pregnancy loss rate.
RESULTS: Whether couples with unexplained recurrent pregnancy loss have higher embryo aneuploidy rates remains equivocal. Euploid blastocyst transfers yielded comparable clinical pregnancy loss rate (OR:1.10, 95%CI:0.57-2.13), and live birth rate (OR:1.04, 95%CI: 0.74-1.44) in patients with and without unexplained recurrent pregnancy loss. Comprehensive chromosome analysis of products of conception shows similar aneuploidy rates between patients with and without recurrent pregnancy loss and does not support less selective endometrium hypothesis. PGT-A decreased clinical pregnancy loss rate (OR: 0.42, 95% CI: 0.27-0.67) and enhanced live birth rate per transfer (OR: 2.17, 95% CI: 1.77-2.65) and live birth rate per patient (OR: 1.85, 95% CI: 1.18-2.91) in unexplained recurrent pregnancy loss patients.
CONCLUSIONS: Current low-quality evidence suggests that PGT-A enhances live birth rate per transfer and per patient in unexplained recurrent pregnancy loss. Well-designed randomized controlled trials comparing ART with-PGT-A versus expectant management for unexplained recurrent pregnancy loss are warranted.

OBJECTIVE: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on first transfer live birth rate (LBR) and cumulative LBR (CLBR) in donor oocyte IVF cycles.
METHODS: Retrospective cohort study of the SART CORS database.
METHODS: 11,348 fresh and 7,214 frozen-thawed donor oocyte IVF cycles were analyzed.
METHODS: The first reported donor stimulation cycle per patient between January 1, 2014 and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014 and December 31, 2016, were included in the study.
METHODS: LBR was compared for patients using fresh and frozen-thawed donor oocytes, with or without PGT-A. Logistic regression models were adjusted for age, body mass index, gravidity, infertility etiology, and prior IVF cycles.
RESULTS: Among patients who had blastocysts available for transfer or PGT-A, use of PGT-A was associated with a decreased first transfer LBR (46.9 vs 53.2%, p <0.001) and CLBR (58.4 vs 66.6%, p <0.001) in fresh oocyte donor cycles compared with no PGT-A. LBR in frozen-thawed oocyte donor cycles with PGT-A were nominally higher than those without PGTA (48.3% vs. 40.5%) but were not statistically significant in multivariable logistic regression models (p=0.14). Early pregnancy loss was not significantly different with and without PGT-A. Multiple gestation, preterm birth, and low birthweight infants were all reduced with addition of PGT-A in fresh donor oocyte cycles, though these outcomes were not significantly different when comparing single embryo transfers in fresh oocyte cycles and also not significantly different among frozen-thawed donor oocyte cycles.
CONCLUSIONS: PGT-A in fresh oocyte donor cycles was associated with decreased LBR and CLBR, while effects on frozen-thawed oocyte donor cycles were clinically negligible. Obstetrical benefits associated with PGT-A in fresh donor cycles appear linked to increased single embryo transfer.

UNASSIGNED: Preimplantation Genetic Testing (PGT) is a cutting-edge test used to detect genetic abnormalities in embryos fertilized through Medically Assisted Reproduction (MAR). PGT aims to ensure that embryos selected for transfer are free of specific genetic conditions or chromosome abnormalities, thereby reducing chances for unsuccessful MAR cycles, complicated pregnancies, and genetic diseases in future children.
UNASSIGNED: In PGT, genetics, embryology, and technology progress and evolve together. Biological and technological limitations are described and addressed to highlight complexity and knowledge constraints and draw attention to concerns regarding safety of procedures, clinical validity, and utility, extent of applications and overall ethical implications for future families and society.
UNASSIGNED: Understanding the genetic basis of diseases along with advanced technologies applied in embryology and genetics contribute to faster, cost-effective, and more efficient PGT. Next Generation Sequencing-based techniques, enhanced by improved bioinformatics, are expected to upgrade diagnostic accuracy. Complicating findings such as mosaicism, mt-DNA variants, variants of unknown significance, or variants related to late-onset or polygenic diseases will however need further appraisal. Emphasis on monitoring such emerging data is crucial for evidence-based counseling while standardized protocols and guidelines are essential to ensure clinical value and respect of Ethical, Legal and Societal Issues.

Objective This study aims to identify factors associated with mosaicism in human embryos at Hung Vuong Hospital. Methods We performed a retrospective analysis of data from 2018 to 2022, approved by the Hung Vuong Hospital Ethics Committee (CS/HV/23/15). We analyzed variables such as demographic characteristics, clinical measurements, and in-vitro fertilization (IVF) cycle outcomes to investigate their relationship with embryo mosaicism. Results A total of 73 couples undergoing IVF with preimplantation genetic testing (PGT) were included in the analysis. Among 308 embryos, 98 (31.8%) were mosaic, 124 (40.3%) were euploid, and 86 (27.9%) were aneuploid. Univariable analysis revealed that female age was significantly associated with increased odds of mosaicism (odd ratio (OR) = 1.11, 95% confidence interval (CI): 1.04 - 1.19, p = 0.003). Male age demonstrated a marginal association with mosaicism (OR = 1.05, 95% CI: 1.00 - 1.11, p = 0.07). Other factors, including body mass index (BMI), anti-Mullerian hormone (AMH) levels, blood types, and sperm quality, were not significantly associated with mosaicism. In the multivariable analysis, controlling for both female and male age, female age showed a trend toward significance (OR = 1.12, 95% CI: 1.02 - 1.23, p = 0.02), while male age showed no significant effect (OR = 0.99, 95% CI: 0.92 - 1.06, p = 0.75). Conclusions The findings suggest that female age is a critical factor influencing the occurrence of mosaicism in embryos. Further research is needed to fully understand the mechanisms underlying mosaicism in human embryos.

IVF laboratories routinely adopt morphological pronuclear assessment at the zygote stage to identify abnormally fertilized embryos deemed unsuitable for clinical use. In essence, this is a pseudo-genetic test for ploidy motivated by the notion that biparental diploidy is required for normal human life and abnormal ploidy will lead to either failed implantation, miscarriage, or significant pregnancy complications, including molar pregnancy and chorionic carcinoma. Here, we review the literature associated with ploidy assessment of human embryos derived from zygotes displaying a pronuclear configuration other than the canonical two, and the related pregnancy outcome following transfer. We highlight that pronuclear assessment, although associated with aberrant ploidy outcomes, has a low specificity in the prediction of abnormal ploidy status in the developing embryo, while embryos deemed abnormally fertilized can yield healthy pregnancies. Therefore, this universal strategy of pronuclear assessment invariably leads to incorrect classification of over 50% of blastocysts derived from atypically pronucleated zygotes, and the systematic disposal of potentially viable embryos in IVF. To overcome this limitation of current practice, we discuss the new preimplantation genetic testing technologies that enable accurate identification of the ploidy status of preimplantation embryos and suggest a progress from morphology-based checks to molecular fertilization check as the new gold standard. This alternative molecular fertilization checking represents a possible non-incremental and controversy-free improvement to live birth rates in IVF as it adds to the pool of viable embryos available for transfer. This is especially important for the purposes of \'family building\' or for poor-prognosis IVF patients where embryo numbers are often limited.

BACKGROUND: Trophectoderm biopsy has become the mainstay assisted reproductive technique performed for preimplantation genetic testing, accounting for 43.8% of embryo transfer cycles in the United States in 2019 alone. Despite its prevalence, data on the obstetric and perinatal outcomes post-trophectoderm biopsy remains sparse and mixed.
OBJECTIVE: This study aimed to examine the risks of adverse perinatal outcomes in birthweights and prematurity after transfers of the vitrified-thawed blastocyst with trophectoderm biopsy for preimplantation genetic testing.
METHODS: This was a retrospective observational cohort study of 45,712 singleton livebirths resulting from autologous vitrified-thawed blastocyst transfer cycles with or without trophectoderm biopsy for preimplantation genetic testing, reported by participating member clinics to the Society for Assisted Reproductive Technology national registry between 2014 and 2017. Adverse perinatal outcomes of preterm births and low birthweights were analyzed. Multivariable regression analyses were performed to control for covariates. Comparing the trophectoderm biopsy (n=21,584) and no trophectoderm biopsy (n=24,128) groups, adjusted odds ratios were calculated for the outcomes of small-for-gestational-age, large-for-gestational-age, low birthweight <2500 g, very low birthweight <1500 g, extremely low birthweight <1000 g, late preterm births <37 weeks, moderate preterm births <34 weeks, and extremely preterm births <28 weeks.
RESULTS: Women in the trophectoderm biopsy group were older and more likely to have prior pregnancies, deliveries, and a history of spontaneous abortions. Tobacco use, diminished ovarian reserve, and recurrent pregnancy loss were also more prevalent in the trophectoderm biopsy group. Trophectoderm biopsy was not associated with small-for-gestational-age (adjusted odds ratio, 0.97; 95% confidence interval, 0.85-1.12; P=.72) or large-for-gestational-age newborns (adjusted odds ratio, 1.10; 95% confidence interval, 0.99-1.22; P=.09). Risks of preterm births <37 weeks gestation were similar between the biopsy and nonbiopsy groups (adjusted odds ratio, 0.93; 95% confidence interval, 0.85-1.02; P=.11). Trophectoderm biopsy was associated with a significantly lower risk of low birthweight <2500 g (adjusted odds ratio, 0.80; 95% confidence interval, 0.70-0.92; P<.001), very low birthweight <1500 g (adjusted odds ratio, 0.62; 95% confidence interval, 0.46-0.83; P<.001), extremely low birthweight <1000 g (adjusted odds ratio, 0.48; 95% confidence interval, 0.31-0.74; P<.001), moderate preterm birth <34 weeks (adjusted odds ratio, 0.76; 95% confidence interval, 0.64-0.91; P=.003), and extreme preterm birth <28 weeks (adjusted odds ratio, 0.63; 95% confidence interval, 0.43-0.92; P=.02).
CONCLUSIONS: Trophectoderm biopsy is not associated with increased risks of small-for-gestational-age, large-for-gestational-age, or late preterm birth. Risks of low birthweight, very low birthweight, and extremely low birthweight from moderate and extreme preterm births are lower after trophectoderm biopsy, possibly by selecting against confined placental mosaicism or inducing placental epigenetic changes, the mechanisms of which warrant further investigation.

OBJECTIVE: What are the perspectives of preimplantation genetic testing (PGT) patients in Belgium on the ethics of PGT for polygenic risk scoring (PGT-P)?
METHODS: In-depth interviews (18 in total, 10 couples, 8 women, n = 28) were performed with patients who had undergone treatment with PGT for monogenic/single-gene defects (PGT-M) or chromosomal structural rearrangements (PGT-SR) between 2017 and 2019 in Belgium. Participants were asked about their own experiences with PGT-M/SR and about their viewpoints on PGT-P, including their own interest and their ideas on its desirability, scope and consequences. Inductive content analysis was used to analyse the interviews.
RESULTS: Participants stated that their experiences with PGT-M/SR had been physically, psychologically and practically difficult. Most participants stated that, partly because of these difficulties, they did not see the added value of knowing the risk scores of embryos via PGT-P. Many participants worried that PGT-P could lead to additional anxieties, responsibilities and complex choices in reproduction and parenthood. They argued that not everything should be controlled and felt that PGT-P, especially non-medical and broad screening, was going too far. With regards to the clinical implementation of PGT-P, participants in general preferred PGT-P to be limited to people with a serious polygenic family history and wanted embryo selection decisions to be made by healthcare professionals.
CONCLUSIONS: This study shows that individuals with experience of PGT-M/SR saw PGT-P as different from PGT-M/SR. They had various ethical concerns with regards to PGT-P, especially regarding broadly offering PGT-P. These stakeholder viewpoints need to be considered regarding potential PGT-P implementation and guidelines.

BACKGROUND: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes.
METHODS: This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses.
METHODS: Single reproductive medical center.
METHODS: All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included.
METHODS: Next-generation sequencing platforms for chromosomal analysis.
METHODS: Blastocyst formation and euploid blastocyst rates.
RESULTS: In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy.
CONCLUSIONS: In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.

OBJECTIVE: To evaluate the technical accuracy, inheritance, and pathogenicity of small copy number variants (CNVs) detected by a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) platform.
METHODS: Retrospective observational study performed between 2020 and 2022.
METHODS: Clinic.
METHODS: A total of 12,157 patients who underwent clinical PGT-A performed by targeted next-generation sequencing for whole chromosome and large segmental aneuploidies.
METHODS: An incidental finding was reported when a CNV gain/loss of at least 3 consecutive amplicons appeared in at least 2 embryos from the same in vitro fertilization cycle.
METHODS: The primary outcome measures were the specificity, incidence, inheritance, and pathogenicity of small CNVs detected by the PGT-A platform. Accuracy of the PGT-A platform CNV calls was assessed via concordance with the CNV calls (size and genomic location) on chromosomal microarray of the gamete provider(s). Parental origin of the CNV and pathogenicity classifications were also reported.
RESULTS: An incidental finding that met reporting criteria was identified in 75 (0.62%; 95% confidence interval, 0.5%-0.8%) of 12,157 unique PGT-A patients. Chromosomal microarray follow-up was requested for all cases, and results were received for 1 or both members of 65 reproductive couples. In all cases, 1 of the gamete providers was confirmed to have the CNV identified in the embryos (100.0%, N = 65/65; 95% confidence interval, 94.5-100). The identified CNV was of maternal origin in 34 cases (52.3%) and of paternal origin in 31 cases (47.7%). A significant correlation was identified between PGT-A-predicted CNV sizes and chromosomal microarray detected sizes (r = 0.81) and genomic coordinates on parental deoxyribonucleic acid. Twenty-six (40%) of the CNVs were classified as benign/likely benign, 30 (46.2%) as a variant of uncertain significance, and 9 (13.8%) as pathogenic/likely pathogenic.
CONCLUSIONS: Certain PGT-A platforms may enable the detection of inherited, small CNVs with extremely high specificity without prior knowledge of parental status. Most CNVs in this data set were confirmed to be benign/likely benign or a variant of uncertain significance. Pathogenic/likely pathogenic CNVs associated with a broad range of phenotypic features may also be detected, although a reliable negative predictive value for small CNVs with current PGT-A technologies is unknown because of the many technical challenges.