Genetic diseases encompass a spectrum of disorders resulting from DNA variations. Preimplantation genetic testing (PGT) is a critical strategy for preventi

While extensive research has compared ICSI and c-IVF in general ART outcomes, limited evidence exists regarding their relative efficacy and safety in PGT-A cycles. Therefore, we conducted a large retrospective cohort study to evaluate the effect of conventional in vitro fertilization (c-IVF) on the outcomes of preimplantation genetic testing for aneuploidy (PGT-A) in couples with non-male factor infertility. We conducted a large retrospective cohort study including 578 PGT-A cycles with c-IVF performed on couples with non-male factor infertility at our center between January 2019 and October 2024. To control for confounding factors, 578 PGT-A cycles with ICSI during the same period were selected as a control group. Matching was based on maternal age (± 2 years), number of oocytes retrieved (± 3), and progressive motile sperm count (± 3 × 10⁶). The primary outcome was PGT-A results, while secondary outcomes included the 2PN fertilization rate, blastocyst available for biopsy per 2PN zygote and blastocyst available for biopsy per oocyte retrieved. Baseline characteristics, including parental age, AMH, antral follicle count (AFC), BMI, progressive motile sperm count, and PGT indications, were comparable between groups. Although the 2PN fertilization rate was significantly higher in the ICSI-PGT-A group (65.88% vs. 78.46%, P < 0.001), the 2 PN fertilization rate per retrieved oocyte (65.88% vs. 60.48%, P < 0.001), transferable embryo rate on day 3 (76.67% vs. 74.38%, P = 0.029), blastocyst formation rate per 2PN zygote (51.54% vs. 48.32%, P = 0.008), blastocyst available for biopsy per 2PN zygote (35.60% vs. 29.46%, P < 0.001), and blastocyst available for biopsy per oocyte retrieved (23.45% vs. 17.82%, P < 0.001) were significantly lower in the ICSI-PGT-A group. PGT-A results from 1,268 biopsy samples in the c-IVF group and 936 samples in the ICSI group revealed no significant differences in chromosomal euploidy, aneuploidy, mosaicism, or “No-call” rates. However, after controlling the potential confounders, c-IVF demonstrated significantly higher euploid embryo rate compared to ICSI (adjusted RR = 1.611, 95% CI 1.228–2.114, P = 0.001). Patterns of chromosomal aberrations were similar between groups, with chromosomes 15, 16, 21, and 22 showing the highest frequencies of abnormalities. Notably, no parental contamination was detected in the c-IVF group, while one case of maternal contamination was reported in the ICSI group. Our data suggested c-IVF could improve PGT-A outcomes in couples with non-male factor infertility and exhibited a low risk of parental contamination. c-IVF-PGT-A represents a safe, effective, and cost-efficient strategy for these couples.

Objectives: This study compared controlled ovarian hyperstimulation (COH) outcomes and chromosomal euploidy results between the Utrogestan-based progesterone-primed ovarian stimulation (PPOS) and gonadotropin-releasing hormone antagonist (GnRH-Ant) protocols in preimplantation genetic testing for monogenic disorders (PGT-M) cycles, and assessed the efficacy and safety of the Utrogestan-based PPOS protocol. Methods: In this retrospective single-center cohort study, 176 PGT-M cycles managed with the Utrogestan-based PPOS protocol were compared with 176 GnRH-Ant cycles using 1:1 direct caliper matching without replacement. Embryos were classified as euploid, mosaic, aneuploid, or no-call according to next-generation sequencing results. The primary outcomes were euploidy rate and chromosomal aberration patterns; secondary outcomes included COH outcomes and pregnancy outcomes. Results: Baseline characteristics were comparable after matching. The total gonadotropin (Gn) dose was significantly lower in the Utrogestan-based PPOS group (2100 (1500–3000) vs. 2250 (1800–3000), p = 0.035). PGT analysis revealed comparable rates of euploidy, aneuploidy, mosaicism, and “No-call” between the Utrogestan-based PPOS (n = 586) and GnRH-Ant (n = 605) groups. The unadjusted difference in euploidy rate per MII oocyte between groups (18.98% vs. 16.36%, p = 0.045) was no longer statistically significant after multivariable adjustment (p = 0.194). In addition, patterns of aneuploidy and chromosomal involvement were similar between groups. The Utrogestan-based PPOS group showed numerically higher clinical pregnancy rate (70.67% vs. 63.22%) and live birth rate (62.67% vs. 51.72%), and a lower early abortion rate (5.66% vs. 12.73%), but none of these differences were statistically significant. Conclusions: Compared with the GnRH-Ant protocol, the Utrogestan-based PPOS protocol required a significantly lower total Gn dose while exhibiting comparable euploidy rate, analogous chromosomal abnormality spectrums, and pregnancy outcomes. The Utrogestan-based PPOS protocol may be a feasible alternative ovarian stimulation strategy in PGT-M cycles.

Genetic diseases encompass a spectrum of disorders resulting from DNA variations. Preimplantation genetic testing (PGT) is a critical strategy for preventing recurrent miscarriage, foetal malformations, and the birth of children affected by chromosomal abnormalities and monogenic disorders. Traditional PGT techniques necessitate comprehensive pedigree genetic data for haplotype linkage analysis, whereas PGT employing third-generation sequencing (TGS) has distinct advantages, particularly in cases of incomplete pedigree information, de novo mutations, and complex pathogenic variants. Nevertheless, the widespread application of TGS-based PGT in clinical practice encounters hurdles owing to its high costs. Targeted sequencing technologies present a promising solution by selectively enriching regions of interest while disregarding nontargeted areas, offering a more cost-effective and flexible alternative. In this study, we employed next-generation sequencing (NGS) and adaptive sampling-based targeted nanopore sequencing (ASTN-seq) to analyse samples from five couples who carried balanced translocations and HBB gene pathogenic mutations, as well as three additional couples with monogenic diseases caused by mutations in PKD1 , ASNS , or ALPL . ASTN-seq successfully identified various mutations and facilitated haplotype linkage analysis, confirming its accuracy and reliability. Successful embryo transfer and subsequent prenatal diagnosis in certain families underscore the potential of ASTN-seq in assisted reproduction. Compared with traditional NGS-based PGT techniques, our work highlights that ASTN-seq is a promising tool for PGT, offering cost-effective solutions for PGT, especially for incomplete pedigrees and de novo mutations.

Background and Clinical Significance: FLNC encodes filamin C, a muscle-scaffolding protein crucial for cardiac integrity. Pathogenic FLNC variants cause diverse cardiomyopathies (hypertrophic, dilated, restrictive, and arrhythmogenic) and myofibrillar myopathies, but their role in congenital cardiac malformations is unclear. Notably, FLNC has not been implicated in structural defects such as Tetralogy of Fallot (TOF) to date. Case Presentation: Two fetuses from the same family were prenatally diagnosed with TOF via ultrasound. The trio whole-exome sequencing of the second fetus and her parents identified a novel heterozygous truncating FLNC variant (NM_001458.5:c.1453C>T, p.Q485*). Sanger sequencing confirmed the same variant in the earlier TOF fetus. The mother carried the variant but was asymptomatic. In vitro mutagenesis in rat cardiomyocytes showed that the mutant FLNC construct produced markedly reduced FLNC proteins compared to the wild type and did not form abnormal cytoplasmic aggregates. Conclusions: We report on a novel FLNC truncating variant associated with fetal TOF, extending the spectrum of FLNC-related cardiac anomalies. The variable outcomes among variant carriers—from fetal TOF to adult cardiomyopathy or no clinical manifestations—underscore the complex genotype–phenotype correlations of filaminopathy. This case highlights the importance of comprehensive genetic evaluation in families with diverse cardiac phenotypes and suggests that additional genetic factors likely influence phenotypic expression.