Several reports have presented that balanced chromosomal rearrangements (BCRs) carriers with normal phenotypes may be carriers of complex rearrangements. However, the incidence and PGT clinical outcomes of cryptic complex chromosome rearrangements (CCCRs) in individuals with BCRs is remain unknown. We recruited a cohort of 1,264 individuals with BCR carriers from 2016 to 2021 at the Reproductive and Genetic Hospital of CITIC Xiangya. Peripheral blood was collected for karyotyping and genomic DNA extraction and the PGT-SR clinical outcomes of CCCRs carriers were analyzed and compared with those of BCR carriers. Our findings revealed that 3.6% (45/1,264) of BCR carriers had CCCRs, involving 3-25 breakpoints on 1-3 chromosomes. Furthermore, when mate-pair sequencing was employed, 63.3% (19/30) of CCCR carriers were found to have chromosome rearrangements that were different from those identified by the MicroSeq technique. And the transferable embryo rate of CCCR carriers with 3 chromosomes was significantly lower than that of CCCR carriers with only 1-2 chromosomes. In this research, we revealed that some of the BCR carriers were actually CCCR carriers, and the prognosis of PGT in CCCR carriers with one or two chromosomes is better than that of CCCR carriers with three chromosomes.

Preimplantation genetic testing (PGT) has become an integral component of assisted reproductive technology (ART), offering couples the opportunity to screen embryos for genetic abnormalities before implantation during in vitro fertilization (IVF). This comprehensive review explores the advancements and applications of PGT in IVF, covering its various types, technological developments, clinical applications, efficacy, challenges, regulatory aspects, and future directions. The evolution of PGT techniques, including next-generation sequencing (NGS) and comparative genomic hybridization (CGH), has significantly enhanced the accuracy and reliability of genetic testing in embryos. PGT holds profound implications for the future of ART by improving IVF success rates, reducing the incidence of genetic disorders, and mitigating the emotional and financial burdens associated with failed pregnancies and genetic diseases. Recommendations for clinicians, researchers, and policymakers include staying updated on the latest PGT techniques and guidelines, exploring innovative technologies, establishing clear regulatory frameworks, and fostering collaboration to maximize the potential benefits of PGT in assisted reproduction. Overall, this review provides valuable insights into the current state of PGT and its implications for the field of reproductive medicine.

OBJECTIVE: The preimplantation genetic testing for aneuploidy (PGT-A) platform is not currently available for small copy-number variants (CNVs), especially those < 1 Mb. Through strategies used in PGT for monogenic disease (PGT-M), this study intended to perform PGT for families with small pathogenic CNVs.
METHODS: Couples who carried small pathogenic CNVs and underwent PGT at the Reproductive and Genetic Hospital of CITIC-Xiangya (Hunan, China) between November 2019 and April 2023 were included in this study. Haplotype analysis was performed through two platforms (targeted sequencing and whole-genome arrays) to identify the unaffected embryos, which were subjected to transplantation. Prenatal diagnosis using amniotic fluid was performed during 18-20 weeks of pregnancy.
RESULTS: PGT was successfully performed for 20 small CNVs (15 microdeletions and 5 microduplications) in 20 families. These CNVs distributed on chromosomes 1, 2, 6, 7, 13, 15, 16, and X with sizes ranging from 57 to 2120 kb. Three haplotyping-based PGT-M strategies were applied. A total of 89 embryos were identified in 25 PGT cycles for the 20 families. The diagnostic yield was 98.9% (88/89). Nineteen transfers were performed for 17 women, resulting in a 78.9% (15/19) clinical pregnancy rate after each transplantation. Of the nine women who had healthy babies, eight accepted prenatal diagnosis and the results showed no related pathogenic CNVs.
CONCLUSIONS: Our results show that the extended haplotyping-based PGT-M strategy application for small pathogenic CNVs compensated for the insufficient resolution of PGT-A. These three PGT-M strategies could be applied to couples with small pathogenic CNVs.

Parents of children with autism who receive genetic diagnoses of de novo variants face challenges in understanding the implications for reproductive decision-making. We interviewed 28 parents who received de novo genetic diagnoses for their child\'s autism and intellectual disability (ID). These genetic variants proved to have reproductive implications for not only the child\'s parents, but the child and his/her neurotypical siblings, aunts, uncles, and cousins. Parents had often already finished building their families but varied, overall, in whether the results had affected, or might have influenced, their reproductive decisions. Parents\' views were shaped by factors related to not only genetics, but also parental age, financial considerations, competing hopes and visions for their family\'s future, perceived abilities to care for an additional child with similar symptoms, and the extent of the child\'s symptoms. Members of a couple sometimes disagreed about whether to have more children. Parents pondered, too, the possibility of preimplantation genetic testing, though misunderstandings about it arose. Children with autism vary widely in their abilities to understand the reproductive implications of genetic diagnoses for themselves. Neurotypical offspring were much relieved to understand that their own children would not be affected. While some autism self-advocates have been concerned that genetic testing related to autism could lead to eugenics, the present data, concerning de novo genetic findings, raise other perspectives. These data, the first to explore several key aspects of the reproductive implications of genetic diagnoses for this group, have important implications for future practice, education, and research-e.g., concerning various family members.

Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytosis, type 1; MIM#182900), SPTB (Spherocytosis, type 2; MIM#616649), SPTA1 (Spherocytosis, type 3; MIM#270970), SLC4A1 (Spherocytosis, type 4; MIM#612653) and EPB42 (Spherocytosis, type 5; MIM#612690) have been confirmed to be related to HS. There have been many studies on the pathogenic variants and mechanisms of HS, however, studies on how to manage the transmission of HS to the next-generation have not been reported. In this study, we recruited a patient with HS. Targeted next-generation sequencing with a panel of 208 genes related to blood system diseases detected a novel heterozygous variant in the SPTB: c.300+2dup in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis of single nucleotide polymorphism (SNP) based on next-generation sequencing were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism. One of two normal embryos was transferred to the proband. Ultimately, a healthy boy was born, confirmed by noninvasive prenatal testing for monogenic conditions (NIPT-M) to be disease-free. This confirmed our successful application of PGT in preventing transmission of the pathogenic variant allele in the HS family.

UNASSIGNED: This study aimed to determine whether controlled ovarian hyperstimulation (COH) parameters influence the incidence of de novo chromosomal abnormalities (> 4 Mb) in blastocysts and, thus, clinical pregnancy outcomes in preimplantation genetic testing (PGT).
UNASSIGNED: Couples who underwent preimplantation genetic testing for structural chromosome rearrangements (PGT-SR) and monogenic disorders (PGT-M) were included in this study. The relationships of maternal age, paternal age, stimulation protocol, exogenous gonadotropin dosage, duration of stimulation, number of oocytes retrieved and estradiol (E2) levels on human chorionic gonadotropin (hCG) trigger day with the incidence of de novo chromosomal abnormalities were assessed. Blastocysts were biopsied, and nuclear DNA was sequenced using next-generation sequencing (NGS). Clinical pregnancy outcomes after single euploid blastocyst transfers under different COH parameters were assessed.
UNASSIGNED: A total of 1,710 and 190 blastocysts were biopsied for PGT-SR and PGT-M, respectively. The rate of de novo chromosomal abnormalities was found to increase with maternal age (p< 0.001) and paternal age (p = 0.019) in the PGT-SR group. No significant differences in the incidence of de novo chromosomal abnormalities were seen for different maternal or paternal age groups between the PGT-SR and PGT-M groups (p > 0.05). Stratification analysis by gonadotropin dosage, stimulation protocol, duration of stimulation, number of retrieved oocytes and E2 levels on hCG trigger day revealed that de novo chromosomal abnormalities and clinical pregnancy outcomes were not correlated with COH parameters after adjusting for various confounding factors.
UNASSIGNED: The rate of de novo chromosomal abnormalities was found to increase with maternal or paternal age. COH parameters were found to not influence the incidence of de novo chromosomal abnormalities or clinical pregnancy outcomes.

OBJECTIVE: To determine if creating voting ensembles combining convolutional neural networks (CNN), support vector machine (SVM), and multi-layer neural networks (NN) alongside clinical parameters improves the accuracy of artificial intelligence (AI) as a non-invasive method for predicting aneuploidy.
METHODS: A cohort of 699 day 5 PGT-A tested blastocysts was used to train, validate, and test a CNN to classify embryos as euploid/aneuploid. All embryos were analyzed using a modified FAST-SeqS next-generation sequencing method. Patient characteristics such as maternal age, AMH level, paternal sperm quality, and total number of normally fertilized (2PN) embryos were processed using SVM and NN. To improve model performance, we created voting ensembles using CNN, SVM, and NN to combine our imaging data with clinical parameter variations. Statistical significance was evaluated with a one-sample t-test with 2 degrees of freedom.
RESULTS: When assessing blastocyst images alone, the CNN test accuracy was 61.2% (± 1.32% SEM, n = 3 models) in correctly classifying euploid/aneuploid embryos (n = 140 embryos). When the best CNN model was assessed as a voting ensemble, the test accuracy improved to 65.0% (AMH; p = 0.1), 66.4% (maternal age; p = 0.06), 65.7% (maternal age, AMH; p = 0.08), 66.4% (maternal age, AMH, number of 2PNs; p = 0.06), and 71.4% (maternal age, AMH, number of 2PNs, sperm quality; p = 0.02) (n = 140 embryos).
CONCLUSIONS: By combining CNNs with patient characteristics, voting ensembles can be created to improve the accuracy of classifying embryos as euploid/aneuploid from CNN alone, allowing for AI to serve as a potential non-invasive method to aid in karyotype screening and selection of embryos.

Low serum progesterone concentration on frozen embryo transfer (FET) day in hormone replacement therapy (HRT) cycles results in lower reproductive outcomes. Recent studies showed the efficiency of a \"rescue protocol\'\' to restore reproductive outcomes in these patients. Here, we compared reproductive outcomes in HRT FET cycles in women with low serum progesterone levels who received individualized luteal phase support (iLPS) and in women with adequate serum progesterone levels who underwent in vitro fertilization for pre-implantation genetic testing for structural rearrangements or monogenic disorders.
This retrospective cohort study included women (18-43 years of age) undergoing HRT FET cycles with pre-implantation genetic testing at Montpellier University Hospital between June 2020 and May 2022. A standard HRT was used: vaginal micronized estradiol (6mg/day) followed by vaginal micronized progesterone (VMP; 800 mg/day). Serum progesterone was measured after four doses of VMP: if <11ng/ml, 25mg/day subcutaneous progesterone or 30mg/day oral dydrogesterone was introduced.
125 HRT FET cycles were performed in 111 patients. Oral/subcutaneous progesterone supplementation concerned 39 cycles (n=20 with subcutaneous progesterone and n=19 with oral dydrogesterone). Clinical and laboratory parameters of the cycles were comparable between groups. The ongoing pregnancy rate (OPR) was 41.03% in the supplemented group and 18.60% in the non-supplemented group (p= 0.008). The biochemical pregnancy rate and miscarriages rate tended to be higher in the non-supplemented group versus the supplemented group: 13.95% versus 5.13% and 38.46% versus 15.79% (p=0.147 and 0.182 respectively). Multivariate logistic regression analysis found that progesterone supplementation was significantly associated with higher OPR ​​ (adjusted OR = 3.25, 95% CI [1.38 - 7.68], p=0.007).
In HRT FET cycles, progesterone supplementation in patients with serum progesterone concentration <11 ng/mL after four doses of VMP significantly increases the OPR.

This article examines the possible effects of the end of a federal constitutional right to abortion on clinical practice and research involving ex vivo human embryos. It first analyzes the likely outcomes of Dobbs v. Mississippi, concluding the Supreme Court will either overrule the federal constitutional abortion right or restrict it in a way that leads to its rapid disappearance. Next, the article discusses a possible increase in use of preimplantation genetic testing as one result. It then forecasts the likely ramifications of such a court decision on state legislation affecting ex vivo human embryos in two ways. It examines the possibility that victory over Roe will inspire embryo support groups to push for limitations on in vitro fertilization, perhaps on its destruction of embryos and more likely on permissible grounds for prospective parents to use in choosing embryos for transfer. It ends by discussing the prospects of new laws in some states banning or limiting research with human embryos.

OBJECTIVE: To compare aneuploidy rates in early aborted tissues or blastocysts between in vitro fertilization (IVF) cycles after the gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) protocol or the GnRH agonist (GnRH-a) long protocol.
METHODS: This was a retrospective cohort study from a university-affiliated fertility center. In total, 550 early miscarriage patients who conceived through IVF/intracytoplasmic sperm injection (ICSI) after receiving the GnRH-ant or GnRH-a long protocol were analyzed to compare aneuploidy rates in early aborted tissues. To compare aneuploidy rates in blastocysts, 404 preimplantation genetic testing for aneuploidy (PGT-A) cycles with the GnRH-ant protocol or GnRH-a long protocol were also analyzed.
RESULTS: For early miscarriage patients who conceived through IVF/ICSI, compared to the GnRH-a long protocol group, the GnRH-ant protocol group had a significantly higher rate of aneuploidy in early aborted tissues (48.51% vs. 64.19%). Regarding PGT-A cycles, the rate of blastocyst aneuploidy was significantly higher in the GnRH-ant protocol group than the GnRH-a long protocol group (39.69% vs. 52.27%). After stratification and multiple linear regression, the GnRH-ant regimen remained significantly associated with an increased risk of aneuploidy in early aborted tissues and blastocysts [OR (95% CI) 1.81 (1.21, 2.71), OR (95% CI) 1.65 (1.13, 2.42)]. Furthermore, the blastocyst aneuploidy rate in the GnRH-ant protocol group was significantly higher but only in young and normal ovarian responders [OR (95% CI) 5.07 (1.99, 12.92)].
CONCLUSIONS: Compared to the GnRH-a long protocol, the GnRH-ant protocol is associated with a higher aneuploidy rate in early aborted tissues and blastocysts. These results should be confirmed in a multicenter, randomized controlled trial.