Objective:To investigate the epidemiological characteristics and trends of birth defects related to assisted reproductive technology (ART) in Jiangxi Province from 2014 to 2023, and to explore the correlation factors of birth defect occurrence.Methods:A retrospective collection of ART treatment data and follow-up results from January 2014 to December 2023 across 18 reproductive centers in Jiangxi Province was conducted. The trend of birth defects and the rank order of defect types were analyzed. Exact probability methods were used to estimate the 95% confidence intervals ( CI) of the incidence rates, and Poisson regression was applied to identify independent correlation factors. Results:A total of 65 003 ART offspring were included in this study, comprising 2 025 offspring from intrauterine insemination (IUI) and 62 978 from in vitro fertilization and embryo transfer (IVF-ET). The overall incidence of birth defects was 13.46‰ (95% CI: 12.59‰-14.38‰), with 9.38‰ (95% CI: 5.66‰-14.61‰) for IUI and 13.59‰ (95% CI:12.70‰-14.53‰) for IVF-ET. The incidence of birth defects showed a decreasing trend from 2014 to 2023 (17.11‰ to 11.47‰, Ptrend=0.003). The top three birth defect types were circulatory system defects (3.71‰, 95% CI: 3.25‰-4.21‰), musculoskeletal system defects (2.37‰, 95% CI: 2.01‰-2.77‰), and congenital malformations of the face, ears, eyes, and neck (1.23‰, 95% CI: 0.98‰-1.53‰). Univariate analysis indicated that male offspring from IVF-ET had a higher incidence of birth defects than that in female offspring (14.72‰ vs. 12.31‰, P=0.009). Additionally, gestational age, birth weight, fetal number, cause of infertility, and year of delivery were significantly associated with birth defect incidence in IVF-ET offspring ( P<0.001, P<0.001, P<0.001, P=0.025, P=0.037). Multivariate analysis showed that in singleton pregnancies, male offspring, gestational age 32-36 weeks birth weight <1 500 g, and infertility with bilateral factors were independent risk factors for birth defects ( OR=1.21, 95% CI: 1.00-1.47, P=0.046; OR=1.90,95% CI: 1.41-2.56, P<0.001; OR=3.37, 95% CI: 1.33-8.51, P=0.010; OR=1.38, 95% CI: 1.12-1.69, P=0.003), while in multiple pregnancies, male offspring, gestational age <32 weeks, gestational age 32-36 weeks, birth weight <1 500 g, birth weight 1 500-2 499 g, maternal age 25-29 years and maternal age 30-34 years were independent risk factors ( OR=1.25, 95% CI: 1.03-1.52, P=0.023; OR=2.06, 95% CI: 1.35-3.15, P=0.001; OR=1.32,95% CI: 1.05-1.66, P=0.016; OR=1.98,95% CI: 1.19-3.28, P=0.009; OR=2.06,95% CI: 1.64-2.60, P<0.001; OR=2.00, 95% CI: 1.31-3.06, P=0.001; OR=1.90,95% CI: 1.24-2.92, P=0.003). Conclusion:Over the past 10 years, the incidence of birth defects in ART offspring in Jiangxi Province has shown a decreasing trend annually, with circulatory system malformations being the most common. The occurrence of birth defects in IVF offspring is primarily associated with maternal and infant characteristics, such as gender, gestational age, birth weight, number of fetuses, and cause of infertility, independent of ART treatment factors.

Objective:To investigate the epidemiological characteristics and trends of birth defects related to assisted reproductive technology (ART) in Jiangxi Province from 2014 to 2023, and to explore the correlation factors of birth defect occurrence.Methods:A retrospective collection of ART treatment data and follow-up results from January 2014 to December 2023 across 18 reproductive centers in Jiangxi Province was conducted. The trend of birth defects and the rank order of defect types were analyzed. Exact probability methods were used to estimate the 95% confidence intervals ( CI) of the incidence rates, and Poisson regression was applied to identify independent correlation factors. Results:A total of 65 003 ART offspring were included in this study, comprising 2 025 offspring from intrauterine insemination (IUI) and 62 978 from in vitro fertilization and embryo transfer (IVF-ET). The overall incidence of birth defects was 13.46‰ (95% CI: 12.59‰-14.38‰), with 9.38‰ (95% CI: 5.66‰-14.61‰) for IUI and 13.59‰ (95% CI:12.70‰-14.53‰) for IVF-ET. The incidence of birth defects showed a decreasing trend from 2014 to 2023 (17.11‰ to 11.47‰, Ptrend=0.003). The top three birth defect types were circulatory system defects (3.71‰, 95% CI: 3.25‰-4.21‰), musculoskeletal system defects (2.37‰, 95% CI: 2.01‰-2.77‰), and congenital malformations of the face, ears, eyes, and neck (1.23‰, 95% CI: 0.98‰-1.53‰). Univariate analysis indicated that male offspring from IVF-ET had a higher incidence of birth defects than that in female offspring (14.72‰ vs. 12.31‰, P=0.009). Additionally, gestational age, birth weight, fetal number, cause of infertility, and year of delivery were significantly associated with birth defect incidence in IVF-ET offspring ( P<0.001, P<0.001, P<0.001, P=0.025, P=0.037). Multivariate analysis showed that in singleton pregnancies, male offspring, gestational age 32-36 weeks birth weight <1 500 g, and infertility with bilateral factors were independent risk factors for birth defects ( OR=1.21, 95% CI: 1.00-1.47, P=0.046; OR=1.90,95% CI: 1.41-2.56, P<0.001; OR=3.37, 95% CI: 1.33-8.51, P=0.010; OR=1.38, 95% CI: 1.12-1.69, P=0.003), while in multiple pregnancies, male offspring, gestational age <32 weeks, gestational age 32-36 weeks, birth weight <1 500 g, birth weight 1 500-2 499 g, maternal age 25-29 years and maternal age 30-34 years were independent risk factors ( OR=1.25, 95% CI: 1.03-1.52, P=0.023; OR=2.06, 95% CI: 1.35-3.15, P=0.001; OR=1.32,95% CI: 1.05-1.66, P=0.016; OR=1.98,95% CI: 1.19-3.28, P=0.009; OR=2.06,95% CI: 1.64-2.60, P<0.001; OR=2.00, 95% CI: 1.31-3.06, P=0.001; OR=1.90,95% CI: 1.24-2.92, P=0.003). Conclusion:Over the past 10 years, the incidence of birth defects in ART offspring in Jiangxi Province has shown a decreasing trend annually, with circulatory system malformations being the most common. The occurrence of birth defects in IVF offspring is primarily associated with maternal and infant characteristics, such as gender, gestational age, birth weight, number of fetuses, and cause of infertility, independent of ART treatment factors.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa

Objective:To explore the value of polar body sequencing in preimplantation genetic testing (PGT) for monogenic disease of a female patient with Van der Woude syndrome.Methods:PGT based on polar body sequencing was performed for a female patient with Van der Woude syndrome caused by a de novoIRF6 pathogenic variant. Totally six oocytes were fertilized by intracytoplasmic sperm injection (ICSI). The first, second polar bodies and the trophoblast ectoderm cells of blastocysts were biopsied respectively. Sanger sequencing was used to detect the pathogenic variant in the biopsied cells after genome-wide amplification. The genotypes and pathogenic possibilities of the embryos were inferred according to the genotypes of corresponding tested polar bodies. In order to prevent the absence of transplantable embryos due to the failure of blastocyst culture, vitrification was performed on an embryo with good morphology and low pathogenic possibility before blastocyst formation. The 175 single nucleotide polymorphisms (SNPs) within the 1M region upstream and downstream from the pathogenic variant location were tested by targeted capture sequencing in the couple and selected polar bodies and embryos to construct the haplotypes. An embryo with low pathogenic possibility was transferred. Prenatal diagnosis was strongly recommended after successful pregnancy. Prenatal and postnatal follow-up were performed. Results:Totally six first polar bodies and six second polar bodies were obtained. The pathogenic variant was successfully sequenced in 11 polar bodies. Among the six embryos, one embryo with low pathogenic possibility was vitrified on day 4 (D4) after fully informed consent of the couple; one embryo developed to blastocyst was detected with high pathogenic possibility; the other four embryos were degenerated during blastocyst culture. The SNP haplotypes closely linked to the pathogenic variant location were successfully constructed by linkage analysis. The haplotype analysis of the embryos was in consistent with Sanger sequencing. The D4 embryo with low pathogenic possibility was transferred. The couple refused to conduct invasive prenatal diagnosis after pregnancy. None orofacial clefts were detected after the baby was born, and the pathogenic variant was not detected in the neonatal cord blood either.Conclusion:This study successfully blocked a female patient with Van der Woude syndrome caused by a de novoIRF6 pathogenic variant give birth to an affected baby by polar body sequencing based preimplantation genetic testing for monogenic disease.

Objective:To explore the value of polar body sequencing in preimplantation genetic testing (PGT) for monogenic disease of a female patient with Van der Woude syndrome.Methods:PGT based on polar body sequencing was performed for a female patient with Van der Woude syndrome caused by a de novoIRF6 pathogenic variant. Totally six oocytes were fertilized by intracytoplasmic sperm injection (ICSI). The first, second polar bodies and the trophoblast ectoderm cells of blastocysts were biopsied respectively. Sanger sequencing was used to detect the pathogenic variant in the biopsied cells after genome-wide amplification. The genotypes and pathogenic possibilities of the embryos were inferred according to the genotypes of corresponding tested polar bodies. In order to prevent the absence of transplantable embryos due to the failure of blastocyst culture, vitrification was performed on an embryo with good morphology and low pathogenic possibility before blastocyst formation. The 175 single nucleotide polymorphisms (SNPs) within the 1M region upstream and downstream from the pathogenic variant location were tested by targeted capture sequencing in the couple and selected polar bodies and embryos to construct the haplotypes. An embryo with low pathogenic possibility was transferred. Prenatal diagnosis was strongly recommended after successful pregnancy. Prenatal and postnatal follow-up were performed. Results:Totally six first polar bodies and six second polar bodies were obtained. The pathogenic variant was successfully sequenced in 11 polar bodies. Among the six embryos, one embryo with low pathogenic possibility was vitrified on day 4 (D4) after fully informed consent of the couple; one embryo developed to blastocyst was detected with high pathogenic possibility; the other four embryos were degenerated during blastocyst culture. The SNP haplotypes closely linked to the pathogenic variant location were successfully constructed by linkage analysis. The haplotype analysis of the embryos was in consistent with Sanger sequencing. The D4 embryo with low pathogenic possibility was transferred. The couple refused to conduct invasive prenatal diagnosis after pregnancy. None orofacial clefts were detected after the baby was born, and the pathogenic variant was not detected in the neonatal cord blood either.Conclusion:This study successfully blocked a female patient with Van der Woude syndrome caused by a de novoIRF6 pathogenic variant give birth to an affected baby by polar body sequencing based preimplantation genetic testing for monogenic disease.

Objective To investigate the dosimetric performance of COMPASS system,a novel 3D quality assurance system for the verification of nasopharyngeal carcinoma volumetric modulated therapy (VMAT) treatment plan.Methods Eight VMAT treatment plans of nasopharyngeal carcinoma patients were performed with MasterPlan,a treatment planning system (TPS),and then these treatment plans were sent to the COMPASS and MOSAIQ system,a coherent control system,respectively.Comparison of the COMPASS reconstructed dose versus TPS dose was conducted by using the dose volume-based indices:dose received by 95％ volume of target ( D95％ ),mean dose ( Dmean ) and γ pass rate,dose to the 1％ of the spinal cord and brain stem volume ( D1％ ),mean dose of leaf and right parotid ( Dmean ),and the volume received 30 Gy for left and right parotid (V30).COMPASS can reconstruct dose with the real measured delivery fluence after detector commissioning.Results The average dose difference for the target volumes was within 1％,the difference for D95 was within 3％ for most treatment plans,and the γ pass rate was higher than 95％ for all target volumes.The average differences for the D1％ values of spinal cord and brain stem were ( 4.3 ± 3.0) ％ and ( 5.9± 2.9 ) ％ respectively,and the average differences for the Dmean values of spinal cord and brain stem were ( 5.3 ± 3.0 ) ％ and ( 8.0 ± 3.5 ) ％ respectively.In general the COMPASS measured doses were all smaller than the TPS calculated doses for these two organs.The average differences of the Dmean values of the left and right parotids were( 6.1± 3.1 ) ％ and ( 4.7 ± 4.4 ) ％ respectively,and the average differences of the V30 values of the left and right parotids were (9.4 ± 7.5 ) ％ and (9.4 ± 9.9)％ respectively.Conclusions An ideal tool for the VMAT verification,the patient anatomy based COMPASS 3D dose verification system can check the dose difference between the real delivery and TPS calculation directly for each individual organ,either target volumes or critical organs.

Objective To discuss the standard diagnosis and treatment for thyroid nodule.Methods 2 581 patients with thyroid nodule from 2005 to 2009 were studied.Common methods of examination and treatment were analyzed to avoid over-examination and over-treatment.Results 90%of the patients underwent ultrasound examination with a 92.9%sensitivity and 44.3%specificity when there were two or more risk characters.All patients underwent certain kinds of surgery according to their clinical conditions.The recurrence rate was 4%two and half years after lateral thyroid adenectomy or thyroid surgery without excision of thyroid isthmus.Conclusions There are many approaches to thyroid nodule examination and treatment,in which ultrasound is recommended for preoperative examination because of its higher sensitivity,specificity and lower cost,and surgery is still the most useful and effective treatment.Choosing the proper method for thyroid nodule diagnosis and treatment is the key point to avoid over-examination and over-treatment.