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 evaluate the effect of Kuntai capsules combined with progestin-primed ovarian stimulation (PPOS) protocol on the ovarian response, laboratory parameters and embryo transfer outcomes of expected poor ovarian response (POR) patients undergoing invitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods:A retrospective cohort study was performed at Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital from June 2020 to July 2023. A total of 1 733 expected POR patients were enrolled and divided into the PPOS only group (control group) and the Kuntai capsules combined with PPOS regimen group (trial group). After a 1∶1 propensity score matching, 423 cases were included in each group. Further analyses and comparisons were made between the two groups, concerning the ovarian stimulation outcomes, embryo laboratory parameters and pregnancy rates after the first frozen-thawed embryo transfer cycles. The primary outcome measure was the number of oocytes retrieved.Results:No statistically significant difference was found in baseline characteristics after matching between the two groups (all P>0.05). Compared with control group, the number of oocytes retrieved did not differ significantly in the trial group ( P=0.295). The level of luteinizing hormone (LH) on the trigger day [3.3 (2.2, 5.0) U/L], the number of available blastocysts formed [1 (0, 1)] and the available blastocyst formation rate [46.2% (85/184)] in the trial group were significantly higher than those in control group [2.9 (1.9, 4.5) U/L, P=0.004; 0 (0, 1), P=0.034; 30.0% (48/160), P=0.002]. However, there were no significant differences in the duration and dosage of gonadotropin used, progesterone and estradiol levels on the trigger day, incidence of premature LH surge, number/rate of fertilized oocytes, number/rate of cleaved embryos, number/rate of high-quality embryos, as well as rate of unavailable embryos (all P>0.05). Compared with control group, the trial group demonstrated comparable implantation rate, clinical pregnancy rate, early miscarriage rate, ongoing pregnancy rate and live birth rate after the first frozen-thawed embryo transfer cycles (all P>0.05). Conclusion:Compared with the PPOS only regimen, the combination of Kuntai capsules and PPOS did not increase the number of oocytes retrieved but could increase the number and rate of available blastocysts formed in expected POR patients.

Objective:To explore the clinical application value of third-generation sequencing technology in preimplantation genetic testing (PGT) of an ATR-X syndrome pedigree with chromosomal microduplication.Methods:The study selected a pedigree with a suspected ATR-X syndrome child at Assisted Reproductive Center of Jiangxi Maternal and Child Health Hospital in October 2022. After chromosome copy number variation sequencing (CNV Seq) detection, it was found that the female carried a 550 kb heterozygous microrepeat with unclear clinical significance in the Xq21.1 region, which involved partial sequences of the ATRX gene. The third generation long read sequencing technology was used to detect the female genome sequence, determine the physical location of the insertion of the above repeat into the genome, clarify the pathogenicity of the repeat, and obtain a single nucleotide polymorphism (SNP) haplotype linked to the above micro repeat inheritance. After the couple's full informed consent, PGT was performed to assist pregnancy. One haploid embryo without pathogenic microduplication was selected for transfer. To verify the consistency with PGT test results, amniocentesis prenatal diagnosis was performed in the second trimester after successful pregnancy, and the fetus was followed up after birth. Results:The results of the third generation long read sequencing and Sanger sequencing verification showed that the Xq21.1 microrepeat carried by the female was inserted into the genome chrX: 76804463-76804464 (GRCh37/hg19), which is an intra tandem repeat of the ATRX gene, and it is predicted that it may cause damage to the normal function of the ATRX protein. After one cycle of PGT treatment, 27 oocytes were obtained and 13 blastocysts were successfully developed after intracytoplasmic sperm injection (ICSI). Through genetic testing, it was found that two blastocysts were haploid embryos without carrying the aforementioned pathogenic microduplication. After thawing and transferring one of the blastocysts, the pregnancy was achieved, and the prenatal diagnosis results of amniocentesis in the second trimester were consistent with the PGT results. In November 2023, at 39 +5 weeks of pregnancy, a female live baby was delivered by natural delivery, and she is in good health. Conclusion:The third-generation sequencing technology has significant advantages in PGT detection of clinically ambiguous microreplicates with functional deficiency due to its long read length characteristics. It can not only determine the location of microreplicates inserted into the genome and determine their pathogenicity, but also obtain SNP haplotypes that are linked to the target mutation, thus preparing for subsequent embryo detection.

Objective:To evaluate the effect of Kuntai capsules combined with progestin-primed ovarian stimulation (PPOS) protocol on the ovarian response, laboratory parameters and embryo transfer outcomes of expected poor ovarian response (POR) patients undergoing invitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods:A retrospective cohort study was performed at Center for Reproductive Medicine, Jiangxi Maternal and Child Health Hospital from June 2020 to July 2023. A total of 1 733 expected POR patients were enrolled and divided into the PPOS only group (control group) and the Kuntai capsules combined with PPOS regimen group (trial group). After a 1∶1 propensity score matching, 423 cases were included in each group. Further analyses and comparisons were made between the two groups, concerning the ovarian stimulation outcomes, embryo laboratory parameters and pregnancy rates after the first frozen-thawed embryo transfer cycles. The primary outcome measure was the number of oocytes retrieved.Results:No statistically significant difference was found in baseline characteristics after matching between the two groups (all P>0.05). Compared with control group, the number of oocytes retrieved did not differ significantly in the trial group ( P=0.295). The level of luteinizing hormone (LH) on the trigger day [3.3 (2.2, 5.0) U/L], the number of available blastocysts formed [1 (0, 1)] and the available blastocyst formation rate [46.2% (85/184)] in the trial group were significantly higher than those in control group [2.9 (1.9, 4.5) U/L, P=0.004; 0 (0, 1), P=0.034; 30.0% (48/160), P=0.002]. However, there were no significant differences in the duration and dosage of gonadotropin used, progesterone and estradiol levels on the trigger day, incidence of premature LH surge, number/rate of fertilized oocytes, number/rate of cleaved embryos, number/rate of high-quality embryos, as well as rate of unavailable embryos (all P>0.05). Compared with control group, the trial group demonstrated comparable implantation rate, clinical pregnancy rate, early miscarriage rate, ongoing pregnancy rate and live birth rate after the first frozen-thawed embryo transfer cycles (all P>0.05). Conclusion:Compared with the PPOS only regimen, the combination of Kuntai capsules and PPOS did not increase the number of oocytes retrieved but could increase the number and rate of available blastocysts formed in expected POR patients.

Objective:To explore the clinical application value of third-generation sequencing technology in preimplantation genetic testing (PGT) of an ATR-X syndrome pedigree with chromosomal microduplication.Methods:The study selected a pedigree with a suspected ATR-X syndrome child at Assisted Reproductive Center of Jiangxi Maternal and Child Health Hospital in October 2022. After chromosome copy number variation sequencing (CNV Seq) detection, it was found that the female carried a 550 kb heterozygous microrepeat with unclear clinical significance in the Xq21.1 region, which involved partial sequences of the ATRX gene. The third generation long read sequencing technology was used to detect the female genome sequence, determine the physical location of the insertion of the above repeat into the genome, clarify the pathogenicity of the repeat, and obtain a single nucleotide polymorphism (SNP) haplotype linked to the above micro repeat inheritance. After the couple's full informed consent, PGT was performed to assist pregnancy. One haploid embryo without pathogenic microduplication was selected for transfer. To verify the consistency with PGT test results, amniocentesis prenatal diagnosis was performed in the second trimester after successful pregnancy, and the fetus was followed up after birth. Results:The results of the third generation long read sequencing and Sanger sequencing verification showed that the Xq21.1 microrepeat carried by the female was inserted into the genome chrX: 76804463-76804464 (GRCh37/hg19), which is an intra tandem repeat of the ATRX gene, and it is predicted that it may cause damage to the normal function of the ATRX protein. After one cycle of PGT treatment, 27 oocytes were obtained and 13 blastocysts were successfully developed after intracytoplasmic sperm injection (ICSI). Through genetic testing, it was found that two blastocysts were haploid embryos without carrying the aforementioned pathogenic microduplication. After thawing and transferring one of the blastocysts, the pregnancy was achieved, and the prenatal diagnosis results of amniocentesis in the second trimester were consistent with the PGT results. In November 2023, at 39 +5 weeks of pregnancy, a female live baby was delivered by natural delivery, and she is in good health. Conclusion:The third-generation sequencing technology has significant advantages in PGT detection of clinically ambiguous microreplicates with functional deficiency due to its long read length characteristics. It can not only determine the location of microreplicates inserted into the genome and determine their pathogenicity, but also obtain SNP haplotypes that are linked to the target mutation, thus preparing for subsequent embryo detection.