Reproductive outcomes in couples with recurrent pregnancy loss after embryonic chromosomal microarray analysis.

BACKGROUND: Chromosomal microarray analysis (CMA) has been widely applied to explore the genetic etiology in recurrent pregnancy loss (RPL). However, the reproductive prognosis in RPL couples with different types of chromosomally abnormal miscarriage remains unclear. OBJECTIVES: The main purpose of this study was to evaluate the reproductive prognosis among RPL couples after genetic testing in products of conception (POCs) by CMA. STUDY DESIGN: In this retrospective study, 1101 RPL couples referred for genetic testing in POCs by CMA. A total of 830 couples who met the inclusion criteria were followed up for at least 24 months after the index miscarriage. The rates of live birth and adverse pregnancy events in subsequent pregnancy and cumulative pregnancies were examined. RESULTS: For couples with three or more miscarriage, compared with those with chromosomally normal miscarriage, a significantly higher subsequent live birth rate was found in couples with chromosomally abnormal miscarriage (66.9% vs 71.6%, P = .040). However, differences in cumulative live birth rate among couples with chromosomally abnormal miscarriage and normal miscarriage were nonsignificant (82.7% vs 80.2%, P = .131). Women with advanced maternal age showed a significant decrease in the live birth rate (P < 0.01) and an increase in the miscarriage rate (P < 0.01) than those aged < 35 years old, regardless of whether the miscarriage was chromosomally normal or abnormal. RPL couples with chromosomally normal miscarriage showed a significant decrease in live birth rates in subsequent pregnancy and cumulative pregnancies, when they had experienced a large number of previous miscarriages; however, no significant difference was observed in those with chromosomally abnormal miscarriage. CONCLUSION: For women with three or more previous miscarriages, RPL couples with chromosomally normal miscarriage manifested a poorer reproductive prognosis than those with chromosomally abnormal miscarriage in subsequent pregnancy, while the cumulative live birth rate was similar. Advanced maternal age was a predictor of adverse pregnancy events, regardless of embryonic chromosomal results. Furthermore, among RPL women with large numbers of previous miscarriages, the supportive care and counselling regarding individual risk is necessary for those with chromosomally normal miscarriage.

Residual risk of clinically significant copy number variations in fetuses with nasal bone absence or hypoplasia after excluding non-invasive prenatal screening-detectable findings.

BACKGROUND: It remains controversial whether prenatal screening or diagnostic testing should be offered to fetuses with nasal bone (NB) absence or hypoplasia, and there are no studies comparing the yield of chromosomal microarray analysis (CMA) to non-invasive prenatal screening (NIPS). The aim of this study was to evaluate the residual risk of clinically significant copy number variations (CNVs) in fetuses with NB absence or hypoplasia after excluding theoretically NIPS-detectable abnormalities, and to assess their clinical outcomes. METHODS: This prospective study encompassed 400 fetuses with NB absence or hypoplasia undergoing CMA testing between 2015 and 2022. Clinically significant CMA findings were categorized into three subgroups, including three-NIPS-detectable (trisomies 21, 18 and 13), five-NIPS-detectable (trisomies 21, 18 and 13 and sex chromosome aneuploidies) and genome-wide NIPS-detectable (variants over 7 Mb). We calculated the theoretical residual risk and compared it with the results of a control cohort of low-risk pregnancies. We further evaluated their clinical outcomes. RESULTS: The overall diagnostic yield in our cohort was 7.8% (31/400). The detection rate of clinically significant CMA findings in fetuses with non-isolated NB absence or hypoplasia was significantly higher than that in fetuses with isolated NB absence or hypoplasia (20.0% vs. 6.6%, P =.005). The theoretical residual risks in all NIPS models were significantly higher when compared with the control cohort. The normal infant rate in fetuses with normal CMA results was 97.9% (323/330), and a significant higher incidence was observed in fetuses with isolated NB absence or hypoplasia compared with non-isolated NB absence or hypoplasia (98.4% vs. 91.7%, P =.028). CONCLUSIONS: The residual risk of clinically significant CNVs in fetuses with NB absence or hypoplasia following the exclusion of theoretically NIPS-detectable findings was higher than that in low-risk pregnancies. This risk should be considered in genetic counseling to make a more comprehensive and precise choice regarding prenatal genetic testing.

Reproductive outcomes in couples with sporadic miscarriage after embryonic chromosomal microarray analysis.

OBJECTIVES: Chromosomal microarray analysis (CMA) has been widely applied to genetic diagnosis in miscarriages in clinical practice. However, the prognostic value of CMA testing of products of conception (POCs) after the first clinical miscarriage remains unknown. The aim of this study was to evaluate the reproductive outcomes after embryonic genetic testing by CMA in SM couples. METHODS: In this retrospective study, a total of 1142 SM couples referred for embryonic genetic testing by CMA, and 1022 couples were successfully followed up after CMA. RESULTS: Among 1130 cases without significant maternal cell contamination, pathogenic chromosomal abnormalities were detected in 680 cases (60.2%). The subsequent live birth rate did not differ significantly between couples with chromosomally abnormal and normal miscarriage (88.6% vs. 91.1%, p = .240), as well as the cumulative live birth rate (94.5% vs. 96.7%, p = .131). Couples with partial aneuploid miscarriage had a higher likelihood of spontaneous abortion both in the subsequent pregnancy (19.0% vs. 6.5%, p = .037) and cumulative pregnancies (19.0% vs. 6.8%, p = .044) when compared with couples with chromosomally normal miscarriage. CONCLUSIONS: SM couples with chromosomally abnormal miscarriage manifested with a similar reproductive prognosis to couples with chromosomally normal miscarriage. Key messagesCMA testing of POCs could provide an accurate genetic diagnosis for couples with SM.The live birth rate of couples with partial aneuploid miscarriage was as high as couples with chromosomally normal miscarriage, despite a higher risk of adverse pregnancy event.Among couples with the most common single aneuploid miscarriage, the cumulative live birth rates of couples with trisomy 16, sex chromosomal abnormalities and trisomy 22 were 94.1%, 95.8% and 84.0%, respectively.

Application of multistage induced electric field for acid hydrolysis of starch in a continuous-flow reactor.

Herein, a multistage induced electric field (IEF) combined with a continuous-flow reactor was utilized to assist the acid hydrolysis of corn, potato, and waxy corn starch for avoiding plate corrosion and heavy metal leakage. It was found that adding IEF stages was beneficial to improve the hydrolysis efficiency. Treating potato, corn, and waxy corn starch via continuous-flow IEF increased the reducing sugar contents up to 78.76 %, 57.86 %, and 66.18 %, respectively. The electrical conductivity of starch grew with the reaction stages, while starch yield demonstrated the opposite trend. Treated starch had higher solubility and gelatinization peak temperature than native starch, with the gelatinization enthalpy showing fluctuations. Meanwhile, the swelling power decreased as the number of IEF stages was increased. Observations of Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy indicated that the treated starch became more ordered, and crystalline regions were destroyed to various degrees with pores forming on particle surfaces. These variations could be attributed to acid hydrolysis and IEF.

Whole-transcriptome sequencing identifies key mRNAs, miRNAs, lncRNAs, and circRNAs associated with unexplained recurrent pregnancy loss.

Recurrent pregnancy loss is a common obstetric complication affecting approximately 1-2% of reproductive population worldwide, but the precise causes for approximately a half of such patients remain unexplained. In this study, we compared the expression profiles of messenger RNA (mRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) in villi tissues from patients with unexplained recurrent pregnancy loss (URPL) and elective termination of pregnancy (ETP) using whole-transcriptome sequencing. A number of differentially expressed RNAs were confirmed by real-time PCR analysis. As a result, we identified a total of 1,703 mRNAs, 798 lncRNAs, 199 miRNAs, and 163 circRNAs that were significantly differentially expressed between villi tissues from URPL and ETP. The data of real-time PCR were consistent with those of the sequencing results. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the majority of differentially expressed mRNAs and target genes of ncRNAs were associated with focal adhesion, extracellular matrix-receptor interaction, and the PI3K-Akt signaling pathway. Additionally, two co-expression networks (lncRNA-miRNA-mRNA and lncRNA-circRNA-miRNA-mRNA) were constructed based on the correlation analysis between the differentially expressed RNAs. Taken together, this study provides a large number of valuable candidates for elucidating regulatory mechanisms of ncRNAs, which may ultimately assist in understanding the pathogenesis of URPL.