The molecular mechanism of ferroptosis-induced spontaneous abortion based on bioinformatics approach.

Spontaneous abortion (SA) is a prevalent placental dysfunction, and ferroptosis may play a crucial role in placental dysfunction and the development of SA. In this study, we employed data mining and analysis techniques to investigate the biological mechanism of SA induced by ferroptosis, resulting in the identification of a total of 79 ferroptosis-related genes in SA were identified. Among them, 3 co-expression modules of ferroptosis risk genes, ten significant functions and six biologically significant pathways were obtained 61 pairs of differentially expressed miRNA-ferroptosis factor relationships were identified, and WIPI1 and GSN were expressed at significantly higher levels in SA. This is extremely helpful for future research on SA.

Genetic Analysis of 1p36 Deletions for Six Aborted Fetuses.

Context: Chromosomal abnormalities in embryos are the most common cause of early spontaneous abortions. Chromosome 1p36 deletion syndrome (OMIM 607872) is the most common subtelomeric, terminal microdeletion syndrome. Objective: The study intended to analyze miscarriage samples using chromosomal microarray analysis (CMA), to explore the mechanism of chromosomal aberrations, and to identify the recurrence risk and a prenatal diagnostic strategy for couples experiencing spontaneous abortions. Design: The research team performed a narrative review by searching PubMed databases. The search used the keywords 1p36 deletion, CMA, karyotype analysis, FISH and aborted fetus. The team also conducted case studies using genetic analyses. Setting: The study took place at Wuxi Maternity and Child Health Care Hospital in Wuxi, Jiangsu, PR China. Participants: Out of 673 abortion samples, six had 1p36 deletions (0.89%). Participants were the six families who had had those spontaneous abortions. Outcome Measures: The research team evaluated the fetal samples using: (1) CMA, (2) karyotype analysis, and (3) novel fluorescence in-situ hybridization (FISH). Results: The CMA showed that: (1) fetus 1 had a 1.75 MB microdeletion at the 1p36.32p36.31 band, which testing didn't detect in fetus 1's parents, but the research team couldn't exclude the possibility that one of the parents was a carrier of a chromosomal insertional translocation; and (2) fetus 2 had a 5.10 MB microdeletion at the 1p36.13p36.12 segment, and fetus 3 had a 9.21 MB deletion at the 1p36.33p36.22 band, and the high-resolution karyotype analysis and FISH of the parents of both fetuses appeared normal, indicating that the chromosomal abnormalities were de novo; (3) fetus 4 had a 9.28 MB deletion at 1p36.33p36.22, although the high-resolution karyotype analysis of fetus 4's parent was normal; (4) fetuses 5 and 6 had a 7.64 MB microdeletion at 1p36.33p36.23 and a 4.45 MB deletion at 1p36.33p36.32, respectively, although the parents of both fetuses waived further testing. Conclusions: This study provides the first report of recurrent spontaneous and sporadic abortions with 1p36 deletion syndrome. The CMA combined with a reasonable family-pedigree investigation can detect cryptic chromosomal aberrations in miscarriages and can determine the mechanism of the chromosomal variations. It thus is invaluable in assessing recurrence risk and providing appropriate prenatal diagnostic strategies for affected families.

Safety and Efficacy of Combined Oral Contraceptive Ethinyl Estradiol/Drospirenone (YAZ) in Chinese Women: A Single-Arm, Open-Label, Multicenter, Post-Authorization Study.

INTRODUCTION: The study was conducted to assess the safety and efficacy of a combined oral contraceptive, YAZ, containing 3 mg drospirenone/20 µg ethinyl estradiol administered in a 24/4 regimen. METHODS: This was a single-arm, open-label, interventional, post-authorization safety surveillance study of YAZ across 6 treatment cycles. Primary objective was assessing its safety profile in Chinese women. Secondary objectives included assessing contraceptive efficacy, cycle control, and bleeding patterns among subjects with and without preceding abortion, along with efficacy in moderate acne vulgaris. Subgroup analyses included assessing efficacy in the dysmenorrhea group using a visual analog scale. All variables were analyzed by descriptive statistical methods. RESULTS: Of 1921 women treated with YAZ (mean age: 29.9 ± 5.5 years), 12.9% reported adverse drug reactions. Most frequently reported adverse events were nausea (2.6%), breast pain (2.3%), and breast swelling (1.3%). Unintended pregnancy rate (adjusted Pearl Index) was 0.3 (n = 2 pregnancies, 95% confidence interval 0.1-1.2). Incidence of overall withdrawal bleeding (cycle 2-cycle 5) was 93.3%-95.2%, of which 87.8%-95.1% in post-abortion subjects and 94.0%-95.3% in subjects without preceding abortion. Intra-cyclic bleeding (cycle 2-cycle 6) decreased in the overall population (from 14.9 to 5.5%), post-abortion subgroup (32.4% to 6.9%), and in subjects without preceding abortion (12.4% to 5.3%). Incidence of onset of withdrawal bleeding < 7 days among abnormal uterine bleeding patients at baseline was 85.2% and 87.2% at cycles 2 and 5, respectively, and incidence of intra-cyclic bleeding was 23.5% and 8.0% at cycles 1 and 6, respectively. Mean percent change in total acne lesion count from baseline to cycle 6 was - 79.9% ,and mean change in pain severity due to dysmenorrhea was - 31.2 mm at cycle 6 when compared with baseline. CONCLUSION: The 24/4 YAZ regimen showed good safety profile, contraceptive reliability, good cycle control along with subgroup of patients. Improvements in dysmenorrhea and acne were also observed. No events of venous thromboembolism/arterial thromboembolism were reported. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02710708; Center for Drug Evaluation (CDE), China Food and Drug Administration (CFDA) number: CTR20160203.

Association between fetal chromosomal abnormalities and the frequency of spontaneous abortions.

Fetal chromosomal abnormalities are a common cause of spontaneous abortion. The present study investigated the association between fetal chromosomal abnormalities and the frequency of spontaneous abortions to enable clinicians to provide more informed genetic counseling. A total of 182 patients with a history of spontaneous abortions were recruited from July 2015 to August 2017. G-banding cytogenetic analysis and novel high-throughput ligation-dependent probe amplification (HLPA) techniques were performed on conception in all 182 patients to detect chromosomal abnormalities. Low-coverage whole-genome sequencing (WGS) was performed in 74 patients to detect copy number variations (CNVs). There were no significant differences in the incidence of karyotype abnormalities between patients with sporadic miscarriages (48.0%; SM group) and patients suffering recurrent spontaneous abortions (44.8%; RSA group). The maternal age was markedly higher in patients with 3 miscarriages. WGS indicated that the incidence of pathogenic CNVs in the RSA group was higher than that in the SM group, but the difference was not significant. In conclusion, a high incidence of karyotype abnormalities and pathogenic CNVs was observed in patients with spontaneous abortion. However, no association between fetal chromosomal abnormalities and the number of spontaneous abortions was observed. HLPA assays may be used as an alternative method for fetal karyotype analysis and determination of CNVs in patients with SM and RSA.