The effects of first-trimester subchorionic hematoma on pregnancy outcomes: a retrospective cohort study.

BACKGROUND: Although first-trimester subchorionic hematoma (SCH) always concerns expectant parents, its clinical significance remains controversial. This study aimed to examine the relationship between SCH and its association with subsequent miscarriage and other perinatal outcomes in singleton pregnancies. METHODS: We conducted a retrospective cohort study including 43,660 women who underwent routine prenatal care since the first trimester and then were followed up for maternal and neonatal outcomes. SCH was detected in the first-trimester ultrasound examinations. Robust Poisson regression was used to estimate adjusted risk associations of SCH with maternal and neonatal outcomes. RESULTS: A total of 815 (1.87%) SCH cases were detected in the first-trimester ultrasound examinations. The rate of miscarriage was statistically significantly higher in women with SCH than without [35.21% vs. 23.92%, P < 0.01; adjusted relative risk (RR):1.44, 95% confidence interval (CI): 1.31-1.58]. Subgroup analysis of women with SCH showed a clear trend that the earlier SCH occurred, the higher the risk of miscarriage was [adjusted RR (95% CI) for onset at the gestational weeks of 8-9, 6-7, and < 6 vs. ≥ 10: 1.30 (0.69-2.46), 2.33 (1.28-4.23), and 4.18 (2.30-7.58), respectively; Ptrend < 0.01]. In addition, women with SCH volume ≥ 1 ml showed higher risk than did those with SCH volume < 1 ml [adjusted RR (95% CI) for 1-4.9 ml, and ≥ 5 ml vs. < 1 ml: 1.36 (1.10-1.68) and 1.56 (1.18-2.07), respectively]. There was no statistically significant difference in the rates of other pregnancy outcomes between women with and without SCH. CONCLUSIONS: First-trimester SCH, particularly when characterized by early presence and large size, might significantly increase the risk of miscarriage. Data from this study suggest no associations between SCH and other maternal and neonatal outcomes.

Androgen-secreting adult granulosa cell tumor in a woman with polycystic ovary syndrome: a case report.

Aim: To present the clinicopathologic findings of the second case of androgen-secreting adult granulosa cell tumor (AGCT) in a woman with polycystic ovary syndrome (PCOS) and discuss in the light of the literature. Methods: Description of a case and discussion of the literature. Results: A patient with oligomenorrhea, amenorrhea and hirsutism who was diagnosed as PCOS and treated by oral contraceptive for three years, then left ovarian solid and liquid mass was found and pathologically confirmed to be androgen-secreting AGCT after left oophorectomy. She got regular menstrual cycle and gave birth naturally, but clinical features of PCOS reappeared after breastfeeding. Conclusion: Androgen-secreting AGCT and PCOS have similar clinical features of hyperandrogenism, it is difficult to diagnose androgen-secreting AGCT when both diseases occur in the same patient. If the size of cystic mass in androgen-secreting AGCT is too small to differentiate from PCOM on imaging, pathological examination after surgery may be the only way to find the disease.

Neuroprotective Effects of Estrogen Through BDNF-Transient Receptor Potential Channels 6 Signaling Pathway in the Hippocampus in a Rat Model of Perimenopausal Depression.

Estradiol (E2) has been proven to be effective in treating perimenopausal depression (PD); however, the downstream signaling pathways have not been fully elucidated. Transient receptor potential channels 6 (TRPC6) plays a vital role in promoting neuronal development and the formation of excitatory synapses. At present, we found that the serum levels of E2 and brain-derived neurotrophic factor (BDNF) declined significantly in the women with PD compared to perimenopausal women, which was accompanied by a clear reduction in TRPC6 levels. To further reveal the effects of TRPC6 on neuronal survival and excitability, the PD-like rat model was established by the total removal of left ovary and 80% removal of right ovary followed by 21 days of the chronic unpredictable mild stress. Intragastric administration of E2 (2 mg/kg), intraperitoneal injection of BDNF/TrB signaling pathway inhibitor (K252a, 100 µg/kg) and TRPC6 agonist (OAG, 0.6 mg/kg), and intracerebroventricular infusion of anti-BDNF antibody for blocking BDNF (0.5 µg/24 µl/rat) daily for 21 days were conducted. The levels of BDNF and TRPC6 in rat serum were lower in PD rats compared to the control rats; the depression-like behavior was induced, the neuronal death rate in the hippocampus increased, and the thickness of postsynaptic density (PSD) and the number of asymmetric synapses decreased significantly in the PD group. E2 treatment greatly upregulated the serum levels of BDNF and TRPC6, the neuronal excitability indicated by an elevation in the PSD thickness and the numbers of asymmetric synapses, and these actions were reversed by K252a; co-administration of TRPC6 agonist and K252a improved neuronal degeneration and increased the neuronal excitability induced in the E2-treated PD rats. K252a or anti-BDNF antibody inhibited the increased neuronal BDNF and TRPC6 expression in E2-treated PD rats; co-treatment of TRPC6 agonist and anti-BDNF antibody reduced neuronal death and increased the BDNF and TRPC6 expression in the hippocampal CA1 neurons in the E2-treated PD rats. These results suggest that the neuroprotective role of E2 in PD is closely related to enhance the activity of BDNF/TRPC6 pathway and is helpful to provide new prevention and strategies.

Genomic imbalance in euploid pregnancy loss.

PURPOSE: This study aims to investigate genomic imbalance in euploid products of conceptions (POCs) detected by chromosomal microarray analysis (CMA) and its association with clinical characteristics. METHODS: In a retrospective cohort study where all women with singleton pregnancy losses underwent CMA detection of POCs, only patients with euploid POCs were included in the analysis. The clinical features were compared between those with and without a copy number variant (CNV). The pathogenic CNVs and the variant of uncertain significance (VOUS) were analyzed, and the common pathogenic CNVs and uniparental disomy (UPD) were investigated. RESULTS: A total of 610 POCs were detected as chromosomal euploid, of which 176 were euploid with CNVs and 434 were euploid without CNVs. Regarding maternal age, gestational age, and history of pregnancy loss, no significant differences were found between the two groups. Furthermore, 104 pathogenic CNVs were identified in 93 POCs, and the deletion of 8p23.3 was found in 10 subjects. All CNVs greater than 3 Mb and 39.5% of CNVs ranging from 1 to 2 Mb were pathogenic, and only 3 CNVs < 1 Mb were pathogenic. UPD was detected in 12 POCs. CONCLUSION: Besides aneuploidy, 15.24% pregnancy loss might have an association with pathogenic genomic imbalance, and the occurrence of genomic imbalance is not related to clinical characteristics. CNVs greater than 3 Mb in pregnancy losses have a high probability to be pathogenic, and approximately 40% of CNVs ranging from 1 to 2 Mb are pathogenic. The deletion of 8p23.3 is the most common pathogenic CVN in POCs of Chinese-Han women. The clinical significance of UPD in pregnancy loss needs further study.

Copy Number Variation Analysis of Euploid Pregnancy Loss.

Objectives: Copy number variant (CNV) is believed to be the potential genetic cause of pregnancy loss. However, CNVs less than 3 Mb in euploid products of conceptions (POCs) remain largely unexplored. The aim of this study was to investigate the features of CNVs less than 3 Mb in POCs and their potential clinical significance in pregnancy loss/fetal death. Methods: CNV data were extracted from a cohort in our institution and 19 peer-reviewed publications, and only those CNVs less than 3 Mb detected in euploid pregnancy loss/fetal death were included. We conducted a CNV map to analyze the distribution of CNVs in chromosomes using R packages karyoploteR_1.10.5. Gene names and annotated gene types covered by those CNVs were mined from the human Release 19 reference genome file and GENECODE database. We assessed the expression patterns and the consequences of murine knock-out of those genes using TiGER and Mouse Genome Informatics (MGI) databases. Functional enrichment and pathway analysis for genes in CNVs were performed using clusterProfiler V3.12.0. Result: Breakpoints of 564 CNVs less than 3 Mb were obtained from 442 euploid POCs, with 349 gains and 185 losses. The CNV map showed that CNVs were distributed in all chromosomes, with the highest frequency detected in chromosome 22 and the lowest frequency in chromosome Y, and CNVs showed a higher density in the pericentromeric and sub-telomeric regions. A total of 5,414 genes mined from the CNV regions (CNVRs), Gene Ontology (GO), and pathway analysis showed that the genes were significantly enriched in multiple terms, especially in sensory perception, membrane region, and tight junction. A total of 995 protein-coding genes have been reported to present mammalian phenotypes in MGI, and 276 of them lead to embryonic lethality or abnormal embryo/placenta in knock-out mouse models. CNV located at 19p13.3 was the most common CNV of all POCs. Conclusion: CNVs less than 3 Mb in euploid POCs distribute unevenly in all chromosomes, and a higher density was seen in the pericentromeric and sub-telomeric regions. The genes in those CNVRs are significantly enriched in biological processes and pathways that are important to embryonic/fetal development. CNV in 19p13.3 and the variations of ARID3A and FSTL3 might contribute to pregnancy loss.

The performance of Cobas HPV test for cervical cancer screening in Chinese female migrant workers.

This study aimed to evaluate the performance of Cobas human papillomavirus (HPV) test in cervical cancer screening. A total of 3442 women aged ⩾20 years used Cobas HPV and hybrid capture 2 (HC2) tests were included in this study. Women with any positive result were examined by liquid-based cytology (LBC) test. Then subjects with abnormal LBC or positive Cobas HPV16/18 were further checked by colposcopy to observe the visible lesions to perform the pathological examination. Of these 3442 women, 328 cases were Cobas HPV positive, and the positive rate was 9.53% (95% confidence interval (CI) 8.50-10.53). The positive rate of HPV16, HPV18, and other 12 types of high-risk HPV were 1.54% (95% CI 1.12-1.95), 0.55% (95% CI 0.30-0.80), and 7.44% (95% CI 6.56-8.32), respectively. The coincidence rate of Cobas HPV test and HC2 test was 90% (95% CI 89.00-91.00; Kappa = 0.526) in the primary screening. Age had a non-linear relationship with Cobas HPV positive rate (χ2 = 4.240, P = 0.040) and HPV16/18 typing positive rate (χ2 = 6.610, P = 0.010). Compared with the LBC test, the Cobas HPV test had higher sensitivity when detecting patients with high cervical intraepithelial neoplasia (CIN2+ and CIN3+).

Chromosomal Aneuploidy Associated With Clinical Characteristics of Pregnancy Loss.

OBJECTIVE: Embryonic aneuploidy is found in about half of sporadic pregnancy losses and the associations between the chromosomal aneuploidy and clinical characteristics of pregnancy loss remain unclear. The aims of this study were to evaluate the associations between chromosomal aneuploidy of products of conception (POC) and clinical features of pregnancy loss. METHODS: We conducted a retrospective cohort study including 1,102 women experienced singleton pregnancy loss and underwent chromosomal microarray analysis (CMA) detection of POC in our hospital. The results of molecular karyotypes and clinical features including maternal age, history of pregnancy loss, gestational age, vaginal bleeding and ultrasonographic findings were extracted from the medical records. χ2 test was used to compare categorical data between groups. RESULTS: 631 (57.26%) POC specimens were detected to be chromosomal aneuploidy. Aneuploid rates were significantly higher in women >35 years (P < 0.001) and pregnancy loss <11 gestational weeks (P = 0.044), but the rates of sex chromosome abnormalities and triploid were significantly higher in women ≤35 years (P < 0.001, P = 0.002) and the rates of viable autosomal trisomy and sex chromosome abnormalities were significantly high in those women with pregnancy loss ≥11 weeks (P < 0.001, P < 0.001). Aneuploid rate was overall similar between the sporadic and the recurrent pregnancy loss (RPL) (P = 0.404), but the rate of sex chromosome abnormalities was higher in women with sporadic pregnancy loss (P = 0.03). Aneuploid rates were higher in subjects with yolk sac or embryo than in those without (P < 0.001 and P = 0.001). CONCLUSION: Advanced maternal age is mainly associated with autosomal trisomy, while sex chromosome abnormalities and triploid might be more likely to occur in younger women. Aneuploidy rates might be no association with previous pregnancy loss except for sex chromosome abnormalities. Pregnancy loss without yolk sac or embryo might be less related to embryonic aneuploidy, and other factors should be emphasized.

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.

Rare copy number variants in the genome of Chinese female children and adolescents with Turner syndrome.

Turner syndrome (TS) is a congenital disease caused by complete or partial loss of one X chromosome. Low bone mineral status is a major phenotypic characteristic of TS that can not be fully explained by X chromosome loss, suggesting other autosomal-linked mutations may also exist. Therefore, the present study aimed to detect potential genetic mutations in TS through examination of copy number variation (CNV). Seventeen patients with TS and 15 healthy volunteer girls were recruited. Array-based comparative genomic hybridization (a-CGH) was performed on whole blood genomic DNA (gDMA) from the 17 TS patients and 15 healthy volunteer girls to identify potential CNVs. The abnormal CNV of one identified gene (CARD11) was verified by quantitative PCR. All cases diagnosed had TS based on genotype examination and physical characteristics, including short stature and premature ovarian failure. Three rare CNVs, located individually at 7p22.3, 7p22.2, and Xp22.33, where six genes (TTYH3, AMZ1, GNA12, BC038729, CARD11, and SHOX (stature homeobox)) are located, were found in TS patients. Quantitative PCR confirmed the CNV of CARD11 in the genome of TS patients. Our results indicate that CARD11 gene is one of the mutated genes involved in TS disease. However, this CNV is rare and its contribution to TS phenotype requires further study.

Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis.

This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents require further investigation.

Body composition and bone mineral status in patients with Turner syndrome.

Turner syndrome (TS) is associated with decreased bone mineral density and increased fracture rate. However, the developmental trajectory of bone density or body composition in patients with TS is still unclear. The present study tested the hypothesis that different karyotypes and/or age contributes to abnormal body composition and decreased bone mineral status parameters in patients with TS. This study included 24 girls with TS, in which 13 girls exhibited X0 karyotype and 11 had mosaicism. Quantitative ultrasound (QUS) assessed the bone mineral status of the calcaneus, including bone mineral density (BMD), amplitude-dependent speed of sound (AD-SOS), broadband ultrasound attenuation (BUA) and InBody 770 assessed body composition. Pearson's test was performed to correlate measured parameters with patient age. The body composition and bone mineral status parameters were not significantly influenced by patient karyotype. There was a correlation between patient age and AD-SOS (r = -0.61, P = 0.002) and BUA (r = 0.50, P = 0.013) but not BMD (r = -0.19, P = 0.379). In conclusion, there was no effect of karyotype on body composition or body mineral status. Bone mineral status, as evidenced by changes in AD-SOS and BUA, alters with age regardless of karyotype. The developmental trajectory demonstrated in the current study warrants further validation in a longitudinal study.