Endometrial microbiota alteration in female patients with endometrial polyps based on 16S rRNA gene sequencing analysis.

Introduction: The potential role of the endometrial microbiota in the pathogenesis of endometrial polyps (EPs) warrants further investigation, given the current landscape of limited and inconclusive research findings. We aimed to explore the microecological characteristics of the uterine cavity in patients with EPs and investigate the potential of endometrial microbiota species as novel biomarkers for identifying EPs. Methods: Endometrial samples were collected from 225 patients who underwent hysteroscopies, of whom 167 had EPs, whereas 58 had non- hyperproliferative endometrium status. The endometrial microbiota was assessed using 16S rRNA gene sequencing. We characterized the endometrial microbiota and identified microbial biomarkers for predicting EPs. Results: The endometrial microbial diversity and composition were significantly different between the EP and control groups. Predictive functional analyses of the endometrial microbiota demonstrated significant alterations in pathways involved in sphingolipid metabolism, steroid hormone biosynthesis, and apoptosis between the two groups. Moreover, a classification model based on endometrial microbial ASV-based biomarkers along with the presence of abnormal uterine bleeding symptoms achieved powerful classification potential in identifying EPs in both the discovery and validation cohorts. Conclusion: Our study indicates a potential association between altered endometrial microbiota and EPs. Endometrial microbiota-based biomarkers may prove valuable for the diagnosis of EPs. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR2100052746).

Robot-Assisted Vaginal Natural Orifice Transluminal Endoscopic Surgery (RvNOTES) with Total Hysterectomy for Management of Stage IV Endometriosis with/without Complete Cul-de-Sac Obliteration: 23-Case Pilot Feasibility Study.

STUDY OBJECTIVE: To show feasibility and short-term outcomes of robot-assisted vaginal NOTES (RvNOTES) for the treatment of stage IV endometriosis during total hysterectomy with/without complete cul-de-sac obliteration. DESIGN: Retrospective case series. SETTING: Single academic tertiary care hospital in Houston, Texas, USA. PATIENTS: Twenty-three adult women with stage IV endometriosis. INTERVENTIONS: RvNOTES with total hysterectomy for excision of severe endometriosis. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for various metrics including total operative time, robot dock time, robot console time, hysterectomy time, estimated blood loss, perioperative pain using the Visual Analogue Scale (VAS), and complications. The mean total operative time was 224.3 minutes. The study also found that patients with complete cul-de-sac obliteration had significantly longer operative times and higher estimated blood loss compared to those with partial or no obliteration. Postoperative VAS pain scores showed a significant reduction over a 6-week period. Complications included one case of complete ureteral transection, pelvic hematoma with infection, vaginal abscess, urinary tract infection, and pneumonia. CONCLUSION: Our findings suggest that RvNOTES may be a feasible surgical approach in expert hands for treating stage IV endometriosis, even in cases with complete obliteration of the cul-de-sac.

Müllerian Duct Anomalies and Anti-Müllerian Hormone Levels in Women With Polycystic Ovary Syndrome.

BACKGROUND: Significant associations between the presence of polycystic ovary syndrome (PCOS) and uterine anomalies have been reported. It is unclear whether high anti-Müllerian hormone (AMH) levels coexist with the development of uterine malformations in women with PCOS. This study sought to investigate the association between Müllerian duct anomalies and anti-Müllerian hormone (AMH) levels in women with PCOS. METHODS: In this retrospective cohort study, the records of 1,391 women with PCOS were analyzed. The cohort was divided into a low-AMH group (n = 700) and a high-AMH group (n = 691), based on an AMH cutoff value of 8.45 ng/ml. Müllerian duct anomalies were classified into four subtypes based on three-dimensional ultrasonography: septate uterus, bicornuate uterus, uterus didelphys, unicornuate uterus, and arcuate uterus. The primary outcome was the overall incidence of Müllerian duct anomalies. The secondary outcome was the prevalence of the abovementioned specific types of Müllerian duct anomalies. The prevalence of Müllerian duct anomalies was analyzed using the chi-squared test or Fisher's exact test. RESULTS: Among the patients with PCOS, the prevalence of unicornuate uterus anomalies was higher in the high-AMH group than in the low-AMH group (1.0% vs. 0.1%, P = 0.04). No statistically significant difference in the overall incidence of uterine malformations was found between the two AMH groups (4.3% vs. 5.7%, P = 0.22). CONCLUSIONS: Our study confirmed a higher prevalence of unicornuate uterus in PCOS women with high AMH levels. Clinicians might decide to investigate the possibility of a unicornuate uterus in PCOS women with high AMH levels.

The Role of FAS Receptor Methylation in Osteosarcoma Metastasis.

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of certain CpG sites that correlated significantly with FAS mRNA expression in a negative manner. Bisulfite sequencing revealed additional CpG sites, which were highly methylated in the metastatic LM7 cell line but unmethylated in its parental non-metastatic SaOS-2 cell line. Treatment with the demethylating agent, 5-azacytidine, resulted in a loss of methylation in CpG sites located within the FAS promoter and restored FAS protein expression in LM7 cells, resulting in reduced migration. Orthotopic implantation of 5-azacytidine treated LM7 cells into severe combined immunodeficient mice led to decreased lung metastases. These results suggest that DNA methylation of CGI shore sites may regulate FAS expression and constitute a potential target for osteosarcoma therapy, utilizing demethylating agents currently approved for the treatment of other cancers.

Genomic Characterization of a Multidrug-Resistant Escherichia coli Isolate Co-Carrying bla NDM-5 and bla CTX-M-14 Genes Recovered from a Pediatric Patient in China.

Background: Public health is seriously threatened by the rise of carbapenem-resistant Enterobacterales (CRE). However, the genomic characteristics of CRE detected in pediatric patients are largely unknown. Here, we reported the genomic characteristics of a multidrug-resistant Escherichia coli strain containing the plasmid-borne bla NDM-5 and bla CTX-M-14 genes recovered from a Chinese pediatric patient. Methods: The genome sequence of E. coli strain B379 was determined using Illumina NovaSeq 6000 and Oxford Nanopore MinION. Multiple bioinformatics tools were used to annotate the genome sequence, identify antimicrobial resistance genes and plasmid replicons and perform the in silico multilocus sequence typing (MLST) analysis. Using BacWGSTdb 2.0 server, a core genome MLST (cgMLST) comparison was made between E. coli B379 and all ST746 E. coli strains downloaded from the public database. Results: The E. coli B379 genome sequence is comprised of six contigs totaling 5,152,502 bp, including one chromosome and five plasmids. Nineteen antimicrobial resistance genes were predicted. The bla NDM-5, which is located on a 46,161 bp IncX3 plasmid and the bla CTX-M-14 gene which is located on a 147,204 bp IncFII/IncFIA/IncFIB plasmid are two examples of these 19 genes. E. coli B379 was resistant to ampicillin, ampicillin/sulbactam, ceftriaxone, ceftazidime, imipenem, cefepime, ciprofloxacin, ertapenem, trimethoprim-sulfamethoxazole. This isolate belonged to ST746 and the closest relative was another one originating from a human material specimen in Denmark, which differed by 273 cgMLST alleles. Conclusion: Our study reports the emergence of a multidrug-resistant E. coli strain co-carrying bla NDM-5 and bla CTX-M-14 recovered from a pediatric patient in China. These data would help us better understand the prevalence, genetic characteristics, and mechanisms of antimicrobial resistance of this recently identified multidrug-resistant bacteria in children.

Genomic Characterization of a Clinical Listeria monocytogenes ST1 Isolate Recovered from the Blood Sample of a Woman with Third Trimester Stillbirth.

Background: Listeria monocytogenes is a foodborne gram-positive bacterium which causes adverse pregnancy outcomes. Here, the genomic and phylogenetic characteristics of a L. monocytogenes isolate obtained from blood sample of a third trimester pregnant woman with stillbirth are investigated. Methods: Whole genome DNA of L. monocytogenes ST1 was sequenced with HiSeq X Ten platform. The NCBI Prokaryotic Genome Annotation Pipeline was used to annotate the genome sequence. The sequence type (ST) and antimicrobial resistance genes were then identified. The core genome multilocus sequence typing (cgMLST) analysis with other closely related L. monocytogenes stored in the NCBI GenBank database was performed using BacWGSTdb 2.0. Results: The complete genome sequence of L. monocytogenes ST1 is made up of 20 contigs totaling 2,914,725 bp, with 2886 protein-coding sequences and a GC content of 37.9%. Fosfomycin [fosX], Lincosamide antibiotic [lin] and peptide antibiotic [mprF] were discovered as antimicrobial resistance genes. In silico serogroup typing prediction revealed that L. monocytogenes ST1 belonged to serotype IVb. The closest relative of L. monocytogenes ST1, obtained from Poland in 2015, differs by only 15 cgMLST alleles. Conclusion: We identified a L. monocytogenes ST1 strain from blood sample of a woman with third trimester stillbirth in China. These discoveries would aid in our understanding of the genomic characteristics, mechanisms of antimicrobial resistance, and epidemiological features of this pathogen.

The therapeutic effect of granulocyte colony stimulating factor (G-CSF) on potential biochemical pregnancy in patients with unexplained repeated transplantation failure (RIF): a case series and literature review.

BACKGROUND: Biochemical pregnancy is a type of embryo transfer failure, patients with unexplained repeated implantation failure (RIF) also have higher biochemical pregnancy rate. Our study intends to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) in patients with unexplained RIF with low hCG levels in early pregnancy. METHODS: Unexplained RIF patients with low hCG levels after embryo transfer were allocated. G-CSF were administrated from the ninth days after embryo transfer. Clinical pregnancy, miscarriage and live birth rates were evaluated. RESULTS: The clinical pregnancy and live birth rates were 52.5% and 30%. CONCLUSION: G-CSF is an effective treatment for potential biochemical pregnancy in unexplained RIF patients.

Reproductive outcomes and reproductive tract microbiota shift in women with moderate-to-severe intrauterine adhesions following 30-day post-hysteroscopic placement of balloon stents or intrauterine contraceptive devices: A randomized controlled trial.

BACKGROUND: Intrauterine adhesions (IUA) develop in up to 20% of women with a history of abortion. After hysteroscopic adhesiolysis, balloon stents are usually placed for seven days to prevent recurrence. The efficacy of prolonged use (30 days) of balloon stents has not been determined. METHODS: The trial was conducted from June 2019 to March 2021. Ninety-one patients who underwent hysteroscopic adhesiolysis for moderate or severe IUA were randomized to receive a 30-day placement of a balloon stent (n = 44) or an intrauterine device (IUD) (n = 47). The primary outcomes were the ongoing pregnancy and miscarriage rates assessed at 15-19 months. The secondary outcomes were the recurrence of IUA and the American Fertility Society (AFS) intrauterine adhesion scores at the first and second hysteroscopies, the diagnosis of new chronic endometritis at the second-look hysteroscopy, and the vaginal/uterine microbiome assessed using 16S rRNA sequencing. The trial was registered at Chinese Clinical Trial Registry (ChiCTR1900023306). FINDINGS: The ongoing pregnancy rates (balloon 56·4% versus IUD 57·1%) and miscarriage rates (balloon 10·3% versus IUD 22·9%) were not significantly different between the groups. No differences in the recurrence of IUA, reduction of AFS scores, or new endometritis rates were detected. The bacterial load in the uterus and vagina increased in the IUD group but not in the balloon group. INTERPRETATION: Balloon placement has a similar effect on ongoing pregnancy rates as intrauterine device (IUD) placement. Patients who underwent balloon placement had a lower miscarriage rate, although the difference was not significant. There were no differences in the recurrence rate of IUA, reduction of American Fertility Society scores, or rate of new chronic endometritis. The balloon stent has less effects on the uterine microbiota. FUNDING: National Natural Science Foundation of China (81802593).

Maternal high-fat-diet exposure is associated with elevated blood pressure and sustained increased leptin levels through epigenetic memory in offspring.

Maternal metabolism dysregulation during pregnancy predisposes offspring to major diseases, including hypertension, in later life, but the mechanism involved remains to be fully elucidated. A high-fat-diet (HFD) pregnant rat model was used to investigate whether excessive intrauterine lipid exposure was associated with elevated blood pressure in offspring and increased levels of leptin, an important biomarker and mediator of vascular dysfunction and hypertension. We found that gestational hyperlipidemia predisposed offspring to blood pressure elevation and sustained increases in leptin levels with no difference in body weight in the rat model. Increased leptin expression and leptin promoter hypomethylation were found in adipose tissues of HFD-exposed offspring. The treatment of mesenchymal stem cells with free fatty acids during adipogenic differentiation resulted in increased leptin expression, accompanied by leptin promoter hypomethylation. In addition, we also followed up 121 children to evaluate the association between maternal triglyceride levels and offspring blood pressure. Consistent with the animal study results, we observed elevated serum leptin levels and blood pressure in the offspring born to women with gestational hypertriglyceridemia. Our findings provide new insights that maternal hyperlipidemia is associated with elevated blood pressure in offspring and is associated with increases in leptin levels through epigenetic memory.

The Association Between Previous TORCH Infections and Pregnancy and Neonatal Outcomes in IVF/ICSI-ET: A Retrospective Cohort Study.

Objective: This study aimed to investigate the associations between previous TORCH infection (cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella) with pregnancy and neonatal outcomes in couples undergoing IVF/ICSI-ET. Materials and Methods: A total of 18,074 couples underwent fresh IVF/ICSI-ET (in vitro fertilization/intracytoplasmic sperm injection-embryo transfer) cycles were included in our analyses. TORCH infection status was determined by serological confirmation of cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella IgG in the absence of IgM antibodies. Clinical pregnancy, ectopic pregnancy, miscarriage, live birth, preterm birth, congenital malformation, and perinatal death were evaluated in both infection and non-infection group. Multivariate logistic regression was applied to calculate odds ratio. Results: Previous toxoplasmosis infection is associated with a significantly decreased preterm birth rate [P = 0.045, OR = 0.755 (95% CI, 0.571-0.997), Adjusted OR = 0.749 (95%CI, 0.566-0.991)]. No differences in clinical pregnancy, ectopic pregnancy, miscarriage, and perinatal death were observed between the corresponding TORCH infection group [IgM (-) IgG(+)] and the non-infection group [IgM (-) IgG (-)]. Conclusions: Previous TORCH infections were not associated with adverse pregnancy and neonatal outcomes in IVF/ICSI-ET overall, and toxoplasmosis infection might be associated with a lower preterm birth rate in patients underwent IVF/ICSI-ET. The necessity of TORCH IgG screening in IVF procedure might need re-evaluation, and further cost-effective analysis might be helpful for the clinical management strategy.

Diminished verbal ability among children conceived through ART with exposure to high serum estradiol in utero.

PURPOSE: Higher serum estradiol levels occur in women undergoing assisted reproductive technology (ART) owing to ovarian stimulation. Here, we investigated the association between maternal serum estradiol levels and the intellectual development of offspring conceived with ART. METHODS: A total of 204 singletons born after fresh embryo transfer were recruited for this cohort study. Among them, 102 children were born from mothers with high serum estradiol levels (> 12,000 pmol/L) on the day that human chorionic gonadotropin was administered. Another 102 children, matched by gestational age and age of the children, were recruited as controls from mothers with low serum estradiol (≤ 12,000 pmol/L). The Wechsler Preschool and Primary Scale of Intelligence was used to evaluate the intellectual development of the children. RESULTS: Children from mothers with higher serum estradiol levels scored lower in the verbal intelligence quotient (IQ) tests and verbal comprehension than children whose mothers had lower estradiol levels. The main difference between the two groups was in verbal subtests including information, vocabulary, and sorting. Partial correlation analysis revealed that the logarithm of maternal serum estradiol level negatively correlated with verbal IQ, performance IQ, and full scale IQ. CONCLUSION: Our data demonstrate that a high maternal serum estradiol level may negatively associate the verbal ability of children conceived via ART.

Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis.

Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging. Genome-wide expression profiling and direct binding studies (by chromatin immunoprecipitation sequencing) with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10 (Klhl10), testis expressed 14 (Tex14), and spermatogenesis and centriole associated 1 (Spatc1). Moreover, biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like (TAF7L), a germ cell-specific paralogue of the transcription factor IID subunit TAF7, both in vitro and in testis, suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis. The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of BNC1, TAF7L, Y-box-binding protein 2 (YBX2), outer dense fiber of sperm tails 1 (ODF1), and glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) were significantly decreased in the testis of men with non-obstructive azoospermia. The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.

An alternative splicing variant of mineralocorticoid receptor discovered in preeclampsia tissues and its effect on endothelial dysfunction.

The pathophysiology of preeclampsia (PE) remains unclear. PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern. We collected placental and umbilical artery samples from nor-motensive and PE pregnancies. Mineralocorticoid receptor (MR) and its alternative splicing variant (ASV) expression and their biological effects on PE were examined. An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples (umbilical artery, ~57.58%; placenta, ~36.84%). The MR ASV expression was positively associated with blood pressure in both groups. The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways. The MR ASV can also impair the proliferation, migration, and tube formation ability of endothelial cells. These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology, especially in endothelial dysfunction, and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases.

Factors affecting the live-birth rate in women with diminished ovarian reserve undergoing IVF-ET.

PURPOSE: The occurrence of diminished ovarian reserve (DOR) in women was growing in recent years. Although in vitro fertilization and embryo transfer (IVF-ET) became an effective treatment for DOR, the live-birth (LB) rate remains unsatisfactory. This study aimed to investigate the impact factors of LB rate in women with DOR undergoing assisted reproduction. METHODS: This was a single-center retrospective cohort study. A total of 2277 IVF-ET or ICSI cycles from 1957 DOR women were analysed. Impact factors of LB rate were explored via Student's t test, Pearson's Chi-square test, and multivariate logistic regression models. RESULTS: There were statistically significant differences in maternal age (P < 0.001), duration of infertility (P < 0.001), female body mass index (P = 0.039), first IVF cycle (P = 0.004), poor ovarian response (P < 0.001), paternal age (P < 0.001), total gonadotropin dose (P = 0.010), endometrial thickness (P = 0.021), number of follicles ≥ 14 mm (P = 0.007), number of oocytes retrieved (P < 0.001), number of frozen embryos (P = 0.014), and the stage (P < 0.001) and number (P < 0.001) of embryos transferred between the non-live-birth (NLB) and LB groups. However, only factors of maternal age, the stage and number of embryos transferred remained different after adjusting for potential confounders. CONCLUSIONS: Maternal age, the stage and number of embryos transferred were independent impact factors affecting the live-birth rate in women with DOR seeking for assisted conception.

Comparative proteomic analysis of maternal peripheral plasma and umbilical venous plasma from normal and gestational diabetes mellitus pregnancies.

Gestational diabetes mellitus (GDM) increases many health risks in offspring. The study aims to investigate the underlying mechanism in fetal risk of GDM.We collected maternal peripheral plasma and umbilical venous plasma samples from 4 GDM and 4 control patients during their delivery at a university-based women's hospital. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed. The enzyme-linked immunosorbent assay was used to confirm the change of cholesteryl ester transfer protein (CETP). Bioinformatic analysis was performed with Ingenuity Pathway Analysis (IPA) software package.We identified 19 up-regulated proteins and 15 down-regulated proteins in GDM peripheral plasma, 29 up-regulated proteins and 69 down-regulated proteins in GDM umbilical venous plasma. CETP concentration was significantly lower in both GDM peripheral plasma and umbilical venous plasma. Upstream regulator analysis predicted follicle-stimulating hormone (FSH) as the activated regulator of differentially expressed proteins.The protein profiles in both GDM peripheral plasma and umbilical venous plasma between normal and GDM patients were significantly different. The results indicated that CETP and FSH might associates with health problem of GDM offspring.

Basonuclin 1 deficiency is a cause of primary ovarian insufficiency.

Primary ovarian insufficiency (POI) leads to infertility and premature menopause in young women. The genetic etiology of this disorder remains unknown in most patients. Using whole exome sequencing of a large Chinese POI pedigree, we identified a heterozygous 5 bp deletion inducing a frameshift in BNC1, which is predicted to result in a non-sense-mediated decay or a truncated BNC1 protein. Sanger sequencing identified another BNC1 missense mutation in 4 of 82 idiopathic patients with POI, and the mutation was absent in 332 healthy controls. Transfection of recombinant plasmids with the frameshift mutant and separately with the missense mutant in HEK293T cells led to abnormal nuclear localization. Knockdown of BNC1 was found to reduce BMP15 and p-AKT levels and to inhibit meiosis in oocytes. A female mouse model of the human Bnc1 frameshift mutation exhibited infertility, significantly increased serum follicle-stimulating hormone, decreased ovary size and reduced follicle numbers, consistent with POI. We report haploinsufficiency of BNC1 as an etiology of human autosomal dominant POI.

Predictive Value of Maternal Serum Biomarkers for Preeclampsia and Birth Weight: A Case-Control Study in Chinese Pregnant Women.

BACKGROUND: In clinical practice, abnormal biochemical changes often occur in women who eventually develop preeclampsia (PE). The study aims to investigate whether maternal serum biochemical markers in the early third trimester can predict PE and neonatal birth weight. STUDY DESIGN: A retrospective case-control study was performed on 287 women who subsequently developed PE (mild = 139; severe = 148) and 143 healthy women. Fasting venous blood samples of all gravidas were drawn for routine biochemical markers screening in the early third trimester (28.49 ± 1.63 weeks). Appropriate statistical methods were selected for analysis with SPSS software. RESULTS: (1) The concentrations of plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL), and uric acid (UA) in the severe and mild subgroups of the PE group were significantly higher compared with the respective levels in the normal pregnancy groups (3.90 vs. 4.03 vs. 3.14 mmol/L; 3.41 vs. 3.33 vs. 2.89 mmol/L; 365.42 vs. 318.91 vs. 284.69 µmol/L; p < 0.0001). Serum calcium levels in PE group were significantly lower than those in control group (2.10 vs. 2.18 vs. 2.22 mmol/L; p < 0.0001). (2) By using the receiver operating characteristic curve to estimate the diagnosis rate of screening for PE of each marker, the highest sensitivity appeared by the combination of TG, total cholesterol (TC), LDL, high-density lipoprotein cholesterol (HDL), LDL/HDL, UA, Ca2+, and homocysteine (HCY) (79%). The area under curve (AUC) of UA was 0.70, which was the highest among these eight markers, but the AUC of an eight-marker combination model (0.85) had a better diagnostic indication. (3) In PE, the maximum systolic/diastolic blood pressure was significantly positively correlated with serum UA (r = 0.212/0.205, p < 0.0001); and negatively correlated with serum total calcium (r = -0.193/-0.196, p = 0.001). The neonatal birth weight of PE group had a positive correlation with serum TG levels (r = 0.141, p = 0.017) and serum total calcium levels (r = 0.221, p < 0.0001), and a negative correlation with UA levels (r = -0.265, p < 0.0001). CONCLUSION: The individual marker really performs terrible in predicting PE. Joint monitoring and evaluation of these parameters may improve the screening efficiency for the prediction of PE and poor fetal growth early.

Reduced Intellectual Ability in Offspring of Ovarian Hyperstimulation Syndrome: A Cohort Study.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. METHODS: We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). FINDINGS: OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ=92.7 (14.7), PIQ=108.9 (13.1), FIQ=100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ=100.1 (13.2), PIQ=113.7 (10.8), FIQ=107.4 (11.5)). The prevalence of low IQ (<80) children was 4.7 times higher in OHSS offspring compared with non-OHSS offspring. Maternal estradiol level on hCG administration day was negatively associated with FIQ in offspring. INTERPRETATION: OHSS offspring displayed reduced intellectual ability. Prenatal estradiol exposure might be involved in underlying mechanism.

Ovarian stimulation perturbs methylation status of placental imprinting genes and reduces blood pressure in the second generation offspring.

OBJECTIVE(S): Assisted reproductive technology (ART) is associated with DNA methylation dysfunction of offspring. However, it is unclear whether ovarian stimulation (OS) is responsible for DNA methylation dysfunction of offspring STUDY DESIGN: We built the first-generation (F1) and second-generation (F2) offspring mice model of ovarian stimulation. Bodyweight of F1 and F2 were measured. Expression levels of several imprinted genes (Impact, H19, Igf2, Plagl1, Mest, and Snrpn) in F1 placenta were tested. Methylation status of Plagl1 and H19 promoters was examined with bisulfite sequencing. Glucose tolerance, blood pressure, and heart rate were evaluated in F2 mice. RESULTS: The OS F1 showed elevated bodyweights in the 2nd, 3rd and 4th weeks, but the difference disappeared in the 5th week. Plagl1 was down-regulated in OS F1. Promoters of Plagl1 and H19 were also hypermethylated in OS F1. F2 of OS mice had the similar bodyweight and glucose tolerance compared with the control F2. However, F2 of OS ♂F1+OS♀ F1 showed the decreased systolic pressure, diastolic pressure, and heart rate. CONCLUSIONS: Ovarian stimulation perturbs expression levels and methylation status of imprinted genes in offspring. The effect of ovarian stimulation may be passed to F2.