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Background With the increased use of assisted reproductive technology (ART), assessing the potential health risks of children conceived on ART important to public health. Most research in this area has focused on the effects of ART on perinatal, metabolic, and oncological risks in children. Although an increased risk of immune-related diseases has been reported in children born after ART, there are no studies on the immunological status of these children. This study aimed to evaluate the impact of different embryo transfer methods and fertilization strategies on the immune status of the offspring. Methods A total of 69 children born to women treated with ART and a matched control group of 17 naturally conceived (NC) children, all aged from 3 to 6 years, were recruited in the reproductive hospital affiliated to Shandong University. The frequency of immune cells in the peripheral blood was assayed using flow cytometry; plasma cytokine levels were determined by multiplex cytokine immunoassay with human cytokine magnetic beads. Results Compared to children born after natural conception, children born after ART had elevated interferon-γ (IFN-γ) levels, regardless of embryo transfer and fertilization strategies. Children in the fresh-embryo transfer group had significantly higher IL-4 levels and a lower ratio of IFN-γ to IL-4 than those in the NC group ((P = 0.004, 10.41 ± 5.76 pg/mL vs 18.40 ± 7.01 pg/mL, P = 0.023, 1.00 ± 0.48 vs 0.67 ± 0.32, respectively). Similar results were shown in either the in vitro fertilization (IVF) group or the intra-cytoplasmic sperm injection (ICSI) group (P P = 0.08 for IVF; P P 2 (estradiol) levels on the day of hCG administration (R = 0.502, P = 0.017; R = − 0.537, P = 0.010, respectively). Consistently, the frozen embryo transfer did not result in alterations of these immune indicators in the offspring. Overall, there were no significant differences between the ART group and NC group in the frequencies of T cells, B cells, natural killer (NK) cells, CD4+T cells, CD8+T cells, T helper (TH)1 cells, TH17 cells, and regulatory T (Treg) cells and cytokine levels of IL-10 and IL-17a (all P > 0.05). Conclusions Immunological alterations existed in children born after the use of ART. The elevated E2 levels before embryo implantation contributed to the increased IL-4 levels in children conceived by fresh embryo transfer. The assessment of immunological alteration is of importance to children conceived by ART for early monitoring and intervention.

A flexible film electrode composed of sodium carboxymethyl cellulose (CMC), polypyrrole (PPy) and reduced graphene oxide (RGO) was designed by in situ polymerization and vacuum filtration. The obtained film displayed CMC–PPy nanospheres wrapped in an RGO framework, resulting in a free-standing and highly flexible supercapacitor electrode. The incorporation of hydrophilic CMC into the film enhanced the diffusion paths of electrolyte ions and prevented the volume deformation of PPy during the long-term charging/discharging. Furthermore, PPy provided a large pseudocapacitance and RGO endowed the film electrode with prominent flexibility. The remarkable interaction between CMC, PPy and RGO achieved a synergistic effect on the structural stability and electrochemical performance of the film electrode. When the mass ratio of CMC–PPy to RGO was 1 : 1, the highest specific capacitance of the sodium carboxymethyl cellulose–polypyrrol@reduced graphene oxide (S-CPR1 : 1) was 489 mF cm−2 (191 F g−1) with a mass of 2.56 mg cm−2 at a current density of 0.5 mA cm−2. And the area specific capacitance of the S-CPR1 : 1 electrode could remain as 101.6% of the original value after 1000 charge/discharge cycles, which was higher than the polypyrrol@reduced graphene oxide (S-PR) electrode (72.4%) prepared under the same conditions. Besides, the S-CPR1 : 1 electrode exhibited remarkable flexibility with 95.6% capacity retention after 500 fold cycles. These above results indicated that the S-CPR1 : 1 film electrode provided a simple way of developing free-standing and flexible electrode materials for next-generation electrochemical electrodes.

Objective The objective of the study is to assess the clinical application of noninvasive prenatal testing (NIPT) for VTS pregnancies after the treatment of assisted reproductive technology (ART). Method This was a retrospective study on VTS pregnancies through ART treatment. Participants underwent NIPT at 11 to 13 weeks gestation by sequencing. Resampling was recommended for both positive and testing failure cases. For NIPT positive results, participants were advised to have invasive testing. Clinical outcomes were obtained by telephone interview. Results In total of 579 cases, testing failure rates after first sampling and resampling were 7.6% and 1.4%, respectively. Twelve positive results were reported by NIPT. But only one true positive was confirmed, giving a PPV of 8%. A total of 576 cases completed the follow-up (including 533 NIPT negative, 12 positive, and 31 testing failure) and three cases lost follow-up. Among the 536 cases with NIPT negative results, 504 (94.0%) resulted in live-birth and 29 (5.4%) resulted in miscarriage or stillbirths. No false-negative result was reported. Conclusion NIPT has the potential to be used in prenatal screening for VTS pregnancies. For the pregnant women who obtained positive and testing failure results, resampling after 15 weeks of gestation is recommended.

Assisted reproductive technology (ART) is the most widely used treatment for infertility and has resulted in millions of births worldwide. The safety of the offspring has been of the utmost concern. Previous studies suggested an increase in metabolic disorders in offspring later in life. The aim of the present study was to investigate metabolic changes at age 6–10 years in offspring conceived as a result of in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). A total of 380 children born from IVF/ICSI and a matched control group of 380 naturally conceived children, all aged 6–10 years, were recruited. Anthropometric measures, ultrasound and serum tests were performed for body mass, glucose metabolism and lipid profiles, and examination of vasculature structure. The children conceived by ART showed significantly higher fasting blood glucose and serum insulin levels and HOMA-IR (adjusted β [95% CI]: fasting blood glucose 0.49 [0.42, 0.55]; loge-transformed insulin 0.28 [0.20, 0.35]; loge-transformed HOMA-IR 0.38 [0.30, 0.46]), as well as a lower HOMA-B and serum apolipoprotein A (ApoA) levels (adjusted β [95% CI]: loge-transformed HOMA-B −0.19 [−0.27, −0.11]; ApoA −0.17 [−0.21, −0.13]), when compared with the control group. Furthermore, the ultrasound scan indicated elevated carotid intima–media thickness in children conceived by ART (β 0.13 [95% CI 0.12, 0.13]). Children conceived by IVF/ICSI have a less favourable glucose and cardiovascular metabolic profile in childhood when compared with naturally conceived children. The underlying mechanisms and potential long-term consequences need to be elucidated in future studies.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play critical roles in female reproduction, while the underlying genetic basis is poorly understood. Genome-wide association studies (GWASs) of FSH and LH levels were conducted in 2590 Chinese females including 1882 polycystic ovary syndrome (PCOS) cases and 708 controls. GWAS for FSH level identified multiple variants at FSHR showing genome-wide significance with the top variant (rs2300441) located in the intron of FSHR. The A allele of rs2300441 led to a reduced level of FSH in the PCOS group (β = −.43, P = 6.70 × 10−14) as well as in the control group (β = −.35, P = 6.52 × 10−4). In the combined sample, this association was enhanced after adjusting for the PCOS status (before: β = −.38, P = 1.77 × 10−13; after: β = −.42, P = 3.33 × 10−16), suggesting the genetic effect is independent of the PCOS status. The rs2300441 explained sevenfold higher proportion of the FSH variance than the total variance explained by the two previously reported FSHR missense variants (rs2300441 R2 = 1.40% vs rs6166 R2 = 0.17%, rs6165 R2 = 0.03%). GWAS for LH did not identify any genome-wide significant associations. In conclusion, we identified genome-wide significant association between variants in FSHR and circulating FSH first, with the top associated variant rs2300441 might be a primary contributor at the population level.

Infertility seriously endangers the reproductive health of women at childbearing age. It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse. Broadly defined, infertility includes two aspects – failure to conceive or have a live birth. This guideline only addressed content relevant to the former. It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology, Chinese Medical Association, based on relevant guidelines of the World Health Organization, the American Society for Reproductive Medicine, the National Institute for Health and Clinical Excellence, as well as the clinical practice in China. The guideline was reviewed by experts and doctors from medical institutions at all levels, which is applicable to the diagnosis of infertility by physicians in obstetrics, gynecology, and andrology at various medical institutions nationwide.

Background Polycystic ovary syndrome (PCOS) is the most common reason of anovulatory infertility. Environmental factor is one of the main causes of PCOS, but its contribution to ovulatory dysfunction in PCOS remains unknown. Methods A total of 2217 infertile women diagnosed as PCOS according to Rotterdam criteria were recruited, including 1979 women with oligo-anovulation (OA group) and 238 women with normal -anovulation (non OA group). Besides, 279 healthy control women of reproductive age were enrolled as controls. Results Frequencies of snoring (PCOS-OA group, PCOS-non-OA group, control group: 29.30% vs 18.10% vs 11.50%, P P P P P Conclusions Smoking, snoring, hyper-caloric diet, plastic tableware usage and indoor decoration were found to be associated with an increased risk for ovulatory dysfunction in women suffering from PCOS.

This cohort study examines the association of conception by assisted reproductive technology with cardiovascular health outcomes among children in China ages 6-10 years., Key Points Question Is conception assisted by reproductive technology associated with offspring cardiovascular health? Findings In this cohort study of 764 children born with or without assisted reproductive technology, children conceived by assisted reproductive technology had statistically significantly worse outcomes in left ventricular function and structure. Meaning These findings suggest the importance of early detection, potential interventions, and improvement of cardiovascular health among offspring conceived by assisted reproductive technology., Importance Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies. Objective To assess the cardiovascular health of children conceived by ART. Design, Setting, and Participants This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child’s birth (2 years older or younger). Data were analyzed from March 2019 through December 2019. Exposures Conception by ART. Main Outcomes and Measures Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more. Results Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P

ObjectiveTo describe the lipidomic characteristics of offspring born to polycystic ovary syndrome (PCOS) women (PCOS-off) and assess the associations between differential lipids and clinical phenotypes.MethodsUltra performance liquid chromatography and mass spectrometry were performed on plasma samples from 70 PCOS-off and 71 healthy controls. The associations of differential metabolites with clinical phenotypes were examined by multiple linear regression.ResultsForty-four metabolites were significantly altered in PCOS-off, including 8 increased and 36 decreased. After stratification according to sex, 44 metabolites (13 increased and 31 decreased) were expressed differently in girls born to PCOS women (PCOS-g), most of which were glycerolipids. Furthermore, 46 metabolites (9 increased and 35 decreased) were expressed differently in boys born to PCOS women (PCOS-b), most of which were glycerophospholipids. Significant associations of metabolites with weight Z-score and high density lipoprotein cholesterol were found in PCOS-off. Triglycerides, low density lipoprotein cholesterol, and thyroid-stimulating hormone were separately correlated with some lipids in PCOS-g and PCOS-b.ConclusionsPCOS-off showed specific lipid profile alterations. The abnormal level of glycerophospholipids and sphingomyelin indicated the risk of glucose metabolism and cardiovascular diseases in PCOS-off. Some lipids, such as phosphatidylcholines, lysophosphatidylcholine and sphingomyelin, may be the potential markers. The results broadened our understanding of PCOS-offs’ cardiometabolic status and emphasized more specific and detailed monitoring and management in this population.

Study question To describe lipidomic characteristics of offspring born to polycystic ovary syndrome (PCOS-off) women and assess the associations of clinical phenotypes changes with differential lipids. Summary answer PCOS-off showed specific changes in lipidomics and some differential lipids (e.g., phosphatidylcholines, lysophosphatidylcholine and sphingomyelin) may be the potential markers of aberrant cardiometabolic health. What is known already Polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism and polycystic ovarian morphology, affects about 8–13% of women of fertile age. Aberrant metabolic pathophysiological changes and increased pregnancy complications associated with PCOS predispose PCOS patients to have suboptimal intrauterine environments and that may produce a detrimental impact on the cardiometabolic health of their children. Study design, size, duration A total of 141 blood plasma samples from 70 children born to PCOS women (43 girls, 27 boys) and 71 healthy control children (44 girls, 27 boys) were obtained for lipidomics. Participants/materials, setting, methods Blood samples were centrifuged at 2000 rpm, 4 °C for 20 min, and the upper plasma was collected and used for lipid extraction. Then the waters ACQUITY UPLC I-Class system and The Xevo G2-S Q-TOF with an electrospray ionization (ESI) source (Waters, Manchester, UK) was used for chromatographic analysis and mass spectrometry analysis separately. Main results and the role of chance In total, 44 metabolites were found to be significantly altered in PCOS-off, including 8 up-regulated and 36 down-regulated metabolites. After stratified by sex, 44 metabolites were found to express differently in girls born to PCOS women (PCOS-g). 13 metabolites were up-regulated, and 31 metabolites were down-regulated, most of which belong to glycerolipids species. While 46 metabolites were found to express differently in boys born to PCOS women (PCOS-b) with 9 increased metabolites and 35 decreased ones, most of which were glycerophospholipids metabolites. Additionally, significant associations between metabolites changes and weight Z-score as well as high density lipoprotein level were found in PCOS-off. In PCOS-g, triglyceride, low density lipoprotein and high density lipoprotein level were found to be correlated with some metabolites, whereas in PCOS-b, thyroid stimulating hormone and high density lipoprotein were correlated with some lipids. Limitations, reasons for caution Other species of metabolites except lipids are not included in this study. Besides, some potential confounding maternal factors, such as smoking, drinking, breastfeeding etc. were not included due to the lack of data. Wider implications of the findings: The results had broadened our understanding of PCOS-off’s cardiometabolic status and emphasized monitor and special management in this susceptible group of population. Trial registration number Not applicable

Perfluoroalkyl substances (PFASs) are a family of synthetic, fluorinated organic compounds. They have been widely used in industrial applications and consumer products and widespread in the environment, wildlife and human. Experimental and epidemiologic evidence suggested that PFASs are capable of interfering with endocrine processes and have potential reproductive and developmental toxicities. Polycystic ovarian syndrome (PCOS), one of the main reasons of female infertility, is a common endocrine disorder in reproductive age women. We performed a case-control study to evaluate associations between PCOS-related infertility and PFASs concentrations in plasma. A total of 180 infertile PCOS-cases and 187 healthy controls were recruited from the Center for Reproductive Medicine of Shandong University. Blood specimens were collected at enrollment and analyzed for ten PFASs using liquid chromatography-tandem mass spectrometry. Multivariable logistic regression procedure was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each PFAS. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the dominant PFASs in the plasma of participants, with the median concentration of 5.07 ng/mL and 4.05 ng/mL, respectively. The median levels of individual PFAS were not significantly different between PCOS-cases and controls. While adjusted for the potential confounders (age, BMI, household income, education level, employment status, age at menarche, menstrual volume), the plasma concentration of perfluorododecanoic acid (PFDoA), a 12 carbons lengths of perfluorocarboxylic acids, was associated with a significantly increased risk of PCOS-related infertility (medium vs low tertile: OR = 2.36, 95% CI: 1.12, 4.99, P = 0.02; high vs low tertile: OR = 3.04, 95% CI: 1.19, 7.67, P = 0.02), with the P trend 0.01. No significant relationship was observed between PCOS-related infertility and other PFAS analytes in the adjusted model, despite perfluoroundecanoic acid showed a negative association (P trend 0.03). The potential reproductive health effects of PFASs and the underlying mechanisms merit further investigation in the future.

Coupling electroactive species with carbon substrates to synthetize composite electrodes holds great promise for obtaining excellent supercapacitors. However, the poor bonding between the carbon supports and the electroactive species is still a bottle-neck to be addressed. Herein, we report a rational design and fabrication of NiCo2Se4 supported on tannin-doped activated carbon by employing tannin as the structure coupling bridge between the two components, which effectively tunes the electronic structural states and results in strong coupling effects with NiCo2Se4. Benefiting from the structural characteristics, the as-obtained N-doped activated carbon–tannin–NiCo2Se4 (NAC–TA–NCS) composites, especially, the NAC–TA–NCS 10 : 1 hybrids (the mass ratio of NAC–TA–NCS to tannin is 10 : 1) deliver the best electrochemical properties. The NAC–TA–NCS 10 : 1 electrode shows the highest specific capacitance value (1262 F g−1 at 0.5 A g−1, 1060 F g−1 even at 30 A g−1), excellent rate property, and outstanding cycling stability (95.095% of the initial value after 10 000 cycles at 5 A g−1). Meanwhile, the as-obtained NAC–TA–NCS 10 : 1//AC could achieve a high energy density of 78.19 W h kg−1 at the power density of 0.859 kW kg−1 at 50 A g−1 as well as the outstanding cycling stability with 97.35% of the initial value after 10 000 cycles. The work exhibits that the NAC–TA–NCS hybrids are promising electrode materials for energy storage. The hydrophilic strategy could be extended to assemble other kinds of active species on different supports, and holds potential for achieving effective and robust electrode materials for energy-related devices.

Activin A promotes human trophoblast invasion during the first trimester of pregnancy and is associated with preeclampsia and pregnancy-induced hypertension (PE/PIH) in naturally conceived pregnancies. However, whether integrin β1 mediates activin A-increased trophoblast invasion remains unknown and the evidence is limited regarding the predictive value of activin A for PE/PIH in women receiving in vitro fertilization (IVF) treatment. Here, we studied the role and underlying molecular mechanisms of integrin β1 in activin A-promoted invasion in immortalized (HTR8/SVneo) and primary human extravillous trophoblast (EVT) cells. A nest case-control study was designed to investigate the predictive/diagnostic value of activin A in IVF pregnancies. Results showed that integrin β1 expression increased after activin A treatment and knockdown of integrin β1 significantly decreased both basal and activin A-increased HTR8/SVneo cell invasion. SB431542 (TGF-β type I receptors inhibitor) abolished activin A-induced SMAD2/SMAD3 phosphorylation and integrin β1 overexpression. Activin A-upregulated integrin β1 expression was attenuated after the depletion of ALK4 or SMAD4 in both HTR8/SVneo and primary EVT cells. Furthermore, we found similar first-trimester activin A levels in IVF patients with or without subsequent PE/PIH. These results reveal that integrin β1 mediates activin A-promoted trophoblast invasion through ALK4-activated SMAD2/3-SMAD4 pathway, and the predictive/diagnostic value of first-trimester maternal serum activin A for hypertensive disorders of pregnancy might be different in IVF population.

Problem Premature ovarian insufficiency (POI) imposes great challenge on female reproduction. Whether immune disturbance in ovarian environment was implicated in POI remains unclear. We aimed to characterize the cytokine profile in follicular fluid (FF) and paired serum in patients with biochemical POI (bPOI). Method of study Multiplex immunoassay containing 45 cytokines was performed for individual FF and paired serum samples from 35 bPOI patients and 37 matched controls. Cytokine profiles were compared between the two groups and cytokines correlated to ovarian reserve, and the rates of day‐3 good‐quality embryos were further analyzed. Results In FF, significantly elevated level of chemokines MIP‐1α (P = .043), CXCL8 (P = .024), IP‐10 (P = .041), and eotaxin‐1 (P = .015) as well as growth factors VEGF‐D (P = .047), BDNF (P = .043), LIF (P = .002), and bFGF (P = .046) was found in bPOI patients compared to controls. Yet RANTES manifested an opposite trend with reduced levels among bPOI patients (P = .006). All these chemokines and growth factors in FF were significantly correlated with ovarian reserve (P

Objective To examine different expression profiles of plasma exosomal microRNA (miRNA) in polycystic ovary syndrome (PCOS) patients and controls, and their potential roles in PCOS pathogenesis. Design Experimental study. Setting Center for reproductive medicine. Patient(s) Seventy-five PCOS patients and 75 age-matched controls. Intervention(s) Plasma exosomes miRNAs sequenced from 15 PCOS patients and 15 controls. Main Outcome Measure(s) Plasma exosomal miRNA expression and the correlation between PCOS phenotypes and miRNA expression. Result(s) The sequenced plasma exosomes miRNAs were further determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in a larger cohort, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Correlation analysis and receiver operating characteristic (ROC) curve analysis were used to determine the association between PCOS phenotypes and miRNA expression. The miRNA sequencing revealed 34 exosomal miRNAs were differentially expressed between PCOS patients and controls. Via qRT-PCR, five differentially expressed miRNAs (miR-126–3p, miR-146a-5p, miR-20b-5p, miR-106a-5p, and miR-18a-3p) were identified. The GO and KEGG analyses predicted their target functions included axon guidance, mitogen-activated protein kinase (MAPK) signaling, endocytosis, circadian rhythms, and cancer pathways. The expression of these miRNAs correlated with menstrual cycle, antral follicle count, hormone level, and combined yielded a ROC curve area of 0.781 in discriminating PCOS patients from the controls. Conclusion(s) Differential expression of plasma exosomal miRNAs may confer a risk of PCOS and may be helpful in distinguishing PCOS patients from controls. Certain miRNA expression may associated to the disease progression, which could help in an epigenetic understanding of the pathophysiology of PCOS.

Research question Does an association exist between serum anti-Mullerian hormone (AMH) level, the marker of biological ovarian age, and embryonic aneuploidy risk in recurrent spontaneous miscarriage (RSM) patients of reproductive age? Design This retrospective study included a total of 422 IVF cycles of 394 unexplained RSM patients undergoing preimplantation genetic testing for aneuploidy (PGT-A), enrolled from January 2014 to December 2016. Subjects were divided into three groups according to the 25th (1.50 ng/ml) and 75th (5.60 ng/ml) percentiles of AMH level (Group 1: low AMH N = 107], Group 2: normal AMH 1.50– N = 210] and Group 3: high AMH ≥ 5.60 ng/ml [ N = 105]). Results There was a significant difference in embryonic aneuploid rate between AMH groups (66.7% versus 42.9% versus 50.0%, Groups 1 to 3, respectively, P = 0.006). It was significantly higher in the low AMH group (Group 1) compared with that in the normal AMH group (Group 2, P 1vs2 = 0.002) and high AMH group (Group 3, P 1vs3 = 0.015). After age stratification, embryonic aneuploidy rate was still significantly different among AMH groups with a similar trend in women ≥35 years old (68.2% versus 54.4% versus 51.0%, P = 0.038, P 1vs2 = 0.025, P 1vs3 = 0.035), but not in young subjects. Conclusions These findings indicate that low AMH level was associated with increased risk of embryo aneuploidy only in women of advanced age. Maternal diminished ovarian reserve along with oocyte ageing may contribute to impaired chromosomal competence of the embryo.

Marine Isotope Stage 3 (MIS 3, at 60–25 ka B.P.) was a short interstadial within the Last Glacial period. A generally warm and wet climatic condition during the MIS 3 period has been suggested by many previous studies. Quantitative climatic reconstruction and studies of seasonality, however, have been seldom attempted given the scarcity of useful proxy indicators. A full understanding the climatic characteristics during this period is hampered by their absence. This is especially the case in the East Asian monsoon region in North China, which is very sensitive to climatic change. To help fill this knowledge gap, we have determined the stable carbon (δ13C) and oxygen isotope (δ18O) compositions of tooth enamel from fossil mammals (Bubalus sp [buffalo] and Cervus elaphus [red deer], dated at ∼33–31 ka B.P.) recovered from Longquan Cave in North China. We use these data to constrain ecology, local air temperature and precipitation amounts during the late MIS 3. The average δ13C (VPDB) of tooth enamel (−14.4‰ and −8.8‰, respectively for buffalo and red deer) indicate that C3 plants comprised the main diet of animals living in this area. Pollen assemblages demonstrated that vegetation mainly consisted of grasses and herbs (∼64%) with trees only accounting for about 26%. These results indicate a landscape of open steppe with sparsely distributed trees. The reconstructed climate derived from tooth enamel δ18O was relatively colder and drier than present-day condition, with mean annual air temperature ranging from 4 to 13 °C and mean annual precipitation ranging from 360 to 670 mm. Moreover, the inferred summer and winter half-year temperatures were respectively 8–24 °C and −2 to 5 °C, which represents either similar or weaker seasonality than at the present time. The inferred cold and dry climate suggested by our study contrasts with the warm and wet conditions previously reconstructed using proxy indicators from bulk soil samples in North China. In comparison to the long-term, time-averaged climatic condition reflected by those soil proxies, the stable isotope compositions of fossil more likely recorded climatic conditions at annual or seasonal time-scale. The inferred annual cold/dry climate at Luanchuan Cave suggested by our data may indicate a short climatic cooling event from Greenland Interstadial (GIS) 5 to its following stadial. Mean annual temperature fluctuated by ∼8 °C during this interstadial-stadial cycle.

Few studies have explored the association between circulatory system diseases (CSDs) and provincial socioeconomic and environmental factors from spatial perspective, although large literature have focused on CSD. The numbers of death of hypertension disease (HD), ischemic heart disease (IHD), and cerebrovascular disease (CVD) are investigated, and 14 representative socioeconomic and environmental factors are collected. Stepwise regression model (SRM) and geographically weighted regression model (GWRM) are applied to determine the spatial correlation between the number of death of those diseases and selected factors. The results are the following: (1) diseases exhibit a pattern of zonal distribution. Higher HD is mostly distributed in south district, whereas higher IHD and CVD are observed in the north area. (2) SO2 emission amount (SO2 EA) is significantly positively related with HD, while coal consumption (CC) and PM2.5 are notably positively correlated with IHD and CVD. (3) A 10,000 tons increase in SO2 EA results in three increases in the numbers of death of HD. For every 100 ten thousand tons (TTTs) increase in CC, the death of IHD and CVD increases by 11.1 and 15.7, while for every 1 μg/m3 increase in ambient PM2.5 concentration, the numbers of death of IHD and CVD increase by 34.773 and 43.222, respectively. (4) Our findings show that there exist spatial differences for SO2 EA, CC, and PM2.5 influencing HD, IHD, and CVD. This study is expected to provide a reference for HD, IHD, and CVD control in different regions.

STUDY QUESTION Does the inheritance of polycystic ovary syndrome (PCOS) susceptibility single-nucleotide polymorphism affect the phenotype of offspring? SUMMARY ANSWER Male offspring who inherit PCOS-related genetic variations from PCOS mothers were more susceptible to developing the metabolic abnormality in their later life. WHAT IS KNOWN ALREADY Genetic factors are considered the major etiology of PCOS. Previous studies have highlighted that offspring of women with PCOS had an increased risk of the same disease or PCOS-like symptoms. STUDY DESIGN, SIZE, DURATION The study involved 172 children born to women with PCOS and 529 children born to non-PCOS women. All offspring were conceived by assisted reproductive technologies. PARTICIPANTS/MATERIALS, SETTING, METHODS The offspring ranged from 1 to 8 years old. Metabolic phenotype analyses were performed in offspring aged from 2 to 8 (N = 619). Sanger sequencing, TaqMan and Sequenom MassARRAY were used to sequence the samples. MAIN RESULTS AND THE ROLE OF CHANCE In male offspring, the fasting insulin (FINS) (P = 0.037) homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.038) and the homeostasis model assessment of pancreatic beta-cell function (HOMA-β) (P = 0.038) levels were higher in offspring of PCOS mothers compared to controls. In female offspring, PCOS offspring had a significantly higher anti-Müllerian hormone levels (P = 0.001) compared to those from control mothers. In male offspring of PCOS mothers, subjects with a T allele at rs2349415 in the gene FSHR had higher FINS (P = 0.023), HOMA-IR (P = 0.030) and HOMA-β levels (P = 0.013) than those in the homozygous CC group. The same increased trend in FINS, HOMA-IR and HOMA-β levels could be found in the CC and TC group in rs2268361 located in gene FSHR compared to the TT group (P = 0.029, P = 0.030, P = 0.046, respectively). As for rs10818854 in the DENND1A gene, the AA and AG group had a higher FINS (P = 0.037) and HOMA-β (P = 0.008) levels than the homozygous CC group. LIMITATIONS, REASONS FOR CAUTION Firstly, the offspring may be too young to see any phenotype changes. Secondly, this study only analyzed the differences of genotype frequency using the dominant model instead of all three models due to the limited sample size of the homozygous model. The results, therefore, should be replicated and performed in a larger sample size population. Thirdly, environmental impacts cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS The findings presented in this thesis add to our understanding the changes in offspring born to PCOS women and remind us to consider early intervention to avoid more severe effects. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China 2017YFC1001000 (to Z.-J.C.), the National Natural Science Foundation of China 81430029 (to Z.-J.C.), 81622021 and 31571548 (to H.Z.), the National Natural Science Foundation of Shandong Province JQ201816 (to H.Z.) and Shandong Provincial Key Research and Development Program 2017G006036 (to L.-L.C.) and 2018YFJH0504 (to Z.-J.C.). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Background To determine the effects of age and the serum anti-Müllerian hormone (AMH) level on in vitro fertilization (IVF) outcomes, especially among young women with low serum AMH levels and older women with high AMH levels. Methods This study was a cohort study in which a total of 9431 women aged 20–51 years who were undergoing their first IVF cycles were recruited. Ovarian response parameters included the number of retrieved oocytes, the number of 2 pronuclear zygotes (2PN), and the frequency of good-quality embryos (GQE). Pregnancy outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), miscarriage rate (MR), and cumulative CPR and LBR (CCPR and CLBR). Results Among women under 35 years of age, the ovarian response, CPR, CCPR, LBR and CLBR (p

Research question Are maternal depression and/or anxiety disorders (MDAD) before and during pregnancy associated with IVF outcomes? Design A total of 5661 women starting their first IVF cycle between 15 August 2014 and 31 December 2015 were pooled from a prospective cohort of IVF-conceived children. The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to determine MDAD. IVF outcomes were compared between MDAD+ and MDAD– groups. Results A total of 10.3% (572/5556) of women had MDAD before IVF (bMDAD). The fertilization rate was lower in the bMDAD+ group (59.41 ± 22.11% versus 61.72 ± 22.18%, Padjust Conclusions MDAD during the first trimester is associated with increased risk of LBW in offspring, whether preconception MDAD exists or not.

Graphene material has a large theoretical specific surface area, excellent theoretical conductivity and mechanical flexibility, and is a promising electrode material for supercapacitors. However, two-dimensional graphene sheets are easy to stack, which affects its electrical properties. Specifically, a sponge-like composite hydrogel for high-performance supercapacitors was prepared by one-step hydrothermal method from activated carbon and graphene oxide. Benefiting from the introduced nitrogen-containing groups and the greatly increased specific surface area, the GAC-2 nitrogen-doped activated carbon/graphene hydrogel electrode showed high specific capacitance of 505.6 F g−1. In addition, the composite hydrogel presented an excellent 3D network structure with abundant internal structural pores, in which graphene and activated carbon were cross-linked by strong covalent bonds. This unique structure greatly improves the mechanical flexibility of the composite electrode (the capacitance retention rate is approximately 87.7% after 500 bending tests). And the self-assembled flexible supercapacitor shows an energy density of 26.9 Wh kg−1 at 242 W kg−1 and outstanding capacitance retention rate of about 92.1% after 5000 charge-discharge cycles, confirming its potential application in supercapacitors.

A recent genome-wide association study (GWAS) has identified three susceptibility loci (8p32.1, 11p14.1, and 9q22.32) for polycystic ovary syndrome (PCOS) in women of European ancestry. The 9q22.32 locus was previously found in our Chinese PCOS GWAS. Replication of the other two loci is necessary to determine whether the same variants confer risk to PCOS in Han Chinese women.This study aimed to investigate the effect of the European GWAS loci on PCOS susceptibility in Han Chinese women.This was a genetic association study at a university hospital in composed of 1601 PCOS cases and 1238 age-matched controls. Interventions and Main Outcome Measure: After screening of the regions that cover 500 kb upstream and downstream of the two single-nucleotide polymorphisms (SNPs) using our previous Chinese GWAS data, rs11031010, located in the region of follicle-stimulating hormone B polypeptide (FSHB) gene, was selected for further replication. The other SNPs near rs804279 (GATA4/NEIL2) were excluded based on our previous GWAS data. Then, the variant rs11031010 was genotyped in an independent cohort and the associations with PCOS, endocrine and metabolic traits were assessed.In the current replication study, rs11031010 was associated with PCOS in Han Chinese women (P = 2.76 × 10(-3)), even after adjustment for age and body mass index. Meta-analysis with our previous GWAS data showed that the allele frequency difference of rs11031010 between PCOS and controls reached genome-wide significance (P = 4.27 × 10(-8)). PCOS women with AA and AC genotypes had a significantly higher LH level than individuals carrying the CC genotype (P =1.60 × 10(-4)). The genetic risk score based on sixteen total Chinese PCOS-risk SNPs, calculated by total number of risk alleles for each subject, was associated with the diagnosis of PCOS (P1.00 × 10(-4)).Variants in FSHB gene are associated with PCOS and LH levels in Han Chinese women. FSHB is thus likely to play an important role in the etiology of PCOS, regardless of ethnicity.

Knowledge of ecophysiological characteristics of different land snail species is crucial for defining climatic significance of snail faunal assemblages. However, little work has been done in this aspect, hindering our obtaining unambiguous paleoclimatic information using these proxy indicators. Here we document for the first time the different ecophysiological characteristics of Cathaica sp. and Bradybaena sp. land snails using the stable isotopes and clumped isotope (Δ47) of the shell carbonates. The Δ47-derived temperatures for both species revealed a robust correlation with environmental temperatures. Moreover, the temperatures for Cathaica sp. are 3–5°C higher than those for Bradybaena sp. land snails, indicating different ecophysiological adaptations or growing seasons of the two species. Specifically, Cathaica sp. snails prefer living in a warm-humid summer, whereas Bradybaena sp. snails are active in the relatively cool-arid spring and/or autumn. The result testifies to the Δ47 in snail shell carbonates as a promising paleothermometer in monsoonal region and presents new insight into paleoclimatic explanation of these land snail species. This finding highlights the importance of climatic seasonality in the changes of the faunal assemblages of land snails.

Objective To explore metabolic disturbances in nonobese women with polycystic ovary syndrome (PCOS) compared with nonobese healthy controls. Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Nonobese women with PCOS and nonobese healthy controls. Intervention(s) None. Main Outcome Measure(s) Prevalence of metabolic disturbances including hyperinsulinemia, insulin resistance (IR), impaired fasting glucose (IFG), impaired glucose intolerance (IGT), prediabetes, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein (low-HDL), as well as other metabolic outcomes such as type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome (Mets), myocardial infarction, stroke, cerebrovascular accident, arterial occlusive disease, and coronary heart disease. Result(s) Compared to nonobese controls, nonobese women with PCOS showed a higher prevalence of hyperinsulinemia (odds ratio [OR], 36.27; 95% confidence interval [CI] 1.76–747.12), IR (OR, 5.70; 95% CI 1.46–22.32), IGT (OR, 3.42; 95% CI 1.56–7.52), T2DM (OR, 1.47; 95% CI 1.11–1.93), hypertriglyceridemia (OR, 10.46; 95% CI 1.39–78.56), low-HDL (OR, 4.03; 95% CI 1.26–12.95), and Mets (OR, 2.57; 95% CI 1.30–5.07). No significant difference was observed for IFG, pre-DM, dyslipidemia, hypercholesterolemia, and hypertension. In subgroup analysis, Whites exhibited increased risks of IR, IGT, IFG, T2DM, hypertension, and Mets, whereas no significant metabolic change was found in Asians. No study reported specifically an incidence of myocardial infarction, stroke, cerebrovascular accident, arterial occlusive disease, and coronary heart disease in nonobese women with PCOS. Conclusion(s) Nonobese women with PCOS also suffer from metabolic disturbances and the risk of long-term metabolic complications. Further efforts should be made to elucidate underlying mechanisms and possible interventions in the early phase.

STUDY QUESTION What is the direct genetic contribution of the polycystic ovary syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNPs), identified by previous genome-wide association studies (GWAS) to the definitive clinical features of the syndrome? SUMMARY ANSWER Each single PCOS clinical feature had a specific genetic association, and rs4385527 in the chromosome 9 open reading frame 3 (C9orf3) conferred a particular risk to the three defined PCOS clinical features in this study, which suggested its fundamental role in the etiology of PCOS. WHAT IS KNOWN ALREADY PCOS is a heterogeneous disorder characterized by anovulation (OA), hyperandrogenism (HA) and polycystic ovary morphology (PCOM). Two previous GWAS in China have identified 15 independent susceptibility SNPs related to PCOS (PCOS-SNPs). However, little is known about the candidate gene of each clinical feature. STUDY DESIGN, SIZE, DURATION Case-control study. Three independent groups of women were recruited from 2010 to 2012: 746 subjects with OA only, 278 subjects with HA only and 536 subjects with PCOM only. A total of 1790 healthy women with none of the above pathological characteristics were also enrolled as control subjects during the same time period. PARTICIPANTS/MATERIALS, SETTING, METHODS All participants were women of reproductive age. Genotype and allelic frequencies of 15 PCOS-SNPs were determined in all subjects using direct sequencing and Sequenom Arrays. The allelic frequencies of each case group were compared with the controls. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age and BMI, variants in luteinizing hormone/choriogonadotropin receptor (LHCGR) (rs13405728), C9orf3 (rs4385527) and insulin receptor gene (INSR) (rs2059807) were strongly associated with OA (Padjust < 0.01

Introduction The objective of this research is to study the performance of noninvasive prenatal testing (NIPT) in monochorionic diamniotic twin pregnancies after the treatment of assisted reproductive technology (ART). Material & methods From March 2015 to December 2016, we provided NIPT targeting trisomy 21 (T21), 18 (T18), and 13 (T13) by sequencing cell-free DNA in maternal plasma, for 2403 chinese pregnant women with monochorionic diamniotic twin pregnancies through ART treatment. Positive NIPT results were validated by karyotyping, while negative results were interviewed after delivery. Results In total of 2403 cases, NIPT had a failure rate of 1.8% (44/2403). 7 cases of T21 were identified by NIPT and confirmed by karyotyping or follow-up interviews, among which 3 were true-positive and 4 were false-positive, making a positive predictive value as 42%. Interestingly, all the 4 false-positive cases were vanishing twins while the 3 true-positive cases were not. 6 cases of T18 were identified by NIPT, among which 5 were false-positive and 1 aborted spontaneously. 4 in the 5 T18 false-positive cases were vanishing twins. Among 2346 cases with NIPT negative results, 2179 cases (92.9%) were confirmed by follow-up survey of postnatal phenotypes, while 111 cases (4.7%) had adverse pregnant outcomes with unconfirmed reasons. The remaining 56 cases (2.4%) refused follow-up interviews. No false negative result was reported. Conclusion Our data implies that NIPT for T21 and T18 has a notable rate of false-positive results, with vanishing twins as the major cause. Nonetheless, NIPT is still a good screening approach for ART monochorionic diamniotic twin pregnancies, as no false-positive case was observed in this study.

We measured the carbon isotope ratio of black carbon (BC) from the Daihai Lake sediment core (DH99a) in north-central China with an objective to examine the effectiveness and sensitivity of the δ13C values of BC (δ13CBC) as a potential indicator of terrestrial environmental changes. We first performed a statistical study on the available data regarding carbon isotope fractionation (CIF) during the conversion of C3 and C4 vegetation to BC and observed that the mean CIF for BC produced from C3 plants is − 0.3‰, whereas that for BC from C4 plants is − 1.7‰. This result provides a solid reference for reconstructing vegetation and environmental changes using the δ13CBC values. The δ13CBC record in the DH99a sediment core spanning the last ca 10,000 years displayed large variations from − 23.7‰ to − 29.2‰, which suggests that C3 plants dominantly occupied the Daihai Lake region during the Holocene. The most negative δ13CBC peaks coincided with high values of tree percentages and grain sizes, which occurred under relatively wetter climatic conditions during the middle Holocene (ca 6500–3200 cal. yr BP) and an interval between 1700 and 1350 cal. yr BP. In contrast, the least negative δ13CBC values corresponded to low values of tree percentages and grain sizes during relatively drier phases of the early and late Holocene. The generally negative correlation of the δ13CBC values with the tree percentages and grain sizes was thought to reflect a negative correlation of the δ13CBC values with the monsoon precipitation. This correlation is consistent with the response of carbon isotope in modern C3 plants to precipitation in north China. Therefore, we developed a computational model to reconstruct the changes in annual precipitation over the Daihai Lake region using the δ13CBC values. The results indicated that the annual precipitation was highly variable, ranging from 170 mm lower to 310 mm higher than that at present during the middle Holocene, whereas the annual precipitation was generally ~ 70 mm lower than that at present during the early and late Holocene. The general features of the inferred precipitation changes using the δ13CBC values are generally consistent with those reconstructed using pollen data of the same sediment core. Meanwhile, the δ13CBC values tend to register some extreme variations of monsoon precipitation, which were not reflected in the pollen assemblages. We conclude that the δ13CBC values in the Daihai Lake sediments may serve as a sensitive and reliable proxy for monitoring monsoon precipitation.

STUDY QUESTION Are there any correlations between the phenotypes of polycystic ovary syndrome (PCOS) and the genotypes of the PCOS susceptibility single nucleotide polymorphisms (SNPs) in THADA, DENND1A and LHCGR? SUMMARY ANSWER The PCOS susceptibility genes, THADA and DENND1A, carry risk alleles that are associated with endocrine and metabolic disturbances in patients with PCOS. WHAT IS KNOWN ALREADY PCOS is a heterogeneous endocrinopathy characterized by oligo-anovulation, hyperandrogenism and polycystic ovaries. In a previous genome-wide association study, the SNP variants rs13429458, rs12478601, rs2479106, rs10818854 and rs13405728 in the THADA, DENND1A and LHCGR genes were identified as being independently associated with PCOS. The aim of this study was to identify any additional correlations between the phenotypes of PCOS and genotypes of the five SNPs described in the previous study. STUDY DESIGN, SIZE, DURATION In the present cross-sectional study, a total of 1731 PCOS patients and 4964 controls were enrolled. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were diagnosed according to Rotterdam criteria. Clinical information was collected from the patients and controls. Endocrine and metabolic parameters were evaluated for phenotype-genotype correlation analyses. MAIN RESULTS AND THE ROLE OF CHANCE Using a recessive model, the AA group for rs13429458 in THADA was associated with increased luteinizing hormone (LH) (P < 0.01) and testosterone (T) (P = 0.02) levels in subjects with PCOS; the LH/follicle-stimulating hormone ratio was also higher in the AA group (P < 0.01). Also using a recessive model, the CC genotype of rs12478601, also in THADA, was associated with increased levels of low-density lipoprotein (P = 0.02). Using a dominant model, the GG + AG group for rs2479106 in DENND1A was associated with elevated serum insulin levels 2 h after a glucose load in the patients with PCOS (P = 0.02). All of the comparisons were adjusted for age and BMI. LIMITATIONS, REASONS FOR CAUTION The relatively younger age of the participants may represent a considerable bias when evaluating metabolic alterations as a function of different genotypes, as significant metabolic disturbances may emerge later in life. Furthermore, the sample sizes of several sub-genotype groups were relatively small; to some extent this limited the statistical power of the analysis. WIDER IMPLICATIONS OF THE FINDINGS The PCOS susceptibility genes, THADA and DENND1A, carry risk alleles that are associated with endocrine and metabolic disturbances in PCOS patients of Han Chinese descent. The findings have shown genuine heterogeneity, stratified on the basis of both clinical findings and genotypes. Replication of these results is expected in other ethnic groups.

Objective To explore the potential damaging effect of chronic pelvic inflammation on ovarian reserve. Design Case-control study. Patients A total of 122 women with bilateral tubal occlusion, diagnosed by hysterosalipingography (HSG) and 217 women with normal fallopians were recruited. Measurements Serum anti-Mullerian hormone (AMH), basic follicle-stimulating hormone (FSH), luteining hormone (LH), estradiol (E2), and testosterone (T) were measured; and antral follicle counts (AFCs) were recorded. Results Significantly lower level of AMH was observed in women with bilateral tubal occlusion compared to control group [2.62 (2.95) ng/ml vs. 3.37 (3.11) ng/ml, P = 0.03], and the difference remained after adjustment of BMI (Padjust = 0.04). However, no statistical difference was found in the levels of FSH [7.00 (2.16) IU/L vs. 6.74 (2.30) IU/L], LH [4.18 (1.52) IU/L vs. 4.63 (2.52) IU/L], E2 [35.95 (20.40) pg/ml vs. 34.90 (17.85) pg/ml], T [25.07±11.46 ng/dl vs. 24.84±12.75 ng/dl], and AFC [6.00 (4.00) vs. 7.00 (4.00)] between two groups (p>0.05). Conclusions Women with bilateral tubal occlusion showed decreased AMH level, suggesting that chronic pelvic inflammation may diminish ovarian reserve. More caution should be paid when evaluating the detriment of PID on female fertility.

Background A previously reported genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese found that several loci of p value around 10e-5 warrant investigation. Replication of the GWAS was applied in this study to determine whether gene YAP1 (yeast associated protein 1) is associated with PCOS. Methods An independent set of 1115 PCOS patients and 1137 controls were recruited; single nucleotide polymorphisms (SNPs) rs11225138, rs11225161, and rs11225166 from YAP1 were selected for the replication study. Real-time quantitative PCR was applied for genotyping by TaqMan-MGB probe assay. Results Meta-analysis showed that the allele frequency of rs11225161 (A/G) was significantly different between PCOS and controls at a GWA significance (Pmeta =3.98e-09). Genotype–phenotype correlation study found 30 min and 60 min glucose of the oral glucose tolerance test were higher in PCOS patients with rs11225161 risk allele A. The G allele of SNP rs11225138 (G/C) was a further risk factor for higher luteinising hormone level in PCOS patients (p=0.041). Conclusion YAP1 appears to be a new susceptibility gene for PCOS in Han Chinese women.

This retrospective cohort study observed the live birth rates as well as cumulative live birth rates in women with poor ovarian response (POR) undergoing IVF-embryo transfer treatment, stratified for age and cycle number. Four hundred and one patients with POR diagnosed according to the Bologna criteria were enrolled and 700 IVF-ET cycles were analysed. The overall live-birth rate per cycle was 18.3%. From cycle 1 up to cycle 3, the live-birth rates decreased significantly from 22.2% to 11.1%. The live-birth rate fell to 2.4% in cycles 4 and over. When age advanced, the live birth rates decreased obviously (P < 0.01): 30.0% for women < 35 years old, 17.0% for those 35-40 years old, and 9.0% for women older than 40 years. Similarly, the cumulative live birth rates dropped from 48.0% (< 35 years) to 16.9% (≥ 40 years) accordingly. Younger patients (< 35 years old) with POR achieved better pregnancy results compared with patients of advanced age. Extremely low live-birth rates could be anticipated after three unsuccessful cycles; therefore it may not be appropriate to suggest more IVF cycles in POR women.

Objective To study the age-specific distribution of antimullerian hormone (AMH) and describe the association of AMH with androgenic and metabolic profiles at different ages. Design Cross-sectional study. Setting University hospital. Patient(s) A total of 6,763 Chinese women from birth to menopause. Intervention(s) None. Main Outcome Measure(s) Anthropometric parameters (height, weight, and blood pressure), and levels of AMH and testosterone, glucose metabolism, and lipid profiles. Result(s) According to the level of AMH, four age phases were established: childhood (0–10 years), adolescence (11–18 years), reproductive age (19–50 years), and advanced age (≥51 years). During childhood and adolescence, AMH levels increased, reaching a peak at 18 years. A decline occurred thereafter during the reproductive-age period until the age of 50 years, and it remained at a low level above 0 onward. We found that AMH was negatively correlated with testosterone in childhood ( r = −0.25), but was positively correlated with testosterone and the free androgen index in adolescence ( r = 0.30; r = 0.26, respectively) as well as during the reproductive phases ( r = 0.28; r = 0.31, respectively). No correlation was observed between AMH and body mass index, fasting blood glucose, fasting insulin, the homeostasis model assessment, total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein at any phase. Conclusion(s) From birth to 18 years, AMH increases, then it declines thereafter, indicating changes of ovarian maintenance. A positive relationship between androgenic profiles and AMH during adolescence and reproductive years implies a synchronism between androgens and ovarian reserve.

A state of systemic chronic low grade inflammation has been observed in polycystic ovary syndrome (PCOS). It has been suggested that inflammation is a potential mechanism influencing the ovaries or endocrine system and might therefore contribute to the pathophysiology of PCOS. The aim of this study was to compare the total white blood cell (WBC), neutrophil granulocyte and lymphocyte differential counts between women with PCOS and controls. In addition, we estimated if the WBC differential counts had a relationship with body mass index (BMI), total testosterone levels, estradiol levels and luteinizing hormone levels of women with PCOS.1016 subjects with PCOS and 1016 age-matched healthy women from a Han Chinese population were enrolled in this case-control study. Blood samples were taken from all the patients and controls to test total WBC counts, lymphocyte counts, neutrophil counts and related serum hormones.Total WBC counts and lymphocyte counts were elevated in PCOS subjects (t-test P0.01). Higher lymphocyte counts which contributed to higher total WBC counts in PCOS women were compared to age-matched controls. When the data were adjusted by BMI, the difference of WBC counts and lymphocyte counts between patients and controls remained significant.The state of chronic low grade inflammation in patients with PCOS might be associated with immunological factors. Obesity and hyperandrogenism may be due to the underlying low grade inflammation.

ObjectiveTo compare the risk of ectopic pregnancy (EP) after embryo transfer on day 3(D3-ET) and day 5(D5-ET).DesignMeta-analysis.PatientsWomen with pregnancy resulting from in vitro undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).Result(s)Twenty-two studies were identified through research conducted using the PubMed, Embase, and Cochrane databases and ClinicalTrials.gov. All studies were conducted prior to October 2016. Adding the reproductive data from our center, a total of 143 643 pregnancies were reviewed(D3-ET: n = 62027,D5-ET:n = 81616). A lower EP rate was found in women undergoing D5-ET than in those undergoing D3-ET [relative risk (RR), 0.67;95% confidence interval (CI), 0.54-0.85;143643 pregnancies in 23 studies; I2 = 67%]. These results were validated in subgroups of fresh embryo-transfer (Fre-ET) cycles [RR, 0.78; 95%CI, 0.69-0.88; 91 871 pregnancies in 21 studies; I2 = 29%] and frozen-thawed embryo-transfer (Fro-ET) cycles [RR, 0.43; 95%CI, 0.36-0.51; 51 772 pregnancies in 10 studies; I2 = 33%]. After separating out the randomized controlled trials (RCTs), a significant difference was found in the retrospective studies in both subgroups [both Fre-ET (RR,0.78;95% CI 0.69-0.88);91182 pregnancies in 14 studies; I2 = 45%] and Fro-ET(RR,0.43;95% CI 0.36-0.51; 51751pregnancies in 9 studies;I2 = 33%)], while the RCTs showed no statistical significance for Fre-ET cycles[RR,0.86;95% CI 0.32-2.26); 689 pregnancies in 7 studies; I2 = 0%].Conclusion(s)The present study indicates that D5-ET reduces the risk for EP in cycles that use IVF or ICSI, compared with D3-ET. It suggests that D5-ET may be a better choice for decreasing the EP rate in assisted reproductive technology. Further high-quality randomized controlled trials are anticipated.