Exposure to thimerosal induces behavioral abnormality in the early life stages of zebrafish via altering amino acid homeostasis.

Thimerosal (THI) has become a significant source of organic mercury pollutants in aquatic ecosystems, but there is limited information regarding its adverse effects on fish. In this study, zebrafish embryos were exposed to THI at 0 (control), 5.0, and 50 ng/L from 0-5 days post fertilization (dpf), and variations in their survival, development, behavior, free amino acid contents, and the biochemical responses involved in monoaminergic systems were examined. Although THI exposure did not significantly affect the survival, heart rate, or hatching time of zebrafish embryos, it substantially increased swimming velocity (136-154 % of the control) and reduced exploratory behavior (141-142 % of the control) in zebrafish larvae at 5 dpf. Exposure also significantly altered the amino acid contents (51-209 % of the control) and monoamine levels (70-154 % of the control) in zebrafish larvae, some of which displayed significant correlations with behavioral traits. THI significantly elevated dopamine receptor gene expression and monoamine oxidase activity in zebrafish larvae. Adding extra phenylalanine or tryptophan to the E3 medium facilitates the recovery of zebrafish larvae from the abnormal behaviors induced by THI. These findings reveal for the first time that THI exposure at the level of ng/L is sufficient to induce neurobehavioral toxic effects in the early life stages of zebrafish, and disrupting amino acid homeostasis is a critical underlying mechanism. This study provides valuable insights into the toxicity of THI to fish and highlights the importance of assessing its potential risks to aquatic ecosystems.

TagP, a PAAR-domain containing protein, plays roles in the fitness and virulence of Acinetobacter baumannii.

Background: Type VI secretion system (T6SS) is widely present in Gram-negative bacteria and directly mediates antagonistic prokaryote interactions. PAAR (proline-alanine-alanine-arginine repeats) proteins have been proven essential for T6SS-mediated secretion and target cell killing. Although PAAR proteins are commonly found in A. baumannii, their biological functions are not fully disclosed yet. In this study, we investigated the functions of a PAAR protein termed TagP (T6SS-associated-gene PAAR), encoded by the gene ACX60_RS09070 outside the core T6SS locus of A. baumannii strain ATCC 17978. Methods: In this study, tagP null and complement A. baumannii ATCC 17978 strains were constructed. The influence of TagP on T6SS function was investigated through Hcp detection and bacterial competition assay; the influence on environmental fitness was studied through in vitro growth, biofilm formation assay, surface motility assay, survivability in various simulated environmental conditions; the influence on pathogenicity was explored through cell adhesion and invasion assays, intramacrophage survival assay, serum survival assay, and G. melonella Killing assays. Quantitative transcriptomic and proteomic analyses were utilized to observe the global impact of TagP on bacterial status. Results: Compared with the wildtype strain, the tagP null mutant was impaired in several tested phenotypes such as surface motility, biofilm formation, tolerance to adverse environments, adherence to eukaryotic cells, endurance to serum complement killing, and virulence to Galleria melonella. Notably, although RNA-Seq and proteomics analysis revealed that many genes were significantly down-regulated in the tagP null mutant compared to the wildtype strain, there is no significant difference in their antagonistic abilities. We also found that Histone-like nucleoid structuring protein (H-NS) was significantly upregulated in the tagP null mutant at both mRNA and protein levels. Conclusions: This study enriches our understanding of the biofunction of PAAR proteins in A. baumannii. The results indicates that TagP involved in a unique modulation of fitness and virulence control in A. baumannii, it is more than a classic PAAR protein involved in T6SS, while how TagP play roles in the fitness and virulence of A. baumannii needs further investigation to clarify.

Development and evaluation of a multi-target droplet digital PCR assay for highly sensitive and specific detection of Yersinia pestis.

BACKGROUND: Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis. However, inhibitors in complex samples such as soil and animal tissues often hamper nucleic acid detection, leading to a reduced rate of identifying low concentrations of Y. pestis. To address this challenge, we developed a sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay for detecting Y. pestis DNA from soil and animal tissue samples. METHODS: Three genes (ypo2088, caf1, and pla) from Y. pestis were used to develop a multi-target ddPCR assay. The limits of detection (LoD), reproducibility, and specificity were assessed for bacterial genomic DNA samples. The ability of the assay to detect low concentrations of Y. pestis DNA from simulated soil and mouse liver tissue samples was respectively evaluated and compared with that of quantitative real-time PCR (qPCR). RESULTS: The results showed that the ddPCR LoDs ranged from 6.2 to 15.4 copies/reaction for the target genes, with good reproducibility and high specificity for Y. pestis. By testing 130 soil and mouse liver tissue samples spiked with Y. pestis, the ddPCR assay exhibited a better sensitivity than that of the qPCR assay used in the study, with LoDs of 102 colony forming units (CFU)/100 mg soil and 103 CFU/20 mg liver. Moreover, the assay presented good quantitative linearity (R2 = 0.99) for Y. pestis at 103-106 CFU/sample for soil and liver samples. CONCLUSION: The ddPCR assay presented good performance for detecting Y. pestis DNA from soil and mouse tissue samples, showing great potential for improving the detection rate of low concentrations of Y. pestis in plague surveillance and facilitating the early diagnosis of plague cases.

An Integrated Gather-and-Distribute Mechanism and Attention-Enhanced Deformable Convolution Model for Pig Behavior Recognition.

The behavior of pigs is intricately tied to their health status, highlighting the critical importance of accurately recognizing pig behavior, particularly abnormal behavior, for effective health monitoring and management. This study addresses the challenge of accommodating frequent non-rigid deformations in pig behavior using deformable convolutional networks (DCN) to extract more comprehensive features by incorporating offsets during training. To overcome the inherent limitations of traditional DCN offset weight calculations, the study introduces the multi-path coordinate attention (MPCA) mechanism to enhance the optimization of the DCN offset weight calculation within the designed DCN-MPCA module, further integrated into the cross-scale cross-feature (C2f) module of the backbone network. This optimized C2f-DM module significantly enhances feature extraction capabilities. Additionally, a gather-and-distribute (GD) mechanism is employed in the neck to improve non-adjacent layer feature fusion in the YOLOv8 network. Consequently, the novel DM-GD-YOLO model proposed in this study is evaluated on a self-built dataset comprising 11,999 images obtained from an online monitoring platform focusing on pigs aged between 70 and 150 days. The results show that DM-GD-YOLO can simultaneously recognize four common behaviors and three abnormal behaviors, achieving a precision of 88.2%, recall of 92.2%, and mean average precision (mAP) of 95.3% with 6.0MB Parameters and 10.0G FLOPs. Overall, the model outperforms popular models such as Faster R-CNN, EfficientDet, YOLOv7, and YOLOv8 in monitoring pens with about 30 pigs, providing technical support for the intelligent management and welfare-focused breeding of pigs while advancing the transformation and modernization of the pig industry.

LINC00265 can Serve as a Potential Biomarker for Predicting Increased Disease Risk, Systemic Inflammation, Disease Severity and Poor Prognosis in Sepsis.

BACKGROUND: Identifying effective therapeutic targets is of great significance for improving early diagnosis and prognosis of sepsis. This study aims to explore the role of LINC00265 in sepsis. METHODS: This is a retrospective study based on data collected from sepsis patients in 2017-2018. The basic clinical information of all subjects were collected and the survival of the sepsis patients within 28 days was monitored. The expression of LINC00265 was detected by qPCR. Receiver operating characteristics and Cox regression analysis were used to evaluate the diagnostic and prognostic value of LINC00265 in patients with sepsiss. RESULTS: Compared with the healthy population, the expression of LINC00265 was significantly upregulated in patients with sepsis distinguishing them from healthy individuals. This expression was patients with sepsis positively correlated with the APACHEII score, tumor necrosis factor α, interleukin-6 (IL-6), IL-8, and IL-17, and negatively correlated with IL-10. LINC00265 expression was upregulated in the sepsis death group, predicting a lower rate in patients with patients with sepsis. The higher expression of LINC00265 was correlated with lower cumulative patient sursvival. CONCLUSION: LINC00265 is upregulated in patients with sepsis, and its high expression predicts increased disease severity, heightened inflammation, and a poorer prognosis.

Sex-specific impacts of thimerosal on the behaviors and brain monoaminergic systems in zebrafish (Danio rerio).

Thimerosal (THI) is the most widely used form of organic mercury in pharmaceutical and personal care products, and has become a major source of ethylmercury pollution in aquatic ecosystems. However, knowledge about its potential risk to aquatic species is limited. In this study, zebrafish were exposed to THI for 7 days, and variations in their behavioral traits, brain monoaminergic neurotransmitter contents, and related gene expression were investigated. After the 7-day exposure, THI reduced locomotor activity and thigmotaxis in males but not females. Exposure to THI increased the social interaction between females but decreased that between males. The THI exposure also significantly reduced the serotonin (5-HT), 5-hydroxyindoleacetic acid, dopamine (DA), and 3,4-dihydroxyphenylacetic acid contents in the brain of males, but only significantly decreased the DA content in females. Correlation analysis revealed that the neurochemical alterations in the brain of zebrafish play critical roles in the behavioral abnormalities induced by THI exposure. Moreover, THI also significantly altered the expression of some genes associated with the synthesis, metabolism, and receptor binding of 5-HT and DA in the brain of zebrafish. The differences in these gene expressions between female and male zebrafish exposed to THI seem to be an important mechanism underlying their sex-specific responses to this chemical. This is the first report on the sex-specific effects of THI on behaviors and brain monoaminergic neurotransmitter contents in zebrafish, which can further improve our understanding of its toxic effects on teleost.

Ethnobotanical Knowledge, Nutritional Composition, and Aroma Profile of Vicia kulingiana Bailey: An Underutilized Wild Vegetable Endemic to China.

Vicia kulingiana, an endemic species, serves as a wild and underutilized vegetable traditionally consumed in China. However, ethnobotanical and chemical studies of this species are not available. This study analyzed its associated ethnobotanical knowledge, nutritional composition and aroma profile. Ethnobotanical surveys revealed its diverse traditional uses, especially as a nutritious vegetable. Further analysis showed V. kulingiana leaves to be high in protein, minerals, vitamin E, and dietary fiber. In total, 165 volatile compounds, such as terpenoids, alcohols, and ketones, were identified. Among them, ß-ionone is the most abundant compound with a relative percentage of 8.24%, followed by 2,2,4,6,6-pentamethylheptane (3.2%), 3-(4-methyl-3-pentenyl)furan (2.37%), and linalool (1.68%). Results supported the traditional uses of V. kulingiana's and highlighted its potential as a valuable food source, encouraging further research on its food applications. The documentation of ethnobotanical knowledge contributes to the conservation of this heritage.

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis.

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism.

Regulatory Functions of PurR in Yersinia pestis: Orchestrating Diverse Biological Activities.

The bacterium Yersinia pestis has developed various strategies to sense and respond to the complex stresses encountered during its transmission and pathogenic processes. PurR is a common transcriptional regulator of purine biosynthesis among microorganisms, and it modulates the transcription level of the pur operon to suppress the production of hypoxanthine nucleotide (IMP). This study aims to understand the functions and regulatory mechanisms of purR in Y. pestis. Firstly, we constructed a purR knockout mutant of Y. pestis strain 201 and compared certain phenotypes of the null mutant (201-ΔpurR) and the wild-type strain (201-WT). The results show that deleting purR has no significant impact on the biofilm formation, growth rate, or viability of Y. pestis under different stress conditions (heat and cold shock, high salinity, and hyperosmotic pressure). Although the cytotoxicity of the purR knockout mutant on HeLa and 293 cells is reduced, the animal-challenging test found no difference of the virulence in mice between 201-ΔpurR and 201-WT. Furthermore, RNA-seq and EMSA analyses demonstrate that PurR binds to the promoter regions of at least 15 genes in Y. pestis strain 201, primarily involved in purine biosynthesis, along with others not previously observed in other bacteria. Additionally, RNA-seq results suggest the presence of 11 potential operons, including a newly identified co-transcriptional T6SS cluster. Thus, aside from its role as a regulator of purine biosynthesis, purR in Y. pestis may have additional regulatory functions.

Effectiveness of prophylactic pharmacological hemostatic agents for reduction of blood loss at vaginal surgery: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the effectiveness of pharmacological hemostatic agents in the reduction of blood loss at vaginal surgery. METHODS: A systematic review of randomized control trials (RCTs) was completed. We searched PubMed (1946-2022), Embase, and CINAHL, using search terms related to vaginal hysterectomies and reconstructive surgeries combined with peri-operative use of hemostatic agents. RCTs comparing hemostatic interventions with placebo or with standard care were analyzed with the primary outcome of estimated blood loss. Secondary outcomes included peri-operative complications, length of stay, blood transfusion, and readmission. Risk of bias was assessed using the Risk of Bias 2 tool. RESULTS: Nine RCTs were included with a total of 903 participants. All trials were considered to have an overall low risk of bias. Meta-analysis of six RCTs (491 participants) favored the use of vasoconstrictive agent (vasopressin/ornipressin) at the surgical site for an overall effect estimate of decreased blood loss by 70 ml (95% CI -125, -14 ml). There was significant heterogeneity of studies with both dose and technique of vasoconstrictive agents used. Only one RCT evaluated tranexamic acid and found a benefit in the prophylactic use of intravenous tranexamic acid. CONCLUSIONS: Peri-operative use of vasoconstrictive agents slightly reduces bleeding in women undergoing elective vaginal surgery. Additional studies evaluating alternative pharmacological agents such as tranexamic acid may be of benefit.

First Fossil Record of Trichomanes sensu lato (Hymenophyllaceae) from the Mid-Cretaceous Kachin Amber, Myanmar.

Hymenophyllaceae (filmy ferns), with ca. 430 species, are the most species-rich family of early diverging leptosporangiate ferns but have a poor fossil record dating back to the Late Triassic period. Traditionally, Hymenophyllaceae comprise two species-rich genera or clades: Hymenophyllum (hymenophylloids) and Trichomanes sensu lato (s.l.) (trichomanoids). Unequivocal fossils of Hymenophyllum have been reported from the Early Cretaceous of central Mongolia and the early Eocene of Okanogan Highlands, Washington, USA. However, despite being a highly diversified lineage with an estimated 184 extant species, Trichomanes s.l. lack a definitive fossil record, which severely affects the reliability of the molecular dating of this group. Here, we report the first unequivocal fossil record of Trichomanes s.l. as T. angustum comb. nov. on the basis of fertile material with tubular involucres and long exserted receptacles from the mid-Cretaceous Kachin amber, Myanmar. This species was previously tentatively assigned to Hymenophyllites due to a lack of fertile evidence. Inferred to be an epiphytic fern, T. angustum further enriches the species diversity of the epiphytic palaeocommunities in the mid-Cretaceous Kachin amber, which are mainly composed of Porellalean leafy liverworts and Dicranalean and Hypnodendralean mosses. Fossil records indicate that Hymenophyllaceae probably originated in the tropical Pangea at the latest in the Triassic when all continents were coalesced into a single landmass and had already accumulated some notable diversity in low-middle latitude areas of Laurasia by the mid-Cretaceous period.

SlbHLH152, a bHLH transcription factor positively regulates iron homeostasis in tomato.

The maintain of iron (Fe) homeostasis is essential for plant survival. In tomato, few transcription factors have been identified as regulators of Fe homeostasis, among which SlbHLH068 induced by iron deficiency, plays an important role. However, the upstream regulator(s) responsible for activating the expression of SlbHLH068 remain(s) unknown. In this study, the bHLH (basic helix-loop-helix) transcription factor SlbHLH152 was identified as an upstream regulator of SlbHLH068 using yeast one-hybrid screening. Deletion of SlbHLH152 led to a significant decline in Fe concentration, which was accompanied by reduced expression of Fe-deficiency-responsive genes. In contrast, SlbHLH152 overexpression plants displayed tolerance to iron deficiency, increased Fe accumulation, and elevated expression of Fe-deficiency-responsive genes. Further analysis indicated that SlbHLH152 directly activates the transcription of SlbHLH068. Taken together, our results suggest that SlbHLH152 may be involved in the regulation of iron homeostasis by directly activating the transcription of SlbHLH068 in tomato.

The impact of polycystic ovary syndrome on placental histopathology patterns in in-vitro fertilization singleton live births.

INTRODUCTION: Pregnant polycystic ovary syndrome (PCOS) patients are at increased risk for myriad obstetric complications, with the placenta thought to play a key role in their development. We aimed to evaluate placental histopathology patterns in placentas of women with PCOS who underwent in-vitro-fertilization (IVF). METHODS: This retrospective study utilized full gross and histopathologic assessment of placentas of all women who had IVF treatment and delivered at the Royal Victoria Hospital from 2009 to 2017, regardless of complications or mode of delivery. Pathologic findings included anatomic, inflammation, villous maturation, and vascular mal-perfusion features. Placentas of PCOS women were compared to those of ovulatory controls. Multivariate logistic regression was used to adjust results for confounding factors potentially associated with significant placental and perinatal characteristics. RESULTS: Women with PCOS (n = 47) were more likely to develop gestational diabetes mellitus compared to ovulatory controls (n = 1121) (38.3% vs. 9.8%, p < 0.001). Placentas from PCOS women were more likely circumvallate placentas (aOR 8.3, 95%CI 1.9-37.3) and more likely to have a hypercoiled umbilical cord (aOR 6.8 95%CI 1.3-36.8) and villitis of unknown etiology (aOR 6.1, 95%CI 1.5-25.6). There was an increased likelihood of chorangiosis (aOR 2.7, 95% CI 1.3-5.8), evidence of fetal vascular malperfusion based on one criteria (aOR 2.7, 95%CI 1.1-7.4), or more than one criteria (aOR 6.4, 95%CI 1.6-25.9), more nucleated fetal red blood cells (aOR 5.2, 95%CI 1.1-24.5), and a higher likelihood of chorangiomas (aOR 9.4, 95%CI 1.6-55.1) in placentas from PCOS women than in controls. DISCUSSION: IVF pregnancies' placental histopathological characteristics are significantly impacted by an underlying diagnosis of PCOS, including important anatomic changes and vascular placental abnormalities.

Palaeobotanical evidence reveals the living conditions of Miocene Lufengpithecus in East Asia.

BACKGROUND: Understanding the relationship between human evolution and environmental changes is the key to lifting the veil on human origin. The hypothesis that environmental changes triggered the divergence of humans from apes (ca. 9.3-6.5 million years ago, Ma) has been poorly tested because of limited continuous environmental data from fossil localities. Lufengpithecus (12.5-6.0 Ma) found on the southeastern margin of the Tibetan Plateau (SEMTP) across the ape-human split provides a good chance for testing this hypothesis. RESULTS: Here, we reconstructed the habitats of L. keiyuanensis (12.5-11.6 Ma) with comprehensive vegetation, climate, and potential food web data by palaeobotanical evidence, together with other multidisciplinary data and partly tested the environment-driven hypothesis by revealing the living conditions of Lufengpithecus. CONCLUSION: A detailed comparison of hominoids on different continents reveals their behaviour and fate divergence across the ape-human split against the background of global climate change, i.e., the stable living conditions of SEMTP not only provided a so-called 'refuge' for arboreal Lufengpithecus but also acted as a 'double-edged sword', preventing their further evolution while vegetation shifts in East Africa probably stimulated the emergence of human bipedalism, and the intense climatic changes in Europe possibly prevented those hominoids from surviving that time interval. Our findings provide interesting insight into the environmental impacts on the behavioural evolution of hominoids.

Does embryo quality at transfer affect obstetric outcomes and placental findings?

STUDY QUESTION: Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? SUMMARY ANSWER: Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. WHAT IS KNOWN ALREADY: A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P < 0.001) and more pregnancies in the poor-quality group were following frozen embryo transfer. After adjustment for confounders, poor-quality embryos were associated with a higher rate of low-lying placentas [adjusted odds ratio (aOR) 2.35, 95% CI 1.02-5.41, P = 0.04] and placentas with a higher rate of villitis of unknown etiology (aOR 2.97, 95% CI 1.17-6.66, P = 0.02), distal villous hypoplasia (aOR 3.78, 95% CI 1.20-11.38, P = 0.02), intervillous thrombosis (aOR 2.41, 95% CI 1.39-4.16, P = 0.001), multiple maternal malperfusion lesions (aOR 1.59, 95% CI 1.06-2.37, P = 0.02), and parenchymal calcifications (aOR 2.19, 95% CI 1.07-4.46, P = 0.03). LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. WIDER IMPLICATIONS OF THE FINDINGS: The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Effect of Parity on Placental Histopathology Features in Singleton Live Births Following IVF.

The aim of this study was to evaluate the effect of parity (primipara vs multipara) on the histopathology of the placenta in singleton live births following in vitro fertilization. We conducted a retrospective cohort study evaluating data of all IVF resulted live births from one university affiliated hospital during 2009-2017. All patients had the placenta sent for pathological evaluation. Exclusion criteria were history of miscarriage or elective termination of pregnancy, abnormal uterine cavity findings, previous uterine surgery, in vitro maturation cycles, gestational carrier cycles, oocyte recipient cycles, preimplantation genetic diagnosis cycles, and multiple pregnancies. The outcomes measured included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. A multivariate analysis was conducted to adjust the results for factors potentially associated with placental pathology features. A total of 395 live births were included in the final analysis and were allocated to the study groups according to parity: primipara (n = 273) and multipara (n = 122). After adjustment for potential confounding factors, multiparity was found to be significantly associated with delayed villous maturation (OR 4.9; 95% CI 1.2-19.8) and primiparity was significantly associated with maternal vascular malperfusion (OR 0.6; 95% CI 0.3-0.8). We showed that parity has an impact on placental histopathological changes which in turn may affect perinatal outcome.

The effect of oestrogen dose and duration in programmed frozen cycles on obstetric outcomes and placental findings.

RESEARCH QUESTION: Does programmed frozen embryo transfer (FET) with high-dose oestrogen affect obstetric outcomes and placental findings? DESIGN: A retrospective cohort of live singleton deliveries at a single institution between 2009 and 2017, including deliveries attained by IVF with programmed FET; oocyte recipients were excluded. High-dose oestrogen was defined as a daily dose >6 mg throughout treatment. All placentas were evaluated regardless of complication status and the Amsterdam classification was used to analyse findings. RESULTS: A total of 57 deliveries in the high-dose oestrogen group were compared with 274 controls. The high-dose oestrogen group displayed significantly longer duration of oestrogen treatment (18.8 ± 4.9 versus 13.3 ± 2.7 days, P < 0.001), total cumulative oestrogen dose (149.7 ± 46.1 versus 80.3 ± 16.8 mg, P < 0.001) and lower endometrial thickness (8.5 ± 1.4 versus 9.8 ± 1.7 mm, P < 0.001). After adjustment for confounders, higher dose oestrogen was found to be associated with a lower average birthweight (coefficient -252.4 g, 95% confidence interval [CI] -483.5 to -21.2), a higher rate of low-birthweight neonates (adjusted odds ratio [aOR] 4.88, 95% CI 1.05 to 22.57), bilobated placentas (aOR 3.36, 95% CI 1.04 to 10.89), accessory lobes (aOR 8.74, 95% CI 1.24 to 61.5), accelerated villous maturation (aOR 2.06, 95% CI 1.09 to 3.87), retroplacental haematoma (aOR 5.39, 95% CI 1.11 to 26.13) and maternal malperfusion lesions (aOR 1.46, 95% CI 1.04 to 2.05). CONCLUSION: A higher daily oestrogen dose in programmed FET is associated with low birthweight and placental changes, although this may relate to altered endometrial properties and not to the treatment itself.

Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions.

OBJECTIVE: To assess obstetric outcomes and placental findings in pregnancies attained by in vitro fertilization (IVF) in patients with diminished ovarian reserve (DOR). DESIGN: Retrospective cohort study. SETTING: University-affiliated tertiary hospital. INTERVENTIONS: DOR, defined as an antral follicle count (AFC) of 6 or less (DOR group), compared with patients with no DOR and an antral count above 6 (control group). PATIENTS: Live singleton births after IVF between 2009 and 2017. MAIN OUTCOME MEASURES: Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes. RESULTS: A total of 110 deliveries of patients with DOR were compared with 772 controls. Maternal age was higher in the DOR group than in the control group (36.3 ± 4.4 years vs. 35.3 ± 4.1 years, P=.02). Patients with DOR were more likely to have a diagnosis of endometriosis (P=.02) and less likely to have a diagnosis of male factor (P<.001), ovulation disorder (P<.001), or tubal factor (P=.04), or a transfer of a blastocyte (P=.007). After adjustment for confounders, pregnancies in the DOR group were notable for a significantly higher rate of preeclampsia (8.1% vs. 2.7%, adjusted odds ratio: 3.05, 95% confidence interval: 1.33-6.97). On placental examination, DOR was associated with a higher rate of fetal vasculopathy (P=.01) and multiple fetal vascular malperfusion lesions (P=.03), and a lower rate of circummarginate insertion (P=.01) and intervillous thrombosis (P=.02). CONCLUSION: DOR, specifically defined as an AFC of 6 or less, is associated with a higher incidence of preeclampsia and multiple placental fetal vascular lesions.

Maternal hypothyroidism and its effect on placental histopathology in singleton live births resulting from in vitro fertilization treatment.

We aimed to examine the impact of maternal hypothyroidism on placental pathology and perinatal outcomes in singleton live births resulting from IVF, using medical records of IVF births between 2009 and 2017 at a tertiary hospital. The primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included foetal, maternal, perinatal, and delivery complications. There were 1,057 live births, of which 103 (9.7%) and 954 (90.3%) were in the study and control groups, respectively. Patients in the study group were more likely to have diabetes mellitus, polycystic ovarian syndrome, gestational diabetes mellitus, and non-reassuring foetal heart rate (NRFHR) tracing during delivery. After adjustment for potential confounding factors, hypothyroidism was significantly associated with the bilobed placenta (aOR 4.1; 95% CI 1.2-14.3), retroplacental haematoma (aOR 2.4; 95% CI 1.2-4.9), decidual arteriopathy (aOR 2.0; 95% CI 1.2-4.1) and subchorionic thrombi (aOR 2.4; 95% CI 1.3-5.0). Additionally, there was a statistically significant relationship with NRFHR tracing. The incidence of acute chorioamnionitis and severe foetal inflammatory response was higher in the study group. In conclusion, the placental histopathology patterns of singleton IVF live births show that maternal hypothyroidism has a significant impact on adverse perinatal outcomes.

Does a history of recurrent pregnancy loss affect subsequent obstetric outcomes and placental findings in in vitro fertilization?

PURPOSE: To assess perinatal outcomes and placental findings in in vitro fertilization (IVF) patients with previous recurrent pregnancy loss (RPL). METHODS: This was a retrospective cohort of live singleton births following IVF at a single university-affiliated center between 2009 and 2017. Outcomes were compared between patients with previous RPL, defined as two miscarriages (RPL group), and patients without RPL (control group). Placental examination was performed for all deliveries irrelevant of complications, and findings categorized according to the Amsterdam Placental Workshop Consensus. RESULTS: One hundred seventy-two deliveries of women with previous RPL (RPL group) were compared to 885 controls. Maternal age, 36.2 ± 4.2 vs. 35.4 ± 4.2 years, p = 0.02, and rate of uterine fibroids, 12.7% vs. 7.3%, p = 0.01, were higher in the RPL group. The rate of nulliparity was lower in the RPL group, 63.3% vs. 74.1%, p = 0.003. Unexplained infertility and diminished ovarian reserve were more common in the RPL group and male factor infertility in controls. There was a lower rate of fresh embryo transfer in the RPL group, 50.5% vs. 64.7%, p < 0.001, and reduced endometrial thickness. Similar obstetric outcomes were noted in the groups after adjustment for confounders. Placental examinations were notable for lower placental thickness, ß - 0.17 cm, 95%CI - 0.30-(- 0.0), a lower rate of velamentous cord insertion, aOR 0.44, 95%CI 0.20-0.95, and a higher rate of villous infarction, aOR 2.82, 95%CI 1.28-6.20 in the RPL group. CONCLUSION: In IVF patients with a history of RPL, subsequent deliveries were associated with a limited number of placental lesions, yet with similar obstetric outcomes.