Toxicological effects and defense mechanisms induced by beta-cypermethrin in Drosophila melanogaster.

Widespread use of the pyrethroid insecticide beta-cypermethrin (beta-CYP) has led to adverse effects on nontarget populations within agroecosystems. Despite the efficacy of beta-CYP in pest control, its toxicological and defense mechanisms remain incompletely understood. In the present study, we explored the toxicological effects, antioxidant mechanisms and immune response against beta-CYP using Drosophila melanogaster, a well-established model organism for the study of insect biology, to represent the broader class of nontarget organisms. We exposed Drosophila larvae to 0.667 µg/mL beta-CYP and revealed that delayed development and caused intestinal epithelial damage in larvae. To gain insights into the molecular underpinnings of these effects, RNA sequencing analysis and quantitative polymerase chain reaction validation were performed. These analyses revealed that the messenger RNA levels of glutathione S-transferase were increased, third instar larvae exhibited an increase in reactive oxygen species content and a corresponding increase in antioxidant enzyme activity in response to beta-CYP exposure, indicating an upregulated response to oxidative stress. Beta-CYP also activated Hippo pathway to resist apoptosis and promote cell proliferation. Moreover, beta-CYP induced melanization and Toll immune pathways involved in immune response in Drosophila larvae, specifically the Toll pathway gene Drs. This activation suggests that Drosophila increases antioxidant defenses and promotes mitosis in damaged tissues as compensatory mechanisms to mitigate the cytotoxic effects of beta-CYP. These findings provide new insight into the mechanisms of beta-CYP-induced toxicity and the defense mechanisms in insects; they may also inform strategies for the sustainable use of insecticides and the development of mitigation measures to protect nontarget species in agroecosystems.

Effects of ovarian stimulation on embryo euploidy: an analysis of 12 874 oocytes and 3106 blastocysts in cycles with preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: Does ovarian stimulation and the ovarian response affect embryo euploidy? SUMMARY ANSWER: Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy. WHAT IS KNOWN ALREADY: Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue. STUDY DESIGN SIZE DURATION: A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 617 women with 867 PGT-M cycles involving 12 874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos). MAIN RESULTS AND THE ROLE OF CHANCE: Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all P > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old (P = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old (P = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved (P = 0.001, <0.001, and 0.012, respectively). LIMITATIONS REASONS FOR CAUTION: Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Environmental exposure patterns to 94 current-use pesticides in women of reproductive age who are preparing for pregnancy.

Current-use pesticides (CUPs), including insecticides, fungicides, and herbicides, are extensively employed in agriculture to manage pests, diseases, and weeds. Nonetheless, their widespread application raises significant concerns regarding potential impacts on human health, particularly with reproductive health. This study focuses on exploring the landscape of CUP exposure among pre-pregnancy women. Based on a cohort study comprising 354 pre-pregnancy women of reproductive age in Beijing, China, we measured the concentrations of 94 CUPs in serum and conducted an in-depth analysis of exposure profiles, health risks, and contributing factors. The results revealed that the serum of pre-pregnancy women was contaminated with CUPs, of which the median concentrations ranged from 0.114 (fenamiphos-sulfone) to 61.2 ng/L (mefenacet). Among the 94 CUPs, 54 exhibited detection rates higher than 50 %, including 26 insecticides, 14 fungicides, and 14 herbicides. The exposure concentration profile highlighted that the insecticides contributed 56 % to the total CUP concentration percentages, with organophosphate insecticides being the primary contributors within this category (63.0 %). The average daily intake (ADI) of CUPs ranged from 2.23 to 16,432.28 ng/kg, while diflubenzuron had the highest ADI. Health risk assessments showed that exposure to a combination of total insecticides or herbicides poses a moderate risk for 15.8 % and 30.2 % of women, with mefenacet being the most significant, which showed moderate hazard in 29.4 % of participants. The overlap analysis showed that methiocarb-sulfone, diflubenzuron, and mefenacet were the dominant pesticides. In addition, maternal age, annual income level, smoking, and vitamin B12 supplementation were associated with serum CUP concentrations. Our study contributes a novel and comprehensive exposure profile of CUPs in pre-pregnancy women in northern China, providing valuable insights for evaluating the potential consequences of pre-pregnancy exposure on reproductive health. SYNOPSIS: We provided a comprehensive exposure landscape, health effects, and influential factors of 94 current-use pesticides among pre-pregnancy women in China.

Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells.

Stigmasterol (ST), a phytosterol found in food, has various biological activities. However, the effect of ST on milk synthesis in dairy cows remains unclear. Therefore, bovine primary mammary epithelial cells (BMECs) were isolated, cultured, and treated with ST to determine the effect of ST on milk synthesis. The study revealed that 10 µM ST significantly increased milk synthesis in BMECs by activating the mammalian target of rapamycin (mTOR) signaling pathway. Further investigation revealed that this activation depends on the regulatory role of oxysterol binding protein 5 (ORP5). ST induces the translocation of ORP5 from the cytoplasm to the lysosome, interacts with the mTOR, recruits mTOR to target the lysosomal surface, and promotes the activation of the mTOR signaling pathway. Moreover, ST was found to increase ORP5 protein levels by inhibiting its degradation via the ubiquitin-proteasome pathway. Specifically, the E3 ubiquitin ligase membrane-associated cycle-CH-type finger 4 (MARCH4) promotes the ubiquitination and subsequent degradation of ORP5. ST mitigates the interaction between MARCH4 and ORP5, thereby enhancing the structural stability of ORP5 and reducing its ubiquitination. In summary, ST stabilizes ORP5 by inhibiting the interaction between MARCH4 and ORP5, thereby activating mTOR signaling pathway and enhancing milk synthesis.

Alkali and alkaline earth elements in follicular fluid and the likelihood of diminished ovarian reserve in reproductive-aged women: a case‒control study.

BACKGROUND: Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR). METHODS: A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions. RESULTS: The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67-4.43)], Li [OR: 1.89 (1.06-3.42)], and Cs [OR: 1.97 (1.10-3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect. CONCLUSION: This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline. TRIAL REGISTRATION: Retrospectively registered.

Exposure to heavy metallic and trace essential elements and risk of diminished ovarian reserve in reproductive age women: A case-control study.

The associations between metallic elements and ovarian reserve function have remained uncertain yet. In this case-control study, we involved 149 women with diminished ovarian reserve (DOR) and 151 women with normal ovarian reserve, and assessed the levels of six heavy metallic (Cr, Cd, As, Hg, Pb, and Mn) and seven trace essential (Se, Fe, Zn, Co, Mo, Cu, I) elements in their follicular fluid with inductively coupled plasma mass spectrometry. Associations were examined with logistic regressions and Bayesian kernel machine regression (BKMR). As a result, we found that the medium and the highest tertiles of Pb were significantly associated with an increased likelihood of DOR compared to the lowest tertile, while the medium or/an the highest tertiles of Cu, I, and Fe showed significantly lower likelihoods of DOR compared to the lowest tertiles. Cu and Pb showed significantly non-linear associations with ovarian reserve markers such as follicle-stimulating, anti-mullerian hormone levels, and antral follicle count. With the rising overall concentrations of heavy metals, the likelihood of DOR increased although not significant. There was a trend of a "U-shaped" association across the whole concentration range of trace essential elements and the likelihood of DOR. Our study revealed that avoiding heavy metallic elements and properly supplementing trace essential elements are conducive to ovarian function.

Description of a new species of the genus Woznessenskia from Xizang, China (Orthoptera: Gryllacrididae).

The gryllacridid genus Woznessenskia Gorochov, 2002 comprises 13 extant species from Asia, with 8 species reported from China and 5 species reported from Vietnam. A new species from Xizang, China, Woznessenskia lianhua sp. nov., is reported in this paper.

A 49-Year-Old Man With Fever and Dyspnea After Endobronchial Ultrasound-Guided Transbronchial Fine Needle Aspiration Biopsy.

CASE PRESENTATION: A 49-year-old man, a farmer, had been experiencing coughing, phlegm, and difficulty breathing for 2 months. He underwent a CT scan at a local hospital that showed a mediastinal mass. Bronchoscopy showed no obstruction in the tracheal lumen, and an endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) biopsy was performed on the mediastinal mass. The cytologic smear of the mediastinal mass showed a few atypical epithelial cells; the possibility of a tumor could not be ruled out. The patient visited our thoracic surgery outpatient department; based on the advice of the thoracic surgeon, the patient underwent another endobronchial ultrasound-guided transbronchial fine needle aspiration biopsy of the mediastinal mass 4 days before this admission. The patient went home and waited for the results. Two days later, the patient experienced a fever and palpitations accompanied by chills, yellow phlegm, and orthopnea. The patient visited our ED, underwent tracheal intubation, and was admitted to our ICU. The patient had had occasional coughing and phlegm for the past 10 years, which were not taken seriously or investigated. The patient does not smoke or drink alcohol, and there is no history of cancer in the family.

Road extraction through Yangwang-1 nighttime light data: A case study in Wenzhou, China.

The extraction of roadways from remote sensing imagery constitutes a pivotal task, with far-reaching implications across diverse domains such as urban planning, management of transportation systems, emergency response initiatives, and environmental monitoring endeavors. Satellite images captured during daytime have customarily served as the primary resource for this extraction process. However, the emergence of Nighttime Light (NTL) remote sensing data introduces an innovative dimension to this arena. The exploration of NTL data for road extraction remains in its nascent stage, and this study seeks to bridge this gap. We present a refined U-Net model (CA U-Net) integrated with Cross-Attention Mechanisms, meticulously designed to extract roads from Yangwang-1 NTL images. This model incorporates several enhancements, thereby improving its proficiency in identifying and delineating road networks. Through extensive experimentation conducted in the urban landscape of Wenzhou City, the model delivers highly accurate results, achieving an F1 score of 84.46%. These outcomes significantly surpass the performance benchmarks set by Support Vector Machines (SVM) and the Optimal Threshold (OT) method. This promising development paves the way towards maximizing the utility of NTL data for comprehensive mapping and analysis of road networks. Furthermore, the findings underscore the potential of utilizing Yangwang-1 data as a reliable source for road extraction and reaffirm the viability of deploying deep learning frameworks for road extraction tasks utilizing NTL data.

Valine promotes milk synthesis by regulating PKM2 nuclear accumulation and histone H3 acetylation through the TAS1R1-mTOR-DDX39B signaling pathway.

Valine, a branched-chain amino acid found in dairy cows, has been recognized for its critical role in milk synthesis. However, the precise effect of valine on lactation in dairy cows remains an area of investigation. In our study, bovine mammary epithelial cells (BMECs) were isolated to explore the mechanism through which valine enhances milk synthesis. The results showed that 100 µM valine significantly boosted the milk synthesis via TAS1R1-mTOR-DDX39B signaling pathway in BMECs. Subsequent investigations revealed that DDX39B governs the accumulation of PKM2 in the nuclei of BMECs. This nuclear buildup of PKM2 weakened the interaction between HDAC3 and histone H3, leading to an increase in the acetylation levels of histone H3. In an vivo context, the 0.25 % valine-enriched drinking water notably elevated in the expression of milk protein and fat in these mice. Further examination showed that 0.25 % valine drinking water considerably augmented the protein expression levels of DDX39B, PKM2, and p-mTOR in the mice mammary glands. In summary, our results suggest that valine, by modulating the TAS1R1-mTOR-DDX39B signaling pathway, directs the accumulation of PKM2 in the nucleus. This, in turn, escalates the acetylation levels of histone H3, promoting the synthesis of both milk protein and fat.

Acylated Ghrelin Activates PI3K/mTOR Signaling Pathway by Promoting ThPOK Acetylation to Promote Milk Fat Synthesis in Bovine Mammary Epithelial Cells.

Ghrelin regulates diverse physiological activities. However, the effects of this hormone on the milk fat synthesis remain unknown. This study aimed to investigate the effect of acylated ghrelin (AG) on milk fat synthesis by modifying the expression (knockdown or overexpression) of growth hormone secretagogue receptor 1a (GHSR1a) and Th-inducing POK (ThPOK) in primary bovine mammary epithelial cells (BMECs). The results showed that AG significantly increased the triglyceride relative content from 260.83 ± 9.87 to 541.67 ± 8.38 in BMECs via GHSR1a. ThPOK functions as a key regulatory target downstream of AG, activating the PI3K and mTOR signaling pathways to promote milk fat synthesis in BMECs. Moreover, AG-regulated ThPOK by increasing the EP300 activity, which promoted ThPOK acetylation to protect it from proteasomal degradation. In conclusion, AG increases ThPOK acetylation and stabilizes ThPOK through GHSR1a, thereby activating the PI3K/mTOR signaling pathway and ultimately promoting the milk fat synthesis in BMECs.

The Long-Term Impacts of COVID-19 on Physical and Psychological Health - Beijing Municipality, China, December 2022-April 2023.

What is already known about this topic?: Reports detailing the clinical presentation of coronavirus disease 2019 (COVID-19) are extensive in China. However, data remains limited regarding the long-term effects of the 2022 outbreak on the community and healthcare workers (HCWs). What is added by this report?: In the follow-up study conducted with 1,069 community members and 3,309 HCWs infected with COVID-19, we observed that five months post-outbreak, 39.2% of community members and 28.7% of HCWs reported experiencing at least one symptom. The symptoms most frequently reported included fatigue or muscle weakness, insomnia, cognitive dysfunction, hair loss, joint or muscle pain, and persistent cough. HCWs tended to experience fewer long-term physical consequences and their symptoms had an expedited recovery time compared to the community members. Nevertheless, HCWs displayed a higher prevalence of moderate to severe depression and anxiety. What are the implications for public health practice?: The establishment of a public healthcare system dedicated to continual monitoring, prevention, and clinical treatment of persistent COVID-19 symptoms is imperative.

The impact of fibronectin knockout on invasion and migration of endometrial cell in adenomyosis.

The present study aimed to investigate the potential effect of fibronectin (FN) in adenomyosis progression. Small guide RNAs were designed to knock down FN expression in Ishikawa cells. The impact of FN on the proliferation, apoptosis, migration, and invasion of the cells was assessed. Cell proliferation was detected using a Celigo Imaging Cytometer system; apoptosis was quantified by flow cytometry; and cell migration and invasion were investigated via transwell assays. Cell proliferation was markedly suppressed in the FN knockout (KO) group compared with the control group, while apoptosis significantly increased. The levels of cell migration and invasion in the KO group were significantly decreased compared with the control group. Our study revealed that downregulation of FN expression is likely to restrain cell proliferation, migration, and invasion in endometrial cells in adenomyosis.

Sequential embryo transfer versus double cleavage-stage embryo or double blastocyst transfer in patients with recurrent implantation failure with frozen-thawed embryo transfer cycles: a cohort study.

Background: Recurrent implantation failure (RIF) is more common among patients receiving assisted reproductive treatment. Many efforts have been made to increase the incidence of clinical pregnancy among patients with RIF. The effect of the sequential transfer procedure, a two-step interval transfer of a cleavage-stage embryo followed by a blastocyst in one transfer cycle, on the clinical outcomes of RIF patients remains controversial. Methods: In total, 1774 frozen-thawed embryo transfer (FET) cycles in RIF patients were included. Of these cycles, 302 were sequential embryo transfer (ET) cycles, 979 were double day 3 cleavage-stage ET cycles, and 493 were double blastocyst ET cycles. The primary outcomes were the rates of implantation, clinical pregnancy and multiple pregnancy, and the secondary outcomes were the rates of hCG positive, early miscarriage and ectopic pregnancy. Results: The implantation, hCG positive, and clinical pregnancy rates in the sequential ET group (32.1%, 58.9%, 50.7%) were significantly higher than those in the day 3 cleavage-stage ET group (24.9%, 46.5%, 40.4%) and were similar to those in the blastocyst transfer group (30.1%, 56.4%, 47.1%). The early miscarriage rate in the blastocyst transfer group was significantly higher than that in the cleavage-stage ET group (17.2% vs. 8.1%, P <0.05), while the ectopic pregnancy rate in the blastocyst transfer group was significantly lower than that in the cleavage-stage ET group (0.4% vs. 3.0%, P <0.05). The multiple pregnancy rate in the sequential ET group was significantly lower than that in the cleavage-stage ET group (17.0% vs. 25.5%, P <0.05) and the blastocyst transfer group (17.0% vs. 27.6%, P <0.05). When cycles of blastocyst culture failure were excluded, the clinical pregnancy rate was significantly higher (55.7% vs. 47.1%, P <0.05), and the early miscarriage rate and multiple pregnancy rate were significantly lower (8.5% vs. 17.2%, 17.7% vs. 27.6%; P <0.05, respectively) in the sequential ET group than in the double blastocyst ET group. Conclusions: Sequential embryo transfer in FET cycles could improve the clinical outcomes of patients with RIF.

Metabolic Syndrome Rather Than Other Phenotypes in PCOS as a Predictive Indicator for Clinical Outcomes in IVF: Comprehensive Phenotypic Assessment across All PCOS Classifications.

Polycystic ovary syndrome (PCOS) is a well-recognized, multi-system metabolic disorder affecting fertility. Although various classification methods have been proposed to assess the phenotypic heterogeneity of PCOS, there is currently no reliable phenotype for predicting clinical IVF outcomes. This retrospective study, as a comprehensive phenotypic assessment across all PCOS classifications, aimed to identify dependable phenotypes that can serve as predictors for IVF and pregnancy outcomes. The study included 1313 PCOS patients who received their initial IVF treatment between January 2019 and December 2021. The phenotypes reflect the diverse metabolic and hormonal characteristics in this study. Phenotype A, within the Rotterdam criteria classification, exhibited the highest anti-Müllerian hormone levels (AMH), while phenotype D displayed the lowest Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) values. Both the hyperandrogenism (HA) phenotype within HA-based classification and the overweight phenotype within the body-mass-index-based classification showed increased HOMA-IR and metabolic syndrome (MetS). The MetS phenotype had higher free androgen index and a lower AMH. Notably, the MetS-based classification system demonstrated an independent association of MetS with cumulative live birth, preterm birth, and gestational diabetes mellitus as a contributing risk factor for PCOS patients undergoing IVF (p < 0.05). These findings carry noteworthy implications for advancing clinical management strategies for PCOS.

Inflammation mediates the effect of adiposity and lipid metabolism indicators on the embryogenesis of PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection.

Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine and metabolic disease affecting women of reproductive age. The low-grade chronic inflammation in PCOS is considered to be associated with obesity and dyslipidemia. We aim to investigate the potential mediating role of white blood cell (WBC) count, a representative inflammatory marker, in the effect of adiposity and lipid metabolism indicators on IVF/ICSI outcomes in PCOS women. Methods: We conducted a retrospective cohort study of 1,534 PCOS women who underwent their first IVF/ICSI cycles with autologous oocytes at a reproductive center from January 2018 to December 2020. The associations between PCOS women's adiposity and lipid metabolism indicators and WBC count and IVF/ICSI outcomes were examined using multivariable generalized linear models. Mediation analyses were conducted to evaluate the possible mediating role of WBC count. Results: We found significant dose-dependent correlations between adiposity and lipid metabolism indicators and IVF/ICSI outcomes (i.e., hormone levels on the ovulatory triggering day, oocyte development outcomes, fertilization, early embryo development outcomes, and pregnancy outcomes) (all p < 0.05), as well as between adiposity and lipid metabolism indicators and WBC count (all p < 0.001). Increasing WBC count was associated with adverse oocyte and embryonic development outcomes (all p < 0.05). Mediation analyses suggested that increasing serum TG and LDL-C levels and decreasing serum HDL-C level were significantly associated with reduced high-quality Day 3 embryo count in PCOS women, with 21.51%, 9.75%, and 14.10% mediated by WBC count, respectively (all p < 0.05). Conclusions: We observed significant associations between lipid metabolism indicators and high-quality Day 3 embryo count in PCOS women, partially mediated by inflammation-related mechanisms, suggesting the potential intervention target for improving embryo quality in PCOS women.

Maternal preconception thyroid autoimmunity is associated with neonatal birth weight conceived by PCOS women undergoing their first in vitro fertilization/intracytoplasmic sperm injection.

BACKGROUND: Thyroid autoimmunity and polycystic ovary syndrome (PCOS) are the most common endocrinopathies and have close relationships based on common etiology and pathogenesis, including genetic susceptibility, metabolic disorders, hormonal dysregulation, immune response, and inflammatory activation. The co-occurrence of both diseases is associated with adverse reproductive outcomes, but its effect on neonatal outcomes remains largely unknown. We aim to explore the effect of thyroid autoimmunity on neonatal birth weight in PCOS women undergoing IVF/ICSI. METHODS: This is a retrospective analysis of 486 PCOS women who underwent the first IVF/ICSI cycles and gave birth to 361 singletons and 125 twins during 2018 - 2020 at a reproductive center. The associations between maternal preconception serum thyroid function and autoimmunity indicators and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs) and generalized estimate equations (GEEs), respectively. Analyses were further stratified by neonatal sex, maternal age, and maternal preconception BMI to assess the possible interaction effects. RESULTS: Maternal preconception serum TPOAb had a significant negative association with singleton birth weight (P for trends = 0.03). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in singleton birth weight of - 119.72 g (95% CI: - 222.68 g, - 16.70 g). Maternal preconception serum TPOAb had a significant positive association with twin birth weight (P for trends = 0.01). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in twin birth weight of 138.62 g (95% CI: 33.96 g, 243.30 g). Besides, maternal preconception serum TPOAb had a specific association with increased twin birth weight for female neonates, a specific association with decreased singleton birth weight for PCOS women under 35 years, and a specific association with decreased twin birth weight for overweight PCOS women (all P for interactions < 0.05). CONCLUSIONS: Maternal preconception thyroid autoimmunity may affect the birth weights of both singleton and twin neonates. Further large cohorts and experimental studies are required to confirm these findings and explore the underlying mechanisms.

Adiposity and lipid metabolism indicators mediate the adverse effect of glucose metabolism indicators on oogenesis and embryogenesis in PCOS women undergoing IVF/ICSI cycles.

BACKGROUND: Polycystic ovary syndrome (PCOS) women have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are fragile to female infertility. Obesity and dyslipidemia may be the intermediate biological mechanism for the associations between glucose metabolism dysfunction and abnormal oogenesis and embryogenesis. METHODS: This retrospective cohort study was performed at a university-affiliated reproductive center. A total of 917 PCOS women aged between 20 and 45 undergoing their first IVF/ICSI embryo transfer cycles from January 2018 to December 2020 were involved. Associations between glucose metabolism indicators, adiposity and lipid metabolism indicators, and IVF/ICSI outcomes were explored using multivariable generalized linear models. Mediation analyses were further performed to examine the potential mediation role of adiposity and lipid metabolism indicators. RESULTS: Significant dose-dependent relationships were found between glucose metabolism indicators and IVF/ICSI early reproductive outcomes and between glucose metabolism indicators and adiposity and lipid metabolism indicators (all P < 0.05). Also, we found significant dose-dependent relationships between adiposity and lipid metabolism indicators and IVF/ICSI early reproductive outcomes (all P < 0.05). The mediation analysis indicated that elevated FPG, 2hPG, FPI, 2hPI, HbA1c, and HOMA2-IR were significantly associated with decreased retrieved oocyte count, MII oocyte count, normally fertilized zygote count, normally cleaved embryo count, high-quality embryo count, or blastocyst formation count after controlling for adiposity and lipid metabolism indicators. Serum TG mediated 6.0-31.0% of the associations; serum TC mediated 6.1-10.8% of the associations; serum HDL-C mediated 9.4-43.6% of the associations; serum LDL-C mediated 4.2-18.2% of the associations; and BMI mediated 26.7-97.7% of the associations. CONCLUSIONS: Adiposity and lipid metabolism indicators (i.e., serum TG, serum TC, serum HDL-C, serum LDL-C, and BMI) are significant mediators of the effect of glucose metabolism indicators on IVF/ICSI early reproductive outcomes in PCOS women, indicating the importance of preconception glucose and lipid management and the dynamic equilibrium of glucose and lipid metabolism in PCOS women.

Effects of Infertility Drug Exposure on the Risk of Borderline Ovarian Tumors: A Systematic Review and Meta-Analysis.

Whether infertility drug exposure increases the risk of borderline ovarian tumors (BOTs) remains controversial. The present study was conducted with a comprehensive search for studies published from January 1990 to December 2021 in the online databases Cochrane Library, PubMed, Web of Science and EMBASE. We considered the first diagnosis of a BOT as the primary outcome. The odds ratio (OR) was calculated with corresponding 95% confidence intervals (CIs) for the risk of BOTs in patients who were treated with infertility drugs. Ten studies, a total of 2,779,511 women, qualified for inclusion in this meta-analysis. The pooled OR of 1.56 (95% CI: 1.09-2.22) revealed a significant positive association between infertility drugs and an increased risk for BOTs, but for specific drugs, only CC plus Gn had statistical significance. No publication bias was detected using the Egger and Begg tests (p > 0.05). A significant difference in BOT incidence was observed among infertile women and nulliparous women who were treated with or without infertility drugs. In conclusion, the use of infertility drugs may increase the risk of BOTs, but a dose-dependent relationship was not observed between the number of assisted reproduction technology cycles and the risk of BOTs, and infertile women who successfully became pregnant might have a reduced risk. Registration: PROSPERO, CRD42022330775.