Comparison between the modified long gonadotropin-releasing hormone agonist protocol and the non-downregulation protocol in POSEIDON groups: a propensity score matching retrospective cohort study.

Background: In vitro fertilization (IVF) is the main technique to address the infertility issue in the patient-oriented strategy encompassing individualized oocyte number (POSEIDON) population. Adopting appropriate protocols for assisted reproduction technologies (ART) cycles in the POSEIDON group may attain more favorable pregnancy outcomes. Objectives: This study aimed to compare the effectiveness of modified long gonadotropin-releasing hormone agonist protocol and non-downregulation protocol in POSEIDON patients undergoing ART, and to identify the factors affecting the pregnancy outcomes in this group. Design: This study was designed as a propensity score-matched (PSM) retrospective analysis. Participants: The study cohort consisted of 910 patients diagnosed with ovarian hyporesponsiveness and treated by IVF from January 2020 to June 2022. They were followed up until the transfer of the last embryo of the IVF cycle and/or pregnancy at 12 weeks. The study was conducted at the Center of Reproductive Medicine, Tongji Medical College, Wuhan Union Hospital, Huazhong University of Science and Technology. Methods: The patients were divided into Group I and Group II. Group I was treated with modified long gonadotropin-releasing hormone agonist protocol while Group II was put on a non-downregulation protocol. Propensity score matching (PSM) was used to select patients for each group. The subjects were compared in terms of the baseline level, process of controlled ovarian hyperstimulation, and pregnancy outcomes. Binary logistic regression analysis was performed to assess the difference in the cumulative pregnancy rate between the two groups. Results: Of the 910 POSEIDON patients who underwent IVF, 213 received the modified long gonadotropin-releasing hormone agonist protocol and 697 were subjected to the non-downregulation protocol. From the original cohort, PSM matched 174 pairs of patients. No statistically significant difference was found in total gonadotropin (Gn) dose between the two PSM groups, but the average daily Gn dose was lower in Group I and the duration of Gn lasted longer. The number of retrieved oocytes, the number of metaphase II (MII) ooctyes retrieved, normal fertilization, and normal cleavage embryos was significantly higher in Group I than in Group II, but there existed no significant difference in the number of high-quality embryos between the two groups. The single-cycle CPR (cumulative pregnancy rate) was higher in Group I than in Group II (for Group I: before PSM, CPR = 52.6%; after PSM, CPR = 51.7%; for Group II: before PSM, CPR = 34.0%; after PSM, CPR = 34.5%), and the difference was statistically significant. A binary logistic regression analysis in the unmatched patients showed that the CPR of Group II was 0.486 times that of Group I (95% CI: 0.303 to 0.779). Conclusions: The modified long gonadotropin-releasing hormone agonist protocol can be used as an optimal protocol for IVF or ICSI (Intracytoplasmic sperm injection) in POSEIDON patients. Level of evidence: Level III.

Brown adipose tissue-derived exosomes delay fertility decline in aging mice.

Introduction: Ovarian aging has steadily grown to be a significant health issue for women as a result of the increase in average life expectancy and the postponement of reproductive age. One of the important pathological foundations of ovarian aging is formed by mitochondrial dysfunction, which causes decreases in follicle quantity and oocyte quality. In recent years, brown adipose tissue (BAT) transplantation has been proven as an effective treatment for aging-related diseases, such as ovarian aging. However, BAT transplantation is an invasive operation with long-term risks. Therefore, we need to find an alternative strategy. Methods: We injected BAT-derived exosomes into eight-month-old C57BL/6 female mice. The fertility was detected by the estrous cycle and mating test. The changes of ovary and oocyte were measured by ovarian volume, organ coefficient, follicle counting, and oocyte maturation rate. ROS level, mitochondrial membrane potential and ATP level were measured to analyze the mitochondrial function of oocytes. The changes in metabolism were explored by cold stimulation test, body weight and blood sugar. The possible molecular mechanism was further investigated by RNA sequencing. Results: In terms of fertility, the estrous cycle of aging mice after BAT-derived exosome intervention was more regular, and the number of progenies and litters was increased. At the tissue level, the ovaries in the BAT-exosome group were larger, and the number of primordial follicles, secondary follicles, antral follicles and total follicles increased. At the cellular level, BAT-derived exosomes improved the maturation of oocytes in vivo and in vitro, increased the mitochondrial membrane potential and ATP levels of oocytes, and decreased ROS levels. Besides, BAT-derived exosomes ameliorated the metabolism and viability of aging mice. Furthermore, mRNA sequencing showed that BAT exosomes altered the expression levels of genes related to metabolism and the quality of oocytes. Conclusion: BAT-derived exosomes enhanced mitochondrial function, promoted follicle survival, improved fertility, and extended ovarian lifespan in aging mice.

Frontier and Hot Topics of Pulsed Fiber Lasers via CiteSpace Scientometric Analysis: Passively Mode-Locked Fiber Lasers with Real Saturable Absorbers Based on Two-Dimensional Materials.

Pulsed fiber lasers, with high peak power and narrow pulse widths, have been proven to be an important tool for a variety of fields of application. In this work, frontier and hot topics in pulsed fiber lasers were analyzed with 11,064 articles. Benefitting from the scientometric analysis capabilities of CiteSpace, the analysis found that passively mode-locked fiber lasers with saturable absorbers (SAs) based on two-dimensional (2D) materials have become a hot research topic in the field of pulsed fiber lasers due to the advantages of self-starting operation, high stability, and good compatibility. The excellent nonlinear optical properties exhibited by 2D materials at nanometer-scale thicknesses have become a particularly popular research topic; the research has paved the way for exploring its wider applications. We summarize the performance of several typical 2D materials in ultrafast fiber lasers, such as graphene, topological insulators (TIs), transition metal dichalcogenides (TMDs), and black phosphorus (BP). Meanwhile, we review and analyze the direction of the development of 2D SAs for ultrafast fiber lasers.

Screening target genes for the treatment of PCOS via analysis of single-cell sequencing data.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a condition of the female reproductive system and it remains imperative to identify target genes responsible for its pathogenesis and develop therapeutic drugs capable of effectively treating it. METHODS: We performed primary screening, staging, functional analysis as well as screening of target genes and therapeutic drugs based on single cell sequencing data of 34 oocytes from the GEO database. RESULTS: Oxidative phosphorylation played a pivotal role in the development of oocytes, insulin resistance and ovulation disorders. At the cellular level, GV and MI phases were particularly critical for the biology of pregnancy. We screened PGR, SIRT1 and ADAMTS1 as hub differentially expressed genes (DEGs) and found relevant drugs using the Drug-Gene Interaction Database. In clinical study, oral contraceptives and insulin sensitisers were found to be effective in the treatment of PCOS. CONCLUSION: PGR, SIRT1 and ADAMTS1 were found to be down-regulated in oocytes, ovulation and female pregnancy. These 3 genes are likely biomarkers important in the treatment of PCOS. Insulin sensitiser in combination with oral contraceptive administration were found to significantly improve PCOS.Key messagesOur study used a new bioinformatics approach to find target genes for the treatment of PCOS.Our study sought to identify target genes that affect human oocyte quality by analysing single-cell sequencing data from oocytes.We testified to our data by analysing a subset of clinical data.

Target identification and drug discovery by data-driven hypothesis and experimental validation in ovarian endometriosis.

OBJECTIVE: To identify targets and discover drugs for ovarian endometriosis (OE) DESIGN: A basic study based on a data-driven hypothesis and experimental validation SETTING: Center for Reproductive Medicine PATIENT(S)/ANIMAL(S): Fourteen patients with OE and 7 healthy donors were recruited, and 15 female C57/BL6 mice were involved. INTERVENTION(S): Samples of OE lesions and normal endometrium were obtained. The ITPR1-knockdowned ectopic human endometrial stromal cells (HESCs) were subjected to ribonucleic acid (RNA) sequencing, cell-counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry. Camptothecin was administered to HESCs and in an OE mouse model. MAIN OUTCOME MEASURE(S): ITPR1 expression in OE lesions and normal endometrium, cell proliferation and apoptosis of HESCs with ITPR1 knockdown or camptothecin treatment, and autograft volume in the OE mouse model RESULT(S): Two significant OE-relevant gene modules were identified and involved the PI3K/Akt and aging-relevant pathways. Fifteen hub genes were identified and confirmed, among which the most significant gene, ITPR1, was robustly elevated in OE lesions. RNA sequencing revealed that ITPR1 was highly relevant to cell proliferation and apoptosis, which was further confirmed by CCK-8 assay, EdU staining, and flow cytometry analysis. ITPR1 knockdown inhibited cell proliferation and induced HESC apoptosis. The candidate drugs targeting these modules were screened, among which camptothecin and irinotecan were identified as promising drugs. Both compounds suppressed HESC proliferation and induced apoptosis; ITPR1 expression was suppressed by camptothecin. The therapeutic effect of camptothecin was also validated in the OE mouse model. CONCLUSION(S): This study identified the therapeutic targets and promising drugs for OE and shed light on the use of camptothecin in OE treatment.

BMMSC-sEV-derived miR-328a-3p promotes ECM remodeling of damaged urethral sphincters via the Sirt7/TGFß signaling pathway.

BACKGROUND: Stress urinary incontinence (SUI) is a common and bothersome condition. Invasive surgery will always be considered after conservative treatment fails, but the rates of postoperative complications and long-term recurrence are high. Thus, a new treatment strategy is still needed. In recent years, bone marrow mesenchymal stem cells (BMMSC) have shown great promise for SUI treatment. The therapeutic effects of BMMSC on SUI are achieved mainly by paracrine pathway signaling molecules, such as small extracellular vesicles (sEV). sEV are recognized as essential mediators of cell-to-cell communication. However, the therapeutic effects and detailed mechanisms of BMMSC-derived sEV in SUI remain mostly unexplored. METHODS: The effects of BMMSC-sEV on extracellular matrix (ECM) metabolism were assessed in vitro and in vivo. In a SUI rat model, TGF-ß1 signaling was examined with or without BMMSC-sEV stimulation. sEV miRNAs were deeply sequenced, and the most likely miRNAs were evaluated as mediators of the TGF-ß1 signaling pathway. RESULTS: BMMSC-sEV enhanced the synthesis of ECM components, including elastin, collagen I, and collagen III, and improved urethral function. Furthermore, BMMSC-sEV activated TGF-ß1 signaling in primary fibroblast cells and in rat urethras. Several differentially expressed miRNAs were identified in the BMMSC-sEV. Bioinformatics analysis and in vitro studies showed that BMMSC-sEV miR-328a-3p can be transferred from BMMSC to fibroblasts and can regulate the Sirt7/TGF-ß1 signaling pathway. CONCLUSION: BMMSC-sEV promote ECM remodeling of damaged urethral sphincters by transferring miR-328a-3p to regulate the Sirt7/TGF-ß1 signaling pathway.