Metabolomics in cirrhosis: Recent advances and opportunities.

Liver cirrhosis (LC) represents a significant hepatic disorder that persistently commands the attention of the scientific community, especially concerning its pathogenesis and therapeutic approaches. Metabolomics, the comprehensive profiling of an organism's metabolome, has been increasingly applied in the research of cirrhosis over the past decade. This review summarizes the recent advancements and applications of metabolomics within the context of LC research, in recent five years. It highlights the role of metabolomics in the diagnosis of LC, the assessment of prognostic markers, and the evaluation of therapeutic outcomes. The discussion focuses on the potential and challenges of metabolomics in LC research, including the evolution of analytical technologies, advancements in bioinformatics, and the challenges impeding clinical implementation. Additionally, the review anticipates the forthcoming developments in metabolomics related to LC research, with the objective of facilitating innovative approaches for early detection and intervention in LC.

The Clinical Efficacy of Three Different Follicle-Stimulating Hormones for Follicle Growth and Development in Long-Protocol Controlled Ovarian Hyperstimulation Treatment.

OBJECTIVE: To compare the use and clinical efficacy of three different follicle-stimulating hormones (FSHs) for follicle growth and development in long-protocol controlled ovarian hyperstimulation (COH). METHODS: A total of 540 gonadotropin-releasing hormone (GnRH) agonists' long protocol treatment cycles at our hospital between January 2015 and May 2020 and met the inclusion criteria were retrospectively analyzed. The cycles were divided into three groups based on their indexes (groups A, B, and C). Each of the groups received a different type of FSH during treatment. A cross-group comparison was then undertaken to evaluate the growth and development of the three largest follicles and the patients' pregnancy-related indexes between the normal-response and high-response populations. RESULTS: In the normal-response populations, the number of high-quality embryos obtained in groups A and B was significantly higher than in group C, and the FSH dosage was significantly lower than in group C (P < 0.05). There were more follicles with a diameter of 16-18 mm found in group A than in group C on the day of hCG injection (hCG day) (P < 0.05), but there were no significant differences in the groups in other indicators. In the high-response populations, the number of oocytes retrieved and high-quality embryos obtained in group A were significantly higher than in group C (P < 0.05), and the total dosage and duration of FSH stimulation in group C were significantly higher than groups A and B (P < 0.05). CONCLUSION: Three different types of FSH led to comparable growth rates of the three largest follicles and clinical pregnancy rates per fresh cycle in long-protocol COH treatment.

Synaptotagmin 1 regulates cortical granule exocytosis during mouse oocyte activation.

Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.

[Impact of elevated basal follicle-stimulating hormone on the quantity and quality of oocytes and embryos and pregnancy outcomes in young women].

OBJECTIVE: To evaluate the effect of elevated basal follicle-stimulating hormone (FSH) on both the quantity and quality of oocytes and embryos and the clinical outcomes of pregnancy in women under 35 years of age. METHODS: A retrospective analysis was conducted for inspecting 294 in vitro fertilization-embryo transfer (IVF-ET) cycles in women under 35 years of age. According to the basal FSH levels, the women were divided into groups A, B, and C with basal FSH of 10-14.99, 15-19.99 and ≥20 IU/L, respectively, to compare the average number of oocytes retrieved, morphologies of the oocytes and embryos, and clinical outcomes of pregnancy. RESULTS: Group A showed greater average numbers of oocytes collected, total embryos and good-quality embryos with a lower gonadotrophin dose required to achieve follicular maturity than groups B and C. The 3 groups showed no significant differences in the percentage of metaphase II oocytes, optimal embryos-blastomere number, normal fertilization rate, cleavage rate, good-quality embryo rate, implantation rate, pregnancy rates, live birth rate or miscarriage rate, but the pregnancy rates and live birth rate tended to decrease in women with basal FSH ≥15 U/L. CONCLUSION: In women below 35 years of age, an elevated serum FSH (especially one ≥15 U/L) indicates diminished ovarian reserve and reduced numbers of oocyte and embryo but not poor oocyte or embryos quality, and good clinical pregnancy rate can still be expected.

[Clinical features of women with idiopathic premature ovarian failure].

OBJECTIVE: To summarize the clinical features of idiopathic premature ovarian failure (POF) and explore the early diagnosis and intervention. METHODS: A retrospective study was conducted in 39 women with idiopathic POF treated between February, 2009 and January, 2010. The clinical data of the patients including the menstrual feature, POF incidence, vaginal ultrasound and pregnancy outcomes were investigated. RESULTS: One patient had primary amenorrhea and 38 had secondary amenorrhea with an average duration of amenorrhea of 5.82 years. Abrupt cessation occurred after 1-2 menstruations following the menarche in 2 cases (5.1%) and without identifiable preceding signs in 9 cases (23%). The mean uterine and ovarian volume was significantly smaller in POF group than in the control group. Antral follicle count (AFC) was also significantly lower in POF group. Vaginal ultrasound detected at least one ovary in 89.7% and follicular activity in 79.5% of the POF patients. Evidence of ovulation was found in 12 patients, and spontaneous pregnancy occurred in 2 patients with a pregnancy rate of 5.1%. CONCLUSION: Patients with menstrual disturbance, polymenorrhea and oligomenorrhea are at risk of developing POF, in which case regular detection of the mean uterine volume, ovarian volume and AFC by vaginal ultrasound may help in early POF detection. Close monitoring can be necessary in the course of hormone replacement therapy, and timely intervention with assisted reproductive techniques may increase the chance of pregnancy.

[Prediction of ovarian reserve, poor response and pregnancy outcome based on basal antral follicle count and age in patients undergoing in vitro fertilization-embryo transfer].

OBJECTIVE: To study the value of basal antral follicle count (AFC) and age in predicting ovarian response and clinical outcome of in vitro fertilization-embryo transfer (IVF-ET). METHODS: A total of 1319 oocyte retrieval cycles in women with an AFC≤10 and complete IVF/ICSI cycles were analyzed retrospectively. According to the AFC, the patients were divided into groups A, B, and C with AFC≤4, of 5-7, and of 8-10, respectively, and each was further divided into <38 years old group and ≥38 years old group. The oocytes retrieved, ovarian response, implantation rate, cancellations, pregnancy, pregnancy loss, and live births were evaluated. RESULTS: As the AFC increased, the total gonadotrophin (Gn) dose increased and the follicles aspirated and oocytes retrieved decreased significantly (P<0.001). Patients below 38 years of age had a lower total Gn dose and more follicles aspirated and oocytes retrieved than older patients. An AFC>7 and age≥38 years was associated with significantly lower total Gn dose, greater number of follicles aspirated and oocytes retrieved, and lower pregnancy rate than an AFC≤7 and age<38 years (P<0.05). Bivariate correlation and linear regression analysis identified AFC as the best single predictor of ovarian response in IVF. The pregnancy rate differed significantly between the 3 groups, and older patients (≥38 years) had higher early miscarriage rate. CONCLUSION: Antral follicle count≤7 or age≥38 years old with AFC≤10 is the suitable threshold of diminished ovarian reserve in controlled ovarian stimulation for infertile women. Combination of AFC and age is the best predictor of ovarian response in IVF. Age has a better predictive value of pregnancy rate than AFC. AFC influences mainly the oocytes quantity, while age also affects oocyte quality.

[Clinical outcomes and birth defects resulting from intracytoplasmic sperm injection using sperms of different origins and parameters].

OBJECTIVE: To explore the quality of the embryos, clinical outcomes and birth defects resulting from intracytoplasmic sperm injection (ICSI) treatment using sperms of different origins and parameters. METHODS: A total of 980 ICSI-ET (embryo-transfer) cycles were divided into 4 groups, namely normal sperm or mild oligozoospermia group (group A), severe oligozoospermia group (group B), epididymal aspirates group (group C) and testicular biopsies group (group D). The cleavage rate, embryo quality, fertilization rate, clinical pregnancy rate, and rates of birth defects were compared between the groups. RESULTS: The fertilization rate, cleavage rate and good-quality embryo rate were not significantly different among the 4 groups (P>0.05), and the embryo implantation rate and clinical pregnancy rate were significantly higher in group C than in groups A and B (P<0.05). Groups A, B and C showed no significant differences in the rates of birth defects (P>0.05), and no birth defects occurred in group D. CONCLUSIONS: Sperms of different parameters and origins used in ICSI treatment can achieve similar fertilization rate, good-quality embryo rate and delivery rate. The embryo implantation rate and clinical pregnancy rate of epididymal sperm group are higher than those of ejaculated groups, possibly due to the younger age of the patients and a greater number of oocytes retrieved in group C than in groups A and B.