Post-trigger luteinizing hormone concentration to positively predict oocyte yield in the antagonist protocol and its association with genetic variants of LHCGR.

BACKGROUND: The concentration of human chorionic gonadotropin (hCG)/ luteinizing hormone (LH) after triggering is generally accepted as a predictor of the normal ovarian response to the trigger, but few studies have explored the distribution model of concentration and its impact on oocyte yield. Genetic variations in LHCGR, known as a receptor for hCG and LH, also play a role in oocyte maturation and retrieval. The objective of the study was to investigate the impact of concentrations of hCG/LH after triggering on oocyte yield and its association with genetic variants of LHCGR. METHODS: A retrospective cohort study including 372 antagonist IVF cycles, in which 205 received the recombinant hCG trigger and 167 received the gonadotropin-releasing hormone agonist (GnRH-a) trigger, was conducted. The post-trigger concentrations of hCG/LH and the LHCGR N312S (rs2293275) genotype were evaluated in patients to analyse the impact of these factors on oocyte yield. RESULTS: The oocyte retrieval rate (ORR) increased significantly among the low-, medium- and high-hCG-concentration groups (0.91 ± 0.25, 0.99 ± 0.23 and 1.08 ± 0.19, P < 0.001) and among the low-, medium- and high-LH-concentration groups (0.80 ± 0.29, 0.95 ± 0.21 and 1.07 ± 0.19, P < 0.001). The Pearson correlation coefficient between the post-trigger hCG concentration and ORR was 0.242 (P < 0.001), and that between the LH concentration and ORR was 0.454 (P < 0.001). After adjustment for confounding factors, high post-trigger LH concentrations remained associated with the significantly higher ORRs (adjusted R2 = 0.541, P < 0.001). Patients with the AG genotype of LHCGR N312S were more likely to have low post-trigger LH concentrations (46.10 IU/L versus 60.91 IU/L, P < 0.001) and a significantly lower ORR (0.85 versus 0.96, P = 0.042) than patients with the GG genotype after the GnRH-a trigger. CONCLUSIONS: The post-trigger LH concentration can positively predict oocyte yield in antagonist IVF cycles, and patients with the AG genotype of LHCGR rs2293275 could have a suboptimal oocyte yield using the GnRH-a trigger.

Risk factors for low oocyte retrieval in patients with polycystic ovarian syndrome undergoing in vitro fertilization.

BACKGROUND: The number of oocytes retrieved does not always coincide with the number of follicles aspirated in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Patients with high expectation of retrieval sometimes obtain few oocytes, which may be induced by improper operation or therapeutic factors. The purpose of this study was to evaluate the distribution data of oocyte retrieval rate (ORR) and to explore the risk factors for low ORR in patients with polycystic ovary syndrome (PCOS) undergoing IVF/ICSI. METHODS: A total of 2478 patients with PCOS undergoing IVF/ICSI were involved in this retrospective case-control study from March 2016 to October 2021. The oocyte retrieval rate was calculated as the ratio of the number of obtained oocytes to the number of follicles (≥ 12 mm) on the trigger day. Patients were divided into a low ORR and a normal ORR group with the boundary of one standard deviation from the mean value of ORR. The patient characteristics, treatment protocols, serum hormone levels, and embryonic and pregnancy outcomes were analyzed. RESULTS: The ORR exhibited a non-normal distribution, with a median of 0.818. The incidence of complete empty follicle syndrome was 0.12% (3/2478). The proportion of patients in the low ORR group who received the progestin-primed protocol was significantly higher than that in the normal ORR group (30.30% vs. 17.69%). A logistic regression analysis showed that the serum estradiol level/follicle (≥ 12 mm) ratio (OR: 0.600 (0.545-0.661)) and progesterone level (OR: 0.783 (0.720-0.853)) on the trigger day were significant factors in the development of a low ORR, with optimal cutoff values of 172.85 pg/ml and 0.83 ng/ml, respectively, as determined by receiver operating curve. Fewer high-quality embryos (2 vs. 5) and more cycles with no available embryos (5.42% vs. 0.43%) were found in the low ORR group. CONCLUSIONS: For patients with PCOS, low estradiol levels/follicles (≥ 12 mm) and progesterone levels on the trigger day and the use of the progestin-primed protocol could be risk factors for low ORR, which leads to a limited number of embryos and more cycle cancellations.

The roles of natural triterpenoid saponins against Alzheimer's disease.

The aging of the world population and increasing stress levels in life are the major cause of the increased incidence of neurological disorders. Alzheimer's disease (AD) creates a huge burden on the lives and health of individuals and has become a big concern for society. Triterpenoid saponins (TS), representative natural product components, have a wide range of pharmacological bioactivities such as anti-inflammation, antioxidation, antiapoptosis, hormone-like, and gut microbiota regulation. Notably, some natural TS exhibited promising neuroprotective activity that can intervene in AD progress, especially in the early stage. Recently, studies have indicated that TS play a pronounced positive role in the prevention and treatment of AD. This review discusses the recent research on the neuroprotection of TS and proceeds to detail the action mechanisms of TS against AD, hoping to provide a reference for drug development for anti-AD.

Identification of ellagic acid and urolithins as natural inhibitors of Aß25-35-induced neurotoxicity and the mechanism predication using network pharmacology analysis and molecular docking.

Ellagic acid (EA) is a dietary polyphenol that widely exists in grapes, strawberries, and walnuts. It usually exerts multiple biological activities together with its in vivo metabolites called urolithins. EA and urolithins had been proposed as natural agents for applying on the early intervention of Alzheimer's disease (AD). However, the neuroprotective effects of those small molecules have not been confirmed, and the action mechanism is not clear. Deposition of beta-amyloid (Aß) protein is well documented as being involved in the initiation and pathological process of AD. In the present study, we investigated the attenuating effects of EA and several urolithins on Aß25-35-induced neuronal injury and its underlying molecular mechanism by constructing the in vitro AD cell model of PC12 cells and primary neurons. The results revealed that EA and urolithins especially the UM5 and UM6 exerted promising neuroprotective effects in improving the Aß25-35-induced cell damage and lactate dehydrogenase (LDH) leakage, reducing reactive oxygen species (ROS) production, inhibiting neuronal apoptosis, and promoting neurite outgrowth. These results provide new insights into the development of UM5 and UM6 as anti-AD candidates. A network pharmacology analysis combining molecular docking strategy was further adopted to predict the signaling pathway involved in the anti-AD action of EA and urolithins, and the activation of PI3K-Akt, as well as the inhibition of MAPK was found to be involved.

Pharmacological effects of Eleutherococcus senticosus on the neurological disorders.

Eleutherococcus senticosus is a medicinal plant widely used in traditional medicine and edible remedies with effects on anti-fatigue, sleep improvement, and memory enhancement. Recently, the application of E. senticosus to neurological disorders has been a focus. However, its overall pharmacological effect on neural diseases and relevant mechanisms are needed in an in-depth summary. In this review, the traditional uses and the therapeutic effect of E. senticosus on the treatment of fatigue, depression, Alzheimer's disease, Parkinson's disease, and cerebral ischemia were summarized. In addition, the underlying mechanisms involved in the anti-oxidative damage, anti-inflammation, neurotransmitter modulation, improvement of neuronal growth, and anti-apoptosis were discussed. This review will accelerate the understanding of the neuroprotective effects brought from the E. senticosus, and impetus its development as a phytotherapy agent against neurological disorders.

Vmat2 heterozygous mutant mice display a depressive-like phenotype.

The vesicular monoamine transporter 2 (VMAT2) is localized primarily within the CNS and is responsible for transporting monoamines from the cytoplasm into secretory vesicles. Because reserpine (a VMAT inhibitor) can precipitate depressive-like symptoms in humans, we investigated whether Vmat2 heterozygous (HET) mice present with depressive-like behaviors. The mutants showed locomotor and rearing retardation in the open field and appeared anhedonic to 1 and 1.5% sucrose solutions. Immobility times for Vmat2 heterozygotes were prolonged in forced swim and imipramine normalized this behavior. HET animals also showed enhanced immobility in tail suspension and this response was alleviated by fluoxetine, reboxetine, and bupropion. Stimulated GTPgammaS binding indicated that alpha2-adrenergic receptors in HET hippocampus were more sensitive to UK 14,304 (5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine) stimulation than in wild type (WT) mice. In learned helplessness, mice were exposed to a shuttle box for 4 d or were given inescapable foot-shocks for the same time period. On day 5, all animals were tested in shock escape. Failure rates and the latency to escape were similar for WT and HET mice that were only pre-exposed to the test apparatus. In foot-shock groups, learned helplessness was more robust in heterozygotes than in WT controls. Basal secretion of serum corticosterone was not distinguished by genotype; however, corticosterone levels in mutants were more responsive to stress. Anxiety-like responses of WT and HET animals in the open field, light-dark exploration, zero maze, and novelty-suppressed feeding tests were indistinguishable. Collectively, these findings suggest that Vmat2 heterozygotes display a depressive-like phenotype that is devoid of anxiety-like behavior.

The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits.

A carboxypeptidase E (CPE) knockout (KO) mouse was generated by deletion of exons 4 and 5 from the CPE gene, and its phenotype was characterized. KO mice became obese by 10-12 wk of age and reached 60-80 g by 40 wk. At this age, body fat content was more than double that in the wild-type (WT) controls. The null animals consumed more food overall, were less physically active during the light phase of the light-dark cycle, and burned fewer calories as fat than WT littermates. Fasting levels of glucose and insulin-like immunoreactivity in plasma were elevated in both male and female KO mice at approximately 20 wk; males recovered fully and females partially from this state by 32 wk. At this time, insulin-like immunoreactivity in the plasma, identified as proinsulin, was 50-100 times higher than that of the WT animals. The KO mice showed impaired glucose clearance and were insulin resistant. High levels of leptin and no circulating fully processed cocaine- and amphetamine-related transcript, a peptide that is responsive to leptin-induced feedback inhibition of feeding, were found in serum. The KO mice were subfertile and showed deficits in GnRH processing in the hypothalamus. Behavioral analyses revealed that KO animals showed diminished reactivity to stimuli and had reduced muscle strength and coordination, as well as visual placing and toe-pinch reflexes. These data demonstrate that CPE KO mice display a wide range of neural and endocrine abnormalities and suggest that CPE may have additional physiological roles beyond those ascribed to peptide processing and sorting of prohormones in cells.