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Diminished ovarian reserve (DOR) is the weakening of ovarian oocyte production and quality. It will further become premature ovarian failure without timely cure. However, disease pathology and diagnostic markers are still incompletely understood. Liu-Wei-Di-Huang (LWDH) pill, a traditional Chinese medicine formula, is commonly used in the treatment of DOR in China. To explore the mechanism of the effect of LWDH on in vitro fertilization (IVF) outcomes in patients with DOR, a pseudotargeted metabolomics study combined with multivariate data processing strategy was carried out. A liquid chromatography tandem mass spectrometry-based metabolomics approach was applied to characterize metabolic biomarker candidates. Multiple pattern recognition was used to determine groups and confirm important variables. A total of 21 potential biomarkers were characterized, and related metabolic pathways were identified. The study displayed that the established pseudotargeted metabolomics strategy is a powerful approach for investigating the mechanism of DOR and LWDH. In addition, the approach may highlight biomarkers and metabolic pathways and can capture subtle metabolite changes from headache, which may lead to an improved mechanism understanding of DOR diseases and LWDH treatment.

Background The optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer. Methods Infertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles. Results A total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00–1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23–0.63, p p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99–1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98–1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47–0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46–0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups. Conclusions In women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived. Trial registration ChiCTR2000033313.

Objective. To identify the biological function and metabolic pathway of differential metabolites in follicular fluid of senile patients with kidney qi deficiency undergoing in vitro fertilization-embryo transfer (IVF-ET) and observe the effect of kidney-invigorating herbs on IVF outcomes in senile patients. Methods. A total of 95 women undergoing IVF treatment were recruited and divided into three groups, including 34 cases in the treatment group (the senile patients with kidney qi deficiency after the intervention of Chinese medicine), 31 cases in the experiment group (the senile patients with kidney qi deficiency of no intervention of Chinese medicine), and 30 cases in the control group (young women with infertility due to male factor). The three groups of women were treated with long protocol ovarian hyperstimulation; the treatment group was given Qi-Zi-Yu-Si decoction on the day of HCG downregulation. Their IVF clinical outcomes were observed. The metabolites changes of kidney qi deficiency syndrome were analyzed in follicular fluid metabolomics using liquid chromatography-mass spectrometry (UPLC-MS/MS). Results. The syndrome score of kidney qi deficiency syndrome in the treatment group was significantly improved after treatment ( P < 0.01 ). Compared with the experiment group, the available embryo rate and implantation rate were increased, and the difference was statistically significant ( P < 0.05 ). Progesterone, indoleacrylic acid, 2-propenyl 1-(1-propenylsulfinyl) propyl disulfide, N-acetyltryptophan, decanoylcarnitine, 20a-dihydroprogesterone, testosterone acetate, eicosatrienoic acid, 1H-indole-3-carboxaldehyde, choline, phosphorylcholine, and tryptophan were downregulated in the treatment group. Through pathway analysis, glycerophospholipid metabolism and steroid hormone biosynthesis were regulated in senile patients with kidney qi deficiency after Qi-Zi-Yu-Si decoction intervention. Conclusion. Qi-Zi-Yu-Si decoction can effectively improve the IVF outcome and clinical symptoms of senile patients. Follicular fluid metabolites were significantly changed in senile infertile women with kidney qi deficiency, and the mechanism by which kidney-invigorating herbs improve IVF treatment outcomes may be related to glycerophospholipid metabolism and steroid hormone biosynthesis. This study was registered in the Chinese Clinical Trials Registry Platform (ChiCTR1800014422).

ObjectiveEarly monitoring of plasma human chorionic gonadotropin (β-hCG) level is vital in predicting pregnancy outcome. This study investigated the predictive value of serum β-hCG level on the seventh day after frozen–thawed embryo transfer (FET) for ongoing pregnancy (OP) and adverse pregnancy (AP).DesignRetrospective study.SettingThe Reproductive and Genetic Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China.Participants1061 pregnant women who underwent FET between January 2014 and January 2017.Primary and secondary outcome measuresPregnancy outcome.ResultsSerum β-hCG levels on the seventh day after FET were higher in the single OP group compared with the biochemical pregnancy group (pConclusionSerum β-hCG on the seventh day after FET has good clinical significance for the prediction of OP and AP.

Hydrogen induced void nucleation of 310 stainless steel was investigated. Experimental results indicated that hydrogen promoted void nucleation. A new model of hydrogen induced void nucleation was proposed. The basic idea of this model is that hydrogen induces void nucleation not only by promoting microcrack nucleation but also by promoting the transition of microcrack to microvoid; hydrogen also increases the stability of a microvoid by forming hydrogen pressure in the microvoid and by decreasing the void surface energy.

The anisotropic behavior of fracture toughness and stress corrosion cracking of materials was analysed by fractal geometry in this paper. The results indicate that the K1c and K1scc in the S-L, L-T and L-S orientations are different and obey K S−L 1c L−T 1c L−S 1c K S−L 1scc L−T 1scc L−S 1scc .

The present work analyzes the effects of a passive film formed during stress corrosion cracking on ductile/brittle fracture behavior, considering the interaction of a screw dislocation with a thin film-covered mode III crack under an applied remote load. Exact solutions are derived, and the results show that the crack stress field due to the applied load is enhanced by a harder film or abated by a softer film. The critical stress intensity factor for dislocation emission from the crack tip is greatly influenced by both the stiffness and thickness of the filn. A dislocation is more easily to be emitted from the crack tip if the covered film has a shear modulus larger than that of the substrate. The opposite is also true, i.e., a softer film makes dislocation emission more difficult. Both phenomena become more significant when the film thickness is smaller.

The mechanisms of hydrogen promoting cleavage crack nucleation have been the subject of research for many years. Wang et al. [1] proposed a mechanism for hydrogen promoting microcrack nucleation in bcc metals. His idea was that the nucleation of a cleavage crack in bcc metals is the dislocation reaction proposed by Cottrell [2]. The core of the gliding dislocation should be saturated with hydrogen, and the dislocation will move along with the hydrogen atmosphere around it. When the two sets of gliding dislocations coalesce and form a cleavage microcrack consisting of a set of the sessile dislocation, the hydrogen atoms carried by the gliding dislocations will enter and be enriched into the microcrack, and the hydrogen pressure in the cleavage microcrack can promote the formation of a stable cleavage crack [1]. Chu et al. recently developed the formula for the threshold stress intensity of cleavage crack initiation [3]. The stress for initiation of the cleavage crack can be reduced through the cooperation of hydrogen induced local plastic deformation and hydrogen decrease of the cohesive strength. Because the formation of a cleavage crack by Cottrell's dislocation reaction mechanism described by Wang et al. [1] can only be applied to bcc metals, this mechanism cannot be used to explain cleavage crack formation in fcc or hcc metals. Although the mechanism for hydrogen promoting microcrack formation in the literature [3] can be used in various structures, it is only the stress condition for microcrack initiation. The aim of the present work was to propose a new mechanism of hydrogen induced cleavage crack nucleation by considering energy changes during cleavage crack nucleation. Most experimental observations have shown that even for brittle materials, a cleavage crack can be nucleated only when local plastic deformation develops to the critical condition [4]. Local plastic deformation leads to the formation of dislocation pile-ups. According to Stroh's calculation [5, 6], the maximum stress of the group of piled-up dislocations is