The role of acupuncture in women with advanced reproductive age undergoing in vitro fertilization-embryo transfer: A randomized controlled trial and follicular fluid metabolomics study.

BACKGROUND: The objective of this study was to determine the efficacy of acupuncture on the outcome of in vitro fertilization (IVF) in elderly infertile patients with kidney qi deficiency, and to explore its possible mechanism from the perspective of pseudo-targeted metabolomics of follicular fluid. METHODS: Sixty cases of elderly women undergoing IVF were sampled and randomly divided into 2 equal groups: the treatment and the elderly control (HA) group. In the treatment group, routine ovulation induction combined with acupuncture treatment was used. Routine ovulation induction combined with sham acupuncture was used in the HA group. Reproductive outcomes of the 2 groups were compared. The follicular fluid of patients obtained on the day of oocyte retrieval was analyzed by the ultra-high-performance liquid chromatography-mass spectrometry analysis system. RESULTS: Compared with the HA group, the score of kidney qi deficiency syndrome in the treatment group was significantly decreased, and the 2 PN fertilization rate, high-quality embryo rate and cumulative pregnancy rate were significantly increased (P < .05). Through the identification of target metabolites, 3 metabolic pathways were found to be closely related to the developmental potential of oocytes, namely: Retinol metabolism pathway; Glycine, serine, and threonine metabolism pathway; Glycerophospholipid metabolism pathway. CONCLUSION: From our findings, acupuncture can improve the quality of oocytes thus bettering the outcome of IVF-assisted pregnancy in elderly patients with kidney qi deficiency. TRIAL REGISTRATION: ChiCTR1800018329.

Transcriptomic profiling of human granulosa cells between women with advanced maternal age with different ovarian reserve.

BACKGROUND: Age-related diminished ovarian reserve (DOR) is not absolute. Some advanced maternal age (AMA) still have normal ovarian reserve (NOR) and often show better pregnancy outcomes. Exploring the transcriptomic profile of granulosa cells (GCs) in AMA could lead to new ideas for mitigating age-related diminished ovarian reserve. AIM: This study aimed to analyze the transcriptomic profile of GCs in AMA with different ovarian reserve. RESULTS: In total, 6273 statistically significant differential expression genes (DEGs) (|log2fc|> 1, q < 0.05) were screened from the two groups, among which 3436 genes were upregulated, and 2837 genes were downregulated in the DOR group. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the potential functions of dysregulated genes in AMA with DOR or NOR were predicted. The GO enrichment analysis revealed that the DEGs were mainly enriched in obsolete oxidation-reduction process, mitochondrion, metal ion binding, ATP binding, etc. The KEGG pathway enrichment analysis revealed that the above-mentioned DEGs were mainly enriched in ferroptosis, regulation of actin cytoskeleton, oxidative phosphorylation, etc. Meanwhile, verification of the mRNA expression levels of DEGs revealed the possible involvement of "ferroptosis" in age-related diminished ovarian reserve. CONCLUSIONS: From a new clinical perspective, we presented the first data showing the transcriptomic profile in GCs between AMA with different ovarian reserve. At the same time, we identified the role of ferroptosis in the GCs of AMA, providing a new biological basis for studying ovarian aging and improving pregnancy outcomes of AMA.

Comparison of two different starting dose of rhFSH in GnRH antagonist protocol for patients with normal ovarian reserve.

Objective: To evaluate different starting doses of recombinant human follicle-stimulating hormone (rhFSH) on pregnancy outcomes for patients with normal ovarian reserve during gonadotropin- releasing hormone antagonist (GnRH-ant) protocol-controlled ovarian stimulation of in vitro fertilization (IVF) cycles. Methods: In this retrospective study, a total of 1138 patients undergoing IVF cycles following the GnRH-ant protocol were enrolled. Patients were divided into two groups according to the starting dose of rhFSH. 617 patients received a starting dose of rhFSH of 150 IU, and 521 patients received a starting dose of rhFSH of 225 IU. We compared demographic characteristics, ovarian stimulation and embryological characteristics, and pregnancy and birth outcomes between the two groups. Multivariate logistic regression analysis was performed to examine the possible effects of the known potential confounding factors on pregnancy outcomes. Results: The number of oocytes retrieved in the 150 IU rhFSH group was significantly lower than those in the 225 IU rhFSH group. There was no significant difference between the two groups referring to embryological characteristics. The proportion of fresh embryo transfer in the 150 IU rhFSH group was significantly higher than that in the 225 IU rhFSH group (48.30% vs. 40.90%), and there was no difference in the risk of ovarian hyperstimulation syndrome and pregnancy outcomes between the two groups. Conclusions: In conclusion, the starting dose of rhFSH of 150 IU for ovarian stimulation has a similar pregnancy outcome as starting dose of rhFSH of 225 IU in GnRH-ant protocol for patients with normal ovarian reserve. Considering the potential cost-effectiveness and shorter time to live birth, the starting dose of rhFSH of 150 IU may be more suitable than 225 IU.

Study on the Mechanism of Action of Different Acupuncture Regimens on Premature Ovarian Failure Model Rats.

Objective: To study the mechanism of acupuncture on premature ovarian failure (POF) through the apoptosis pathway mediated by Bcl-2/Bax. Methods: POF rats were successfully obtained by cyclophosphamide. They were divided into five groups. After that, acupuncture was performed. The blank group and model group were not treated. The routine acupuncture group was acupuncture at Guanyuan, Sanyinjiao, Zhongji, and Guilai four points. The Neck-seven-acupuncture group was selected from Fengchi, Fengfu, Tianzhu, and Wangu four acupoints; the three-viscera simultaneous treatment group selected Guanyuan, Shenshu, Sanyinjiao, Taichong, and Baihui five points; and the data mining group selected Guanyuan and Sanyinjiao two points for 14 days of treatment. During the treatment, some rats were shed one after another due to the side effects of bone marrow suppression caused by mold-making. After treatment, serum estradiol (E2), follicle forming hormone (FSH), and luteinizing hormone (LH) were detected by radioimmunoassay, Bcl-2 and Bax proteins were analyzed by Western blot method, and Bcl-2 and Bax RNA were analyzed by PCR method. Results: Bcl-2 increased and Bax decreased in rats with premature ovarian failure treated with acupuncture. It shows that acupuncture can affect the secretion of ovarian-related hormones and the expression of apoptosis-related proteins, which is more significant in the conventional acupuncture point group. Conclusion: Acupuncture can inhibit the apoptosis of granulosa cells in ovarian tissue of rats with premature ovarian failure and improve ovarian function. The mechanism of its effect is to promote Bcl-2 gene expression and protein synthesis and inhibit Bax gene expression and protein synthesis. The conventional treatment group works best. This provides an experimental basis for the clinical use of acupuncture to intervene in the treatment of premature ovarian failure.

Efficacy of Acupoint Application on In Vitro Fertilization Outcome in Patients with Polycystic Ovary Syndrome: A UHPLC-MS-Based Metabolomic Study.

Objective: To explore the clinical effect of acupoint application on the outcome of in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) of the phlegm-dampness type and elucidate its possible mechanism of action from the perspective of follicular fluid metabolomics. Methods: A total of 90 patients undergoing IVF-ET due to infertility were selected and divided into three groups: the treatment group (PCOS with acupoint application, n = 30), the control group (PCOS without acupoint application, n = 30), and the normal group (non-PCOS, n = 30). All patients received a gonadotropin-releasing hormone agonist (GnRH-a) long protocol for controlled ovarian hyperstimulation (COH). Among them, the treatment group was also given the acupoint application from the day of pituitary downregulation to the day of the human chorionic gonadotrophin (hCG) trigger. Ultrahigh-performance liquid chromatography connected with quadrupole time-of-flight mass spectrometry (UHPLC-MS) was adopted for untargeted metabolomic analysis of follicular fluid collected from the three groups of patients on the day of oocyte pick-up (OPU). The significantly differential metabolites were screened using univariate and multivariate statistical analysis, and the related metabolic pathways were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Metabolomic analysis showed that the treatment group's follicular fluid samples were aggregated with the normal group and separated from the control group. A total of 34 significantly differential metabolites were found in the follicular fluid of patients with phlegm-dampness PCOS and normal people. With the intervention of acupoint application, seven metabolites (pseudouridine, phenol, 2-oxoadipic acid, 9R,10S-EpOME, DL-lactate, nicotinamide, and DL-indole-3-lactic acid) were all downregulated, mainly involving the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism. Conclusions: Acupoint application can effectively improve the clinical symptoms and the outcome of IVF-ET treatment in patients with PCOS of the phlegm-dampness type, and its mechanism of action may be related to the regulation of the pathways of pyruvate metabolism, nicotinate and nicotinamide metabolism, protein digestion and absorption, biosynthesis of amino acids, and pyrimidine metabolism.

Antibacterial, wearable, transparent tannic acid-thioctic acid-phytic acid hydrogel for adhesive bandages.

Making a hydrogel-based first-aid bandage with green resources, desirable biocompatibility, universal adhesive properties, low cost and simple production is a long-standing research aspiration. Considering this, three naturally existing organic acids, namely tannic acid, thioctic acid and phytic acid, were used to construct a novel adhesive gel (TATAPA hydrogel) for epidermal tissue bandage applications. This hydrogel could be synthesized under mild conditions with no need for a freeze-thawing shaping procedure, and was transparent, moldable and stretchable with good stability under continuous water immersion. In lap-shear tests, the TATAPA hydrogel could adhere to various hydrophilic and hydrophobic surfaces. Moreover, in the case of skin tissue adhesion, the hydrogel could be easily peeled off from the skin, meeting wearability requirements. Rheological tests showed that the hydrogel possessed thermal sensitive properties derived from multi-supramolecular interactions. The methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wound test demonstrated that the hydrogel had desirable antibacterial activity and was beneficial for wound healing. A femoral artery bleeding assay was also used to reveal that the TATAPA hydrogel could be directly pasted onto the bleeding site for hemostasis. Overall, this hydrogel demonstrates potential as a surgical bioadhesive for a broad range of medical applications.

Effectiveness of herb-partitioned moxibustion on the navel for pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer: a study protocol for a randomized controlled trial.

BACKGROUND: Recurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER), and immunity. The incidence of RIF is usually between 5 and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aims to evaluate the effectiveness and safeness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF. METHODS: This study conducts a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. No intervention will be used in the control group for 3 menstrual cycles. In the fourth menstrual cycle, all patients will undergo artificial cycle to prepare the endometrium for FET. The pregnancy outcomes will be recorded after a 3-month follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate, and clinical pregnancy rate. DISCUSSION: If the results show that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100043954 . Registered on 8 July 2021.

Efficacy and safety of acupuncture for adenomyosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Adenomyosis (AM) is a disease in which the endometrium (including glands and stroma) invades the myometrium and grows. The main clinical symptoms include menorrhagia, dysmenorrhea, chronic pelvic pain, metrorrhagia, and dyspareunia, which will seriously affect the physical and mental health of patients, and most of which occur in women of childbearing age. Acupuncture, as a special external treatment of Traditional Chinese medicine, has shown good effects in the treatment of adenomyosis. At present, there is a lack of systematic review on acupuncture in the treatment of adenomyosis. We conduct this study to evaluate the efficacy and safety of acupuncture in the treatment of adenomyosis. METHODS: We will search Chinese and English databases: Medline, Pubmed, EMBASE, Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Scientific and Journal Database, Wan Fang database (Wanfang), Chinese Biomedical Literature Database (CBM) to identify articles of randomized clinical trials of acupuncture for adenomyosis. All above electronic databases will be searched from inception to September 30, 2021. RevMan 5.3 software will be used to conduct this systematic review. No language and publication status restrictions will be applied. RESULTS: The study will prove the efficacy and safety of acupuncture for adenomyosis. CONCLUSION: We plan to submit this systematic review to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42021277136.

[Herb-separated moxibustion on navel combined with Ningmitai capsule for non-liquefaction semen with dampness and heat diffusing downward: a randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect between herb-separated moxibustion on navel combined with Ningmitai capsule and simple Ningmitai capsule for non-liquefaction semen with dampness and heat diffusing downward. METHODS: A total of 66 patients with non-liquefaction semen of dampness and heat diffusing downward were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the control group, Ningmitai capsule was given orally 3 times a day. On the basis of the control group, herb-separated moxibustion on navel was applied in the observation group, 5 moxa-cones each time, once a week. The 4-time treatment was as one course and totally 3 courses were required in the both groups. Before and after treatment, the semen quality indexes (time of semen liquefaction, sperm viability, total sperm motility, number of progressive motility sperms, sperm concentration and semen volume) and TCM syndrome score were observed, the clinical therapeutic efficacy and spouse pregnancy rate were evaluated in the two groups. RESULTS: After treatment, the time of semen liquefaction was shortened (P<0.05), the sperm viability, total sperm motility, number of progressive motility sperms, sperm concentration and semen volume were increased in the both groups (P<0.05); the time of semen liquefaction in the observation group was shorter than the control group (P<0.05), the sperm viability, total sperm motility and number of progressive motility sperms in the observation group were superior to the control group (P<0.05). After treatment, the TCM syndrome score was decreased compared before treatment in the observation group (P<0.05), and that in the observation group was lower than the control group (P<0.05). The total therapeutic effect rate and spouse pregnancy rate were 93.5% (29/31) and 67.7% (21/31) in the observation group, which were higher than 71.0% (22/31) and 41.9% (13/31) in the control group respectively (P<0.05). CONCLUSION: Herb-separated moxibustion on navel combined with Ningmitai capsule can effectively treat non-liquefaction semen with dampness and heat diffusing downward, improve the clinical symptoms, semen quality and spouse pregnancy rate, the therapeutic effect is superior to simple oral Ningmitai capsule.

Effects of moxibustion for COVID-19 convalescence: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still spreading around the world. Moxibustion, as a significant therapy in traditional Chinese medicine (TCM), has been widely used to treat COVID-19, especially in recovery period. The study will aim to assess the efficacy and safety of moxibustion for COVID-19 convalescence. METHODS: We will systematically search the relevant randomized controlled trials in the 7 databases from inception to February 2021, including PubMed, MEDLINE, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure and Chinese Biomedical Literature Database. No language and publication status restrictions will be applied. Two reviewers will independently conduct and screen all included studies and the meta-analysis will be performed with RevMan V5.3 (The Cochrane Collaboration, Oxford, England). RESULTS: The study will provide a high-quality convincing assessment of the efficacy and safety of moxibustion for the treatment of COVID-19 convalescence, which will be published in a peer-reviewed journal. CONCLUSION: Our study will give more comprehensive evidence of the effectiveness of moxibustion for COVID-19 convalescence. TRIAL REGISTRATION NUMBER: CRD42021230364.

Efficacy and safety of acupuncture for elderly patients with coronavirus disease 2019 (COVID-19): A protocol for systematic review and meta-analysis.

BACKGROUND: The study aims to evaluate the effectiveness and safety of acupuncture therapy for elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Relevant articles from December 2019 to December 2020 will be searched in the following electronic databases: Medline, PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and China Scientific Journals Database. All published randomized controlled trials (RCTs) and credible clinical observations about this topic will be included. Two independent researchers will operate article retrieval, duplication removing, screening and data analysis by EndNote X9.0 and Stata 15.0. We will use the Cochrane risk of bias tool for randomized trials to assess the risk of bias of included studies. Meta-analysis, subgroup analysis, and/or descriptive analysis will be performed according to the data conditions included. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from mortality rate, cure rate, C-reactive protein (CRP), creatine, troponin, aspartate aminotransferase, alanine aminotransferase, and improvements in chest CT scans, clinical symptoms (including fever, fatigue, cough, nausea, vomiting and diarrhea) and the side effects of acupuncture. CONCLUSION: This study will provide evidence of whether acupuncture is an effective and safe intervention for the elderly with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020225245.

Relation of Chlamydia trachomatis infections to ectopic pregnancy: A meta-analysis and systematic review.

BACKGROUND: In a multitude of previous studies, Chlamydia trachomatis (CT) plays an important role in the occurrence of ectopic pregnancy (EP). However, the predictive value of CT infections in the occurrence of EP has not been estimated worldwide. We thus evaluated, by means of a meta-analysis, the current status of the association between CT infections with EP and the potential predictive value of CT infections in EP. METHODS: We evaluated studies performed between the database construction time and August 2018 published in PubMed, the Cochrane Library, EMBASE, and the Web of Science (SCI). The relationship between CT and EP was calculated based upon the predetermined entry criteria for control group selection and the original data. The related articles were analyzed using a random-effects model, and the heterogeneity of the studies was assessed using the I index. Data were analyzed with the STATA 12.0 software. RESULTS: Twenty-five studies that recruited 11960 patients were included in the present meta-analysis, and the relation of CT infections with EP were assessed. The association between CT infections and EP risk showed an odds ratio (OR) of 3.03, with a 95% confidence interval (CI) of 2.37 to 3.89. Our results showed that there was a statistically significant difference between the intervention and control groups. The prevalence of CT infections in EP was then calculated by a subgroup analysis: African (OR, 2.22; 95% CI, 1.14-4.31), European (OR, 3.16; 95% CI, 2.10-4.47), North American (OR, 3.07; 95% CI, 1.78-5.31), and Asian (OR, 3.39; 95% CI, 1.95-5.90). CONCLUSIONS: From the results of numerous studies conducted on different continents, this meta-analysis showed a clear association between EP and prior CT infections, that is, CT infections increase the risk of EP occurrence.

Effect of duration of gonadotropin releasing hormone agonist on the outcome of in vitro fertilization-embryo transfer in a short-acting long regimen.

Objective: To investigate the effect of the duration of gonadotropin releasing hormone agonist (GnRH-a) use on the outcome of in vitro fertilization and embryo transfer (IVF-ET) during the short-acting long-term hyperstimulation cycle. Methodology: Clinical data from 776 patients receiving controlled ovarian stimulation (COS) after short-term regimen downregulation were retrospectively analyzed. According to the duration of GnRH-a, the patients were divided into 3 groups: Group A, 14 days for GnRH-a; Group B, 15-17 days for GnRH-a; and Group C, >18 days for GnRH-a. The clinical data, treatment and clinical outcomes were compared among the groups. Results: There were no significant differences in fertilization rate, implantation rate, clinical pregnancy rate, abortion rate, ovarian hyperstimulation syndrome (OHSS) rate(P > 0.05). The total costs in group A were significantly less than those in group B and C(P < 0.001). The number of eggs and quality embryos generated in group A was significantly higher than that in groups B and C (P = 0.014, P = 0.005). Conclusions: In the short-acting GnRH agonist long protocol, satisfactory IVF-ET pregnancy outcome was obtained with the use of GnRH-a for 14 days under the premise of lowering the receptor-regulating standard. Excessive application of GnRH-a will affect the number of eggs and embryos and increase the cost of medical treatment.