Factors affecting clinical pregnancy in controlled ovarian hyperstimulation with GnRH-a long protocol: a retrospective cross-sectional study.

This retrospective cross-sectional study was to investigate factors affecting clinical pregnancy in patients who received gonadotropin-releasing hormone agonist luteal phase long protocol (GnRH-a long protocol) and underwent fresh in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer cycle. One thousand five hundred and twenty-five patients who received GnRH-a long protocol and underwent fresh IVF/ICSI embryo transfer cycle were enrolled. The clinical pregnancy rate (63.1 vs. 22.4%, p < .05) and live birth rate (53.8 vs. 14.5%, p < .05) were significantly higher while the miscarriage rate (12.5 vs. 35.3%, p < .05) was significantly lower in the two embryo group than those in the one embryo group. The clinical pregnancy rate (48.5 vs. 64.1%, p < .05) and live birth rate (38.4 vs. 55.0%, p < .05) were significantly lower in patients older than 33.5 years than those in younger patients. The clinical pregnancy rate (52 and 60.6 vs. 79.7%, p < .05) and live birth rate (36 and 51.4 vs. 69.6%, p < .05) of the thin and mediate groups were significantly lower than those in the thick group, whereas the ectopic pregnancy rate (11.5 and 1.9 vs. 0%, p < .05) was significantly higher in the thin group than in the mediate and thick group. Multivariate logistic regression analysis showed that age (OR = 0.956, 95% CI [0.931, 0.982], p < .05), number of embryos transferred (OR = 2.491, 95% CI [1.670, 3.715], p < .05) and endometrial thickness on the transplantation day (OR = 1.124, 95% CI [1.067, 1.185], p < .05) were independent factors significantly associated with clinical pregnancy. In conclusion, endometrial thickness (>14.69 mm) on the day of transfer, two cleavage embryos transferred, and female age (≤33.5 years) are independent factors affecting clinical pregnancy outcomes in controlled ovarian hyperstimulation with GnRH-a long protocol for assisted conception. IMPACT STATEMENTWhat is already known on this subject? Fresh embryo transfer cycle with GnRH-a long protocol will result in a higher pregnancy rate in controlled ovarian hyperstimulation cycles.What do the results of this study add? Endometrial thickness on the day of transfer, number of embryos transferred, and female age were independent factors affecting clinical pregnancy outcomes.What are the implications of these findings for clinical practice and/or further research? When performing a fresh IVF/ICSI embryo transfer cycle with GnRH-a long protocol for ovulation induction, the independent affecting factors should be taken into consideration.

Jejunogastric intussusception after Whipple procedure with B-II reconstruction: a case report.

BACKGROUND: Jejunogastric intussusception (JGI) is a rare but severe complication after gastric surgery. JGI can occur from a few days to 55 years postoperatively and has a reported incidence of < 0.1% in patients who undergo gastric surgery. We firstly report a male patient with duodenal cancer who underwent Whipple's procedure with side-to-side gastrojejunostomy and who subsequently developed JGI. A literature review is provided. CASE PRESENTATION: A 68-year-old man was admitted to our emergency department with left upper quadrant abdominal pain and hematemesis of 4 h' duration. He had undergone Whipple's procedure (duct-to-mucosa pancreaticojejunostomy and side-to-side gastrojejunostomy) with B-II reconstruction for duodenal papillary adenocarcinoma 5 years earlier. His vital signs were stable with a blood pressure of 163/93 mmHg, temperature of 37.0 °C; and heart and respiratory rates of 86 per/min and 20 per/min, respectively. Physical assessment showed mild tenderness in the left upper quadrant, only. A complete blood count showed white cell and platelet counts of 11.69 × 103/L and 196 × 103/L, respectively, and a hemoglobin level of 13.5 g/L. Abdominal computed tomography (CT) suggested a retrograde intussusception of the intestines into the stomach with dilatation of the remnant stomach. The patient immediately underwent exploratory laparotomy, which revealed a 20-cm retrograde efferent limb at the remnant stomach that had travelled through the previous gastrojejunostomy. There was no evidence of malignancy. We manually reduced the intussuscepted loop using gentle traction, and the viability of the intestinal loop was preserved. The patient had an uneventful postoperative recovery. CONCLUSION: JGI is a rare but potentially fatal complication after gastric surgery, especially following Whipple's procedure. Early diagnosis and treatment are crucial, and surgery is considered the most effective treatment for JGI.

A piggyBac-based TANGO GFP assay for high throughput screening of GPCR ligands in live cells.

BACKGROUND: GPCRs are considered essential for various physiological processes and have been the most productive drug targets. Therefore, development of the methods of GPCR ligands screening is a high priority for pharmaceutical industries and research institutions. METHODS: We developed a potential method (piggyBac-TANGO) based on the TANGO and PRESTO-TANGO assays. The system was optimized with a piggyBac transposon as a transgene vehicle, and eGFP was used as a reporter instead of luciferase. The assay was validated in the HEK 293T and U87-MG cell lines and antagonist activities of the compounds were assessed. The transgene copy number and long-term stability were evaluated by qPCR. Then, we performed a DRD2-targeted screening for natural products using the piggyBac-TANGO assay. RESULTS: The validation assay showed that using the piggyBac transposon as a transgene vehicle produced high signal-to-background ratio and stable readout confirmed by investigation of the transgene copy number and long-term stability. Use of eGFP instead of luciferase as a reporter enabled to create a high throughput system suitable for live cells. Moreover, the piggyBac-TANGO assay permitted versatile detection of antagonist activity of compounds and was not limited to a particular cell type. With the use of the piggyBac-TANGO assay, we have successfully identified a novel agonist of DRD2. CONCLUSION: Thus, the results indicate that the piggyBac-TANGO method is a user-friendly, robust and imaging-based assay that provides a novel approach to high throughput GPCR-targeted ligand screening and drug development.

Iron-catalyzed radical aryldifluoromethylation of activated alkenes to difluoromethylated oxindoles.

An iron-catalyzed aryldifluoromethylation of activated alkenes under mild reaction conditions has been developed, which is a rare example where a cosolvent is used to improve the reaction yield along with Fenton's reagent and thus provides an economic and green method for the synthesis of a variety of difluoromethylated oxindoles. Preliminary mechanistic investigations indicate a radical addition path.

In vivo microdialysis for the evaluation of transfersomes as a novel transdermal delivery vehicle for cinnamic acid.

In this study, cinnamic acid-loaded transfersomes were prepared and dermal microdialysis sampling was used in Sprague-Dawley rats to compare the amount of drug released into the skin using transfersomes as transdermal carriers with that released on using conventional liposomes. The formulation of cinnamic acid-loaded transfersomes was optimized by a uniform design through in vitro transdermal permeation studies. Hydration time was confirmed as a significant factor influencing the entrapment efficiency of transfersomes, further affecting their transdermal flux in vitro. The fluxes of cinnamic acid from transfersomes were all higher than those from conventional liposomes, and the flux from the optimal transfersome formulation was 3.01-fold higher than that from the conventional liposomes (p < 0.05). An in vivo microdialysis sampling method revealed that the dermal drug concentrations from transfersomes applied on various skin regions were much lower than those required with conventional liposomes. After the administration of drug-containing transfersomes and liposomes on abdominal skin regions of rats for a period of 10 h, the Cmax of cinnamic acid from the compared liposomes was 3.21 ± 0.25 µg/mL and that from the transfersomes was merely 0.59 ± 0.02 µg/mL. The results suggest that transfersomes can be used as carriers to enhance the transdermal delivery of cinnamic acid, and that these vehicles may penetrate the skin in the complete form, given their significant deformability.

Determination of the water vapor transmission rate of cellulose-based papers by multiple headspace extraction analysis.

This paper presents a multiple headspace extraction (MHE) analysis technique to determine the water vapor transmission rate of cellulose-based papers. The water vapor passing through the sample in a closed headspace vial is determined by MHE-gas chromatography. The results show that the employed method offers good precision (the relative standard deviation < 3.49 %) and good accuracy. The method is rapid and accurate, and is promising for the determination of the water vapor transmission rate of cellulose-based papers in future studies.

Effect of Endometrium Thickness on Clinical Outcomes in Luteal Phase Short-Acting GnRH-a Long Protocol and GnRH-Ant Protocol.

Objective: To investigate the factors that influence luteal phase short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH-antagonist (GnRH-ant) protocol on pregnancy outcome and quantify the influence. About the statistical analysis, it is not correct for the number of gravidities. Methods: Infertile patients (n = 4,631) with fresh in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer were divided into GnRH-a long protocol (n =3,104) and GnRH-ant (n =1,527) protocol groups and subgroups G1 (EMT ≤7mm), G2 (7 mm 10 mm) according to EMT on the trigger day. The data were analyzed. Results: The GnRH-ant and the GnRH-a long protocols had comparable clinical outcomes in the clinical pregnancy, live birth, and miscarriage rate after propensity score matching. In the medium endometrial thickness of 7-10 mm, the clinical pregnancy rate (61.81 vs 55.58%, P < 0.05) and miscarriage rate (19.43 vs 12.83%, P < 0.05) of the GnRH-ant regime were significantly higher than those of the GnRH-a regime. The EMT threshold for clinical pregnancy rate in the GnRH-ant group was 12 mm, with the maximal clinical pregnancy rate of less than 75% and the maximal live birth rate of 70%. In the GnRH-a long protocol, the optimal range of EMT was >10 mm for the clinical pregnancy rate and >9.5 mm for the live birth rate for favorable clinical outcomes, and the clinical pregnancy and live birth rates increased linearly with increase of EMT. In the GnRH-ant protocol, the EMT thresholds were 9-6 mm for the clinical pregnancy rate and 9.5-15.5 mm for the live birth rate. Conclusions: The GnRH-ant protocol has better clinical pregnancy outcomes when the endometrial thickness is in the medium thickness range of 7-10 mm. The optimal threshold interval for better clinical pregnancy outcomes of the GnRH-ant protocol is significantly narrower than that of the GnRH-a protocol. When the endometrial thickness exceeds 12 mm, the clinical pregnancy rate and live birth rate of the GnRH-ant protocol show a significant downward trend, probably indicating some negative effects of GnRH-ant on the endometrial receptivity to cause a decrease of the clinical pregnancy rate and live birth rate if the endometrial thickness exceeds 12 mm.

High BMI and Insulin Resistance Are Risk Factors for Spontaneous Abortion in Patients With Polycystic Ovary Syndrome Undergoing Assisted Reproductive Treatment: A Systematic Review and Meta-Analysis.

Background: The risk of spontaneous abortion in patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART) is higher than that in patients without PCOS, however, no definitive risk factors have been confirmed to associate with the high spontaneous abortion rate in PCOS patients undergoing ART. This study was performed to assess the impact of relevant risk factors on spontaneous abortion in patients with PCOS. Clinical questions were formulated and organized according to the PICOS principle. Methods: A systematic review and meta-analysis were conducted on all published studies on PCOS and spontaneous abortion in Embase, PubMed, Web of Science and Cochrane Library. Related risk factors included body mass index (BMI), age, insulin resistance (IR), hyperandrogenism, and chromosome aberrations. All patients were diagnosed as PCOS using the Rotterdam criteria. The primary endpoint was miscarriage and live birth rate. Fixed-effect models were used to analyze homogeneous data, and subgroup and sensitivity analyses were performed on heterogeneous data. The source of heterogeneity was evaluated, and the random effect model was used to summarize the heterogeneity. Results: Among 1836 retrieved articles, 22 were eligible and included in the analysis with 11182 patients. High BMI (OR = 1.48, 95% CI [1.32, 1.67], MD = 1.35, 95% CI [0.58,2.12]) and insulin resistance (MD = 0.32, 95% CI [0.15, 0.49]) were associated with an increased risk of spontaneous abortion in PCOS patients undergoing ART. Older age (OR = 0.29, 95% CI [0.29, 0.44], MD = 2.01, 95% CI [0.04, 4.18]), embryonic chromosomal aberrations (OR = 0.75, 95%CI [0.31,1.77]), and hyperandrogenism (MD = 0.10, 95% CI [- 0.02, 0.22]) were not associated with the high spontaneous abortion rate in patients with PCOS. A subgroup analysis of BMI showed that there was no statistically significant difference in the effect between overweight and obesity on spontaneous abortion in PCOS patients undergoing ART (OR = 1.34, 95% [0.97, 1.85]). Conclusion: High BMI and insulin resistance are two risk factors for an increased risk of spontaneous abortion in PCOS patients undergoing ART, and losing weight and mitigating insulin resistance may decrease the spontaneous abortion rate in these patients undergoing ART.

Effects of age on pregnancy outcomes in patients with simple tubal factor infertility receiving frozen-thawed embryo transfer.

This study was to retrospectively analyze the effect of the age of embryos transfer and oocyte retrieval on the clinical pregnancy outcome in patients with simple tubal factor infertility (TFI) who received frozen-thawed embryo transfer. Patients (n = 3619) with simple TFI who underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) frozen-thawed embryo transfer at our hospital were enrolled. Univariate logistic regression analysis, categorical multivariate logistic regression analysis, curve fitting and threshold effect analysis were performed. Age of embryo transfer was a significant (P < 0.05) independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rates. The Clinical pregnancy outcome declined significantly after the age of 34 years. After limiting the female oocyte retrieval age to ≤ 34 years, no significant change was detected in the clinical pregnancy, live birth, or miscarriage rate with increase of transplantation age. In conclusion, in patients with simple TFI undergoing IVF/ICSI frozen-thawed embryo transfer, age is a significant independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rate. Aging of oocytes has a greater impact on the clinical pregnancy in women with simple TFI than the aging of the body. Patients with TFI can freeze embryos in advance to preserve fertility.

Application of Growth Hormone in in vitro Fertilization.

Growth hormone (GH) is a peptide hormone secreted mainly by the anterior part of the pituitary gland and plays a critical role in cell growth, development, and metabolism throughout the body. GH can not only directly influence human oocytes and cumulus cells but also indirectly improve oocyte quality through activating synthesis of insulin-like growth factor-I or promoting follicle-stimulating hormone-induced ovarian steroidogenesis. Since GH can regulate female and male infertility, it has been applied in the management of infertility for many years, especially in patients with poor ovarian response or poor prognosis. During ovarian stimulation, GH administration might improve the success rate of in vitro fertilization (IVF) probably through the beneficial effects of GH on oocyte quality as indicated by a higher number of mature oocytes and embryos arriving at the transfer stage and a higher fertility rate in GH-treated patients. However, there is still great controversy in the application of GH in IVF. While some researchers showed that pregnancy, implantation and live birth rates could be increased by ovarian pretreatment with GH, others did not support GH as an effective adjuvant for infertility treatment because the live birth rate was not increased. This study reviewed and summarized recent advancements and benefits in clinical application of GH, trying to reach a just unbiased conclusion regarding the effect of GH therapy in IVF.

Proteomic evaluation of urine from renal cell carcinoma using SELDI-TOF-MS and tree analysis pattern.

There is no useful marker in screening and early diagnosis for renal cell carcinomas (RCCs), especially in the urine. To screen for specific markers in the urine of RCCs patients, surface enhanced laser desorption and ionization time of flight mass spectrometry (SELDI-TOF-MS) was used and coupled with a tree analysis pattern to develop SELDI protein profiling of urine. Urine samples from 58 RCC patients, 45 healthy volunteers, and 56 patients with other urogenital diseases were analyzed using IMAC-Cu ProteinChip capable of specifically binding metal interesting proteins. Proteomic spectra were generated by mass spectrometry. Bioinformatic calculations were performed with Biomarker Wizard software 3.0 (Ciphergen). Four differentially expressed potential biomarkers from urine were identified with the relative molecular weights of 4020, 4637, 5070, and 5500. The discriminatory classifier with a panel of the four biomarkers determined in the training set could precisely detect 24 of 30 (sensitivity, 80.0%) RCC and 52 of 58 (specificity, 89.6%) non-RCC samples. Furthermore, a sensitivity of 67.8% (19/28) and a specificity of 81.4% (35/43) for the blinded test were obtained when comparing the RCC vs. non-RCC. So SELDI-TOF combined with a tree analysis pattern could potentially serve as a useful tool for diagnosis of RCC by urine samples.

Morinda officinalis How. - A comprehensive review of traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Morinda officinalisHow. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis. AIM OF THE REVIEW: This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant. METHODS: A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines. RESULTS: The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases. CONCLUSION: MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant.

Pd(0)-Catalyzed radical aryldifluoromethylation of activated alkenes.

A Pd(0)-catalyzed intramolecular aryldifluoromethylation of activated alkenes under mild reaction conditions has been developed. This reaction provides a new method for construction of a variety of difluoromethylated oxindoles. Mechanistic investigations indicate that a difluoromethyl radical, which was triggered by Pd(0), initiated the cascade sequence through an addition to the alkene.

Visible light-mediated C-H difluoromethylation of electron-rich heteroarenes.

A novel method for visible-light photoredox-catalyzed difluoromethylation of electron-rich N-, O-, and S-containingheteroarenes under mild reaction conditions is developed. Mechanistic investigation indicates that the net C-H difluoromethylation proceeds through an electrophilic radical-type pathway.