Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis.

This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I2 = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I2 = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I2 = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I2 = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I2 = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENTWhat is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women.What do the results of this study add? This systematic review and meta-analysis of data from ten studies (n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls.What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.

Continuous artificial light potentially disrupts central and peripheral reproductive clocks leading to altered uterine physiology and reduced pregnancy success in albino mice.

AIMS: The mechanism behind clock coordination in female reproductive disorders is poorly understood despite the known importance of coordinated and synchronized timing of central and clocks in reproductive organs. We investigated the effect of continuous artificial light (LL) on the central and peripheral reproductive clock gene (Bmal1, Clock, Per1, Per2 and Cry1) and its downstream regulators (Hgf, PR-A and HOXA10) during non-pregnancy and pregnancy phases of female mice. MAIN METHODS: Mice (n = 60) in two sets, were maintained under continuous light (LL) and natural day cycle (LD;12L: 12D) for both non-pregnant and pregnant study. Tissues from hypothalamus-containing SCN, ovary, uterus and serum were collected at different zeitgeber time points (ZT; at 4-h intervals across 24-h periods). KEY FINDINGS: LL exposure desynchronized the expressions of the clock mRNAs (Bmal1, Clock, Per1, Per2 and Cry1) in SCN, ovary, and uterus along with Hgf mRNA rhythm. LL significantly increased the thickness of endometrial tissues. Furthermore, the pregnant study revealed lower serum progesterone level during peri- and post-implantation under LL along with downregulated expression of progesterone receptor (PR) as well as progesterone dependent uterine Homeobox A-10 (Hoxa10) proteins with lowered pregnancy outcomes. SIGNIFICANCE: Our result suggests that LL disrupted the circadian coordination between central and clock genes in reproductive tissue leading to interrupted uterine physiology and altered pregnancy in mice. This led us to propose that duration of light exposure at work-places or home for females is very important in prevention of pregnancy anomalies.

Manipulative Reduction for Abnormal Uterine Inclination in Vaginal Delivery.

OBJECTIVE: To investigate the manipulative reduction in abnormal uterine inclination in vaginal delivery. METHODS: With the independently developed uterine inclination surveyor, 40 primiparas with abnormal uterine inclination were randomly divided into two groups: treatment group (Group A, 20 cases) and control group (Group B, 20 cases). The general condition of the primipara, the labor stages, the changes in uterine inclination after treatment, postpartum hemorrhage at 2 hours, and the general condition of fetuses were observed to study the therapeutic value of manual reduction in abnormal uterine inclination. RESULT: In the control group, one uterine inclination was not corrected with the change in labor process, and the pregnancy was terminated due to stagnation of the active phase. In the first stage of labor, the time spent in the treatment group (393.4 ± 31.3 mins) was significantly lower than that in the control group (440.7 ± 34.9 mins) (P = 0.001). Compared with the control group (49.8 ± 6.5 mins), the treatment group (42.6 ± 7.2 mins) also exhibited a significantly shortened second stage of labor (P = 0.02). Sixteen cases (16/20) in the treatment group returned to normal after manual reduction, and 9 cases (9/20) in the control group returned to normal with the progression of natural labor. Manual reduction could be used as an option to treat abnormal uterine inclination (P = 0.01). There was no significant difference in the third stage of labor (P = 0.2), 2-hour postpartum hemorrhage (P = 0.35), Apgar score (P = 0.64), or body weight (P = 0.76) between the two groups. CONCLUSION: Manual reduction in the treatment of abnormal uterine inclination has obvious effects, shortens the birth process, and is safe for the fetus.

Bioactive constituents and the molecular mechanism of Curcumae Rhizoma in the treatment of primary dysmenorrhea based on network pharmacology and molecular docking.

BACKGROUND: Curcumae Rhizoma (CR) has a clinical efficacy in activating blood circulation to dissipate blood stasis and has been used for the clinical treatment of qi stagnation and blood stasis (QSBS) primary dysmenorrhea for many years. However, its molecular mechanism is unknown. OBJECTIVE: The present study aimed to demonstrate the multicomponent, multitarget and multipathway regulatory molecular mechanisms of CR in the treatment of QSBS primary dysmenorrhea. METHODS: Observations of pathological changes in uterine tissues and biochemical assays were used to confirm that a rat model was successfully established and that CR was effective in the treatment of QSBS primary dysmenorrhea. The main active components of CR in rat plasma were identified and screened by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The component-target-disease network and protein-protein interaction (PPI) network of CR were constructed by a network pharmacology approach. Then, we performed Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was adopted to verify the interactions between the core components and targets of CR to confirm the accuracy of the network pharmacology prediction results. Furthermore, we evaluated the bioactive constituents of CR and molecular mechanism of by which CR promote blood circulation and remove blood stasis via platelet tests in vivo and in vitro and Western blot analysis. RESULTS: The results of HE staining and biochemical assays of PGF2α, TXB2 and Ca2+ showed that CR was effective in the treatment of QSBS primary dysmenorrhea. A total of 36 active components were identified in CR, and 329 common targets were obtained and used to construct the networks. Of these, 14 core components and 10 core targets of CR in the treatment of primary dysmenorrhea were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the calcium, cAMP, MAPK, and PI3K-Akt signaling pathways, as well as platelet activation, which is closely related to platelet aggregation. The molecular docking results showed that the 14 core components and 10 core targets could bind spontaneously. Two core targets (MAPK1 and CCR5) and 7 core components (Isoprocurcumenol, Curcumadione, Epiprocurcumenol, (+)-Curdione, Neocurdione, Procurcumenol, and 13-Hydroxygermacrone) were closely related to CR in the treatment of primary dysmenorrhea. Furthermore, the in vivo platelet test showed that CR clearly inhibited platelet aggregation. Five core components ((+)-Curdione, Neocurdione, Isoprocurcumenol, Curcumadione and Procurcumenol) obviously inhibited platelet aggregation in vitro. In addition, based on the relationships among the signaling pathways, we confirmed that CR can effectively inhibit the expression of MAPK and PI3K-Akt signaling pathway-related proteins and decrease the protein expression levels of ERK, JNK, MAPK, PI3K, AKT and CCR5, thereby inhibiting platelet aggregation. CONCLUSION: This study demonstrated the bioactive constituents and mechanisms of CR in promoting blood circulation and removing blood stasis and its multicomponent, multitarget and multipathway treatment characteristics in primary dysmenorrhea. The results provide theoretical evidence for the development and utilization of CR.

Intraoperative local injection of uterosacral ligaments with ropivacaine during uterine surgery: A systematic review and meta-analysis of randomized controlled trials.

AIM: To perform a systematic review and meta-analysis of all randomized controlled trials that examined the efficacy of intraoperative local injection of the uterosacral ligaments with ropivacaine on postoperative pain and opioids consumption in patients undergoing uterine surgery for hysterectomy/myomectomy. METHODS: PubMed, Scopus, Web of Science and Cochrane Library databases were screened from inception to September 5th, 2020. We appraised the risk of bias using the Cochrane's risk of bias tool. Resting postoperative pain scores and cumulative consumption of postoperative opioids were regarded as continuous data, analyzed using the inverse variance method and reported as standardized mean difference (SMD) and weighted mean difference (MD), respectively, with 95 % confidence intervals (95 % CIs). RESULTS: Five studies met the inclusion criteria comprising 230 patients (117 and 113 patients received ropivacaine and placebo, respectively). The studies had an overall low risk of bias. Resting postoperative pain scores were not significantly different between both groups at 2 h (SMD = -0.30, 95 % CI [-0.70, 0.11], p = 0.15), 12 h (SMD = 0.04, 95 % CI [-0.26, 0.37], p = 0.81) and 24 h (SMD = -0.06, 95 % CI [-0.32, 0.20], p = 0.68). However, the ropivacaine group had significantly reduced cumulative opioid consumption during the first 24 h postoperatively (MD = -9.07, 95 % CI [-14.47, -3.66], p = 0.001). CONCLUSION: Intraoperative local infiltration of uterosacral ligaments with ropivacaine is technically feasible and significantly reduces postoperative opioid consumption in women undergoing gynecologic surgery of the uterus.

Mitigation of arsenic driven utero-ovarian malfunction and changes of apoptotic gene expression by dietary NAC.

An oral painless dietary therapy is also indispensable in the management of arsenic toxicity despite of its conventional painful therapeutic management. The present study focused on the management of arsenic mediated female reproductive dysfunctions by dietary therapy of N-acetyl cysteine (NAC). Here, sodium arsenite was given at the dose of 10 mg/kg body weight orally for the first 8 day. Day 9 onwards up to day 16 these arsenicated rats were provided with NAC (250 mg/kg body weight) enriched basal diet once daily. Arsenic intoxicated group exhibited a comparable inactivation of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) due to oxidative stress in reproductive organs along with a simultaneous elevation of lipid peroxidation state and decline in non-protein soluble thiols (NPSH) level in female reproductive organs. Arsenic intoxication also accomplished with the up-regulation of inflammatory markers tumour necrosis factor (TNF α) and nuclear factor κB (NF κB). Pro-apoptotic Bax gene and p53 gene expressions were also raised due to arsenic intoxication while anti-apoptotic Bcl-2 gene expression was suppressed. In fact, arsenication decreased the circulating level of vitamin B12 and folic acid. Dietary NAC supplementation significantly reversed back the activity of antioxidant enzymes in arsenite fed rats towards normalcy and also sustained the normal reproductive cyclicity, utero-ovarian histo-morphology and estradiol receptor α (ER-α) expression in these reproductive organs. Dietary NAC exerted its positive action against arsenic intoxication by up-regulation of Bcl-2 gene expression along with the suppression of pro-apoptotic Bax gene and p53 gene. Thus, dietary NAC also plays anti-apoptotic, anti-inflammatory, and anti-oxidative role against arsenic toxicity. NAC also regulates the components (vitamin B12 and folic acid) of S-adenosylmethionine pool in the way of probable removal of arsenic from the system.

Effects of modified Wenjing decoction on microcirculation in reproductive organs in rats with symptom patterns of cold coagulation and blood stasis.

OBJECTIVE: To investigate the relationship between symptom patterns of cold coagulation and blood stasis (CCBS) and microcirculation disturbance. In addition, we determined the efficacy of modified Wenjing decoction (WJD) for the treatment of CCBS. METHODS: CCBS was induced in rats with an ice-water bath treatment. The ovarian function, microvascular and circulatory status of reproductive organs, and function of local microvascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were evaluated. RESULTS: Ovarian dysfunction was observed in the rats with CCBS. It was characterized by the presence of an estrous cycle disorder and a decrease in reproductive hormone levels. Microvascular circulation disorders were associated with an imbalance in vasoconstriction, relaxation substances, nitric oxide, abnormal blood flow in whole blood, and decreased blood flow in the auricle and uterus. VECs were damaged, and VSMCs contracted and proliferated in ovarian and uterine tissues. CONCLUSION: Our findings suggest that the dysfunctional reproductive organs observed in gynecological CCBS may be closely related to the microcirculation disturbance of local tissues, microvascular contraction, and vascular remodeling. Modified WJD can be used to treat CCBS by improving microcirculation in reproductive organs.

Uterine Patterning, Endometrial Gland Development, and Implantation Failure in Mice Exposed Neonatally to Genistein.

BACKGROUND: Embryo implantation relies on precise hormonal regulation, associated gene expression changes, and appropriate female reproductive tract tissue architecture. Female mice exposed neonatally to the phytoestrogen genistein (GEN) at doses similar to those in infants consuming soy-based infant formulas are infertile due in part to uterine implantation defects. OBJECTIVES: Our goal was to determine the mechanisms by which neonatal GEN exposure causes implantation defects. METHODS: Female mice were exposed to GEN on postnatal days (PND)1-5 and uterine tissues collected on PND5, PND22-26, and during pregnancy. Analysis of tissue weights, morphology, and gene expression was performed using standard histology, confocal imaging with three-dimensional analysis, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), and microarrays. The response of ovariectomized adults to 17ß-estradiol (E2) and artificial decidualization were measured. Leukemia inhibitory factor (LIF) injections were given intraperitoneally and implantation sites visualized. Gene expression patterns were compared with curated data sets to identify upstream regulators. RESULTS: GEN-exposed mice exhibited reduced uterine weight gain in response to E2 treatment or artificial decidualization compared with controls; however, expression of select hormone responsive genes remained similar between the two groups. Uteri from pregnant GEN-exposed mice were posteriorized and had reduced glandular epithelium. Implantation failure was not rescued by LIF administration. Microarray analysis of GEN-exposed uteri during early pregnancy revealed significant overlap with several conditional uterine knockout mouse models, including Foxa2, Wnt4, and Sox17. These models exhibit reduced endometrial glands, features of posteriorization and implantation failure. Expression of Foxa2, Wnt4, and Sox17, as well as genes important for neonatal uterine differentiation (Wnt7a, Hoxa10, and Msx2), were severely disrupted on PND5 in GEN-exposed mice. DISCUSSION: Our findings suggest that neonatal GEN exposure in mice disrupts expression of genes important for uterine development, causing posteriorization and diminished gland function during pregnancy that contribute to implantation failure. These findings could have implications for women who consumed soy-based formulas as infants. https://doi.org/10.1289/EHP6336.

The phytoestrogen, quercetin, in serum, uterus and ovary as a potential treatment for dehydroepiandrosterone-induced polycystic ovary syndrome in the rat.

The exact mechanisms of polycystic ovary syndrome (PCOS) are unknown and there is no effective cure for the disease. The aim of this study was to evaluate the alterations in serum oestradiol and adiponectin levels and in the expression of some important genes in the uterine and ovarian tissues of PCOS rats. The therapeutic effect of quercetin on PCOS was also assessed. Rats were divided into five groups: control, ethanol, quercetin (Q), PCOS and PCOS+Q. After 30 days of oral treatments, the rats' ovaries and uteri were removed and nesfatin-1, aromatase and adipoR1 expressions were quantified with real-time polymerase chain reaction. Serum adiponectin and oestradiol levels were evaluated using enzyme-linked immunosorbent assay technique. The results of this study showed that expression of nesfatin-1 and adipoR1 genes and adiponectin serum levels decreased in the PCOS rats, but aromatase expression and oestradiol level increased. Treatment with quercetin increased the adiponectin level and expression of adipoR1 and nesfatin-1 and decreased both the expression of aromatase and the oestradiol level. Quercetin improved PCOS by phytoestrogenic effects and mimicking oestrogen's function. Quercetin also affects important factors in both the uterus and ovary and could improve the obesity and the diabetic and infertility symptoms of PCOS.

L-(+)-Ergothioneine Significantly Improves the Clinical Characteristics of Preeclampsia in the Reduced Uterine Perfusion Pressure Rat Model.

Preeclampsia is a multifactorial hypertensive disorder of pregnancy founded on abnormal placentation, and the resultant placental ischemic microenvironment is thought to play a crucial role in its pathophysiology. Placental ischemia because of fluctuations in the delivery of oxygen results in oxidative stress, and recent evidence suggests that mitochondrial dysfunction may be a prime mediator. However, large clinical trials of therapeutic antioxidants such as vitamins C and E for the treatment of preeclampsia have been disappointing. L-(+)-ergothioneine (ERG)-an unusual amino acid betaine derived from histidine-has important cytoprotective and antioxidant properties under conditions of high oxidative stress. In this study, we investigated the potential therapeutic effects of administration of ERG in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. ERG (25 mg/kg per day) was administered to rats on gestational day 11. On gestational day 14, RUPP surgery was performed, and on gestational day 19, blood pressure (mean arterial pressure) and fetal growth were measured. Production of mitochondria-specific H2O2 was analyzed in vivo in kidney samples. ERG ameliorated the hypertension (129±3 versus 115±4 mm Hg; P=0.01; n=8) and significantly increased pup weight in RUPP rats. ERG also significantly decreased circulating levels of antiangiogenic sFlt-1 (soluble fms-like tyrosine kinase-1) in RUPP rats (1367±245 pg/mL; P=0.04). Mitochondria-specific H2O2 (0.022±0.003 versus 0.029±0.001; MitoP/B ratio, n=3; P=0.05) was also significantly decreased in kidney tissue in RUPP rats treated with ERG. These data support the potential use of ERG for the treatment of preeclampsia.

Evaluation of uterine receptivity after gonadotropin releasing hormone agonist administration as an oocyte maturation trigger: a rodent model.

In natural cycle or minimal stimulation cycle IVF, buserelin acetate (buserelin), a gonadotropin-releasing hormone agonist, is often used as a maturation trigger; however, its effect on pregnancy outcomes remains unclear. Therefore, in the present study, we compared uterine receptivity in buserelin-administered mice with that in human chorionic gonadotropin (hCG)-administered mice during the peri-implantation period. Implantation, decidualisation, and term-pregnancy were impaired following hCG, but not buserelin administration. hCG stimulated the synthesis and secretion of progesterone and oestradiol, whereas ovarian steroidogenesis in the buserelin-treated group was comparable with that in the control group. Furthermore, similar to the observation in controls, the buserelin-treated group exhibited activation of progesterone receptor signalling and inhibition of oestrogen receptor signalling in the endometrial epithelium on the day of implantation. However, epithelial progesterone signalling was not detected, and a high expression of genes downstream to oestrogen was observed on day 4 following hCG administration. These results suggest that buserelin administration does not impact uterine receptivity as it did not affect ovarian steroidogenesis and endometrial steroid signalling. Therefore, buserelin is preferred as an oocyte maturation trigger to optimise uterine receptivity during treatments involving timed intercourse, intrauterine insemination, or fresh embryo transfer following in vitro fertilisation.

Review of Endometriosis Diagnosis through Advances in Biomedical Engineering.

Endometriosis is characterized as the ectopic presence of endometrium in various locations within the abdominal cavity, such as the fallopian tube, the pouch of Douglas, the ovaries, outside the ovaries, and more. The inner lining of the uterus, endometrium, is a dynamic tissue that undergoes morphological and functional changes cyclically. The proliferation of endometrial cells during menstruation is influenced by increasing circulating estrogen levels. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity and hence, enhanced capacity to generate endometriosis. This chronic estrogen-dependent disease is characterized by the ectopic endometrial implant. The disorder occurs in 6%-10% of reproductive-aged women and in 35%-50% of women with pelvic pain and infertility. Currently, the preferred diagnostic methods are laparoscopic inspection by transvaginal ultrasound, MRI, and sensors. Diagnoses with transvaginal ultrasound have 92.7% sensitivity and 97% specificity in detecting endometriotic lesions. On average, MRI diagnoses of DIE have 74% sensitivity and 95% specificity. Lastly, chemical sensors have 91.7% sensitivity and 90.0% specificity in detecting endometriosis. The standard of care includes personalizing the treatment plan based on the individual's set of symptoms and their severity. Advances in biomedical engineering have aided professionals in personalizing the course of treatments as well as to increasing the quality of life of these patients through various therapies for managing pain. Because no one theory provides a full explanation for the manifestation of the disease, hormonal therapies, targeted therapeutics, and surgical options have emerged as elements of disease management. Clinicians are in the process of developing advanced pharmaceutical drugs with specific orphan target receptors of the ectopic tissue. Possible complications that accompany the condition include dyspareunia, hyperalgesia, infertility, and many others.

Observation on Shenqi Fuzheng injection combined with cefoxitin sodium after cesarean section.

This paper aims to observe the effect of Shenqi Fuzheng Injection combined with cefoxitin sodium after cesarean section. Clinical data of 126 puerperae were retrospectively analyzed. They randomized into control group and treatment group, and there were 63 cases in each group. Patients in control group were given Cefoxitin Sodium treatment. And patients in treatment group were given Shenqi Fuzheng Injection on the basis of control group. After 7 days of treatment, the clinical curative effect of the two groups was observed and compared. The body temperature of the patients in treatment group was significantly decreased when compared with control group on the 2nd and 3rd day after operation (P<0.05); the first exhaust time and defecation time of patients in treatment group were significantly shortened when compared with control group (P<0.05); the postoperative hemoglobin and red blood cell count in both groups were all significantly increased when compared with before treatment (P<0.05), and the treatment group were evidently higher than control group (P<0.05); the postoperative neutrophilic granulocyte percentage, white blood cell count and lymphocytes percentage in both groups were all significantly lowered when compared with before treatment (P<0.05), and the neutrophilic granulocyte percentage, white blood cell count and lymphocytes percentage in treatment group were significantly lowered when compared with control group (P<0.05). Shenqi Fuzheng injection combined with cefoxitin sodium after cesarean section can effectively reduce the postoperative maternal body temperature and promote the recovery of maternal gastrointestinal function, which is conducive to the repair of uterus, further correct anemia after cesarean section and prevent postpartum infection. Its clinical curative effect is ideal, with certain clinical application value.

Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status.

BACKGROUND: Associations between vitamin D and pregnancy outcomes have been inconsistent. OBJECTIVES: We described the distribution of 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and 25(OH)D2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestational-age (SGA) birth, which are indicative of uteroplacental dysfunction. DESIGN: The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 52°N. Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatography-tandem mass spectrometry method. RESULTS: The mean ± SD total 25(OH)D concentration was 56.7 ± 25.9 nmol/L, and 17% and 44% of women had 25(OH)D concentrations <30 and <50 nmol/L, respectively. The prevalence of pre-eclampsia was 3.8%, and 10.7% of infants were SGA. There was a lower risk of pre-eclampsia plus SGA combined (13.6%) at 25(OH)D concentrations >75 nmol/L (adjusted OR: 0.64; 95% CI: 0.43, 0.96). The main predictors of 25(OH)D were the use of vitamin D-containing supplements (adjusted mean difference: 20.1 nmol/L; 95% CI: 18.5, 22.7 nmol/L) and summer sampling (adjusted mean difference: 15.5 nmol/L; 95% CI: 13.4, 17.6 nmol/L). Non-Caucasian ethnicity (adjusted mean difference: -19.3 nmol/L; 95% CI: -25.4, -13.2 nmol/L) and smoking (adjusted mean difference: -7.0 nmol/L; 95% CI: -10.5, -3.6 nmol/L) were negative predictors of 25(OH)D. The mean ± SD concentration of 3-epi-25(OH)D3, which was detectable in 99.9% of samples, was 2.6 ± 1.6 nmol/L. Determinants of 3-epi-25(OH)D3 were 25(OH)D3 (adjusted mean difference: 0.052 nmol/L; 95% CI: 0.050, 0.053 nmol/L) and maternal age (adjusted mean difference: -0.018 nmol/L; 95% CI: -0.026, -0.009 nmol/L). The mean ± SD concentration of 25(OH)D2 was 3.1 ± 2.7 nmol/L, which was present in all samples. No adverse effects of 25(OH)D concentrations >125 nmol/L were observed. CONCLUSIONS: In the first report to our knowledge of CDC-accredited 25(OH)D data and pregnancy outcomes from a large, clinically validated, prospective cohort study, we observed a protective association of a 25(OH)D concentration >75 nmol/L and a reduced risk of uteroplacental dysfunction as indicated by a composite outcome of SGA and pre-eclampsia. Well-designed, adequately powered randomized controlled trials are required to verify this observation. The SCOPE pregnancy cohort was registered at www.anzctr.org.au as ACTRN12607000551493.

Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrhea via attenuating uterus contraction.

ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi Fuling formula, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, is composed of Cinnamomum cassia (L.) J.Presl (Cassia bark), Poria cocos (Schw.) Wolf (Poria), Paeonia suffruticosa andrews (Moutan Cortex), Paeonia lactiflora Pall (Herbaceous peony), and Amygdalus persica L.(Persicae Semen). It has clinical efficacy of activating blood circulation to dissipate blood stasis and is commonly used for the treatment of primary dysmenorrhea. However, its therapeutic mechanism has not been clearly elucidated. The aim of this study is to reveal molecular mechanisms of action using in vivo and in vitro experimental models. MATERIAL AND METHODS: The ICR mouse uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment. Mice were given GZFLC (0.54, 1.08g/kg) by gavage. The levels of NO, PGF2α and Ca(2+) in uterine tissue were determined according to instructions. Cyclooxygenase-2 (COX-2) and oxytocin receptor (OTR) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of GZFLC on spontaneous uterine contraction, and uterine contraction induced by oxytocin, PGF2α was observed. Myometrial cells were exposed to oxytocin (5U/L) to induce calcium release, and the effect of GZFLC and its components (PL, PGG, CA) on intracellular Ca(2+) was analyzed with fluorometry imaging. RESULTS: In vivo study demonstrated that GZFLC significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 55%. It also decreased the levels of NO, PGF2α and Ca(2+) in oxytocin-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and OTR expressions in uterine tissue of dysmenorrhea mice were significantly reduced. GZFLC inhibited spontaneous uterus contractions in a dose-dependent manner, and the IC50 value was 0.99mg/ml. The IC50 values of GZFLC on PGF2α, oxytocin-induced contractions were 1.45mg/ml, 3.53mg/ml, respectively. Further in vitro studies indicated that GZFLC and its components (PL, PGG, CA) could restrain intracellular calcium levels in favour of uteri relaxation. CONCLUSIONS: Both in vivo and in vitro results indicated that GZFLC possessed a significant spasmolytic effect on uterine tetanic contraction. The present study provides in vivo and in vitro experimental evidence to support the use of GZFLC for the clinical treatment of primary dysmenorrheal (PD).

Ge-Gen Decoction attenuates oxytocin-induced uterine contraction and writhing response: potential application in primary dysmenorrhea therapy.

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

Vitamin D supplementation improves pathophysiology in a rat model of preeclampsia.

Deficiency of vitamin D (VD) is associated with preeclampsia (PE), a hypertensive disorder of pregnancy characterized by proinflammatory immune activation. We sought to determine whether VD supplementation would reduce the pathophysiology and hypertension associated with the reduced uterine perfusion pressure (RUPP) rat model of PE. Normal pregnant (NP) and RUPP rats were supplemented with VD2 or VD3 (270 IU and 15 IU/day, respectively) on gestation days 14-18 and mean arterial pressures (MAPs) measured on day 19. MAP increased in RUPP to 123 ± 2 mmHg compared with 102 ± 3 mmHg in NP and decreased to 113 ± 3 mmHg with VD2 and 115 ± 3 mmHg with VD3 in RUPP rats. Circulating CD4+ T cells increased in RUPP to 7.90 ± 1.36% lymphocytes compared with 2.04 ± 0.67% in NP but was lowered to 0.90 ± 0.19% with VD2 and 4.26 ± 1.55% with VD3 in RUPP rats. AT1-AA, measured by chronotropic assay, decreased from 19.5 ± 0.4 bpm in RUPPs to 8.3 ± 0.5 bpm with VD2 and to 15.4 ± 0.7 bpm with VD3. Renal cortex endothelin-1 (ET-1) expression was increased in RUPP rats (11.6 ± 2.1-fold change from NP) and decreased with both VD2 (3.3 ± 1.1-fold) and VD3 (3.1 ± 0.6-fold) supplementation in RUPP rats. Plasma-soluble FMS-like tyrosine kinase-1 (sFlt-1) was also reduced to 74.2 ± 6.6 pg/ml in VD2-treated and 91.0 ± 16.1 pg/ml in VD3-treated RUPP rats compared with 132.7 ± 19.9 pg/ml in RUPP rats. VD treatment reduced CD4+ T cells, AT1-AA, ET-1, sFlt-1, and blood pressure in the RUPP rat model of PE and could be an avenue to improve treatment of hypertension in response to placental ischemia.

Uterine Tonus Assessment by Midwives versus Patient self-assessment in the active management of the third stage of labor (UTAMP): study protocol for a randomized controlled trial.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and accounts for one third of maternal deaths in low-income and middle-income countries. PPH can be prevented by active management of the third stage of labor (AMTSL), a series of steps recommended by the World Health Organization to be performed by skilled birth attendants (SBAs). Task shifting in the AMTSL step of uterotonic drugs administration to community health workers, traditional birth attendants and self-administration has been investigated as a strategy to increase access to quality obstetric care considering persistent SBA and facility-based delivery shortages. The aim of this study is to assess task shifting in the final step of AMTSL and compare uterine tonus assessment by a SBA to self-assessment. METHODS AND DESIGN: The study is an individual-level two-arm non-inferiority randomized controlled trial (RCT). A total of 800 women will be recruited in Korle Bu Teaching Hospital in Accra, Ghana. Adult women in labor at term with an expected vaginal delivery who received antenatal instructions for self-assessment of uterine tonus will be eligible for inclusion. Women with an increased risk for PPH will be excluded. Women will be randomized to uterine tone assessment by a skilled birth attendant (midwife) or uterine tone self-assessment (with the safety back-up of a midwife present in case of PPH or uterine atony). Postpartum blood loss will be measured through weighing of disposable mats. The main study endpoints are PPH (≥500 ml blood loss), severe PPH (≥1000 ml blood loss), mean blood loss, and routine maternal and neonatal outcomes. Participants and caregivers will not be blinded given the nature of the intervention. DISCUSSION: A reduction of PPH-related maternal mortality requires full implementation of AMTSL. Task shifting of uterine tone assessment may contribute to increased AMTSL implementation in (clinical) settings where SBAs capacity is constrained. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02223806 , registration August 2014. PACTR: PACTR201402000736158 , registration July 2014. University of Ghana, Medical School Ethical and Protocol Review Committee: MS-Et/M.8-P4.1/2014-2015.

[Dynamics of the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis under effect of contrast massage].

The objective of the present work was to study the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis before and after a course of contrast massage. Three types of functional changes in the microcirulation system were distinguished based on the results of laser-assisted Doppler flowmetry. All of them were characterized by high coefficients of correlation with the results of dopplerometry of uterine blood flow and underwent dynamic changes in the course of the treatment. The study has demonstrated the high therapeutic effectiveness of the contrast massage technique as a tool for inducing hemodynamic changes in the small pelvis basin in the women suffering from chronic endometritis.

[Clinical research on acupoint catgut implantation in the prevention and treatment of postpartum pain of uterine contraction with qi and blood deficiency].

OBJECTIVE: To observe the impacts of the acupoint catgut implantation on postpartum pain of uterine contraction with qi and blood deficiency. METHODS: One hundred and ten primiparas of natural delivery differentiated as qi and blood deficiency pattern in TCM were selected as the subjects. They were randomized into an acupoint catgut implantation group (55 cases) and a routine nursing group (55 cases). In the acupoint catgut implantation group, the catgut was implanted in Zigong (EX-CA 1), Zusanli (ST 36), Sanyinjiao (SP 6), Pishu (BL 20) and Geshu (BL 17) in 6 h after delivery; additionally, the routine post-delivery nursing was adopted. In the routine nursing group, the routine post-delivery nursing was applied simply. Visual analogue scale (VAS) and the pain relief time of uterine contraction were compared in 24 h, 48 h, 72 h and 96 h after acupoint catgut implantation between the two groups. RESULTS: VAS Scores in 24 h, 48 h, 72 h and 96 h after acupoint catgut implantation in the acupoint catgut implantation group were lower apparently than those in the routine nursing group (3.31 +/- 0.39 vs 4.31 +/- 0.29, 1.86 +/- 0.29 vs 2.66 +/- 0.25, 0.89 +/- 0.21 vs 1.59 +/- 0.24, 0.35 +/- 0.10 vs 0.69 +/- 0.13, all P < 0.05). The pain relief was achieved in (72.06 +/- 6.83) h in the acupoint catgut implantation group and was (123.42 +/- 11.12) h in the routine nursing group. The pain relief in the acupoint catgut implantation group was achieved more quickly (P < 0.01). CONCLUSION: The intervention of acupoint catgut implantation in 6 h after natural delivery in primiparas prevents effectively postpartum pain of uterine contraction.