RESUMO
BACKGROUND: Serum uric acid levels are elevated in polycystic ovary syndrome, however, the relationship between serum uric acid level and reproductive outcomes in women with polycystic ovary syndrome remains unclear. OBJECTIVE: This study aimed to investigate the association between serum uric acid level and the reproductive outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles. STUDY DESIGN: This was a retrospective cohort study performed at a university-affiliated reproductive medicine center. A total of 1903 women with polycystic ovary syndrome undergoing their first in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles between January 2010 and January 2021 were initially included. The trends for reproductive outcomes in polycystic ovary syndrome across quartiles of serum uric acid levels were assessed. A logistic regression analysis was performed to obtain the odds ratios for in vitro fertilization outcomes based on the quartiles of serum uric acid with or without adjusting for potential confounding variables. Using generalized additive models, serum uric acid was further treated as its original continuous property to visualize its nonlinear relationship with in vitro fertilization outcomes. The live birth rate was the main outcome. RESULTS: After exclusions, a total of 883 women with polycystic ovary syndrome with their first fresh-embryo transfer cycles were included. In quartiles of serum uric acid levels, there was a significant decreasing trend in the live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4: 45.9%) (Ptrend=.002). The percentage of low birthweight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend=.049). Compared with those in Q1, women in Q4 showed a significant lower probability of live birth and clinical pregnancy and a higher risk for low birthweight (all P<.05). Both the unadjusted and adjusted generalized additive models indicated that as the serum uric acid level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk for low birthweight showed an increasing profile. CONCLUSION: An elevated serum uric acid level is associated with decreased probabilities of live birth and clinical pregnancy and an increased risk for low birthweight in women with polycystic ovary syndrome. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.
Assuntos
Síndrome do Ovário Policístico , Gravidez , Masculino , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Injeções de Esperma Intracitoplásmicas , Ácido Úrico , Estudos Retrospectivos , Peso ao Nascer , Sêmen , Fertilização in vitro/efeitos adversos , Transferência Embrionária , Nascido Vivo/epidemiologia , Taxa de GravidezRESUMO
BACKGROUND: The prevalecne of hyperuricemia in polycystic ovary syndrome (PCOS) is still uncertain. We aimed to investigate the prevalence of hyperuricemia in PCOS and to determine the influence of reproductive hormones on uric acid concentration. METHODS: This retrospective cross-sectional study was performed at a large reproductive medicine center. Between March 2007 and October 2016, a total of 1,183 women with PCOS and 10,772 women without PCOS were included. PCOS was diagnosed according to the Rotterdam criteria. Anthropometric parameters, blood pressure, uric acid, reproductive hormones, glucose and lipids were measured in all subjects. RESULTS: The serum uric acid (SUA) level was higher in women with PCOS than in women without PCOS. The prevalence of hyperuricemia in women with PCOS (25.48%) was significantly higher than that in women without PCOS (8.74%). Analysis stratified for age and body mass index (BMI) showed that both the SUA level and the prevalence of hyperuricemia were higher in women with PCOS of different age and BMI groups than in women without PCOS. After adjusting for age, BMI and estimated glomerular filtration rate (eGFR), logistic regression analysis revealed that the luteinizing/follicle-stimulating hormone (LH/FSH) ratio (odds ratio (OR) = 1.20, 95% CI = 1.01-1.43) and testosterone level (OR = 1.56, 95% CI = 1.27-1.90) were positively associated with the prevalence of hyperuricemia in females with PCOS. CONCLUSIONS: The serum uric acid (SUA) level and the prevalence of hyperuricemia markedly increased in women with PCOS. The testosterone level was positively associated with the SUA level and the prevalence of hyperuricemia in females with PCOS.
Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hiperuricemia/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Testosterona/sangue , Adulto , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiperuricemia/epidemiologia , Prevalência , Estudos Retrospectivos , Ácido Úrico/sangueRESUMO
Ovarian cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely used in locally advanced ovarian cancer patients. Acquired or de novo cisplatin resistance remains the barrier to patient survival, and the mechanisms of cisplatin resistance are still not well understood. In the current study, we found that colony-stimulating-factor-1 receptor (CSF-1R) was upregulated in cisplatin-resistant SK-OV-3 and CaoV-3 cells. Colony-stimulating-factor-1 receptor knockdown suppressed proliferation and enhanced apoptosis in cisplatin-resistant SK-OV-3 and CaoV-3 cells. However, CSF-1R overexpression had inverse effects. While parental SK-OV-3 and CaoV-3 cells were more resistant to cisplatin after CSF-1R overexpression, CSF-1R knockdown in SK-OV-3 and CaoV-3 cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that CSF-1R significantly promoted active AKT and ERK1/2 signalling pathways in cisplatin-resistant cells. Furthermore, a combination of cisplatin and CSF-1R inhibitor effectively inhibited tumour growth in xenografts. Taken together, our results provide the first evidence that CSF-1R inhibition can sensitize cisplatin-refractory ovarian cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumours.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
OBJECTIVE: To investigate the composition, function, and regulatory mechanisms of the secreted phosphoprotein 1 (SPP1) gene in metastatic prostate cancer. METHODS: We obtained the data about the whole genomic expression profiles on prostate cancer metastasis from the GEO database, and performed data-mining and bioinformatic analysis using BRB-Array Tools and such softwares as Protparam, MotifScan, SignalP 4.0, TMHMM, NetPhos2.0, PredictProtein, GO, KEGG, and STRING. RESULTS: Totally, 73 co-expressed differential genes in prostate cancer metastasis were identified, 21 up-regulated and 52 down-regulated (P <0.01). Bioinformatic analysis indicated that the highly expressed SPP1 gene encoded 314 amino acids and contained 2 N-glycosylation sites, 8 casein kinase II phosphorylation sites and 3 protein kinase C phosphorylation sites, playing essential roles in extracellular matrix (ECM) binding, ossification, osteoblast differentiation, cell adhesion, PI3K-Akt signaling pathway, focal adhesion, Toll-like receptor signaling pathway, and ECM-receptor interaction. CONCLUSION: The bioinformatic method showed a high efficiency in analyzing microarray data and revealing internal biological information. SPP1 may play an important role in prostate cancer metastasis and become a novel biomarker for the diagnosis of prostate cancer metastasis and a new target for its treatment.
Assuntos
Osteopontina/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Biologia Computacional , Mineração de Dados , Regulação para Baixo , Humanos , Masculino , Análise em Microsséries , Osteopontina/química , Osteopontina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismoRESUMO
BACKGROUND: Various methods for ex utero culture systems have been explored. However, limitations remain regarding the in vitro culture platforms used before implanting mouse embryos and the normal development of mouse blastocysts in vitro. Furthermore, vascular niche support during mouse embryo development from embryonic day (E) 3.5 to E7.5 is unknown in vitro. METHODS: This study established a three-dimensional (3D) "sandwich" vascular niche culture system with in vitro culture medium (IVCM) using human placenta perivascular stem cells (hPPSCs) and human umbilical vein endothelial cells (hUVECs) as supportive cells (which were seeded into the bottom layer of Matrigel) to test mouse embryos from E3.5 to E7.5 in vitro. The development rates and greatest diameters of mouse embryos from E3.5 to E7.5 were quantitatively determined using SPSS software statistics. Pluripotent markers and embryo transplantation were used to monitor mouse embryo quality and function in vivo. RESULTS: Embryos in the IVCM + Cells (hPPSCs + hUVECs) group showed higher development rates and greater diameters at each stage than those in the IVCM group. Embryos in the IVCM + Cells group cultured to E5.5 morphologically resembled natural egg cylinders and expressed specific embryonic cell markers, including Oct4 and Nanog. These features were similar to those of embryos developed in vivo. After transplantation, the embryos were re-implanted in the internal uterus and continued to develop to a particular stage. CONCLUSIONS: The 3D in vitro culture system enabled embryo development from E3.5 to E7.5, and the vascularization microenvironment constructed by Matrigel, hPPSCs, and hUVECs significantly promoted the development of implanted embryos. This system allowed us to further study the physical and molecular mechanisms of embryo implantation in vitro.
Assuntos
Desenvolvimento Embrionário , Células Endoteliais , Gravidez , Feminino , Humanos , Animais , Camundongos , Técnicas de Cocultura , Implantação do Embrião , Transferência Embrionária/métodos , Técnicas de Cultura Embrionária/métodosRESUMO
PURPOSE: The present study was designed to compare the efficiency of the progestin-primed ovarian stimulation (PPOS) protocol with clomiphene citrate (CC) supplementation (PPOS+CC) and the standard PPOS protocol for women of different ages with diminished ovarian reserve (DOR). PATIENTS AND METHODS: This retrospective cohort study included 364 DOR women who underwent controlled ovarian stimulation with PPOS+CC (n = 223) or standard PPOS (n = 141). They were divided into subgroups based on age: ≤35 years and >35 years. Differences in baseline characteristics, ovarian stimulation characteristics, endocrinological characteristics, and clinical outcome between the two groups were assessed. Statistical analyses were stratified by age. RESULTS: In all women with DOR, PPOS+CC was associated with a lower percentage of women with profound pituitary suppression than standard PPOS (0.0% vs 18.6%, P < 0.001 and 1.3% vs 11.0%, P = 0.002). In young women with DOR, more high-quality cleavage-stage embryos were harvested (1.96 vs 1.38, P = 0.018) and a lower dosage of gonadotropin per oocyte retrieved was required (558.37 vs 909.82, P = 0.036) in PPOS+CC. In older women with DOR, PPOS+CC led to an increase in the incidence of luteinizing hormone (LH) surge levels above 10 IU/L on trigger day (12.7% vs 4.9%, P = 0.028) and a decrease in the rate of oocyte maturation (84.7% vs 89.9%, P = 0.034) compared to standard PPOS. CONCLUSION: Clomiphene citrate is an effective adjuvant to alleviate pituitary suppression in PPOS protocols; for young women with DOR, CC supplementation had a positive impact on the number of high-quality embryos. However, older women with DOR would be at risk of developing a premature LH surge and having poor oocyte maturation rate under the PPOS+CC protocol.
Assuntos
Clomifeno/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Indução da Ovulação/métodos , Progestinas/administração & dosagem , Adulto , Fatores Etários , Feminino , Fertilização in vitro , Humanos , Estudos RetrospectivosRESUMO
Objective: The primary objective of the study was to assess traditional Chinese formula DKP supplementation in terms of efficacy and safety on reproductive outcomes of expected poor ovarian responder (POR, POSEIDON Group 4) undergoing in vitro fertilization-embryo transfer (IVF-ET). Design Setting and Participants: Women eligible for IVF-ET were invited to participate in this randomized, double-blind, placebo-controlled, superiority trial at academic fertility centers of ten public hospitals in Chinese Mainland. A total of 462 patients (35-44 years) equally divided between DKP and placebo groups with antral follicle count (AFC) <5 or anti-müllerian hormone (AMH) <1.2 ng/ml were randomized. Interventions: All participants were given DKP or 7 g placebo twice daily on the previous menstrual cycle day 5 until oocyte retrieval, which took approximately 5 to 6 weeks. Main Outcome Measure: The primary outcome was the ongoing pregnancy defined as more than 20 gestational weeks of an intrauterine living fetus confirmed by pelvic ultrasonography. Results: Demographic characteristics were equally distributed between the study populations. Intention-to-treat (ITT) analysis revealed that ongoing pregnancy rate (OPR) was not significantly different between DKP and placebo groups [26.4% (61/231) versus 24.2% (56/231); relative risk (RR) 1.09, 95% confidence interval (CI) 0.80 to 1.49, P = 0.593]. No significant differences between groups were observed for the secondary outcomes. The additional per protocol (PP) analysis was in line with ITT results: OPR in DKP group was 27.2% (61/224) versus 24.1% (55/228) in placebo group [RR 1.13, 95%CI (0.82 to 1.55), P = 0.449]. After subgroup analysis the findings concluded that POR population of 35-37 years had a significantly higher OPR after 5-6 weeks of oral DKP (41.8%, 33/79) versus placebo (25.4%, 18/71) [RR 1.65, 95% CI (1.02 to 2.65), P = 0.034, P for interaction = 0.028]. Conclusion: This well-designed randomized controlled trial (RCT) offers new high-quality evidence to supplement existing retrospective literature concerning DKP performance in expected PORs. DKP could be recommended as a safe and natural remedy for expected PORs (aged 35-37 years) who fulfill the POSEIDON group 4 criteria. However, additional interventional clinical studies are undoubtedly required to be conducted in the future to validate this hypothesis. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1900026614.
Assuntos
Transferência Embrionária/métodos , Fertilização in vitro/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Indução da Ovulação/normas , Adulto , China/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Infertilidade Feminina/epidemiologia , Recuperação de Oócitos , Gravidez , Taxa de Gravidez , PrognósticoRESUMO
Background: The aim of this retrospective study was to analyze the association between prolactin (PRL) and metabolic parameters in infertile patients with polycystic ovary syndrome (PCOS). Methods: A total of 2,052 patients with PCOS and 9,696 patients with tubal infertility (non-PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET) at the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University from January 2007 to July 2017 were enrolled in this study. Serum PRL, basic endocrine hormones, fasting plasma lipid, fasting plasma glucose (FPG), liver function, thyroid hormone and other parameters were measured and analyzed. Result: PRL levels were significantly lower in PCOS patients than controls over all age groups (p < 0.05). In the PCOS patients, serum PRL was significantly and positively correlated with FPG, serum TSH and serum FT4, and significantly and negatively correlated with LH, LH/FSH, TC, TG, LDL-C, AST, ALT, γ-GGT, FT3, and FT3/FT4 (p < 0.05 or 0.01). After adjusted for age and body mass index (BMI), serum PRL was positively correlated with FPG, TSH, and FT4, and negatively correlated with LH and LH/FSH. Conclusion: Low serum PRL may be an important cause of metabolic risk in infertile patients with PCOS.
Assuntos
Biomarcadores/sangue , Infertilidade Feminina/complicações , Doenças Metabólicas/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Prolactina/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Fertilização in vitro , Seguimentos , Humanos , Infertilidade Feminina/terapia , Resistência à Insulina , Doenças Metabólicas/sangue , Doenças Metabólicas/etiologia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
In the past decade, the number of frozen-thawed embryo transfer (FET) has increased dramatically with the expansion of surgical indications and the improvement of freezing related technologies. How to improve the success rate and reduce the adverse effects of FET is our research priorities. This study aimed to investigate the safety and effectiveness of Gushen'antai pills (GSATP) by measuring the ongoing pregnancy rate (OPR) in patients from FET and hormone therapy (HT) cycle. From November 2019 to May 2020, 5 Chinese hospitals conducted a multi-center, randomized, double-blind, placebo-controlled study. In total, 271 HT FET cycles in patients were randomly divided (1:1 ratio) to receive GSATP (6 g, tid) or placebo (6g, tid) for 12 weeks of pregnancy. Patients, clinicians, and researchers were blinded to treatment allocation. The primary endpoint was the OPR at week 12 of pregnancy. The secondary endpoints were vaginal bleeding or brown discharge rate, implantation rate (IR), clinical pregnancy rate (CPR) and abortion rate (AR). Adverse events were recorded during the treatment period. The results showed that the OPR remained higher in the GSATP group when compared to placebo group (56.62% vs. 44.44%, p = 0.045). Vaginal bleeding or brown discharge rate was lower in the GSATP group than the placebo group (10% vs. 23.08%, p = 0.032), while the IR (35.16% vs. 27.64%, p = 0.070), CPR (58.82% vs. 48.15%, p = 0.078), incidence of total adverse events (8.09% vs. 3.22%, p = 0.051) and AR (3.75% vs. 7.69%, p = 0.504) were similar between GSATP and placebo groups. Subgroup analysis showed that there were significant differences in CPR (74.19% vs. 54.17%, p = 0.004) and OPR (72.04% vs. 51.04%, p = 0.003) between GSATP group and Placebo group when the patient was younger than 35 years old. This multi-center, randomized, double-blinded, placebo-controlled clinical study showed for the first evidence that GSATP may have potential to improve the OPR and decrease vaginal bleeding or brown discharge rate in HT FET cycle patients.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Transferência Embrionária/métodos , Nascido Vivo/epidemiologia , Medicamentos sem Prescrição/administração & dosagem , Indução da Ovulação/métodos , Progesterona/administração & dosagem , Adulto , China/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Implantação do Embrião , Feminino , Congelamento , Humanos , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Progestinas/administração & dosagem , Adulto JovemRESUMO
OBJECTIVE: To investigate the effects of Erzhi Tiangui Granule (ETG) on the concentration of leukemia inhibitory factor (LIF) in follicular fluid (FF) and quality of oocytes/embryos after in vitro fertilization and embryo transfer (IVF-ET). METHODS: Women undergoing IVF-ET were randomly assigned to two groups: the treated group (42 cases) treated with ETG combined with Western medicine and the control group (38 cases) treated with Western medicine alone. Syndrome of Shen-deficiency, amount of oocytes, rates of mature oocytes, fertilization, cleavage, high-quality embryos and pregnancy, as well as LIF level in FF were observed and compared between the two groups. The relationship of LIF level with mature oocyte rate and high-quality embryo rate was analyzed, respectively. RESULTS: In the treated group after treatment, the syndrome of Shen-deficiency and the above-mentioned indexes tested were improved better than those in the control group, respectively. Correlation analysis showed that the LIF level in FF was positively correlated with the rate of mature oocyte, high-quality embryo and the outcome of pregnancy. CONCLUSION: ETG can distinctively increase the amount of oocyte, elevate the quality of embryo and raise the successful rate of IVF-ET. The mechanism maybe correlated to the increase of LIF level in FF and the activating of microenvironment for its full expression.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fertilização in vitro/métodos , Líquido Folicular/metabolismo , Infertilidade Feminina/tratamento farmacológico , Fator Inibidor de Leucemia/metabolismo , Fitoterapia , Adulto , Transferência Embrionária , Feminino , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Oócitos/citologia , Deficiência da Energia Yang/tratamento farmacológicoRESUMO
AIM: To investigate the role of gelsolin-like actin-capping protein (CapG) in prostate cancer (PCa). MATERIALS & METHODS: CapG expression and its correlation with clinicopathological characters and patient prognosis were analyzed in 76 cases of PCa by immunohistochemistry and qRT-PCR. Then, the influence of CapG downregulation on cell apoptosis and proliferation were assessed. RESULTS: CapG expression in PCa was significantly higher compared with those in matched adjacent noncancerous prostate tissues, and significantly correlated with clinicopathological characters. Survival analysis indicated that CapG could be an independent prognostic factor in PCa. Moreover, CapG depletion significantly affected cellular proliferation and apoptosis by regulating Caspase 6/Caspase 9/Bcl-2/p-Akt/Akt signaling pathway. CONCLUSION: CapG, as a potential biomarker in PCa, is associated with patient prognosis, cellular apoptosis and proliferation.