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OBJECTIVE@#To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated.@*METHODS@#A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay.@*RESULTS@#Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05).@*CONCLUSIONS@#ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).
Subject(s)
Infant, Newborn , Pregnancy , Female , Humans , Fertilization in Vitro/methods , Ovarian Reserve , Prospective Studies , Premature Birth , Embryo Transfer/methods , Ovulation Induction/methods , Gonadotropin-Releasing Hormone/therapeutic useABSTRACT
Objective To investigate the effect of Zishen Yutai Pills on follicle apoptosis and related protein expression in diminished ovarian reserve(DOR) rat model induced by tripterygium glycosides.Methods Forty rats were divided into the control group,model group,progynova group,and Zishen Yutai Pills high and low dose groups,8 cases in each group.Tripterygium Wilfordii Glycosides Tablets were given by gavage for establishing the rat DOR model.Then the HE staining was used to detect the pathological morphology of rat ovary.All levels of follicles were counted.Expression levels of Bcl-2 and Bax protein in follicle and ovarian stroma of each group were detected by using the immunohistochemical method.Results Compared to the control group,the number of great and small follicles in the model control group was decreased,number of atretic follicles was increased,Bcl-2 expression in all kinds of follicles was decreased,and Bax expression was increased,the differences were statistically significant(P＜0.05).Compared to the model group,the number of great and small follicles in the Zishen Yutai Pills high and low dose groups and progynova group was increased,number of atretic follicles was decreased,the Bcl-2 expression in great and small follicles was significantly increased and the Bax expression was significantly decreased,the differences were statistically significant(P＜0.05).Conclusion Zishen Yutai Pills can inhibit the premature and too fast follicles apoptosis by upregulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein,thus plays the effect for treating DOR.
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To establish the HPLC fingerprint and determine five index components (loganic acid， chlorogenic acid， loganin， sweroside and asperosaponin Ⅵ) of Zishen Yutai pills by high performance liquid chromatography, and provide a scientific basis for its quality control. The fingerprint chromatogram was analysed by the chromatographic fingerprint similarity evaluation system for tradition Chinese medicine (2012), fifteen common peaks were obtained at the wavelength of 254 nm. Different batches of Zishen Yutai pills showed a similarity of above 0.90 in HPLC fingerprint profiles. For the quantitive analysis method, The separation of five components showed good regression (>0.999 2) with linear ranges, and the mean recoveries were in the range of 97.62%-101.9%, with the RSD (=9) less than 3%. The established fingerprint and quantitative analysis methods are highly specific, simple and accurate, which can reflect the quality of Zishen Yutai pills more comprehensively, and can be used for its quality control.
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AIM To observe the effect of Zishen Yutai Pills (Cuscutae Semen,Ginseng Radix et Rhizoma,Dipsaci Radix,etc.) on RAS,VEGF,VEGFR-2,sVEGFR-1 and MAPK in recurrent miscarriage mice,and to explore its mechanism.METHODS CBA/J female mice + DBA/2 male mice,and CBA/J female mice + BALB/c male mice were mated by 2 females and 1 male in cage to establish the RSA model and the normal pregnancy CBA × BALB/c mouse model respectively.Since the zeroth day of pregnancy,a total of 24 CBA/J × DBA/2 mice were randomly divided into model control group,Zishen Yutai Pills group and progesterone capsule group,and 10 CBA × BALB/c mice were used as normal pregnancy control group.Mice of all groups after the respective 15-day intervention had their rate of uterine embryo loss measured and calculated.Their pathological changes of decidual tissue were determined by HE staining,their RAS,VEGF,VEGFR-2,sVEGFR-1,MAPK protein and mRNA expressions were detected by immunohistochemistry and real-time PCR.RESULTS Zishen Yutai Pills significantly reduced the rate of embryo loss and improved pathological changes of decidual tissue in RSA mice through regulating mouse decidual tissue angiogenesis and recasting,as revealed by the lowered levels of RAS,VEGF,VEGFR-2 and MAPK,and increased expression of sVEGFR-1.CONCLUSION Zishen Yutai Pills can lower the rate of embryo loss and improve decidual angiogenesis in RSA mice through altering the expression of RAS,VEGF,VEG-FR-2,sVEGFR-1 and MAPK.
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AIM To study the effects of Zishen Yutai Pills (Codonopsis Radix,Dipsaci Radix,Morindae officinalis Radix,etc.) on endocrine in diminished ovarian reserve (DOR) rats.METHODS Female SD rats with normal oestrous cycle were induced by intragastric administration of 55 mg/(kg · d) tripterygium glycosides for fourteen days to establish DOR model,and then divided into Zishen Yutai Pills high-,low-dose groups,Bujiale group,model control group and negative control group.After 35 days' administration,serum estradiol (E2),follicle-stimulating hormone (FSH),luteinizing hormone (LH) and progesterone (P) levels were detected by ELISA.And ovarian tissue estrogen receptor (ER),follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) expressions were detected by immunohistochemical method.RESULTS Compared with the negative control group,there were significant changes in levels of E2,FSH,LH,P,and expressions of ER,FSHR,LHR in the model control group (P ＜ 0.05),but there were no statistical significances in body weight,ovary index,uterus index and serum FSH/LH level between the two groups (P ＞ 0.05).Compared with the model control group,E2 level was increased in the Zishen Yutai Pills high-,low-dose groups and Bujiale group,FSH,LH levels were decreased,and they also promoted ER expression and restrained FSHR,LHR excessive expressions,which were statistically significant (P ＜ 0.05).P level was significangly increased in different dose groups (P ＜ 0.05),FSH/LH in the high-dose group was obviously decreased (P ＜ 0.05),and body weight,ovary index,uterus index in various intervening groups showed no statistical significances (P ＞ 0.05).CONCLUSION Zishen Yutai Pills can improve ovarian reserve function in DOR rats by affecting the expression of ovarian tissue hormone receptor and regulating endocrine function.
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Objective To investigate the regulatory effects of Zishen Yutai Pills on the expression levels of homeboxA10 (HOXA10) and its downstream target gene empty spiracles homebox 2 (EMX2) in the endometria of ovulation-inducing mice at different implantation stages. Methods Seventy-five estrous female Kunming mice were randomly divided into 5 groups, namely normal group, model group 1, model group 2, treatment group 1, treatment group 2, 15 mice in each group. The model group 1 was given short-term protocol for ovulation induction; the model group 2 was given long-term protocol for ovulation induction; the treatment group 1 was given Zishen Yutai pills (at the dose of 0.4 g/mL) on the basis of the protocol for the model group 1; the treatment group 2 was given Zishen Yutai Pills (at the dose of 0.4 g/mL) on the basis of the protocol for the model group 2; the normal group was given intragastric administration or intraperitoneal injection of the same volume of normal saline. The mRNA and protein expression levels of HOXA10 and EMX2 in mouse uterus were detected by real-time fluorescent quantitative polymerase chain reaction (qPCR) and Western blot method, respectively. Results Compared with the normal group, the mRNA and protein expression levels of HOXA10 were decreased, and the mRNA and protein expression levels of EMX2 were increased in model group 1 and model group 2(P< 0.01). Compared with the corresponding model group 1 and 2, the mRNA and protein expression levels of HOXA10 were significantly up-regulated (P < 0.01) , and the mRNA and protein expression levels of EMX2 were decreased in the treatment group 1 and 2 (P < 0.01), respectively. Conclusion Zishen Yutai Pills may improve mouse endometrial receptivity by up-regulating HOXA10 expression and inhibiting EMX2 expression.