Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve:A Prospective,Open-Labeled,Randomized and Controlled Study

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 fertilizationembryo 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(Gn RH)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 enzymelinked 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.Chi CTR2100048441).

Clinical efficacy of Chinese herbal compound in the treatment of infertility with kidney deficiency:A meta-analysis

Objective:Based on the current evidence system to evaluate the effect of traditional Chinese medicine compound on the clinical efficacy of infertility patients with kidney deficiency.Methods:Search the China Knowledge Resources Database(CNKI),Chinese Science and Technology Journal Database(VIP),China Academic Journal Database(Wanfang),PubMed,EMBASE,Ovid.The included studies are randomized controlled trials.The experimental group is Chinese medicine compound or Chinese medicine compound combined with western medicine,and the control group is western medicine.Two reviewers independently extracted and evaluated the literature data according to the Cochrane manual standards,and used Rev Man5.3 software for data synthesis and Meta-analysis.Results:32 studies were selected,a total of 2715 cases of infertility patients.The clinical pregnancy rate of the experimental group and the control group[n=29,OR(95%CI)=2.47(2.07,2.96),P<0.00001],the clinical total effective rate[n=20,OR(95%CI)=3.77(2.83,5.03),P<0.00001],TCM syndrome score[n=14,MD(95%CI)=4.34(3.08,5.61),P<0.00001],ovulation rate[n=20,OR(95%CI)=2.21(1.85,2.63),P<0.00001],the occurrence rate of two-way BBT[n=11,OR(95%CI)=2.65(2.02,3.48),P<0.00001].The GRADE scoring results show that the level of evidence is low and very low.Conclusion:Traditional Chinese medicine compound can increase the clinical pregnancy rate and clinical total effective rate of infertility with kidney deficiency syndrome,improve the scores of Chinese medical syndromes,increase its ovulation rate and the occurrence rate of BBT bidirectional type,and confirm the clinical efficacy of Chinese medicine compound from the perspective of evidence-based medicine.

Xiaoyi Yusi decoction(消异育嗣汤)improves in vitro fertilization and embryo transfer outcomes in patients with endometriosis

OBJECTIVE:To investigate the effect of—Xiaoyi Yusi decoction(XYYSD,消异育嗣汤),a Traditional Chinese Medicine(TCM),on in vitro fertilization and embryo transfer(IVF-ET)in patients with endometriosis,and to study the mechanism underpinning the action.METHODS:Women who underwent IVF-ET were divided into three groups by simple randomization:the treatment(n=32;with TCM treatment),patient(n=28;with endometriosis alone),and control(n=33;with male factor alone)groups.The luteal phase short-acting gonadotropin-releasing hormone agonist prolonged protocol was used in all three groups.To compare the changes in TCM scores and reproductive outcomes before and after TCM intervention in patients with endometriosis,partial least-squares discriminant analysis was used to analyze the follicular fluid samples of each group and screen and compare metabolites using the MetaboA nalyst software.RESULTS:The clinical data indicated that following TCM intervention,kidney deficiency and blood stasis symptom patterns improved dramatically in patients with endometriosis and that their clinical pregnancy rate increased significantly(71.9%vs 57.1%,P<0.05).Metabolomics showed that the two groups of samples were separated before and after TCM intervention.After TCM intervention,the intervention group was close to the control group,indicating that the TCM had a certain effect.Pathway analysis revealed that after TCM intervention,the metabolism of glycerin phospholipid,pyruvate,and citric acid was regulated.CONCLUSIONS:Through the pyruvate and glycerophospholipid metabolism pathways and tricarboxylic acid cycle,the TCM XYYSD successfully improved kidney deficiency and blood stasis symptom pattern,as well as the clinical reproductive outcomes of patients with endometriosis-related infertility.

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome

Objective:To evaluate the effect of electro-acupuncture(EA)in infertile patients with phlegmdampness polycystic ovary syndrome-insulin resistance(PCOS-IR).Methods:Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer(IVF-ET)were equally assigned to two groups according to a random digital table:the EA group and the control group,with 38 cases in each group.Before undergoing IVF,the two groups were treated with EA or pseudo-acupuncture,respectively,for 3 menstrual cycles.The intervention was 25 min twice a week until the day of oocyte collection.The selected acupoints were Zhongwan(RN 12),Tianshu(ST 25),Daheng(SP 15),Daimai(GB 26),Qihai(CV 6),Guanyuan(CV 4),and bilateral points including Xuehai(SP 10),Fenglong(ST 40),Zusanli(ST 36),and Yinlingquan(SP 9).Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment.Additionally,the number of oocytes retrieved,transplantable embryo rate,high-quality embryo rate,clinical pregnancy rate and live birth rate were compared between the two groups.Real-time polymerase chain reaction analysis was used to monitor the m RNA expression of the insulin receptor substrate(IRS-1),phosphatidylinositiol 3-kinase(PI3 K)and glucose transport factor 4(GLUT4)in ovarian granulosa cells.Results:EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group(P<0.05).No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups(P>0.05).Moreover,the transplantable embryo rate[49.0%(284/580)vs.41.9%(273/652)],high-quality embryo rate[36.6%(104/284)vs.27.8%(76/273)],and live birth rate[50%(19/38)vs.26.3%(10/38)]in the EA group were significantly higher than in the control group(P<0.05).Gene expression analyses revealed significantly elevated IRS-1,PI3 K and GLUT4 m RNA in ovarian granulosa cells of the EA group compared with the control group(P<0.05).Conclusions:EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients.Mechanistically,this effect might be through an upregulation of the IRS-1/PI3 K/GLUT4 signaling pathway,which may result in improved oocyte quality and embryonic development potential.(Registration No.Chi CTR1800015453)