Effects of the Zishen Yutai Pill compared with placebo on pregnancy outcomes among women in a fresh embryo transfer cycle: a Post Hoc subgroup analysis of a randomized controlled trial
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SUBMITTER: Chen X
PROVIDER: S-EPMC10703301 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles.MethodsWe conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study.ResultsRecruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02-1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05).ConclusionThe Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo.Clinical trial registrationChictr.org.cn, Chictr-TRC-14004494.
| S-EPMC8759541 | biostudies-literature
Project description:ObjectiveTo investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles.MethodsA retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate.ResultsAfter propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model.ConclusionThe use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.
| S-EPMC11390590 | biostudies-literature
Project description:ObjectiveZishen Yutai Pill (ZYP), containing 15 Chinese traditional medicine, is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction. The current study was designed to investigate the therapeutic effects of ZYP on sperm quality and testis in varicocele (VC) rats.Materials and methodsMale Wistar rats were randomly divided into four groups (n = 6), i.e., a sham group, a VC group, and VC groups treated with different dose of ZYP (1575 and 3150 mg/kg/d, respectively). The experimental VC model was established by partial ligation of left renal vein. Six weeks after model establishment, ZYP was orally administered once a day for the next 6 weeks. Parameters relating to testis and sperm quality were assessed. Hematoxylin-eosin staining was used to showed testicular tissue damage in experimental VC rats. Expressions of proteins relating to NLRP3 inflammasome pathways were determined using Western blot (WB). The mRNA expressions of relating genes were determined using quantitative real-time PCR (qRT-PCR) analysis.ResultsZYP could significantly improve sperm motility and decrease sperm DNA fragmentation index in VC rats (P < 0.05). Hematoxylin-eosin (HE) staining showed that ZYP could alleviate testicular tissue damage caused by experimental varicocele in rats. Compared to the VC model, expressions of NLRP3, ASC, and caspase-1 in rats treated with ZYP were significantly down-regulated, as validated by both qRT-PCR and WB analysis (P < 0.05).ConclusionsIn brief, ZYP could improve sperm DNA integrity by inhibiting the NLRP3 inflammasome pathway and alleviating the chronic inflammation of testicular tissue induced by experimental varicocele in rats.
| S-EPMC10361325 | biostudies-literature
Project description:ObjectiveZishen Yutai Pill (ZYP) is a frequently used traditional Chinese medicine (TCM) preparation in women's health. However, the effects of ZYP on endometrial epithelial response have not been fully explored. Herein, uterine natural killer cell (uNK) secretion medium was used to mimic the uterine microenvironment. Thereafter, an endometrial epithelial cell line (Ishikawa cells) was treated with ZYP-containing serum to elucidate the effects of ZYP on endometrial receptivity.Methods: uNK cells were isolated from decidual tissues of pregnant women undergoing pregnancy termination surgery, and thereafter, uNK secretion medium was collected. ZYP-containing serum was collected from rats after intragastrical administration of ZYP. Ishikawa cells were divided into three groups, one treated with blank control (control group), one treated with uNK secretion medium (uNK group), and one treated with both uNK secretion medium and ZYP-containing serum (ZYP + uNK group). Total RNAs were extracted. Gene expression profiles of Ishikawa in different groups were determined through microarray analysis. mRNA expressions of selected genes were determined through quantitative real-time polymerase chain reaction (qRT-PCR). Expression of intercellular cell adhesion molecule-1 (ICAM-1) was determined using Western blotting (WB).ResultsCompared with the uNK group, the gene expressions of ZYP group with a total of 1117 genes were significantly altered, among which 510 genes were upregulated and 607 genes were downregulated. Compared with uNK group, expressions of CSF1, CSF2, SPP1, and ICAM1 were upregulated (P < 0.05). Up-regulation of ICAM-1 expression after treatment of ZYP was further confirmed by WB analysis.ConclusionIn brief, in the presence of uNK cell medium, ZYP could improve the expressions of ICAM1, CSF1, CSF2, TNF, SPP1, etc. However, further exploration should be carried out in in vivo experiments for the validation of the mechanisms of ZYP on endometrial epithelial response.
| S-EPMC10558344 | biostudies-literature
Project description:Introduction: The current quality evaluation of traditional Chinese medicine (TCM) is difficult to attribute to clinical efficacy due to the complexity of TCM. Zishen Yutai pill (ZYP), a well-known traditional Chinese patent medicine, has been widely used to prevent recurrent miscarriage and treat threatened abortion. However, the chemical components of ZYP are unknown, and there is no convincing quality control method applied on ZYP. Although ZYP has been found to promote endometrial receptivity and treat impending abortion, the substantial basis of the therapeutic effects is unclear. The aim of this study was to clarify the quality markers correlated with the potential medicinal activities and provide a theoretical foundation for scientific quality control and product quality improvement of ZYP. Methods: The chemical constituents of ZYP were comprehensively analyzed by offline two-dimensional liquid chromatography-mass spectrometry (2DLC-LTQ-Orbitrap-MS). The efficacy of the 27 ZYP orthogonal groups was investigated using the HTR-8/SVneo oxidative damage model and migration model in vitro, as well as the endometrial receptivity disorder mouse model and premature ovarian failure mouse model in vivo. Based on the efficacy and mass spectral results, spectrum-effect relationship analysis was used to identify the chemical components with corresponding pharmacological activities. Results: A total of 589 chemical components were found in ZYP, of which 139 were not identified in the literature. The potential quality markers for ZYP were successfully identified through orthogonal design and spectrum-effect relationship analysis. By combining mass spectrum data and pharmacological results of 27 orthogonal groups, 39 substances were identified as potential quality markers. Conclusion: The approaches used in this study will provide a feasible strategy for the discovery of quality markers with bioactivity and further investigation into the quality evaluation of TCM.
| S-EPMC10311498 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to evaluate the efficacy and safety of Zishen Yutai Pill combined with western medicine for the treatment of women with threatened miscarriage during the first trimester of pregnancy.MethodsRandomized controlled trials published before the end of Apr 1, 2023 on Zishen Yutai Pill and threatened miscarriage were systematically retrieved from China National Knowledge Infrastructure, Wanfang, Sinomed, VIP, PubMed, EMBASE, Web of Science and the Cochrane Library. The international clinical trial registration platform and the Chinese clinical trial registration platform of clinical trials was searched from their inception until Apr 1, 2023. Meta analysis of random effect model was used to combine the research data. Chi-squared test and I2 statistics were used for heterogeneity test.ResultsTwenty-three trials (enrolling 2411 participants) were included in the review. Zishen Yutai pill combined with western medicine therapy showed significant improvement on human chorionic gonadotropin [MD 19.33 IU/ml, 95% CI (15.84, 22.81)], the total effective rate [RR 1.19, 95% CI (1.15-1.23)], progesterone [MD 7.14 ng/ml, 95% CI (6.14, 8.13)], estradiol [MD 33.69 pg/ml, 95% CI (27.42, 39.96)], duration of abdominal pain [MD -2.36 d, 95% CI (- 3.54, - 1.18)], duration of vaginal bleeding [MD -1.94 d, 95% CI (- 2.93, - 0.94)], and fibrinogen [MD -0.34 g/L, 95% CI (- 0.57, - 0.11)]. There was no significant difference in hematocrit [MD 0.68%, 95% CI (- 0.08, 1.44)] between the experimental and the control group. Zishen Yutai Pill may improve the clinical symptoms in women with threatened miscarriage, such as human chorionic gonadotropin the total effective rate, progesterone, estradiol, duration of abdominal pain, duration of vaginal bleeding, and fibrinogen. Especially for progesterone, the effect of treatment ≦2 weeks is significantly better than treatment of >2 weeks. For estradiol, the effect of treatment >2 weeks is significantly better than treatment of ≦ 2 weeks.ConclusionZishen Yutai Pill, as a complementary therapy, significantly improved human chorionic gonadotropin, the total effective rate, progesterone, estradiol, abdominal pain, vaginal bleeding, and fibrinogen in patients with threatened miscarriage in first-trimester pregnancy. However, the systematic review has some limitations, such as degraded information quality, no blinding of patients or doctors, etc. Due to the small sample size and low quality of research, it needs to be further confirmed by large sample and high-quality randomized controlled trials, such as blinding of patients, doctors and outcome assessment should be complemented, clinical follow-up, live birth rate, fetal growth should be supplemented.Systematic review registrationINPLASY202320039.
| S-EPMC10238576 | biostudies-literature
Project description:Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.
| S-EPMC8327273 | biostudies-literature
Project description:PurposeTo compare the reproductive outcomes of fresh embryo transfer (ET) cycles utilizing fresh versus frozen ejaculated sperm.MethodsFirst autologous fresh embryo transfer cycles at a single high-volume academic institution between 2013 and 2019 were retrospectively reviewed. IVF cycles using ejaculated sperm were included, and cycles using donor or surgically retrieved sperm were excluded. Sperm concentration was stratified as ≥ 5 and < 5 million/ml. The primary outcome was live birth, and the secondary outcomes were clinical intrauterine pregnancy (IUP) and miscarriage. A multivariable logistic regression model for the aforementioned outcomes was adjusted a priori for sperm concentration as well as maternal and paternal age.ResultsA total of 6128 couples were included. Of these, 5780 (94.3%) utilized fresh sperm, and 348 (5.7%) frozen sperm. A total of 5716 (93.2%) had sperm concentrations ≥ 5 million/ml and 412 (6.7%) had sperm concentrations < 5 million/ml. On multivariable logistic regression, the use of freshly ejaculated sperm was not associated with significantly different odds of clinical IUP, miscarriage, or live birth when compared to cycles using frozen sperm.ConclusionFor couples conceiving via fresh ET, the use of fresh versus frozen ejaculated sperm is not associated with reproductive outcomes.
| S-EPMC9174364 | biostudies-literature
Project description:MethodsA comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking.ResultsA total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized.ConclusionIntriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.
| S-EPMC8357500 | biostudies-literature
Project description:In this study, we analyzed the clinical efficacy of Zishen Yutai pills (ZSYTP) combined with metformin hydrochloride on infertile women diagnosed with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET). Patients were assigned into 3 groups: the ZSYTP group (n = 50), the metformin group (n = 50), and the combination group (ZSYTP combined with metformin hydrochloride, n = 50), based on their respective and the indicated treatments before undergoing IVF-ET. Then, their glucose metabolism indices, sex hormone indices, traditional Chinese medicine (TCM) syndrome scores, and outcomes of IVF-ET were compared. Baseline characteristics were not significantly different between the 2 groups. After treatment, various parameters such as body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FIN), homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T) levels, and TCM syndrome scores were found to be reduced compared to pretreatment levels in both groups. Moreover, the improvement observed in the treatment group exceeded that of the control group. Specifically, the observation group displayed significantly lower gonadotropin (Gn) dosage and duration, as well as a reduced abortion rate compared to the control group. Furthermore, the observation group had higher numbers of obtained eggs, high-quality embryos, eggs obtained through IVF-ET, average transferred embryos, clinical pregnancy rate, and embryo implantation rate compared to the control group. Pretreatment with ZSYTP combined with metformin before IVF-ET in PCOS patients improves the outcome of IVF-ET.
| S-EPMC11296412 | biostudies-literature