Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed.@*RESULTS@#Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results.@*CONCLUSIONS@#QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).

Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer / 中国结合医学杂志

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on reproductive outcomes in women with Shen (Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer (IVF-ET), and explore the underlying molecular mechanism.@*METHODS@#Sixty-six infertile patients with Shen deficiency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table, 33 cases in each group. Before undergoing IVF, patients in the EA and control groups received EA therapy and placebo needle puncture, respectively, for 3 menstrual cycles. Shen deficiency syndrome scores were assessed. Other outcome measures included the number of retrieved oocytes and fertilization, high-quality embryo and clinical pregnancy rates. Follicular fluid was collected on the day of oocyte retrieval, and granulosa cell expression of phosphatidylinositide 3-kinases (PI3K), serine-threonine kinase (Akt) and forkhead box O3 (Foxo3a) mRNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction.@*RESULTS@#Syndrome scores for pre- versus post-treatments decreased significantly (16.53±1.75 to 8.67±1.61) in the EA group (P<0.05), but showed no significant change in the control group (17.18±1.58 to 14.74±1.58). A significant difference in score change was found between the EA and control groups (P<0.05). High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15% (195/282) vs. 60.27% (176/292) and 66.67% (22/33) vs. 42.42% (14/33), respectively, P<0.05]. The fertilization rate was equivalent in EA and control groups. No difference was found in the number of retrieved oocytes between the two groups. Granulosa cell expression levels of PI3K and Akt mRNA were significantly increased in the EA group compared with the control group, while the expression of Foxo3a was reduced (all P<0.05).@*CONCLUSIONS@#For infertile patients with Shen deficiency syndrome undergoing IVF, EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate. The EA-induced mechanism may involve regulation of PI3K/Akt/Foxo3a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis, possibly contributing to the improved clinical pregnancy rate (Registration No. ChiCTR 1800016217).

Advances in research on anti-Müllerian tube hormone and male reproductive endocrine-related diseases / 基础医学与临床

Anti-Müllerian tube hormone(AMH), also known as Müllerian inhibitory substances, is a member of the transformation system. In males, AMH is secreted by immature Sertoli cell which promotes the degradation of male fetal Müllerian tubes,and participates in testicular development and spermatogenesis.AMH can regulate gona-dotropin-releasing hormone (GnRH), pituitary secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH),testicular stromal cells secrete testosterone(T) and inhibin B causes male reproductive endocrine related diseases through HPG axis.

Effect of yougui formula granule on ovarian granulosa cells gene expression profiles in IVF patients of shen yang deficiency syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Yougui Formula Granule (YFG) on ovarian granulosa cells gene expression profiles in in vitro fertilization-embryo transfer (IVF-ET) patients of Shen yang deficiency syndrome (SYDS) from the viewpoint of genomics.</p><p><b>METHODS</b>Totally 72 infertility patients undergoing IVF-ET were randomly assigned to the treatment group and the control group according to random digit table, 36 in each group. Patients in the treatment group took YFG combined gonadotropin (Gn), while those in the control group took placebos combined Gn. All medication lasted for 3 menstrual cycles before IVF. With high-throughput gene sequencing technology, gene expression profiles of ovarian granulosa cells in the two groups were analyzed to explore the difference by gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis.</p><p><b>RESULTS</b>Ovarian granulosa cell gene expression profiles from the follicular fluid showed, when compared with the control group, 391 differential genes were found in the syndrome-control group, 153 down-regulated and 238 upregulated. Enrichment of differentially expressed cellular location and molecular function of genes involved cell proliferation and apoptosis associated cyclin, protein ubiquitination, construction of microtubules and microfilament, mitochondrial function and energy-related factors, regulatory factors for hormone synthesis. Participated pathways involved energy metabolism pathway and transforming growth factor-β (TGF-β) signaling pathway.</p><p><b>CONCLUSIONS</b>There existed significant difference in gene expression profiles of ovarian granulosa cells between the treatment group and the control group. Differentially expressed genes involved in biological processes correlates with Shen yang deficiency induced proliferation of germ cells, confused apoptosis, and hindered process during which mitochondria produced energy.</p>

Effects of Liuwei Dihuang Granule (symbols; see text) on the outcomes of in vitro fertilization pre-embryo transfer in infertility women with Kidney-yin deficiency syndrome and the proteome expressions in the follicular fluid / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of Liuwei Dihuang Granule ([symbols; see text], LDG) for tonifying Kidney (Shen) on the outcomes of in vitro fertilization pre-embryo transfer (IVF-ET) of infertility women with Kidney-yin deficiency syndrome and to explore its mechanism by detecting the proteome expression in the follicular fluid.</p><p><b>METHODS</b>Sixty-six infertility patients of Kidney-yin deficiency syndrome who would undergo IVF-ET, were randomly assigned to a treatment group and a control group according to a random number table, 33 cases in each group. Another 33 cases of non-Kidney-yin deficiency syndrome was taken as a syndrome-control group. Besides Western routine therapy, LDG was given 3 menstrual cycles before IVF to the treatment group, and a placebo granule to the control and syndrome-control groups. The scores of Kidney-yin deficiency symptoms (sore waist and knees, dry vagina, dysphoria with feverish sensation in the chest, palms and soles, etc.) were assessed, the number of retrieved oocytes, rates of high quality oocytes and embryos, fertility rate and clinical pregnancy rate were recorded, and the follicular fluid was collected on the day when the ovum was picked up, the differential protein expression was detected using two-dimensional gel electrophoresis, and then, matrix assisted laser desorption ionization time-of flight mass spectrometry (MALDI-TOF-MS) was applied to identify the proteins.</p><p><b>RESULTS</b>The syndrome score in the treatment group decreased significantly from 16.09±2.58 to 8.67±2.13, while it changed insignificantly in the control group, with a significant difference in the lowering score between the two groups (P<0.05); the high quality rates of oocytes and embryos and clinical pregnancy rate were all superior in the treatment group to the control group (82.29% vs 78.08%, 76.76% vs 68.79%, 63.64% vs 36.36%, all P<0.05). The protein expression map from the follicular fluid showed that compared with the control group, 33 differential protein expressions were found in the syndrome-control group, among which 18 were down-regulated, and 15 up-regulated; in the treatment group 28 differential protein expressions were found, among which 15 were down-regulated, and 13 up-regulated. Through MALDI-TOF-MS, 14 proteins were identified (P<0.05).</p><p><b>CONCLUSIONS</b>For the infertility patients undergoing IVF, LDG could alleviate clinical symptoms, improve rates of high quality oocytes and embryos, so as to raise clinical pregnancy rate. The mechanism may be through regulating proteome expression in the follicular fluid to improve the developmental microenvironment for oocytes which would lead to a successful embryo implantation.</p>

Effects of Er'zhi Tiangui Granule () on sequential expressions of integrin β 3 and its ligand osteopontin in mouse endometrium during controlled ovarian hyperstimulation / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Er'zhi Tiangui Granule (, ETG) on sequential expressions of integrinβ3 and its ligand osteopontin in the mouse endometrium during controlled ovarian hyperstimulation (COH) and implantation period.</p><p><b>METHODS</b>Seventy-five Mature female Kunming mice were randomly divided into 3 groups, a normal control group, a model group, and a treatment group administrated with ETG for 10 days, 25 in each group. After mated with male mice, every 5 mice were sacrified in each group at the 0, 2nd, 4th, 6th, and 8th days to take their endometrium. In-situ hybridization was used to detect the expressions of integrinβ3 and osteopontin in the endometrium.</p><p><b>RESULTS</b>mRNA expressions of integrinβ3 and osteopontin in the endometrium during implantation period showed similar time sequence rules in the treatment group to those in the normal control group; the peak values of them were a little lower in the treatment group than the normal control without significant differences. In the model group, integrinβ3 mRNA expression was higher at the 2nd day, obviously lower at the 4th and 6th days, and insignificantly lower at the 8th day; and osteopontin expression was remarkably lower at the 4th, 6th, and 8th days, compared with the normal control and the treatment groups (P<0.05, P<0.01).</p><p><b>CONCLUSIONS</b>COH might influence the sequential expressions of integrinβ3 and its ligand osteopontin, bring forward the integrinβ3 expression peak, impact on the cooperation of integrinβ3 and osteopontin, so as to damage the endometrial receptivity. ETG could regulate the sequential expressions of integrinβ3 and its ligand osteopontin to improve the mouse endometrial receptivity during COH.</p>

Effects of acupuncture combined Chinese materia medica for tonifying shen and soothing gan on the anxiety and depression of patients with in vitro fertilization and embryo transplantation and on the treatment outcomes / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the effects of acupuncture combined Chinese materia medica for tonifying shen and soothing gan (CMMTSSG) on the anxiety and depression of patients with in vitro fertilization and embryo transplantation (IVF-ET), and to observe the treatment outcomes.</p><p><b>METHODS</b>Totally 97 IVF-ET patients were randomly assigned to two groups, the acupuncture combined CMMTSSG (group A, 51 cases) and the Western medicine treatment group (group B, 46 cases). The long protocol of IVF-ET in a mid luteal phase was performed in all patients. Patients in group A received acupuncture and CMMTSSG (erzhi tiangui granule and xiaoyao granule) during the process of ovarian hyperstimulation, while those in group B only received the routines of IVF-ET. The improvement of Shen deficiency Gan depression syndrome (SDGDS) between after and before treatment were observed in the two groups. The changes of self-rating anxiety scale (SAS) and Beck depression inventory (BDI) score were observed. The endometrial thickness, typing, and endometrial blood flow resistance index (RI) on the day of injecting HCG, the number of retrieved oocytes, the rate of high quality oocytes, the fertilization rate, the rate of high quality embryos, and the clinical pregnancy rate were respectively compared between the two groups.</p><p><b>RESULTS</b>The scores of SDGDS, SAS, and BDI were improved more obviously in group A than in group B, showing statistical difference (P < 0.01). There was no statistical difference in the endometrial thickness on the day of injecting HCG between the two groups (P > 0.05). The proportion of type A endometrium was 74.5% (38/51 cases) in group A and 45.7% (21/46 cases) in group B, showing statistical difference between the two groups (P < 0.01). The RI was significantly lower in group A (0.48 +/- 0.03) than in group B on the day of injecting HCG (0.52 +/- 0.06, P < 0.01). There was no statistical difference in the number of retrieved oocytes and the fertilization rate between the two groups (P > 0.05). The rate of high quality oocyte, the rate of high quality embryos, and the clinical pregnancy rate were all improved more significantly in group A than in group B, showing statistical difference between the two groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Acupuncture combined CM-MTSSG could obviously alleviate unfavorable emotions as anxiety and depression in patients with IVF-ET, effectively improve the treatment outcomes. Its effects might be correlated with lowering the excitability of the sympathetic nervous system, elevating the quality of oocytes, and improving the endometrial receptivity.</p>

Shengjing prescription improves semen parameters of oligoasthenozoospermia patients: efficacy and mechanism / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of Shengjing prescription for oligoasthenozoospermia and its action mechanism.</p><p><b>METHODS</b>We equally assigned 120 patients with oligoasthenozoospermia to receive Shengjing prescription (treatment group) and vitamin E (control group), respectively, for 12 weeks. Before and after the treatment, were obtained sperm concentration, sperm motility, the percentage of morphologically normal sperm, the levels of serum follicle-stimulating hormone (FSH), testosterone (T) and luteinizing hormone (LH), sperm DNA fragmentation index (DFI), the percentage of hypotonic swelling sperm, and the levels of seminal plasma elastase, x-glucosidase, fructose, zinc and acrosin.</p><p><b>RESULTS</b>Compared with vitamin E, Shengling prescription significantly improved sperm concentration, motility and morphology (P < 0.01), decreased the serum FSH level, elevated the serum T level (P <0. 01) , reduced DFI and seminal plasma elastase, and increased the percentage of hypotonic swelling sperm as well as the levels of seminal plasma cx-glucosidase, fructose, zinc and acrosin.</p><p><b>CONCLUSION</b>Shengjing prescription improves semen parameters of patients with oligoasthenozoospermia at multiple levels and through multiple channels.</p>

Effect of Quyu Jiedu granule on microenvironment of ova in patients with endometriosis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of Quyu Jiedu Granules (, QJG) on the micro- microenvironment of ova in patients with endometriosis (EM). environment</p><p><b>METHODS</b>Twenty EM patients who received in vitro fertilization and embryo transfer (IVF-ET) were randomized equally into a treated group and a control group. Further, 20 patients who received IVF-ET due to oviduct factors were enrolled into a non-endometriosis group. The dosage of gonadotrophic hormone used, the number of ova attained, fertilization rate and clinical pregnancy rate were all observed, and the levels of tumor necrosis factor alpha (TNF-right harpoon over left harpoon) and interleukin 6 (IL-6) in follicular fluid as well as their mRNA expressions in ovarian granular cells were detected by RT-PCR on the very day of ovum attainment.</p><p><b>RESULTS</b>The ova attainment (13.80+/-6.87) and fertilization rate (0.69+/-0.31) in the treated group were all higher than the corresponding values in the control group (9.80+/-5.32 and 0.47+/-0.22); the follicular fluid contents of TNF-alpha and IL-6 in the treated group were 1.38+/-0.21 ng/mL and 130.56+/-12.81 pg/mL, respectively, which were lower than those in the control group (1.98+/-0.34 ng/mL and 146.83+/-17.65 pg/mL, respectively). Further, the treated group showed much lower mRNA expressions of TNF-alpha and IL-6 in ovarian granular cells.</p><p><b>CONCLUSIONS</b>The elevation of TNF-alpha and IL-6 contents in follicular fluid and their mRNA expressions in ovarian granular cells are possibly related to the low quality of ova in EM; QJG might raise the ova quality by reducing TNF-alpha and IL-6 levels to improve the living micro-environment for the ova.</p>

Combined therapy of Chinese medicine with in vitro fertilization and embryo transplantation for treatment of polycystic ovarian syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the validity of Chinese drugs for reinforcing Shen and regulating Chong channel (RSRCC) on patients with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilization and embryo transplantation (IVF-ET).</p><p><b>METHODS</b>Sixty-four patients with PCOS undergoing IVF-ET were randomly assigned to two groups, the treated group (36 cases) and the control group (28 cases), to the former, Chinese recipe for RSRCC was given additionally.</p><p><b>RESULTS</b>On the human chorionic gonadotrophin (HCG) injecting day, the percentage of three-line sign of endometrium (type A) in the treated group was 75.0% (27/36), which was higher than that in the control group (42.9%, 12/28), showing significant difference between the two groups (P < 0.01). The rates of mature oocytes, fertilization, high-qualified embryo rate, clinical pregnancy rate and incidence rate of ovary hyper-stimulating syndrome (OHSS) in the treated group were (76.8 +/- 8.2)%, (73.5 +/- 8.9)%, (89.4 +/- 14.4)%, 36.11% (13/36) and 5.56% (2/36), respectively; whereas those in the control group (64.4 +/- 8.7)%, (68.2 +/- 10.0)%, (79.5 +/- 15.2)%, 21.43% (6/28) and 10.71% (3/28); the dosage of gonadotrophin administered in the treated group was 33.8 +/- 12.5 ampoules, and in the control group 47.6 +/- 18.2 amp oules, statistical significance was shown between groups in comparing all the above-mentioned parameters (P <0.05, P <0.01). However, the number of oocytes obtained in the two groups was insignificantly different (P > 0.05).</p><p><b>CONCLUSION</b>Combined use of Chinese drugs for RSRCC in IVF-ET can reduce the dosage of gonadotrophin administered and raise the clinical pregnant rate.</p>

Expressions of VEGF and Ki-67 in eutopic endometrium of patients with endometriosis and effect of Quyu Jiedu Recipe on VEGF expression / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy of Quyu Jiedu Recipe (, QJR) in treating endometriosis (EM), and to explore the levels of vascular endothelial growth factor (VEGF) and cell proliferative nucleoprotein antigen (Ki-67), their changes before and after treatment and the clinical significance in the trial.</p><p><b>METHODS</b>Fifty patients of EM were randomly assigned to two groups. The 26 patients in the QJR group were treated with QJR, and the 24 patients in the gestrinone (GT) group with gestrinone. Besides, a normal control group with 20 healthy women was set up. The therapeutic effects in the two treated groups were compared. Expressions of VEGF and Ki-67 in eutopic endometrium of all subjects (with both patients and healthy women at the median secretive phase) were determined with immunohistochemical stain before treatment, and the determination in the two treated groups was repeated after 3-month treatment in the same phase.</p><p><b>RESULTS</b>Before treatment, the VEGF and Ki-67 expression positive rates and their mean optic density (MOD) were higher in patients than in healthy women (P<0.05). After treatment, the positive rate and MOD of VEGF expression lowered significantly than before treatment (P<0.05), but those of Ki-67 changed insignificantly, and comparison between the two treated groups showed no significant difference (P>0.05).</p><p><b>CONCLUSION</b>QJR could markedly improve the symptoms of menorrhagia and menstrual disorder, and its mechanism might be related with the lowering of eutopic endometrial VEGF expression. VEGF and Ki-67 show a high expression in eutopic endometrium of patients with EM.</p>

Experimental study on effect of er'zhi tiangui granule in improving quality of oocyte and its correlation with level of insulin-like growth factor-1R mRNA expression in ovary of mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of Er'zhi Tiangui Granule (ETG) in improving the quality of oocyte.</p><p><b>METHODS</b>Ninety mice were randomly divided into 6 groups. The number of high-quality oocytes was comparatively observed in the 1st experimental group and the 1st control group; the embryonic cleavage rate was observed in the 2nd experimental group and the 2nd control group and the quantity of insulin-like growth factor-1R mRNA (IGF-1R mRNA) expression in ovarian granular cells was determined by using in situ hybridization in the 3rd experimental group and the 3rd control group.</p><p><b>RESULTS</b>The high-quality oocytes rate, the embryonic cleavage rate and the quantity of IGF-1R mRNA expression in the three paired groups was (78 +/- 8)% vs (71 +/- 5)%, (88 +/- 3)% vs (83 +/- 5)%, 0.4890 +/- 0.0454 vs 0.4439 +/- 0.0283, respectively. The difference between the experimental groups to the respective control groups was significant (all P < 0.05), and positive correlation was shown between the high-quality oocytes rate and the quantity of IGF-1R mRNA expression.</p><p><b>CONCLUSION</b>The mechanism of ETG in improving the quality of oocyte may be related with the elevation of IGF-1R mRNA level in ovarian granular cells.</p>