Long-term gonadotropin-releasing hormone agonist(Gn RHa) administration before in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) in infertile women with endometriosis or adenomyosis significantl...Long-term gonadotropin-releasing hormone agonist(Gn RHa) administration before in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term Gn RHa treatment might also be beneficial for the idiopathic repeated implantation failure(RIF) patients. In the 21 patients receiving Gn RHa and hormone replacement therapy(G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone(previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior Gn RHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.展开更多
Objective:The objective of this study is to study whether preimplantation genetic testing for aneuploidy(PGT-A)improves the clinical outcomes of infertile patients with repeated implantation failure(RIF)undergoing fro...Objective:The objective of this study is to study whether preimplantation genetic testing for aneuploidy(PGT-A)improves the clinical outcomes of infertile patients with repeated implantation failure(RIF)undergoing frozen-thawed embryo transfer.Methods:This is a retrospective analysis of clinical pregnancy,live birth,miscarriage rates,and obstetric and perinatal outcomes of women with RIF with or without PGT-A.Statistical analyses of categorical data were performed using propensity score matching(PSM),χ^(2)test,and Student’s t test.Results:We enrolled 466 patients with RIF,of which,209 were in the RIF-PGT-A group.The rate of euploid blastocysts was significantly associated with age and day 5 or 6 blastocysts.There were significant differences between the RIF-PGT-A group and the RIF-non-PGT-A group across several parameters.After PSM,positive serum human chorionic gonadotropin(56.9%and 33.9%,P<0.01),clinical pregnancy(49.5%and 31.2%,P<0.01),live birth(43.1%and 25.7%,P<0.01),and fetal heart rates(50.0%and 29.8%,P<0.01)per transfer were significantly higher in the RIF-PGT-A group.Conclusion:Elective single-embryo transfer PGT-A can minimize the risk of obstetric and perinatal outcomes,especially fetal body weight,in women with RIF.Additionally,PGT-A can significantly improve pregnancy and live birth rates.展开更多
Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to expl...Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.展开更多
Objectives: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) an...Objectives: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. Methods: In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometfial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. Results: Endometrial thickness, E2 and P levels, and the EJP ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P〈0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. Conclusions: Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of RIF-FET cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.展开更多
Background: At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial micr...Background: At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis. Methods: A total of 12 repeated implantation failure (RIF) patients and I0 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs. Results: Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stern cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations ofmicroRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result ofmicroarray analysis. Conclusions: There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.展开更多
目的评估宫腔灌注富血小板血浆(PRP)对反复种植失败(RIF)妇女妊娠结局的影响。方法使用PubMed、Embase、Scopus、Web of Science、CochraneLibrary、中国知识基础设施工程、维普数据库、万方数据库,检索PRP宫腔灌注治疗RIF患者的临床研...目的评估宫腔灌注富血小板血浆(PRP)对反复种植失败(RIF)妇女妊娠结局的影响。方法使用PubMed、Embase、Scopus、Web of Science、CochraneLibrary、中国知识基础设施工程、维普数据库、万方数据库,检索PRP宫腔灌注治疗RIF患者的临床研究。提取数据后使用固定效应模型或随机效应模型进行Meta分析。结果共纳入7项研究。接受PRP宫腔灌注女性的生化妊娠率[OR=2.18,95%CI:[1.34,3.52],P<0.05]、临床妊娠率(OR=2.47,95%CI:[1.66,3.68],P<0.05)、活产率(OR=5.00,95%CI:[1.09,22.99],P<0.05)和胚胎种植率(OR=1.99,95%CI:[1.36,2.93],P<0.05)高于对照组,流产率低于对照组(OR=0.28,95%CI:[0.10,0.77],P<0.05)。亚组分析显示宫腔灌注0.5 mL PRP组的临床妊娠率高于宫腔灌注1.0 mL PRP组(P<0.05),流产率低于宫腔灌注1.0 mL PRP组(P<0.05)。结论宫腔灌注PRP可提高RIF患者的胚胎种植率、活产率、生化妊娠率和临床妊娠率,且显著降低流产的风险,宫腔灌注0.5 mL PRP具有更好的临床效果。展开更多
Endometrial stromal cell decidualization is a crucial step in endometrial remodeling during pregnancy.Decidualization is controlled by orchestrated ovarian hormones,followed by the activation of various downstream sig...Endometrial stromal cell decidualization is a crucial step in endometrial remodeling during pregnancy.Decidualization is controlled by orchestrated ovarian hormones,followed by the activation of various downstream signaling pathways.Accumulating evidence has shown multiple functions of decidualized endometrial stromal cells during embryo implantation,including tissue remodeling,antioxidative stress,angiogenesis,and immune tolerance.The distinct secretomes of decidualized stromal cells also reveal their intensive interactions with epithelial,endothelial,and immune cells.However,aberrant decidualization leads to pregnancy failures,such as recurrent pregnancy loss and repeated implantation failure.This review aimed to provide an overview of the molecular mechanisms underlying the divergent functions of decidualized endometrial stromal cells and their potential clinical applications.Moreover,the use of single-cell RNA sequencing data further enhances our understanding of these biological processes.This review discusses decidualization-related signaling pathways that serve as potential therapeutic targets for treating implantation failure in in vitro fertilization and provides novel approaches to investigate the underlying causes of female infertility.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81100401 and No.81470063)Guangdong Natural Science Foundation of China(No.2014A030313129)the Doctoral Fund of the Ministry of Education of China(No.20110171120096)
文摘Long-term gonadotropin-releasing hormone agonist(Gn RHa) administration before in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term Gn RHa treatment might also be beneficial for the idiopathic repeated implantation failure(RIF) patients. In the 21 patients receiving Gn RHa and hormone replacement therapy(G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone(previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on-going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior Gn RHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients.
基金National Natural Science Foundation of China(No.81901558)
文摘Objective:The objective of this study is to study whether preimplantation genetic testing for aneuploidy(PGT-A)improves the clinical outcomes of infertile patients with repeated implantation failure(RIF)undergoing frozen-thawed embryo transfer.Methods:This is a retrospective analysis of clinical pregnancy,live birth,miscarriage rates,and obstetric and perinatal outcomes of women with RIF with or without PGT-A.Statistical analyses of categorical data were performed using propensity score matching(PSM),χ^(2)test,and Student’s t test.Results:We enrolled 466 patients with RIF,of which,209 were in the RIF-PGT-A group.The rate of euploid blastocysts was significantly associated with age and day 5 or 6 blastocysts.There were significant differences between the RIF-PGT-A group and the RIF-non-PGT-A group across several parameters.After PSM,positive serum human chorionic gonadotropin(56.9%and 33.9%,P<0.01),clinical pregnancy(49.5%and 31.2%,P<0.01),live birth(43.1%and 25.7%,P<0.01),and fetal heart rates(50.0%and 29.8%,P<0.01)per transfer were significantly higher in the RIF-PGT-A group.Conclusion:Elective single-embryo transfer PGT-A can minimize the risk of obstetric and perinatal outcomes,especially fetal body weight,in women with RIF.Additionally,PGT-A can significantly improve pregnancy and live birth rates.
基金This work was supported by the Shenzhen Healthcare Research Project,China(SZXJ2018004)Clinical Research Program of Chinese Medical Association,China(17020340703)the Sanming Project of Medicine in Shenzhen,China(SZSM201502035).
文摘Natural killer(NK)cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo.The aim of this study was to explore the cell number,immunophenotypic characteristics,and activities of peripheral blood NK cells in women with repeated implantation failure(RIF).Peripheral blood was obtained from 27 women with RIF and 11 healthy,fertile controls during the middle luteal phase of the menstrual cycle.CD3^-CD56^+NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules(granzyme B,granulysin,and perforin)as well as cell surface receptors responsible for NK cell activation or inhibition(NKG2D,NKp30,NKp46,CD158a,CD158b).NK cytotoxicity was measured at three effector-to-target cell ratios.Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3CD56t NK cells,or in the proportions of these cells that expressed granzyme B,granulysin,or perforin.The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D,NKp30,NKp46,CD158a or CD158b.General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio.However,NK cytotoxicity did not differ significantly between patients with RIF and fertile controls.These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.
基金Supported by Shanghai Municipal Health Bureau Foundation of Chinese Traditional Medicine(No.2010L026A)
文摘Objectives: To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney (Shen) and Spleen (Pi) in advance] in Chinese medicine (CM) and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure (RIF); and to study the differences in patients' endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. Methods: In the clinical study, 168 frozen-thawed embryo transfer (FET) cycles for couples with RIF conforming to the research protocol were randomly divided into three groups: a CM group with 56 cycles (CM combined with FET), a hysteroscopy group with 55 cycles (hysteroscopic endometfial mechanical stimulation), and a control group with 57 cycles (conventional FET). Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol (E2) and progesterone (P) on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. Results: Endometrial thickness, E2 and P levels, and the EJP ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group (P〈0.05), and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. Conclusions: Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of RIF-FET cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.
文摘Background: At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis. Methods: A total of 12 repeated implantation failure (RIF) patients and I0 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs. Results: Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stern cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations ofmicroRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result ofmicroarray analysis. Conclusions: There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.
文摘目的评估宫腔灌注富血小板血浆(PRP)对反复种植失败(RIF)妇女妊娠结局的影响。方法使用PubMed、Embase、Scopus、Web of Science、CochraneLibrary、中国知识基础设施工程、维普数据库、万方数据库,检索PRP宫腔灌注治疗RIF患者的临床研究。提取数据后使用固定效应模型或随机效应模型进行Meta分析。结果共纳入7项研究。接受PRP宫腔灌注女性的生化妊娠率[OR=2.18,95%CI:[1.34,3.52],P<0.05]、临床妊娠率(OR=2.47,95%CI:[1.66,3.68],P<0.05)、活产率(OR=5.00,95%CI:[1.09,22.99],P<0.05)和胚胎种植率(OR=1.99,95%CI:[1.36,2.93],P<0.05)高于对照组,流产率低于对照组(OR=0.28,95%CI:[0.10,0.77],P<0.05)。亚组分析显示宫腔灌注0.5 mL PRP组的临床妊娠率高于宫腔灌注1.0 mL PRP组(P<0.05),流产率低于宫腔灌注1.0 mL PRP组(P<0.05)。结论宫腔灌注PRP可提高RIF患者的胚胎种植率、活产率、生化妊娠率和临床妊娠率,且显著降低流产的风险,宫腔灌注0.5 mL PRP具有更好的临床效果。
基金supported by the RGC General Research Fund(17120720 to K.F.L.)the Professor PC Ho Research and Development Fund in Reproductive Medicine from the Department of Obstetrics and Gynecology,University of Hong Kong and Health and Medical Research Fund,Hong Kong(L.H.J.)a Conference and Research Committee grant from the University of Hong Kong(K.F.L.).
文摘Endometrial stromal cell decidualization is a crucial step in endometrial remodeling during pregnancy.Decidualization is controlled by orchestrated ovarian hormones,followed by the activation of various downstream signaling pathways.Accumulating evidence has shown multiple functions of decidualized endometrial stromal cells during embryo implantation,including tissue remodeling,antioxidative stress,angiogenesis,and immune tolerance.The distinct secretomes of decidualized stromal cells also reveal their intensive interactions with epithelial,endothelial,and immune cells.However,aberrant decidualization leads to pregnancy failures,such as recurrent pregnancy loss and repeated implantation failure.This review aimed to provide an overview of the molecular mechanisms underlying the divergent functions of decidualized endometrial stromal cells and their potential clinical applications.Moreover,the use of single-cell RNA sequencing data further enhances our understanding of these biological processes.This review discusses decidualization-related signaling pathways that serve as potential therapeutic targets for treating implantation failure in in vitro fertilization and provides novel approaches to investigate the underlying causes of female infertility.