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Objective: This study investigated the metabolic status of the spent culture media from embryos of patients with repeated implantation failure (RIF) undergoing in vitro fertilization–intracytoplasmic sperm injection cycles in comparison with the embryos from healthy fertile women. Methods: Metabolite levels in spent culture media were assessed and compared between embryos from RIF patients (n=35) and oocyte donors as controls (n=15). Protein levels of insulin-like growth factor 1 (IGF-1) were determined using Western blotting. Concentrations of glucose, pyruvate, and lactate were measured using spectrophotometry. Ionic colorimetric assay kits were utilized to analyze the concentrations of sodium, chloride, calcium, and magnesium ions. High-performance liquid chromatography was employed to measure the concentrations of glutamic acid, aspartic acid, methionine, phenylalanine, and histidine. Results: Glucose consumption and lactate secretion were higher in the control group than in the RIF group. The magnesium concentration was significantly higher in the control group than in the RIF group, but glutamic acid and aspartic acid concentrations were lower in the control group than in the RIF patients (p<0.05). The levels of IGF-1, sodium, calcium, chloride, methionine, histidine, and phenylalanine did not show statistically significant differences between the two groups. Conclusion: The metabolic profile of the culture medium of the embryos in the RIF group differed from that of the control group. These findings suggest potential factors that may affect implantation capacity in RIF patients and provide a new perspective on embryo selection. [ABSTRACT FROM AUTHOR]

Abstract Purpose To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. Methods A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. Results Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P 0.05). Conclusion Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

Objectives: This prospective study evaluated whether endometriosis is associated with chronic endometritis (CE) and affects the uterine endometrium microbiome (UEM) in women with repeated implantation failure (RIF). Methods: Forty-three women with RIF were divided into 12 with endometriosis (EM) and 31 without endometriosis (non-EM). The UEM was examined by 16S ribosomal RNA (rRNA) sequencing, and CE was determined by CD 138 staining (plasma cells > 5.15/10 mm2) simultaneously. Results: The EM group had a higher bacterial number (EM vs. non-EM; median [range], 6.5 vs. 3 [3–11, 1–16], p = 0.009), while the frequency of Lactobacillus species did not change. The rates of presence of Dialister (41.7% [5/12] vs. 3.3% [1/31], p = 0.004) and Streptococcus species (58.3% [7/12] vs. 16.1% [5/31], p = 0.017) were higher in the EM group. The prevalence of CE did not differ between the two groups. Multivariable logistic regression analysis revealed that the presence of Dialister species (odds ratio, 10.97, 95% confidence interval, 1.17–249.37, p = 0.036) was associated with endometriosis. In the EM group, five women with Dialister species had a higher number of bacterial species (10 vs. 5 [6–11, 3–7], p = 0.021) and higher Shannon diversity index (0.50 vs. 0.20 [0.19–1.39, 0.03–0.46], p = 0.026) than seven without Dialister species. Conclusions: Dialister and Streptococcus species, and the increased number of bacterial species in UEM may be related to the pathogenesis of RIF complicated by endometriosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE. Methods: A retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up. Results: Out of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05). Conclusion: Infertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF. [ABSTRACT FROM AUTHOR]

Abstract Objective To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone. Data source Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023. Study Selection Randomized clinical trials and observational studies with the outcomes of interest were included. Data collect We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy. Data synthesis Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42). Conclusion Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure. PROSPERO CRD42023449655

Purpose: Gene expression analysis of the endometrium has been shown to be a useful approach for identifying the molecular signatures and pathways involved in recurrent implantation failure (RIF). Nevertheless, individual studies have limitations in terms of study design, methodology and analysis to detect minor changes in expression levels or identify novel gene signatures associated with RIF. Method: To overcome this, we conducted an in silico meta-analysis of nine studies, the systematic collection and integration of gene expression data, utilizing rigorous selection criteria and statistical techniques to ensure the robustness of our findings. Results: Our meta-analysis successfully unveiled a meta-signature of 49 genes closely associated with RIF. Of these genes, 38 were upregulated and 11 downregulated in RIF patients' endometrium and believed to participate in key processes like cell differentiation, communication, and adhesion. GADD45A, IGF2, and LIF, known for their roles in implantation, were identified, along with lesser-studied genes like OPRK1, PSIP1, SMCHD1, and SOD2 related to female infertility. Many of these genes are involved in MAPK and PI3K-Akt pathways, indicating their role in inflammation. We also investigated to look for key miRNAs regulating these 49 dysregulated mRNAs as potential diagnostic biomarkers. Along with this, we went to associate protein–protein interactions of 49 genes, and we could recognize one cluster consisting of 11 genes (consisted of 22 nodes and 11 edges) with the highest score (p = 0.001). Finally, we validated some of the genes by qRT-PCR in our samples. Conclusion: In summary, the meta-signature genes hold promise for improving RIF patient identification and facilitating the development of personalized treatment strategies, illuminating the multifaceted nature of this complex condition. [ABSTRACT FROM AUTHOR]

Aim: Reduced Lactobacillus occupancy in the uterine microflora has been associated with implantation failure. This study aimed to evaluate a treatment for improving the uterine microflora. Methods: This study included patients diagnosed with repeated implantation failure—defined as failure to achieve pregnancy after two or more transfers of viable embryos—who were classified as non‐Lactobacillus dominant. Treatment A comprised oral administration of antibiotics for 1 week, followed by oral probiotic butyrate tablets (3 g/day) for approximately 30 days. Treatment B comprised a 1‐week course of oral (750 mg/day) and vaginal (250 mg/day) metronidazole, followed by a 1‐week intravaginal administration of probiotic capsules (1 capsule/day) and continued oral administration of probiotics (1 capsule/day). Both treatments were compared in terms of efficacy in improving vaginal flora. Improvement was defined as Lactobacillus occupancy >90% or an increase in Lactobacillus occupancy >20%. Results: Seven (41.2%) of 17 patients in the Treatment A group improved in response to the treatment. Contrastingly, 9 (90.0%) of 10 patients improved in the Treatment B group (p = 0.0127). Following treatment, Lactobacillus occupancy in the Treatment B group (62.9% ± 12.7%) was significantly higher than that in the Treatment A group (5.7% ± 9.8%) (p = 0.0242). Conclusions: This study demonstrates the effectiveness of combining antibiotics and probiotics in vaginal formulations for treating abnormal uterine microflora. However, its potential impact on in vitro fertilization outcomes remains unclear and warrants further investigation through larger, more comprehensive studies. [ABSTRACT FROM AUTHOR]

Background: Repeated implantation failure has been one of the concerns in ICSI in recent years. It's linked to maternal or embryonic influences. One of the maternal factors is chronic endometritis (CE) which may affect the outcome of ICSI and so, its treatment may improve the results of ICSI. Objectives: To evaluate the effect of chronic endometritis treatment on the outcome of ICSI in repeated implantation failure (RIF). Methods: This is a prospective study conducted at the International Islamic Center for Population Studies and Research, Al-Azhar University on 120 patients with RIF. Patients were scheduled for hysteroscopic endometrial biopsy with histopathological examination. If there was no evidence of CE, the patients were scheduled for ICSI directly (Group A). Patients with CE received antibiotics and endometrial biopsy was done in the next cycle. According to the result of the second biopsy, patients were divided into 2 groups: - Patients with cured CE (Group B) and patients with persistent CE (Group C). We compared the chemical pregnancy rate, clinical pregnancy rate, and the miscarriage rate in study groups. Results: Patients with cured chronic endometritis had a significant higher chemical and clinical pregnancy rate compared with patients with persistent chronic endometritis (43.5% vs. 17.9% and 39.1% vs. 10.7% respectively). The miscarriage rate was higher in patients with persistent CE than other groups but with no significant difference. Conclusion: Treatment of chronic endometritis improved the outcome of ICSI regarding the chemical and clinical pregnancy rate. [ABSTRACT FROM AUTHOR]

Purpose: To identify potential biomarkers and the molecular mechanisms associated with repeated implantation failure (RIF), three microarray datasets, GSE71331 (lncRNA + mRNA), GSE111974 (lncRNA + mRNA), and GSE71332 (miRNA), were retrieved from the Gene Expression Omnibus (GEO) database. Methods: The differentially expressed mRNAs (DEMs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) between normal control samples (C group) and RIF samples (RIF group) were identified, and then a module partition analysis was performed based on weighted correlation network analysis (WGCNA). Following enrichment analysis of the genes, the lncRNA-miRNA-mRNA interactions (ceRNA) were examined. The mRNAs in the ceRNA network were evaluated using the GSE58144 dataset. Finally, the key RNAs were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Fifty-three DEmiRNAs, 327 DEMs, and 13 DElncRNAs were identified between the C and RIF groups. According to WGCNA, the magenta module was positively correlated with RIF disease status. The lncRNA-mRNA interaction analysis based on genes in the magenta module revealed the intersecting lncRNAs, including peptidylprolyl isomerase E-like pseudogene (PPIEL) and the testis-specific transcript, y-Linked 14 (TTTY14); these lncRNAs are mainly involved in functions, such as plasma membrane organization. The ceRNA network analysis revealed several interactions, such as TTTY14-miR-6088-semaphorin 5 A (SEMA5A). Finally, SEMA5A and the zinc finger protein 555 (ZNF555) were identified to be significantly upregulated in the RIF group compared with those in the C group in the GSE58144 dataset. The RT-qPCR results aligned with the above results. Conclusions: Overall, TTTY14, ZNF555, SEMA5A, PPIEL, and miR-6088 could serve as novel biomarkers of RIF. Highlights: TTTY14, ZNF555, SEMA5A, PPIEL and miR-6088 could be serve as novel biomarkers of RIF. TTTY14 may participate in RIF progression by regulating the miR-6088/SEMA5A axis. This study provides new insights for the diagnosis and treatment of RIF. [ABSTRACT FROM AUTHOR]

Objective: To explore the characteristics of vaginal microbiota in patients with repeated implantation failure (RIF). Methods: A total of 49 patients undergoing the frozen-thawed embryo transfer (FET) cycles were recruited. In the observation group, patients (n=29) with a history of RIF have failed pregnancy during the FET cycles. In the control group, patients (n=20) underwent the FET for the first time and achieved clinical pregnancy. In both groups, artificial hormone cycles were performed, and the top-quality blastocysts cultured on Day 5 were tranferred. Vaginal samples were collected on the FET day. Microbial diversity, microbial community composition and differential bacterial genera between the two groups were analyzed by 16S rRNA sequencing. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of the abundance of Lactobacillus for RIF. Results: The α diversity analysis showed that the microbial diversity (Shannon: P=0.049 8) and richness (Chao: P =0.047 1) of the observation group were significantly higher than those of the control group. The β diversity analysis showed that there was significant difference in the vaginal microbial community composition between the two groups (P=0.016). At the genus level, Lactobacillus was dominant in both groups. The abundance of Lactobacillus of the observation group was significantly lower than that of the control group, while the abundances of Acinetobacter and Pseudomonas of the observation group were significantly higher than those of the control group (LDA＞3, P＜0.05). The optimal cutoff value for diagnosing RIF with the abundance of Lactobacillus was 70%, and the area under curve (AUC) was 0.77. Conclusions: Vaginal microbiota was showed differences in RIF patients, including the decreased abundances of Lactobacillus. The low abundance of vaginal Lactobacillus may be related with the pathogenesis of RIF [ABSTRACT FROM AUTHOR]

Objective: The primary objective was to investigate whether the utilization of next-generation sequencing (NGS) for preimplantation genetic testing for aneuploidy (PGT-A) could enhance the reproductive outcomes in patients with unexplained recurrent pregnancy loss (uRPL) or unexplained repeated implantation failure (uRIF) undergoing intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: We studied the reproductive outcomes of uRPL or uRIF sufferers in Chengdu women and children's central hospital from July 2020 to Jan 2024 retrospectively. These patients were categorized into two groups based on whether they underwent PGT-A or not. As the patients in the PGT-A group all had ICSI and frozen-thawed embryo transfer (FET), only patients who underwent ICSI and FET were included in the non-PGT-A group for comparison. Demographic characteristics and reproductive outcomes were compared in uRPL or uRIF sufferers. Results: For uRPL group, a significant increased ongoing pregnancy rate (63.6 % vs 26.1 %, p = 0.002) and reduced pregnancy loss rate (18.4 % vs 73.3 %, p

Abstract Background Platelet-rich plasma (PRP) is an autologous platelet concentration recently used in the reproductive field. Studies had conflicting results regarding its effect on pregnancy outcomes. We aimed to solve the debate on the safety and efficacy of PRP in women undergoing assisted reproduction and assess the influence of covariates on the outcomes of PRP infusion. Methods We searched PubMed, Scopus, Cochrane, and Web of Science in May 2023. We included randomized and non-randomized clinical trials as well as cohort studies assessing intrauterine PRP in sub fertile women undergoing assisted reproduction (IVF/ICSI). For the quality assessment, We used the Cochrane Risk of Bias Tool 1, the ROBINS-I tool, and the Newcastle–Ottawa Scale. We pooled the data using RevMan version 5.4. Results The data from 23 studies were pooled. PRP had favorable outcomes compared with the control group on clinical pregnancy rate (RR: 1.84, 95% CI 1.62 to 2.09; P

To explore the application value of endometrial receptivity test (ERT) in frozen-thawed embryo transfer(FET) in patients with repeated implantation failure, and to analyze the influencing factors of clinical pregnancy. The clinical data of 150 patients with repeated implantation failure who were admitted to Hainan Women and Children's Medical Center from October 2019 to April 2022 were retrospectively analyzed, patients were divided into ERT group (n=78, received ERT technology) and non-ERT group (n=72, did not receive ERT technology) according to whether they received ERT technology. Patients were divided into clinical pregnancy group and non-clinical pregnancy group according to the clinical pregnancy of patients with repeated implantation failure. The influencing factors of clinical pregnancy were analyzed by univariate and multivariate Logistic regression models. There was no significant difference in ectopic pregnancy rate between two groups (P>0.05). The clinical pregnancy rate and live birth rate in ERT group were higher than those in non-ERT group, the endometrial thickness on the day of transplantation was greater than that in non-ERT group, the number of transplanted embryos was less than that in non-ERT group, and the abortion rate was lower than that in non-ERT group (P<0.05). All patients were divided into clinical pregnancy group (n=85) and non-clinical pregnancy group (n=65). The results of univariate analysis showed that, clinical pregnancy was related to age, type of transplanted embryos, number of transplanted embryos, total number of cycles, FSH, endometrial thickness and endometrial type (P<0.05), and it was not related to body mass index(BMI), infertility years, infertility type, and Embryos were cryopreserved for the storage time (P>0.05). Multivariate Logistic regression analysis showed that, older age and higher FSH were risk factors for clinical pregnancy, while type of transplanted embryos is blastocyst and more transplanted embryos were protective factors for clinical pregnancy (P<0.05). ERT technology can effectively improve the clinical pregnancy of patients with repeated implantation failure in FET. Age, FSH, type of transplanted embryos and number of transplanted embryos are the influencing factors of clinical pregnancy. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the effect of long‐acting gonadotropin‐releasing hormone agonist (GnRHa) long protocol on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes of patients with repeated implantation failure (RIF). Methods: The present study was carried out from June 1, 2016 to June 30, 2021. A total of 665 patients with RIF were enrolled into the study and classified by the ovarian stimulation protocols. The outcome parameters were compared in each group. In addition, we evaluated the expression of homeobox A10 (HOXA10), integrin β3 and leukemia inhibitory factor (LIF) in endometrial tissues between groups by quantitative RT‐PCR. Results: Patients who received the long‐acting GnRHa long protocol had significantly higher clinical pregnancy rates (58.0%, 41.7% and 39.9%, respectively; P = 0.008 and 0.003), implantation rates (38.1%, 30.3%, and 30.1%, respectively; P = 0.001 and <0.001) and live birth rates (50.3%, 36.3%, and 31.3%, respectively; P = 0.020 and 0.002) compared with the short‐acting GnRHa long protocol and GnRH antagonist protocol. In addition, we found that long‐acting GnRHa could improve the expression of HOXA10 (P < 0.05). Conclusion: The long‐acting GnRHa long protocol could improve endometrial receptivity and IVF/ICSI clinical outcomes of RIF patients compared with the short‐acting GnRHa long protocol and GnRH antagonist protocol. Synopsis: The long‐acting GnRHa long protocol could improves the clinical pregnancy rate, implantation rate and live birth rate of RIF patients. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the relationships among irrational conceptions of parenthood, fertility stress, and social support, as well as the mediating effect of fertility stress, in patients with repeated implantation failure. Methods: Patients who underwent assisted reproductive technology due to repeated implantation failure at the Reproductive Centre at Women's Hospital between January 2020 and August 2022 were selected using cross-sectional research and convenience sampling. A total of 129 patients with recurrent implantation failure were investigated using the Irrational Parenthood Cognitions Questionnaire (IPCQ), Fertility Problem Inventory (FPI), and Social Support Rating Scale (SSRS). Results: The differences in irrational parenthood cognitions, fertility, stress, and social support among patients with repeated implantation failure in the education and yearly household income subgroups were statistically significant (P<0.001). Pearson correlation analysis revealed that irrational parenthood cognitions were favorably correlated with all measures of reproductive stress (r=0.384 to 0.664, all P<0.01) and negatively correlated with social support (r=-0.310, p<0.01). The fertility stress of patients with repeated implantation failure fit the structural equation model of irrational parenthood cognitions and social support well [X2/df=2.04, Comparative Fit Index (CFI)=0.944, Tucker–Lewis (TLI)=0.905, Root Mean Squared Error of Approximation (RMSEA)=0.090]. The bootstrap test results revealed that the mediating effect of the 95% CI ranged between -0.506 and -0.109, and the interval did not contain 0. Fertility stress had a strong mediating effect on the relationship between irrational parenthood cognitions and social support. Conclusions: The mediating effect of reproductive stress on the relationship between irrational parenthood cognitions and social support in patients with repeated implantation failure was significant. It is important for medical and nursing staff to address physical and psychological illnesses and develop effective intervention strategies from the perspectives of fertility stress, social support, and cultural background, with the ultimate goal of improving mental health. [ABSTRACT FROM AUTHOR]

BACKGROUND The establishment of maternal–fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal–fetal interface and their associations with pathological processes. OBJECTIVE AND RATIONALE This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal–fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal–fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed. SEARCH METHODS A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal–fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included. OUTCOMES The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal–fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal–fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal–fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groundwork for further exploration of glycans in reproductive biology under both physiological and pathological conditions. WIDER IMPLICATIONS A deep understanding of the functions of glycan structures would provide insights into the molecular mechanisms underlying their involvement in the physiological and pathological regulation of early pregnancy. Glycans may also potentially serve as novel early predictive markers and therapeutic targets for repeated implantation failure, pregnancy loss, and other pregnancy complications. [ABSTRACT FROM AUTHOR]

Recent studies have investigated if and how the vaginal and endometrial microbiome might affect endometrial receptivity and reproductive health. Although there is no consensus on the existence of a core uterine microbiome yet, evidence shows that the dominance of Lactobacillus spp. in the female reproductive tract is generally associated with eubiosis and improved chances of successful implantation and an ongoing pregnancy. Conversely, vaginal and endometrial dysbiosis can cause local inflammation and an increase of pro-inflammatory cytokines, compromising the integrity and receptivity of the endometrial mucosa and potentially hampering successful embryonic implantation. This review provides a critical appraisal of the influence of the vaginal and endometrial microbiome as parts of the female reproductive tract on fertility outcomes, focusing on repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It seems that RIF as well as RPL are both associated with an increase in microbiome diversity and a loss of Lactobacillus dominance in the lower female reproductive system. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) is an autologous platelet concentration recently used in the reproductive field. Studies had conflicting results regarding its effect on pregnancy outcomes. We aimed to solve the debate on the safety and efficacy of PRP in women undergoing assisted reproduction and assess the influence of covariates on the outcomes of PRP infusion. Methods: We searched PubMed, Scopus, Cochrane, and Web of Science in May 2023. We included randomized and non-randomized clinical trials as well as cohort studies assessing intrauterine PRP in sub fertile women undergoing assisted reproduction (IVF/ICSI). For the quality assessment, We used the Cochrane Risk of Bias Tool 1, the ROBINS-I tool, and the Newcastle–Ottawa Scale. We pooled the data using RevMan version 5.4. Results: The data from 23 studies were pooled. PRP had favorable outcomes compared with the control group on clinical pregnancy rate (RR: 1.84, 95% CI 1.62 to 2.09; P < 0.00001), live birth rate (RR: 1.75, 95% CI: 1.24 to 2.47; P = 0.001), and miscarriages (RR: 0.51, 95% CI: 0.36 to 0.72; P = 0.0002). Women with repeated implantation failure had a significantly improved clinical pregnancy rate (RR: 1.83, 95% CI: 1.49 to 2.24; P < 0.00001), live birth rate (RR:1.83, 95% CI: 1.33 to 2.51; P = 0.002), and miscarriage rate (RR: 0.46, 95% CI: 0.31 to 068; P = 0.0001). Conclusion: PRP showed promising results in assisted reproductive techniques. Further large and multicenter RCTs are required to compare the doses of PRP while identifying the specific population with the most benefits from PRP. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether maternal obesity affects the immune status of peripheral blood and endometrium in patients with recurrent reproductive failure classified according to their body mass index (BMI). A total of 228 repeated implantation failure (RIF) and 266 recurrent miscarriage (RM) patients were enrolled in the study and further subdivided into three groups according to their BMI: (i) normal weight (18.5≤ BMI <23); (ii) overweight (23≤ BMI <25); and (iii) obese (BMI ≥25). Peripheral blood and endometrium samples were collected in the mid-luteal phase before IVF treatment or natural pregnancy. Peripheral immunocytes were analyzed by flow cytometry, while uterine immune cells were subjected to immunohistochemistry. In RM patients, significantly increased peripheral helper T cells and decreased cytotoxic T cells, NK cells were observed in the obese group compared with the normal-weight group. Meanwhile, in the endometrium, the percentage of NK cell, macrophage cell, M2 macrophage cell, and Treg cell significantly reduced with increased BMI in RIF patients, and the percentage of NK cell and M2 macrophage cell significantly decreased with increased BMI in RM patients. In conclusion, obesity may cause endometrial immune disorder in recurrent reproductive failure women, but was only associated with the peripheral immune change in RM patients. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to investigate the optimal frozen embryo transfer (FET) strategy for recurrent implantation failure (RIF) patients with three consecutive failed cleaved embryo implantations and no blastocyst preservation. This retrospective analysis was divided into three groups based on the FET strategy: thawed day 3 embryo transfer (D3 FET group); and extended culture of frozen–thawed day 3 embryos to day 5 blastocysts transfer (D3–D5 FET group); thawed blastocyst transfer (D5 FET group). Transplant cycle data were compared between the three groups. In total, 43.8% of vitrified–thawed cleavage embryos developed into blastocysts. Analysis of the three transplantation strategies showed that, compared with the D3 FET group, D3–D5 had a significantly better hCG-positivity rate and live-birth rate (P < 0.05). Pregnancy outcomes in the D3–D5 FET group and D5 FET group were similar regarding hCG-positivity rate, implantation rate, clinical pregnancy rate, and live-birth rate. Our findings propose two potentially valuable transfer strategies for patients experiencing repeated implantation failures. The D3–D5 FET approach presents a greater potential for selecting promising embryos in cases without blastocyst preservation; however, this strategy does entail the risk of cycle cancellation. Conversely, in instances where blastocyst preservation is an option, prioritizing consideration of the D5 FET strategy is recommended. [ABSTRACT FROM AUTHOR]

IntroductionEmbryo implantation requires synchronous communication between the embryo and maternal endometrium. Inadequate maternal endometrial receptivity is one of the principal causes for embryo implantation failure [especially repeated implantation failure (RIF)] when biopsied good-quality euploid embryos are transferred. An RNA-seq-based endometrial receptivity test (rsERT) was previously established to precisely guide successful embryo implantation. In this study, we aimed to evaluate the effect of personalized embryo transfer (pET) via rsERT on the clinical outcomes in patients with RIF.MethodsA total of 155 patients with RIF were included in the present retrospective study and were divided into two groups: 60 patients who underwent rsERT and pET (Group rsERT) and 95 patients who underwent standard frozen embryo transfer (FET) without rsERT (Group FET). Reproductive outcomes were compared for patients who underwent rsERT-guided pET and standard FET.ResultsForty percent (24/60) of the patients who underwent rsERT were receptive, and the remaining 60% (36/60) were non-receptive. The positive human chorionic gonadotropin (β-hCG) rate (56.3% vs. 30.5%, P = 0.003) and clinical pregnancy rate (43.8% vs. 24.2%, P = 0.017) were significantly higher in Group rsERT patients than in FET group patients. Additionally, Group rsERT patients also showed a higher implantation rate (32.1% vs. 22.1%, P = 0.104) and live birth rate (35.4% vs. 21.1%, P = 0.064) when compared with FET patients, although without significance. For subpopulation analysis, the positive β-hCG rate, clinical pregnancy rate, implantation rate, and live birth rate of receptive patients were not statistically significant different from those of non-receptive patients.ConclusionsThe rsERT can significantly improve the pregnancy outcomes of RIF patients, indicating the clinical potential of rsERT-guided pET.

Yin-Ling Xiu, Kai-Xuan Sun, Qian Zhang, Yu-Hong Xiao, Xue Bai, Yong Chen, Meng-Si Zhao, Yue-Xin Yu Center of Reproductive Medicine, General Hospital of Northern Theatre Command, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Yue-Xin Yu, Center of Reproductive Medicine, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, 110016, People’s Republic of China, Tel +86-18809881296, Email yuyuexinpingan@163.comAim: To compare the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles among women with repeated implantation failure (RIF) treated with various endometrial preparation protocols.Methods: A total of 605 women with RIF were retrospectively recruited between January 2017 and December 2020 from Northern Theater General Hospital. Patients were divided into natural cycles, hormone replacement therapy (HRT) cycles, depot gonadotropin-releasing hormone (GnRH) agonist-HRT, and endometrial scratching (ES) plus depot GnRH agonist-HRT. The primary endpoint was clinical pregnancy rate, while secondary endpoints included live birth rate and pain assessment.Results: Of the 605 recruited patients, 63 were undergoing natural cycles, 281 were treated with HRT cycles, 141 treated with depot GnRH agonist-HRT, and 120 treated with ES combined with depot GnRH agonist-HRT. There were significant differences among protocols on clinical pregnancy rate (P=0.029), while no significant difference was observed among protocols on live birth rates (P=0.108). Multivariate analyses suggested that HRT (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.28– 0.89; P=0.019) and depot GnRH agonist-HRT (OR: 0.49; 95% CI: 0.27– 0.91; P=0.021) cycles were associated with a lower clinical pregnancy rate as compared with natural cycles, while no significant difference between ES combined with depot GnRH agonist-HRT and natural cycles for clinical pregnancy rates (OR: 0.72; 95% CI: 0.38– 1.36; P=0.313). Moreover, the HRT (OR: 0.70; 95% CI: 0.39– 1.28; P=0.239), depot GnRH agonist-HRT (OR: 0.67; 95% CI: 0.35– 1.29; P=0.229), and ES combined with depot GnRH agonist-HRT (OR: 1.11; 95% CI: 0.58– 2.14; P=0.754) cycles had no significant effects on live birth rate as compared with natural cycles. A total of 87.50% patients treated with ES combined with depot GnRH agonist-HRT reported pain during the procedure.Conclusion: ES and depot GnRH agonists could be considered for RIF women with high-quality blastocysts, 14 days after verified transplantation failure.Keywords: endometrial scratching, depot GnRH agonist, repeated implantation failure, blastocysts, clinical pregnancy rate, live birth rate

Abstract Objective To explore the effect of sequential embryo transfer (ET) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycle and the indications of sequential transfer. Methods A total of 1440 FET cycles were enrolled in this retrospective study, of which 1080 patients received conventional ET and 360 patients received sequential ET. Further stratified analysis was performed according to the number of previous failed cycles, the number of embryos transferred and the stage of blastocyst (day 5 or 6, denoted D5 or D6) transferred. Comparison of pregnancy rates, implantation rate, miscarriage rate and multiple pregnancy rate among the groups of patients. Results The clinical pregnancy rate and implantation rate of the sequential ET group were higher than those of the conventional ET group (P 0.05). In sequential transfer, the number of transferred embryos (2 or 3) and the stage of transferred blastocysts (D5 or D6) had no effect on clinical pregnancy rate, implantation rate, multiple pregnancy rate and miscarriage rate (P > 0.05). In patients with three or more previous failure cycles, the sequential ET group showed higher clinical pregnancy rate and implantation rate (P > 0.05). Conclusions Compared with conventional ET in FET cycle, sequential ET strategy could significantly improve the clinical pregnancy rate and implantation rate. In sequential transfer, patients with three embryos transferred don’t have higher pregnancy rate and implantation rate. Besides, sequential transfer is more suitable for patients with repeated implantation failures (RIF), and increase the utilization rate of D6 blastocysts.

Background: We conducted a comprehensive systematic review and meta-analysis to evaluate the diverse impacts of combining aspirin with prednisone or prednisolone on patients undergoing in vitro fertilization (IVF) or experiencing recurrent implantation failure (RIF). Our analysis encompassed parameters such as clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, and fertilization rate. Our primary objective was to resolve the debate regarding the comparative efficacy of prednisone versus prednisolone when administered alongside aspirin in women undergoing assisted reproduction. Methods: A variety of electronic databases were searched between 1984 and December 2023, including PubMed, Web of Science, Embase, the China National Knowledge Infrastructure (CNKI), the China Biology Medicine Disc (CBM), and the CQVIP Database. We employed the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool for the quality evaluation. We used Stata 12.0 and Revman 5.4 to pool the data. Results: In this meta-analysis, 10 trials, including 2902 individuals, were considered. Aspirin plus prednisone or prednisolone might improve clinical pregnancy rates (relative risk (RR) = 1.13; 95% confidence interval (95% CI) = 1.03–1.23) and implantation rates (RR = 1.27; 95% CI = 1.01–1.60) compared with the placebo or no treatment group. Conclusions: Our findings suggest that aspirin plus prednisone or prednisolone may improve clinical pregnancy rates and implantation rates in patients with IVF or RIF, and in the subgroup of ANA-positive patients, it may also improve implantation rates. Further design of larger randomized controlled trials is required to determine whether aspirin in combination with prednisone or prednisolone may improve assisted reproductive outcomes in patients undergoing IVF or RIF, considering the limits of study enrollment.

Abstract Background The aim of this retrospective study was to investigate whether oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone) are beneficial for patients with repeated implantation failure (RIF) and chronic endometritis (CE) to improve clinical pregnancy outcomes. Methods Patients with RIF and CE were diagnosed using hysteroscopy and histology together. A total of 42 patients were enrolled in the study. All patients received oral antibiotics (doxycycline combined with metronidazole) and 22 patients underwent intrauterine perfusion (gentamicin combined with dexamethasone) immediately after the end of oral antibiotic therapy. Pregnancy outcomes were evaluated during the first in vitro fertilization (IVF) and embryo transfer (ET) cycle. Results For the first D3 ET after treatment with oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone), higher embryo implantation rate (30.95% vs. 26.67%, P = 0.0308), clinical pregnancy rate (30% vs. 50%, P

BackgroundSequential embryo transfer has been recognized as a strategy to increase pregnancy rates in women undergoing in vitro fertilization and embryo transfer (IVF-ET). However, its impact on assisted reproductive outcomes remains to be substantiated by robust evidence. This systematic review aims to summarize and analyze the available evidence to investigate the effect of sequential embryo transfer on assisted reproductive outcomes.MethodsA comprehensive literature search was executed across the Pubmed, Cochrane Library, Web of Science, and Scopus databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were aggregated utilizing a random effects model, and the resultant outcomes were articulated as odds ratios (ORs) along with their 95% confidence intervals (CIs).ResultsThe pooled results revealed a statistically significant enhancement in reproductive outcomes for infertile patients undergoing sequential embryo transfer as evidenced by elevated rates of chemical pregnancy (OR = 1.67, 95% CI = 1.23–2.27), clinical pregnancy (OR = 1.78, 95% CI = 1.43–2.21), and ongoing pregnancy (OR = 1.54, 95% CI = 1.03–2.31). Compared with cleavage-stage embryo transfer, sequential transfer yielded superior outcomes in terms of chemical pregnancy rate (OR = 2.08, 95% CI = 1.35–3.19) and clinical pregnancy rate (OR = 1.78, 95% CI = 1.37–2.31). Furthermore, among the repeated implantation failure (RIF) cohort, sequential embryo transfer surpassed blastocyst-stage transfer, delivering a heightened chemical pregnancy rate (OR = 1.66, 95% CI = 1.19–2.53) and clinical pregnancy rate (OR = 1.65, 95% CI = 1.19–2.27).ConclusionOur meta-analysis indicates that sequential transfer may enhance clinical pregnancy rate in a small subgroup of well-selected women. While promising, further evidence from prospective studies is needed.

Objective: To explore the effect of sequential embryo transfer (ET) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycle and the indications of sequential transfer. Methods: A total of 1440 FET cycles were enrolled in this retrospective study, of which 1080 patients received conventional ET and 360 patients received sequential ET. Further stratified analysis was performed according to the number of previous failed cycles, the number of embryos transferred and the stage of blastocyst (day 5 or 6, denoted D5 or D6) transferred. Comparison of pregnancy rates, implantation rate, miscarriage rate and multiple pregnancy rate among the groups of patients. Results: The clinical pregnancy rate and implantation rate of the sequential ET group were higher than those of the conventional ET group (P < 0.01); however, there was no statistical difference in multiple pregnancy rate and miscarriage rate (P > 0.05). In sequential transfer, the number of transferred embryos (2 or 3) and the stage of transferred blastocysts (D5 or D6) had no effect on clinical pregnancy rate, implantation rate, multiple pregnancy rate and miscarriage rate (P > 0.05). In patients with three or more previous failure cycles, the sequential ET group showed higher clinical pregnancy rate and implantation rate (P > 0.05). Conclusions: Compared with conventional ET in FET cycle, sequential ET strategy could significantly improve the clinical pregnancy rate and implantation rate. In sequential transfer, patients with three embryos transferred don't have higher pregnancy rate and implantation rate. Besides, sequential transfer is more suitable for patients with repeated implantation failures (RIF), and increase the utilization rate of D6 blastocysts. [ABSTRACT FROM AUTHOR]

Background: Uterine blood supply has been identified as a potential factor in implantation failure. Objective: This study aimed to investigate Doppler indices in the uterine artery, including vascular flow and resistance, as well as the amount of sub-endometrial blood supply in women with a history of repeated implantation failure (RIF) compared to the non-RIF group. Materials and Methods: This cross-sectional study was conducted with 139 women candidates for frozen embryo transfer in Yazd Reproductive Sciences Institute, Yazd, Iran from February to July 2023. Group A (n = 68) included women with a history of more than 2 RIF, and group B (n = 71) included women candidates for implantation for the first time without RIF. Doppler ultrasound indices of uterine artery and sub-endometrium, including sub-endometrial flow, uterine artery flow, uterine artery resistance, and peak systolic velocity, were recorded. Results: No significant differences were observed in uterine artery Doppler pulsatility index and peak systolic velocity between groups, but the uterine artery resistance index was significantly higher in the A group (p < 0.001). A significant difference was observed in the perfusion area between groups. 60/68 women in the group A had endometrial perfusion in areas 2 and 3 (p < 0.001). Conclusion: Our study revealed that women with RIF exhibited higher resistance index in sub-endometrial arteries compared to the non-RIF group. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid syndrome (APS) is a group of clinical syndromes of thrombosis or adverse pregnancy outcomes caused by antiphospholipid antibodies, which increase the incidence of in vitro fertilization failure in patients with infertility. However, the common mechanism of repeated implantation failure (RIF) with APS is unclear. This study aimed to search for potential diagnostic genes and potential therapeutic targets for RIF with APS. Methods: To obtain differentially expressed genes (DEGs), we downloaded the APS and RIF datasets separately from the public Gene Expression Omnibus database and performed differential expression analysis. We then identified the common DEGs of APS and RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and we then generated protein-protein interaction. Furthermore, immune infiltration was investigated by using the CIBERSORT algorithm on the APS and RIF datasets. LASSO regression analysis was used to screen for candidate diagnostic genes. To evaluate the diagnostic value, we developed a nomogram and validated it with receiver operating characteristic curves, then analyzed these genes in the Comparative Toxicogenomics Database. Finally, the Drug Gene Interaction Database was searched for potential therapeutic drugs, and the interactions between drugs, genes, and immune cells were depicted with a Sankey diagram. Results: There were 11 common DEGs identified: four downregulated and seven upregulated. The common DEG analysis suggested that an imbalance of immune system-related cells and molecules may be a common feature in the pathophysiology of APS and RIF. Following validation, MARK2, CCDC71, GATA2, and KLRC3 were identified as candidate diagnostic genes. Finally, Acetaminophen and Fasudil were predicted as two candidate drugs. Conclusion: Four immune-associated candidate diagnostic genes (MARK2, CCDC71, GATA2, and KLRC3) were identified, and a nomogram for RIF with APS diagnosis was developed. Our findings may aid in the investigation of potential biological mechanisms linking APS and RIF, as well as potential targets for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients. Methods: We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to August 24, 2022, with language in both English and Chinese. Randomized controlled trials (RCTs) and observational studies that provided data with one of pregnancy outcomes on RIF patients were included in the network meta-analysis (NMA). The odds ratios (OR) and 95% credible interval (CrI) on pregnancy outcomes were summarized by NMA with a random-effects model. We also analyzed data from only RCTs and compared whether the optimal treatment is the same for different failed embryo transfer attempts. Results: The total of 29,906 RIF patients from 154 clinical studies (74 RCTs and 80 non-RCTs) were included in the NMA. In terms of implantation rate (IR), growth hormone (GH) (OR: 3.32, 95% CrI: 1.95–5.67) is the best treatment in all included studies; IVIG+PBMC (5.84, 2.44–14.1) is the best for clinical pregnancy rate (CPR); hyaluronic acid (HA) (12.9, 2.37–112.0) for live birth rate (LBR); and aspirin combined with glucocorticoids (0.208, 0.0494–0.777) for miscarriage rate (MR). The two-dimensional graphs showed that GH could maximize IR and CPR simultaneously; HA and GH could simultaneously increase IR and LBR to a large extent; HA could maximize IR and minimize MR. Conclusion: IVIG+PBMC, GH, and embryo medium enriched with HA could significantly improve pregnancy outcomes in patients with RIF. It appears that combination therapy is a potential administration strategy. Trial registration: This study has been registered on PROSPERO (CRD42022353423). [ABSTRACT FROM AUTHOR]

Background: Recurrent implantation failure (RIF) is more common among patients receiving assisted reproductive treatment. Many efforts have been made to increase the incidence of clinical pregnancy among patients with RIF. The effect of the sequential transfer procedure, a two-step interval transfer of a cleavage-stage embryo followed by a blastocyst in one transfer cycle, on the clinical outcomes of RIF patients remains controversial. Methods: In total, 1774 frozen-thawed embryo transfer (FET) cycles in RIF patients were included. Of these cycles, 302 were sequential embryo transfer (ET) cycles, 979 were double day 3 cleavage-stage ET cycles, and 493 were double blastocyst ET cycles. The primary outcomes were the rates of implantation, clinical pregnancy and multiple pregnancy, and the secondary outcomes were the rates of hCG positive, early miscarriage and ectopic pregnancy. Results: The implantation, hCG positive, and clinical pregnancy rates in the sequential ET group (32.1%, 58.9%, 50.7%) were significantly higher than those in the day 3 cleavage-stage ET group (24.9%, 46.5%, 40.4%) and were similar to those in the blastocyst transfer group (30.1%, 56.4%, 47.1%). The early miscarriage rate in the blastocyst transfer group was significantly higher than that in the cleavage-stage ET group (17.2% vs. 8.1%, P <0.05), while the ectopic pregnancy rate in the blastocyst transfer groupwas significantly lower than that in the cleavage-stage ET group (0.4% vs. 3.0%, P <0.05). The multiple pregnancy rate in the sequential ET group was significantly lower than that in the cleavage-stage ET group (17.0% vs. 25.5%, P <0.05) and the blastocyst transfer group (17.0% vs. 27.6%, P <0.05). When cycles of blastocyst culture failure were excluded, the clinical pregnancy rate was significantly higher (55.7% vs. 47.1%, P <0.05), and the early miscarriage rate and multiple pregnancy rate were significantly lower (8.5% vs. 17.2%, 17.7% vs. 27.6%; P <0.05, respectively) in the sequential ET group than in the double blastocyst ET group. Conclusions: Sequential embryo transfer in FET cycles could improve the clinical outcomes of patients with RIF. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether chronic endometritis (CE) and uterine endometrium microbiota were associated with repeated implantation failures (RIFs) and recurrent pregnancy losses (RPLs). In this prospective study, uterine endometrial specimens were obtained from 24 women with RIF, 27 with RPL, and 29 fertile control women. Immunohistochemical staining of CD138 for CE and 16S ribosomal RNA (rRNA) sequencing analysis for uterine endometrium microbiota were performed simultaneously. To assess CE, Liu's method, McQueen scores and plasma cell count/10 mm2 were used. The frequency of CE (plasma cells > 5.15/10 mm2) was higher in women with RPL (29.6%) than in fertile controls (6.8%, p < 0.05). The plasma cell count/10 mm2 in women with RPL (median 1.53, range 0–252.6, p < 0.01) and women with RIF (median 0.6, range 0–6.98, p < 0.05) was higher than in fertile controls (median 0, range 0–29). The uterine endometrium microbiota in women with RPL or RIF was not significantly different from that in fertile controls. However, the relative dominance rate of Lactobacillus iners (median 4.7%, range 0–99.9 vs. median 0%, range 0–100, p < 0.001) and the positive rate of Ureaplasma species (36.3% vs. 8.6%, p < 0.05) were higher in 11 women with CE than in 69 women without CE. The results suggest that CE may be involved in the pathophysiology of RPL and RIF. Lactobacillus iners and Ureaplasma species may be associated with the etiology of CE. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) for infertility and recurrent spontaneous abortion. Methods Existing research was searched in PubMed, Embase and Cochrane Library till Dec 2021. Randomized control trials (RCTs) that compared G-CSF administration with the control group in infertility women undergoing IVF were included. The primary outcomes included clinical pregnancy rate; the secondary outcomes included live birth rate, abortion ratebiochemical pregnancy rate, embryo implantation rate, as well as endometrial thickness. Result(s) 20 RCTs were included in this study. G-CSF increased the clinical pregnancy rate (RR = 1.85; 95% CI: 1.07, 3.18) and the endometrial thickness (MD = 2.25; 95% CI: 1.58,2.92;) in patients with thin endometrium undergoing IVF. G-CSF increased the biochemical pregnancy rate (RR = 2.12; 95% CI: 1.54, 2.93), the embryo implantation rate (RR = 2.51; 95% CI: 1.82, 3.47) and the clinical pregnancy rate (RR = 1.93; 95% CI: 1.63, 2.29) in patients with a history of repeated implantation failure undergoing IVF. No differences were found in pregnancy outcomes of general IVF patients. Conclusions Granulocyte colony-stimulating factor is likely to be a potential option for infertility women undergoing IVF with thin endometrium or recurrent implantation failure . Trial registration Retrospectively registered (The PROSPERO registration number: CRD42022360161).

Abstract Objective To evaluate the clinical availability and stability of histological endometrial dating as a tool for personalized frozen-thawed embryo transfer (pFET) in patients with repeated implantation failure (RIF) in natural cycles. Methods A total of 1245 RIF patients were recruited to the present study. All of the patients received an endometrial dating evaluation on day 7 post-ovulation (PO + 7) to guide their first pFET. The second and third pFETs were executed according to histological examination (again employing biopsy) or by reference to previous results. Subsequent pregnancy outcomes for all of the cycles were ultimately tracked. Results The out-of-phase rate for RIF patients was 32.4% (404/1245) and the expected dating rate (the probability of the expected endometrial dating aligning with repeat biopsy) for endometrial dating reevaluation was as high as 94.3% (50/53). The clinical pregnancy rates of first, second, and third pFETs were 65.3%, 50.0%, and 44.4%, respectively; and the cumulative clinical pregnancy rate attained 74.9% after three transfers. Endometrial dating reevaluations met expectations with more than a 2-year duration in three cases and elicited favorable clinical outcomes. Conclusion We validated the relatively high stability of the histological endometrial dating platform—including the out-of-phase rate and the expected dating rate of reevaluation in patients with RIF—by expanding the sample size. The pFET, based on histological endometrial dating, was of acceptable clinical value and was worthy of promotion in patients with unexplained RIF.

ObjectiveEndometrial scratching (ES) during hysteroscopy before embryotransfer (ET) remains doubtable on whether it benefits the reproductive outcomes. The optimal technique is not clear and repeated implantation failure as a challenging field in in vitro fertilization (IVF) seems to be the springboard for clinicians to test its effectiveness.MethodsMedline, PMC, ScienceDirect, Scopus, CENTRAL, Google Scholar were searched from their inception up to April 2023 for studies to evaluate the effectiveness of adding endometrial scratching during hysteroscopy before ET.ResultsThe initial search yielded 959 references, while 12 eligible studies were included in the analyses, involving 2,213 patients. We found that hysteroscopy and concurrent ES before ET resulted in a statistically significant improvement in clinical pregnancy rate (CPR) [RR = 1.50, (95% CI 1.30–1.74), p

Introduction: Successful embryo implantation, is the initiating step of pregnancy, relies on not only the high quality of the embryo but also the synergistic development of a healthy endometrium. Characterization and identification of biomarkers for the receptive endometrium is an effective method for increasing the probability of successful embryo implantation. Methods: Endometrial tissues from 22 women with a history of recurrent implantation failure (RIF) and 19 fertile controls were collected using biopsy catheters on 7-9 days after the peak of luteinizing hormone. Differentially expressed proteins (DEPs) were identified in six patients with RIF and six fertile controls using isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis. Results: Two hundred and sixty-three DEPs, including proteins with multiple bioactivities, such as protein translation, mitochondrial function, oxidoreductase activity, fatty acid and amino acid metabolism, were identified from iTRAQ. Four potential biomarkers for receptive endometrium named tubulin polymerizationpromoting protein family member 3 TPPP3, S100 Calcium Binding Protein A13 (S100A13), 17b-hydroxysteroid dehydrogenase 2 (HSD17B2), and alpha-2-glycoprotein 1, zinc binding (AZGP1) were further verified using ProteinSimple Wes and immunohistochemical staining in all included samples (n=22 for RIF and n=19 for controls). Of the four proteins, the protein levels of TPPP3 and HSD17B2 were significantly downregulated in the endometrium of patients with RIF. Discussion: Poor endometrial receptivity is considered the main reason for the decrease in pregnancy success rates in patients suffering from RIF. iTRAQ techniques based on isotope markers can identify and quantify low abundance proteomics, and may be suitable for identifying differentially expressed proteins in RIF. This study provides novel evidence that TPPP3 and HSD17B2 may be effective targets for the diagnosis and treatment of non-receptive endometrium and RIF. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures? SUMMARY ANSWER The use of TER-guided pET is not supported by current published evidence in women without repeated implantation failure (RIF), while in women with RIF more research is needed to assess a potential benefit. WHAT IS KNOWN ALREADY Implantation rates are still far from ideal, especially in some patients that have RIF with good-quality embryos. As a potential solution, a wide range of diverse TER use different sets of genes to identify displacements of the window of implantation to adjust the individual length of progesterone exposure in a pET. STUDY DESIGN, SIZE, DURATION A systematic review with meta-analysis was performed. Search terms included endometrial receptivity analysis, ERA, personalized embryo transfer. CENTRAL, PubMed, Embase, reference lists, clinical trials registers, and conference proceedings (search date October 2022) were searched, with no language restrictions. PARTICIPANTS/MATERIALS, SETTING, METHODS Randomized controlled trials (RCTs) and cohort studies comparing a pET guided by TER vs standard embryo transfer (sET) in different subgroups that undergo ART were identified. We also investigated pET in non-receptive-TER vs sET in receptive-TER, and pET in a specific population vs sET in a general population. Risk of bias (RoB) was assessed with the Cochrane tool and ROBINS-I. Only those with low/moderate RoB underwent meta-analysis. The GRADE approach was used to evaluate the certainty of evidence (CoE). MAIN RESULTS AND THE ROLE OF CHANCE We screened 2136 studies and included 35 (85% used ERA and 15% used other TER). Two studies were RCTs comparing endometrial receptivity analysis (ERA)-guided pET vs sET in women with no history of RIF. In women without RIF, no important differences (moderate-CoE) were found in live birth rates and clinical pregnancy rates (CPR). We also performed a meta-analysis of four cohort studies that were adjusted for confounding. In agreement with the RCTs, no benefits were found in women without RIF. However, in women with RIF, low CoE suggests that pET might improve the CPR (OR 2.50, 95% CI 1.42–4.40). LIMITATIONS, REASONS FOR CAUTION We found few studies with low RoB. Only two RCTs in women without RIF were published, and none in women with RIF. Furthermore, the heterogeneity observed in populations, interventions, co-interventions, outcomes, comparisons, and procedures limited the pooling of many of the included studies. WIDER IMPLICATIONS OF THE FINDINGS In the population of women without RIF, in agreement with previously published reviews, pET did not prove to be more effective than sET and, therefore, it precludes the routine use of this strategy in this population until more evidence is available. However, more research is advisable in women with RIF as low-certainty evidence from observational studies adjusted for confounders suggests that the CPR might be higher with pET guided by TER in this population. Although this review presents the best available evidence, it is still insufficient to change current policies. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained for this study. There are no conflicts of interest to declare. REGISTRATION NUMBER PROSPERO CRD42022299827. [ABSTRACT FROM AUTHOR]

After more than a decade of increasingly widespread clinical use, personalized embryo transfer guided by endometrial receptivity analysis (ERA) remains controversial and unproven. One key element missing from the historical literature is the recognition that potential benefits from personalized embryo transfer are entirely dependent on the accuracy and predictive value of the ERA test. Results from the first comprehensive clinical trial, designed in a way that allowed independent evaluation of both potential benefits of personalized embryo transfer and the predictive value of the ERA test upon which it is based, were recently published. However, the authors failed to conduct an appropriate analysis or recognize the significance of their results. Here, we present a simple reanalysis of data from this otherwise excellent randomized controlled trial, demonstrating for the first time that the ERA was unable to identify the window of implantation as purported and that, as a result, personalized embryo transfer based on the ERA actually reduced rather than increased the birth rates. Based on these results and the lack of any contradictory evidence, it is our opinion that all clinical use of ERA-guided personalized embryo transfer should be discontinued immediately, outside of a controlled experimental setting with appropriate informed consent of all participating patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective study was to investigate whether oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone) are beneficial for patients with repeated implantation failure (RIF) and chronic endometritis (CE) to improve clinical pregnancy outcomes. Methods: Patients with RIF and CE were diagnosed using hysteroscopy and histology together. A total of 42 patients were enrolled in the study. All patients received oral antibiotics (doxycycline combined with metronidazole) and 22 patients underwent intrauterine perfusion (gentamicin combined with dexamethasone) immediately after the end of oral antibiotic therapy. Pregnancy outcomes were evaluated during the first in vitro fertilization (IVF) and embryo transfer (ET) cycle. Results: For the first D3 ET after treatment with oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone), higher embryo implantation rate (30.95% vs. 26.67%, P = 0.0308), clinical pregnancy rate (30% vs. 50%, P < 0.001), live birth rate (33.33% vs. 45.45%, P < 0.0001). No fetal malformations or ectopic pregnancies were observed. Conclusion: We report oral antibiotics (doxycycline and metronidazole) combined with intrauterine perfusion (gentamicin and dexamethasone) as a novel treatment for CE to improve the outcomes of successful pregnancy compared with those of oral antibiotics alone. [ABSTRACT FROM AUTHOR]

Introduction: Repeated implantation failure is a common challenge in daily practice. Homocysteine and vitamin B12 have been associated with reproductive processes among patients undergoing in vitro fertilization; however, their involvement in repeated implantation failure has not been assessed. We explored possible associations of serum homocysteine and vitamin B12 with repeated implantation failure. Material and methods: A retrospective analysis of 127 women who underwent ≥ 3 unsuccessful embryo transfers during 2005–2016, at the Fertility and In Vitro Fertilization Unit at Carmel Medical Center. After at least 3 IVF failures serum levels of homocysteine and vitamin B12 were measured. Results: The mean patient age was 33.5 ± 5.2 years. The mean number of embryo transfers was 4.6 ± 1.5. The mean total cumulative number of embryos transferred was 10.4 ± 5.2. Mean serum levels of homocysteine were 8.6 ± 3.7 µM/L, and of vitamin B12 were 302.5 ± 155.3 pg/ml. Homocysteine levels were within the normal range (< 14 µM/L) in 95.8% of the patients. Yet, the levels of homocysteine correlated with both the number of failed embryo transfers (r = 0.34, p = 0.004) and the total cumulative number of transferred embryos (r = 0.36, p = 0.002). Conclusions: Our findings suggest an association between serum homocysteine levels and the occurrence of repeated implantation failure, even when homocystein levels were within the normal range. It should be studied whether nutritional supplementation to modulate serum homocysteine levels may improve treatment outcome. [ABSTRACT FROM AUTHOR]

Objective: To assess whether chronic endometritis (CE) affects embryo implantation in patients with repeated implantation failure (RIF). Materials and methods: We retrospectively analyzed 126 RIF patients who were never diagnosed with CE and received no prior antibiotic therapy. Endometrial specimens obtained by endometrial scratching during mid-luteal phase were immunostained by CD138, a hallmark plasmacyte marker, to identify CE. Pregnancy outcome in RIF patients who underwent IVF-ET frozen-embryo within transfers 6 months after endometrial scratching was compared between women with and without CE. Results: The prevalence of CE in patients with RIF was found to be 11.9% (15/126). Moreover, a significantly reduced clinical pregnancy rate was observed in RIF patients with CE (20% vs. 46.85%; p = 0.04). The live birth rate also exhibited a decreasing trend in RIF patients with CE, although there was no statistically significant difference (20% vs. 41.58%; p = 0.109). Conclusions: CE may be involved in the failure of embryo implantation and reduced clinical pregnancy outcome in patients with RIF.

Objective: This study aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) for infertility and recurrent spontaneous abortion. Methods: Existing research was searched in PubMed, Embase and Cochrane Library till Dec 2021. Randomized control trials (RCTs) that compared G-CSF administration with the control group in infertility women undergoing IVF were included. The primary outcomes included clinical pregnancy rate; the secondary outcomes included live birth rate, abortion ratebiochemical pregnancy rate, embryo implantation rate, as well as endometrial thickness. Result(s): 20 RCTs were included in this study. G-CSF increased the clinical pregnancy rate (RR = 1.85; 95% CI: 1.07, 3.18) and the endometrial thickness (MD = 2.25; 95% CI: 1.58,2.92;) in patients with thin endometrium undergoing IVF. G-CSF increased the biochemical pregnancy rate (RR = 2.12; 95% CI: 1.54, 2.93), the embryo implantation rate (RR = 2.51; 95% CI: 1.82, 3.47) and the clinical pregnancy rate (RR = 1.93; 95% CI: 1.63, 2.29) in patients with a history of repeated implantation failure undergoing IVF. No differences were found in pregnancy outcomes of general IVF patients. Conclusions: Granulocyte colony-stimulating factor is likely to be a potential option for infertility women undergoing IVF with thin endometrium or recurrent implantation failure. Trial registration: Retrospectively registered (The PROSPERO registration number: CRD42022360161). [ABSTRACT FROM AUTHOR]

Can time-lapse parameters and the transcriptional profile of cumulus cells be used to achieve a more stringent and non-invasive method of embryo assessment and to identify possible factors affecting the embryo's ability to implant in repeated implantation failure (RIF) patients? A total of 190 embryos from 18 oocyte donors and 145 embryos from 15 RIF patients were evaluated based on time-lapse parameters. Three morphokinetic parameters including T5 (time to reach five cells), T3 (time to reach three cells) and CC2 (time to two to three cells) were recorded for all embryos. Embryos that had all three parameters in the normal range were graded as high quality and comparison between these parameters were compared in high-quality embryos between two groups. The transcriptional profile of cumulus cells related to high-quality embryos of both groups were analysed by RNA sequencing and compared. Finally, the possible relationship between differentially expressed genes and time-lapse parameters was examined. T5 was significantly lower in the RIF group than the donor group (P = 0.011). The cumulus cell transcriptome analysis showed 193 genes were down-regulated and 222 genes up-regulated. The mammalian target of rapamycin and the transforming growth factor beta pathways were significantly increased in the RIF group compared to the donor group (P = 0.007 and 0.01, respectively). Vitamin B12 and fatty acid beta-oxidation pathways were also significantly reduced in the RIF group compared to the donor group (P = 0.006 and 0.01, respectively). Differences in the transcriptomic profiles of cumulus cells and some morphokinetic parameters may be one of the main factors contributing to unexplained RIF. [Display omitted] [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of sequential transfer that one cleavage-stage embryo on day 3 and one blastocyst on day 5 are sequentially transferred in the same treatment cycle over conventional day 3 embryo transfer and blastocyst transfer in patients with repeated implantation failure (RIF). Study Design: 2836 frozen embryo transfer (FET) cycles in patients with RIF were divided into three groups according to female age: <35, 35–39 and >39 years old groups, and four groups depending on the number and period of embryo transferred: two day 3 embryo, two blastocyst, single blastocyst and sequential transfer groups; Pregnancy outcomes including implantation rate (IR), clinical pregnancy rate (CPR), abortion rate (AR), ectopic pregnancy rate (EPR), multiple pregnancy rate (MPR), live birth rate (LBR) and neonatal characteristics from all the groups were assessed. Sequential transfer caused a significant increase in the IR, CPR and LBR over two day 3 embryo transfer and did not improve the IR, CPR and LBR over two blastocyst transfer in patients with RIF. Sequential transfer had higher CPR, MPR and LBR and lower IR than single blastocyst transfer. No significant differences were present in neonatal characteristics among the transfer protocol groups. Singleton group had a higher average gestational age and birthweight as well as a lower cesarean section rate, preterm labor rate and low birthweight rate than twin group. Additionally, the AR had no significant difference and the EPR of blastocyst transfer was low. Sequential transfer was not an effective method to improve IR in patients with RIF, and blastocyst transfer with higher IR was suggested. Single blastocyst transfer could serve as an effective transfer protocol to reduce MPR. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical availability and stability of histological endometrial dating as a tool for personalized frozen-thawed embryo transfer (pFET) in patients with repeated implantation failure (RIF) in natural cycles. Methods: A total of 1245 RIF patients were recruited to the present study. All of the patients received an endometrial dating evaluation on day 7 post-ovulation (PO + 7) to guide their first pFET. The second and third pFETs were executed according to histological examination (again employing biopsy) or by reference to previous results. Subsequent pregnancy outcomes for all of the cycles were ultimately tracked. Results: The out-of-phase rate for RIF patients was 32.4% (404/1245) and the expected dating rate (the probability of the expected endometrial dating aligning with repeat biopsy) for endometrial dating reevaluation was as high as 94.3% (50/53). The clinical pregnancy rates of first, second, and third pFETs were 65.3%, 50.0%, and 44.4%, respectively; and the cumulative clinical pregnancy rate attained 74.9% after three transfers. Endometrial dating reevaluations met expectations with more than a 2-year duration in three cases and elicited favorable clinical outcomes. Conclusion: We validated the relatively high stability of the histological endometrial dating platform—including the out-of-phase rate and the expected dating rate of reevaluation in patients with RIF—by expanding the sample size. The pFET, based on histological endometrial dating, was of acceptable clinical value and was worthy of promotion in patients with unexplained RIF. [ABSTRACT FROM AUTHOR]

The tolerance of the immune system for the semi-allogeneic embryo is promoted by several factors and the cells involved in the immune system and factors in the mother during pregnancy. The dysregulation of the immune responses between the mother and fetus is a risk factor that raises the likelihood of rejection of the embryo and reproductive failure. To safeguard embryos and prevent immunological attacks, it is critical to suppress immunological rejection and encourage immunological tolerance. Based on current medical literature, it seems that immune cell management through immunosuppressive therapies can address reproductive failures. Immunosuppressive treatment has demonstrated encouraging results in terms of enhancing outcomes related to pregnancy and rates of live birth by regulating the immune responses of mothers and positively impacting the reproductive processes of humans. Currently, there is scarcity of high-quality data regarding the safety and efficacy of immunosuppressive therapies for children and mothers. Therefore, it is important to exercise caution while selecting use of any immunosuppressive therapy in pregnancy. This mini review provides a comprehensive overview of the existing literature regarding the impact of Calcineurin Inhibitors and anti-TNF treatment on improving the live birth rate following embryo transfer.

Background: A major challenge in reproductive medicine is repeated implantation failure (RIF). Possible benefits of platelet-rich plasma (PRP) for pregnancy outcomes are still uncertain, and more evidence is required to properly evaluate this. The current meta-analysis was therefore carried out to assess the impact of intrauterine PRP infusion on pregnancy outcomes in women with RIF. Methods: Various databases (Web of Science, PubMed, Cochrane Library, Embase) were screened for English-language papers that investigated the effect of PRP treatment on pregnancy outcomes in RIF women who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This effect was analyzed in both frozen-thawed and fresh cycles. These studies involved randomized controlled trial (RCT) and quasi-experimental (non-randomized experimental) studies, but excluded case-control, case series, self-control, cross-sectional studies. The Newcastle-Ottawa Scale was employed to determine study quality. Risk ratios (RRs) were calculated for dichotomous outcome variables, and weighted mean difference (WMD) with 95% confidence interval (95% CI) for continuous outcome variables. These were performed under fixed- or random-effect models. Results: This meta-analysis evaluated 15 articles from the literature. Improved pregnancy outcomes were observed in RIF women who received PRP, including higher rates of implantation, clinical pregnancy and live birth compared to control patients. Conclusions: The results of this study indicate that PRP could be a useful treatment strategy for RIF patients and those with a thin endometrium. Additional large RCTs are required to identify the subpopulation of women who could derive the maximum benefit from PRP.

Recent studies have investigated if and how the vaginal and endometrial microbiome might affect endometrial receptivity and reproductive health. Although there is no consensus on the existence of a core uterine microbiome yet, evidence shows that the dominance of Lactobacillus spp. in the female reproductive tract is generally associated with eubiosis and improved chances of successful implantation and an ongoing pregnancy. Conversely, vaginal and endometrial dysbiosis can cause local inflammation and an increase of pro-inflammatory cytokines, compromising the integrity and receptivity of the endometrial mucosa and potentially hampering successful embryonic implantation. This review provides a critical appraisal of the influence of the vaginal and endometrial microbiome as parts of the female reproductive tract on fertility outcomes, focusing on repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It seems that RIF as well as RPL are both associated with an increase in microbiome diversity and a loss of Lactobacillus dominance in the lower female reproductive system.

OBJECTIVE: To probe into the effects of autologous platelet-rich plasma (PRP) combined with granulocyte colony-stimulating factor (G-CSF) for intrauterine perfusion on endometrial receptivity (ER) and clinical outcome in patients with repeated implantation failure (RIF). METHODS: Totally 76 patients with RIF admitted into this hospital from Jan. 2020 to Jul. 2022 were selected and divided into PRP+G-CSF perfusion group (38 cases) and control group (no perfusion, 38 cases) according to whether or not intrauterine perfusion was performed before frozenthawed embryo transfer. The embryo implantation rates, chemical pregnancy rates, clinical pregnancy rates, early miscarriage rates and ectopic pregnancy rates of both groups were recorded, the thickness, morphology, blood flow type and hemodynamic indexes [uterine artery pulsatility index (PI), resistance index (RI)] of endometrium were compared between two groups on the day of embryo transfer, and the incidence of adverse events of uterine perfusion in the PRP+G-CSF group was recorded. RESULTS: After treatment, the embryo implantation rate, chemical pregnancy rate and clinical pregnancy rate of the PRP+G-CSF group were respectively 46. 88% (30/38), 60. 53% (23/38) and 60. 53% (23/38), which were higher than those of the control group [26. 56%(17/38), 31. 58%(12/38) and 31. 58%(12/38)], with statistically significant differences (P<0. 05). The early abortion rates were 4. 35% (1/23) and 16. 67% (2/12) in the two groups, with no statistically significant difference (P>0. 05). No ectopic pregnancy occurred in both groups, and there were no adverse events of intrauterine perfusion in the PRP+G-CSF group. On the day of embryo transfer, the endometrial thickness of patients in the PRP +G-CSF group was (10. 20±2. 02) mm, which was thicker than that of the control group [(9. 15±1. 51) mm], with statistically significant difference (P < 0. 05); the percentage of endometrial blood flow type GⅡ or above and the percentage of C-type endometrium were respectively 86. 84% (33/38) and 89. 47% (34/38), which were higher than those in the control group [65. 79% (25/38) and 71. 05%(27/38)], with statistically significant differences (P<0. 05). On the day of embryo transfer, the uterine artery PI and RI levels of patients in the PRP+G-CSF group were 2. 35±0. 53 and 0. 83±0. 08, which were lower than those of the control group (2. 69±0. 49 and 0. 87±0. 09), with statistically significant differences (P < 0. 05). CONCLUSIONS: PRP combined with G-CSF intrauterine perfusion can improve endometrial thickness and blood perfusion in patients with RIF, thus improve their ER and pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Chronic endometritis (CE) is a local mucosal inflammatory disorder of the uterine lining, which is histopathologically recognized as the unusual infiltration of CD138(+) plasmacytes into the endometrial stromal compartment. Accumulating body of research documented that CE is associated with female infertility and several obstetric/neonatal complications. The major cause of CE is thought to be intrauterine infection represented by common bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus, and Staphylococcus), Mycoplasma/Ureaplasma, and Mycobacterium. Additionally, local dysbiosis in the female reproductive tract may be involved in the onset and development of CE. Antibiotic treatments against these microorganisms are effective in the elimination of endometrial stromal plasmacytes in the affected patients. Meanwhile, endometriosis is a common female reproductive tract disease characterized by endometriotic tissues (ectopic endometrium) growing outside the uterus and potentially causes chronic pelvic symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), infertility, and ovarian cancers. Endometriosis involves endocrinological, genetic, and epigenetic factors in its etiology and pathogenesis. Recent studies focus on immunological, inflammatory, and infectious aspects of endometriosis and demonstrate several common characteristics between endometriosis and CE. This review aimed to better understand the immunological and microbial backgrounds underlying endometriosis and CE and look into the therapeutic potential of the novel antibiotic treatment strategy against endometriosis in light of endometrial infectious disease. [ABSTRACT FROM AUTHOR]