Platelet rich plasma alleviates endometritis induced by lipopolysaccharide in mice via inhibiting TLR4/NF-κB signaling pathway.

BACKGROUND: Endometritis is an inflammatory reaction of the lining of uterus, leading to the occurrence of infertility. Platelet rich plasma (PRP) has been proven to exhibit extremely effective for the treatment of endometrium-associated infertility, but the mechanism of its prevention for endometritis remains unclear. OBJECTIVE: The present study aimed to investigate the protective effect of PRP against endometritis induced by lipopolysaccharide (LPS) and elucidate the mechanism underlying these effects. METHODS: Mouse model of endometritis was established by intrauterine perfusion of LPS. PRP intrauterine infusion was administered at 24 h after LPS induction. After another 24 h, the uterine tissues were harvested to observe histopathological changes, production of proinflammatory cytokines, variation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathways, and validated the anti-inflammatory effect of PRP. The myeloperoxidase (MPO) activity and concentration of nitric oxide (NO) were determined using assay kit. Proinflammatory chemokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)) were measured by ELISA and Real-Time PCR. The activity of TLR4/NF-κB pathway in uterine tissues was measured by Western blotting. RESULTS: Hematoxylin-eosin staining (H&E) appeared that PRP remarkably relieved the impairment of uterine tissues. Detection of MPO activity and concentration of NO revealed that PRP treatment distinctly mitigated infiltration of inflammatory cells in mice with endometritis induced by LPS. PRP treatment significantly affected the expression of TNF-α, IL-1ß, and IL-6. PRP was also found to suppress LPS-induced activation of TLR4/NF-κB pathway. CONCLUSION: PRP effectively alleviates LPS-induced endometritis via restraining the signal pathway of TLR4/NF-κB. These findings provide a solid foundation for PRP as a potential therapeutic agent for endometritis.

Prediction model for missed abortion of patients treated with IVF-ET based on XGBoost: a retrospective study.

Aim: In this study, we established a model based on XGBoost to predict the risk of missed abortion in patients treated with in vitro fertilization-embryo transfer (IVF-ET), evaluated its prediction ability, and compared the model with the traditional logical regression model. Methods: We retrospectively collected the clinical data of 1,017 infertile women treated with IVF-ET. The independent risk factors were screened by performing a univariate analysis and binary logistic regression analysis, and then, all cases were randomly divided into the training set and the test set in a 7:3 ratio for constructing and validating the model. We then constructed the prediction models by the traditional logical regression method and the XGBoost method and tested the prediction performance of the two models by resampling. Results: The results of the binary logistic regression analysis showed that several factors, including the age of men and women, abnormal ovarian structure, prolactin (PRL), anti-Müllerian hormone (AMH), activated partial thromboplastin time (APTT), anticardiolipin antibody (ACA), and thyroid peroxidase antibody (TPO-Ab), independently influenced missed abortion significantly (P < 0.05). The area under the receiver operating characteristic curve (AUC) score and the F1 score with the training set of the XGBoost model (0.877 ± 0.014 and 0.730 ± 0.019, respectively) were significantly higher than those of the logistic model (0.713 ± 0.013 and 0.568 ± 0.026, respectively). In the test set, the AUC and F1 scores of the XGBoost model (0.759 ± 0.023 and 0.566 ± 0.042, respectively) were also higher than those of the logistic model (0.695 ± 0.030 and 0.550 ± 049, respectively). Conclusions: We established a prediction model based on the XGBoost algorithm, which can accurately predict the risk of missed abortion in patients with IVF-ET. This model performed better than the traditional logical regression model.

Application of artificial neural networks in reproductive medicine.

With the emergence of the age of information, the data on reproductive medicine has improved immensely. Nonetheless, healthcare workers who wish to utilise the relevance and implied value of the various data available to aid clinical decision-making encounter the difficulty of statistically analysing such large data. The application of artificial intelligence becoming widespread in recent years has emerged as a turning point in this regard. Artificial neural networks (ANNs) exhibit beneficial characteristics of comprehensive analysis and autonomous learning, owing to which these are being applied to disease diagnosis, embryo quality assessment, and prediction of pregnancy outcomes. The present report aims to summarise the application of ANNs in the field of reproduction and analyse its further application potential.

Association between hysteroscopic features of chronic endometritis and pregnancy outcomes of patients after in vitro fertilization: a retrospective cohort study.

This retrospective cohort study explored the morphological features of chronic endometritis (CE) and pregnancy outcomes during in vitro fertilization (IVF) in women with CE (429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The primary outcome was the clinical pregnancy rate (CPR). The women displayed haemorrhagic spots (175), hyperaemia (122), micropolyps (75), hyperaemia combined with micropolyps (49) and others (8). The CPR and live birth rate (LBR) were different among the hysteroscopic features of CE in fresh embryo transfer cycles (p = .002, p = .011). The miscarriage and premature birth rates were not significantly different among groups (p > .05). Hyperaemia (0.47 [95% CI, 0.29; 0.77]), micropolyps (0.40 [95% CI, 0.23; 0.72]), hyperaemia combined with micropolyps (0.35 [95% CI, 0.18; 0.69]) and others (0.36 [95% CI, 0.19; 0.69]) were associated with the CPR. In conclusion, the hysteroscopic features of CE are associated with IVF pregnancy outcomes, and there were differences in pregnancy outcomes with different CE hysteroscopic features.IMPACT STATEMENTWhat is already known on this subject? Chronic endometritis (CE) is associated with adverse pregnancy outcomes such as infertility, premature delivery and miscarriage. CE can reduce the success rate of pregnancy and even lead to obstetric and neonatal complications, and is an adverse factor for the success of in vitro fertilization (IVF). There are different types of CE, but their impact on IVF outcomes is unknown.What the results of this study add? The CPR and LBR were different among the hysteroscopic features of CE in fresh embryo transfer cycles (p = .002, p = .011). The miscarriage and premature birth rates were not significantly different among groups (p > .05). After adjustment, the multivariable analysis showed that hyperaemia (OR = 0.47, p = .002), micropolyps (OR = 0.40, p = .002), hyperaemia combined with micropolyps (OR = 0.35, p = .002) and others (OR = 0.36, p = .002) were associated with the CPR among patients with CE.What the implications are of these findings for clinical practice and/or further research? The hysteroscopic features of CE are associated with IVF pregnancy outcomes, and there were differences in pregnancy outcomes with different CE hysteroscopic features. Hence, women with repeated IVF failure should undergo hysteroscopy to examine for the presence of CE and its nature.

Investigation of the Relationship between Chronic Endometritis Manifestations under Hysteroscope and CD138 Expression.

Methods: This study was performed to retrospectively analyze clinical cases of 523 CE patients from January 2018 to June 2020 that were confirmed by hysteroscopy before in vitro fertilization. Based on manifestations of CE under hysteroscopy, the cases were divided into three cohorts, i.e., hyperemia cohort where the patients had diffuse endometrium hyperemia; endometrial micropolyp cohort, and endometrial stroma edema and hyperplasia cohort. Small amount of endometrial tissue was collected from the patients, and CD138 IHC examination was performed. According to the results of CD138 IHC, positive patients were given antibiotic treatment (doxycycline 100 mg BID orally for 14 days), and hysteroscopy was performed again after treatment to check the efficacy of antibiotics. Results: In the comparison of overall status for all patient cohorts, infertility type, BMI, bFSH, bLH, bP, bT, PRL, AMH, and CA125 were varied markedly across all cohorts (P < 0.05), with predominant incidences of polycystic ovary syndrome (PCOS) peaking within hyperemia cohort. Incidence/diagnostic rate for CD138 within hyperemia cohort was 10.06%, which was lower than the 63.16% in micropolyp cohort and 74% in edema and hyperplasia cohort (P < 0.05). No major variation existed within CD138 across micropolyp cohort/edema and hyperplasia cohort (P > 0.05). After CD138-positive CE patients were treated with antibiotics, the effective rate (0/16) within hyperemia cohort was lower than micropolyp cohort (73.61%, 53/72) and edema and hyperplasia cohort (83.24%, 154/185) (P < 0.05). The effective rate across micropolyp cohort/edema and hyperplasia cohort was not significantly different (P > 0.05). Conclusion: Cases of diffuse endometrial hyperemia under hysteroscope had the lowest positive rate of CD138, and the effect of antibiotic treatment on these patients was poor. The positive rate of CD138 in patients with endometrial micropolyps and endometrial stroma edema and hyperplasia under hysteroscope was high, and the effect of antibiotic treatment was better.

Intrauterine Perfusion of Autologous Platelet-Rich Plasma Before Frozen-Thawed Embryo Transfer Improves the Clinical Pregnancy Rate of Women With Recurrent Implantation Failure.

Objective: To evaluate whether the intrauterine perfusion of platelet-rich plasma (PRP) before frozen-thawed embryo transfer (FET) improves the pregnancy outcomes of patients with repeated implantation failure (RIF). Methods: This retrospective study included 288 infertile women with RIF after undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment from October 1, 2019, to January 1, 2021, at Qingdao Women and Children's Hospital. Patients were divided into two groups according to whether they received PRP intrauterine perfusion before embryo transfer in FET cycles. 138 women were in the PRP group, 150 women were in the control group. The primary outcome measure was live birth rates and the secondary outcome were clinical pregnancy, positive ß hCG, miscarriage and implantation rates. Results: No significant differences in baseline demographic and clinical characteristics were observed between the two groups. Overall, significantly more women in the PRP group than in the control group achieved a live birth rate (41 women; 29.71% vs. 27 women; 18%) and a clinical pregnancy (50 women; 36.23% vs. 37 women; 24.67%). The PRP group had a higher implantation rate and lower spontaneous miscarriage rate than the control group, but these differences were not statistically significant. No pregnancy outcome difference between two groups in PCOS patients with RIF. Conclusion: Our results showed that intrauterine perfusion of PRP before embryo transfer in FET cycles can significantly increase the live birth and clinical pregnancy rates in patients with RIF.

Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle: A Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles. METHODS: We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study. RESULTS: Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01-1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02-1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00-1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05). CONCLUSION: The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, Chictr-TRC-14004494.

Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.

BACKGROUND: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF). METHODS: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age. Three blastocysts were screened by next-generation sequencing in the PGT-A group or were chosen by morphologic criteria in the conventional-IVF group and then were successively transferred one by one. The primary outcome was the cumulative live-birth rate after up to three embryo-transfer procedures within 1 year after randomization. We hypothesized that the use of PGT-A would result in a cumulative live-birth rate that was no more than 7 percentage points higher than the rate after conventional IVF, which would constitute the noninferiority margin for conventional IVF as compared with PGT-A. RESULTS: A total of 1212 patients underwent randomization, and 606 were assigned to each trial group. Live births occurred in 468 women (77.2%) in the PGT-A group and in 496 (81.8%) in the conventional-IVF group (absolute difference, -4.6 percentage points; 95% confidence interval [CI], -9.2 to -0.0; P<0.001). The cumulative frequency of clinical pregnancy loss was 8.7% and 12.6%, respectively (absolute difference, -3.9 percentage points; 95% CI, -7.5 to -0.2). The incidences of obstetrical or neonatal complications and other adverse events were similar in the two groups. CONCLUSIONS: Among women with three or more good-quality blastocysts, conventional IVF resulted in a cumulative live-birth rate that was noninferior to the rate with PGT-A. (Funded by the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03118141.).

The effect of thyroid autoantibody on assisted reproduction technology outcome in euthyroid women: One center experience.

Thyroid dysfunction is an important factor to cause failure in assisted reproduction technology (ART) procedures. In this study, we recorded the serum level of thyroid autoantibody to fig. out its relationship with the ART outcome. The results showed that the serum concentrations of TSH had a statistically significant increase between the basal level and the levels at time of serum pregnancy test both in women with and without thyroid autoantibody (p= 0.002 and p=0.019, respectively). Additionally, the TSH level increased significantly in thyroid autoantibody-positive group than those in thyroid autoantibody-negative group during controlled ovarian hyper stimulation (COH) process(p = 0.006). The risk of preterm delivery was lower in thyroid autoantibody-negative group. In sum, the present study provided evidence of an association between thyroid autoantibody and preterm delivery in euthyroid women.

Effect of Orlistat on Live Birth Rate in Overweight or Obese Women Undergoing IVF-ET: A Randomized Clinical Trial.

CONTEXT: Obesity management prior to infertility treatment remains a challenge. To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no evidence of improved live birth rate. OBJECTIVE: This work aimed to determine whether pharmacologic weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25 or greater were randomly assigned to receive orlistat (n = 439) or placebo (n = 438) treatment for 4 to 12 weeks. The main outcome measurement was the live birth rate after fresh ET. RESULTS: The live birth rate was not significantly different between the 2 groups (112 of 439 [25.5%] with orlistat and 112 of 438 [25.6%] with placebo; P = .984). No significant differences existed between the groups as to the rates of conception, clinical pregnancy, or pregnancy loss. A statistically significant increase in singleton birth weight was observed after orlistat treatment (3487.50 g vs 3285.17 g in the placebo group; P = .039). The mean change in body weight during the intervention was -2.49 kg in the orlistat group, as compared to -1.22 kg in the placebo group, with a significant difference (P = .005). CONCLUSION: Orlistat treatment, prior to IVF-ET, did not improve the live birth rate among overweight or obese women, although it was beneficial for weight reduction.

Acute retroperitoneal hemorrhage after oocyte retrieval: a case report.

A 29-year-old woman with a 5-year history of primary infertility underwent in vitro fertilization-embryo transfer (IVF-ET) treatment. Hemorrhagic shock caused by retroperitoneal hematoma after oocyte retrieval was treated promptly by the evaluation of diagnostic laparoscopy and angiography. The patient was recovered and discharged from the hospital 7 days later without any complications. She was later diagnosed with Von Willebrand disease by a hematologist.

Association between exposure of light rare earth elements and outcomes of in vitro fertilization-embryo transfer in North China.

The adverse health effects of rare earth elements (REEs) on reproductive health remain a subject of debate, and few clinical observations are available. This study investigated the association between light REEs (LREEs) exposure and the outcome of in vitro fertilization-embryo transfer (IVF-ET). We recruited a total of 305 women undergoing IVF-ET in Beijing City and Shandong Province of northern China. Their demographic information and lifestyle characteristics were collected using questionnaires at enrollment. Fasting blood samples were collected on the day before the IVF-ET treatment cycle began. Serum concentrations of the LREEs of concern were analyzed using inductively coupled plasma-mass spectrometry, and four LREEs were measured with a high detection rate, including lanthanum (La), cerium (Ce), praseodymium (Pr), and neodymium (Nd). We found that a higher serum La concentration was associated with a 30% increased likelihood of clinical pregnancy failure [relative risk (RR) = 1.30, 95% confidence interval (CI): 1.00-1.67] and a 230% increased likelihood of preclinical spontaneous abortion (RR = 3.30, 95% CI: 1.57-6.94). There was a negative correlation between serum La concentration and the number of good-quality oocytes. For the other LREEs, no statistically significant associations were observed. We concluded that a high serum La concentration may have an adverse effect on IVF-ET outcomes.

Follicular fluid estradiol is an improved predictor of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer outcomes.

The present study is a clinical trial analyzing follicular fluid. The current study aimed to assess whether a correlation exists among estradiol (E2), anti-Mullerian hormone (AMH) and prokineticin 1 (PROK1) levels in the follicular fluid. A total of 81 infertile patients (53 with primary infertility and 28 with secondary infertility) who received routine in vitro fertilization (IVF) and embryo transfer (ET) or intracytoplasmic sperm injection at Yuhuangding Hospital (Yantai, China) were included in the present study. On the day of egg retrieval, follicular puncture and follicular fluid extraction were performed on patients using double lumen needles under the guidance of a vaginal ultrasound. In 77 cases, follicular fluid was collected from the follicle with the largest diameter. A total of 53 cases underwent ET and subsequent pregnancy outcomes were traced. Concentrations of E2, AMH and PROK1 in the single follicular fluid specimens were determined. The concentration of E2 in follicular fluid from the largest follicles in absolute pregnancy group was significantly lower than that in absolute non-pregnancy group. The concentrations of PROK1 and AMH in follicular fluid from the largest follicles in absolute pregnancy group were not significantly different from those in absolute non-pregnancy group. The concentration of E2 was associated with the dosage of gonadotropin, but was not associated with age, AMH and PROK1 levels in follicular fluid, fertilization rate or number of usable blastocysts. The area under curve revealed that E2 level in the follicular fluid exhibited a low predictive value for pregnancy outcome. The present study demonstrated that E2 level is a better predictor for the outcome of IVF-ET than AMH or PROK1 levels in the follicular fluid.

Weighted gene correlation network analysis reveals novel regulatory modules associated with recurrent early pregnancy loss.

At present, the etiology and pathogenesis of recurrent early pregnancy loss (REPL) are not completely clear. Therefore, identifying the underlying diagnostic and prognostic biomarkers of REPL can provide new ideas for the diagnosis and treatment of REPL. The chip data of REPL (GSE63901) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to construct a co-expression module for studying the relationship between gene modules and clinical features. In addition, functional analysis of hub genes in modules of interest was performed. A total of 23 co-expression modules were identified, two of which were most significantly associated with three clinical features. The MEbrown module was positively correlated with cyclin E level and the out-of-phase trait while the MEred module was positively correlated with the effect of progesterone. We identified 17 hub genes in the MEred module. The functional enrichment analysis indicated that such hub genes were mainly involved in pathways related to cellular defense response and natural killer (NK) cell-mediated cytotoxicity. In the MEbrown module, we identified 19 hub genes, which were mainly enriched in cell adhesion molecule production, regulation of cellular response to growth factor stimulus, epithelial cell proliferation, and transforming growth factor-ß (TGF-ß) signaling pathway. In addition, the hub genes were validated by using other datasets and three true hub genes were finally obtained, namely DOCK2 for the MEred module, and TRMT44 and ERVMER34-1 for the MEbrown module. In conclusion, our results screened potential biomarkers that might contribute to the diagnosis and treatment of REPL.

Regenerative Potential of Menstrual Blood-Derived Stem Cells and Platelet-Derived Growth Factor in Endometrial Injury.

BACKGROUND Endometrial regeneration is essential for normal endometrial function; however, it is unclear whether and how menstrual blood-derived stem cells (MenSCs) and platelet-derived growth factor (PGDF) are associated with this phenomenon. The present study explored this topic. MATERIAL AND METHODS EM-E6/E7/hTERT cells were divided into 5 groups: control group, NC group, PDGF group, MenSCs group, and PDGF+MenSCs group. The effects of MenSCs and PDGF on cell proliferation, invasion, and microvascular formation of endometrial epithelium were investigated by CCK-8, Transwell, and tube formation assays, respectively. Mouse endometrial injury models were established and mice were randomly divided into control, model, PDGF, MenSCs, and PDGF+MenSCs groups. Pathological change was examined with hematoxylin and eosin (H&E) staining. Microvessel formation of endometrial epithelium was estimated by detecting the expression of CD34 protein with immunohistochemical (IHC) staining. Western blot analysis was used to detect the activation of Akt and Bad proteins in endometrial tissue. RESULTS MenSCs, PDGF, and the combination treatments significantly promoted the proliferation, migration, and tube formation of endometrial epithelium compared to the control and NC group. The combination of MenSCs and PDGF remarkably promoted re-epithelialization and endometrial repair. IHC staining analysis showed significant increases in CD34 expression of the endometrial tissue following treatment with PDGF and MenSCs. The combination treatments also markedly enhanced the phosphorylation of Akt and Bad in endometrial tissue. CONCLUSIONS These results suggest that MenSCs and PDGF may be candidate substances for endometrial injury repair.

Advanced maternal age alters expression of maternal effect genes that are essential for human oocyte quality.

To investigate the effects of maternal age on the quality of oocytes, we used single-cell RNA sequencing to detect global gene transcriptome and identify key genes affected by advanced age in human mature oocytes. We isolated mRNA from mature oocytes obtained from IVF or ICSI patients (three oocytes from younger (≤30 years) and three oocytes from older (≥40 years) patients for scRNA-seq. We identified 357 genes differentially expressed between matured oocytes from older and younger women's. The up-regulated genes were significantly enriched with annotations related to transcriptional activation, oxidative stress and immune function, while down-regulated genes were enriched with catalytic activity. The key candidate gene TOP2B was found by protein interaction network analysis, and knockdown verification on younger mouse matured oocytes showed that TOP2B was a key gene affecting the oocyte quality and early embryo development. These results will contribute new knowledge on the molecular mechanisms of female ovary aging and establish a criterion to evaluate the quality of oocytes in women with advanced maternal age.

Mesenchymal stem cells-derived exosomes improve pregnancy outcome through inducing maternal tolerance to the allogeneic fetus in abortion-prone mating mouse.

Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. In the present study, bone marrow mesenchymal stem cells were isolated from CBA/J female mice and exosomes were isolated from cell culture medium by ultracentrifugation. CBA/J female mice were paired with male DBA/2 to generate abortion prone mouse model, and CBA/J females paired with male BALB/c mice were used as control. Exosomes were injected through uterine horns into pregnant CBA/J mice on day 4.5 of gestation in abortion-prone matting. On day 13.5 of pregnancy, abortion rates were calculated and the level of transforming growth factor-ß (TGF-ß), interleukin 10 (IL-10), interferon g (IFN-γ), and tumor necrosis factor a (TNF-α) in CD4+ T cells and macrophages in deciduas were evaluated by flow cytometry. Exosomes injection improved the pregnancy outcomes in abortion prone mice. The IL-4 and IL-10 levels on CD4+ T cells were upregulated in the maternal-fetal interface; meanwhile, the TNF-α and IFN-γ levels on CD4+ T cells were reduced. The IL-10 level was increased and IL-12 was reduced on the monocytes that separated from deciduas. miR-101 level was increased in the CD4+ T cells in the deciduas. In conclusion, the treatment of ESCs-derived exosomes modulates T cells' function and macrophages activities in the maternal-fetal interface that resulted in a decreased embryo resorption rate, and provides a therapeutic potential to treat RPL.

Potential effect of inflammation on the failure risk of in vitro fertilization and embryo transfer among infertile women.

This study investigated the association between inflammation in infertile women and the risk of IVF-ET failure, as well as the potential effects of various lifestyles on this association. A total of 84 women undergoing IVF-ET in Beijing China were recruited, including 38 women who did not achieve pregnancy after undergoing IVF-ET and 46 women who conceived. Serum samples were collected on the second day of menstruation before the treatment cycle and the inflammatory cytokines (interleukin-1ß, interleukin-6, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)) were measured. Information about their lifestyle was collected by questionnaire. It was found that the serum IL-8 concentration in the women who did not become pregnant (cases) was significantly higher than in the women who did achieve a pregnancy (controls). A dose-response relationship between the serum IL-8 concentration and the risk of IVF-ET failure was observed, especially when the IL-8 concentration was >11.2 pg/mL. The same relationship was not found for MCP-1. Among the environmental factors investigated, only the frequency of staying up late was positively correlated with the serum IL-8 concentration, as well as positively associated with the risk of IVF-ET failure. It was concluded that excessive inflammation may have an adverse effect on the IVF-ET success rate in infertile women.

Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome.

PURPOSE: Circular RNAs (circRNAs) mediate the posttranscriptional regulation of multiple genes by functioning as microRNA (miRNA) sponges. This study aimed to detect the novel expression of circRNAs in the cumulus cells (CCs) of polycystic ovary syndrome (PCOS) patients and their potential significance in the pathogenesis of PCOS. METHODS: circRNAs in the CCs from 6 PCOS patients and 6 normal control individuals were collected for microarray analysis, and an independent cohort study including 25 PCOS patients and 25 normal control individuals was conducted to validate the circRNA microarray results using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman's rank correlation and receiver operating characteristic (ROC) were performed to delineate the potential correlation between novel circRNAs and patients' clinical characteristics and their potential efficacy for the diagnosis of PCOS. Bioinformatics analysis was applied to investigate the potential roles of circRNAs in the pathogenesis of PCOS. RESULTS: A total of 286 circRNAs (167 upregulated and 119 downregulated) were identified by microarray that was differentially expressed between the PCOS and non-PCOS groups. After qRT-PCR validation, the expression levels of hsa_circ_0043533 (p < 0.05) and hsa_circ_0043532 (p < 0.01) were significantly higher in the PCOS group, while the expression level of hsa_circ_0097636 (p < 0.01) was prominently lower versus the non-PCOS group. Spearman's rank correlation indicated that the serum testosterone (T) level positively correlated with the expression of hsa_circ_0043533 and hsa_circ_0097636 in the PCOS group. The ROC curve analysis found that the combination of hsa_circ_0097636 and T resulted in a larger area under the curve (AUC) (0.893) compared with each circRNA alone (0.709, 0.738, and 0.718 for hsa_circ_0043533, hsa_circ_0097636 and hsa_circ_0043532, respectively). Bioinformatics analysis revealed that the dysregulated circRNAs were potentially involved in cell cycle, oocyte meiosis, progesterone-mediated oocyte maturation, the FOXO signaling pathway, phosphatidylinositol signaling and glycerophospholipid metabolism. CONCLUSIONS: The expression of circRNAs in CCs was significantly different between PCOS and normal control individuals. We validated three circRNAs, which could lead to a better understanding of disease pathogenesis and the development of effective therapeutic interventions for PCOS patients.