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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

Objective: The effects investigated in this study for the therapy with autologous platelet-rich plasma (PRP) on the thin endometrium in a rat model and patients with repeated implantation failure (RIF). Methods: PRP were immediately injected into uterine cavity after the establishing a model of thin endometrial injury by injection with 95% ethanol into uterus of SD rat. We have used H&E staining to explore the endometrial morphological alteration. The immunohistochemistry, Western blots, and quantitative RT-PCR were used to determine the endometrial receptivity. RL95-2 cells were incubated with RPR at the different concentrations to detect the effect of PRP on the endometrial epithelial cell proliferation. Patients (n = 51) were divided into the control and PRP treatment groups. Patients in the PRP treatment group received PRP by intrauterine perfusion. Results: Endometrial morphology was significantly improved after PRP intrauterine infusion thrice-administered SD rats. PRP increased the thickness of thin endometrium in rats and up-regulate the expression of receptivity markers, including vimentin, vascular endothelial growth factor (VEGF) and integrin β3. In the control (n = 25) and PRP treatment (n = 26) groups, no significant differences were observed in rates of clinical pregnancy (50.0% vs. 44.0%, p = 0.67), implantation (40.5% vs. 26.0%, p = 0.15) and miscarriage (30.8% vs. 18.2%, p = 0.48). Conclusions: The transplantation of PRP repairs the endometrial injury by suppressing receptivity, enhancing endometrial cell proliferation and vascular remodeling. PRP improves the pregnancy rate in RIF patients.

Objective This retrospective study was conducted to explore causes of unsynchronized follicular maturation (UFM) and analyze the effects of large follicle puncture on embryo quality and pregnancy outcome. Methods Clinical features and controlled ovulation hyperstimulation (COH) were compared between the puncture group (n = 48) and the control group (n = 2545). We analyzed the COH process with in vitro fertilization during fresh cycle embryo transfer with different clinical pregnancy outcomes. We compared clinical characteristics and COH process of patients in the clinical pregnancy (n = 774) and non-clinical pregnancy (n = 527) groups. Finally, factors related to pregnancy outcomes were analyzed using multivariate logistic regression analysis. Results Age, level of estradiol on down-regulation day, and initial gonadotropin dose were significantly higher in the puncture group than in the control group. We detected significant differences in age, infertility, and body mass index (BMI) between the clinical and non-clinical pregnancy groups. Age, BMI, and endometrial thickness on the day of human chorionic gonadotropin administration were the independent factors influencing pregnancy outcome. Conclusions Patient’s age and level of anti-Müllerian hormone were the main factors causing UFM in patients undergoing COH. Large follicle puncture had no significant effect on pregnancy outcome.

Repeated implantation failure (RIF) frustrates both patients and their clinicians. Our aim was to observe the effects of intrauterine administration of human chorionic gonadotropin (hCG) on pregnancy outcomes of patients who received frozen-thawed embryo transfer (FET). A prospective cohort study was conducted to evaluate the impact of intrauterine administration of hCG on pregnancy outcomes in FET cycles of patients with RIF from January 1st 2016 to December 31st 2016. The treatment group (n = 153, 152 cycles) received an infusion of 500 IU of hCG diluted in normal saline 3 days before embryo transfer. The control group (n = 152, 151 cycles) received embryo transfer with a previous intrauterine injection of normal saline without hCG. Early morning fasting blood samples were obtained from each patient for the measurement of peripheral regulatory T cells (Tregs) on the day of embryo transfer. The outcome parameters including Tregs in each group were compared. The patients in the hCG-treated group had significantly higher clinical pregnancy rates, implantation rates and live birth rates than the controls (37.5% versus 25.17%, 29.19% versus 19.4%, 26.97% versus 17.22%, respectively). They also had significantly higher percentages of peripheral Tregs than the controls (6.1 ± 0.6% versus 5.4 ± 1.0%). In addition, the clinical pregnancy rate, implantation rate and live birth rate in patients who received blastocyst transfer were significantly higher in the hCG-treated group when compared to the control group (41.38% versus 26.44%, 42.22% versus 26.14%, 33.33% versus 17.24%, respectively). We also showed that the clinical pregnancy rate, implantation rate and live birth rate were significantly higher in hCG-treated group when compared to the control group (49.12% versus 28.07%, 49.15% versus 28.07%, 40.35% versus 17.54%, respectively) of RIF patients with blastocyst transfer under 35 years, while there was on difference in patients above 35 years. Intrauterine administration of hCG significantly improves the clinical pregnancy rate, implantation rate and live birth rate in FET cycles of patients with RIF by increasing Tregs. The treatment improves the pregnancy outcomes much more for younger RIF patients transferred blastocysts.

Background Platelet-rich plasma (PRP) contains abundant growth factors and is gradually used in the field of reproduction. A thin endometrium is recognized as a critical factor in embryo implantation failure. Endometrial mesenchymal stem cells (EnMSCs), which were isolated from human menstrual blood, are highly proliferative and show multiple differentiation capacity. The current study was to investigate the effect of PRP on the proliferation and migration of EnMSCs, and the effectiveness of PRP in the treatment of patients with thin endometrium. Materials and methods EnMSCs were treated with PRP in vitro, followed by measuring cell proliferation, migration, and adhesion by using CCK8, scratch, and adhesion test, respectively. Twenty patients undergoing in vitro fertilization (IVF) with refractory thin endometrium history were given PRP by infusion into the uterine cavity after the treatment of hormone replacement therapy (HRT). Results All components of PRP significantly stimulated the growth, migration, and adhesion of EnMSCs when compared with the negative control. Cell proliferation and migration were induced by PRP in a dose-dependent manner with maximum proliferation at a 2% PRP dose. The clinical data showed that successful endometrial expansion and pregnancy were discovered in 12 patients after PRP infusion, and the pregnancy rate increased to 60%. Conclusion Intrauterine PRP infusion represents a new way for female patients with thin endometrium with poor response. This study lays the foundations for the potential treatment of thin endometrium with PRP in vivo.

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 o...

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.

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.

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.

The aim of this work was to study the expression of the cytokines IFN-γ, IL-4, IL-17 A, and TGF-β1 in peripheral blood and follicular fluid (FF) of patients positive for antithyroid autoantibodies (ATA摘要 这项工作的目的是研究甲状腺功能正常的抗甲状腺自身抗体阳性（ATA +）患者细胞因子IFN-γ, IL-4, IL-17A和TGF-b1在外周血和卵泡液（FF）中的表达, 以及探究这些自身抗体对体外受精和胚胎移植（IVF-ET）妊娠结局的影响。ATA +组中共计19名患者, 对照组为检测为抗甲状腺自身抗体（ATA-）阴性的27位患者。在取卵日, 移植后的第5天和第14天从两组患者中抽取血样, 另外, 在两组患者的取卵日提取卵泡液, 并通过酶联免疫吸附测定（ELISA）测量IFN-γ, IL-4, IL-17A和TGF-β1的表达水平。ATA +组在取卵日IFN-γ浓度增加, 外周血中TGF-β1浓度降低（p.05）；ATA +组移植后第5天和第14天外周血中IL-4浓度降低（p.05）; 在卵泡液中, IL-17A浓度增加而TGF-β1浓度降低（p.05）。 在取卵日和移植后第14天, ATA +组卵泡液和外周血中IL-17A / TGF-β1的比例显著增加（p.05）。 妊娠患者卵泡液IL-17 A / TGF-β1的比例显著低于非妊娠患者（p.05）。 研究结果表明, ATA +患者促炎细胞因子和抗炎细胞因子比例受到了不利影响; 接受IVF-ET治疗的ATA +患者的不良妊娠结局可归因于免疫机制。.

Background Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) are given letrozole before a trigger injection of human chorionic gonadotropin (hCG) to lower estrogen (E2) levels, but can experience ovarian hyperstimulation syndrome (OHSS). The aim of this study was to evaluate the effect of oral letrozole, prior to administration of hCG, on the outcome of IVF and development of OHSS. Material/Methods Retrospective clinical review included 181 cases of women with PCOS who underwent IVF cycles with intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF/ICSI-ET). The day before the use of hCG, cases were divided into a letrozole-treated group (N=78) and a non-letrozole group (N=103). An oral dose of 2.5 mg qd of letrozole was given when the peak level of E2 was ≥4000 pg/ml during ovarian stimulation and ceased before the day of egg retrieval. Results The letrozole-treated group had a significant increase in the number of retrieved oocytes, viable embryos, and fresh ET rate (P>0.05); peak levels of E2, and E2 levels on the day of the egg retrieval, were significantly higher, and the fertilization rate was significantly lower (P0.05). The incidence OHSS was lower in the letrozole-treated group, but this difference did not reach statistical significance (P>0.05). Conclusions Women with PCOS who underwent IVF, oral treatment with letrozole a day prior to treatment with hCG lowered E2 levels, but did not significantly reduce the incidence of OHSS.

Purpose This study aimed to screen key genes and pathways involved in obese polycystic ovary syndrome (PCOS), and predict drugs for treatment of obese PCOS via bioinformatics approaches. Methods Microarray dataset GSE10946 were downloaded from the Gene Expression Omnibus database, including 7 cumulus cell samples from obese PCOS patients and 6 lean control samples. Differentially expressed genes (DEGs) between obese PCOS and controls were obtained using Bayesian test after data preprocessing, followed by functional enrichment analyses for DEGs. Besides, protein-protein interaction (PPI) network and sub-network analyses were performed. Furthermore, drug prediction was carried out based on the DEGs. Results A total of 793 DEGs were identified in PCOS compared with control, including 352 up-regulated and 441 down-regulated DEGs. Specifically, upregulated RNA polymerase I subunit B (POLR1B), DNA polymerase epsilon 3, accessory subunit (POLE3), and DNA polymerase delta 3, accessory subunit (POLD3) were enriched in pathway of pyrimidine metabolism associated with obesity and PCOS, and 5-hydroxytryptamine receptor 2C (HTR2C) was enriched calcium signaling pathway. Additionally, 10 significant potential drugs, such as spironolactone targeting androgen receptor (AR), trimipramine targeting adrenoceptor beta 2 (ADRB2), and L-ornithine targeting ornithine decarboxylase antizyme 3 (OAZ3), were obtained. Conclusions In conclusion, POLR1B, POLE3, POLD3, and HTR2C might play important roles in obese PCOS via involvement of pyrimidine metabolism and calcium signaling pathway. Moreover, AR, ADRB2, and OAZ3 might be targets of spironolactone, trimipramine, and L-ornithine in the treatment of obese PCOS.

This study aimed to study the expression of homeobox (HOX)A11-AS1 ( HOXA11 antisense RNA) long noncoding RNA (lncRNA) and the expression of homeobox A ( HOXA9, HOXA10, HOXA11, and HOXA13) genes in the eutopic (EU) and ectopic (EC) endometria of women with peritoneal endometriosis. A total of 30 women undergoing laparoscopic surgery for peritoneal endometriosis and 15 infertile women without endometriosis were enrolled in this study. Peritoneal EC tissue samples were obtained through surgery. The EU tissues were obtained by curettage. The EC and EU lncRNA and messenger RNA (mRNA) expression levels were measured using real-time reverse transcriptase-polymerase chain reaction. The HOXA11-AS1 lncRNA and HOXA9, HOXA10, HOXA11, and HOXA13 mRNA were expressed at significantly lower levels in the EU than in the EC, that is, in women with peritoneal endometriosis ( P .05). In conclusion, the study findings suggest that HOXA11-AS1 lncRNA may play a role in the development of peritoneal endometriosis, but HOXA11-AS1 may not influence endometrial receptivity in endometriosis-associated infertility.

Sodium fluoride (NaF) is used as a medicine to prevent tooth decay; however, excessive NaF could cause a pathological damage to the health. Recent studies showed that NaF impaired mouse oocyte maturation, included of abnormal spindle configuration, actin cap formation, cortical granule-free domain formation, and the following development after fertilization. However, few studies used large animals as models to study the toxicology of NaF on oocytes maturation. We proposed a hypothesis that NaF would affect the nuclear and cytoplasmic maturation of porcine oocytes and DNA methylation pattern of imprinted genes in oocytes. Our results showed that NaF affected cumulus expansion, polar body emission, spindle morphology, cortical granule distribution, early apoptosis, and the following development after parthenogenetic activation during porcine oocyte maturation. Moreover, NaF increased the DNA methylation of NNAT and decreased its expression, which disturbed the glucose transport in oocytes. These results suggest that NaF impairs the porcine oocytes maturation epigenetically, which provides a new toxicological mechanism of NaF on the oocyte maturation. Environ. Mol. Mutagen. 59:223-233, 2018. © 2017 Wiley Periodicals, Inc.

The present study aimed to explore the therapeutic effects of the Tiaogeng Yijing decoction on patients with poor ovarian response (POR) undergoing in vitro fertilization-embryo transfer (IVF-ET), in addition to the underlying molecular mechanisms of these effects. A total of 40 patients were randomly and equally assigned to the treatment or control group. Patients in the treatment group received the Tiaogeng Yijing decoction continuously for three menstrual cycles in addition to microstimulation, while patients in the control group underwent microstimulation only. The following molecules were measured following treatment: Serum levels of sex hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti-mullerian hormone (AMH); follicular fluid levels of cytokines, including growth differentiation factor (GDF)-9, transforming growth factor (TGF)-β1, leukemia inhibitory factor (LIF), granulocyte-colony stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF); and endometrial levels of cytokines, including integrin αVβ3, TGF-β1, LIF, G-CSF and VEGF. In addition, the antral follicle count (AFC), mean ovarian diameter (MOD) and pregnancy outcomes were measured. The results revealed that the Tiaogeng Yijing decoction significantly decreased serum levels of FSH and E2, and significantly increased serum AMH levels, the AFC, follicular fluid levels of GDF-9, TGF-β1 and VEGF, and endometrial levels of integrin αVβ3, TGF-β1 and VEGF, in addition to pregnancy outcomes (all P

Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer-associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA-494 in EOC tissues and cell lines. The clinical significance of miRNA-494 in patients with EOC was also evaluated. The results demonstrated that miRNA-494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA-494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA-494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA-494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA-494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA-494 expression and SIRT1 restoration. Together, these findings suggest that miRNA-494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.

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.

DEP domain containing 1 (DEPDC1) is a novel tumor-associated gene, which is aberrantly expressed in multiple types of cancer and involves in tumorigenesis and cancer progression. Here, we examined the functional involvement and underlying mechanism of DEPDC1 in breast cancer. In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation indicated DEPDC1's ability of promoting breast cancer cells migration and invasion. In addition, we discovered that DEPDC1 caused hyper-activation of PI3K/AKT/mTOR signaling in breast cancer cells. Therefore, the increased DEPDC1 expression in breast cancer is correlated with disease progression and poor survival, which suggested that DEPDC1 might be a potential therapeutic target against this disease.

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.

To identify the quantitative profiling of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) in cumulus cells (CCs) and to evaluate their roles in the early embryo development of polycystic ovary syndrome (PCOS) patients, in part, with obesity.Fifty-five subjects were divided into two groups according to the body mass index. Oocytes were further inseminated and only mature and normal fertilized oocytes (2PN) were included in this research. Real-time PCR and western blot were performed to identify adiponectin and its receptors in CCs.Adiponectin and receptors were ubiquitously expressed in CCs of PCOS and non-PCOS patients. The level of AdipoR2 in CCs from the oocytes yielding blastocyst after 5/6 days in vitro culture was markedly higher than in those from oocytes could not develop to blastocyst stage after Day 6, for non-obese or obese PCOS patients (0.1647 ± 0.0161 versus 0.0783 ± 0.0385, 0.1948 ± 0.0307 versus 0.1057 ± 0.0236, respectively, p 0.05). In addition, only in patients with PCOS and concurrent obesity the AdipoR1 in CCs was considerably increased in CC-BThe development of early embryo was associated with the up-regulation of AdipoR1 and AdipoR2 in PCOS patients. Our results suggested that adiponectin could positively modulate embryo development in humans. Further investigations should be carried out to unlock the crucial role that adiponectin plays in embryo development.

The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).

Objective To evaluate the effect of DHEA supplementation on in vitro fertilization (IVF) parameters and pregnancy outcomes in patients older than 37 years with normal ovarian reserve. Study design A retrospective cohort study was conducted to evaluate the impact of DHEA supplementation on IVF outcome of infertile women over 37 years with normal ovarian reserve between January 2012 and July 2014. 243 patients (study group) received 75 mg of DHEA daily (25 mg three times daily) before the IVF cycle. Another 243 patients (control group) received infertility treatment, but did not receive DHEA. The IVF outcome parameters in each group were compared. Results Both groups did not show statistically significant differences in terms of patient demographics characteristics, mean numbers of oocytes retrieved and mature oocytes rate. While patients in the DHEA group have the significantly higher implantation rate and live birth rate compared with controls (30.13% versus 22.70%, 43.33% versus 28.26%). We also found that the cycle cancellation rate and miscarriage rate were lower in the DHEA group (1.23% versus 5.34%, 13.33% versus 28.89%). Conclusion DHEA supplementation may significantly improve IVF outcomes in infertile women over the age of 37.

γ-Aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in the central nervous system (CNS) of vertebrates. However, GABA and its receptor are found not only in peripheral neuronal tissue but also in many peripheral nonneuronal tissues, and thought to have multiple physiological functions. The bidirectional communication between oocytes and cumulus cells (CCs) plays a significant role in oocyte maturation and metabolism. In our previously study, the expression level of α5 subunit in CCs isolated from oocytes of patients with polycystic ovary syndrome had been found to be associated with oocyte nuclear maturity. In this study, we investigated the transcriptional levels of GABAA receptor subunits in germinal vesicle (GV) and metaphase II (MII) mouse CCs, and explored the role of GABA-A receptor subunits during ovarian follicular development and oocyte maturation. We found that GABAA receptor subunits exhibited differential transcriptional levels in CCs at different oocyte nuclear maturity stages. It suggested an involvement of GABA-A receptor subunits related to oocyte maturation and certain functions.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women and is characterised by polycystic ovaries, hyperandrogenism and chronic anovulation. Although the clinical and biochemical signs of PCOS are typically heterogeneous, abnormal folliculogenesis is considered a common characteristic of PCOS. Our aim is to identify the altered miRNA and mRNA expression profiles in the cumulus cells of PCOS patients to investigate their molecular function in the aetiology and pathophysiology of PCOS. In this study, the miRNA expression profiles of the cumulus cell samples isolated from five PCOS and five control patients were determined by an miRNA microarray. At the same time, the altered mRNA profiles of the same cumulus cell samples were also identified by a cDNA microarray. From the microarray data, 17 miRNAs and 1263 mRNAs showed significantly different expression in the PCOS cumulus cells. The differentially expressed miRNA-509-3p and its potential target gene (MAP3K8) were identified from the miRNA and mRNA microarrays respectively. The expression of miRNA-509-3p was up-regulated and MAP3K8 was down-regulated in the PCOS cumulus cells. The direct interaction between miRNA-509-3p and MAP3K8 was confirmed by a luciferase activity assay in KGN cells. In addition, miRNA-509-3p mimics or inhibitor transfection tests in KGN cells further confirmed that miRNA-509-3p improved oestradiol (E2) secretion by inhibiting the expression of MAP3K8. These results help to characterise the pathogenesis of anovulation in PCOS, especially the regulation of E2 production.

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. 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. 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

Objective To compare the clinical outcomes of follicular versus luteal phase ovarian stimulation in women with poor ovarian response (Bologna criteria) undergoing IVF. Methods This retrospective study investigated 446 patients submitted to 507 cycles in three groups. First, the two larger cohorts were examined: 154 patients treated with luteal phase ovarian stimulation (Group Lu); and 231 patients administered follicular phase ovarian stimulation (Group Fo). Then the clinical outcomes of 61 patients submitted to double ovarian stimulation were analyzed. Clinical outcomes included number of retrieved oocytes, fertilization rate, cleavage rate, top-quality embryo rate, clinical pregnancy rate (CPR), and live birth rate (LBR). Results Longer stimulation, higher dosages of HMG, and higher MII oocyte rates were achieved in Group Lu (p

Summary Objective: We conducted the research in order to explore the impact of hydrosalpinx fluid (HSF) on endometrium. Method: HSF group: 261 patients with HSF scheduled to undergo laparoscopic surgery 3 to 7 days after menstruation in our center. Hysteroscopy would also be performed in order to observe the endometrial morphology during the surgery. Sixty (60) patients would be randomly selected for endometrial biopsy in order to detect the inflammatory cytokines TNF-a and IL-2 mRNA. Non-HSF group: 210 patients with no evidence of HSF due to chronic salpingitis or pelvic adhesion. IVF-ET treatment was performed after eliminating the factor of male infertility and hysteroscopy was conducted before the treatment. Fifty (50) patients underwent endometrial biopsy in order to detect TNF-a and IL-2 mRNA. Results: Hysteroscopy was performed in 261 patients with HSF and 210 patients without HSF. The incidence rate of endometritis manifestation among these two groups of patients was 37.2% (97/261) and 20.5% (43/210), respectively. The incidence rate of endometritis in the patients with HSF is significantly higher than in the patients without HSF (p

Objective To study the effects of PDGF-Rb antagonists imatinib on endometrial injury repairing in the mouse model. Methods The cultured MSCs cells from male mice were marked with BrdU in vitro , and then transplanted to the female mice which suffered from radiation injury through tail vein, PDGF-Rb antagonists imatinib was injected through abdominal cavity. Four groups were arranged, which were radiation transplantation group, normal control group, imatinib intervention group and radiation control group. BrdU incorporation, SRY expression and MVD status were detected in uterus of mice. Results SRY gene was negative expressed in normal control group and radiation control group. SRY gene presented positive in radiation transplantation group and imatinib intervention group; BrdU incorporation showed negative in radiation control group and normal control group which died in the early stage in mice; the incorporation of BrdU was higher in radiation transplantation group compared with imatinib intervention group; CD34 was positive on the uterus of all the four groups, which showed highest in radiation control group and lowest in radiation control group; The MVD in imatinib intervention group was lower than radiation control group; the difference of MVD was significantly compared with normal control group ( P Conclusions PDGF-Rb antagonists imatinib could inhibit the repairing function of MSCs in the endometrial lesions in mice.

Polycystic ovary syndrome (PCOS) is currently considered a predominantly hyperandrogenic syndrome. In theory, hyperandrogenism can be caused by high level of testosterone (T) as well as by enhanced androgen receptor (AR) activity. C-Terminal binding protein 1 antisense (CTBP1-AS) was a novel long noncoding RNA (lncRNA) to regulate AR activity. In this study, we found that expression level of CTBP1-AS in peripheral blood leukocytes was significantly higher in women with PCOS than that in controls after adjustment for age and body mass index (BMI). Individuals having higher expression of CTBP1-AS had significantly greater disease risk than those having lower expression. We also identified expression of CTBP1-AS as an independent risk factor for PCOS. A positive correlation was observed between the CTBP1-AS expression and the total T (TT) concentration either unadjusted or after adjusting for age, BMI, and homeostatic model assessment insulin resistance. Taken together, our current study presented the first evidence that the lncRNA CTBP1-AS, a novel AR modulator, is associated with PCOS in Chinese population and established the possibility that abnormal CTBP1-AS expression is a risk factor for PCOS and it is a predictor of variability in serum TT level in Chinese women with PCOS.

The present study investigated the effects of endometrial stem cell (EnSCs) transplantation combined with estrogen in the repair of endometrial injury. A total of 30 patients with intrauterine adhesions (IUA) and 30 healthy individuals were selected. Expression of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-BB in endometrial tissue was assessed. Additionally, expression levels of epithelial membrane antigen (EMA), cytokeratin (CK), integrin α-6 (CD49f), Thy-1 membrane glycoprotein (THY-1), collagen type 1 (Col I), fibroblast (5B5) and vimentin in EnSCs were detected using western blot analysis and reverse transcription-quantitative polymerase chain reaction. A rat model of IUA was established and female rats were divided into the control, model, EnSCs, estrogen and estrogen plus EnSCs (E+EnSCs) groups. Blood was extracted at 1 and 5 weeks post-treatment, and serum levels of transforming growth factor (TGF)-β1, EGF, 17 β-estradiol (E2) and PDGF-BB were measured using ELISA. Hematoxylin and eosin staining was performed to observe the pathological changes of endometrial tissue in rats. Western blot analysis was used to detect the expression of estrogen receptor (ESR1) and matrix metalloproteinase (MMP)-9 in the endometrium. The results revealed that patients with IUA exhibited increased expression levels of EGF and PDGF-BB compared with those in control group. Additionally, EnSCs exhibited significantly increased expression levels of EMA, CD49f, CK, Col I, THY-1, 5B5 and vimentin compared with the remaining groups. An increased number of newly formed glands was observed in the E+EnSCs group compared with that in the EnSCs group. Increased levels of E2, but decreased levels of TGF-β1, EGF, PDGF-BB, ESR1 and MMP-9 were detected in EnSCs and estrogen groups compared with those in E+EnSCs group. These results suggest that EnSCs transplantation combined with estrogen could improve endometrial abnormalities.

This study aimed to investigate the impact of hydrosalpinx fluid (HF) on early human embryonic development. A total of 33 patients who underwent laparoscopic surgery for hydrosalpinx were selected, and the HF specimens obtained from these patients were subjected to bacterial culture, Chlamydia antigen detection, biochemical analysis, and cytokine detection. Meanwhile, human embryos derived from three pronuclei (3PN) were cultured in various HF concentrations. There was no significant difference in the chemical components and physical characteristics between colorless and colored HF specimens, apart from the glucose concentration which was significantly higher in colorless HF. K+ and HCO3− were significantly increased (P < 0.05 and P < 0.01), and Ca2+, Mg2+, and glucose were significantly decreased (P < 0.05, P = 0.006, and P = 0.007) in the two HF specimens, compared to blastocyst culture medium (G-2 medium); no phosphates were detected in the HF specimens. Compared to colorless HF, the concentrat...

Embryo implantation is associated with an hypoxic endometrial microenvironment. Hypoxia‑inducible factor‑1α (HIF‑1α) is activated under hypoxic conditions. In the present study, the expression pattern of HIF‑1α in endometrial tissue was investigated and its effects on endometrial receptivity in patients with polycystic ovary syndrome (PCOS) were examined. A total of 81 patients were enrolled for in vitro fertilization and embryo transfer. They were divided into PCOS (n=40) and Control groups (n=41); both groups were further divided based on body weight (overweight and normal weight subgroups). The expressions of HIF‑1α, vascular endothelial growth factor (VEGF) and glucose transporter protein (GLUT)‑1 and GLUT4 were determined by reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. The results demonstrated that mRNA and protein expression levels of HIF‑1α and VEGF in the PCOS group were significantly lower compared with expression levels in the Control group. However, there were no statistically significant differences in the expression levels of GLUT1 and GLUT4 between groups. In patients with PCOS, GLUT1 and GLUT4 were mainly localized in the nuclei and cytoplasm, but not in the cell membrane. Overweight patients had the lowest expression levels of HIF‑1α, VEGF and GLUT1 expression compared with normal weight patients. In conclusion, HIF‑1α may be involved in the molecular mechanisms of endometrial dysfunction in women with PCOS, particularly in those who are overweight. HIF‑1α might therefore be a novel target for improving the endometrial receptivity and successful embryo implantation in PCOS women.

To investigate the effect and possible mechanism of downregulation of gonadotropin-releasing hormone agonist (GnRHa) on Th17/Treg (regulatory T cell) cells in peripheral blood of patients with unexplained repeated implantation failure (RIF).Fifty-two patients who had RIF (≥ 3 consecutive transfers of ≥ 4 high-grade embryos in women under the age of 40 (excluding 40)) of frozen-thawed embryos were studied. Twenty-nine cases receiving simple hormone replacement therapy (HRT) were defined as transfer group, and the remaining 23 cases with HRT combined with GnRHa downregulation were defined as GnRHa downregulation group. In addition, 30 cases of the normal early pregnancy group were selected as control group.Before HRT, the number of Th17 and Treg cells in CD4+ lymphocytes was increased and decreased, respectively, with the ratio of Th17/Treg cells increased in HRT group compared with the control group (p 0.05). On the day of progesterone conversion, compared with the HRT group, the percentage of Th17 and Treg cells was decreased and increased, respectively, with the ratio of Th17/Treg cells decreased significantly in GnRHa downregulation group (p 0.05). The estrogen E2 levels of the GnRHa downregulation group were slightly higher than those of the HRT group, with no significant difference between the two groups (p 0.05). Further, there was no significant difference in the levels of chorionic gonadotropin at the 14th day and the 21st day after transplantation between HRT group and GnRHa downregulation group (p 0.05).There were an increase and a decrease in the number of Th17 and Treg cells, respectively, with Th17/Treg cells imbalanced in unexplained RIF. GnRHa downregulation may play a direct immunomodulatory role in disrupting the imbalance and then improve the endometrial receptivity. These effects did not depend on the E2 levels in peripheral blood, nor affect early embryonic development.

Background Elective frozen-embryo transfer has been shown to result in a higher live-birth rate than fresh-embryo transfer among anovulatory women with the polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer increases live-birth rates among ovulatory women with infertility. Methods In this multicenter, randomized trial, we randomly assigned 2157 women who were undergoing their first in vitro fertilization cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up to two cleavage-stage embryos were transferred in each participant. The primary outcome was a live birth after the first embryo transfer. Results The live-birth rate did not differ significantly between the frozen-embryo group and the fresh-embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between-group differences in the rates of implantation, clinical pregnancy, o...

This study assessed the true accuracy of follicular output rate (FORT) as a prognostic indicator of response to FSH and reproductive competence after IVF/intracytoplasmic sperm injection. A total of 1643 cycles, including 140 polycystic ovary syndrome (PCOS) patients who underwent ovarian stimulation, were studied. FORT was calculated as the ratio of preovulatory follicle count on the day of stimulation×100/small antral follicle count (3-10mm in diameter) at baseline. Low, medium and high FORT groups were defined according to tertile values. Among 1503 non-PCOS cycles, numbers of retrieved oocytes and of all embryos that could be transferred, as well as rates of good-quality embryos, embryo implantations and clinical pregnancies, progressively increased with FORT. In PCOS patients, FORT were significantly lower in patients who achieved clinical pregnancy compared with those who did not (0.56±0.21 versus 0.66±0.29, P=0.031). Fertilization and good-quality embryo rates were significantly higher with medium FORT than low and high FORT (P=0.001 and P=0.047, respectively). Medium FORT in PCOS patients and high FORT in non-PCOS patients may predict better outcomes for IVF/ICSI.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. The abnormalities of endocrine and intra-ovarian paracrine interactions may change the microenvironment for oocyte development during the folliculogenesis process and reduce the developmental competence of oocytes in PCOS patients who are suffering from anovulatory infertility and pregnancy loss. In this microenvironment, the cross talk between an oocyte and the surrounding cumulus cells (CCs) is critical for achieving oocyte competence. The aim of our study was to investigate the gene expression profiles of CCs obtained from PCOS patients undergoing IVF cycles in terms of oocyte maturation by using human Genome U133 Plus 2.0 microarrays. A total of 59 genes were differentially expressed in two CC groups. Most of these genes were identified to be involved in one or more of the following pathways: receptor interactions, calcium signaling, metabolism and biosynthesis, focal adhesion, melanogenesis, leukocyte transendothelial migration, Wnt signaling, and type 2 diabetes mellitus. According to the different expression levels in the microarrays and their putative functions, six differentially expressed genes (LHCGR,ANGPTL1,TNIK,GRIN2A,SFRP4, andSOCS3) were selected and analyzed by quantitative RT-PCR (qRT-PCR). The qRT-PCR results were consistent with the microarray data. Moreover, the molecular signatures (LHCGR,TNIK, andSOCS3) were associated with developmental potential from embryo to blastocyst stage and were proposed as biomarkers of embryo viability in PCOS patients. Our results may be clinically important as they offer a new potential strategy for competent oocyte/embryo selection in PCOS patients.

Treg cells have been shown to be important in maintaining maternofetal tolerance, but the expression of Tregs in assisted reproductive technology (ART) in women on the day of embryo transfer (D0), 5days (D5) and 14days after ET (D14); the related factors influencing the expression levels of Tregs; the proliferation ability and the relevant cytokine epression by Tregs on D14 have not been investigated. In this study, 124 women undergoing in vitro fertilization-intracytoplasmic sperm injection (IVF/ICSI) were enrolled. Early morning fasting blood samples were obtained for the measurement of Tregs and other relevant indicators on the D0, D5and D14days after ET. we showed that the Tregs were increased on D0 and D14 in pregnant women, while there was no obvious fluctuation in non-pregnant women. IL-10 and TGF-β levels and the expansion of Tregs were significantly higher in successfully pregnant women than in non-pregnant women on D14. The levels of E2, P did not significantly differ between the groups. We suggest that periodic elevation of Tregs on the day of ET was associated with higher embryo implantation rate after ART.

This retrospective study aimed to evaluate the association between elevated serum estradiol (E 2) levels on the human chorionic gonadotrophin (hCG) administration day and in vitro fertilization (IVF) pregnancy and birth outcomes in the long GnRH-agonist protocol. This study analyzed the data of 3393 infertile women who underwent initial fresh IVF. The patients were categorized into high and low E 2 groups based on their serum E 2 levels on the hCG day. Pregnancy and birth outcomes were compared. The implantation rate, clinical pregnancy rate, and live birth rate were all significantly higher in the high E 2 group than in the low E 2 group (p

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with obesity, insulin resistance, hyperandrogenism, alterations in ovarian angiogenesis and impaired oocyte competence. Emerging evidence demonstrates that angiopoietin-like protein 1 (ANGPTL1) and angiopoietin-like protein 2 (ANGPTL2) have an important influence on angiogenesis, androgen biosynthesis, insulin resistance and adipocytes function. In this study, we set out to determine the potential relationship between ANGPTL1, ANGPTL2 and oocyte competence in PCOS through analyzing the expression levels and dynamic pattern of the two genes in cumulus cells (CCs) during different phases of nuclear maturation of PCOS patients and control groups undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer. We found that the relative abundance of ANGPTL1 and ANGPTL2 transcripts in CCs from patients with PCOS showed dynamic changes during oocyte maturation. Specifically, their expressions were increased significantly at the Metaphase II stage. In summary, the present novel evidence indicates that the expression patterns of ANGPTL1 and ANGPTL2 mRNAs are disordered during oocyte maturation in PCOS, which were potentially related to aberrant oocyte quality and developmental potency, at least in part, via pathological angiogenesis and metabolism.

Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.

CD4 + CD25 + T cells (Treg cells) and macrophages play roles in the maintenance of maternal–fetal immunological tolerance. Treg cells suppress the function of macrophages via mechanisms mediated by cell–cell contact and production of soluble factors. The purpose of this study was to investigate regulation of macrophages by Treg cells within decidua from patients with unexplained recurrent miscarriage (RM) and normal control women during early pregnancy. Treg cells and macrophages were isolated from deciduas of unexplained RM ( n = 15) and control women ( n = 15) by magnetic cell separation and co-cultured for six days. Regulation of macrophages by Treg cells was assessed in the presence and absence of neutralizing anti-TGFβ antibodies and in transwell experiments. Expression of CD80, CD86, IL10, and IFNγ by macrophages was measured by flow cytometry or ELISA. Macrophage expression of CD80 and CD86 was higher in deciduas of unexplained RM patients compared with controls whereas the expression of IL10 was lower. There was no difference in the expression of IFNγ by macrophages between the two groups. Treg cells inhibited macrophage expression of CD80, CD86 and IFNγ and increased the expression of IL10. The regulatory effects of Treg cells were abrogated in the presence of neutralizing anti-TGFβ antibodies or by transwell culture. The phenotype of macrophages therefore differed in unexplained RM patients compared with normal early pregnant subjects. Macrophage regulation by Treg cells was shown to be mediated by cell–cell contact and TGFβ and this capacity was decreased in unexplained RM patients.

Objective To investigate the reproduction-assisting effects of laparoscopic “core-pulling” salpingectomy for patients with hydrosalpinx on ovarian reserve, responsiveness to stimuli and outcomes of in vitro fertilization and embryo transfer (IVF-ET). Methods Infertile females receiving treatment in Reproductive Medicine Center of Yantai Yuhuangding Hospital due to fallopian tube disorders (n=214) were enrolled from July 2006 to December 2007 and further divided into three groups. “Core-pulling” procedure group (group A) consisted of patients receiving pretreatment with “core-pulling” salpingectomy due to hydrosalpinx in our center (n=31), wherein 16 patients received IVF-ET. Conventional procedure group (group B) consisted of patients receiving conventional salpingectomy for hydrosalpinx or ectopic pregnancy in our center or other institutes prior to IVF-ET (n=59). Control group (group C) consisted of patients receiving IVF-ET without the history of previous hydrosalpinx or salpingectomy (n=124). Results At baseline, the antral follicle count of group B was significantly less than that of groups A and C (8.6 ± 2.5 vs 8.3 ± 2.0 vs 9.8 ± 2.4). The mature oocytes retrieved numbered less than the other two groups, in a statistically significant manner compared with group C (13.1 ± 5.7 vs 10.6 ± 5.0 vs 12.0 ± 6.2). Patients of groups A and B received more gonadotropin while the dosage of group B differed significantly from group C (31.0 ± 17.7 vs 37.6 ± 8.3 vs 30.0 ± 4.6). E 2 level on hCG injection day was slightly lower in group B than in the other two groups, statistically significant compared with that of group C, but not compared with that of group A. After receiving IVF-ET, patients of group A showed significantly higher conception rate than groups B and C (62.5% vs 43.6% vs 39.2%). Conclusion Compared with the conventional procedure, laparoscopic “core-pulling” salpingectomy should be recommended for patients with hydrosalpinx intending to receive IVF-ET, which did not interfere with the ovarian reserve or responsiveness but improve the conception rate in clinical practice.

background: CD4 + CD25 + regulatory T cells (Tregs) are important for the maintenance of immune homeostasis by virtue of their ability to control T-cell proliferation in the peripheral blood (PB). We recently demonstrated that the prevalence of Tregs is decreased, whereas that of Th17 cells is increased, in the PB and decidua samples of patients with unexplained recurrent miscarriage (RM). In this study, we investigated whether the cytokine production of Th17 cells can be suppressed by the Tregs and elucidated the mechanism by which Tregs exert this suppressive effect. methods: Flow cytometry was used to analyze the surface phenotype and cytokine production of Th17 cells in the PB of women with unexplained RM (n ¼ 17) and healthy women in early stages of pregnancy who underwent elective abortion (n ¼ 20). The suppressive ability of Tregs on Th17 cells was assessed in in vitro co-cultures and transwell experiments. The amount of secreted interleukin-17 (IL-17) in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The inhibitory activity of transforming growth factor-b (TGF-b) and IL-10 on IL-17 expression in CD4 + T cells was assessed using ELISA. results: The proportions of IL-17-positive CD4 + T cells, CC chemokine receptor type 6 (CCR6)-positive CD4 + T cells and CCR6 expression of IL-17-positive CD4 + T cells were higher in the PB samples of patients with unexplained RM than in PB of healthy control subjects. In vitro, Tregs could inhibit the expression of IL-17; more Th17 cells were inhibited in the control group than in the unexplained RM group. High-dose TGF-b inhibited the expression of IL-17, whereas IL-10 inhibited IL-17 expression in a dose-dependent manner. conclusions: IL-17 expression can be inhibited by Tregs. The suppressive activity of Tregs on Th17 cells was decreased in patients with unexplained RM. The ability of Tregs to suppress cytokine secretion might be effected by a cell–cell contact. TGF-b and IL-10 could inhibit the expression of IL-17.

Polycystic ovary syndrome (PCOS) has been recognized as a common reproductive and endocrine disorder. Long noncoding RNA (lncRNA) steroid receptor RNA activator (SRA) affects multiple biological processes. However, it is not known whether lncRNA SRA is associated with PCOS. In the study, we measured the expression level of lncRNA SRA in PCOS patients, and analyzed the association between lncRNA SRA and multiple key endocrine parameters of PCOS. LncRNA SRA expression was significantly higher in the women with PCOS than that in the controls. There was a significant positive correlation between lncRNA SRA expression and BMI in PCOS group. Furthermore, obesity positively associates with the high expression of lncRNA SRA in PCOS women but without the association in control women. In conclusion, we found that the lncRNA SRA expression is potentially associated with PCOS and it has positive correlation with obesity in PCOS, thereby suggesting that elevated lncRNA SRA might be an important mediator in adiposity-related processes in PCOS for susceptible individuals.

STUDY QUESTION Could adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells (Tregs) reverse the increase in abortion rate caused by interleukin 17 (IL-17) in the CBA/J × BALB/c mouse model? SUMMARY ANSWER The effects of exogenous IL-17 on increased abortion rate, as well as decreased transforming growth factor (TGF)-β and IL-10 expression, are reversed by a pre-mating transfusion of Tregs in a mouse model of pregnancy. WHAT IS KNOWN ALREADY IL-17 is a pro-inflammatory cytokine mainly expressed by T helper 17 cells, and plays a pivotal role in the pathogenesis of endometriosis, miscarriage, preterm labor and pre-eclampsia. The activity of Th17 cells is attenuated by the anti-inflammatory action of Tregs. STUDY DESIGN, SIZE, DURATION Fifty microliters of phosphate-buffered saline (PBS) (Group 1,) or recombinant IL-17 (rIL) (10 µg/mouse) supernatant (Group 2) was administered in the vaginal vaults of anesthetized pregnant CBA/J mice on Day 1 of pregnancy. Tregs (2 × 10(5) cells) purified from pregnant CBA/J × BALB/c mice were given i.v. via the tail vein 2 days before mating (Group 3) or on Day 7 of pregnancy (Group 4). PARTICIPANTS/MATERIALS, SETTING, METHODS Mice (n = 40) were randomly assigned to one of four experimental groups. The numbers of surviving and reabsorbed fetuses in each group were counted on Day 14 of pregnancy, and the expression of interferon (IFN)-γ, IL-4, TGF-β and IL-10 in the decidual tissue was assessed by real-time RT-PCR and western blotting. MAIN RESULTS AND THE ROLE OF CHANCE Normal pregnant CBA/J mice mated with BALB/c males which received transvaginal rIL-17 presented with a significantly increased abortion rate compared with the group which received PBS (27.7 versus 9.9%, respectively; P < 0.05). The transfusion of pregnancy-induced Tregs from 14-day normal pregnant mice 2 days before mating reduced the abortion rate caused by IL-17 (12.5 versus 27.7%, respectively; P < 0.05), while transfusion of Tregs on Day 7 of pregnancy had no effect. Transfusion of Tregs did not affect IFN-γ or IL-4 expression in the decidual tissue at either the mRNA or protein level. Administration of rIL-17 resulted in a decrease in production of TGF-β and IL-10 at both mRNA and protein levels (P < 0.05). Transfusion of Tregs before mating increased TGF-β and IL-10 mRNA and protein levels (P < 0.05), while Tregs transfusion at Day 7 of pregnancy had no effect on TGF-β or IL-10 expression. LIMITATIONS, REASONS FOR CAUTION These data derive from only a small number of mice. It is unclear whether the same effects would be seen in humans. WIDER IMPLICATIONS OF THE FINDINGS Abnormally elevated expression of IL-17 in the feto-maternal interface may result in miscarriage. Transfer of antigen-specific Tregs before mating takes place may have potential applications in the prevention of recurrent spontaneous abortion. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a grant from the National Natural Science Foundation of China (81370013, 81000277 and 81300533) and Shandong Provincial Natural Science Foundation, China (ZR2013HQ002). There were no conflicts of interest.

In normal pregnancy, tolerance of the maternal immune system with regard to the genetically incompatible fetus depends on the interactions of an array of cytokines secreted by maternal and fetal cells at the site of implantation. Earlier research indicating that altered immunity exists in unexplained recurrent miscarriage (RM) has been dominated by the Th1/Th2 hypothesis. Recently, the Th1/Th2 paradigm has been expanded into the Th1/Th2/Th17 and regulatory T cells paradigm. We recently demonstrated a prevalence of Th17 cells, an inverse relationship between Th17 cells and regulatory T cells and deregulation of Th17 cells by regulatory T cells in early pregnancy in unexplained RM patients. In this study, we investigated the expression of IL-27 and the role of the cytokine IL-27 in the regulation of Th17/Treg expression. Quantitative real-time RT-PCR and Western blot analyses were performed to evaluate IL-27 expression in deciduas from unexplained RM patients, spontaneous miscarriage (SM) patients and healthy women following elective abortion in the early stages of normal pregnancy (control). Regulation of IL-17, TGF-β and IL-10 expression in CD4 + T cells in unexplained RM patients by IL-27 was assessed using enzyme-linked immunosorbent assay (ELISA). Expression of IL-27 was lower in deciduas of patients with unexplained RM compared with SM and control subjects. IL-27 inhibited IL-17 expression and enhanced IL-10 expression in a dose-dependent manner. IL-27 had no effect on TGF-β expression. IL-27 regulates the expression of IL-17 and IL-10, which are predominantly secreted by Th17 cells and regulatory T cells in unexplained RM patients.