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Background Spontaneous ovarian hyperstimulation syndrome (sOHSS) is extremely rare. It can be divided into four types according to its clinical manifestations and follicle stimulating hormone receptor mutations. Case summary Here we report two cases of sOHSS in Chinese women, one with a singleton gestation developing sOHSS in the first trimester who conceived naturally and the other with a twin pregnancy developing sOHSS in the second trimester after a thawed embryo transfer cycle. Both patients were admitted to the hospital with abdominal distension, ascites, and enlarged ovaries. Conservative treatment was the primary option of management. The first patient had spontaneous onset labor at 40 wk of gestation and underwent an uncomplicated vaginal delivery of a male newborn. The second patient delivered a female baby and a male baby by caesarean section at 35 wk and 1 d of gestation. Conclusion Patients with a history of ovarian hyperstimulation syndrome should be closely monitored. Single embryo transfer might reduce the risk of this rare syndrome.

SummaryEstablishment of cellular polarity is one of the key events during oocyte maturation. Inscuteable (Insc) has been identified as a key regulator of cell polarity during asymmetric division in Drosophila. However, the function of its evolutionarily conserved mammalian homologue, mInscuteable (mInsc), in mouse meiotic maturation is not clear. In this study, we investigated the roles of mInsc in mouse oocyte maturation. mInsc was detected at all stages of oocyte maturation. The protein level of mInsc was slightly higher at the germinal vesicle breakdown (GVBD) stage and remained constant during mouse oocyte maturation. The subcellular localization of mInsc overlapped with spindle microtubules. Disruption of microtubules and microfilaments caused changes in the localization of mInsc. Depletion or overexpression of mInsc significantly decreased the maturation rates of mouse oocytes. Depletion of mInsc significantly affected asymmetric division, spindle assembly, alignments of chromosomes and actin cap formation. Taken together, our results demonstrated that mInsc regulates meiotic spindle organization during mouse meiotic maturation.

miRNA-339 participates in diseases with endothelial progenitor cell (EPC) dysfunction. What is the role of miRNA-339-5p in EPC of polycystic ovary syndrome (PCOS)?Clinical data were collected from 76 controls and 84 PCOS patients. Noradrenaline, asymmetric dimethylarginine (ADMA), advanced glycation end products (AGE) and silent information regulator 1 (SIRT1) in the serum were measured. The functions of EPC and the expressions of PI3K, AKT, SIRT1 and PGC-1α in EPC before and after transfection with miRNA-339-5p mimic or miRNA-339-5p inhibitor were compared.Serum concentrations of noradrenaline, ADMA and AGE were significantly higher (P = 0.009, P = 0.044, P 0.001) and the SIRT1 concentration was significantly lower (P 0.001) in PCOS patients, especially obese ones (P = 0.034, P = 0.032, P 0.001, P = 0.023) than in the control group. When compared with the controls, proliferation of the EPC was slightly lower (without a significant difference), the migration and tubular formation were significantly decreased (P = 0.037, P = 0.011), the expression of miRNA-339-5p in EPC was significantly higher (P = 0.035) and the expressions of PI3K, AKT, SIRT1 and PGC-1α were significantly lower in the PCOS group (mRNA: P = 0.033, P = 0.027, P = 0.027, P = 0.032; protein: P = 0.036, P = 0.028, P = 0.039, P = 0.023). After transfection, the functions of EPC from PCOS patients were best in the miRNA-339-5p inhibitor group, and weakest in the miRNA-339-5p mimic group. The miRNA-339-5p inhibitor group had higher protein expressions of PI3K, AKT and SIRT1 but lower expression of PGC-1α in PCOS patients (P 0.001, P = 0.030, P = 0.047, P = 0.003). Similar results were obtained from the controls after transfection.Increased sympathetic excitation and damage to EPC were observed in PCOS patients, especially obese ones. Up-regulated miRNA-339-5p could inhibit the function of EPC by inhibiting the PI3K/AKT and SIRT1/PGC-1α signalling pathways.

BACKGROUND This study aims to explore the effect of Sinomenine (SIN) on pregnancy outcomes of recurrent spontaneous abortion (RSA) in a mouse model. MATERIAL AND METHODS Thirty female CBA/J mice were allocated into 3 groups randomly, then mated with BALB/c mice (CBA/J×BALB/c) as normal-pregnancy group (n=10), or mated with DBA/2 mice (CBA/J×DBA/2) as RSA model (n=10), or CBA/J×DBA/2 mice treated with SIN as RSA+SIN group (n=10). The number of surviving and reabsorbed embryos in each group were counted on day 13.5 of gestation. The mouse serum was collected to determine the levels of interferon-γ (IFN)-γ and IL-4 by ELISA. Immunohistochemistry, qRT-PCR and immunoblotting were used to determine the location, mRNA and protein expressions of IFN-γ, IL-4, T-bet and GATA3 in the decidual and placental tissue. RESULTS In the RSA group, the amount of reabsorbed embryo was significantly higher than that in the normal-pregnancy group. However, SIN treatment showed a rescue effect on spontaneous abortion in RSA mice. IFN-γ, IL-4, T-bet, and GATA3 were all expressed in placental tissues and mainly located in the cytoplasm. The RSA group demonstrated higher expression levels of IFN-γ and T-bet than in the RSA+SIN and normal-pregnancy groups. Although RSA and RSA+SIN groups showed lower expression levels of IL-4 and GATA3 than in the normal-pregnancy group, there was no significant difference between RSA and RSA+SIN groups regarding IL-4 and GATA expression levels. CONCLUSIONS SIN treatment demonstrates a therapeutic effect on spontaneous abortion in RSA mice, possibly through regulating the balance of Th1/Th2 in maternal circulation and decidual tissues.

Aiming at the existing single image haze removal algorithms, which are based on prior knowledge and assumptions, subject to many limitations in practical applications, and could suffer from noise and halo amplification. An end-to-end system is proposed in this paper to reduce defects by combining the prior knowledge and deep learning method. The haze image is decomposed into the base layer and detail layers through a weighted guided image filter (WGIF) firstly, and the airlight is estimated from the base layer. Then, the base layer image is passed to the efficient deep convolutional network for estimating the transmission map. To restore object close to the camera completely without amplifying noise in sky or heavily hazy scene, an adaptive strategy is proposed based on the value of the transmission map. If the transmission map of a pixel is small, the base layer of the haze image is used to recover a haze-free image via atmospheric scattering model, finally. Otherwise, the haze image is used. Experiments show that the proposed method achieves superior performance over existing methods.

The part-based weighting aggregation (PWA) method is a simple and straightforward way for creating powerful image representations in image retrieval. In this paper we analyze the burstiness among the responses of the aggregated channels in the PWA method, and propose a channel-wise weights utilizing the sum-pooling aggregation of the deep features’ responses to regulate the burstiness among the feature maps. Firstly, we apply the channel weights to the aggregation stage of PWA. The regulation of the burstiness among the aggregated channels boosts the PWA performance. Secondly, we use the channel weights to the part selection stage, namely, selecting the part detectors based on the channel weighted feature maps to obtain more discriminate parts to further improve the PWA performance. Comprehensive experiments on four standard datasets have demonstrated the effects of the proposed method.

AIM Recent studies have revealed positive effects of endometrial injury on clinical pregnancy rates, but with inconsistent results. The aim of this meta-analysis was to assess the efficacy of endometrial injury (biopsy and/or hysteroscopy) as a potential treatment measure for implantation failure in the in vitro fertilization population. METHODS We searched in PubMed for studies comparing the efficacy of endometrial injury versus no intervention in women with at least one implantation failure. A random-effects model was used to evaluate the clinical pregnancy rate (CPR) and the live birth rate (LBR). RESULTS Seventeen studies (11 randomized and 6 non-randomized studies) were included in this meta-analysis, including 1864 women in the intervention group and 2193 women in the control group. Overall, the CPR and LBR were significantly higher in the intervention group than in the control group (for CPR, n = 3997, 16 studies, P

A variety of natural and artificial cryoprotectant extenders have been explored to enhance sperm recovery following cryopreservation-thawing process. The current investigation is aimed at evaluating the effect of acetyl-L-carnitine on human spermatozoa and reactive species oxygen (ROS) level after freezing-thawing process. The spermatozoa were collected from 35 male patients diagnosed as having asthenospermia. The cryopreservation of human spermatozoa treated with acetyl-L-carnitine at different concentrations (group B: 2.5 mmol/L, group C: 7.5 mmol/L, group D: 15 mmol/L) was compared with control (group A: no acetyl-L-carnitine given). For the frozen-thawed spermatozoa, the viability, motility and DNA integrity were measured by comet assay, acrosome integrity by FITC-PNA staining and ROS level was determined in each group. The results showed that there were no significant differences in motility and viability between group A and group B, while the motility and viability of spermatozoa in group C and group D were significantly increased as compared with those in group A. As compared with group A, the values for DNA integrity parameters including comet rate (CR), tail DNA percentage (TD), tail length (TL) and Oliver tail moment (OTM) were significantly reduced in group C and group D. Group C and group D also displayed a higher proportion of intact acrosome than group A. No significant difference in ROS level was found between group A and group B, while with the increase in acetyl-L-carnitine concentration, the ROS level in groups C and D was significantly reduced as compared with that in group A. In conclusion, acetyl-L-carnitine at a concentration of 7.5 mmol/L is an effective antioxidant against cryo-damage on post-thawed human spermatozoa.

Background Obesity and low-grade chronic inflammation play critical roles in pathological process of PCOS. PGRN is an adipokine and was recently reported that it could induce a low-grade chronic inflammatory state and plays a functional role in insulin resistance associated with obesity. The overall goal of the present study was to evaluate the levels of PGRN in follicular fluid (FF) and the expression of PGRN in granulosa cells (GCs) with respect to the quality of the oocytes both in patients with PCOS and in the normal ovary during COH cycles. Methods Ninety-two patients underwent IVF-ET were divided into four groups based on body mass index: normal-weight PCOS group; overweight PCOS group; non-overweight control group and overweight control group. FF samples and GCs were collected at the time of oocyte retrieval. The PGRN, TNF-α, IL-6 and MCP-1 levels were measured by ELISA, and the mRNA expression of PGRN in GCs was detected by real-time polymerase chain reaction. Results Analysis of PGRN expression revealed that PGRN levels in FF and the mRNA expression of PGRN in GCs were higher in patients with PCOS than in control patients, and higher in overweight patients than in the normal-weight patients; PGRN in FF of PCOS was positively correlate with basal testosterone and FF TNF-α，but negative correlation with retrieved oocytes number Conclusion This study suggests that PGRN may be a crucial determinant of fertilization success for PCOS patients.

To explore the genetic etiology of a child with autism, mental retardation and epilepsy.Conventional G-banding chromosomal analysis was carried out. Chromosomal variation was also detected by single nucleotide polymorphism microarray (SNP array). Pathogenic mutations were screened by high-throughput sequencing and validated by Sanger sequencing. Pathologic significance of the candidate mutations was analyzed through search of database and literature review.No karyotypic abnormality was found with the child and his parents, while SNP array has detected a 460 kb deletion in the 14q11.2 region in the child. High-throughput and Sanger sequencing revealed a novel mutation of the NALCN gene in the child, in addition with a hemizygous mutation of the COL4A5 gene in the child and his mother.The 14q11.2 microdeletion and NALCN mutation may contribute to the autism, mental retardation and epilepsy in this child.

In this paper, we propose an adaptive binarization method to handle different degraded document images. Firstly, a contrast image robust to background variations caused by different types of degradation is generated after preprocessing the input image. Secondly, an image contrast enhancement technique is used to strengthen the edges of the strokes to make them more complete. Then, the OTSU method is applied on the enhanced contrast image to obtain the stroke edge pixels, and the final binarization image is returned according to the threshold determined from the mean and the standard deviation of the intensity of these edge pixels. Experimental results on two public datasets indicate that the proposed method can deal with various degraded images, improve the continuity of the strokes and achieve superior binarization performance when compared with other methods.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

During pregnancy, the placenta is a site of active oxygen metabolism that continuously generates oxidative stress (OS). Overproduction of reactive oxygen species and reactive nitrogen species can destroy normal placental functions. Therefore, the feto-placental unit generates abundant antioxidants to keep OS under control. Properly controlled oxidative species have been proven to serve as indispensable cellular signal messengers by regulating gene expression and downstream cellular activities. OS also plays an important immunoregulatory role during pregnancy. Oxidative disorder and immune disturbances are associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and intrauterine growth restriction. In this review, we introduce recent studies revealing basal functions and regulatory roles of placental OS in metabolism and immunity. The relationships between OS- and pregnancy-related disorders are also discussed.

Fetal trophoblasts invade endometrium and establish a complex interaction with the maternal microenvironment during early pregnancy. However, the molecular mechanisms regulating trophoblast migration and invasion at the maternal–fetal interface remain poorly understood. Immunohistochemistry and immunoblotting have shown that stathmin-1 (STMN1) was down-regulated significantly in placental villi tissue and trophoblasts from patients with recurrent miscarriage. In vitro , overexpression of STMN1 promoted human trophoblast proliferation, migration, and invasion, whereas knockdown of STMN1 inhibited these processes. In addition, knockdown of STMN1 down-regulated N-cadherin and up-regulated E-cadherin in trophoblasts, whereas E-cadherin was up-regulated and N-cadherin was down-regulated in recurrent miscarriage villi tissue. Knockdown of STMN1 attenuated cytoplasmic–nuclear translocation of β-catenin and in turn down-regulated trophoblast matrix metalloproteases. Furthermore, tumor necrosis factor-α (TNF-α) down-regulated STMN1 expression, and serum TNF-α expression correlated inversely with trophoblast STMN1 levels. Interestingly, M1 macrophage–derived TNF-α reduced trophoblast migration and invasion, and an anti–TNF-α antibody reversed this effect. Collectively, this study indicated that STMN1 may play a key role in regulating trophoblast invasion, and that impaired STMN1 expression may lead to abnormal trophoblast invasion and result in recurrent miscarriage.

In this paper, a retrospective cohort study was conducted to the high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. The purpose of the study is to investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) can improve the clinical outcome compared with traditional dose (10000IU) HCG trigger and low-dose (8000IU) HCG trigger for high ovarian responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Our study included 226 couples with high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. Standard dosage of HCG trigger (10000 IU of recombinant HCG) versus dual trigger (0.2 mg of triptorelin and 2000 IU of recombinant HCG) and low-dose HCG trigger (8000IU of recombinant HCG) were used for final oocyte maturation. Our main outcome measures were high quality embryo rate, the number of usable embryos, the risk of OHSS, duration of hospitalization and incidence rate of complications. Our evidence demonstrated that dual trigger is capable of preventing severe OHSS while still maintaining excellent high quality embryo rate in in high ovarian responders of GnRH-antagonist protocols.

Objective Intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated by HCG in vitro is reported to improve implantation rates in patients with repeated failure of IVF-ET. In this article, the impact of intrauterine administration of PBMCs on embryo implantation, pregnancy rate and the underlying mechanisms will be investigated. Methods Pregnant mice were randomly divided into three groups, including control group; embryo implantation dysfunction (EID) group; EID with PBMCs group. Uterine horns were excised to determine the number of pregnant mice and implantation sites on the Day 7.5 postcoitum. The expression levels of LIF and VEGF during the implantation window were detected with immunohistochemistry and Real Time-PCR analysis. Results Embryo implantation dysfunction model group showed a significant decrease in pregnancy rate, implantation sites and the expression of both the endometrial LIF and VEGF during the implantation window. EID with PBMCs group showed a higher pregnancy rate and endometrial LIF and VEGF expression compared to EID group. Conclusion Intrauterine administration of mouse PBMCs derived from unpregnant mice prior to embryo implant has a good influence on endometrial receptivity and embryonic implantation in EID mice.

Embryo implantation is a highly synchronized bioprocess between an activated blastocyst and a receptive uterus. In mice, successful implantation relies on the dynamic interplay of estrogen and progesterone; however, the key mediators downstream of these hormones that act on blastocyst competency and endometrium receptivity acquisition are largely unknown. In this study, we showed that the expression of osteopontin (OPN) in mouse blastocysts is regulated by ovarian estrogen and uterine micro-environment. OPN mRNA is up-regulated in mouse blastocyst on day 4 of pregnancy, which is associated with ovarian estrogen secretion peak. Hormone treatment in vivo demonstrated that OPN expression in a blastocyst is regulated by estrogen through an estrogen receptor (ER). Our results of the delayed and activated implantation model showed that OPN expression is induced after estrogen injection. While estrogen treatment during embryo culture in vitro showed less effect on OPN expression, the tubal ligation model on day 3 of pregnancy confirmed that the regulation of estrogen on OPN expression in blastocyst might, through some specific cytokines, have existed in a uterine micro-environment. Collectively, our study presents that estrogen regulates OPN expression and it may play an important role during embryo implantation by activating blastocyst competence and facilitating the endometrium acceptable for active blastocyst.

Recurrent implantation failure refers to unsuccessful implantation after repeated transfers of morphologically good quality embryos into a normal uterus. Recently, accumulating evidence has suggested that local immune cells at the implantation site have actively contributed to embryo implantation. Our aim was to study the effects of intrauterine administration of hCG-activated autologous human PBMC on clinical pregnancy, implantation rates and live birth rate of patients who received frozen/thawed embryo transfer. We observed patients with one to three failed transplantations cannot benefit from the administration, but the rate of clinical pregnancy (39.58% vs. 14.29%), live birth (33.33% vs. 9.58%) and implantation (22.00% vs. 4.88%) were significantly increased in patients with four or more failures, respectively. For patients with endometrial thickness more than 7mm and less than 8mm on day of embryo transfer, the implantation rate (22.69% vs. 14.21%) and the live birth rate significantly higher in the PBMC-treated group; For patients who had RIF and received frozen/thawed early cleavage stage embryo transfer, the live birth delivery rate (29.63% vs. 13.33%) significant higher in PBMC-treated group. These findings indicate that intrauterine administration of hCG-activated autologous PBMC effectively improves the IVF outcomes for RIF patients, especially for the RIF patients with cleavage stage embryo transfer, patients with thin endometrial thickness also benefit from this approach.

Genital tract infections with ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) are the most frequent sexually-transmitted disease worldwide. UU and CT infections are considered to be the leading cause for infertility and adverse pregnancy outcomes. However, little is known about the specific effect of cervical UU and CT infections on the etiology of female infertility, as well as the pregnancy outcomes of the patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). In order to find the association between cervical UU and/or CT infection and pregnancy outcomes, we conducted a retrospective case-control study on the patients undergoing IVF/ICSI-ET with cervical UU and/or CT infection. A total of 2208 patients who received IVF/ICSI-ET were enrolled in this study. Data on the general conditions, pregnancy history and clinical pregnant outcomes were analyzed in terms of the cervical UU and CT detection. Our results revealed that cervical UU and CT infections were the risk factors for ectopic pregnancy and tubal factor-induced infertility. Moreover, the pregnancy rate, abortion rate, ectopic pregnancy rate and premature birth rate in patients with UU and/or CT infections showed no significant difference when compared with the control group. We recommend that cervical UU and CT detection should be an optional item for infertility patients and clinical UU detection should differentiate the subtypes of cervical UU. Positive cervical UU and CT infections should not be taken as strict contraindications for IVF/ICSI-ET.

Embryo implantation is a crucial process for successful pregnancy. To date, the mechanism of embryo implantation remains unclear. Ezrin-radixin-moesin-binding protein-50-kDa (EBP50) is a scaffold protein, which has been shown to play an important role in cancer development. Embryo implantation and cancer follow a similar progression. Thus, in this article, we utilized immunohistochemical staining and western blot analyses to examine the spatiotemporal expression and regulation of EBP50 both in the mouse uterus during embryo implantation as well as in other related models. We found that EBP50 was detected in epithelial cells in all of the groups used in our study. During the peri-implantation period, EBP50 mainly localized in apical membranes. At the implantation site (IS) on day 5 (D5) of pregnancy, EBP50 was mainly expressed in the nuclei of stroma cells, whereas from day 6 to day 8 (D6–D8) of pregnancy, the expression of EBP50 was noted in the cytoplasm of decidual cells. The expression of EBP50 was not significantly different in the pseudopregnant uterus and decreased in the uteri subjected to activation of delayed implantation. Artificial decidualization also decreased EBP50 expression. Thus, the expression levels and location were affected by active blastocysts and decidualization during the window of implantation.

To compare the reproductive outcomes of Yqh+-carrying and control couples undergoing IVF/ICSI treatments.Retrospective analysis of 72 Yqh+ carriers and 986 Yqh+ non-carriers undergoing their first cycle of ART in a single centre between August 2005 and May 2011.Yqh+ carrying couples had significantly worse reproductive outcomes compared with control couples undergoing IVF treatment. There were a significantly higher cancellation rate (20.69% vs 7.9%; P0.05; OR, 3.03; CI, 1.18-7.79) and a significant lower fertilisation rate (50.05% vs 66.01%; P0.05; OR, 0.61; CI, 0.49-0.57), implantation rate (8.33% vs 20.87%; P0.05; OR, 0.35; CI, 0.14-0.87), good quality embryo ratio (44.70% vs 57.89%; P0.05; OR, 0.59; CI, 0.43-0.80) and clinical pregnancy rate (17.39% vs 39.59%; P0.05; OR, 0.32; CI, 0.11-0.96) in Yqh+ group compared with control group undergoing IVF treatment. Yqh+ carrying couples had similar reproductive outcomes compared with control couples undergoing ICSI treatment.The Y chromosome polymorphic variant Yqh+ most likely plays a role in infertility. Yqh+ couples with poor reproductive outcomes in IVF treatment can be advised to undergo ICSI to improve their reproductive results in the next cycle.

PROBLEM: To examine the immunocontraceptive properties of the plasmid pcDNA-mCRISP1 and compare them to the corresponding recombinant mCRISP1 (r-mCRISP1). METHOD OF STUDY: RT-PCR and indirect immunofluorescence were performed to observe the mCRISP1 protein expression in COS-7 cells. Three groups of mice received three injections of r-mCRISP1 pcDNA-mCRISP1 or pcDNA vector respectively. ELISA and Western blot were used to examine the immune responses and immunoreactivity of antisera. Sperm-egg penetration assay was performed to examine the effect of anti-mCRISP1 antibodies in vitro fertilization of mouse oocytes. Fertility and mean litter size were analysed by natural mating. Histological analysis was carried out to look for potential immunopathologic effects of the antibodies. RESULTS: COS-7 cells transfected with pcDNA-mCRISP1 present the expression of mCRISP1. Both r-mCRISP1 and pcDNA-mCRISP1 raised an immune response against r-mCRISP1 protein and native CRISP1 in mouse sperm. The titres of anti-mCRISP1 antibodies from DNA immunized mice were significantly lower than that of r-mCRISP1 immunized mice but it lasted relatively longer. Male and female pcDNA-mCRISP1 injected animals presented a statistically significant reduction in their fertility with no signs of immunopathologic effects. CONCLUSION: These studies demonstrated the feasibility of generating an immune response to mCRISP1 protein by DNA vaccine and pcDNA-mCRISP1 plasmid causing significant anti-fertility potential. (c) 2012 John Wiley & Sons A/S.

Objective To study the relationship between perifollicular blood flow and follicule development, oocyte maturing rate, fertilizing rate, cleaving rate, embryo quality and the outcomes of embryo transfer. Methods The samples were selected from 66 suffers who underwent in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI). Eeach patients' perifollicular blood flow(diameter ≥ 12mm)was estimated on the day of human chorionic gonadotropin(HCG)administration. Results Among 66 cycles,26(39.4%) cycles resulted in pregnancy. perifollicular blood flow resistance index(RI), peak systolic velocity/end diastasis velocity(S/D) of non-pregnant group was significantly higher than that of the pregnant group(P 0.05). There were no statistical difference between non-pregnant group and pregnant group in S and D (P >0.05). There was no correlation between periFollicular blood flow RI and follicular diameter by linear regression analysis. Conclusion Our study shows that perifollicular blood flow RI and S/D are effective indices of predicting the pregnancy outcome of IVF-ET.

Whether the type of culture media utilized in assisted reproductive technology has impacts on laboratory outcomes and birth weight of newborns in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was investigated. A total of 673 patients undergoing IVF/ICSI and giving birth to live singletons after fresh embryo transfer on day 3 from Jan. 1, 2010 to Dec. 31, 2012 were included. Three types of culture media were used during this period: Quinn's Advantage (QA), Single Step Medium (SSM), and Continuous Single Culture medium (CSC). Fertilization rate (FR), normal fertilization rate (NFR), cleavage rate (CR), normal cleavage rate (NCR), good-quality embryo rate (GQER) and neonatal birth weight were compared using one-way ANOVA and χ (2) tests. Multiple linear regression analysis was performed to determine the impact of culture media on laboratory outcomes and birth weight. In IVF cycles, GQER was significantly decreased in SSM medium group as compared with QA or CSC media groups (63.6% vs. 69.0% in QA; vs. 71.3% in CSC, P=0.011). In ICSI cycles, FR, NFR and CR were significantly lower in CSC medium group than in other two media groups. No significant difference was observed in neonatal birthweight among the three groups (P=0.759). Multiple linear regression analyses confirmed that the type of culture medium was correlated with FR, NFR, CR and GQER, but not with neonatal birth weight. The type of culture media had potential influences on laboratory outcomes but did not exhibit an impact on the birth weight of singletons in ART.

PROBLEM: To evaluate the effectiveness and security of a contraceptive vaccine using plasmid DNA encoding mouse CRISP1 as antigen and chitosan nanoparticles as the carrier. METHOD OF STUDY: Chitosan-pcDNA3.1-mCRISP1 Nanoparticles (CS-DNA NPs) were prepared and characterized in terms of morphology zeta potential polydispersity index and binding capacity of pDNA. The cytotoxicity and gene transfer capability of CS-DNA NPs were assessed in COS-7 cells compared to Lipofectamine 2000 . Four groups of mice received three injections of 0.9% normal saline pcDNA3.1 vector pcDNA3.1-CRISP1 or CS-DNA NPs respectively. ELISA was used to examine the immune responses. Fertility and mean litter size were analyzed by natural mating. RESULTS: CS-DNA NPs have a spherical or elliptical shape with a mean diameter of 189.3 nm positive zeta potential and good DNA condensation. It also showed high DNAse resistance and good transfection efficiency without cell toxicity. The titers of anti-mCRISP1 antibodies from CS-DNA NP-immunized mice were significantly higher than that of pcDNA3.1-CRISP1 group. Male and female CS-DNA NP-immunized animals were recognized with a statistically significant reduction in their fertility compared with pcDNA3.1-CRISP1-immunized mice. CONCLUSION: This study demonstrated that using chitosan-DNA nanoparticles as the carrier can improve the immunogenicity of mCRISP1 DNA contraceptive vaccine with good security. (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Problem Many researchers have demonstrated that the expression of interleukin-17(IL-17) is higher in spontaneous abortion. However, whether Th17 cells are an independent factor in inducing abortion is not known. Method of study This study investigated the effect of exogenous recombinant IL-17 and an anti-IL-17 antibody in a normal and an abortion mouse model using flow cytometry, enzyme-linked immunosorbent assay, real-time PCR, and Western blot. Results Th17 cells and the related factors, IL-17 and RORγt, were significantly upregulated in abortion mice, and Treg cells and the related factor, Foxp3, were downregulated. Intraperitoneal injection of recombinant IL (rIL)-17 induced fetal loss in a normal mouse model, and an anti-IL-17 antibody prevented fetal loss in an abortion mouse model. Conclusion This study confirmed an imbalance of the Th17/Treg paradigm in abortion mice and IL-17 as a risk factor of fetal loss. An anti-IL-17 antibody may prevent abortion.

Bacteria and viruses activate the host innate immune response via Toll-like receptor (TLR)-involved signaling and potentially cause pregnancy failure. TLR7 and TLR9 respond to single-stranded RNA (a viral intermediate) and hypomethylated CpG DNA motifs (specific molecular constituents of bacteria) respectively. In this study, we treated murine RAW264.7 cells with R837, CpG1826, or a combination of the two. RT-PCR was performed to detect cytokines, Tlr7, and Tlr9. WT and nonobese diabetic murine embryo resorption models were established by i.p. injections of TLR7 and TLR9 ligands. Neutralizing antibodies and the IL1β and TNFα inhibitors were used. The specific inhibitors anakinra and etanercept effectively prevented TLR7 and TLR9 ligand-induced embryo loss. Notably, this effect was not observed in decidual NK cell-depleted mice. Our findings suggest that anakinra and etanercept may have potential for preventing TLR7 or TLR9 ligand-induced abortion in the presence of decidual NK cells.

Selective serotonin re-uptake inhibitors (SSRIs), has been increasingly used for the treatment of premature ejaculation over the past 5 years. It was reported that folic acid plays important roles in synthesis of 5-HT. Therefore, we hypothesize that folic acid supplementation may cures premature ejaculation by the same mechanism of interacting with monoamine neurotransmitters in brain, to be the replacement of RRSIs. Folic acid supplementation cures premature ejaculation more safely. These new views will help to understand the diagnosis and treatment methods for premature ejaculation.

The aim of the present study was to evaluate the association between follicular fluid (FF) levels of high-mobility group box 1 (HMGB1) protein and the reproductive outcome in patients undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). FF samples were collected from the ovarian follicles (≥14 mm) of 143 infertile patients that had undergone IVF/ICSI, and the HMGB1 expression levels were determined using ELISA. Spearman's correlation and receiver operating characteristic (ROC) curve analysis were applied to analyze the results. Significantly increased levels of HMGB1 protein (7.38±2.02 vs. 6.14±2.52 ng/ml; P

To optimize the cutoff level for serum beta human chorionic gonadotropin (beta-hCG) determination on day 12 after embryo transfer (ET).This was a retrospective data analysis.beta-hCG values on day 12 after ET of 1,057 clinical pregnancies undergoing in vitro fertilization were analyzed. Receiver operating characteristic curves and optimal cutoff values to discriminate between singleton and multiple pregnancies, intrauterine pregnancy and ectopic pregnancy, and live-birth pregnancy and miscarriage were calculated separately. Cutoff values were found at 239 IU/L for multiple pregnancies (sensitivity 69.0%, specificity 74.5%, positive predictive value [PPV] 48.4%, negative predictive value [NPV] 86.1%), 91 IU/L for ectopic pregnancy (sensitivity 82.7%, specificity 71.1%, PPV 15.5%, NPV 98.5%), and 143 IU/L for miscarriage (sensitivity 72.3%, specificity 63.0%, PPV 33.1%, NPV 90.0%), respectively.beta-hCG cutoff values on day 12 after ET determined by a ROC curve analysis are useful to predict the final type of clinical pregnancy.

Objectives To explore the relationship between coping strategies and depression, and the risk factors of depression among Chinese women in infertile couples undergoing in-vitro fertilization (IVF). Study design Two hundred and eighty-eight women undergoing IVF completed the Center for Epidemiologic Studies Short Depression Scale and the Brief COPE Inventory. Demographic data were collected, hormone levels were tested and oocyte numbers were counted. Results The incidence of depression was 22.6%. The prevalence of depression was higher among women who had been married for >8 years, women who had been infertile for >6 years and women with a family income ≤3000 CNY/month. High basal follicle-stimulating hormone, oocyte number and denial score were associated with greater risk of depression. High oestradiol (basal and peak), and substance use and humour scores were associated with lower risk of depression. Conclusion Many women in infertile couples undergoing IVF have depression. Preventive interventions should be provided for women with risk factors of depression, such as long duration of marriage, long duration of infertility, low monthly family income, high basal follicle-stimulating hormone, low serum oestradiol, high oocyte number, and use of denial as a coping strategy.

We undertook this retrospective variables-control analysis to compare the reproductive outcomes of frozen-thawed embryo transfer using endometrial preparation with either natural cycle or hormone replacement therapy cycle. Patients were divided into three subgroups. Subgroup A (n = 32) consisted of patients having three 8-cell post-thawed embryos transferred. Subgroup B (n = 404) consisted of patients having three good quality post-thawed embryos transferred. Subgroup C (n = 578) consisted of patients having two or three all intact and mitosis resumption post-thawed embryos transferred. Implantation rate, biochemical pregnancy rate, and clinical pregnancy rate were measured. In subgroup A, significantly higher implantation rate, clinical pregnancy rate ongoing pregnancy rate, and lower biochemical pregnancy rate were observed in the natural cycle compared with hormone replacement therapy (HRT) cycle. Subgroup B, had a significantly higher rate of implantation, ongoing pregnancy, and a significantly lower rate of biochemical pregnancy in natural cycle compared with HRT cycle. The natural cycle had a higher trend of clinical pregnancy rate without reaching statistical significance. No statistical difference in reproductive outcomes between natural cycle and HRT cycle was observed in subgroup C. The results suggest the superiority of the natural cycle as compared with the HRT cycle under certain circumstances in a selected population of patients.

To investigate factors that can affect compliance with treatment of polycystic ovary syndrome (PCOS) in infertile patients and to provide a basis for clinical treatment, specialist consultation and health education.Patient compliance was assessed via a questionnaire based on the Morisky-Green test and the treatment principles of PCOS. Then interviews were conducted with 99 infertile patients diagnosed with PCOS at Renmin Hospital of Wuhan University in China, from March to September 2009. Finally, these data were analyzed using logistic regression analysis.Logistic regression analysis revealed that a total of 23 (25.6%) of the participants showed good compliance. Factors that significantly (p0.05) affected compliance with treatment were the patient's body mass index, convenience of medical treatment and concerns about adverse drug reactions.Patients who are obese, experience inconvenient medical treatment or are concerned about adverse drug reactions are more likely to exhibit noncompliance. Treatment education and intervention aimed at these patients should be strengthened in the clinic to improve treatment compliance. Further research is needed to better elucidate the compliance behavior of patients with PCOS.

This study examined the impact of luteinized unruptured follicle (LUF) on endometrial receptivity. The menstrual cycle of 17 LUF patients (LUF group) and 13 ovulatory women (control group) was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E(2) and P were detected by chemiluminescence. The results exhibited that (1) The mean serum P level in LUF group (7.32±2.56 ng/mL) was significantly lower than that in control group (11.17±3.17 ng/mL) (P0.01). But there was no significant difference in the mean serum E2 levels between LUF group (179.35±81.60 pg/mL) and the control group (198.58±75.23 pg/mL) (P0.05); (2) The mean expression intensities of ER, PR in endometrium of LUF group (183.86±2.43, 167.94±3.04) were significantly higher than those in control group (109.35±6.31, 105.98±4.07) (P0.01); (3) The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients (114.90±11.38) were significantly lower than those in control group (191.34±1.82) (P0.01); (4) The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level (r=0.77, P0.01), but bore no significant relationship with serum E(2) level (r=0.01, P0.05). It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.

A 29-year-old woman presented 77 days after she had undergone in-vitro fertilization and embryo transplantation with a 15-day history of vague pain in the hypogastrium which had increased over the last 8 days. Her pulse rate was 75 bpm and blood pressure was 100/70 mmHg. Abdominal examination revealed tenderness of the hypogastrium and rebound in the left lower quadrant. A routine blood test showed her haemoglobin levels were 79 g/litre. Transvaginal sonography revealed an enlarged uterus with evidence of intrauterine pregnancy and a complex 10.4×5.5 cm mass in the left adnexal region (Figure 1). After admission, the patient was prescribed antibiotic (penicillin) and antihaemorrhagic (aminomethylbenzoic acid and Dicynone) medication, but her symptoms did not improve. On the 85th day of pregnancy, the patient complained of severe and persistent hypogastric pain. Ultrasound showed that the complex structure was now 12.6×10.5 cm. Immediate laparotomy revealed 700 ml haemoperitoneum, 300 ml of sludgy blood in the rectouterine pouch, a normal pregnant uterus, a dark smooth left ovary with a crevice on the back and the left fallopian tube adherent to the abdominal membrane. Pathology showed ovarian pregnancy with bleeding. After ovary wedge resection the patient felt better and the intrauterine pregnancy continued. To the authors' knowledge, this is the first reported case of ovarian pregnancy along with intrauterine pregnancy after in-vitro fertilization and embryo transplantation. In this case, the transferred embryo moved from the uterus into the ovary.