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Purpose: This study aims to identify the mechanism of Inhibin Subunit Beta B (INHBB), a member of the transforming growth factor-β (TGF-β) family involved in the regulation of human endometrial stromal cells (HESCs) decidualization in recurrent implantation failure (RIF). Methods: RNA-seq was conducted to identify the differentially expressed genes in the endometria from control and RIF patients. RT-qPCR, WB, and immunohistochemistry were performed to analyse the expression levels of INHBB in endometrium and decidualised HESCs. RT-qPCR and immunofluorescence were used to detect changes in the decidual marker genes and cytoskeleton after knockdown INHBB. Then, RNA-seq was used to dig out the mechanism of INHBB regulating decidualization. The cAMP analogue (forskolin) and si-INHBB were used to investigate the involvement of INHBB in the cAMP signalling pathway. The correlation of INHBB and ADCY expression was analysed by Pearson's correlation analysis. Results: Our results showed significantly reduced expression of INHBB in endometrial stromal cells of women with RIF. In addition, INHBB was increased in the endometrium of the secretory phase and significantly induced in in-vitro decidualization of HESCs. Notably, with RNA-seq and siRNA-mediated knockdown approaches, we demonstrated that the INHBB-ADCY1-mediated cAMP signalling pathway regulates the reduction of decidualization. We found a positive association between the expression of INHBB and ADCY1 in endometria with RIF (R2 = 0.3785, P = 0.0005). Conclusions: The decline of INHBB in HESCs suppressed ADCY1-induced cAMP production and cAMP-mediated signalling, which attenuated decidualization in RIF patients, indicating that INHBB is an essential component in the decidualization process. [ABSTRACT FROM AUTHOR]

Pedicle screw (PS) implantation is an ideal treatment for severe multilevel vertebra instabilities. The accuracy of fixating PS is a key factor of spinal surgery. We developed a near-infrared spectroscopy device with a needlelike optical fiber probe to monitor optical parameters (reduced scattering coefficient) of vertebra models in real time. The fresh-frozen cadaver, cats and porcine vertebras were first studied in the experiments. Moreover, the reduced scattering coefficient (μ' s) along the different trajectories of PS insertion was obtained. In the fresh-frozen cadavera experiment, μ' s values could be used to distinguish the different compositions of the thoracic vertebra. In cat vertebra experiment, μ' s values of vertebrae bones, including cortical bone (15.30 ± 0.18 cm(-1)), cancellous bone (7.84 ± 1.11 cm(-1)) and spinal cord (19.46 ± 0.21 cm(-1)), were different in vivo. In the pig vertebrae experiment, there were obvious differences between the normal and abnormal PS puncture curves based on μ' s values. Thus, μ' s values measured by using the proposed device could be used as the pattern factor in spinal fusion surgery. Our studies demonstrate that near-infrared spectroscopy method may be potentially used for assisting the PS insertion. [ABSTRACT FROM AUTHOR]

Background: Although exogenous follicle-stimulating hormone (FSH) has been used for decades and millions of cycles have been performed worldwide until now, criteria for selecting the proper FSH starting dose have not been clearly identified. The aim of this study was to elaborate a formula based on markers of ovarian reserve for the calculation of the appropriate starting dose of FSH.Methods: A total of 931 patients underwent in vitro fertilization (IVF) treatment using long GnRH agonist protocol was retrospectively identified and reviewed. 673 cases of them with a normal ovarian response (4-14 retrieved oocytes) were used to analysis the predictive formula. All follicles 4-7 mm in diameter were counted in the same day of blood sample in both ovaries using transvaginal ultrasound scan. The modified protocol of each patient was recorded and analyzed in the same center. In another center were the numbers of retrieved oocytes of 750 validated patients recorded and analyzed.Results: A formula model based on age, AMH, and antral follicle count (AFC) was able to accurately predict the ovarian sensitivity and accounted for 57.2% of the variability of ovarian response to FSH. When tested in the same total population used to elaborate the model it predicts a high 46.88% rate of step-down protocol in higher-starting FSH dose group and about 57.92% of patients had their dose step-up modified in lower-starting FSH dose group during their treatment, respectively. And when tested in different population from another center used to elaborate the model it predicts a high 64.40% rate of ≥ 15 retrieved oocytes in higher-starting FSH dose group and about 22.50% of patients had ≤ 7 retrieved oocytes in lower-starting FSH dose group during their treatment, respectively.Conclusions: In the present study we demonstrated that the individualized FSH starting dose may be calculated on the basis of a woman's age, AMH and AFC. The formula model might be a useful, immediate, and easily applicable tool for clinicians to predict the tailored starting dose of FSH during their daily clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of culture duration (embryo (day 3) transfer vs. blastocyst (day 5-6) transfer) on the birthweight of singletons from frozen embryo transfer (FET) cycles.Methods: A total of 1092 singletons were analyzed in this retrospective study. The distribution of large for gestational age (LGA) infants, the mean birthweight, and z scores of singletons were compared between the day 3 and day 5-6 transfer groups. Multiple linear regression analysis was performed to evaluate the relationships between confounding factors and singleton birthweight.Results: The proportion of LGA infants significantly increased with BMI (BMI < 20, 12.8%; 20 ≤ BMI ≤ 25, 23.2%; BMI > 25, 32.3%; P < 0.0001). However, the proportions of small for gestational age (SGA) and LGA infants were not significantly different between day 3 and day 5-6 transfers. The absolute mean birthweight of singletons was not significantly different between day 3 transfer (3422 ± 547 g) and day 5-6 transfer (3433 ± 559 g; P = 0.732). The z scores (calculated from a reference population) of singletons were also not significantly different between the two groups (0.499 vs. 0.533, P = 0.625). Multiple linear regression analysis showed that maternal BMI, gestational age, and infant gender had significant effects on singleton birthweight, while culture duration (P = 0.731) did not significantly affect singleton birthweight.Conclusions: In vitro culture duration did not affect the birthweight of newborns resulting from day 3 to day 5-6 transfers in FET cycles. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between the numbers of oocytes retrieved and the cumulative live birth rates (LBR) in women aged 35-40 years undergoing long GnRH agonist IVF/ICSI cycles.Methods: A total of 931 women aged 35-40 years who underwent their first cycle of IVF/ICSI treatment between January 2010 and December 2013 at Nanjing Drum Tower Hospital were identified and reviewed. The main endpoint of this study was the cumulative LBR after one complete oocyte retrieval, which included fresh and all subsequent frozen-thaw embryo transfer cycles. Odds ratios (OR) and 95% confidence interval (CI) for live birth were estimated by multivariate logistic regression analysis. Furthermore, all the women were divided into four groups based on the number of oocytes retrieved: 0-4, 5-9, 10-14 or ≥15 oocytes group. Variables were then compared among groups.Results: We found that 634 out of the 931 patients (68.1%) achieved at least one live birth. The number of oocytes retrieved was an independent predictive factor for live birth, with OR 1.20 (95% CI 1.15-1.26) when adjusted for age (years), duration of infertility and Gn (gonadotrophin) doses. The cumulative LBR in the four different oocyte groups was 35.6, 68.8, 83.4 and 89.2%, respectively. When the 1-4 oocytes group was issued as a reference, the ORs for cumulative LBR gradually increased to 3.66, 6.74 and 11.77 in other three oocytes groups, respectively. The moderate-severe ovarian hyperstimulation syndrome (OHSS) rate was dramatically increased in the ≥15 oocytes group (6.9%) when compared to that in the 10-14 oocytes group (0.8%), while the cumulative LBR only increased 5.8% (from 83.4 to 89.2%).Conclusions: The ideal number of oocytes retrieved in women aged 35-40 years is 10-14 oocytes, which achieves a high cumulative LBR while maintaining an acceptable low OHSS rate. [ABSTRACT FROM AUTHOR]

Introduction: Excessive inflammation results in adverse pregnancy outcomes, including embryonic resorption, fetal growth restriction, and preeclampsia. This study investigated whether curcumin, a highly safe anti-inflammation drug, had protective effect on lipopolysaccharide (LPS)-treated pregnant mice. Method: A mouse model of LPS-induced adverse pregnancy outcomes was generated by daily administering LPS from GD 13.5 to GD 16.5. Curcumin was given from GD 0.5. The effects of curcumin on maternal hypertension, proteinuria, pregnancy outcomes, as well as proinflammatory factors, chemokines, Akt, JNK, and P38 levels in placenta were examined. Results: Systolic blood pressure (156.6 ± 5.056 versus 125.5 ± 3.617 mmHg; P < 0.05) and proteinuria (22.36 ± 2.22 versus 12.70 ± 1.04 mg/L; P < 0.05) were decreased in the LPS+curcumin-treated group, as compared with the LPS-treated group. Curcumin also increased the number of live pups, fetal weight, and placental weight, while it decreased fetal resorption rate. Moreover, increased placental TNF-α, IL-1β, and IL-6 expressions in LPS-treated group were significantly suppressed after curcumin administration. Furthermore, decreased p-Akt level in placenta induced by LPS was improved by curcumin. Of note, the expression of p-Akt increased by curcumin was accompanied by the decreased chemokines MCP-1 and MIP-1 levels and fewer CD68-positive macrophages in the placenta. Conclusion: Curcumin inhibited the expression of proinflammatory factors and macrophage infiltration in placenta and ameliorated LPS-induced adverse pregnancy outcomes in mice by inhibiting inflammation via upregulation of phosphorylated Akt. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the usefulness of preimplantation genetic diagnosis (PGD) for the patient affected by congenital contractural arachnodactyly (CCA) and spinal and bulbar muscular atrophy (SBMA). Methods: Multiple displacement amplification (MDA) was performed for whole genome amplification (WGA) of biopsied trophectoderm (TE) cells. Direct mutation detection by sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used for CCA diagnosis. Direct sequencing of the PCR products and sex determination by amplification of sex-determining region Y (SRY) gene were used for SBMA diagnosis. After PGD, the unaffected blastocyst (B4) was transferred in the following frozen embryo transfer (FET). Results: In this PGD cycle, sixteen MII oocytes were inseminated by ICSI with testicular spermatozoa. Four blastocysts (B4, B5, B10, B13) were utilized for TE cell biopsy on day 5 after ICSI. After PGD, B4 was unaffected by CCA and SBMA. B5 was affected by CCA and carried SBMA. B10 was unaffected by CCA and carried SBMA. B13 was affected by CCA and unaffected by SBMA. B4 was the only unaffected blastocyst and transferred into the uterus for the subsequent FET cycle. The accuracy of PGD was confirmed by amniocentesis at 21 weeks of gestation. A healthy boy weighing 2850 g was born by cesarean section at the 38th week of gestation. Conclusions: PGD is a valid screening tool for patienst affected of CCA and SBMA to prevent transmission of these genetic diseases from parents to children. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of early rescue ICSI on neonatal outcome. Methods: This retrospective study compared the neonatal outcome of early rescue ICSI and ICSI with ejaculated sperm, including 233 children who were conceived after early rescue ICSI and a control group of 906 children who were conceived after ICSI with ejaculated sperm, and all of the children had a gestational age of 20 weeks or more. The numbers of live and stillbirths, perinatal deaths, prematurity, birthweights and birth defects of the children were compared. Results: Children in the early rescue ICSI group showed no increased risk of stillbirths, perinatal death or birth defects. Those children also did not differ from those of the ICSI with ejaculated sperm group in gender rate, birthweight, gestational age or prematurity. Conclusions: Early rescue ICSI did not increase the adverse effect on the neonatal outcome when compared to that of ICSI with ejaculated sperm. [ABSTRACT FROM AUTHOR]

Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. [ABSTRACT FROM AUTHOR]