Publications by authors named "Ningling Wang"

40 Publications

Risks of Placenta Previa and Hypertensive Disorders of Pregnancy Are Associated With Endometrial Preparation Methods in Frozen-Thawed Embryo Transfers.

Front Med (Lausanne) 2021 22;8:646220. Epub 2021 Jul 22.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Endometrial preparation is essential in frozen-thawed embryo transfer (FET) cycles. Recent studies suggested that different endometrial preparation methods may influence obstetrical complications. However, the association between hormone replacement therapy (HRT) and ovarian stimulation (OS) FET endometrial preparation and obstetrical complications remains unknown. This retrospective cohort study included a total of 79,662 confirmed embryo transfer cycles during the period from January 2003 to December 2019. After exclusion, the remaining cases were categorized into an ovarian stimulation FET group (OS FET group, = 29,121) and a hormone replacement therapy FET group (HRT FET group, = 26,776) and subjected to the analyses. The primary outcome was the rate of obstetrical complications included placenta previa, placenta abruption, hypertensive disorders of pregnancy (HDP), placenta accreta, gestational diabetes mellitus (GDM), preterm premature rupture of the membrane (pPROM). The secondary outcome was pregnancy outcomes such as live birth rate, birth weight, pre-term and post-term delivery and cesarean sections. In order to minimize the bias, 10 pregnancy-related factors were adjusted in multiple logistic regression analysis. Placenta previa (0.6 vs. 1.2%, < 0.001) and HDP (3.5 vs. 5.3%, < 0.001) were found lower in the OS FET than HRT FET group. Cesarean section was observed lower in the OS than HRT group (76.3 vs. 84.3%, < 0.001). After adjustment for 10 important pregnancy-related confounding factors, we found that the risk of placenta previa (aOR 0.54, 95% CI 0.39-0.73) and HDP (aOR 0.65, 95% CI 0.57-0.75) and cesarean section (aOR 0.61, 95% CI 0.57-0.66) were still significantly reduced in the OS than HRT group. Furthermore, live birth rates were higher (80.0 vs. 76.0%, < 0.001), and the miscarriage rate was lower (17.7 vs. 21.3%, < 0.001) for pregnancies conceived with OS FET than with HRT FET. And the average birth weight was lower in the OS group compared to HRT group (2982.3 ± 636.4 vs. 3025.0 ± 659.0, < 0.001), as well as the small-for-gestational age (SGA) was higher (8.7 vs. 7.2%, < 0.001) and the large-for-gestational age (LGA) was lower (7.2 vs. 8.6%, < 0.001) in the OS group than in the HRT group. The risks of placenta previa and HDP were lower in patients conceiving after OS FET than in those after HRT FET. Further prospective studies are required to further clarify the mechanism underlying the association between endometrium preparation and obstetrical complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.646220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339408PMC
July 2021

Cumulative live birth rates over multiple complete cycles of in vitro fertilisation cycles: 10-year cohort study of 20,687 women following freeze-all strategy from one single centre.

Arch Gynecol Obstet 2021 Aug 4. Epub 2021 Aug 4.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital affiliated to JiaoTong University School of Medicine, Zhi zao ju Road No. 639, Shanghai, China.

Purpose: To explore the cumulative live birth rates (CLBRs) over multiple complete cycles of in vitro fertilization (IVF) among patients following freeze-all strategy METHODS: A retrospective cohort study was performed among 20,687 women undergoing their first and following IVF cycles from 2007 to 2016. The main outcomes of present study were live birth rate per cycle, conservative CLBR and optimal CLBR.

Results: The CLBR increased from 50.74% for the first complete cycle to 64.41% for the conservative estimate and 84.77% for the optimal estimate after seven complete cycles. The CLBRs varied by age. The conservative estimate of CLBR after five complete cycles declined from 77.11% for women younger than 31 years, to 8.63% for women older than 40 years. The optimal CLBRs were 91.82% and 13.74%, respectively. The predictors of live birth over multiple complete cycles for patients embarking on IVF following freeze-all strategy were women's age and causes of infertility. For patients finishing the first complete cycle, the number of oocytes retrieved at complete cycle one also played an important predictive role.

Conclusions: Among women undergoing IVF following freeze-all strategy, the CLBR after seven complete IVF cycles was 84.77% if there were not barriers to continue the IVF treatment, with variation by age. Two prediction models were developed to estimate their probability of having a baby over multiple complete IVF cycles with freeze-all strategy among patients before starting IVF and patients after the first complete cycle, which is critical for patients to make treatment decisions and preparations physically, emotionally, and financially.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-021-06063-1DOI Listing
August 2021

Pulse therapy with vincristine and dexamethasone for childhood acute lymphoblastic leukaemia (CCCG-ALL-2015): an open-label, multicentre, randomised, phase 3, non-inferiority trial.

Lancet Oncol 2021 09 27;22(9):1322-1332. Epub 2021 Jul 27.

Department of Hematology/Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China.

Background: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia.

Methods: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m) plus oral dexamethasone (6 mg/m per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706.

Findings: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060).

Interpretation: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia.

Funding: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(21)00328-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416799PMC
September 2021

Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.

J Clin Oncol 2021 Jun 2:JCO2003096. Epub 2021 Jun 2.

Anhui Provincial Children's Hospital, Hefei, China.

Purpose: Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes.

Methods: We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years.

Results: We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment.

Conclusion: Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.03096DOI Listing
June 2021

Effect of Day 3 and Day 5/6 Embryo Quality on the Reproductive Outcomes in the Single Vitrified Embryo Transfer Cycles.

Front Endocrinol (Lausanne) 2021 23;12:641623. Epub 2021 Apr 23.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, School of Medicine, JiaoTong University, Shanghai, China.

Objective: To explore the live birth rate and neonatal outcome after single vitrified blastocyst transfer versus single vitrified cleavage-stage embryo transfer at different grades of embryo quality.

Methods: A retrospective cohort study including 6077 single vitrified-thawed embryo transfer cycles was performed in the time-period from January 2013 to December 2018.

Results: After controlling for potential confounding variables, there are 161% increased odds of a live birth after transfer of single good quality embryo at day 5, 152% increased odds of a live birth after transfer of single poor quality embryo at day 5, 60% increased odds of a live birth after transfer of single good quality embryo at day 6 compared with transfer of single good quality embryo at day 3. Results from the generalized estimated equation regression showed significant relationship of unadjusted birth weight with development stage of embryo and embryo quality (good quality embryo on day 5 vs. Good quality embryo on day 3:β=108.55, SE=34.89, P=0.002; good quality embryo on day 6 vs. Good quality embryo on day 3:β=68.80, SE=33.75, P=0.041). However, no significant differences were seen in birth weight between transfer single poor quality embryo on day 5, 6 and transfer single good quality embryo on day 3.

Conclusion: A significant increase in live birth rate and birth weight after transfer of single good quality embryo on day 5 and day 6 compared with transfer of single good quality embryo on day 3 in the vitrified embryo transfer cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.641623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147686PMC
April 2021

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Sci Rep 2021 05 6;11(1):9656. Epub 2021 May 6.

Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 10/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88912-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102476PMC
May 2021

Betalain Alleviates Airway Inflammation in an Ovalbumin-Induced-Asthma Mouse Model via the TGF-β1/Smad Signaling Pathway.

J Environ Pathol Toxicol Oncol 2021 ;40(2):11-21

Department of Pediatrics, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.

Global industrialization not only improved the quality life of millions but also paved the way to solving many health problems. One among them is allergic asthma, which affects approximately 20% of the global population. Poor air quality is the major culprit in allergic asthma, which not only affects the individual's health, but also impairs his or her life quality and that of family members. Asthma is a chronic pulmonary inflammatory disease characterized by excess mucus production, airway hyperresponsiveness, and bronchoconstriction. Inhalation of corticosteroids, leukotriene modifiers, and β-adrenergic agonists is one treatment prescribed to control the symptoms of asthma, but there is still no effective cure. Phytochemicals such as carotenoids, phenolics, alkaloids, and nitrogen and organosulfur compounds are proven to possess immense pharmacological properties. Betalain is one such phytochemical present in plants of the order Caryophyllales. It is a water-soluble nitrogen-based pigment proven to possess antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, antilipidemic, antidiabetic, and anticancer properties. We examined the curative potential of betalain against allergic asthma in a mouse model. Betalain treatment effectively decreased lung weight and infiltration of inflammatory cells in BAL fluid, and lowered IgE, eotaxin, and cytokine levels in asthma-induced mice. It also improved pulmonary mechanics and decreased oxidative stress and nitric oxide levels. Betalain significantly decreased gene expression of TGF-β and its downstream signaling Smad proteins. Lung histology confirmed that betalain protected the lung tissue of mice from ovalbumin-induced allergic asthma. Overall, our results show that betalain is a potent antiallergic drug that effectively protects mice from ovalbumin-induced allergic asthma. With further research, it can be prescribed as a treatment for asthma in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2021037050DOI Listing
April 2021

Prognostic factors for CNS control in children with acute lymphoblastic leukemia treated without cranial irradiation.

Blood 2021 Jul;138(4):331-343

Departments of Oncology, Global Pediatric Medicine, Biostatistics and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN.

To identify the prognostic factors that are useful to improve central nervous system (CNS) control in children with acute lymphoblastic leukemia (ALL), we analyzed the outcome of 7640 consecutive patients treated on Chinese Children's Cancer Group ALL-2015 protocol between 2015 and 2019. This protocol featured prephase dexamethasone treatment before conventional remission induction and subsequent risk-directed therapy, including 16 to 22 triple intrathecal treatments, without prophylactic cranial irradiation. The 5-year event-free survival was 80.3% (95% confidence interval [CI], 78.9-81.7), and overall survival 91.1% (95% CI, 90.1-92.1). The cumulative risk of isolated CNS relapse was 1.9% (95% CI, 1.5-2.3), and any CNS relapse 2.7% (95% CI, 2.2-3.2). The isolated CNS relapse rate was significantly lower in patients with B-cell ALL (B-ALL) than in those with T-cell ALL (T-ALL) (1.6%; 95% CI, 1.2-2.0 vs 4.6%; 95% CI, 2.9-6.3; P < .001). Independent risk factors for isolated CNS relapse included male sex (hazard ratio [HR], 1.8; 95% CI, 1.1-3.0; P = .03), the presence of BCR-ABL1 fusion (HR, 3.8; 95% CI, 2.0-7.3; P < .001) in B-ALL, and presenting leukocyte count ≥50×109/L (HR, 4.3; 95% CI, 1.5-12.2; P = .007) in T-ALL. Significantly lower isolated CNS relapse was associated with the use of total intravenous anesthesia during intrathecal therapy (HR, 0.2; 95% CI, 0.04-0.7; P = .02) and flow cytometry examination of diagnostic cerebrospinal fluid (CSF) (HR, 0.2; 95% CI, 0.06-0.6; P = .006) among patients with B-ALL. Prephase dexamethasone treatment, delayed intrathecal therapy, use of total intravenous anesthesia during intrathecal therapy, and flow cytometry examination of diagnostic CSF may improve CNS control in childhood ALL. This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020010438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323972PMC
July 2021

Adjuvant Vaginal Use of Sildenafil Citrate in a Hormone Replacement Cycle Improved Live Birth Rates Among 10,069 Women During First Frozen Embryo Transfers.

Drug Des Devel Ther 2020 1;14:5289-5297. Epub 2020 Dec 1.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated to JiaoTong University School of Medicine, Shanghai, People's Republic of China.

Purpose: To investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT).

Patients And Methods: This retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded.

Results: Baseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.3% vs 36.1%). After adjustment for 12 pregnancy-related confounding factors, logistic regression analysis showed that LBR remained significantly higher in the scHRT-FET group than in the HRT-FET group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.14-1.49). Furthermore, after adjustment, the ongoing pregnancy rate was significantly higher (aOR 1.29, 95% CI 1.13-1.47), and the miscarriage rate was significantly lower (aOR 0.58, 95% CI 0.43-0.77), in the scHRT-FET group compared to the HRT-FET group. Adjuvant vaginal use of SC did not increase the endometrial thickness and had no significant effect on birth weight or PTB.

Conclusion: Adjuvant vaginal use of SC in HRT FET was associated with higher LBR and improved pregnancy outcomes in an infertile population with adequate endometrial thickness. The beneficial effect of SC may be due not to an increase in EMT but instead to improve endometrial blood flow and receptivity, which might merit clinicians' attention for improving general IVF practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S281451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718965PMC
September 2021

Comparison of a progestin-primed ovarian stimulation protocol with a flexible GnRH antagonist protocol in patients with polycystic ovary syndrome who are participating in an IVF programme: study protocol for a randomised controlled trial.

BMJ Open 2020 12 2;10(12):e038153. Epub 2020 Dec 2.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Introduction: Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) protocols are typically characterised by an increased number of oocytes retrieved. The oocytes are often of poor quality, leading to lower pregnancy rates, higher miscarriage rates and an increased risk of developing ovarian hyperstimulation syndrome (OHSS). Since our previous preliminary study showed that a novel progestin-primed ovarian stimulation (PPOS) protocol blocked the luteinising hormone (LH) surge during IVF and achieved a higher pregnancy rate with a lower incidence of OHSS, we designed a prospective randomised controlled trial to compare the efficacy and safety of this PPOS protocol with the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS who are undergoing IVF procedures.

Methods And Analysis: Patients with PCOS will be randomised to one of two controlled ovarian stimulation regimens-GnRH antagonist or PPOS-using a computer-generated random number. A freeze-all strategy using embryo vitrification techniques and frozen embryo transfer will be performed in both groups. The primary outcome is the live-birth rate per transfer. Secondary outcomes include the incidence of premature LH surges, the duration and total dose of human menopausal gonadotropin stimulation, the number of oocytes retrieved, the incidence of moderate or severe OHSS, the number of embryos available for transfer, implantation rates, clinical pregnancy rates, pregnancy loss rates, ectopic pregnancy rates, pregnancy and neonatal complications, and congenital anomalies. The necessary sample size for this trial was estimated as 392 participants, with 196 participants in each group. Intention-to-treat analysis was used in processing our experimental data.

Ethics And Dissemination: This study was approved by the Institutional Review Board of the hospital (2016-133-T82). The trial will be conducted according to the principles of the World Medical Association's Declaration of Helsinki and in accordance with Good Clinical Practice standards. The findings of this trial will be published in a peer-reviewed journal.

Trial Registration Number: ChiCTRIPR16009580.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-038153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713223PMC
December 2020

Syringin alleviates ovalbumin-induced lung inflammation in BALB/c mice asthma model via NF-κB signaling pathway.

Environ Toxicol 2021 Mar 4;36(3):433-444. Epub 2020 Nov 4.

Department of Pediatric, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Asthma is an allergic chronic inflammatory disease of the pulmonary airways, characterized by the infiltration of white blood cells and release of inflammatory cytokines of complex pathways linked to its pathogenesis. Syringin extracted from various medicinal plants has been used extensively for the treatment of inflammatory diseases. Hence, this study was conducted to further explore the protective effects of the syringin in ovalbumin (OVA) induced-asthma mice model. OVA-sensitized BALB mice were treated intraperitonealy with three doses (25, 50 and 100 mg/kg) of the syringin which was validated by the alteration in the immunoglobulin E (IgE) levels, cytokines levels, histopathological evaluation inflammatory cell count, lung weight, nitrite (NO) levels, oxidative stress biomarkers and gene markers. The treatment of syringin intensely reduced the increased IgE, inflammatory cytokines, WBC count and restored the antioxidant stress markers OVA stimulated animals. In addition, a significant reduction in inflammation and mucus production was evidenced in histopathological analysis which was further validated by suppression NF-κB pathway activation by syringin. These results suggest that syringin may improve asthma symptoms in OVA-induced mice by modulating NF-κB pathway activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tox.23049DOI Listing
March 2021

Corrigendum. The effect of storage time after vitrification on pregnancy and neonatal outcomes among 24 698 patients following the first embryo transfer cycles.

Hum Reprod 2020 11;35(11):2637

Department of Assisted Reproduction, Shanghai Ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/deaa220DOI Listing
November 2020

The Association Between Embryo Quality, Number of Transferred Embryos and Live Birth Rate After Vitrified Cleavage-Stage Embryos and Blastocyst Transfer.

Front Physiol 2020 14;11:930. Epub 2020 Aug 14.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated to Jiao Tong University School of Medicine, Shanghai, China.

Objective: The single-embryo transfer (SET) is the recommended approach to improve the live birth rate and reduce the complications related with multiple pregnancies. However, the physicians generally chose to transfer two embryos when the embryo quality decreased. The effect on the fertilization (IVF) or intracytoplasmic sperm injection (ICSI) outcomes following the transfer of a poor-quality embryo (PQE) along with a good-quality embryo (GQE) has been explored. However, previous studies were limited by the fresh embryo transfer cycles or the small sample size.

Methods: A retrospective cohort study was performed among 26,676 women (the mean age was 31.72 years) undergoing first frozen embryo transfer (FET) from January 2011 to December 2017. Patients were grouped into five subgroups, including SET with one GQE (SET-GQE, 2235 patients for cleavage-stage embryo transfer and 756 patients for blastocyst transfer), SET with one PQE (SET-PQE, 148 patients for cleavage-stage embryo transfer and 362 patients for blastocyst transfer), double-embryo transfer with two GQE (DET-2GQE, 20,461 patients for cleavage-stage embryo transfer and 519 patients for blastocyst transfer), double-embryo transfer (DET) with one GQE plus one PQE (DET-GQE+PQE, 1541 patients for cleavage-stage embryo transfer and 266 patients for blastocyst transfer), and DET with two PQE (DET-2PQE, 228 patients for cleavage-stage embryo transfer and 160 patients for blastocyst transfer). Multivariable logistic regression models were performed after controlling for other potential confounders to estimate the effect of number and quality of transferred embryos on pregnancy outcomes.

Result: Although the live birth rate was significantly higher after DET-GQE+PQE compared with SET-GQE for cleavage-stage embryo transfer [574 of 1541 (37.25%) vs. 571 of 2235 (25.55%)], no significant difference was found between DET-GQE+PQE and SET-GQE for blastocyst transfer [143 of 266 (53.76%) vs. 325 of 756 (42.99%)]. However, DET-GQE+PQE also had the highest multiple live births in both cleavage-stage embryo transfer [134 of 1541 (8.70%)] and blastocyst transfer [46 of 266 (17.29%)]. The live birth rate after SET-PQE significantly decreased in comparison with SET-GQE [cleavage-stage embryo transfer: 18 of 148 (12.16%) vs. 571 of 2235 (25.55%); blastocyst transfer: 107 of 362 (29.56%) vs. 325 of 756 (42.99%)] and significantly increased after DET-2GQE compared with SET-GQE [cleavage-stage embryo transfer: 9357 of 20,461 (45.73%) vs. 571 of 2235 (25.55%); blastocyst transfer: 313 of 519 (60.31%) vs. 325 of 756 (42.99%)]. The live birth rate was also not different between DET-2PQE and SET-GQE for cleavage-stage embryo transfer and blastocyst transfer [cleavage-stage embryo transfer: 75 of 228 (32.89%) vs. 571 of 2235 (25.55%); blastocyst transfer: 74 of 160 (46.25%) vs. 325 of 756 (42.99)].

Conclusion: In order to minimize the risk of multiple births, the data from this study did not support transferring DET with a GQE plus a PQE compared with SET with a GQE, especially for blastocyst transfer. However, the proportion of patients older than 35 years was small (12.07% for patients aged 36-39 years and 7.31% for patients 40 years or older), which limited the generalization of these results to other population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456822PMC
August 2020

Long-term follow-up of acute lymphoblastic leukemia in young children treated by the SCMC-ALL-2009 protocol.

Leuk Lymphoma 2020 12 9;61(12):2850-2858. Epub 2020 Jul 9.

Department of Pediatrics, The Second Hospital of Anhui Medical University, Hefei, China.

This study evaluated the long-term therapeutic effect and prognostic factors of acute lymphoblastic leukemia (ALL) in 100 young Chinese children (<2 years old) who were enrolled in the Shanghai Children's Medical Center (SCMC)-ALL-2009 study in five pediatric hematological disease centers based on collaboration. The 5-year and 10-year event-free survivals (EFS) were 74.7 ± 3.2% and 73.3 ± 3.4%. The 10-year EFS rates for low risk, intermediate-risk, and high-risk patients were 81.9 ± 5.0%, 71.3 ± 4.3%, and 22.2 ± 13.9%, respectively. Relapse occurred in 19 patients. MRD results on day 55, good or poor response to prednisolone, and age at diagnosis were shown to have important prognostic and therapeutic implications. Compared with the SCMC-ALL-2005 protocol, showed that the 10-year-EFS and 10-year-overall survival of the SCMC-ALL-2009 protocol were better than that of the -2005 protocol. Notably, the intermediate-risk group was improved after the chemotherapy intensity was strengthened.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1786557DOI Listing
December 2020

The effect of storage time after vitrification on pregnancy and neonatal outcomes among 24 698 patients following the first embryo transfer cycles.

Hum Reprod 2020 07;35(7):1675-1684

Department of Assisted Reproduction, Shanghai Ninth people's hospital affiliated to JiaoTong University School of Medicine, Shanghai, China.

Study Question: To evaluate the impact of storage time after vitrification on embryo viability, pregnancy outcomes and neonatal outcomes.

Summary Answer: The prolonged storage time of vitrified embryos negatively affected pregnancy outcomes, including biochemical pregnancy rate, clinical pregnancy and live birth rate; but did not influence neonatal outcomes.

What Is Known Already: Although vitrification has been the fundamental tool of ART treatments in recent years, few studies have explored the influence of storage period after vitrification on embryonic and clinical outcomes.

Study Design, Size, Duration: A retrospective study was performed among 24 698 patients with the first vitrified embryo transfer following a freeze-all strategy during the period from January 2011 to December 2017.

Participants/material, Setting, Methods: A total of 24 698 patients met the inclusion criteria and were grouped according to the storage time (11 330 patients in Group 1 with storage time <3 months, 9614 patients in Group 2 with storage time between 3 and 6 months, 3188 patients in Group 3 with storage time between 6 and 12 months and 566 in Group 4 with storage time between 12 and 24 months). The pregnancy outcomes and neonatal outcomes were compared between different storage time groups. Multivariate logistic regression and linear regression were performed to evaluate the independent effect of storage time on clinical outcomes, adjusting for important confounders.

Main Results And The Role Of Chance: After adjustment for potential confounding factors, the chance of biochemical pregnancy (Group 1 as reference; Group 2: adjusted odds ratio (aOR) = 0.92, 95% CI 0.87-0.97; Group 3: aOR = 0.83, 95% CI 0.76-0.90; Group 4: aOR = 0.68, 95% CI 0.56-0.81), clinical pregnancy (Group 2: aOR = 0.91, 95% CI 0.86-0.96; Group 3: aOR = 0.80, 95% CI 0.73-0.87; Group 4: aOR = 0.65, 95% CI 0.54-0.79) and live birth (Group 2: aOR = 0.89, 95% CI 0.85-0.95; Group 3: aOR = 0.83, 95% CI 0.76-0.91; Group 4: aOR = 0.59, 95% CI 0.48-0.72) significantly decreased with the increasing storage time, whereas the relationship between miscarriage, ectopic pregnancy and storage time did not reach statistical significance. In addition, there was no evidence of differences in adverse neonatal outcomes (preterm birth, low birthweight, high birthweight, macrosomia or birth defects) between groups.

Limitation, Reasons For Caution: Our study was limited by the retrospective design from a single center, the conclusion from our study needs to be verified in further studies.

Wider Implications Of The Findings: This study provides new findings about the relationship between prolonged storage time of vitrified embryos and clinical outcomes and offers evidence for the safety of using long-stored embryos after vitrification.

Study Funding/competing Interest(s): This work was supported by the National Natural Science Foundation of China (grant nos. 81903324, 81771533, 81571397, 81701523), National Key Research and Development Program of China (grant no. SQ2018YFC100163). None of the authors have any conflicts of interest to declare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/deaa136DOI Listing
July 2020

Septicemia after chemotherapy for childhood acute lymphoblastic leukemia in China: A multicenter study CCCG-ALL-2015.

Cancer Med 2020 03 28;9(6):2113-2121. Epub 2020 Jan 28.

Department of Paediatrics, Hong Kong Children's Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied.

Methods: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected.

Results: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%.

Conclusion: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.2889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064088PMC
March 2020

Effect of Dasatinib vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

JAMA Oncol 2020 03;6(3):358-366

State Key Laboratory of Experimental Hematology and Division of Pediatric Blood Diseases Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin, China.

Importance: A randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

Objective: To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation.

Design, Setting, And Participants: This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019.

Interventions: Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy.

Main Outcomes And Measures: The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival.

Results: Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups.

Conclusions And Relevance: Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-14005706.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2019.5868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990720PMC
March 2020

Effects of pre-pregnancy body mass index on pregnancy and perinatal outcomes in women with PCOS undergoing frozen embryo transfer.

BMC Pregnancy Childbirth 2019 Dec 10;19(1):487. Epub 2019 Dec 10.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.

Background: Previous studies have shown that among women with polycystic ovary syndrome who have difficulties conceiving, frozen-embryo transfer resulted in increased live birth rates and decreased ovarian hyperstimulation syndrome risk than did fresh-embryo transfer. In the present retrospective analysis, we sought to determine the effect of body mass index (BMI) on pregnancy and perinatal outcomes in women with PCOS undergoing FET.

Methods: Women with PCOS (n = 1556) undergoing FET were divided into groups based on weight, with those with normal weight having a BMI of 18.5-24.9 kg/m,those who were overweight having a BMI of 25-29.9 kg/m, and those who were obese having a BMI ≥30 kg/m. Both pregnancy and perinatal outcomes were compared among these groups.

Results: The normal-weight, overweight, or obese groups exhibited similar pregnancy outcomes, including clinical pregnancy rate, miscarriage rate, ongoing pregnancy rate and live birth rate. In singletons, birth characteristics regarding newborn gender, gestational age, birthweight and length at birth were comparable between the three groups. For adverse neonatal outcomes, the three groups showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, and very preterm birth after adjustment. In addition, the obstetric complications and the frequencies of live-birth defects were also comparable between the three groups except that overweight and obese women were more likely than women of normal weight to have delivered via cesarean section.

Conclusion: BMI did not affect the pregnancy or perinatal outcomes in women with PCOS undergoing FET.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-019-2611-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902324PMC
December 2019

Pregnancy And Neonatal Outcomes Of hMG Stimulation With Or Without Letrozole In Endometrial Preparation For Frozen-Thawed Embryo Transfer In Ovulatory Women: A Large Retrospective Cohort Study.

Drug Des Devel Ther 2019 14;13:3867-3877. Epub 2019 Nov 14.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Objective: Frozen-thawed embryo transfer enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred in subsequent cycles into a more "physiologic environment". This study aimed to investigate the clinical effect of letrozole use or hMG stimulation on pregnancy and neonatal outcomes in ovulatory patients undergoing FET.

Methods: This study includes a total of 5901 FET cycles with letrozole use (n = 1569), HMG (n =1827) or letrozole + HMG (n = 2505). In the letrozole group, 2.5 mg of letrozole was administered on menstrual cycle day 3 to 5 for 3 days for patients, and then follicle growth was monitored beginning on day 10. If the follicular diameter was ≥14 mm on the 10th day, no other ovarian stimulation drugs were needed. If the follicular diameter was <14 mm on the 10th day, 150 IU human menopausal gonadotropin (hMG) was added to stimulate follicle growth every two days (hMG + letrozole group). In hMG stimulation group, a total of 150 IU of hMG was injected every two days to stimulate development of follicles from cycle day 10 to 12.

Results: Compared with the patients undergoing hMG stimulation, the group receiving letrozole or letrozole+HMG stimulation exhibits significantly higher clinical pregnancy rates per transfer (hMG: 47.02% vs letrozole: 52.07% vs letrozole+HMG: 52.26%) and implantation rates (hMG: 31.76% vs letrozole: 34.36% vs letrozole+HMG: 34.24%). In addition, the letrozole group was associated with a statistically significantly lower incidence of miscarriage (hMG: 14.78% vs letrozole: 10.53% vs letrozole+HMG: 14.13%) and ectopic pregnancies (hMG: 1.83% vs letrozole: 0.97% vs letrozole+HMG: 1.58%) than the letrozole + HMG and HMG groups. Neonatal outcomes are similar among the three groups.

Conclusion: Our data demonstrate that the letrozole use may improve clinical pregnancy outcomes and decrease the risk of ectopic pregnancies and miscarriage in ovulatory patients who receive FET cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S212235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861551PMC
June 2020

Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia.

Blood 2020 01;135(1):41-55

Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Department of Hematology & Oncology, Shanghai Children's Medical Center-National Children's Medical Center, and.

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2019002220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940198PMC
January 2020

A Higher Estradiol Rise After Dual Trigger in Progestin-Primed Ovarian Stimulation Is Associated With a Lower Oocyte and Mature Oocyte Yield in Normal Responders.

Front Endocrinol (Lausanne) 2019 9;10:696. Epub 2019 Oct 9.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Prior studies have shown that patients with a >10% estradiol (E) rise after trigger had more oocytes retrieved than plateauing or decreasing E responders. However, multiple follicles develop at different stages of maturation during controlled ovarian stimulation (COS) and may exhibit different responses to trigger. The association between the magnitude of E increase and oocyte retrieval outcomes is still unclear. This was a retrospective cohort study of 2,898 women undergoing their first COS cycles with normal response from January 2014 to December 2017 at a tertiary-care academic medical center. Patients were categorized into five groups according to the percentage increase in E levels before and after dual trigger: <10.0%, 10.0-19.9%, 20.0-29.9%, 30.0-39.9%, and ≥40.0%. Univariable and multivariable linear regression analysis were performed to explore the association between E increase and oocyte/mature oocyte yield, while logistic regression was used to assess its effect on low oocyte/mature oocyte yield (<10th percentile). The post-trigger E increase was negatively associated with both oocyte yield (-trend < 0.001, adjusted -trend = 0.033) and mature oocyte yield (-trend < 0.001, adjusted -trend = 0.002). Compared with a <10.0% E increase after trigger, patients with a ≥40.0% rise had fewer mature oocyte yield [adjusted mean absolute difference [MD] = -5.2, 95% confidence interval [CI]: -8.2--1.8] and higher risk of low mature oocyte yield (adjusted odds ratio [OR] = 1.64, 95% CI: 1.04-2.60), whereas no statistical significance was found in oocyte yield (adjusted MD = -2.7, 95% CI: -6.1-0.8) and low oocyte yield (adjusted OR = 1.48, 95% CI: 0.96-2.28). In addition, the rates of implantation, positive pregnancy test, clinical pregnancy, ongoing pregnancy, pregnancy loss, and live birth were comparable among the 1,942 frozen embryo transfer cycles with embryos originating from different groups of E increase (all > 0.05). A higher E rise after dual trigger is independently associated with a lower oocyte and mature oocyte yield in normal responders. Further studies are needed to explore the efficacy of individualized time interval from trigger to oocyte retrieval based on the magnitude of E increase after trigger.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2019.00696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794366PMC
October 2019

Neonatal outcomes and congenital malformations in children born after dydrogesterone application in progestin-primed ovarian stimulation protocol for IVF: a retrospective cohort study.

Drug Des Devel Ther 2019 26;13:2553-2563. Epub 2019 Jul 26.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People's Republic of China.

Purpose: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear.

Patients And Methods: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors.

Results: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40-2.39) and 0.90 (95% CI: 0.33-2.41) in singletons and twins, respectively.

Conclusion: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S210228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667350PMC
April 2020

Promoter methylation and expression of SOCS3 affect the clinical outcome of pediatric acute lymphoblastic leukemia by JAK/STAT pathway.

Biomed Pharmacother 2019 Jul 1;115:108913. Epub 2019 May 1.

Pediatrics, the Second Hospital of Anhui Medical University, Hefei, 230601, China. Electronic address:

Suppressor of cytokine signaling 3 (SOCS3) has been characterized as one of the most crucial negative regulator in the JAK2/STAT3 signaling pathway. However, there are few studies on the relationship between SOCS3 and pediatric acute lymphoblastic leukemia (ALL). This study analyzes the influence of SOCS3 expression on the risk and the progression of pediatric ALL and the underlying mechanism. The levels of SOCS3, p-JAK2, p-STAT3, SOCS3 methylation, CD4+CD25+CD127lowTreg were detected by PCR, laser confocal microscopy, western blot, bisulfite sequencing and flow cytometry at different progression of ALL. We found that the SOCS3 expression level at initial diagnosis (DG) of ALL patients was significantly lower than that of healthy controls (HC), while the expression of SOCS3 methylation was opposite. The expression of SOCS3 and SOCS3 methylation were returned to normal in the complete remission (CR) stage, and there were no difference between resistance, relapse and initial diagnosis. The expression of SOCS3 decreased and weakened the inhibition of pSTAT3 expression in DG, resistance and relapse groups. The levels of Treg cells in ALL children were significantly higher than those in the HC children. There was a positive correlation between the expression level of STAT3 and the expression level of Treg cells in children with ALL, while that was negatively correlated with the expression levels of Treg cells. Compared with high-level of SOCS3, the low-level of SOCS3 patients had more high risk factors, as higher WBC counts, LDH level and much more poor prognostic genes. SOCS3 methylation leads to low-expression of SOCS3, which can lead to continuous activation of JAK/STAT3 and increased expression of Treg cells, which in turn affects the anti-tumor immunological effect of the body. Taken together, our data show that monitoring the level of SOCS3 can contribute to the understanding of the state of illness and evaluate the risk of progression of ALL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2019.108913DOI Listing
July 2019

Live birth rate and neonatal outcome following cleavage-stage embryo transfer versus blastocyst transfer using the freeze-all strategy.

Reprod Biomed Online 2019 Jun 23;38(6):892-900. Epub 2018 Dec 23.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Zhizaoju Road No.639, Huangpu District, Shanghai 200011, People's Republic of China. Electronic address:

Research Question: What are the live birth rates and neonatal outcomes following cleavage-stage embryo transfer and blastocyst transfer in a freeze-all treatment scenario?

Design: This was a retrospective cohort study. All good-quality embryos were frozen on the third day; the remaining embryos were grown on until they reached blastocyst stage and then frozen. Between 2007 and 2016, 11,801 patients underwent cleavage-stage embryo transfer and 1009 patients underwent blastocyst transfer in the first treatment cycle using the freeze-all strategy. The live birth rate and neonatal outcomes were evaluated.

Results: The live birth rate in the first frozen embryo transfer cycle was higher following blastocyst transfer than following cleavage-stage transfer (69.1% versus 55.5%, P < 0.01), but there was no difference in live birth rate in the second frozen embryo transfer cycle between blastocyst transfer and cleavage-stage transfer (45.2% versus 52.7%, P > 0.05). Similarly, no difference was found in the cumulative live birth rate for the first complete IVF cycle (71.1% versus 69.2%, P > 0.05). Blastocyst transfer gave a higher risk of preterm singleton delivery than did cleavage-stage transfer. However, there was no difference in the risk of early preterm delivery, low birth weight, very low birth weight, high birth weight and very high birth weight between the two groups.

Conclusions: There is no evidence to support the superiority of blastocyst transfer compared with cleavage-stage transfer in a freeze-all treatment scenario. There may be a higher risk of preterm singleton delivery following blastocyst transfer than following cleavage-stage transfer but further studies are needed to verify this.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rbmo.2018.12.034DOI Listing
June 2019

Treatment abandonment in childhood acute lymphoblastic leukaemia in China: a retrospective cohort study of the Chinese Children's Cancer Group.

Arch Dis Child 2019 06 31;104(6):522-529. Epub 2019 Jan 31.

Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Key Lab of Pediatric Hematology and Oncology of China Ministry of Health, and National Children's Medical Center, Shanghai, China.

Objectives: Before 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children's Cancer Group ALL protocol between 2015 and 2016.

Methods: Demographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government.

Results: At a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications.

Conclusions: The rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment.

Clinical Trial Registration Number: ChiCTR-IPR-14005706, pre-results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2018-316181DOI Listing
June 2019

Cesarean scar endometriosis: presentation of 198 cases and literature review.

BMC Womens Health 2019 01 18;19(1):14. Epub 2019 Jan 18.

The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.

Background: Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures.

Methods: A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017.

Results: A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars.

Conclusions: The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-019-0711-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339338PMC
January 2019

Comparison of neonatal outcomes and live-birth defects after progestin-primed ovarian stimulation versus conventional ovarian stimulation for in vitro fertilization: A large retrospective cohort study.

Medicine (Baltimore) 2018 Aug;97(34):e11906

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation regimen for in vitro fertilization (IVF), with the advantages of an oral administration route and more control over preovulatory luteinizing hormone (LH) levels. Assessing the safety of this novel regimen is an important premise for its routine practice.We conducted a large retrospective cohort study for infants born between August 2014 and April 2017 from IVF and embryo transfer cycles after either PPOS and the conventional gonadotropin-releasing hormone-agonist (GnRH-a) short protocol at our center. Around 1589 live-born infants were finally enrolled, corresponding to 1258 frozen-thawed (FET) cycles, which led to 855 live-born infants from PPOS (659 FET cycles) and 734 live-born infants from the short protocol (599 FET cycles).Birth characteristics regarding gestational age, birth weight and length, infant sex, and early neonatal death were comparable between the 2 groups. The incidence of live-birth defects in the PPOS group (1.52%) was similar to that in the short protocol group (1.63%) and was not statistically significant. For birth defects, the risk significantly increased for multiple births, and the adjusted odds ratio was 3.14 (95% confidence interval [CI]: 1.25-7.88). No associations were found between congenital birth defects and maternal age, body mass index (BMI), the duration of infertility, method of insemination, infant sex, embryo stage at transfer, the number of embryos transferred or ovarian stimulation regimen.Our study shows that the neonatal outcomes and risk of congenital malformations were similar between the PPOS and conventional GnRH-a short protocol. However, multiple pregnancy led to a higher likelihood of birth defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000011906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112954PMC
August 2018

The risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers.

Arch Gynecol Obstet 2018 10 23;298(4):833-840. Epub 2018 Aug 23.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated to Jiaotong University, School of Medicine, Zhizaoju Road No. 639, Shanghai, China.

Purpose: To explore the risk of birth defects among children born after vitrified blastocyst transfers and those born after fresh and vitrified cleavage-stage embryo transfers.

Methods: A retrospective cohort study was conducted including infants born after fresh and vitrified day 3 embryo transfers and those born after vitrified day 5 or 6 blastocyst transfers from January 2005 through December 2016. The outcome measures included any birth defect, multiple birth defects and 13 individual categories of birth defects.

Results: Any birth defect occurred in 1.15% of infants born after fresh day 3 embryo transfers, 1.75% of infants born after vitrified day 3 embryo transfers, 1.60% of infants born after vitrified day 5 blastocyst transfers and 1.10% of infants born after vitrified day 6 blastocyst transfers. There was no difference in the risk of birth defects between vitrified blastocyst-stage transfers and vitrified cleavage-stage transfers (including day 5 vs. day 3 and day 6 vs. day 3) among all births or in only singletons or twins. For infants born after cleavage-stage embryo transfers at day 3, there was no difference in the risk of birth defects between fresh embryo transfers and vitrified embryo transfers among all births or in only singletons or twins.

Conclusions: Transfer of vitrified day 5 or 6 blastocysts does not increase the risk of birth defects compared with vitrified day 3 embryos. However, randomized control trials and follow-up studies of the long-term outcome of children born after blastocyst-stage transfers are needed to confirm the clinical safety of extending embryo culture to the blastocyst stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-018-4870-xDOI Listing
October 2018

Comprehensive Evaluation of Coal-Fired Power Units Using Grey Relational Analysis and a Hybrid Entropy-Based Weighting Method.

Entropy (Basel) 2018 Mar 23;20(4). Epub 2018 Mar 23.

National Research Center for Thermal Power Engineering and Technology, North China Electric Power University, Changping District, Beijing 102206, China.

In recent years, coal-fired power plants contribute the biggest part of power generation in China. Challenges of energy conservation and emission reduction of the coal-fired power plant encountering with a rapid growth due to the rising proportion of renewable energy generation in total power generation. Energy saving power generation dispatch (ESPGD) based on power units sorting technology is a promising approach to meet the challenge. Therefore, it is crucial to establish a reasonable and feasible multi-index comprehensive evaluation (MICE) framework for assessing the performance of coal-fired power units accessed by the power grid. In this paper, a hierarchical multiple criteria evaluation system was established. Except for the typical economic and environmental indices, the evaluation system considering operational flexibility and power quality indices either. A hybrid comprehensive evaluation model was proposed to assess the unit operational performance. The model is an integration of grey relational analysis (GRA) with analytic hierarchy process (AHP) and a novel entropy-based method (abbreviate as BECC) which integrates bootstrap method and correlation coefficient (CC) into entropy principle to get the objective weight of indices. Then a case study on seven typical 600 megawatts coal-fired power units was carried out to illustrate the proposed evaluation model, and a weight sensitivity analysis was developed in addition. The results of the case study shows that unit 4 has the power generating priority over the rest ones, and unit 2 ranks last, with the lowest grey relational degree. The weight sensitivity analysis shows that the environmental factor has the biggest sensitivity coefficient. And the validation analysis of the developed BECC weight method shows that it is feasible for the MICE model, and it is stable with an ignorable uncertainty caused by the stochastic factor in the bootstrapping process. The elaborate analysis of the result reveals that it is feasible to rank power units with the proposed evaluation model. Furthermore, it is beneficial to synthesize the updated multiple criteria in optimizing the power generating priority of coal-fired power units.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/e20040215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512730PMC
March 2018

Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial.

Medicine (Baltimore) 2016 Mar;95(9):e2939

From the Department of Assisted Reproduction, Shanghai Ninth People's Hospital, JiaoTong University School of Medicine, Shanghai, China.

Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS. The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET). In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60). In the study group, hMG (150-225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control. The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS. Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference. The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000002939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782886PMC
March 2016
-->