Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Effect of small follicles on clinical pregnancy and multiple pregnancy rates in intrauterine insemination: a cohort study.

STUDY QUESTION: What is the effect of small follicles on clinical pregnancy and multiple pregnancy rates in women undergoing IUI with ovarian stimulation (IUI-OS)? SUMMARY ANSWER: The presence of ≥2 small follicles with a diameter of 10-12 or 12-14 mm was associated with an increased chance of clinical pregnancy and the presence of any 12-14 mm or larger follicles, but not smaller follicles, was statistically significantly associated with an increased risk for multiple pregnancy. WHAT IS KNOWN ALREADY: IUI-OS is widely used as the first-line treatment for unexplained or mild male factor infertility. However, IUI is associated with the risk of multiple pregnancy. While the positive association between the number of follicles ≥14 mm and the chance of pregnancy and the risk of multiple pregnancy is known, the impact of smaller follicles is uncertain. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study that included women undergoing IUI cycles from January 2007 to May 2021 in one assisted reproduction center. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied the impact of the number and size of follicles on trigger day on clinical pregnancy and multiple pregnancy rates. Generalized estimation equation regression models were used to compute unadjusted and adjusted odds ratios and 95% CI in all women and only women who achieved clinical pregnancy separately. The chance of clinical pregnancy and multiple pregnancy for different numbers of small follicles in cycles with one >18-mm follicle was calculated using marginal effects estimate. MAIN RESULTS AND THE ROLE OF CHANCE: This cohort included 12 933 IUI cycles in 7504 women. The overall clinical pregnancy rate was 16.1% (2081/12 933), with a multiple pregnancy rate of 10.5% (218/2081). In the adjusted analysis, the chance of clinical pregnancy increased significantly with the increase in the number of follicles with the diameter of 14-16, 16-18, and 18-20 mm. As for 10-12 mm [adjusted odds ratio (aOR) 1.22, 95% CI 1.02-1.46] and 12-14 mm (aOR 1.29, 95% CI 1.07-1.56) follicles, only groups with ≥2 follicles of those sizes showed significantly increased chance of clinical pregnancy. In cycles that led to pregnancy, follicles with the diameter of 12-14 mm were associated with an increased risk of multiple pregnancy (aOR 1.73, 95% CI 1.19-2.53 for one such follicle; aOR 2.27, 95% CI 1.44-3.56 for ≥2 such follicles), while 10- to 12-mm follicles were not significantly associated with multiple pregnancy (aOR 1.18, 95% CI 0.72-1.95 for ≥2 such follicles). The associations of multiple pregnancy were similar when including all cycles. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective observational study from a single center. The records of follicle diameter in our center were of a 2-mm interval which limited our ability to analyze the size of follicle as a continuous variable. Also, the number of cycles with a high number of small follicles was still limited which impeded more detailed analysis on the ≥2 follicles subgroup. Similarly, the value of some parts of the marginal probability estimation for multiple pregnancy versus pregnancy according to size and number of follicles was also limited by the low sample size of certain combinations. WIDER IMPLICATIONS OF THE FINDINGS: Follicles larger than 10 mm, especially those ≥12 mm, may need to be clearly recorded during transvaginal ultrasound surveillance and their potential effects on both pregnancy and multiple pregnancy can be discussed with couples undergoing IUI. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (Grant numbers 82201912, 82371651, and 82071615) and Shanghai Sailing Program (21YF1423200). B.W.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. B.W.M. has received research funding from Ferring and Merck. The authors declare no other competing interests. TRIAL REGISTRATION NUMBER: N/A.

Research on robust fault-tolerant control of the controllable suspension based on knowledge-data fusion driven.

For the robust fault-tolerant control of the controllable suspension system, a control strategy driven by knowledge-data fusion is proposed. Firstly, the boundary fuzziness between perturbation type uncertainty and gain type fault is analyzed, and then a data-driven method is introduced to avoid the state estimation of system uncertainty and fault. The proximal policy optimization algorithm in reinforcement learning is selected to construct a "data control law", to deal with uncertainty and fault. On the other hand, based on the classical sky-hook control, the "knowledge control law" for system performance optimization is designed, taking into account the nonlinear and non-stationary characteristics of the system. Furthermore, the dependency between robust fault tolerance and performance optimization control is revealed, and the two control laws are fused by numerical multiplication, to realize the performance matching optimization control of robust fault tolerance of controllable suspension system driven by knowledge-data fusion. Finally, the effectiveness and feasibility of the proposed method are verified by the simulation and real-time experiment of non-stationary excitation and near-stationary excitation under the combination of uncertainty and fault.

Ubiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers.

Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs.

GM-CSF improves endometrial receptivity in a thin endometrium rat model by upregulating HOXA10.

Endometrial receptivity is a prerequisite for the success of assisted reproduction. Patients with a consistently thin endometrium frequently fail to conceive, owing to low endometrial receptivity, and there are currently very few therapeutic options available. Our previous study demonstrated that intrauterine granulocyte-macrophage colony-stimulating factor (GM-CSF) administration resulted in a significant improvement in clinical pregnancy and implantation rates and was an effective means of increasing endometrial thickness on the day of embryo transfer in patients with thin endometrium. In order to explore the underlying process, an animal model with a thin endometrium was constructed, the homeobox A10 gene (HOXA10) was downregulated, and an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) was employed. Our findings strongly suggest a marked decrease in GM-CSF levels in the thin endometrial rat model, and the suppression of HOXA10 impeded the therapeutic efficacy of GM-CSF in this model. Moreover, we showed that GM-CSF significantly increases endometrial receptivity in the rat model and upregulates HOXA10 via the MAPK/ERK pathway. Our data provide new molecular insights into the mechanisms underlying formation of a thin endometrium and highlight a novel, potential clinical treatment strategy as well as directions for further research.

Extracellular vesicles encapsulated with caspase-1 inhibitor ameliorate experimental autoimmune myasthenia gravis through targeting macrophages.

Cysteinyl aspartate-specific proteinase-1 (caspase-1) is a multifunctional inflammatory mediator in many inflammation-related diseases. Previous studies show that caspase-1 inhibitors produce effective therapeutic outcomes in a rat model of myasthenia gravis. However, tissue toxicity and unwanted off-target effects are the major disadvantages limiting their clinical application as therapeutic agents. This study shows that dendritic cell-derived extracellular vesicles (EVs) loaded with a caspase-1 inhibitor (EVs-VX-765) are phagocytized mainly by macrophages, and caspase-1 is precisely expressed in macrophages. Furthermore, EVs-VX-765 demonstrates excellent therapeutic effects through a macrophage-dependent mechanism, and it notably inhibits the level of interleukin-1ß and subsequently inhibits Th17 response and germinal center (GC) reactions. In addition, EVs-VX-765 demonstrates better therapeutic effects than routine doses of VX-765, although drug loading is much lower than routine doses, consequently reducing tissue toxicity. In conclusion, this study's findings suggest that EV-mediated delivery of caspase-1 inhibitors is effective for treating myasthenia gravis and is promising for clinical applications.

Factors affecting male-to-female ratio at birth in frozen-thawed embryo transfer cycles: a large retrospective cohort study.

Background: ICSI (intracytoplasmic sperm injection) leads to a reduced male-to-female ratio at birth, whereas blastocyst transfer results in an increased male-to-female ratio. However, limited knowledge exists regarding the impact of these factors on the live birth rate for each gender. This study aimed to investigate the influence of patient characteristics and treatment parameters on the live birth rate for each gender, as well as the ultimate male-to-female ratio at birth in frozen-thawed embryo transfer (FET) cycles. Method: This retrospective cohort study involved a total of 28,376 FET cycles and 9,217 subsequent deliveries, spanning from January 2003 to December 2015. The study consisted of two parts. First, logistic regression models were constructed to determine the factors influencing the male-to-female ratio among babies born after FET. Second, we aimed to investigate the mechanisms underlying this sex ratio imbalance by analyzing data from all transfer cycles. Generalized estimated equations were employed to assess the impact of risk factors on rates of male and female live births separately. Results: ICSI resulted in a lower proportion of male offspring compared to in vitro fertilization (IVF) (50.1% vs. 53.7%, aOR: 0.87, 95% CI: 0.80-0.96). Conversely, blastocyst transfer yielded a higher proportion of male offspring than cleavage-stage embryo transfer (58.7% vs. 51.6%, aOR: 1.32, 95% CI: 1.17-1.48). Analysis of all cycles indicated that ICSI resulted in a reduced likelihood of male live birth in comparison to IVF (19.8% vs. 21.6%, aOR: 0.90, 95% CI: 0.83-0.97). However, the transfer of blastocysts rather than cleavage-stage embryos not only increased the chance of male live birth (26.9% vs. 20.2%, aOR: 1.70, 95% CI:1.56-1.85) but also facilitated female live birth (20.3% vs. 19.3%, aOR: 1.26, 95% CI: 1.15-1.39). Conclusion: ICSI was associated with a reduction in the male-to-female sex ratio and a lower rate of male live births, while blastocyst transfer was associated with an increased male-to-female sex ratio at birth and a higher rate of male live births.

Methylglyoxal suppresses microglia inflammatory response through NRF2-IκBζ pathway.

Methylglyoxal (MGO) is a highly reactive metabolite generated by glycolysis. Although abnormal accumulation of MGO has been reported in several autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, the role of MGO in autoimmune diseases has not yet been fully investigated. In this study, we found that the intracellular MGO levels increased in activated immune cells, such as microglia and lymphocytes. Treatment with MGO inhibited inflammatory cell accumulation in the spinal cord and ameliorated the clinical symptoms in EAE mice. Further analysis indicated that MGO suppressed M1-polarization of microglia cells and diminished their inflammatory cytokine production. MGO also inhibited the ability of microglial cells to recruit and activate lymphocytes by decreasing chemokine secretion and expression of co-stimulatory molecules. Furthermore, MGO negatively regulated glycolysis by suppressing glucose transporter 1 expression. Mechanically, we found that MGO could activate nuclear factor erythroid 2-related factor 2 (NRF2) pathway and NRF2 could bind to the promoter of IκBζ gene and suppressed its transcription and subsequently pro-inflammatory cytokine production. In conclusion, our results showed that MGO acts as an immunosuppressive metabolite by activating the NRF2-IκBζ.

Relationships between birth weight discordance and maternal and perinatal risks among twin pregnancies conceived following frozen embryo transfer.

STUDY QUESTION: Is intertwin birth weight discordance associated with adverse maternal and perinatal outcomes following frozen embryo transfer (FET)? SUMMARY ANSWER: For twins conceived following FET, intertwin birth weight discordance is related to elevated risks of neonatal mortality irrespective of chorionicity, and the risk of hypertensive disorders of pregnancy (HDP) is elevated for the mothers of dichorionic twins affected by such birth weight discordance. WHAT IS KNOWN ALREADY: While the relationships between intertwin birth weight discordance and adverse maternal or fetal outcomes have been studied for naturally conceived twins, similarly comprehensive analyses for twins conceived using ART remain to be performed. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study of all twin births from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China that were conceived following FET (N = 6265). PARTICIPANTS/MATERIALS, SETTING, METHODS: Intertwin birth weight discordance was defined as a 20% difference in neonatal birth weights. The primary study outcome was the incidence of HDP and neonatal death while secondary outcomes included gestational diabetes, placenta previa, placental abruption, intrahepatic cholestasis of pregnancy, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, stillbirth, birth defect, neonatal jaundice, necrotizing enterocolitis, and pneumonia incidence. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for maternal and neonatal outcomes. Subgroup analyses were conducted, and Kaplan-Meier survival analysis was used to estimate the survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model, an inverse probability weighting model, a restricted cubic spline analysis, and logistic regression models using other percentage cutoffs for discordance. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6101 females that gave birth to dichorionic twins during the study interval, birth weight discordance was observed in 797 twin pairs (13.1%). In this cohort, intertwin birth weight discordance was related to an elevated risk of HDP (aOR 1.56; 95% CI 1.21-2.00), and this relationship was confirmed through sensitivity analyses. Hypertensive disease risk rose as the severity of this birth weight discordance increased. Discordant birth weight was also linked to increased odds of neonatal mortality (aOR 2.13; 95% CI 1.03-4.09) and this risk also increased with the severity of discordance. Of the 164 women with monochorionic twins, the discordant group exhibited an elevated risk of neonatal death compared to the concordant group (crude OR 9.00; 95% CI 1.02-79.3). LIMITATIONS, REASONS FOR CAUTION: The limitations of this study are its retrospective nature and the fact that the available data could not specify which twins were affected by adverse outcomes. There is a lack of an established reference birth weight for Chinese twins born at a gestational age of 24-41 weeks. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that twins exhibiting a birth weight discordance are related to an elevated risk of adverse maternal and perinatal outcomes, emphasizing a potential need for higher levels of antenatal surveillance in these at-risk pregnancies. STUDY FUNDING/COMPETING INTEREST(S): Authors declare no conflict of interest. This study was funded by the Clinical Research Program of Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYLJ202118) and the National Natural Science Foundation of China (Grant Nos 82271693 and 82273634). TRIAL REGISTRATION NUMBER: N/A.

Does Day 3 embryo status matter to reproductive outcomes of single blastocyst transfer cycles? A cohort study.

OBJECTIVE: To investigate whether Day 3 (D3) embryo status matter to reproductive outcomes of blastocyst transfer cycles. DESIGN: Retrospective cohort study. SETTING: Assisted Reproduction Department of Shanghai Ninth People's Hospital, Shanghai, China. POPULATION: A total of 6906 vitrified-thawed single blastocyst transfer cycles in 6502 women were included. METHODS: Generalised estimated equation regression models were used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations between embryo status and pregnancy outcomes. MAIN OUTCOME MEASURES: Biochemical pregnancy, miscarriage, live birth. RESULTS: High-quality blastocysts derived from poor-grade D3 embryos had comparable pregnancy outcomes to those derived from high-grade D3 embryos (40.0% versus 43.2%, aOR 1.00, 95% CI 0.85-1.17 for live birth rate; 8.3% versus 9.5%, aOR 0.82, 95% CI 0.63-1.07 for miscarriage rate). Cycles with low D3 cell number (five cells or fewer) had significantly higher miscarriage rate (9.2% versus 7.6%, aOR 1.33, 95% CI 1.02-1.75) compared with cycles with eight cells on D3. CONCLUSIONS: Poor-quality cleavage embryos should be cultivated to the blastocyst stage because high-quality blastocysts derived from poor-grade D3 embryos had acceptable pregnancy outcomes. When the blastocyst grade is identical, choosing embryos with higher D3 cell number (eight or more cells) for transfer could reduce the risk of early miscarriage.

Circulating CXCR5+ natural killer cells are expanded in patients with myasthenia gravis.

Objectives: Myasthenia gravis (MG) is a classic autoantibody-mediated disease in which pathogenic antibodies target postsynaptic membrane components, causing fluctuating skeletal muscle weakness and fatigue. Natural killer (NK) cells are heterogeneous lymphocytes that have gained increasing attention owing to their potential roles in autoimmune disorders. This study will investigate the relationship between the distinct NK cell subsets and MG pathogenesis. Methods: A total of 33 MG patients and 19 healthy controls were enrolled in the present study. Circulating NK cells, their subtypes and follicular helper T cells were analysed by flow cytometry. Serum acetylcholine receptor (AChR) antibody levels were determined by ELISA. The role of NK cells in the regulation of B cells was verified using a co-culture assay. Results: Myasthenia gravis patients with acute exacerbations had a reduced number of total NK cells, CD56dim NK cells and IFN-γ-secreting NK cells in the peripheral blood, while CXCR5+ NK cells were significantly elevated. CXCR5+ NK cells expressed a higher level of ICOS and PD-1 and a lower level of IFN-γ than those in CXCR5- NK cells and were positively correlated with Tfh cell and AChR antibody levels. In vitro experiments demonstrated that NK cells suppressed plasmablast differentiation while promoting CD80 and PD-L1 expression on B cells in an IFN-γ-dependent manner. Furthermore, CXCR5- NK cells inhibited plasmablast differentiation, while CXCR5+ NK cells could more efficiently promote B cell proliferation. Conclusion: These results reveal that CXCR5+ NK cells exhibit distinct phenotypes and functions compared with CXCR5- NK cells and might participate in the pathogenesis of MG.

Type 2 diabetes mellitus as a possible risk factor for myasthenia gravis: a case-control study.

Background: A certain number of myasthenia gravis (MG) patients clinically had type 2 diabetes mellitus (T2DM) prior to MG onset, which suggests that the onset of MG may correlate with the history of T2DM. This study aimed to examine the correlation between MG and T2DM. Methods: In a single-center, retrospective, 1:5 matched case-control study, all 118 hospitalized patients with a diagnosis of MG from 8 August 2014 to 22 January 2019 were enrolled. In total, four datasets with different sources of the control group were retrieved from the electronic medical records (EMRs). Data were collected at the individual level. A conditional logistic regression analysis was used to test the risk of MG associated with T2DM. Findings: The risk of MG was significantly associated with T2DM, and there were notable differences by sex and age. Whether compared to the general population, general hospitalized patients without autoimmune diseases (AIDs), or patients with other AIDs except MG, women aged over 50 years with T2DM had an increased risk of MG. The mean onset age of diabetic MG patients was more than that of the non-diabetic MG patients. Interpretation: This study demonstrates that T2DM is strongly associated with the subsequent risk of MG and varies significantly by sex and age. It reveals that diabetic MG may be a unique subtype that is different from the conventional MG subgroup classification. More clinical and immunological features of diabetic MG patients need to be explored in further studies.

Identification of key genes related to immune infiltration in cirrhosis via bioinformatics analysis.

Cirrhosis is the most common subclass of liver disease worldwide and correlated to immune infiltration. However, the immune-related molecular mechanism underlying cirrhosis remains obscure. Two gene expression profiles GSE89377 and GSE139602 were investigated to identify differentially expressed genes (DEGs) related to cirrhosis. Enrichment analysis for DEGs was conducted. Next, the immune infiltration of DEGs was evaluated using CIBERSORT algorithm. The hub DEGs with tight connectivity were identified using the String and Cytoscape databases, and the expression difference of these hub genes between normal liver and cirrhosis samples was determined. Moreover, in order to evaluate the discriminatory ability of hub genes and obtained the area under the receiver operating characteristic curve values in the GSE89377 and GSE139602 datasets. Finally, the association between hub DEGs and immune cell infiltration was explored by Spearman method. Among the 299 DEGs attained, 136 were up-regulated and 163 were down-regulated. Then the enrichment function analysis of DEGs and CIBERSORT algorithm showed significant enrichment in immune and inflammatory responses. And four hub DEGs (ACTB, TAGLN, VIM, SOX9) were identified, which also showed a diagnostic value in the GSE89377 and GSE 139,602 datasets. Finally, the immune infiltration analysis indicated that, these hub DEGs were highly related to immune cells. This study revealed key DEGs involved in inflammatory immune responses of cirrhosis, which could be used as biomarkers for diagnosis or therapeutic targets of cirrhosis.

Identification of key immune-related genes in dilated cardiomyopathy using bioinformatics analysis.

Dilated cardiomyopathy (DCM) is characterized by the left ventricular dilatation and impaired myocardial systolic dysfunction with high mortality and morbidity. However, the underlying mechanisms remain elusive. We first identified the differentially expressed genes (DEGs) between the DCM and control group using two expression profiles from GSE3585 and GSE84796. Enrichment analysis was conducted to explore the potential mechanisms underlying DCM. A total of four algorithms, including key module of MCODE, degree, maximum neighborhood component (MNC), and maximal clique centrality (MCC), were used to identify the hub genes within Cytoscape. The correlation between hub genes and infiltrated immune cells was evaluated to determine potential immune-related genes. The expression analysis and diagnosis value analysis of potential immune-related genes were performed. Finally, the expression analysis with GSE57338 and relationship analysis with the comparative toxicogenomics database (CTD) were performed to identify the key immune-related genes in DCM. A total of 80 DEGs were screened for DCM. Enrichment analysis revealed that DEGs were involved in the immune-related pathological process. Immune infiltration analysis indicated a potentially abnormal immune response in DCM. Four up-regulated genes (COL1A2, COL3A1, CD53, and POSTN) were identified as potential immune-related genes. Finally, three genes (COL1A2, COL3A1, and POSTN) were determined as the key immune-related genes in DCM via expression analysis with a validation set (GSE57338) and relationship analysis with CTD. Our study suggested that the upregulated COL1A2, COL3A1, and POSTN might be the key immune-related genes for DCM. Further studies are needed to validate the underlying mechanisms.

Impact of recurrent pregnancy loss history on reproductive outcomes in women undergoing fertility treatment.

BACKGROUND: Recurrent pregnancy loss negatively affects the reproductive outcomes of natural conception. Preimplantation genetic testing for aneuploidies has been the focus of interventions in women with recurrent pregnancy loss. However, the risk of no embryos being available, high costs, and uncertainties surrounding its effectiveness limit its use. Factors beyond euploidy, such as an appropriate intrauterine environment, are also important for improving the reproductive outcomes in women with recurrent pregnancy loss. It remains unknown whether a history of recurrent pregnancy loss can affect reproductive outcomes after fertility treatment. OBJECTIVE: This study aimed to investigate the impact of history of recurrent pregnancy loss on the reproductive outcomes of women undergoing fertility treatment. STUDY DESIGN: This was a retrospective cohort study of women who underwent their first frozen embryo transfer cycle or intrauterine insemination cycle between January 2014 and July 2020 in Shanghai, China. We excluded couples with known karyotypic abnormalities (eg, balanced translocation) or uterine malformation. We performed multivariate binary logistic regressions for biochemical pregnancy, miscarriage, and live birth rates to investigate the associations between recurrent pregnancy loss history and reproductive outcomes. RESULTS: A total of 29,825 women who underwent frozen embryo transfer cycles and 5476 women who underwent intrauterine insemination cycles were included in this study. In those who underwent frozen embryo transfer, history of recurrent pregnancy loss was not significantly associated with biochemical pregnancy (adjusted odds ratio, 1.19; 95% confidence interval, 0.87-1.63), miscarriage (adjusted odds ratio, 0.99; 95% confidence interval, 0.78-1.26), or live birth rates (adjusted odds ratio, 0.91; 95% confidence interval, 0.79-1.06). Similarly, in frozen embryo transfer cycles that led to clinical pregnancy, recurrent pregnancy loss history was not significantly associated with live birth (adjusted odds ratio, 0.99; 95% confidence interval, 0.76-1.28) or miscarriage rates (adjusted odds ratio, 1.04; 95% confidence interval, 0.81-1.35). In women with intrauterine insemination, history of recurrent pregnancy loss showed no significant associations with fertility outcomes in all cycles ([adjusted odds ratio, 1.36; 95% confidence interval, 0.88-2.10] for live birth rate and [adjusted odds ratio, 1.74; 95% confidence interval, 0.75-4.01], for miscarriage rate) and in cycles that led to clinical pregnancy ([adjusted odds ratio, 0.70; 95% confidence interval, 0.31-1.63] for live birth rate and [adjusted odds ratio, 1.45; 95% confidence interval, 0.58-3.63] for miscarriage rate). CONCLUSION: In women without obvious chromosome abnormality and uterine malformation who undergo fertility treatment, recurrent pregnancy loss history was not significantly associated with miscarriage and live birth rates, suggesting that it has little or no prognostic value in predicting the reproductive outcomes of frozen embryo transfer or intrauterine insemination cycles.

Live birth rate and neonatal outcomes following interventional embolization of hydrosalpinx.

BACKGROUND: Hydrosalpinx has a negative effect on the pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET), and the pretreatment for hydrosalpinx play an important role in improving the outcomes of IVF-ET. This study aimed to investigate the impacts of interventional embolization of hydrosalpinx on the live birth rate and neonatal outcome after in-vitro fertilization. METHOD: In the present retrospective study, 3351 women receiving the first frozen embryo transfer (FET) after freeze-all policy were reviewed. Patients who received interventional embolization of hydrosalpinx (n = 1268) were included in the study group and those with hydrosalpinx-free bilateral fallopian tube obstruction (n = 2083) in the control group. The primary outcome was live birth (LB) rate; the secondary endpoints included rates of implantation, clinical pregnancy (CP), multiple pregnancy, and pregnancy loss. RESULTS: The LB rate was similar between embolization group (39.91%) and control group (43.21%) (P > 0.05). The rate of implantation (35.81% vs. 32.24%), CP (50.84% vs. 47%) and multiple pregnancy rate (28.71% vs. 24.16%) in the control group were significantly higher than in the embolization group (P < 0.05). The miscarriage rate (39.91%, vs 43.21%, P > 0.05), ectopic gestation rate (2.35% vs 2.83%, P > 0.05), and ongoing pregnancy rate (41.56% vs 44.89%, P > 0.05) were comparable between two groups. After adjustment for confounding factors, interventional embolization of hydrosalpinx was found to have no influence on the LB rate. The thicker endometrium, more embryos transferred, and transfer of blastocyst stage embryos significantly increased the LB rate and CP rate. CONCLUSION: The interventional embolization of hydrosalpinx can achieve the LB rate similar to that of hydrosalpinx-free obstruction patients with less risk, less pain and reduced medical cost. Thus, embolization of hydrosalpinx is one of the preferable clinical treatments for patients with hydrosalpinx.

The comparison of two different protocols ultra-long versus medroxyprogesterone acetate in women with ovarian endometriosis: a prospective randomized controlled trial.

BACKGROUND: This study aimed to investigate the medroxyprogesterone acetate (MPA) + HMG protocol vs ultra-long gonadotrophin releasing hormone (GnRH) agonist protocol in patients with advanced ovarian endometriosis who received in vitro fertilization (IVF). METHODS: Three hundred patients with advanced ovary endometriosis who underwent IVF were included, and embryological and clinical outcomes were assessed between March 2017 and September 2017. Patients were divided into MPA + HMG group and 1-month ultra-long GnRHa protocol group. RESULTS: Lower hMG dose and shorter medication time were found in the MPA + HMG group than in the GnRHa group (P < 0.05). Follicle to-Oocyte Index was significantly different between MPA + HMG group and GnRHa group (P < 0.001). No differences were found in the ovary response and numbers of mature oocytes, fertilized oocytes and viable embryos. The clinical pregnancy and live birth outcomes were similar between MPA + HMG group and GnRHa group, and these outcomes were independent of fresh or frozen embryo transfer in the GnRHa protocol group. There were no significant differences in the time to embryo transfer, medical cost and adverse effects. CONCLUSION: The number of oocytes retrieved and pregnancy outcomes after MPA + HMG protocol are similar to those after ultra-long GnRHa protocol in women with ovarian endometriosis. MPA + HMG protocol may be an alternative to ultra-long GnRHa protocol for IVF in ovary endometriosis patients. Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17010924) In conclusion, the administration of MPA in COH showed similar number of oocytes retrieved, no premature LH surge, and similar pregnancy and live birth outcomes in patients with advanced ovarian endometriosis undergoing IVF/ICSI as compared to the one-month long protocol. The use of MPA in COH appears to be promising although many questions remain to be elucidated, including the dose and time of progestin priming as well as its possible influence on the oocyte development potential and microenvironment. Given their good tolerability, few metabolic influence, and low cost, progestogens provide a novel alternative to the conventional protocol for patients with endometriosis.

Diabetes mellitus aggravates humoral immune response in myasthenia gravis by promoting differentiation and activation of circulating Tfh cells.

Myasthenia gravis (MG) is a T-cell-dependent, antibody-mediated autoimmune disease. Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia and emerging evidence indicates its profound impacts on the immune homeostasis. Previous studies and our data showed DM might serve as an independent risk factor of MG, yet the underlying immune and molecular mechanisms remain to be addressed. Our study observed that circulating Tfh (cTfh) cells were increased in MG patients with DM and expressed a high level of ICOS. Besides, positive correlations between activated cTfh cells and plasmablasts were documented. Further studies demonstrated hyperglycemia promoted the differentiation and activation of Tfh cells which, in turn, caused abnormal plasmablasts differentiation and antibody secretion through the mTOR signaling pathway. These results indicated DM might aggravate the aberrant humoral immunity in MG patients by augmenting Tfh cells differentiation and function and tight glycemic control might be beneficial for MG patients with DM.