Mfn2 regulates mitochondria-associated ER membranes to affect PCOS oocyte development.

This study aimed to investigate the role of mitochondrial-related protein Mfn2 in polycystic ovary syndrome (PCOS) and its impact on oocyte development. The pathological features of PCOS model mice were confirmed by hematoxylin-eosin staining and immunohistochemistry. The expression of Mfn2 and mitochondrial-related proteins in PCOS oocytes and granulosa cells was detected by qRT-PCR and Western blot. Mitochondrial quantity was measured by Mito-Tracker staining, and the structure of mitochondria-associated ER membranes (MAMs) was observed by transmission electron microscopy. The results showed that Mfn2 was significantly downregulated in PCOS oocytes and granulosa cells, and its expression was inhibited in oocytes at different developmental stages. Moreover, the structure of MAMs was also disrupted. Downregulation of Mfn2 expression led to a reduction in mitochondrial quantity in oocytes and granulosa cells, as well as disruption of MAM structure, while overexpression of Mfn2 had the opposite effect. In conclusion, this study indicates that Mfn2 affects the development of PCOS oocytes by regulating MAMs and may be involved in maintaining the stability of MAM structure and function, thereby affecting mitochondrial quantity and function. These findings provide new insights into the pathogenesis and treatment of PCOS.

Impact of thyroid autoimmunity on pregnancy outcomes in euthyroid women following fresh/frozen-thawed embryo transfer.

OBJECTIVE: To investigate whether thyroid autoimmunity (TAI) is associated with assisted reproductive technology (ART) outcomes in euthyroid women undergoing fresh embryo transfer (ET) and frozen-thawed embryo transfer (FET). DESIGN: A retrospective cohort study. Pregnancy and neonatal outcome after fresh ET or FET were compared between the positive and negative thyroid autoimmune antibody groups. PATIENTS: A total of 5439 euthyroid women who started their ART cycle at our centre between 2015 and 2019 were included. RESULTS: The thyroid antibody positive group had a greater mean age than the thyroid antibody negative group (32(29,35) vs. 31(28,34), p < .001). Women with positive thyroid antibody presented with a higher prevalence of diminished ovarian reserve (DOR) (9.1% vs. 7.1%, p = .026) and lower number of oocyte retrieved (9(5,15) vs. 10(6,15), p = .020), but difference was not significant after adjusting for age. The pregnancy rate, live birth rate, pregnancy loss rate, preterm delivery rate and low birthweight rate between the thyroid antibody positive and thyroid antibody negative groups were comparable both in fresh ET cycles and FET cycles. Subanalysis of the treatment outcomes when using a stricter threshold of TSH of 2.5 mIU/L showed no difference to that achieved when using an upper limit of 4.78 mIU/L. CONCLUSIONS: The present study reveals that patients with anti-thyroid peroxidase antibodies (TPOAbs) and/or antithyroglobulin antibodies (TgAbs) showed no significant differences in pregnancy outcomes following fresh ET and FET when compared with patients with negative thyroid antibodies.

Update on the Relationship Between Depression and Neuroendocrine Metabolism.

Through the past decade of research, the correlation between depression and metabolic diseases has been noticed. More and more studies have confirmed that depression is comorbid with a variety of metabolic diseases, such as obesity, diabetes, metabolic syndrome and so on. Studies showed that the underlying mechanisms of both depression and metabolic diseases include chronic inflammatory state, which is significantly related to the severity. In addition, they also involve endocrine, immune systems. At present, the effects of clinical treatments of depression is limited. Therefore, exploring the co-disease mechanism of depression and metabolic diseases is helpful to find a new clinical therapeutic intervention strategy. Herein, focusing on the relationship between depression and metabolic diseases, this manuscript aims to provide an overview of the comorbidity of depression and metabolic.

Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates. However, evidence regarding the effectiveness of vitamin D supplementation in women with PCOS is inconclusive. This multicentre randomised, double-blinded, placebo-controlled trial aims to evaluate the effectiveness of vitamin D supplementation prior to in vitro fertilisation (IVF) on the live birth rate in women with PCOS. METHODS AND ANALYSIS: We plan to enrol women with PCOS scheduled for IVF. After informed consent, eligible participants will be randomised in a 1:1 ratio to receive oral capsules of 4000 IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out routinely in each centre. The primary outcome is live birth after the first embryo transfer. The primary analysis will be by intention-to-treat analysis. To demonstrate or refute that treatment with vitamin D results in a 10% higher live birth rate than treatment with placebo, we need to recruit 860 women (48% vs 38% difference, anticipating 10% loss to follow-up and non-compliance, significance level 0.05 and power 80%). ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee in Women's Hospital of Zhejiang University on 2 March 2020 (reference number: IRB-20200035-R). All participants will provide written informed consent before randomisation. The results of the study will be submitted to scientific conferences and a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04082650.

D6 blastocyst transfer on day 6 in frozen-thawed cycles should be avoided: a retrospective cohort study.

BACKGROUND: There is no definitive evidence about the suitable timing to transfer blastocysts formed and cryopreserved on day 6 (D6 blastocysts) in frozen-thawed embryo transfer (FET) cycles. This study aimed to investigate the suitable timing to transfer D6 blastocysts in FET cycles and to identify factors affecting clinical pregnancy rate (CPR) and early miscarriage rate (EMR) in FET cycles with blastocysts. METHODS: This retrospective cohort study included 1788 FET cycles with blastocysts. There were 518 cycles with D6 blastocysts, and 1270 cycles with blastocysts formed and cryopreserved on day 5 (D5 blastocysts) (D5 group). According to the blastocyst transfer timing, the cycles with D6 blastocysts were divided into cycles with D6 blastocysts transferred on day 5 (D6-on-D5 group, 103 cycles) and cycles with D6 blastocysts transferred on day 6 (D6-on-D6 group, 415 cycles). The chi-square test, independent t-test or Mann-Whitney test, and logistic regression analysis were used for data analysis. RESULTS: The CPR and implantation rate (IR) were significantly higher in the D6-on-D5 group than in the D6-on-D6 group (55.3% vs. 37.3%, 44.8% vs. 32.6%, P < 0.01). The CPR and IR were significantly higher in the D5 group than in the D6-on-D5 group (66.0% vs. 55.3%, 62.1% vs. 44.8%, P < 0.05), and the EMR was significantly lower in the D5 group than in the D6-on-D5 group (11.2% vs. 21.1%, P < 0.05). Logistic regression analysis demonstrated that transfer D6 blastocysts on day 5, instead of day 6, could significantly increase the CPR (odds ratio[OR]: 2.031, 95% confidence interval (CI): 1.296-3.182, P = 0.002). FET cycles with D6 blastocysts transferred on day 5 had a higher EMR than those with D5 blastocysts (OR: 2.165, 95% CI: 1.040-4.506, P = 0.039). Hormone replacement therapy (HRT) cycles exhibited a higher EMR than natural cycles (OR: 1.953, 95% CI: 1.254-3.043, P = 0.003), while no difference was observed in the CPR (P > 0.05). CONCLUSIONS: These results indicate that the suitable timing to transfer D6 blastocysts in FET cycles may be day 5, and D6 blastocyst transfer on day 6 in FET cycles should be avoided. D6 blastocysts transfer and HRT cycles may be associated with a higher EMR.

Isoflavone combined with exercise on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis of randomized control trials (RCTs) aimed to evaluate the effects of isoflavones supplementation combined with exercise training on bone mineral density (BMD) in postmenopausal women. METHODS: Two reviewers did a complete search of two electronic database (Medline, PubMed) records up to January 31, 2019. Risk of bias was classified based on the Cochrane Collaboration tool. The pooled standard mean difference (SMD) combined with 95% confidence interval (CI) was used as the effect size of BMD values. RESULTS: A total of four RCTs with 609 participants were included for meta-analysis. The BMD did not differ significantly between isoflavone supplementation combined with exercise training group and placebo group (sub-whole body: SMD = 0.00, 95% CI, -0.23 to 0.24; lumbar spine: SMD = 0.15, 95% CI, -0.30 to 0.60; total hip: SMD = 0.05, 95% CI, -0.18 to 0.298; femoral neck: SMD = 0.10, 95% CI, -0.23 to 0.43; trochanter: SMD = 0.09, 95% CI, -0.14 to 0.33; ward's triangle: SMD = -0.03, 95% CI, -0.24 to 0.30). In addition, combined intervention did not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone. The trials included in this meta-analysis were small and some had methodological limitations. CONCLUSION: The present meta-analysis reveals that isoflavone supplements combined with exercise training do not significantly increase BMD in postmenopausal women. In addition, combined intervention does not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone.

Physical activity and mortality in patients with colorectal cancer: a meta-analysis of prospective cohort studies.

The association between physical activity (PA) and colorectal cancer (CRC) patients' survival is inconsistent. We conducted a systematic review and meta-analysis to summarize published articles on this issue. We performed a comprehensive search of the PubMed, Embase, and Web of Science databases for relevant articles through 28 February 2018. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Eighteen prospective cohort studies were included in the meta-analysis, with a total of 9257 cases of total mortality (TM) and 4015 cases of colorectal cancer-specific mortality (CRCSM) among 31 873 CRC survivors and 557 150 general populations. Among CRC survivors, the highest versus the lowest levels of prediagnosis PA showed decreased risks of TM (summary HR = 0.81, 95% CI: 0.76-0.87, I = 1.8%) and CRCSM (summary HR = 0.85, 95% CI: 0.77-0.98, I = 0), respectively. Significant risk reductions for TM and CRCSM were also demonstrated for postdiagnosis PA (HR = 0.63, 95% CI: 0.54-0.74; and HR = 0.64, 95% CI: 0.47-0.88, respectively). The inverse association between prediagnosis PA and cancer mortality was more pronounced for colon cancer than that for rectal cancer (P = 0.08). The summary HRs (95% CIs) of TM were 0.89 (0.83-0.97) and 0.79 (0.69-0.90) per 10 metabolic equivalent task-h/week increase in prediagnosis and postdiagnosis PA, respectively. Our meta-analysis provides comprehensive evidence that PA performed before or after cancer diagnosis is related to reduced mortality risk among CRC survivors.

Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and meta-analysis.

BACKGROUND: Some studies have investigated the association between soy and isoflavones consumption and breast cancer survival, but the results are far from conclusive. Accordingly, we performed a systematic review and meta-analysis to explore this issue. METHODS: We performed a comprehensive search of Web of Science, PubMed, and Embase from inception to January 2018. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random effects model. RESULTS: A total of 12 articles were included, which reported overall survival (OS), breast cancer specific survival (BCSS), and recurrence in 5770, 2386, and 1500 cases, respectively, among 37,275 women with breast cancer. The summary HR (95% CI) for the association (highest vs. lowest) of pre-diagnosis soy and isoflavones consumption with OS and BCSS was 0.84 (0.71-0.98) and 0.89 (0.74-1.07), respectively. Stratified analyses suggested that the reduced OS was more easily detected in studies that focused on post-menopausal patients. No significant association was found between post-diagnosis soy and isoflavones consumption with OS and BCSS, with summary HRs (95% CIs) of 0.80 (0.62-1.04) and 0.83 (0.64-1.07), respectively. Pre- and post-diagnosis soy isoflavones consumption were associated with reduced risk of recurrence. CONCLUSION: This study provides limited evidence that pre-diagnosis soy and isoflavones intake is associated with a small reduction in post-menopausal breast cancer OS.