Impact of body mass index on assisted reproductive technology outcomes in patients with polycystic ovary syndrome: a meta-analysis.

The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight.

Inhibition of AKT induces p53/SIRT6/PARP1-dependent parthanatos to suppress tumor growth.

BACKGROUND: Targeting AKT suppresses tumor growth through inducing apoptosis, however, during which whether other forms of cell death occurring is poorly understood. METHODS: The effects of increasing PARP1 dependent cell death (parthanatos) induced by inhibiting AKT on cell proliferation were determined by CCK-8 assay, colony formation assay, Hoechst 33,258 staining and analysis of apoptotic cells by flow cytometry. For the detailed mechanisms during this process, Western blot analysis, qRT-PCR analysis, immunofluorescence and co-immunoprecipitation were performed. Moreover, the inhibition of tumor growth by inducing p53/SIRT6/PARP1-dependent parthanatos was further verified in the xenograft mouse model. RESULTS: For the first time, we identified that inhibiting AKT triggered parthanatos, a new form of regulated cell death, leading to colon cancer growth suppression. For the mechanism investigation, we found that after pharmacological or genetic AKT inhibition, p53 interacted with SIRT6 and PARP1 directly to activate it, and promoted the formation of PAR polymer. Subsequently, PAR polymer transported to outer membrane of mitochondria and resulted in AIF releasing and translocating to nucleus thus promoting cell death. While, blocking PARP1 activity significantly rescued colon cancer from death. Furthermore, p53 deletion or mutation eliminated PAR polymer formation, AIF translocation, and PARP1 dependent cell death, which was promoted by overexpression of SIRT6. Meanwhile, reactive oxygen species production was elevated after inhibition of AKT, which might also play a role in the occurrence of parthanatos. In addition, inhibiting AKT initiated protective autophagy simultaneously, which advanced tumor survival and growth. CONCLUSION: Our findings demonstrated that AKT inhibition induced p53-SIRT6-PARP1 complex formation and the activation of parthanatos, which can be recognized as a novel potential therapeutic strategy for cancer. Video Abstract.

Association between melatonin receptor gene polymorphisms and polycystic ovarian syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a kind of common gynecological endocrine disorder. And the mutations of melatonin receptor (MTNR) genes are related to the occurrence of PCOS. But previous researches have shown opposite results. So, the object of our systematic review and meta-analysis is to investigate the relationship between MTNR 1A/B polymorphisms and PCOS. METHODS: PubMed, Embase, Ovid, the Cochrane Library, Web of Science and three Chinese databases (VIP, CNKI and Wanfang) were used to retrieve eligible articles published between January 1980 and February 2020. And we used the odds ratio (OR) and its 95% confidence interval (CI) to investigate the strength of the association by six genetic models, allelic, codominant (homozygous and heterozygous), dominant, recessive and superdominant models. Review Manager 5.3, IBM SPSS statistics 25 and Stata MP 16.0 software were used to do this meta-analysis. RESULTS: Our meta-analysis involved 2553 PCOS patients and 3152 controls, for two single nucleotide polymorphisms (rs10830963 C> G in MTNR1B and rs2119882 T> C in MTNR1A) and significant associations were found in some genetic models of these single nucleotide polymorphisms (SNPs). For rs10830963, strongly significant was found in the heterozygote model (GC vs. CC, P=0.02). Additionally, a slight trend was detected in the allelic (G vs. C), homozygote (GG vs. CC) and dominant (GG+GC vs. CC) model of rs10830963 (P=0.05). And after further sensitivity analysis, a study with high heterogeneity was removed. In the allelic (P=0.000), homozygote (P=0.001), dominant (P=0.000) and recessive (GG vs. GC+CC, P=0.001) model, strong associations between rs10830963 and PCOS were found. Moreover, for rs2119882, five genetic models, allelic (C vs. T, P=0.000), codominant (the homozygote (CC vs. TT, P=0.000) and heterozygote model (CT vs. TT, P=0.02), dominant (CC + CT vs. TT, P=0.03) and recessive model (CC vs. CT + TT, P=0.000) showed significant statistical associations with PCOS. CONCLUSION: MTNR1B rs10830963 and MTNR1B rs2119882 polymorphisms are associated with PCOS risk. However, the above conclusions still require being confirmed by much larger multi-ethnic studies.