Purpose This study aims to identify genetic causes of female infertility associated with recurrent failure of assisted reproductive technology (ART) characterized by embryonic developmental arrest. Methods We recruited infertile patients from two consanguineous families from the Reproductive Medicine Center of Guizhou Provincial People’s Hospital. Peripheral blood was collected for genomic DNA extraction. Two affected individuals and their family members were performed with whole-exome sequencing and Sanger validation in order to identify possible causative genes. For further analyzing the effect of splicing mutation on mRNA integrity in vivo, TLE6 cDNA from the peripheral blood lymphocyte of the affected individual was sequenced. In addition, the possible impact of the pathogenic mutation on the structure and function of the protein were also assessed. Results Two novel homozygous mutations in the peptidylarginine deiminase type VI (PADI6) and the transducin-like enhancer of split 6 (TLE6) genes were identified in the two families. One patient carried the frameshift deletion mutation c.831_832del:p.S278Pfs*59 of the PADI6 gene and the other patient carried the splicing mutation c.1245-2 A>G of the TLE6 gene. The analysis of the mRNA from the proband’s peripheral blood leukocytes confirmed aberrant splicing. Conclusions Our findings expand the mutational spectrum of PADI6 and TLE6 associated with embryonic developmental arrest and deepen our understanding of the genetic causes of infertility with recurrent ART failure.

Background: Increasing studies suggest that tumor immune infiltration is a relative factor of prognosis in ovarian cancer (OvCa). This study explored the composition of tumor infiltrating immune cells (TIICs) in OvCa using CIBERSORT algorithm and further assessed their values for prognosis and therapeutic strategies by molecular subtypes. Methods: Publicly available databases including The Cancer Genome Atlas (TCGA) and GTEx were searched. Ovarian tumor samples were available from TCGA, and normal ovarian samples were obtained from the GTEx dataset. The relative proportions of immune cell profiling in OvCa and normal samples were evaluated by CIBERSORT algorithm. Association between each immune cell subtype and survival was inferred by the fractions of 22 immune cell types. “CancerSubtypes” R-package was employed to identify the three types of molecular classification and analyze the functional enrichment in each subclass. Response to immunotherapy and anti-cancer drug targets was predicted via TIDE algorithm and GDSC dataset. Results: Substantial variation reflecting individual difference was identified between cancer and normal tissues in the immune infiltration profiles. T cells CD4 memory activated, Macrophages M1 were associated with improved overall survival (OS) as evaluated by univariate Cox regression and multivariate Cox. Three subtypes were identified by “CancerSubtypes” R-package and every sub-cluster possessed specific immune cell characterization. Meanwhile, Cluster II exhibited poor prognosis and sensitive response to immunotherapy. Conclusions: The cellular component of immune infiltration shows remarkable variation in OvCa. Profiling of immune infiltration is useful in prediction of prognosis of OvCa. The results from profiling might be considered in therapeutic modulation.

Objective:We aimed to evaluate the effectiveness of placebo, oral opioid analgesic (OOA), intravenous opioid analgesic (IOA), non-opioid analgesic (NOA), topical anesthetic (TA) and locally injected anesthetic (LIA) for pain relief duringhysterosalpingography (HSG) using a Bayesian network meta-analysis of data from randomized controlled trials.Methods:PUBMED, EMBASE, and CENTRAL search engines were used to search and identify clinical trials that evaluated interventions for pain relief in HSG. Methodological studies quality was assessed by the Cochrane Collaboration tool for assessing risk of bias.Result:Sixteen trials involving 1263 participants were included in this study. IOA got excess but not statistically significant lower visual analogue score (VAS) pain score during HSG or more than 30 minutes after HSG compared with the other groups. OOA resulted in excess but not statistically significant higher VAS pain score during HSG compared with the other groups except placebo group. According to SUCRA regarding the lower VAS pain score during HSG, the treatments rank was the following: IOA, TA, NOA, LIA, OOA and placebo; as regard lower VAS pain score at 30 minutes or more after HSG, the treatments rank was the following: IOA, LIA, OOA, TA, NOA and placebo.Conclusion:This new Bayesian data network meta-analysis from randomized controlled trials demonstrated that IOA resulted in the highest probability to reduce the pain during HSG or at 30 minutes or more after HSG among the six interventions considered.

We aimed to investigate the association of two SNPs in the promoter region of IL-18 (IL-18-607C/A rs1946518 and-137G/C rs187238) with the risk of PCOS in a Chinese Han population. A total of 210 patients with PCOS and 408 subjects without PCOS were selected between June 2015 and December 2016. The genotyping of IL-18-607C/A rs1946518 and-137G/C rs187238 polymorphisms was carried out by an iPlex GOLD SNP genotyping analysis using the Sequenom MassARRAY ® System. Unconditional multivariate logistic regression analysis was taken to calculate the relationship of IL-18-607C/A rs1946518 and-137G/C rs187238 polymorphisms with risk of PCOS. We found that BMI ≥ 24 (OR=2.78, 95% CI=1.85-4.17), ever smoking (OR=2.51, 95% CI=1.08-5.79) and ever drinking (OR=3.64, 95% CI=2.33-5.69) were associated with higher risk of PCOS. Those carrying the CC genotype were associated with 2.40 fold risk of developing PCOS (OR=2.40, 95% CI=1.22-4.72), and the GC+CC genotype displayed an increased risk of PCOS (OR=2.34, 95% CI=1.23-4.48). We suggest that IL-18-137G/C could be considered as a predictive factor for the pathogenesis of PCOS in the Han population of China.

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