Objective: The objective of this study is to investigate the association between methylation levels of HOXA10 and HOXA11 promoters, clinical parameters, and implantation outcomes after in vitro fertilizationembryo transfer (IVT-ET) cycles in women with repeated implantation failures and tubal infertility. Methods: Endometrium samples were collected from 34 women during implantation window before IVF-ET cycle to assess methylation status of HOXA10 and HOXA11 promoters using bisulfite sequencing. All participants had a tubal factor of infertility and at least two implantation failures in the anamnesis. A logistic regression model was used to predict the implantation outcome depending on methylation status and clinical parameters. Results: The methylation of CpG-islands of HOXA10 and HOXA11 promoters was identified in 76.5 and 100% of participants, respectively. The median methylation levels did not differ significantly between the groups with different implantation outcomes, but a logistic regression model based on HOXA10 and HOXA11 methylation and clinical parameters allowed to classify the implantation outcomes with the total percentage of correct predictions of 85.19%. Conclusions: Abnormal methylation levels of the HOXA10 and HOXA11 promoters were found in the endometrium of women with tubal infertility and repeated implantation failures. The findings suggest that methylation status could be an important factor of implantation failure during IVF-ET cycles.

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Аннотация. В статье рассматривается воздушное судно как предмет и как средство совершения актов незаконного вмешательства в деятельность гражданской авиации. Авиационные перевозки получили широкое распространение в середине XX в. и по сей день пользуются популярностью, но в то же время появилась и относительная уязвимость воздушного транспорта, что привело к многочисленным актам незаконного вмешательства в деятельность гражданской авиации, в том числе использование воздушного судна в качестве орудия и предмета преступления. Выявлено, что воздушное судно может быть захвачено в полёте либо на земле с целью его дальнейшего удержания, с целью его дальнейшего перемещения, с целью его дальнейшего уничтожения. Воздушное судно может быть также захвачено с целью дальнейшего удержания на его борту пассажиров и членов экипажа. Существуют и прямые действия, направленные против воздушного судна, такие как его уничтожение посредством использования взрывных устройств. Для решения обозначенных в статье проблем выявлено, что существует целый комплекс мер борьбы против использования воздушного судна как орудия и как предмета незаконного вмешательства в деятельность гражданской авиации. Ключевые слова: воздушное судно, захват, акты незаконного вмешательства, взрывные устройства, угон, безопасность, гражданская авиация.

Relevance. The success of the in vitro fertilisation (IVF) program, among other factors, depends on the readiness of the endometrium to accept the embryo. It is believed that this is possible during the so-called implantation window, the timing of which can be shifted under the influence of various factors. Evaluation of endometrial receptivity and the implantation window based on analysis of endometrial gene expression before embryo transfer is a promising approach for predicting the likelihood of pregnancy in IVF programs. Aim. To construct a classifier based on the expression of endometrial genes for predicting the outcome of an IVF program in patients with tubal-peritoneal infertility factor and repeated failed IVF attempts in history. Materials and methods. Before the IVF program, a genome-wide transcriptome profiling of endometrial samples of 15 women with tubal-perioneal infertility factor and repeated unsuccessful IVF attempts in history was carried out using Affymetrix arrays. Potential genes capable of classifying IVF program outcomes were selected, after which the expression of these genes was analyzed by qPCR-RT in the endometrium of 47 women to construct IVF outcome classifiers based on the expression of pairs or triples of genes. Results. A classifier based on the expression of the triple of genes MSX1 (HOX7), HOXA11, and TP53I3 made it possible to determine the onset of pregnancy in an IVF program with a sensitivity of 73% and a specificity of 71% with an area under the ROC-curve (AUC) of 0.738 (95% confidence interval 0.5770.898). Earlier, a relationship was found between the expression of these genes and receptivity of the endometrium, which suggests that these genes play a role in the onset of the implantation window. Conclusions. The use of a classifier based on the genes MSX1 (HOX7), HOXA11, and TP53I3 can determine the readiness of the endometrium to accept an embryo and create an individual prognosis of the outcome of an IVF program in women with tubal-peritoneal infertility factor and repeated failed IVF attempts in history.