Pilot Study on Molecular Quantitation and Sequencing of Endometrial Cytokines Gene Expression and their Effect on the Outcome of In-Vitro Fertilization (IVF) Cycle

Abstract

Background: Human trophoblast invasion and differentiation are essential for successful pregnancy outcome. The molecular mechanisms; however, are poorly understood. Interleukin (IL)-11, a cytokine that regulates endometrial epithelial cell adhesion, trophoblast motility and invasion during implantation, may be involved in some of these processes. Leukemia inhibitory factor (LIF) is one of the key cytokines in the embryo implantation regulation. The present study aimed to assess the levels of LIF, IL-11 and IL-11 α receptor gene expression in the endometrium of women undergoing IVF, and correlate their levels with the IVF pregnancy outcome. Also, the study aimed to detect any sequence mutation in these three genes among IVF pregnant and non-pregnant women versus control menstrual blood of fertile women. Methods: Endometrial tissue biopsies were taken from 15 women undergoing IVF on the day of oocyte retrieval. The quantitative expression of IL-11, IL-11Rα and LIF genes were assessed by real time PCR and PCR products were sequenced by DNA sequencer to detect any DNA sequence changes. Menstrual blood from 10 fertile women was used as control to compare the DNA sequence versus DNA sequence of the studied genes in endometrial biopsies. Luteinizing hormone (LH), follicular stimulating hormone (FSH) and estradiol (E2) were assessed for enrolled patients by ELISA. Endometrial thickness was also assessed by pelvic ultrasonography. Results: No significant difference was detected between quantitative expression of the three studied genes and pregnancy IVF outcome. Although DNA sequence changes were found in IL-11 and LIF genes of women with negative pregnancy IVF outcome compared to women with positive pregnancy IVF outcome. No DNA sequence changes were detected for IL-11Rα. Other studied parameters (age, LH, FSH, E2 and endometrial thickness) showed no significant differences or correlation with quantitative expression of the three studied involved genes. Conclusions: Data suggested that no significant differences between quantitative expression of IL-11, IL-11Rα and LIF genes and the IVF pregnancy outcome. The present study may reveal that changes in IL-11 and LIF genes sequence may contribute in pregnancy IVF outcome.

Association between leukaemia inhibitory factor gene polymorphism and pregnancy outcomes after assisted reproduction techniques

“…Kralickova et al (2006) investigated the prevalence of LIF gene mutations in a population of infertile women and found a significantly higher frequency of the functionally relevant mutation (the G to A transitions at the position 3400). Novotny et al (2009) (G > A transition at position 3400) and Sabry et al (2014) (C > T at nucleotide 351) also observed the effect of LIF mutations on the outcome of IVF treatment.…”

“…Novotny et al (2009) analysed 15 infertile women with the G to A transition at position 3400 and observed that in mutation-positive women, idiopathic infertility and endometriosis have a negative effect on the outcome of IVF treatment. In their study of sequence mutations in LIF genes among pregnant and non-pregnant women who underwent IVF, Sabry et al (2014) detected a DNA sequence transition from C (in IVF positive pregnancy cases) to T (in IVF negative pregnancy cases) at nucleotide 351 (NT_011520.12). To the best of our knowledge, this present study is the first to relate the LIF SNP T/G (rs929271) with clinical outcomes after IVF treatment; therefore, a comparison of results is difficult.…”

Augmented reality-based border management

“…In order to understand how much the responses of the participants in the feedback of the BM AR system are related to their experience in border management, which are familiar with AR, and conducting an activity in a border region, eight questions (5-7 and 10-25) were considered in the correlations calculations. The correlations were calculated using Spearman's rank correlation coefficient, which is a nonparametric measure (Kumar and Abirami 2018) that is used to measure similar patterns (Levitt et al 2019) and is useful for non-normal variables (Sabry et al 2014). This coefficient was selected because it is suitable for ordinal data and is relatively robust to outliers (Schober et al 2018).…”

Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients?

“…DNA sequence changes have been found in the LIF genes of women with negative IVF outcome. LIF gene mutation may thus contribute to IVF failure [18].…”