Currently, recurrent implantation failure (RIF) after in vitro fertilization is a problem that is commonly faced by reproductive specialists. The phenomenon of a thin endometrium in RIF patients is not yet completely understood or sufficiently treated. This study aimed to reveal the dysregulated expression of selected genes between RIF patients with a thin endometrium and fertile women. Endometrial samples were collected in the implantation window (21–24 days of the natural menstrual cycle) from RIF patients (n = 20) and fertile women (n = 14). Ten genes were chosen as target genes regarding their possible relations with the implantation process. The endometrial gene expression levels showed differences in RIF samples compared to fertile samples. Significant downregulation was observed for the CXCL1 (p = 0.005) and C4BPA (p = 0.03) genes. There was no statistically significant difference between the RIF group and the fertile group in the expression of eight genes: CXCL8, HPRT1, MMP10, INFG, VEGFB, HAND2, IL-15, and TNC (p > 0.05). The use of a combination of two markers (C4BPA + CXCL1) allows for the good discrimination of RIF patients from fertile women (AUC 0.806).

The article presents the results of examination of 30 patients with a history of miscarriage and ‘thin’ endometrium in comparison with 20 patients without reproductive loss and the presence of normal endometrial thickness. The dynamics of intracellular production of γ-INF, IL-1 and IL-10 by cytotoxic endometrial lymphocytes was studied by flow cytometry. It was found that before treatment in patients with miscarriage and thin endometrium syndrome there was a significant (12-fold) decrease in the level of CD8+ cytotoxic/suppressor lymphocytes (p < .01), a 2.8-fold decrease in the level of CD56+ cells, and also a sharp inhibition of the level of intracellular production of cytokines - γ-INF (8 times), IL-1 (11 times) and IL-10 (15 times). Against the background of complex therapy, including the elimination of pathogenic pathogens, antiplatelet therapy, intrauterine ultrasound cavitation and personalized hormonal therapy using intravaginal micronized progesterone (Luteina), an increase of endometrial thickness was observed: M-echo from 5.9 ± 0.1 to 10.2 ± 0.2 mm; the frequency of visualization of uterine vessels increased to 80–100%; in the spiral arteries, the pulsation index significantly decreased—PI (1.43 ± 0.04 vs. 0.79 ± 0.06), resistance index RI (0.96 ± 0.05 vs. 0.54 ± 0.04), systolic–diastolic ratio S/D in the uterine (4.5 ± 0.04 vs. 2.3 ± 0.05) and arcuate arteries (3.67 ± 0.04 vs. 2.41 ± 0.02); and there was also a positive dynamics of intracellular cytokine production with a significant (p < .05) increase in the level of IL-1 and IL-10, as well as the level of γ-IFN CD56+ by endometrial lymphocytes.

Reproductive disorders are common events in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies on the molecular mechanisms of implantation disorders in thin endometria, including the study of gene transcriptional activities, have shed light on the identification of the potential biological markers of endometrial receptivity. Background/Objectives: The goal of this study was to reveal the significantly dysregulated selected gene expressions between RIF and RPL patients with thin endometria. Methods: Endometrial samples were collected from RIF patients (n = 20) and RPL patients (n = 19) during the implantation window days (LH + 7—LH + 10) of their natural menstrual cycles. Ten genes were chosen as the target genes regarding their possible relations with the implantation process. The total RNA was purified and reverse-transcribed, and gene expressions were quantified by RT-PCR. Results: The expressions of the IL-15, INFG, and HPRT1 genes were significantly decreased in the RIF patients with thin endometria compared to the RPL patients (log₂ fold change = 0.92, p = 0.023 for IL-15; log₂ fold change = 1.24, p = 0.046 for INFG; and log₂ fold change = 0.579, p = 0.046 for HPRT1). There were no significant differences in the expressions of the CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB, and HAND2 genes between the groups. Conclusions: Decreased expressions of the IL-15, INFG, and HPRT1 genes were found in patients with RIF with thin endometria compared to the endometria of women with RPL. This has practical significance for clinicians for the differentiated prescription of immunomodulatory therapy in patients undergoing ART programs.

Background: Recurrent pregnancy loss (RPL) remains etiologically unexplained in 40–50% of cases following standard diagnostic workup. Non-criteria antiphospholipid antibodies (non-criteria aPL) are increasingly considered potential markers of seronegative obstetric antiphospholipid syndrome (APS); however, their diagnostic value in this clinical setting requires further investigation. Objective: To assess the diagnostic value of non-criteria aPL in women with RPL and to construct an exploratory immunological scoring model for diagnostic stratification. Methods: Antiphospholipid antibody detection was performed using a single-measurement semi-quantitative line immunoblot assay (Anti-Phospholipid 10 Dot, Generic Assays, Germany). Statistical analysis included χ², Fisher’s exact test, Mann–Whitney U test, binary logistic regression, and ROC analysis. Results: Statistically significant associations with RPL were observed for anti-prothrombin antibodies (OR = 11.1; 95% CI 1.8–68.0; p = 0.022 [Haldane–Anscombe correction]), anti-annexin V (OR = 4.28; 95% CI 1.18–15.6; p = 0.023), and anti-β₂GP I (OR = 3.31; 95% CI 1.18–9.28; p = 0.019). The exploratory composite immunological score demonstrated moderate discriminatory performance (AUC = 0.701; 95% CI 0.588–0.814; p = 0.005). The overall logistic regression model was statistically significant (χ² = 8.564; p = 0.036), although none of the individual predictors retained independent significance, indicating a contribution of cumulative immunological burden rather than any single marker. Conclusions: In this single-center cross-sectional study, non-criteria aPL were frequently detected in women with RPL and were statistically associated with the condition. The findings should be interpreted as hypothesis-generating only, given the cross-sectional design, single-measurement immunoblot, small control group, and absence of external validation. Confirmation in larger prospective multicenter cohorts using ELISA-based assays with the internationally recommended 12-week repeat measurement is required before any clinical implementation.

Reproductive disorders are a common event in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies of the molecular mechanisms of implantation disorders in thin endometrium, including the study of gene transcriptional activity, have shed light on the identification of potential biological markers of endometrial receptivity. Background/Objectives: to reveal significantly dysregulated selected genes expression between RIF and RPL patients with thin endometrium. Methods: Endometrial samples were collected in the implantation window days (LH+7 – LH+10) of the natural menstrual cycle from RIF patients (n=20) and RPL patients (n=19). Ten genes were chosen as target genes regarding their possible relations with the implantation process. Total RNA was purified, reverse-transcribed; gene expression was quantified by RT-PCR. Results: The expression of the IL-15, INFG and HPRT1 genes were significantly decreased in RIF with thin endometrium patients compared to the RPL patients (log2 fold change=0.92, p=0.023 for IL-15, log2 fold change=1.24, p=0.046 for INFG, and log2 fold change=0.579, p=0.046 for HPRT1). There were not significant differences in expression of CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB and HAND2 genes between groups. Conclusions: decreased expression of IL-15, INFG and HPRT1 genes was found in patients with RIF with thin endometrium compared to the endometrium of women with RPL. This has practical significance for clinicians for differentiated prescription of immunomodulatory therapy in patients undergoing ART programs.

Background: Recurrent pregnancy loss (RPL) is frequently linked to antiphospholipid antibodies, yet many affected women are seronegative for the classical (Sydney) criteria antibodies. In a previously characterized cohort, an extended antiphospholipid antibody panel was positive in 79% of women with RPL, with the strongest associations for antibodies against prothrombin, annexin V and β₂-glycoprotein I. Whether this association reflects molecular endometrial dysfunction was unclear. Objective: To examine endometrial expression of ten decidualization- and inflammation-related genes in women with RPL, stratified by APL status, focusing on the dominant antibody specificity: anti-β₂-glycoprotein I. Methods: Thirty-nine women with RPL (≥2 losses), a subsample of a published 100-patient cohort, underwent mid-luteal Pipelle endometrial biopsy followed by RT-PCR for C4BPA, CXCL1, HAND2, HPRT1, IFNG, IL15, IL8 (CXCL8), MMP10, TNC and VEGFB. Antibodies were measured by antiphospholipid 10 Dot line immunoblot (Generic Assays, Germany). The analysis used Mann–Whitney U, Fisher’s exact test, Benjamini–Hochberg correction and ROC analysis. Results: Antibody prevalence in the subsample matched the parent cohort (Pearson r = 0.999). Of ten transcripts, only HAND2 showed a nominally significant reduction in APL+ women (median ΔCt −2.04 vs. −1.30; p = 0.037; rank-biserial r = −0.47); this signal did not survive Benjamini–Hochberg correction (q = 0.372). The signal was specific to anti-β₂GPI (p = 0.064; AUC 0.700), not to annexin V or prothrombin. A cut-off of HAND2 ΔCt ≤ −1.60 identified APL+ status with 73% sensitivity, 78% specificity and OR 9.62 (95% CI 1.64–56.4; p = 0.015). HAND2 clustered with IL15 (ρ = 0.65) and VEGFB (ρ = 0.70). Conclusions: Anti-β₂-glycoprotein I antibodies, the dominant APL specificity in RPL, are associated with reduced endometrial HAND2 expression. This exploratory data outline a candidate molecular pathway linking extended antiphospholipid serology to impaired endometrial receptivity.