Preeclampsia (PE) is one of the main causes of obstetric complications and leads to both maternal and neonatal mortality. The maternal innate immune system plays an important role throughout pregnancy by providing protection against pathogens, while simultaneously inducing tolerance to a semi-allogenic developing fetus and placental development. Background/Objectives: To conduct a comparative study of immunological markers in the blood and placenta in preeclampsia. Methods: A total of 35 pregnant women were enrolled in a comparative study with preeclampsia (7) and with physiological pregnancy (28). A study of the immune status in peripheral blood and placenta was conducted with an examination of the subpopulation of lymphocytes profile and intracellular cytokines production by flow cytometry. Results: In the blood of pregnant women with PE, there was a decrease in CD14+ monocytes, as well as a significant increase of natural killers CD16+, CD56+ and activation markers HLA-DR+ and CD95+, as well as a significant rise in production of IL-10, TNF, Perforin, GM-CSF, and IGF. At the same time, in placental tissue in patients with preeclampsia, on the contrary, a significant decrease in regulatory cells CD4+, CD8+, CD14+, CD56+, CD59+, activation markers CD95+, as well as anti-inflammatory cytokine IL-10, growth factors VEGFR and IGF was detected. Conclusions: The maternal–fetal immune profile is crucial for successful fetal development and dysregulation of T-, B-, and NK cells can contribute to inflammation, oxidative stress, and the development of preeclampsia.

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.

Thrombophilia is considered one of the key mechanisms underlying reproductive disorders. Clinical heterogeneity of reproductive disorders and a lack of stratification by phenotype often limit interpretation. Therefore, evaluating thrombophilia-associated genetic markers separately in fetal loss syndrome, postpartum hemorrhage (PPH), and hypertensive disorders of pregnancy is essential. Background/Objectives: To assess the frequency of thrombophilia-related genetic polymorphisms in women with various reproductive disorders and evaluate their association with clinical–anamnestic characteristics and obstetric antiphospholipid syndrome. Methods: A total of 132 women with reproductive disorders (fetal loss syndrome, postpartum hemorrhage, preeclampsia). Results: Statistically significant differences were found when comparing between the groups. Thus, heterozygous F13 genetic polymorphisms were statistically more common in the group with a history of preeclampsia compared to the group with PPH (the G/A genotype was detected in 22.2% versus 10.7%, p = 0.045), and heterozygous ITGA2 gene genetic polymorphisms were also more common (the C/T genotype was detected in 66.7% versus 42.9%, p = 0.023). In women with a history of PPH, homozygous ITGA2 genetic polymorphisms were statistically more common (the T/T genotype was detected 2.6 times more often—21.4% versus 8.8% compared to the group with fetal loss syndrome, p = 0.022; and 3.8 times more often—21.4% versus 5.6% compared to the group with PE, p = 0.022). Conclusions: A study of thrombophilia gene polymorphisms in women with reproductive disorders showed that the G/A genotype of F13, the C/T genotype of ITGA2, and the A/G genotype of MTR:2756 were significantly more common in women with preeclampsia than in the group with postpartum hemorrhage; the T/T genotype of the ITGA2 gene was detected in postpartum hemorrhage. The MTHFR 1286A > C (A/C) polymorphism was associated with a reduced risk of postpartum hemorrhage. In contrast, the MTR 2756A > G (A/G) genotype was associated with an increased risk of preeclampsia.

Background: Hypertensive conditions during pregnancy, such as preeclampsia (PE), are multisystem obstetric complications, accompanied by changes in the immunological status. Although several types of immune cells are involved in pathogenesis of preeclampsia, such as regulatory T cells, macrophages, natural killer cells, and neutrophils, most studies have focused on the concentration of circulating cytokines. Much less is known about intracellular cytokine production at the level of individual groups of peripheral blood immune cells. This gap limits our understanding of the early immunological changes that precede the clinical manifestation of the disease. Thus, the study of intracellular cytokine production in various leukocyte populations may provide new biomarkers for predicting preeclampsia. Objectives: To test the hypothesis that women with preeclampsia exhibit distinct intracellular cytokine profiles in specific peripheral blood immune cell subsets compared with normotensive pregnant women, and to assess whether these differences could serve as potential biomarkers for disease prediction. Methods: The study included a total of 78 pregnant women admitted to labor with physiological pregnancy (n = 32) and with gestational hypertension (GH) (n = 39) and PE (n = 7). The multicolor immunophenotyping with intracellular cytokine production of TNF, GM-CSF, IGF and receptor VEGFR-2 by different immunocompetent cell types was evaluated on a BD FACS CALIBUR flow cytometer. Results: Flow cytometry revealed a marked increase in the proportion of CD8⁺ GM-CSF⁺, CD56⁺VEGFR2⁺, CD14⁺IL-10⁺, and CD19⁺IGF⁺ cells in both hypertensive groups versus controls (p < 0.001). In contrast, CD56⁺TNF⁺ levels were significantly reduced (p < 0.001). For differentiating PE from GH, CD56+VEGFR2+ and CD19+IGF+ should be prioritized (AUC~0.66–0.78) with good specificity and moderate sensitivity. Conclusions: These data will not only expand existing knowledge about the role of intracellular cytokines in the pathogenesis of preeclampsia, but will also help to obtain new markers for predicting preeclampsia.

Background: Endometriosis is a chronic estrogen-dependent inflammatory disease estimated to affect up to 190 million women of reproductive age worldwide based on clinical and population-based estimates, although only 22.3 million prevalent cases were formally documented—a gap that itself reflects substantial under-diagnosis. Despite an exponential increase in systematic reviews (SRs) and meta-analyses (MAs), the evidence base remains fragmented across clinical domains. An umbrella review provides the methodologically highest level of evidence synthesis and allows critical appraisal and hierarchical classification of published SRs and MAs. Objective: The aim of this study was to conduct a comprehensive critical synthesis of published SRs and MAs on the epidemiology, pathogenesis, diagnosis, treatment, and long-term consequences of endometriosis and to assess their methodological quality using AMSTAR-2. Methods: Systematic searches were conducted in PubMed, Embase, Cochrane Library, and Scopus (2016–2026). Eligibility: SRs with or without MA covering any clinical aspect of endometriosis in women were considered eligible. Quality was assessed using AMSTAR-2. Association strength was classified as convincing (Class I), highly suggestive (Class II), suggestive (Class III), weak (Class IV), or non-significant (NS). Results: Fifty-two SRs and MAs were included (total sample > 6,000,000 participants). AMSTAR-2 quality: high 25% (n = 13), moderate 40% (n = 21), low 29% (n = 15), critically low 6% (n = 3). Class I evidence: short menstrual cycle (<27 days) associated with endometriosis risk (OR 1.68; 95% CI 1.48–1.89). Class II: post-operative dienogest reduces recurrence by 70% (OR 0.30; 95% CI 0.18–0.53); the risks of anxiety (RR 2.82; 95% CI 1.69–4.68) and depression (RR 2.78; 95% CI 1.63–5.25) are markedly elevated. Diagnostic delay persists at 4–12 years globally. Multi-biomarker platforms and AI-assisted imaging (e.g., PromarkerEndo and IMAGENDO) have shown promising preliminary diagnostic performance (reported AUCs of 0.997 and 0.906, respectively) in initial validation studies, although external validation in larger and more diverse cohorts is required before clinical implementation can be recommended. Conclusions: Endometriosis is a systemic, chronically under-diagnosed disease requiring a multidisciplinary approach. The available evidence supports dienogest as one of the preferred options for post-operative maintenance therapy, identifies multi-biomarker platforms as a promising—though not yet clinically validated—avenue for non-invasive diagnosis, and underscores the importance of incorporating psychological assessment into multidisciplinary management.

Background/Objectives: Obstetric hemorrhage remains a leading cause of maternal morbidity and mortality. We examined five-year institutional trends in the recorded hemorrhage rate, cesarean delivery, uterus-preserving hemostatic procedures, uterotonic and antifibrinolytic use, and blood product consumption at a high-volume tertiary maternity center in Kazakhstan. Methods: This was a retrospective time-series analysis of aggregated annual and monthly records for 2018–2022 (46,554 deliveries). The outcome was hemorrhage as entered on the hemorrhage line of the institutional register against the national threshold of 500 mL after vaginal birth and 1000 mL after cesarean; measured blood loss and severity grade were not recorded, so the study describes incidence rather than severity, and blood product figures are hospital-wide adult transfusion volumes. We calculated rates per 1000 deliveries with Wilson confidence intervals, fitted Poisson regression with delivery volume as an offset to estimate incidence rate ratios (IRRs), compared recorded hemorrhage by delivery route with Fisher’s exact test, screened for seasonality and out-of-limit months with process control charts, and correlated the monthly hemorrhage rate with service-use variables before and after detrending, with false-discovery-rate correction. Results: The recorded hemorrhage rate fell from 11.39 to 3.62 per 1000 deliveries (rate ratio 0.318, 95% CI 0.217–0.466; 68.2% relative reduction), an average decline of 27.6% per year (IRR 0.724, 95% CI 0.665–0.788, p < 0.001). No reproducible seasonal pattern was found. The cesarean rate declined from 24.90% to 19.36%. Carbetocin and tranexamic acid use rose several-fold, while red cell volume per delivery fell by about 48%. Raw inverse correlations between medication use and hemorrhage were explained by the shared time trend and did not survive detrending and correction. Conclusions: The center recorded a substantial, statistically robust decline in recorded obstetric hemorrhage alongside expanded pharmacologic prophylaxis and reduced transfusion. Because the data are aggregate and neither placental pathology nor other patient case mix could be measured, the parallel trends cannot show that any intervention caused the fall, and a shift in documentation practice cannot be excluded. The findings support prospective monitoring and patient-level study. Because severe hemorrhage and the surgery used to control it may compromise later fertility, the reproductive outcomes of these women are a priority for further research.