Search Results (689)

Maternal immune tolerance and controlled inflammatory responses are essential for fetal development and successful pregnancy. Regulatory T cells (Tregs) and B cells with regulatory properties (Bregs) maintain this balance by limiting excessive immune activation through the secretion of anti-inflammatory and tolerogenic cytokines, such as IL-10, TGF-β, and IL-35. Moreover, alterations in the costimulatory potential of antigen-presenting cells (APCs), including B cells, modulate the activation and differentiation of T cells. Toll-like receptors (TLRs), particularly TLR9, influence B-cell antigen presentation and cytokine production, thereby affecting the balance between pro-inflammatory and tolerogenic responses at the maternal–fetal interface. TLR9 overexpression has been observed in several pregnancy-related disorders in both humans and murine models. In this study, we examine whether blocking TLR9 shortly after mating could improve pregnancy outcomes and modulate the regulatory and antigen-presenting functions of B cells, as well as their interactions with T cells. Using an abortion-prone murine model (CBA/J × DBA/2J), we show that intraperitoneal administration of a TLR9 antagonist (ODN 2088) shortly after mating increases embryo resorption in CBA/J females compared to controls without affecting implantation. Flow cytometry analysis further reveals that mice receiving the TLR9 antagonist are characterized by downregulation of CD80 and upregulation of CD86 on B cells, accompanied by reduced expression of CD40L and CD28 on T cells, as well as a lower percentage of Tregs and activated T cells. In conclusion, blocking TLR9 signaling shortly after mating does not improve pregnancy outcomes; conversely, it exacerbates pregnancy loss in the CBA/J × DBA/2J abortion-prone model, while altering the costimulatory phenotype of B and T cells and impairing Treg development during pregnancy. Full article

Each year, around 23 million miscarriages occur worldwide, which have a substantial emotional impact on parents, and impose significant societal costs. While medical care accounts for most expenses, work productivity loss contributes significantly. Addressing underlying causes of miscarriage could improve parents’ mental health and potentially their economic impact. In most countries, investigations into miscarriage causes are only recommended after recurrent cases, focusing mainly on maternal factors. Fetal and placental tissue are rarely examined, as current guidelines do not advise routine genetic analyses of pregnancy tissue, because the impact of further clinical decision making and individual prognosis is unclear. However, this leaves over 90% of all miscarriage cases unexplained and highlights the need for alternative methods. We therefore conducted a narrative review on genetic analysis, autopsy, and imaging of products of conception (POC). Karyotyping, QF-PCR, SNP array, and aCGH were reviewed in different research settings, with QF-PCR being the most cost-effective, while obtaining the highest technical success rate. Karyotyping, historically being considered the gold standard for POC examination, was the least promising. Post-mortem imaging techniques including post-mortem ultrasound (PMUS), ultra-high-field magnetic resonance imaging (UHF-MRI), and microfocus computed tomography (micro-CT) show promising diagnostic capabilities in miscarriages, with micro-CT achieving the highest cost-effective performance. In conclusion, current guidelines do not recommend diagnostic testing for most cases, leaving the majority unexplained. Although genetic and imaging techniques show promising diagnostic potential, they should not yet be implemented in routine clinical care and require thorough evaluation within research settings—assessing not only diagnostic and psychosocial outcomes but also economic implications. Full article

Hepatitis E virus (HEV) is a zoonotic pathogen that can infect pregnant women and cause adverse pregnancy outcomes, including miscarriage and preterm delivery. The previous study demonstrated that HEV genotype 3 (HEV-3) inhibits complete autophagic flux in both mouse placental tissue and human trophoblast cells (JEG-3), evidenced by reduced expression of ATG proteins (including LC3, Beclin1, ATG4B, ATG5, and ATG9A) and accumulation of p62. However, the specific regulatory pathway involved remains unclear. Thus, eukaryotic expression vectors for HEV open reading frames (ORFs) were constructed, and ORF2 and ORF3 proteins were transiently overexpressed in JEG-3 cells via liposome transfection. While both ORF2 and ORF3 significantly reduced LC3B protein levels (p < 0.01), only ORF2 induced p62 accumulation (p < 0.01), indicative of autophagic inhibition, which indicates that ORF2 was the key viral protein mediating autophagy suppression in JEG-3. The results of WB and RT-qPCR showed that ORF2 suppressed the PI3K/Akt/mTOR pathway while enhancing nuclear translocation of TFEB (p < 0.01) and AMPK phosphorylation (p < 0.01), suggesting paradoxical activation of upstream autophagy regulators. Through co-transfection of mCherry-LC3 with ORF2, co-localization studies, and AlphaFold 3-based intermolecular interaction predictions, we propose that ORF2 directly binds LC3B to block autophagosome formation. Finally, co-immunoprecipitation confirmed physical interaction between HEV ORF2 and LC3B, elucidating the molecular mechanism of HEV-induced autophagy suppression in trophoblasts. These findings reveal the molecular mechanism by which HEV inhibits autophagy leading to miscarriage in mice, providing new insights into HEV-induced reproductive damage. Full article

Obstructive sleep apnea (OSA) is a highly prevalent disorder with far-reaching systemic consequences. While its cardiometabolic and neurocognitive impacts are well established, growing evidence highlights OSA as a contributor to infertility in both men and women. The pathophysiological mechanisms include intermittent hypoxia, oxidative stress, systemic inflammation, and endocrine disruption, all of which can impair spermatogenesis, reduce semen quality, alter gonadal hormone secretion, and compromise ovarian function. Clinical studies consistently demonstrate associations between OSA and impaired semen parameters, reduced testosterone, and erectile dysfunction in men. In women, OSA is frequently observed in those with polycystic ovary syndrome, is associated with ovulatory dysfunction, and negatively affects in vitro fertilization outcomes, pregnancy rates, and miscarriage risk. Despite these findings, infertility is not systematically included in global burden estimates of OSA, leading to the underestimation of its true health and socioeconomic impact. Therapeutic strategies such as weight loss, continuous positive airway pressure, and integrative approaches show promise, though robust evidence from randomized trials is still lacking. Integrating sleep health into reproductive medicine may provide a cost-effective and equitable pathway to improve fertility outcomes worldwide. Full article

Background and Clinical Significance: This report presents the case of a 33-year-old female with recurrent miscarriage, investigated for an adrenal cortical adenoma characterized by autonomous secretion of 17-hydroxyprogesterone (17-OHP). The findings challenge the established diagnostic paradigm, which predominantly attributes elevated serum 17-OHP to congenital adrenal hyperplasia (CAH) or non-classical CAH (NCCAH). Case Presentation: The patient was found to have elevated serum 17-OHP and a 2 cm left adrenal mass. Normal testosterone and precursor levels, along with whole-exome sequencing (WES), argued against a diagnosis of non-classical 21-hydroxylase deficiency (NC-21OHD). An ACTH stimulation test elicited a mild-to-moderate rise in 17-OHP, while adrenal venous sampling (AVS) confirmed marked lateralization of 17-OHP hypersecretion to the left side. Postoperative normalization of 17-OHP levels further supported the diagnosis of a 17-OHP-secreting tumor. Histopathological analysis identified tumor regions with non-uniformly high expression of CYP17A1 and CYP21A2. Preliminary transcriptomic profiling revealed that differentially expressed genes (DEGs) were enriched in microRNA-related and PI3K-Akt signaling pathways. Conclusions: This paradigm-shifting case indicates that, in addition to 21OHD, a 17-OHP-hypersecreting adrenal adenoma should be considered in the differential diagnosis of elevated 17-OHP. The integration of multimodal diagnostic techniques, particularly AVS, is valuable for localizing hormonally active tumors. Preliminary mechanistic insights suggest a potential role for epigenetic dysregulation in the pathogenesis of this tumor type. Full article

Background/Objectives: The first 1000 days of life represent a critical window for growth and neurodevelopment, during which nutrition strongly influences brain development and metabolic programming. In phenylketonuria (PKU), dietary management is essential to prevent neurological impairment and later-life risk of non-communicable diseases (NCDs). This review examines current evidence on PKU from pregnancy through complementary feeding, highlighting the impact of nutritional strategies on neurodevelopmental and metabolic outcomes. Methods: This narrative review, following PRISMA guidelines, used a systematic search of PubMed and Scopus with defined PICO questions. Original research, reviews, and guidelines on PKU nutrition during the first 1000 days were included, emphasizing neurological and metabolic outcomes. Results: Articles addressed prenatal and postnatal factors in PKU. Optimised metabolic control in women with PKU is critical to prevent maternal PKU syndrome, reducing risks of miscarriage, congenital heart defects, microcephaly, and neurocognitive impairment. Pre-conception dietary management, frequent blood Phe monitoring, supplementation with Phe-free protein substitutes (PSs), micronutrients, and emerging pharmacological therapies support maternal and foetal health. Following newborn screening, early dietary treatment in infants with PKU maintains plasma Phe within safe ranges, promoting growth and neurodevelopment. Breastfeeding, combined with Phe-free infant PSs, is feasible, and complementary feeding should be introduced carefully. Frequent monitoring and tailored dietary adjustments, including second-stage PSs, support metabolic control, while data on gut microbiota remain limited. Conclusions: Early multidisciplinary interventions are crucial to optimise metabolic and neurodevelopmental outcomes during this window of opportunity. Further research is needed to address remaining gaps and optimise PKU management across the first 1000 days. Full article

In 2020, 128.5 million new chlamydia infections were reported worldwide in adults aged 15–49 years. Notably, the prevalence of Chlamydia trachomatis infection in pregnant women varies between 2% and 35%, correlating with increased risks of low birth weight, preterm birth, and neonatal death. C. trachomatis is a leading preventable cause of miscarriage. Recurrent first-trimester pregnancy loss can be induced by asymptomatic chlamydia infection through the immune response. In this study, we performed immunohistochemical characterization of the immune response in endometrial tissue biopsies from women diagnosed with chronic endometritis caused by C. trachomatis. Hematoxylin and eosin staining was used for histological evaluation of endometrial biopsies, and immunohistochemical detection was performed for the following markers: CD138, CD45, CD3, CD4, CD8, CD20, CD56, and CD68. As a result, we observed the presence of edematous tissue with hemorrhage; we also observed a heightened inflammatory response with the presence of plasma cells, CD4 and CD8 T lymphocytes, B lymphocytes, NK cells, and macrophages. The findings described here can help better understand the disease and its histopathological diagnosis. Full article

Background/Objectives: Uterine fibroids are the most common benign neoplasms of the female genital tract, with a prevalence of 20% to 40% among women of reproductive age. Their management in the context of Assisted Reproductive Technologies (ART) represents a major clinical challenge, characterized by controversies, contrasting approaches, and a lack of shared guidelines. Indeed, the detrimental effects of fibroid treatments are not well known and may be influenced by the size, location, and number of fibroids. The impact of hysteroscopic myomectomy in women affected by submucosal myomas (FIGO classification type: G0–G2) is well documented in the current literature; however, the impact of intramural and subserosal myoma removal (FIGO types 3–8), in particular those <4/5 cm in diameter, remains controversial. The aim of the present study is to introduce and share a pragmatic surgical approach to uterine fibroid management prior to In Vitro Fertilization (IVF), to reduce the knowledge gap regarding uterine fibroid treatment. Methods: We conducted a retrospective observationally study that included 94 cases of infertile women, who underwent myomectomy at our IVF centre at Sandro Pertini Hospital, Rome, Italy, between 2020 and 2025. These patients met the inclusion criterion of having an idiopathic/tubal factor of infertility and were aged < 40. We evaluated a group of 17 women (group A) who underwent hysteroscopic myomectomy for submucosal fibroids (FIGO types 0–2) and a group of 39 women (group B) who underwent open (laparotomic) myomectomy for intramural/subserosal fibroids (FIGO types 3–8). Group B was compared with a control group of 38 women who were similar in terms of all demographic and clinical parameters and myoma features (group C) and did not want to undergo a myomectomy procedure. All surgical procedures were executed by the same expert surgeon following our proposed model: submucosal fibroids were always removed by operative hysteroscopy, while intramural/subserosal fibroids were removed if there were three or more and if they were at least 1 ≥ 3 cm in size. All enrolled patients subsequently underwent IVF treatment at our centre, which consisted of an antagonist protocol for ovarian stimulation, and all transferred embryos were of good quality according to the recent European Society of Human Reproduction and Embryology (ESHRE) classification. Results: In group A, we observed an implantation rate of 41% and a clinical pregnancy rate of 35.2%, and these results are consistent with the current literature. In group B, we obtained statistically significant differences in the implantation (31% vs. 12.9%) and pregnancy rates (28.1% vs. 7.8%) compared to group C (p = 0.02 and p = 0.03, respectively). In addition, the live birth rate was statistically higher compared to that in group C (p < 0.01). Miscarriage and preterm delivery rates were lower in group B, although the differences were not statistically significant. No severe post-surgical complications, such as uterine rupture, were observed during subsequent pregnancies. Conclusions: Despite the limited patient sample size, the monocentric experience, and the retrospective design, we emphasize the effectiveness of our proposed surgical model in women affected by myomas. Indeed, the surgical treatment of submucosal, intramural, and subserosal lesions may improve ART and pregnancy outcomes (through a higher implantation rate, pregnancy rate, and live birth rate, as well as a lower miscarriage/preterm rate). Full article

Background/Objectives: Vitamin D deficiency has been associated with an increased risk of adverse perinatal outcomes (APOs). This study aimed to examine whether vitamin D deficiency during the first trimester of pregnancy is linked to the development of gestational diabetes mellitus (GDM) in a Mexican population. Methods: A total of 404 pregnant women from the Biochemical and Epigenetic Origin of Overweight and Obesity (OBESO) cohort were included. Maternal vitamin D levels were measured between 11 and 14 weeks of gestation. Vitamin D deficiency was defined as a level below 20.0 ng/mL. The primary goal was to compare APOs between Group 1 (women with vitamin D deficiency) and Group 2 (women without vitamin D deficiency). Adjusted odds ratio (aOR) for APOs—including GDM, preeclampsia, preterm birth, miscarriage, cesarean section, and neonatal size—were calculated, adjusting for pregestational body mass index (BMI) and obesity, with 95% confidence interval (95% CI). Results: Vitamin D deficiency was present in 40.5% of women. Pre-pregnancy BMI and obesity were significantly higher in women with deficiency; other baseline characteristics did not differ between groups. Women with vitamin D deficiency had a higher risk of GDM (aOR 2.04, 95% CI 1.14–3.65, p = 0.01). No association was found between vitamin D deficiency and other APOs. Conclusions: The incidence of vitamin D deficiency in the first trimester was 40.5%. Early pregnancy vitamin D deficiency increases the risk of GDM among Mexican women. These findings highlight the importance of monitoring and supplementing vitamin D during pregnancy to reduce the risk of GDM. Full article

Objective: The aim of this study was to evaluate whether intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated with interferon tau (IFN-τ) before embryo transfer improves implantation and pregnancy outcomes in IVF patients. Methods: This single-center, prospective, randomized, controlled trial was conducted at Nadezhda Women’s Health Hospital (Approval No.: 6/28022023). The study was registered at ClinicalTrials.gov (NCT05775198). Randomization was computer-generated with allocation concealed via sealed envelopes. Participants and statisticians were blinded to group assignment; clinicians were not. Women aged 21–50 undergoing frozen–thawed embryo transfer with euploid embryos were included. Exclusion criteria included uterine anomalies, autoimmune, oncologic conditions, infections, or use of immunosuppressants. Participants (n = 340) were randomized 1:1 to receive either intrauterine infusion of autologous PBMCs activated in vitro with IFN-τ or standard IVF care without PBMC treatment. PBMCs were cultured with recombinant IFN-τ, washed, and infused 24 h prior to single euploid blastocyst transfer. A total of 14 patients were excluded from analysis because of early dropout, leaving 326 (n = 167; n = 159) patients for modified intention-to-treat analysis. Primary outcomes included implantation rate (elevated urinary or blood hCG), clinical pregnancy (fetal heartbeat at 6–8 weeks), and live birth rates. Miscarriage rate and safety were secondary objectives. Patients were followed up until 6 weeks post pregnancy resolution. Results: In the intervention group, 38.3% of patients achieved implantation, compared to 27.7% in the controls (OR 1.6, 95% CI: 1.0–2.6, p = 0.04). Live birth rates were also significantly higher in the IFN-τ-modulated PBMC group (28.7% vs. 17.6%, OR 1.9, 95% CI: 1.1–3.2; p = 0.02). While the clinical pregnancy rate was higher, it did not reach statistical significance (34.7% vs. 25.8%, p = 0.08). There was no difference between the groups in terms of miscarriage (p = 0.4). No serious adverse events were reported after treatment, during pregnancy or in the postnatal period. Conclusions: Intrauterine treatment with IFN-τ-activated PBMCs before ET significantly improves implantation and live birth rates in IVF patients. Full article

Listeria monocytogenes is a foodborne pathogen of significant concern. While it typically causes mild, self-limiting gastroenteritis, it poses a much higher threat to immunocompromised individuals and pregnant women, where it may lead to miscarriage. Numerous outbreaks have been linked to ready-to-eat foods. Although heat treatment is commonly used for microbial decontamination, it is unsuitable for fresh produce such as fruits and vegetables. Other physical (e.g., UV, gamma irradiation) and chemical (e.g., NaOCl, ozone) methods can compromise sensory qualities or face limited consumer acceptance. Photodynamic Inactivation (PDI) has emerged as a promising alternative, particularly when using natural photosensitizers. Because PDI efficacy depends on photosensitizer diffusion, there is a need to further explore how different and complex fruit surface structures may influence its performance. Three fruit models were therefore selected to represent distinct surface textures and were evaluated in situ: apples (smooth), strawberries (irregular), and kiwis (fuzzy and hairy surface). The influence of contamination order was also evaluated, as this factor is highly relevant to real-world supply-chain scenarios but has been largely overlooked in prior research. Additionally, the study investigated how the order of contamination affected the decontamination outcome. Sodium-magnesium-chlorophyllin (Na-Mg-Chl), an approved food additive (E140), was used as photosensitizer. Fruits were cut into 1 cm² squares and inoculated with L. monocytogenes. A 100 µM Na-Mg-Chl solution was applied either before or after bacterial inoculation. All samples were then illuminated using a 395 nm LED (radiant exposure 15 J/cm²). When L. monocytogenes was applied first, followed by the addition of Na-Mg-Chl, a 5.96 log reduction was observed in apples, a 5.71 log reduction in strawberries, and a 6.02 log reduction in kiwis. Conversely, when Na-Mg-Chl was applied prior to bacterial deposition, apples showed a 5.61 log reduction, strawberries demonstrated a 6.34 log reduction, and kiwis achieved the highest inactivation, at 6.74 log units. These results indicate that PDI consistently achieved substantial bacterial reductions across all fruit types, regardless of surface characteristics or application order. This supports PDI as a powerful method for fruit surface decontamination, reducing public health risks and economic losses while preserving product quality and consumer confidence. Full article

Background/Objectives: The establishment of strong prenatal bonding is a key determinant of perinatal well-being, influencing maternal psychological adaptation and infant development. Numerous studies have examined risk factors and psychopathology during pregnancy, but limited research has explored the role of positive psychological constructs, such as positive mental health (PMH). This study aimed to assess whether anxiety mediates the relationship between PMH and the quality of prenatal bonding. Methods: A total of 90 pregnant women participated. PMH was assessed using the Abbreviated Positive Mental Health Questionnaire; anxiety using the Hospital Anxiety and Depression Scale; and prenatal bonding using the Prenatal Assessment Scale for Pregnant Women (EVAP). A simple mediation model was tested, with anxiety as a mediator between PMH (predictor) and prenatal bonding (outcome), controlling the analysis for previous miscarriages, relationship stability, high-risk pregnancy, and employment. Results: The model revealed partial mediation (F = 16.617, p < 0.001). Higher PMH was associated with lower anxiety (B = −0.297, SE = 0.062, p < 0.001) and stronger prenatal bonding (B = 0.777, SE = 0.091, p < 0.001). Interestingly, anxiety emerged as an adaptive response, which could improve maternal sensitivity and communication with the unborn child (B = 0.316, SE = 0.145, p = 0.032). The model explained 56% of the variance in prenatal bonding, even after accounting for relevant covariates. Conclusions: These findings underscore the importance of considering contextual and psychosocial factors when assessing the role of emotions such as anxiety during pregnancy. Rather than being inherently maladaptive, anxiety may play a functional role in facilitating maternal engagement with the baby, especially when grounded in PMH. Given the limited research, our findings support the integration of positive psychology frameworks into perinatal health interventions. Full article

This study investigated the relationship between maternal barium (Ba) exposure and the risk of miscarriage using metabolomics and machine learning. Analyses were performed on samples from 183 pregnant women from Nanjing: the concentration of Ba in whole blood was measured using inductively coupled plasma mass spectrometry (ICP-MS), and untargeted metabolomics was performed on decidual tissue using high-resolution accurate mass spectrometry (UHPLC-QExactive HF-X). A metabolome-wide association study (MWAS) and mediation interaction effect analysis (MITM) identified metabolites and pathways linked to Ba exposure and miscarriage risk. Among 523 detected metabolites, 19 metabolites and 5 pathways were significantly associated with both Ba exposure and miscarriage, particularly glycerophospholipid metabolism. The effect of Ba exposure on miscarriage risk was mediated by five metabolites, with cuminaldehyde showing the highest share of the total mediating effect (54.74%). These metabolites, including N-acetyl-L-methionine, 4-hydroxynonenal, DG(18:0/18:3(9Z,12Z,15Z)/0:0), 10-formyldihydrofolate, and eicosadienoic acid, were used as biomarkers in a predictive model. The XGBoost model achieved an optimal AUC of 0.90 (95%CI: 0.83–0.96). This study suggests that maternal Ba exposure increases miscarriage risk, potentially through disruptions in amino acid metabolism, oxidative stress, and lipid peroxidation, and highlights the potential of metabolite biomarkers for predicting adverse birth outcomes. Full article

Background: With advances in cancer diagnosis and therapy, survival after childhood and young-adult cancers has improved markedly. As survivorship extends, understanding long-term health sequelae, including obstetric outcomes, has become increasingly important. However, the reproductive safety of pregnancy following cancer remains insufficiently characterized. This systematic review and meta-analysis aims to provide a comprehensive evaluation of obstetric outcomes following pregnancy in survivors of childhood and young-adult cancers. Methods: We conducted a systematic review and meta-analysis (PROSPERO: CRD42024573707) of PubMed, Embase, and Cochrane databases to identify controlled studies assessing obstetric complications among female cancer survivors, published between 1 January 2000 and 31 June 2024. Random effects meta-analyses were used to estimate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity, subgroup analyses, and meta-regression were performed to identify sources of variation. Results: Of 6032 records screened, 16 studies involving 89,123 survivors and 21,569,191 controls were included. Cancer survivorship was associated with higher risks of preeclampsia (RR 1.37, 95% CI 1.17–1.62), gestational diabetes (RR 1.29, 95% CI 1.05–1.59), and miscarriage (RR 1.16, 95% CI 1.01–1.35), but not with anemia in pregnancy (RR 1.16, 95% CI 0.98–1.39) or hypertensive disorders (RR 1.21, 95% CI 0.99–1.49). Cancer type emerged as a potential prognostic factor for preeclampsia. Conclusions: Female cancer survivors are at significantly increased risk of major obstetric complications, underscoring the need for anticipatory preconception counselling and enhanced antenatal surveillance. Future research should delineate cancer- and treatment-specific risks to inform precision reproductive care in this growing survivorship population. Full article

Background: Recurrent pregnancy loss (RPL) is a multifactorial condition in which genetic variants associated with thrombophilia may contribute to altered coagulation and adverse pregnancy outcomes. Objective: This study aimed to investigate the association between thrombophilia-related single nucleotide variants (SNVs) and coagulation-related metabolites in a cohort of Mexican women with RPL. Methods: A retrospective and descriptive design was conducted including 105 women with at least two consecutive miscarriages and with a multidisciplinary approach that included a thrombophilia-associated SNVs panel. Peripheral blood samples were collected after fasting for biochemical and molecular analyses. Genotyping of thrombophilia-associated SNVs was performed using real-time PCR with custom-designed TaqMan probes on a Rotor-Gene Q platform, including variants in AGT (rs4762, rs699), F7 (rs6046), FGB (rs1800790), MTR (rs1805087), MTRR (rs1801394), MTHFR (rs1801133, rs1801131), F2 (rs1799963), F5 (rs6025), SERPINE1 (rs1799889), F12 (rs1801020), and F13A1 (rs5985) genes. Coagulation parameters evaluated were folic acid, cobalamin, fibrinogen, D-dimer, homocysteine, antithrombin III activity, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and Factor XII activity. Results: Significant differences were found in INR values across F7-rs6046 genotypes (p = 0.006), with an additive model showing a mean difference of 0.05 (p = 0.0009). The F12-rs1801020 variant was strongly associated with Factor XII activity (p = 0.002) and aPTT (p = 0.045). Conclusions: These findings indicate that F7-rs6046 and F12-rs1801020 genotypes influence specific coagulation parameters, suggesting that certain thrombophilia-associated SNVs may modulate the hemostatic profile in Mexican women with RPL and contribute to personalized risk assessment in reproductive medicine. Full article