Search Results (68)

Background: Infertility is a multifactorial condition that causes significant emotional distress and financial burden for couples. Despite advances in assisted reproductive technologies (ARTs), many patients experience recurrent implantation failure (RIF) or pregnancy loss. Intralipid, an intravenous lipid emulsion, has been proposed as an adjunctive therapy due to its immune-modulatory effects, particularly in reducing elevated natural killer (NK) cell activity, which may be associated with poor reproductive outcomes. This study evaluated the effect of intralipid infusion on pregnancy rates and miscarriage rates in women with recurrent implantation failure undergoing in vitro fertilization (IVF). Materials and Methods: This was a retrospective study of women who had suffered from recurrent implantation failure and underwent IVF between September 2023 and September 2024. A comparative group undergoing IVF but who did not have recurrent implantation failure matched for age was selected. Outcomes of clinical pregnancy, miscarriage and livebirth rates were compared in both groups. Results: A total of 113 women undergoing IVF were identified and 51 received intralipid. Intralipid was initiated at varying stages of the IVF process, a day before embryo transfer (ET) (18 or 35.3%), on the day of ET (20 or 39.2%) and after ET (13 or 25.5%). The clinical pregnancy rate was 44.2% in the treatment group compared to 29% in the comparator group (p < 0.05) while the miscarriage rates were 13.7% versus 11.3% (p > 0.05). Elevated NK cells were present in 65.4% of the patients who received intralipid, but the correlation between NK cell levels and pregnancy outcomes was weak (Spearman ρ = 0.032). No adverse effects were reported in any of the women. Conclusions: Intralipid infusion increased the successful pregnancy rates in women who had recurrent implantation failure during IVF. The successful pregnancy rate was significantly higher than that in those undergoing ART who had not suffered from RIF. These findings support several studies on the potential benefit and safety of intralipids in women undergoing ART, but the numbers remain small and more prospective studies are needed to confirm these findings Full article

Embryo implantation requires a finely tuned immune balance at the maternal–fetal interface. Interferon tau (IFN-τ), a key immunomodulator in ruminant implantation, may have therapeutic potential in human reproduction. This study investigated its effects on peripheral blood mononuclear cells (PBMCs) in vitro and the subsequent impact on endometrial immune composition following intrauterine administration of these cells. The work was conducted in two stages. First, in vitro assays were performed with PBMCs from 20 patients with recurrent implantation failure (RIF) cultured with or without IFN-τ for 24 h. Cytokines (IL-10, IL-4, TNF-α, IL-6) were measured by ELISA, and T cell subsets (Th, cytT, Th1, Th2, Th9, Tfh, Th17, Treg) were analyzed by flow cytometry. IFN-τ increased IL-4 and reduced TNF-α and IL-6, indicating a Th2 profile shift. T-cell analysis revealed fewer cytT, Th1, Th9, and Th17 cells, more Th2 cells, and improved Th/Tk, Th1/Th2, and Th17/Treg ratios after IFN-τ. A second clinical study included 55 RIF patients who received intrauterine IFN-τ-modulated PBMCs. Post-treatment endometrial biopsies revealed more helper T cells and macrophages, with higher Th/total T, Th/cytT, and Th/macrophage ratios, suggesting a tolerogenic environment. Overall, IFN-τ modulates PBMCs in vitro and promotes a favorable endometrial immune profile in vivo, highlighting its potential as an immunotherapy in assisted reproduction. Full article

The immunological factor of sterility, specifically the abnormal count and activity of uterine NK (uNK) cells, may represent one of the potential contributors affecting specific subgroups of sterile couples undergoing assisted reproductive treatment (ART). Therefore, the primary purpose of the present paper was to assess uNK cell count. A total of 387 endometrial biopsies from patients with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) were analyzed to identify abnormalities in uNK cell count, using immunohistopathological evaluation. ANOVA analysis revealed a strong association with factor 0.161 with p-value < 0.01, indicating that higher uNK cell count is associated with the presence of clusters (multicellular aggregates of uNK cells). These results suggest that the formation of clusters and the spatial distribution of uNK cells are significant factors in the context of the aforementioned clinical questions. However, the actual translational potential to clinical practice has not yet been established due to several challenges, namely: 1. the constantly changing definitions and diagnostic criteria for RIF and RPL, 2. varying sampling approaches for uNK cells, and 3. the historical lack of clear differentiation between uterine and peripheral NK cells. When all these issues are resolved, the observed tendency of uNK cells to form clusters will need to be a central focus of future investigations addressing RIF and RPL, thus improving ART outcomes. Full article

Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, it is limited by its invasiveness, potential for embryo damage, and diagnostic errors due to mosaicism. Rationale/Objectives: This review critically evaluates the emerging role of noninvasive PGT (niPGT). NiPGT analyzes cell-free DNA from spent blastocyst culture media, thus, it is a potential alternative for managing RPL and RIF. Hence, the primary objective is to determine whether current evidence supports niPGT as a reliable replacement for conventional biopsy-based PGT-A in these high-risk populations. Outcomes: The analysis reveals that niPGT offers significant theoretical advantages. These include complete non-invasiveness, enhanced embryo preservation, and high patient acceptability. However, its clinical application is hampered by substantial limitations. Key amongst them is the inconsistent and often suboptimal diagnostic accuracy (sensitivity 70–85%, specificity 88–92%) compared to biopsy. Other significant factors include the high rates of amplification failure (10–50%), vulnerability to maternal DNA contamination, as well as low DNA yield. Crucially, there is a definitive lack of robust, prospective randomized controlled trial (RCT) data demonstrating improved live birth rates or reduced miscarriage rates specifically in RPL and RIF cohorts. As such, niPGT is not yet ready to be a standalone clinical adoption in RPL and RIF cases. However, it may serve as a valuable adjunct for rescue scenarios following biopsy failure or for ethical reasons. Wider Implications: The integration of niPGT with artificial intelligence, time-lapse imaging, and multi-omics profiling underlies a promising future. However, its transition from a predominantly research tool to a clinical standard necessitates various critical undertakings. These include rigorous multicenter RCTs, standardizing international protocol, and tailoring validation for the RPL and RIF subgroups. This review highlights the need for cautious optimism, positing that evidence-based integration, rather than premature adoption, is essential to realizing niPGT’s full potential without compromising patient care in these complex fertility scenarios. Full article

Infertility remains a major global health concern, with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and impaired endometrial receptivity representing key contributors to poor assisted reproductive technology (ART) outcomes. Platelet-rich plasma (PRP), an autologous blood-derived concentrate enriched with growth factors and cytokines, has emerged as a promising regenerative therapy with angiogenic, anti-apoptotic, and proliferative properties. In reproductive medicine, intraovarian PRP has been evaluated for its potential to restore ovarian function in women with DOR and POI, improve oocyte competence and embryo euploidy, and promote ovulation in PCOS. Similarly, intrauterine PRP infusion or subendometrial zone injections has shown encouraging results in women with recurrent implantation failure and thin endometrium, enhancing endometrial thickness, receptivity, and implantation potential. Evidence from preclinical animal models and early clinical studies suggests multi-level mechanisms of action, including modulation of endocrine pathways, reduction in oxidative stress, activation of dormant follicles, and improvement of endometrial angiogenesis and receptivity. Despite these promising findings, results remain inconsistent due to heterogeneity in PRP preparation protocols, administration routes, timing, and study designs. Even though robust randomized controlled trials with standardized methodologies are needed to determine the efficacy and long-term reproductive outcomes of PRP in infertility treatment and anovulation in PCOS, PRP represents a novel and potentially transformative adjunct in reproductive endocrinology. Full article

Couple infertility is a multifactorial condition that involves, among other factors, immunological alterations of the endometrium. CD138⁺ plasma cells and uterine Natural Killer (NK) cells have been associated with implantation failures and recurrent pregnancy loss, although the literature presents considerable heterogeneity in findings. This narrative review aims to synthesize current evidence on the role of these two immunological biomarkers in the pathophysiology of infertility. According to the current literature, the presence of CD138⁺ plasma cells was strongly associated with chronic endometritis and adverse reproductive outcomes, with improvement following targeted antibiotic therapy. NK cells, particularly in their hyperactive peripheral form, were elevated in infertile women, although data on uterine NK cells remain controversial. Recent studies suggest a possible interaction between chronic inflammation and NK dysfunction. A combined evaluation of CD138⁺ and NK cells may represent an integrated diagnostic approach in idiopathic infertility. Prospective studies are needed to standardize cut-off values and validate these markers in clinical practice. Full article

Objectives: The aim of this study is to demonstrate the efficacy of the modified technique of radical organ-preserving surgery of invasive cervical cancer (CC) in patients of reproductive age. Methods: This study included 118 patients of reproductive age (34.9 ± 4.8 years) with a morphologically verified diagnosis of invasive CC (T1a-1bNxM0). All patients underwent organ-preserving surgery in the scope of radical trachelectomy. A shape memory mesh implant woven in the form of a stocking from superelastic nickelide titanium thread with subsequent fixation with separate sutures around the perimeter was used to form the uterine closure apparatus and to strengthen the utero-vaginal anastomosis. The mesh implant was made of superelastic thin nickelide titanium threads with a diameter of 60–40 microns on a metal knitting machine. All patients were prospectively followed up for a mean of 120 months. Results: No intraoperative or postoperative complications were revealed when using a shape memory implant made of titanium nickelide during radical trachelectomy to form a locking apparatus and strengthen the anastomosis zone. No cervical stenoses or mesh failures were noted in any case. The 5-year overall and recurrence-free survival rates were 100% and 98%, respectively. Two patients indicated recurrence; it occurred in 3 and 36 months. There were 42 spontaneous pregnancies, and 29 resulted in full-term delivery, whereas 2 and 11 ended in miscarriage and early abortion, respectively. Currently, 18 patients are at different stages of the use of assisted reproductive technologies. Conclusions: The shape memory implant made of titanium nickelide integrates well into the surrounding tissues and successfully imitates the effect of the cervix. The use of this sparing-surgery technique has shown reasonably good results in carrying the pregnancy to term and good reproductive outcomes. Full article

Understanding the molecular basis of endometrial receptivity is crucial for improving implantation outcomes in assisted reproduction, especially for patients with recurrent implantation failure (RIF). This study investigates the timing relationship between microRNA (miRNA) and messenger RNA (mRNA) profiles in the endometrium using simultaneously the endometrial receptivity array (ERA) and the microRNA receptivity assay (MIRA) in 100 RIF patients undergoing euploid blastocyst transfer. The concordance rate between ERA and MIRA was 72% (Kappa = 0.50), suggesting partial overlap in profiling. Patients were stratified by the timing sequence of miRNA relative to mRNA into Fast, Equal, and Slow groups. Those with delayed miRNA expression (Slow group) had significantly lower pregnancy rates (54.5%) than those with synchronous or leading miRNA expression (81.9% and 94.1%, respectively; p = 0.031). Moreover, the Slow group exhibited higher prior implantation failure counts and altered expression in 15 miRNAs, many involved in aging-related pathways. These findings highlight that asynchronous miRNA–mRNA profiles may reflect impaired receptivity and suggest that miRNA-based staging adds valuable diagnostic insight beyond mRNA profiling alone. Dual assessment of mRNA and miRNA profiles may offer additional diagnostic insight into endometrial receptivity but requires further validation before clinical application. Full article

Immunological factors have gained growing recognition as key contributors to recurrent pregnancy loss (RPL) after in vitro fertilization (IVF), representing a major challenge in reproductive medicine. RPL affects approximately 1–2% of women trying to conceive naturally and up to 10–15% of those undergoing IVF, where overall success rates remain around 30–40% per cycle. An imbalance in maternal immunological tolerance toward the semi-allogeneic fetus during pregnancy may lead to miscarriage and implantation failure. IVF-related ovarian stimulation and embryo modification offer additional immunological complications that can exacerbate existing immune dysregulation. Recent advances in reproductive immunology have significantly deepened our understanding of the immune mechanisms underlying RPL following IVF, particularly highlighting the roles of regulatory T cells (T regs), natural killer cells, cytokine dysregulation, and disruptions in maternal–fetal immune tolerance. In order to better customize therapies, this evaluation incorporates recently discovered immunological biomarkers and groups patients according to unique immune profiles. Beyond conventional treatments like intralipid therapy and intravenous immunoglobulin, it also examines new immunomodulatory medications that target certain immune pathways, such as precision immunotherapies and novel cytokine modulators. We also discuss the debates over immunological diagnostics and therapies, such as intralipid therapy, intravenous immunoglobulin, corticosteroids, and anticoagulants. The heterogeneity of patient immune profiles combined with a lack of strong evidence highlights the imperative for precision medicine to improve therapeutic consistency. Novel indicators for tailored immunotherapy and emerging treatments that target particular immune pathways have encouraging opportunities to increase pregnancy success rates. Improving management approaches requires that future research prioritize large-scale clinical trials and the development of standardized immunological assessments. This review addresses the immunological factors in RPL during IVF, emphasizing underlying mechanisms, ongoing controversies, and novel therapeutic approaches to inform researchers and clinicians. Full article

Background: Recurrent implantation failure (RIF) poses a major challenge in assisted reproductive technologies, with thin endometrium (≤7 mm) being a frequently observed yet poorly understood condition. Emerging evidence implicates nuclear factor-kappa B (NF-κB), a key transcription factor in inflammatory signaling, in impaired endometrial receptivity. However, its clinical relevance and prognostic value for live birth outcomes still need to be fully elucidated. Objective: We aim to evaluate the expression levels of endometrial NF-κB in patients with RIF and thin endometrium and to determine its potential as a predictive biomarker for live birth outcomes following IVF treatment. Methods: In this prospective case–control study, 158 women were categorized into three groups: Group 1 (RIF with thin endometrium, ≤7 mm, n = 52), Group 2 (RIF with normal endometrium, >7 mm, n = 38), and fertile controls (n = 68). NF-κB levels were assessed using ELISA and immunohistochemical histoscore. Pregnancy outcomes were compared across groups. ROC analysis and multivariable logistic regression were performed to assess the predictive value of NF-κB. Results: NF-κB expression was significantly elevated in Group 1 compared to Group 2 and controls (p = 0.0017). ROC analysis identified a cut-off value of 7.8 ng/mg for live birth prediction (AUC = 0.72, sensitivity 74%, specificity 75%). Multivariable analysis confirmed NF-κB is an independent predictor of live birth (p = 0.045). Histological findings revealed increased NF-κB staining in luminal and glandular epithelial cells in the thin endometrium group. Conclusions: Increased endometrial NF-κB expression is associated with thin endometrium and reduced live birth rates in RIF patients. NF-κB may serve not only as a biomarker of pathological inflammation but also as a prognostic tool for treatment stratification in IVF. Based on findings in the literature, the therapeutic targeting of NF-κB may represent a promising strategy to improve implantation outcomes. Full article

Nitric oxide (NO) predominantly regulates endometrial receptivity, angiogenesis, immunological tolerance, and trophoblast invasion throughout the implantation period. Both insufficient and excessive nitric oxide production have been linked to suboptimal embryo implantation and infertility. The primary enzymatic source of uterine nitric oxide, along with hormonal, metabolic, and immunological variables and genetic variations in the endothelial nitric oxide synthase gene (NOS3), affects endothelial nitric oxide synthase (eNOS). Despite its considerable importance, there is limited knowledge regarding the practical implementation of nitric oxide-related diagnoses and therapies in reproductive medicine. A comprehensive assessment was performed in accordance with the PRISMA principles. Electronic searches were carried out in PubMed, Scopus, and Embase, and we analyzed the literature published from 2000 to 2024 regarding the association between NO, its metabolites (NO₂⁻ and NO₃⁻), eNOS expression, NOS3 gene variants, and reproductive outcomes. Relevant studies encompassed clinical trials, observational studies, and experimental research using either human or animal subjects. We collected data about therapeutic interventions, hormonal and immunological associations, nitric oxide measurement techniques, and in vitro fertilization success rates. A total of thirty-four studies were included. Dysregulated nitric oxide signaling, characterized by modified eNOS expression, oxidative stress, or NOS3 polymorphisms (e.g., Glu298Asp and intron 4 VNTR), was linked to diminished endometrial receptivity and an elevated risk of implantation failure and miscarriage. The dynamics of local uterine NO are essential as elevated and diminished systemic levels of NO₂⁻/NO₃⁻ corresponded with enhanced and decreased implantation rates, respectively. Among many therapeutic approaches, targeted hormone treatments, antioxidant therapy, and dietary nitrate supplements have demonstrated potential in restoring nitric oxide balance and enhancing reproductive outcomes. In animal models, the modification of nitric oxide significantly impacted decidualization, angiogenesis, and embryo viability. Nitric oxide is a multifaceted molecular mediator with considerable ramifications for successful implantation. Its therapeutic and diagnostic efficacy increases with its sensitivity to environmental, hormonal, and genetic alterations. Integrating targeted nitric oxide modulation, oxidative stress assessment, and NOS3 genotyping with personalized reproductive therapy will enhance endometrial receptivity and improve IVF outcomes. Future translational research should incorporate nitric oxide signaling into personalized treatment protocols for patients with unexplained infertility or recurrent implantation failure. Full article

Dysbiosis, or an altered microbiota composition, has been implicated in chronic endometrial inflammation and recurrent implantation failure. Despite growing research on the relationship between the genital microbiome and reproductive health, few studies have examined its role in ectopic pregnancy. Therefore, our study focuses on the microbiota of the cervical canal in women diagnosed with an ectopic pregnancy. Material and methods: The study group consisted of nine women of a reproductive age who were hospitalized at the Department of Maternal and Child Health, Gynecology and Obstetrics, Clinical Hospital of the University of Poznań, between February and September 2023. In nine patients, an ectopic pregnancy was diagnosed based on a transvaginal ultrasound examination. The swabs were collected for quantitative microbiological culture (using Amies transport medium). The microbiological analyses involved quantitative culture on selected selective and differential media, following the Standard Operating Procedure developed by the Institute of Microecology. Results: A reduced Lactobacillus spp. count (≤5 × 10⁷ CFU/mL) was observed in 78% of the patients participating in the study, including those that produce H₂O₂, i.e., with strong protective properties for the environment of the female reproductive tract. The molecular analyses revealed Ureaplasma spp. (U. parvum and U. urealyticum) in 33% of the samples (three patients). However, Chlamydia trachomatis and Mycoplasma genitalium were not detected in any of the analyzed samples. Conclusions: The ease of obtaining material and the minimally invasive nature of lower reproductive tract examinations may allow for the evaluation of microbiota imbalances, helping to identify individuals at an increased risk of reproductive complications. Full article

Chronic endometritis (CE) is a persistent, often asymptomatic inflammatory condition of the endometrium, increasingly recognized as a potential contributor to infertility and recurrent implantation failure. Despite its clinical significance, CE remains underdiagnosed due to a lack of standardized diagnostic criteria and its subtle clinical presentation. Objective: This review aims to synthesize the current evidence on the pathophysiology, diagnosis, and treatment of CE, highlighting its impact on reproductive outcomes and the effectiveness of therapeutic interventions. A comprehensive literature review was conducted, analyzing 85 peer-reviewed studies published in the last decade, of which 65 were deemed relevant and retained for further analysis. These studies were selected based on their relevance to the pathophysiology, diagnostic methodologies, and treatment outcomes for CE, focusing on their implications for fertility and assisted reproductive technologies (ARTs). The findings suggest that CE is associated with impaired endometrial receptivity, increased inflammatory markers, and reduced implantation and pregnancy rates with ARTs. Histopathological assessment using CD138 immunostaining remains the gold standard for diagnosis, while hysteroscopy and molecular microbiological techniques provide complementary diagnostic value. Antibiotic treatment has been shown to significantly improve implantation rates and pregnancy outcomes, particularly in women with recurrent implantation failure. Emerging therapies, including probiotics and regenerative medicine approaches, are being explored as potential adjuncts to the conventional treatment. Early and accurate diagnosis of CE is essential for optimizing reproductive outcomes. Standardized diagnostic protocols and individualized treatment strategies are crucial for improving implantation success and pregnancy rates in affected women. Future research should focus on refining the diagnostic methods and exploring novel therapeutic options to enhance endometrial health and fertility outcomes. Full article

Background: Endometrial receptivity is crucial for successful embryo implantation in assisted reproductive technologies (ARTs). MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as important post-transcriptional regulators of endometrial function, although their diagnostic and molecular functions are poorly understood. Methods: A systematic review was conducted following PRISMA 2020 principles and registered in PROSPERO (CRD420251001811). We looked at 28 peer-reviewed publications published between 2010 and 2025 that used endometrial tissue, blood, uterine fluid, saliva, and embryo culture medium to study miRNAs and other non-coding RNAs in endometrial receptivity, recurrent implantation failure (RIF), and infertility. Results: MiRNAs like miR-145, miR-30d, miR-223-3p, and miR-125b influence implantation-related pathways such as HOXA10, LIF-STAT3, PI3K-Akt, and Wnt/β-catenin. Dysregulated expression profiles were linked to inadequate decidualization, immunological imbalance, and poor angiogenesis. CeRNA networks that include lncRNAs (e.g., H19 and NEAT1) and circRNAs (e.g., circ_0038383) further regulate miRNA activity. Non-invasive biomarkers derived from plasma, uterine fluid, and embryo media showed high prediction accuracy for implantation outcomes. Conclusions: MiRNA signatures offer a functional and diagnostic blueprint for endometrial receptivity. This systematic review provides a timely and thorough synthesis of the existing literature, with the goal of bridging the gap between molecular discoveries and therapeutic applications. By emphasizing both the mechanistic importance and diagnostic value of certain miRNA signatures, it paves the way for future precision-based techniques in embryo transfer and endometrial assessment in ART. Full article

Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut–endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites—including short-chain fatty acids, bile acids, and tryptophan catabolites—in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host–microbiota interactions in female fertility. Full article