Search Results (90)

Background/Objectives: Laser-assisted zona pellucida (ZP) drilling on day 4 embryos is routinely performed in IVF laboratories to facilitate trophectoderm (TE) herniation for blastocyst biopsy. Nevertheless, inner cell mass (ICM) herniation through the initial ZP opening occasionally occurs and may interfere with standard TE biopsy. Methods: This retrospective study assessed the clinical and obstetric safety of a double ZP drilling strategy for TE biopsy in preimplantation genetic testing for aneuploidy (PGT-A) cycles. A total of 560 single euploid embryo transfer cycles were analyzed. Blastocysts were categorized (Groups 1–6) based on ICM/TE herniation patterns and the corresponding biopsy approach. Clinical outcomes were compared between cycles undergoing TE biopsy through a single ZP opening (TE hatching with ICM remaining within the ZP) and cycles requiring a second opening to relocate the biopsy site when the ICM herniated through the original opening or was positioned externally. Results: The single-opening approach of Group 1 accounted for 295 cycles (52.7%), with implantation, miscarriage, and live birth rates of 65.4%, 14.0%, and 56.3%, respectively. The double-opening approach of Group 3 was applied in 21 cycles (3.8%), yielding implantation, miscarriage, and live birth rates of 66.7%, 0%, and 66.7%, respectively. No significant differences were observed between the two strategies in implantation, miscarriage, or live birth rates. Obstetric and neonatal outcomes, including gestational age, birth weight, and monozygotic twinning incidence, were comparable. Fifteen healthy infants were delivered following TE biopsy using the double-opening strategy. Conclusions: These data support incorporating ICM position into TE biopsy decision-making and suggest that creating a second ZP opening to reposition the biopsy site is clinically feasible and does not compromise reproductive or obstetric outcomes in PGT-A cycles. Full article

Background/Objectives: Pregnancy loss is a common and multifactorial complication of human reproduction, traditionally attributed to fetal chromosomal abnormalities, maternal anatomical and endocrine disorders, and immune dysfunction. Growing evidence now indicates that the maternal microbiome, particularly within the reproductive tract, plays a critical role in implantation, placental development, and the maintenance of immune tolerance during early pregnancy. Importantly, the influence of the microbiome on miscarriage appears to be strongly modulated by host genetic background and immune regulation. Methods: This narrative review summarizes current evidence linking alterations in the vaginal, endometrial, placental, and gut microbiomes to miscarriage, with a specific focus on host genetics and immune–microbial interactions. Results: We discuss how genetic variation in innate and adaptive immune pathways, inflammatory signaling, and mucosal barrier function may shape host responses to microbial communities, thereby influencing susceptibility to PL. In addition, we highlight emerging data on microbiome-driven regulation of gene expression and epigenetic modifications in the endometrium and decidua, emphasizing the role of microbial metabolites in immune tolerance and placental function. Conclusions: By integrating findings from microbiome research, host genomics, immunology, and epigenetics, this review proposes a framework in which miscarriage is viewed as a consequence of disrupted host–microbe crosstalk rather than isolated pathology. Finally, we address key methodological challenges and outline future research directions aimed at advancing mechanistic understanding and translational applications. Full article

Background and Objectives: Aneuploidy is the leading cause of implantation failure and miscarriage, with prevalence increasing with maternal age. Embryos classified as chaotic, characterized by the presence of five or more chromosomal abnormalities, and those with complex aneuploidies, defined by two to four abnormalities, represent a controversial category in preimplantation genetic testing for aneuploidy (PGT-A), as the potential for misclassification remains a significant concern. Materials and Methods: We performed a retrospective study at the Calla IVF Center, Oradea, analyzing 230 blastocysts grouped by maternal age (25–30, 31–35, 36–40, and 41–50 years). A trophoblast biopsy was performed on days 5–7, and the samples were analyzed by next-generation sequencing (NGS). Embryos were classified as euploid, aneuploid, mosaic, or chaotic. The 19 embryos initially diagnosed as chaotic were thawed and subjected to re-biopsy. Statistical analysis included descriptive statistics (chi-square tests and ANOVA) and multivariable regression models, with p < 0.05 as the criterion for statistical significance. Results: Aneuploidy increased with maternal age, from 29.6% in women aged 25–30 years to 68.7% in those aged 41–50 (p = 0.002). Poor-quality blastocysts exhibited higher aneuploidy rates (72.4%) than good-quality embryos (34.6%; p = 0.004). Chaotic embryos comprised 8.3% of the cohort. Upon re-biopsy, none were confirmed as euploid; all remained abnormal and were reassigned to aneuploid, mosaic, or persistently chaotic categories. This finding suggests that apparent euploid results reported elsewhere may reflect technical variability and sampling limitations in PGT-A rather than accurate chromosomal normalization. Conclusions: The prevalence of aneuploid embryos showed a progressive increase with advancing maternal age. Chaotic embryos are heterogeneous, and re-biopsy may help refine the interpretation of complex PGT-A profiles, supporting its role as a diagnostic and quality control tool rather than a strategy to identify euploid embryos. Our study offers novel insights through age-stratified analysis, the integration of morphology with genetics in a Romanian IVF cohort, and a detailed evaluation of chaotic embryos, providing clinical recommendations for patient counseling and embryo selection. 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

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

Aim: This study aimed to characterize and compare the composition of central (TCM), effector (TEM), tissue-resident (TRM), and terminally differentiated (TEMRA) memory T cells in mid-luteal endometrium during the window of implantation (WOI) in women with and without a previous miscarriage. Methods: Stromal lymphocytes from endometrial samples (P + 5) were analyzed by multicolor flow cytometry to quantify total, CD4⁺ and CD8⁺ TCM (CD45RA⁻CCR7⁺), TEM (CD45RA⁻CCR7⁻), TRM (CD69⁺), and TEMRA (CD45RA⁺CCR7⁻) subsets. Participants were grouped as having no previous miscarriage (n = 38) or ≥1 previous miscarriage (n = 33), and the relative distribution of these memory subsets was compared between groups. Correlations, PCA and logistic regression were used to assess global memory network organization. Results: Women with prior miscarriage exhibited higher TCM proportions among total and CD8⁺ lymphocytes (p < 0.01), alongside lower CD8⁺ TEM (p = 0.02) and higher CD4⁺ TEM (p = 0.01). TRM showed a mild, non-significant increase (p = 0.18), while TEMRA remained stable. TRM correlated positively with both TCM (r = 0.51) and CD4⁺ TEM (r = 0.40), indicating coordinated organization among memory subsets. Multivariate analyses (PCA and logistic regression) confirmed these trends and identified the TCM/TEM ratio as the most discriminative parameter. Conclusions: Endometrial memory T-cell composition during the WOI differs in women with miscarriage history, characterized by central memory expansion and reduced effector memory proportions, with parallel increases in tissue-resident cells. These changes suggest persistent remodeling of the local immune memory network toward a long-lived, less differentiated phenotype that may influence implantation readiness in subsequent cycles. Full article

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

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

Background: Homocysteine (Hcy) plays a pivotal role in human reproduction, influencing gamete quality, embryo development, implantation, and pregnancy outcomes. It is central to folate and methionine metabolism and supports methylation-dependent epigenetic processes. Hyperhomocysteinemia (HHcy) exerts diverse biological effects and is associated with reproductive impairments in both sexes, affecting both spontaneous fertility and the outcome of assisted reproduction, including In Vitro Fertilization (IVF). Although the mechanisms of HHcy toxicity in reproduction are not fully understood, significant progress has been made in elucidating its effects. The emerging picture is complex, as Hcy and its metabolites impact biomolecules and cellular processes in a tissue- and sex-specific manner. Results: In men, HHcy compromises sperm deoxyribonucleic acid (DNA) integrity, methylation, and testicular microcirculation, reducing fertility potential. In women, HHcy disrupts follicular growth, oocyte competence, embryo quality, and endometrial receptivity, increasing the risk of implantation failure, miscarriage, and pregnancy complications. In assisted reproduction, HHcy and 5,10-methylenetetrahydrofolate reductase (MTHFR) variants may lower oocyte yield and embryo quality, although folate and B-vitamin supplementation can mitigate these effects. Conclusions: These effects largely reflect oxidative, inflammatory, vascular and epigenetic mechanisms, highlighting Hcy as a modifiable factor for improving natural fertility, optimizing IVF outcomes, and supporting healthy offspring development. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article

Preimplantation genetic testing (PGT) reports play a decisive role in determining the fate of IVF-generated embryos. The identification of a chromosomal or genetic abnormality that could impact the health of the resulting newborn often leads to embryo disposal or indefinite storage in cryogenic containers. As a growing proportion of IVF cycles include PGT assessment, greater scrutiny is being placed on its clinical validity. Initially developed to detect monogenic disorders (PGT-M) and later expanded to identify full chromosomal aneuploidies, PGT is primarily used to identify embryos unlikely to implant (aneuploid), those that would lead to miscarriage, or those causing chromosomal syndromes or monogenic conditions. Advancements in genetic analysis now allow for the assessment of more complex traits and chromosomal features from a trophectoderm biopsy, including segmental aneuploidies, chromosomal mosaicism, and polygenic conditions. However, as technology pushes the limits of biological resolution, questions arise regarding the accuracy, clinical utility, and representativeness of these findings for the entire embryo. This article reviews the gold standards for validating clinical findings and reporting strategies, aiming to maximize diagnostic utility while minimizing false positives towards appropriately defined reproductive outcomes and phenotypes. 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

Background/Objectives: The management of patients with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) is a real challenge. Studying endometrial proliferation and vascularization by ultrasound during the embryo implantation window is an option for investigating these failures. This approach involves measuring the endometrial volume, the uterine arteries pulsatility index (PI), and the sub-endometrial flow index (VFI). Methods: The aim of our single-center retrospective study was to evaluate the benefit of treatment with pentoxifylline (400 mg twice daily) and alpha-tocopherol (500 IU twice daily), which was administered for at least 3 months. This study included 52 patients presenting abnormal ultrasound criteria, i.e., endometrial volume less than 2 cm³ and/or PI greater than 2.8 and/or VFI less than 0.25. Results: After treatment, we observed a significant increase in endometrial volume of 0.32 cm³ (p = 0.0054), as well as a significant increase in VFI of 0.49 (p = 0.041) in comparison to the control group. After treatment, the PI of the right uterine artery decreased significantly by 0.25 (p = 0.029) and the PI of the left uterine artery decreased by 0.27, but not significantly. In addition, our study showed that the clinical pregnancy rate (CPR) was more improved in the treated group compared to controls. Conclusions: Our study showed a promising benefit of pentoxifylline and alpha-tocopherol on endometrial properties; this needs to be corroborated by a larger prospective study. Full article

Background/Objectives: GnRH agonists may offer potential benefits when used for luteal phase support in assisted reproductive treatments. This systematic review and meta-analysis of randomized controlled trials evaluates the effect of a single-dose administration of gonadotropin-releasing hormone (GnRH) agonist on the day of frozen-thawed embryo transfer (FET) in artificial cycles, in terms of reproductive outcomes. Methods: A comprehensive literature search was performed using the PubMed and Cochrane databases to identify relevant studies. The outcomes assessed were live birth rate, clinical pregnancy rate, positive pregnancy test, implantation rate, and miscarriage rate. Three randomized controlled trials were included in the analysis. Results: The clinical pregnancy rate (56.5% vs. 47.4%; OR 1.27; 95% CI: 1.01–1.60; p = 0.0426) and live birth rate (34.3% vs. 23.9%; OR 1.71; 95% CI: 1.00–2.91; p = 0.0483) were significantly higher in the treatment group compared to the control group. No statistically significant differences were observed between the groups in terms of positive pregnancy test, implantation rate, or miscarriage rate, although the analysis revealed a trend toward improved outcomes in the intervention group. Conclusions: In summary, although our meta-analysis indicates that a single dose of GnRH agonist in artificial FET cycles may be associated with improved clinical pregnancy and live birth rates, these findings are based on a limited number of available trials. Larger, well-designed randomized controlled trials are urgently needed before any changes to clinical recommendations can be justified. Full article

Uncontrolled and excessive inflammation could negatively impact embryo implantation, potentially leading to implantation failure or miscarriage. Small extracellular vesicles (sEVs) secreted by extravillous trophoblasts (EVTs) play a significant role in mediating the homeostasis at the maternal–fetal interface. In the present work we assessed the role of EVT-derived sEVs in the protection of the human blastocyst’s integrity and function in a microenvironment with excessive Th1-induced inflammation using the Sw71 blastocyst-like surrogate (Sw71 BLS) as a model of implanting a human embryo. Conditioned media from primary trophoblast-derived EVT cells were used as the source for sEVs’ isolation by precipitation. sEVs were characterized by TEM, IEM, and protein content. To simulate Th1-induced inflammation, we performed TCR stimulation and polyclonal activation of isolated T cells, which preferentially led to Th1 cytokine production. The use of the Sw71 spheroid model allowed us to monitor directly the damaging effect of high levels of Th1 cytokines on the ability of trophoblast cells to self-organize and migrate. The addition of EVT-sEVs unlocked the absolute migration capacity of the trophoblast cells in a healthy microenvironment. However, EVT-sEV treatment could not counteract the adverse effects of excessive Th1-mediated inflammation. This study provides a platform for further elucidation of the EVT-sEV dosage and potency for trophoblast functional recovery. Full article