Recurrent implantation failure (RIF) remains a major challenge in assisted reproductive technology (ART), reflecting multifactorial and incompletely understood etiologies. Although embryonic competence is widely regarded as the primary determinant of implantation success, increasing attention has been directed toward endometrial and immunological factors that may contribute to repeated failure in selected patient populations. Among proposed immunomodulatory interventions, intravenous lipid emulsions (intralipids) have been investigated as a strategy to modulate uterine immune responses, particularly natural killer (NK) cell activity, in women undergoing in vitro fertilization (IVF). The biological rationale for intralipid therapy derives from observations that uterine NK (uNK) cells play essential roles in early placentation, including regulation of angiogenesis, trophoblast invasion, and cytokine balance. However, the clinical significance of altered NK cell numbers or function in RIF remains debated, and evidence linking immune modulation to improved live birth rates is inconsistent. Variability across studies is further compounded by heterogeneity in diagnostic criteria, immune testing methodologies, and treatment protocols. This narrative review aims to critically evaluate the available mechanistic and clinical evidence regarding intravenous intralipid infusion in IVF patients, with emphasis on recurrent implantation failure. We examine proposed mechanisms of action, summarize randomized controlled trials and meta-analyses, assess methodological limitations, and consider current professional society recommendations. Although some reports describe improvements in clinical pregnancy rates, conflicting findings and the absence of large, adequately powered trials preclude definitive conclusions. Current guidelines do not recommend routine intralipid use outside research settings. Future investigations should prioritize immune assessment and live birth as the primary endpoint.

Adropin is a new protein that regulates energy homeostasis. The serum and follicular fluid (FF) levels of adropin are decreased in women with polycystic ovarian syndrome (PCOS); however, its role in ovarian function is unknown. The aims were to determine the expression of adropin and its receptor G protein-coupled receptor 19 (GPR19) in human granulosa cells (GC), its immunolocalization and its in vitro effects on GC function. Blood plasma, FF and GC samples were obtained from normal weight, obese and diagnosed with or without PCOS women (n=8). The in vitro effects of adropin on GC proliferation, apoptosis, cell cycle progression, steroidogenesis were analyzed. The results revealed that adropin plasma concentration was decreased in obese patients, with a similar reduction observed in obese patients with PCOS, while GPR19 expression was decreased in the GC of obese and PCOS women, as well as in obese PCOS patients. We noted that in all investigated patients groups adropin reduced GC proliferation and cell cycle progression, negatively influenced steroidogenesis enzyme levels and promoted apoptosis. Such disruptions in GC function are likely to impair ovarian follicular maturation and contribute to the subfertility commonly observed in PCOS. Such alterations may ultimately affect oocyte competence and ovarian responsiveness, parameters that are clinically relevant for in vitro fertilization outcomes. Our findings suggest that adropin may act as a novel regulator of ovarian function and could contribute to the pathophysiology of PCOS, highlighting its potential clinical value as a marker of altered ovarian follicular function in affected women.

Decidual changes in deep pelvic endometriosis (DPE) are extremely rare. During pregnancy, endometriotic activity and symptoms diminish due to hormonal changes, whereas the endometrial lining undergoes decidualization in response to progesterone. In some cases, a significant hormonal boost can promote the decidualization of endometriotic implants, with endometriomas being the most common sites for such changes. Decidualized endometriosis at sites outside the ovaries is a rarer phenomenon, and the associated imaging features have been studied less. We present a case of non-pregnancy-related decidualization involving multiple sites of DPE. A 33-year-old woman exposed to ovarian stimulation before in vitro fertilization (IVF) presented with chronic pelvic pain and vaginal bleeding. Emergency CT demonstrated irregular solid tissue in the pouch of Douglas and along the bowel loops, raising concern for a neoplastic process. Tumor markers were negative. Transvaginal ultrasound showed a hypoechoic, irregular, hypervascular lesion, and ultrasound-guided biopsy demonstrated decidualized stromal endometriosis. MRI confirmed a solid mass centered in the posterior cul-de-sac with intermediate T2-weighted (W) signal intensity, hemorrhagic foci on fat-suppressed T1W images, marked diffusion restriction, and avid post-contrast enhancement. Similar solid components were also present at multiple pelvic sites, adjacent to DPE implants. Short-interval MRI follow-up showed size reduction; however, due to persistent pain, fertility-sparing surgery was performed, and histology confirmed decidualization of DPE at all sites. This rare case emphasizes that decidualization can also occur on DPE and outside pregnancy, potentially mimicking malignant transformation, highlighting the role of MRI in aiding diagnosis and guiding proper management for these patients.

Prophylactic low-dose aspirin is recommended to reduce the risk of preeclampsia in pregnant persons with risk factors. Sixteen distinct risk factors are recognized, including elements of current and past medical and obstetrical history, family history, and examination findings. In 2020, the Society for Maternal-Fetal Medicine published checklists intended to reduce the chance that risk factors might be inadvertently overlooked and to improve the probability of aspirin being recommended for all appropriate candidates. In 2021, the U.S. Preventive Services Taskforce published an updated Recommendation Statement expanding the number of persons for whom aspirin prophylaxis is recommended. Here, the Society for Maternal-Fetal Medicine presents updated checklists incorporating the new recommendations. We also suggest steps for implementing such a checklist into routine practice. This statement replaces the 2020 Society for Maternal-Fetal Medicine Special Statement: Checklists for preeclampsia risk-factor screening to guide recommendations for prophylactic low-dose aspirin.

Mitochondria are preferentially transmitted from the maternal plant in most angiosperms, including rice, and paternal mitochondria are generally eliminated during microgametogenesis and/or in zygotes. The mechanism by which paternal mitochondria are eliminated progresses during plant reproductive processes. In the present study, we examined the distribution of paternal mitochondria in rice sperm cells and zygotes produced through the in vitro fertilization (IVF) of isolated rice gametes. Male gametes of rice possess mitochondria with nucleoids, suggesting the potential transfer of paternal mitochondria and their DNA into zygotes upon fertilization and subsequent selective elimination of paternal mitochondria in the zygote. To intensively monitor the fate of rice paternal mitochondria in zygotes immediately after gamete fusion, time-lapse observations were conducted in paternal mitochondria labeled with green fluorescent protein from rice zygotes produced using an IVF system. The results showed that the paternal mitochondria are progressively degraded during the early developmental stage at 1-3 hours after fusion (HAF), leaving a small number of paternal mitochondria at 6 HAF. The remaining paternal mitochondria were considered to be degraded in later developmental stage zygotes because paternal mitochondrial DNA-derived single nucleotide polymorphisms were not detected in the sequencing reads of genomic DNA prepared from inter-subspecific hybrid rice. In addition, treatment with autophagy inhibitors stabilized the paternal mitochondria in zygotes. This suggests that the autophagy-dependent massive and selective elimination machinery for male mitochondria functions in rice zygotes immediately after gamete fusion and supports the strict maternal inheritance of mitochondria in rice.

Sire-dependent variation in bovine in vitro fertilization (IVF) success is poorly explained by conventional semen parameters once samples meet standard quality thresholds. Sperm capacitation is required for acquisition of fertilization competence, yet its contribution to sire-dependent variation in bovine IVF outcomes remains unclear. Fifteen bulls (Bos taurus) were evaluated across five IVF replicates using 30 abattoir-derived oocytes per bull per replicate. Sperm were analyzed before (0 h) and after 3 h of in vitro capacitation using image-based flow cytometry to quantify zinc ion localization patterns (zinc signatures; Fluo-Zin 3 AM), acrosome remodeling (peanut agglutinin conjugated to Alexa Fluor 647; PNA-AF647), and plasma membrane integrity (propidium iodide). Motility parameters were assessed using computer-aided sperm analysis (CASA). Cleavage rate was assessed on Day 3 and blastocyst development on Day 7. Substantial bull-to-bull variation was observed for both cleavage (31.5-76.3%) and blastocyst development (7.3-40%). Bull effects on cleavage were significant (p < 0.0001). Predictive modeling revealed that CASA or biomarker variables alone explained limited variance in embryo development. In contrast, models incorporating capacitation-induced changes in zinc signatures and acrosome remodeling significantly improved prediction of IVF outcomes. Integration of biomarker and motility parameters across time points yielded the highest explanatory power, with zinc signature dynamics among the most consistently informative predictors. These findings demonstrate that sperm capacitation-associated zinc flux and acrosomal remodeling are biologically relevant determinants of bull-specific variation in bovine IVF embryo development and provide mechanistic biomarkers that improve prediction beyond conventional motility assessment alone.

Recurrent pregnancy loss (RPL) continues to be a significant challenge in reproductive medicine, particularly in women for whom standard examinations do not reveal a conclusive underlying reason. There is growing evidence that several instances may result from nuanced alterations in the endometrial milieu, particularly with decidualization and maternal-fetal immune tolerance. In recent years, vitamin D has gained recognition for its significance in early pregnancy, serving not only as a regulator of calcium metabolism but also as an active contributor to endometrial and immunological functions. The human endometrium exhibits the vitamin D receptor (VDR) and the enzyme CYP27B1, facilitating the local activation and signaling of vitamin D inside the uterine milieu. Experimental investigations have shown that vitamin D influences many processes critical for effective implantation and placentation, including stromal cell differentiation, cytokine equilibrium, trophoblast invasion, oxidative stress responses, and immune cell communication. Aberrant vitamin D signaling has been associated with heightened inflammatory activity, impaired decidual transformation, altered uterine natural killer cell functionality, and alteration of the Treg/Th17 equilibrium, all of which have been implicated in recurrent pregnancy loss. Concurrently, there is an increasing emphasis on the association between vitamin D and mitochondrial function as well as oxidative stress in decidual and endometrial cells. Interruption of these pathways may influence implantation and early embryonic development by impacting cellular metabolism and immunological control at the maternal-fetal interface. The clinical interest in vitamin D supplementation for women experiencing repeated reproductive failure is increasing; nevertheless, the existing results are conflicting, mostly due to the predominance of research focusing on circulating vitamin D levels rather than localized tissue-specific processes. Our review encapsulates new findings about the function of vitamin D in endometrial biology and reproductive immune regulation, emphasizing its involvement in decidualization, inflammatory signaling, oxidative stress, and maternal-fetal immunological tolerance in recurrent pregnancy loss. The potential ramifications for assisted reproduction and forthcoming tailored therapy techniques are also examined.

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with placental structural and functional alterations that may impair trophoblast integrity and maternal-fetal exchange. Ezrin, radixin, and moesin (ERM) proteins are membrane-cytoskeleton linker proteins involved in microvillous organization, cell polarity, and signal transduction. This study aimed to investigate placental ERM protein expression in GDM and to explore ERM-associated molecular pathways through bioinformatic analysis. Methods: This prospective observational study included placental tissues obtained from 40 women with GDM and 40 healthy pregnant women. Immunohistochemical staining for ezrin, radixin, and moesin was performed on paraffin-embedded placental sections, and quantitative image analysis was conducted using QuPath software (version 0.7.0) to calculate H-scores. Correlation and receiver operating characteristic (ROC) analyses were performed to evaluate associations between ERM expression and clinical parameters. In addition, bioinformatic analyses were conducted using the publicly available GSE154414 placental transcriptomic dataset to investigate ERM-associated signaling pathways and interaction networks. Results: Ezrin immunoreactivity was significantly increased in the GDM group compared with controls (118.63 ± 20.56 vs. 107.95 ± 17.41, p = 0.026), whereas Radixin and Moesin expression levels did not differ significantly between groups (p > 0.05). Ezrin expression demonstrated significant positive correlations with maternal body mass index, birth weight, fasting glucose, and HbA1c levels. ROC analysis demonstrated modest discriminatory performance of the Ezrin H-score for distinguishing GDM from control pregnancies (AUC = 0.645, p = 0.018). Bioinformatic analyses identified enrichment of ERM-associated pathways involved in cytoskeletal remodeling, inflammatory signaling, and protein phosphorylation-related cellular processes. Conclusions: Placental Ezrin expression was significantly increased in women with GDM and was positively associated with maternal glycemic parameters. These findings suggest that altered Ezrin expression may reflect adaptive cytoskeletal remodeling in diabetic placentas. ERM-associated signaling pathways may contribute to placental responses to metabolic stress in GDM.