Search Results (282)

Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article

Endometriosis significantly impacts fertility through complex mechanisms. These include chronic inflammation, oxidative stress, and anatomical distortion. These mechanisms impair oocyte quality, embryo development, and implantation. While in vivo challenges persist, in vitro fertilization (IVF) offers a controlled environment to overcome some barriers. A systematic review of evidence is presented for (1) endometriosis-associated oocyte dysfunction, (2) conflicting IVF outcomes, and (3) innovative strategies. Significant medical advancements have been made. However, gaps remain in personalized prognosis and targeted therapies. Emerging tools, specifically AI-driven embryo selection, single-cell omics, and immunomodulation, are promising for improving outcomes. Hence, a patient-centered approach, balancing science with personalized care, is essential to navigate endometriosis-related infertility. Full article

Semen cryopreservation is associated with sperm vulnerability to oxidative stress and ice crystal-induced damage, adversely affecting in vitro fertilization (IVF) success. This study aimed to investigate the effects of freezing diluent supplemented with antioxidant limonin (Lim), myo-inositol (MYO), and the ice crystal formation inhibitor L-proline (LP) through sperm motility, morphological integrity, and antioxidant capacity. The Lim (150 mM), MYO (90 mM), and LP (100 mM) significantly ameliorated the quality of post-thaw sperm in Debao boar, and combined treatment of these agents significantly enhanced sperm motility, structural integrity, and antioxidant capacity compared with individual agents (p < 0.05). Notably, the combined use of these agents reduced glycerol concentration in the freezing diluent from 3% to 2%. Meanwhile, the integrity of the sperm plasma membrane, acrosome membrane, and mitochondrial membrane potential was significantly improved (p < 0.05), and the result of IVF revealed the total cell count of the blastocysts was also greater in the 2% glycerol group (p < 0.05). In conclusion, the newly developed freezing diluent for semen, by adding Lim (150 mM), MYO (90 mM), and LP (100 mM), can enhance the quality of frozen–thawed Debao boar sperm and reduce the concentration of glycerol from 3% to 2% as high concentrations of glycerol can impair the quality of thawed sperm and affect in vitro fertilization outcomes. In conclusion, the improved dilution solution formulated demonstrated efficacy in enhancing the quality of porcine spermatozoa following cryopreservation and subsequent thawing. Full article

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013–2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04–1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

Background: Nitric oxide (NO) is an important modulator of ovarian physiology, which contributes to angiogenesis, steroidogenesis, and redox control. The stable metabolites nitrate (NO₃⁻) and nitrite (NO₂⁻) may indicate real-time follicular function during IVF. Methods: In this prospective study, we included 89 women who underwent controlled ovarian stimulation. The Griess test was used to measure NO₂-NO₃ concentrations in follicular fluid collected on the day of oocyte retrieval. Non-parametric and correlation tests were used to investigate the associations between oocyte yield, maturity (MII), fertilization (2PN), embryo development, and hormone levels. Results: Higher NO₂-NO₃ levels were substantially associated with increased total oocyte count, MII oocytes (p = 0.014), and 2PN embryos (p = 0.029). This suggests a strong relationship between NO bioavailability and oocyte competence. NO₂-NO₃ levels showed a positive correlation with estradiol (p < 0.001) and progesterone (p < 0.001), suggesting a possible function in granulosa cell steroidogenesis. Conclusions: Follicular NO metabolites are candidate functional indicators for oocyte quality evaluation and intrafollicular steroidogenic activity. Their predictive value may improve customized IVF treatment, especially in individuals with complicated ovarian phenotypes such as PCOS or decreased ovarian reserve. 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

Per- and polyfluoroalkyl substances (PFASs) comprise a diverse array of synthetic chemicals that resist environmental degradation. They are increasingly recognised as endocrine-disrupting compounds (EDCs). These chemicals, found in non-stick cookware, food packaging, and industrial waste, accumulate in human tissues and fluids, raising substantial concerns regarding their impact on female reproductive health. Epidemiological studies have demonstrated associations between PFAS exposure and reduced fertility; nevertheless, the underlying molecular pathways remain inadequately understood. This narrative review investigates the multifaceted effects of PFASs on ovarian physiology, including its disruption of the hypothalamic–pituitary–ovarian (HPO) axis, alteration of anti-Müllerian hormone (AMH) levels, folliculogenesis, and gonadotropin receptor signalling. Significant attention is directed towards the emerging association between PFASs and polycystic ovarian syndrome (PCOS), wherein PFAS-induced hormonal disruption may exacerbate metabolic issues and elevated androgen levels. Furthermore, we analyse the current data regarding PFAS exposure in women undergoing treatment based on assisted reproductive technologies (ARTs), specifically in vitro fertilisation (IVF), highlighting possible associations with diminished oocyte quality, suboptimal embryo development, and implantation failure. We examine potential epigenetic and transgenerational alterations that may influence women’s reproductive capabilities over time. This study underscores the urgent need for further research and regulatory actions to tackle PFAS-related reproductive toxicity, particularly in vulnerable populations, such as women of reproductive age and those receiving fertility treatments. 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

The increasing use of assisted reproductive technologies (ARTs) globally, such as intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), has highlighted the pressing need to determine the modifiable factors affecting the success of implantation and the outcomes of early pregnancy. Scientific interest in the role of nutrition in fertility is growing, but outside of celiac disease, little is known about gluten, a dietary protein with immunogenic and inflammatory properties. With an emphasis on ART results, this narrative review summarizes the most recent data regarding the possible effects of gluten consumption on reproductive health, focusing primarily on individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS). In addition to discussing potential molecular processes connecting gluten-induced inflammation, increased gut permeability, autoimmune, and decreased endometrial receptivity, we further explore the documented link between CD and infertility and investigate new information on NCGS. These findings are tentative and based on scant low-quality evidence, although some case reports and small clinical studies have indicated that avoiding gluten may help some people undergoing ART, especially those with immune-mediated diseases or infertility that cannot be explained. There is currently no robust prospective evidence confirming that gluten restriction improves infertility outcomes. Therefore, before gluten elimination is advised in this situation, more carefully planned extensive research is required to generate reliable scientific proof. Beyond traditional celiac disease, we suggest that gluten sensitivity might be an underappreciated factor in ART failure that merits more research. A gluten-free diet may serve as a low-risk supplementary option for appropriately selected patients, pending the results of more extensive controlled studies. Full article

The efficacy of in vitro fertilization (IVF) is significantly hindered by early embryonic developmental failure and oocyte maturation arrest. Recent findings in reproductive genetics have identified several oocyte-specific genes—TUBB8, KIF11, and CKAP5—as essential regulators of meiotic spindle formation and cytoskeletal dynamics. Mutations in these genes can lead to significant meiotic defects, fertilization failure, and embryo arrest. The links between genotype and phenotype, along with the underlying biological mechanisms, remain inadequately characterized despite the increasing number of identified variations. This systematic review was conducted in accordance with PRISMA 2020 guidelines. Relevant papers were retrieved from the PubMed and Embase databases using combinations of the keywords “TUBB8,” “KIF11,” “CKAP5,” “oocyte maturation arrest,” “embryonic arrest,” and “IVF failure.” Studies were included if they contained clinical, genomic, and functional data on TUBB8, KIF11, or CKAP5 mutations in women undergoing IVF. Molecular data, including gene variant classifications, inheritance models, in vitro tests (such as microtubule network analysis in HeLa cells), and assisted reproductive technology (ART) outcomes, were obtained. Eighteen trials including 35 women with primary infertility were included. Over fifty different variants were identified, the majority of which can be attributed to TUBB8 mutations. TUBB8 disrupted α/β-tubulin heterodimer assembly due to homozygous missense mutations, hence hindering meiotic spindle formation and leading to early embryo fragmentation or the creation of many pronuclei and cleavage failure. KIF11 mutations resulted in spindle disorganization and chromosomal misalignment via disrupting tubulin acetylation and microtubule transport. Mutations in CKAP5 impaired bipolar spindle assembly and microtubule stabilization. In vitro validation studies showed cytoskeletal disturbances, protein instability, and dominant negative effects in transfected animals. Donor egg IVF was the sole effective treatment; however, no viable pregnancies were documented in patients with pathogenic mutations of TUBB8 or KIF11. TUBB8, KIF11, and CKAP5 are essential for safeguarding oocyte meiotic competence and early embryonic development at the molecular level. Genetic differences in these genes disrupt microtubule dynamics and spindle assembly, resulting in various aspects of oocyte maturation and fertilization. Functional validation underscores the necessity of routine genetic screening for women experiencing unresolved IVF failure, as it substantiates their causal role in infertility. Future therapeutic avenues in ART may be enhanced by tailored counseling and innovative rescue methodologies like as gene therapy. Full article

The success of in vitro fertilization (IVF) and female reproductive capacity are significantly determined by oocyte quality. Increasing data highlights the significance of oxidative stress—a state of imbalance between reactive oxygen species (ROS) and antioxidant defenses—in regulating oocyte competence. Normal folliculogenesis and ovulation rely on optimal ROS levels; excessive oxidative stress (OS) can lead to DNA fragmentation, undermine meiotic spindle integrity, and trigger apoptosis in cumulus and granulosa cells. Molecular insults impair nuclear and cytoplasmic maturation, thereby impacting fertilization potential and embryonic development. Individuals with polycystic ovarian syndrome (PCOS), endometriosis, advanced maternal age, and metabolic disorders—conditions associated with suboptimal IVF outcomes—frequently exhibit redox imbalance. This narrative review examines significant oxidative markers in the follicular environment, exploring the molecular processes linking OS to diminished oocyte quality and discussing therapy techniques aimed at mitigating oxidative damage. Maintaining redox homeostasis in the ovarian milieu appears to be an effective strategy for enhancing oocyte competence and optimizing outcomes in assisted reproduction. Full article

Objectives: To investigate the impact of α-chymotrypsin treatment on sperm recovery rate and total motile sperm count (TMC) in highly viscous semen for intrauterine insemination (IUI) and in vitro fertilization (IVF), particularly in cases of severely low sperm count. Methods: High viscosity was defined by the inability to form a thread exceeding 2 cm from a semen drop after 30 min of incubation at 37 °C with repeated pipetting. Semen samples were treated with 5 mg of α-chymotrypsin for 5–10 min at 37 °C and washed using a 90% gradient solution. A total of 35 patients were included, with comparisons made to the same patients’ prior untreated samples using paired t-tests. Severely low sperm count was classified as TMC below 10 million. Results: Treatment with α-chymotrypsin significantly improved TMC (22.2 million vs. 11.6 million, p = 0.0004) and motile sperm recovery rate (38.9% vs. 16.2%, p = 0.00002). In cases of severely low sperm count, α-chymotrypsin treatment resulted in a marked increase in recovery rate (43.0% vs. 10.0%, p = 0.02) and TMC (5.89 million vs. 1.21 million, p = 0.004). Fertilization using treated samples achieved an 87.8% success rate, with a 56.4% usable blastocyst rate, comparable to standard IVF outcomes (n = 9, average age = 34.9 years). Conclusions: α-chymotrypsin treatment significantly enhances sperm recovery and TMC in highly viscous semen, demonstrating particular efficacy in patients with severely low sperm counts without affecting fertilization or blastocyst rate in IVF. Full article

Insulin resistance (IR) frequently develops in women with polycystic ovary syndrome (PCOS), an endocrinological disorder typified by hyperandrogenaemia, erratic menstrual cycles, and the presence of multiple cysts in the ovaries. It results in elevated androgen production contributing to the clinical manifestations of the syndrome including associated co-morbidities such as obesity and type 2 diabetes (T2D). Mounting data suggest the involvement of free fatty acids, reactive oxygen species (ROS) signalling, and mitochondrial dysfunction with IR. In recent years, numerous reports have suggested that mitochondrial dysregulation is associated with the pathogenesis of PCOS. Increased ROS, mutations/variants in mitochondrial DNA (mtDNA), and the altered expression of nuclear-related mitochondrial genes in insulin-resistant women with PCOS provide sufficient evidence for mitochondrial dysfunction as one of the factors contributing to PCOS pathogenesis. Despite the advancements in the field of interconnecting links between mitochondrial dysfunction, IR, and PCOS, various underlying mechanisms needs to be elucidated. Advancements in therapeutic interventions showed promising results in improving mitochondrial functions and IR in PCOS pathogenesis, including evolving mitochondrial transfer approaches that may improve in vitro fertilisation (IVF) outcomes in obese and insulin-resistant women with PCOS in future. Full article

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with the endocrine system by mimicking or blocking the action of endogenous hormones such as estrogens, androgens, and thyroid hormones. This systematic review aims to evaluate the current epidemiological evidence linking EDC exposure with adverse reproductive outcomes in males and females of reproductive age. A total of 14 observational studies published between 2014 and 2024 were included following structured searches in PubMed, Scopus, and Google Scholar. The most commonly studied EDCs included bisphenol A (BPA), its analogs (such as bisphenol S, BPS), phthalates, parabens, per- and polyfluoroalkyl substances (PFAS), and persistent organic pollutants (POPs). The review found consistent associations between EDC exposure and multiple reproductive endpoints, such as impaired semen quality, decreased ovarian reserve, infertility, polycystic ovary syndrome (PCOS), altered hormone levels—specifically estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)—and adverse outcomes in assisted reproductive technologies (ART), including in vitro fertilization (IVF). Despite methodological heterogeneity, the findings support the biological plausibility of EDCs in disrupting reproductive function. The review highlights the urgent need for regulatory measures, increased public awareness, and longitudinal studies to assess the cumulative effects of chronic EDC exposure on human fertility. Full article