Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis

Human Reproduction Update, Journal Year: 2023, Volume and Issue: 29(5), P. 570 - 633

Published: May 16, 2023

Abstract BACKGROUND A normal chromosomal constitution defined through PGT-A assessing all chromosomes on trophectoderm (TE) biopsies represents the strongest predictor of embryo implantation. Yet, its positive predictive value is not higher than 50–60%. This gap knowledge causes euploid blastocysts’ reproductive failure known as ‘the black box implantation’. OBJECTIVE AND RATIONALE Several embryonic, maternal, paternal, clinical, and IVF laboratory features were scrutinized for their putative association with success or implantation blastocysts. SEARCH METHODS systematic bibliographical search was conducted without temporal limits up to August 2021. The keywords ‘(blastocyst OR day5 day6 day7 embryo) (euploid chromosomally preimplantation genetic testing) (implantation miscarriage abortion live birth biochemical pregnancy recurrent failure)’. Overall, 1608 items identified screened. We included prospective retrospective clinical studies randomized-controlled-trials (RCTs) that assessed any feature associated live-birth rates (LBR) and/or (MR) among non-mosaic blastocyst transfer after TE biopsy PGT-A. In total, 41 reviews 372 papers selected, clustered according a common focus, thoroughly reviewed. PRISMA guideline followed, PICO model adopted, ROBINS-I ROB 2.0 scoring used assess bias. Bias across regarding LBR also using visual inspection funnel plots trim fill method. Categorical data combined pooled-OR. random-effect conduct meta-analysis. Between-study heterogeneity addressed I2. Whenever suitable meta-analysis, simply described results. study protocol registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42021275329). OUTCOMES original (335 studies, 30 7 RCTs) reviews. However, most retrospective, characterized by small sample sizes, thus prone bias, which reduces quality evidence low very low. Reduced inner cell mass (7 OR: 0.37, 95% CI: 0.27–0.52, I2 = 53%), (9 0.53, 0.43–0.67, 70%), overall worse Gardner’s BB-grade (8 0.40, 0.24–0.67, 83%), developmental delay (18 0.56, 0.49–0.63, 47%), (by qualitative analysis) some morphodynamic abnormalities pinpointed time-lapse microscopy (abnormal cleavage patterns, spontaneous collapse, longer time morula formation I, blastulation (tB), duration blastulation) poorer outcomes. Slightly lower LBR, even in context PGT-A, reported women ≥38 years 0.87, 0.75–1.00, 31%), while obesity both (2 0.66, 0.55–0.79, 0%) MR 1.8, 1.08–2.99, 52%). experience previous repeated failures (RIF) (3 0.72, 0.55–0.93, 0%). By analysis, hormonal assessments, only abnormal progesterone levels prior Among protocols used, vitrified-warmed more effective fresh 1.56, 1.05–2.33, 23%) Lastly, multiple vitrification-warming cycles 0.41, 0.22–0.77, 50%) high cells biopsied may slightly reduce simultaneous zona-pellucida opening allowed better results Day 3 hatching-based 1.41, 1.18–1.69, WIDER IMPLICATIONS Embryo selection aims shortening time-to-pregnancy, minimizing risks. Knowing are competence blastocysts therefore critical define, implement, validate safer efficient workflows. Future research should be directed towards: (i) investigations mechanisms involved aging beyond de novo abnormalities, how lifestyle nutrition accelerate exacerbate consequences; (ii) improved evaluation uterine blastocyst-endometrial dialogue, represent boxes themselves; (iii) standardization/automation assessment protocols; (iv) additional invasive preferably non-invasive tools selection. Only filling these gaps we finally crack riddle behind

Language: Английский

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Gut microbiota-gonadal axis: the impact of gut microbiota on reproductive functions

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 28, 2024

The influence of gut microbiota on physiological processes is rapidly gaining attention globally. Despite being under-studied, there are available data demonstrating a microbiota-gonadal cross-talk, and the importance this axis in reproduction. This study reviews impacts In addition, possible mechanisms by which modulates male female reproduction presented. Databases, including Embase, Google scholar, Pubmed/Medline, Scopus, Web Science, were explored using relevant key words. Findings showed that promotes gonadal functions modulating circulating levels steroid sex hormones, insulin sensitivity, immune system, microbiota. Gut also alters ROS generation activation cytokine accumulation. conclusion, demonstrate existence axis, role functions. However, majority compelling evidences from animal studies with great dearth human data. Therefore, validating reports experimental models important.

Language: Английский

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A disturbed communication between hypothalamic-pituitary-ovary axis and gut microbiota in female infertility: is diet to blame?

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 21, 2025

Female infertility is a multifactorial condition influenced by various genetic, environmental, and lifestyle factors. Recent research has investigated the significant impact of gut microbiome dysbiosis on systemic inflammation, metabolic dysfunction, hormonal imbalances, which can potentially impair fertility. The gut-brain axis, bidirectional communication system between brain, also plays role in regulating reproductive functions. Emerging evidence suggests that influence brain functions behavior, further emphasizing importance microbiota-gut-brain axis reproduction. Given their as major modulator microbiome, diet dietary factors, including patterns nutrient intake, have been implicated development management female infertility. Hence, this review aims to highlight patterns, such Western (WD) Mediterranean (MD), decipher modulatory action infertile women. By contrasting detrimental effects WD with therapeutic potential MD, we emphasize pivotal balanced rich nutrients promoting healthy microbiome. These insights underscore targeted interventions modifications promising strategies enhance outcomes subfertile

Language: Английский

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How Can Selected Dietary Ingredients Influence the Development and Progression of Endometriosis?

Nutrients, Journal Year: 2024, Volume and Issue: 16(1), P. 154 - 154

Published: Jan. 2, 2024

Endometriosis is a chronic, hormone-dependent disease characterized by the presence of endometrial tissue in ectopic locations. Since treatment options for this are still limited, and cure rate unsatisfactory, search ways to treat symptoms modify course key importance improving quality life patients with endometriosis. So far, literature has shown that nutrition can influence endometriosis through hormonal modification altering inflammatory or oxidative response. subject scientific research, we aimed summarize current knowledge on role dietary modifications Our review showed nutrients anti-inflammatory antioxidant properties, including most vitamins several trace elements, may pathogenesis be considered as preventing development However, despite many discoveries described review, further interdisciplinary research topic seems extremely important, future, it result personalized therapies supporting

Language: Английский

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Novel first-trimester serum biomarkers for early prediction of gestational diabetes mellitus

Nutrition and Diabetes, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 12, 2025

Gestational diabetes mellitus (GDM) is a common obstetric complication worldwide that seriously threatens maternal and fetal health. As the number of women conceiving through in vitro fertilization (IVF) continues to rise, this population recognized as being at an elevated risk for GDM. However, there still no consensus on early prediction GDM IVF patients due lack reliable biomarkers. We compared first-trimester serum cytokine antibody profiles 38 matched controls undergoing treatment, based extensive human biobank our large‑scale assisted reproductive cohort platform. The 76 samples were divided into training set (n = 53) testing 23) using 7:3 ratio, five diverse machine-learning models predicting constructed. By combining top differentially expressed first‑trimester biomarkers [including total immunoglobulin (Ig)G, IgM, interleukin (IL)-7, anti‑phosphatidylserine (aPS)-IgG immune complexes (IC), IL-15], novel model was constructed, which achieved superior predictive value [area under curve (AUC) 95% confidence interval (CI) 0.906 (0.840-0.971), with sensitivity 75% specificity 94.7%] development. eXtreme Gradient Boosting (XGBoost) AUC 0.995 (95% CI: 0.995-1.000, P < 0.001) 0.867 0.789-0.952, test identified cytokines immune-related constructed efficient population. These findings are expected aid development strategies offer immunological insights further mechanistic studies

Language: Английский

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Gut microbiome and reproductive endocrine diseases: a Mendelian randomization study

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 4, 2023

Observation studies have confirmed the association between gut microbiome and reproductive endocrine diseases (REDs), namely, polycystic ovary syndrome (PCOS), endometriosis, female infertility. However, their has never been by a two-sample Mendelian randomization (MR) analysis.We conducted MR analysis to evaluate relationship three aforementioned REDs. In order get more comprehensive results, two different thresholds were adopted select instrumental variables (IVs): one was locus-wide significance threshold (P <1.0×10-5) other genome-wide level (P< 5×10-8). Summary-level statistics for REDs collected from public databases. Inverse-variance weighted (IVW) main method used estimate causality, sensitivity analyses validate results.At level, we identified that genera Streptococcus (OR=1.52, 95%CI: 1.13-2.06, P=0.006) RuminococcaceaeUCG005 (OR=1.39, 1.04-1.86, P=0.028) associated with high risk of PCOS, while Sellimonas (OR= 0.69, 0.58-0.83, P=0.0001) RuminococcaceaeUCG011(OR=0.76, 0.60-0.95, P=0.017) linked low PCOS risk. The genus Coprococcus2 (OR=1.20, 1.01-1.43, P=0.039) correlated an increased infertility, Ruminococcus torques (OR=0.69, 0.54-0.88, P=0.002) negatively Olsenella 1.11, 1.01-1.22, P=0.036), Anaerotruncus 1.25, 1.03-1.53, P=0.025), Oscillospira 1.21, 1.01-1.46, P=0.035) endometriosis. results showed did not possess causal link based on level. Sensitivity further robustness results.Our study provides evidence is closely related Subsequent should be promote microbiome-orientated therapeutic strategies managing

Language: Английский

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Translational Research on Bee Pollen as a Source of Nutrients: A Scoping Review from Bench to Real World

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2413 - 2413

Published: May 22, 2023

The emphasis on healthy nutrition is gaining a forefront place in current biomedical sciences. Nutritional deficiencies and imbalances have been widely demonstrated to be involved the genesis development of many world-scale public health burdens, such as metabolic cardiovascular diseases. In recent years, bee pollen emerging scientifically validated candidate, which can help diminish conditions through nutritional interventions. This matrix being extensively studied, has proven very rich well-balanced nutrient pool. this work, we reviewed available evidence interest source. We mainly focused richness nutrients its possible roles main pathophysiological processes that are directly linked imbalances. scoping review analyzed scientific works published last four focusing clearest inferences perspectives translate cumulated experimental preclinical into clinically relevant insights. promising uses for malnutrition, digestive health, disorders, other bioactivities could helpful readjust homeostasis (as it also true case anti-inflammatory or anti-oxidant needs), well benefits diseases, were identified. knowledge gaps identified, along with practical challenges hinder establishment fructification these uses. A complete data collection made major range botanical species allows more robust clinical information.

Language: Английский

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The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF

Nutrients, Journal Year: 2023, Volume and Issue: 15(20), P. 4444 - 4444

Published: Oct. 20, 2023

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive metabolic. Overweight/obesity a risk factor in terms of adverse effects during hormone stimulation, reduced response to ovulation induction regimens, success IVF, an increased obstetric complications. To resolve this vicious cycle events, weight loss lifestyle modifications are promising strategies. Among these possible approaches, consumption very-low-calorie ketogenic diet (VLCKD) or Mediterranean (MD) represents valid option. In our study, 84 obese/overweight PCOS patients were recruited evaluate induced by VLCKD MD on weight, hormonal, metabolic parameters. BMI decreased significantly among VLKCD compared (both presenting p values < 0.0001 at 90 120 days), significant reduction body circumference was observed. At same time, HOMA index statistically for those (p value 0.001 days 0.05 phenomenon also observed AFC 0.001) AMH 0.05). Interestingly, ovarian hyperstimulation (OHSS) incidence lower 0.001). We state that dietary regimes may improve anthropometric parameters (such as BMI) women’s health, restore menstrual regularity, reduce OHSS. Regarding different nutritional therapies, results suggest optimal choice entry into especially time range which achieved.

Language: Английский

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Terminal deoxynucleotidyl transferase combined dual-toehold catalytic hairpin assembly for sensitive sperm DNA integrity evaluation

Microchimica Acta, Journal Year: 2025, Volume and Issue: 192(3)

Published: Feb. 13, 2025

Language: Английский

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Holistic Approaches to managing female infertility: A comprehensive review

Journal of Drug Delivery and Therapeutics, Journal Year: 2025, Volume and Issue: 15(3), P. 180 - 189

Published: March 15, 2025

Background: Female infertility is a multifactorial condition influenced by hormonal imbalances, metabolic disorders, and lifestyle factors. Conventional allopathic treatments, while effective, often have limitations, prompting interest in holistic approaches that integrate diet therapy, physical activity, modifications, medicinal plants. Objective: This review aims to provide comprehensive analysis of managing female infertility, focusing on diet, exercise, changes, herbal remedies, treatments. Methods; A systematic literature was conducted using databases such as PubMed, Scopus, Google Scholar. Studies exploring the role plants, conventional therapies improving fertility outcomes were analyzed. Results: Holistic management strategies for encompass: (1) Diet Therapy- Nutrient-rich diets, emphasizing antioxidants, omega-3 fatty acids, low glycemic index foods, improve balance reproductive function, (2) Exercise Lifestyle Modifications – Regular stress reduction, weight enhance regulating ovulation reducing inflammation, (3) Medicinal Plants- Ashwagandha (Withania somnifera)- Adaptogenic properties reduce stress-related infertility. Manjistha/majeeith (Rubia cordifolia)- Detoxifies body improves uterine health. Kalonji (Nigella sativa)- Enhances ovarian function balance. Shatavari (Asparagus racemosus)- Supports regulation Asarun (Asarum europaeum)- Improves menstrual cycle regulation. Ashoka (Saraca asoca)- Strengthens endometrium alleviates (4) Allopathic Interventions-Hormonal therapies, ovulation-inducing drugs, assisted technologies (ART) remain primary but their effectiveness when combined with strategies. Conclusion: approach integrating treatments provides promising strategy Future research should focus clinical validation remedies synergistic effects integrative Keywords: approach, modification, treatment

Language: Английский

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