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Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential.

Background: Infertility affects around 17.5% of reproductive-aged individuals worldwide, posing significant personal and public health challenges. Although Medically Assisted Reproduction and Assisted Reproductive Technology (ART; e.g., in vitro fertilization) have advanced outcomes, many couples fail to conceive due to unaddressed pelvic, uterine, or systemic factors. Objectives: We aim to (1) define the current usage of Restorative Reproduction Medicine (RRM) in clinical practice, (2) compare RRM outcomes with conventional ART, and (3) propose an integrated model of RRM plus ART for optimal fertility care. Design: A systematic review following PRISMA guidelines was conducted (INPLASY registration no. INPLASY2024110069). Data sources and methods: We searched PubMed, Scopus, and Web of Science (January 1995–October 2024), combining terms such as “restorative reproductive medicine,” “intrauterine adhesions,” “myomas,” “polyps,” “hydrosalpinx,” “endometritis,” “BMI,” “thyroid dysfunction,” “microbiome,” and “assisted reproductive technology.” Inclusion criteria: studies on uterine/systemic factors affecting infertility, focusing on surgical/pharmacological RRM interventions and ART limitations. Exclusion criteria: male-only infertility, case reports, narrative reviews, non-English publications. Quality assessment employed the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool. We also briefly noted potential publication bias due to language and study-type restrictions. Results: From >25,000 initial titles, 3 sequential screenings yielded 145 key articles addressing uterine (septum, myomas, polyps, adhesions) and systemic (body mass index (BMI) extremes, thyroid dysfunction, microbiome imbalance) factors. Surgical corrections (e.g., hysteroscopic removal of polyps/myomas, salpingectomy for hydrosalpinx) significantly improved natural conception and ART success (⩾20%–40% increase in clinical pregnancy). Chronic endometritis treatment, endometrial microbiome modulation, and BMI/thyroid optimization further improved pregnancy rates by 15%–20%. Comparisons of RRM versus ART alone indicated that RRM often lowers overall cost and may reduce miscarriage, while ART offers immediate embryo transfer. Combining RRM to correct pathologies prior to ART can boost implantation and live birth rates (⩾40%–70% improvement in some studies). Conclusion: Restorative Reproductive Medicine comprehensively addresses pelvic and systemic abnormalities, thereby enhancing fertility outcomes and complementing ART. A proposed integrated model—RRM diagnostics/interventions followed by ART if needed—maximizes success, reduces time/cost, and emphasizes holistic reproductive health. Further multicenter trials are warranted to standardize protocols and fully realize RRM’s potential in modern fertility care.

To identify and address systemic barriers undermining the meritocratic advancement of medical professionals in Italy and to propose a transparent, performance-driven recruitment model. A critical narrative review and conceptual framework proposal supported by an analysis of current systemic limitations and international benchmarking data. We conducted a narrative review involving structured searches of international and Italian sources, followed by thematic synthesis and the development of two merit frameworks-Merit-based Professional Value Score (MPVS) and Integrity and Impact Score (IIS)-featuring standardized indicators and peer-normalized scoring metrics. Italy's medical system, despite high economic capacity, underperforms due to persistent non-meritocratic structures. Key challenges include political interference in residency selection, low return rates of expatriated physicians (>11,000 currently practicing abroad), and biased hiring mechanisms. Women and internationally trained candidates encounter disproportionate barriers. Across medical systems, output-only metrics (e.g., H-index) has proven insufficient. We propose MPVS and IIS as transparent, auditable tools that integrate risk-adjusted outcomes, patient safety indicators, patient-reported measures, teaching, research, and integrity domains. A worked example illustrates end-to-end scoring process and decision thresholds. Furthermore, a new protocol is proposed featuring anonymized candidate evaluation based on two metrics: -integrates clinical outcomes, teaching performance, and professional conduct. -evaluates research relevance, innovation capacity, and applied contributions. Cross-linked digital verification, external audits, and rotating blinded selection panels under national anti-corruption oversight form the governance backbone. Implementing this model would help reverse Italy's brain drain, restore merit-based standards in healthcare sector, and provide a replicable framework for other health systems pursuing transparency, quality, and equity.

Purpose We used computer assisted sperm selection (MSOME) during cycles of intracytoplasmic sperm injection to test whether this technique improves results over traditional ICSI protocols. We also used the TUNEL assay to test whether MSOME could deselect physiologically abnormal spermatozoa. Methods Individual spermatozoa were examined with MSOME. Normal and abnormal spermatozoa were tested for the level of DNA fragmentation using TUNEL assay. In a prospective, randomized trial, patients were selected for standard ICSI, or IMSI techniques. We tested the two groups for biological and clinical parameters. Results 64.8% of spermatozoa, otherwise selectable for ICSI, were characterized by abnormalities after computer-assisted sperm analysis. These sperm were also characterized by an increase in the level of DNA fragmentation. We noted an increase in embryo quality, pregnancy and implantation rates after computerized sperm selection during ICSI procedures. Conclusions Computerised selection of spermatozoa during ICSI procedures deselects physiological abnormal spermatozoa and improves clinical results.

The inability to support the growth and development of a mature fetus up to delivery results in significant human suffering. Current available solutions include adoption, surrogacy, and uterus transplantation. However, these options are subject to several ethical, religious, economic, social, and medical concerns. Ectogenesis is the process in which an embryo develops in an artificial uterus from implantation through to the delivery of a live infant. This current narrative review summarizes the state of recent research focused on human ectogenesis. First, a literature search was performed to identify published reports of previous experiments and devices used for embryo implantation in an extracorporeally perfused human uterus. Furthermore, studies fitting that aim were selected and critically evaluated. Results were synthesized, interpreted, and used to design a prospective strategy for future research. Therefore, this study suggests that full ectogenesis might be obtained using a computer-controlled system with extracorporeal blood perfusion provided by a digitally controlled heart–lung–kidney system. From a clinical perspective, patients who will derive significant benefits from this technology are mainly those women diagnosed with anatomical abnormalities of the uterus and those who have undergone previous hysterectomies, numerous abortions, and experienced premature birth. Ectogenesis is the complete development of an embryo in an artificial uterus. It represents the solutions for millions of women suffering from premature deliveries, and the inability to supply growth and development of embryos/fetuses in the womb. In the future, ectogenesis might replace uterine transplantation and surrogacy.

The custom microenvironment “vascular niche” is a potential therapeutic target for several pathophysiological conditions. Osteoblasts act as regulators of the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor may increase the number of cells mobilized into the bloodstream. The authors demonstrate that PTH may enhance the efficiency of hematopoietic stem cell-based therapy in a recognized model of peripheral ischemia. Background The custom microenvironment 'vascular niche' is a potential therapeutic target for several pathophysiological conditions. Osteoblasts regulate the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor can increase the number of cells mobilized into the bloodstream. Methods C57Bl/6 mice were randomly assigned treatment with granulocyte-colony stimulating factor (G-CSF), PTH, G-CSF plus PTH or saline. All mice underwent hindlimb ischemia. Blood flow was measured by laser Doppler imaging. Indices of capillary activity were determined by electron microscopy in muscle tissue. CD34 + and Ki67 + cells were detected and evaluated by immunofluorescence, apoptosis by TUNEL, surface antigen and endothelial progenitor cells by fluorescence-activated cell sorting analysis, and vascular endothelial growth factor-164 and angiopoietin-1 expression by reverse-transcriptase polymerase chain reaction. Frozen bone marrow sections were stained for antigen-specific B cells and fibronectin and analyzed by confocal laser scanning microscopy. Results Following mobilization induced by G-CSF treatment, mice also treated with PTH showed increases in blood flow, capillary density, nitrite/nitrate release, angiogenic factors and circulating progenitor cells, as well as reduced apoptosis, fibrosis, oxidative stress and inflammation in ischemic muscles. Furthermore, hematopoietic antigen-specific B cells in the bone marrow were also increased by G-CSF alone and in combination with PTH. Conclusions PTH might increase the efficiency of hematopoietic stem-cell-based therapy in a recognized model of peripheral ischemia. Our translational experimental therapeutic targeting of the vascular niche points to novel clinical targets for the hematopoietic stem-cell treatment of ischemic vascular diseases. Key Points The vascular niche is a potential therapeutic target for peripheral arterial disease We present a translational research study investigating whether targeting the niche with parathyroid hormone (PTH) might improve stem cell-based therapy in an experimental model of hindlimb ischemia that would be relevant to the clinical use of hematopoietic stem-cell-driven angiogenesis After mobilization induced by granulocyte-colony stimulating factor (G-CSF), mice also receiving PTH showed increased blood flow, capillary density, nitrite/nitrate release, angiogenic factors and circulating progenitor cells together with reduced apoptosis, fibrosis, oxidative stress and inflammation in ischemic muscles Our translational study could stimulate clinical trials aimed at increasing the effectiveness of hematopoietic stem cell therapy in peripheral arterial disease by targeting the hematopoietic stem cell niche with PTH In a recent phase I clinical trial, 38 PTH (up to 100µg for 14 days) was tolerated well and there was no dose-limiting toxicity; thus, the clinical efficacy of PTH will need to be tested in a larger phase II study

Objective The objective of this study is to evaluate patient concerns about in vitro fertilization (IVF) errors and electronic witness systems (EWS) satisfaction. Design The design of this study is a prospective single-center cohort study. Setting The setting of this study was located in the private IVF center. Patient(s) Four hundred eight infertile patients attending an IVF cycle at a GENERA center in Italy were equipped with an EWS. Intervention(s) Although generally recognized as a very rare event in IVF, biological sample mix-up has been reported in the literature. For this reason, some IVF laboratories have introduced EWS with the aim to further reduce the risk of error during biological samples handling. Participating patients received a questionnaire developed through a Likert scale ranging from 1 to 6. Main outcomes measure(s) Patient concerns about sample mix-up without and with an EWS were assessed. Result(s) 90.4 % of patients expressed significant concerns relating to sample mix-up. The EWS reduced these concerns in 92.1 % of patients, 97.1 % of which were particularly satisfied with the electronic traceability of their gametes and embryos in the IVF laboratory. 97.1 % of patients felt highly comfortable with an IVF center equipped with an EWS. Female patients had a significantly higher appreciation of the EWS when compared to their male partners ( p  = 0.029). A significant mix-up event occurred in an Italian hospital during the study and patient’s satisfaction increased significantly towards the use of the EWS after the event ( p  = 0.032). Conclusion(s) EWS, by sensibly reducing the risk for sample mix-up in IVF cycles, has been proved to be a trusted strategy from patient’s perspective.

Pre-implantation genetic diagnosis for aneuploidy testing (PGD-A) is a tool to identify euploid embryos during IVF. The suggested populations of patients that can benefit from it are infertile women of advanced maternal age, with a history of recurrent miscarriages and/or IVF failures. However, a general consensus has not yet been reached.After the clinical failure of its first version based on cleavage stage biopsy and 9 chromosome-FISH analysis, PGD-A is currently performed by 24 chromosome screening techniques on trophectoderm (TE) biopsies. This approach has been clearly demonstrated to involve a higher clinical efficiency with respect to the standard care, in terms of sustained pregnancy rate per transfer and lower miscarriage rate. However, data about PGD-A efficacy calculated on a per intention-to-treat basis, as well as an analysis of its cost-effectiveness, are still missing.TE biopsy is a safe and extensively validated approach with low biological and technical margin of error. Firstly, the prevalence of mosaic diploid/aneuploid blastocysts is estimated to be between 0 and 16 %, thus largely tolerable. Secondly, all the comprehensive chromosome screening (CCS) technologies adapted to, or designed to conduct PGD-A are highly concordant, and qPCR in particular has been proven to show the lowest false positive error rate (0.5 %) and a clinically recognizable error rate per blastocyst of just 0.21 %.In conclusion, there is a sufficient body of evidence to support the clinical application of CCS-based PGD-A on TE biopsies. The main limiting factor is the need for a high-standard laboratory to conduct blastocyst culture, biopsy and vitrification without impacting embryo viability.