Medicine and Pharmacology

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Brief Report
Medicine and Pharmacology
Reproductive Medicine

Da Kuang

,

John Quain

,

Cathy Tie

,

Eriona Hysolli

Abstract: Pre-birth gene correction offers a precise and potentially transformative strategy to prevent severe genetic diseases by repairing pathogenic variants in embryos or gametes. Unlike selection-based preimplantation genetic testing (PGT), which depends on the availability of unaffected embryos, pre-birth gene correction directly addresses the underlying mutation, expanding the number of viable embryos available for transfer. We modeled the prospective impact of this technology in the United States across four exemplar monogenic diseases (sickle cell disease, cystic fibrosis, Marfan syndrome, and Huntington’s disease) under scenarios reflecting current and expanded access to assisted reproductive technologies. Depending on accessibility and implementation, pre-birth gene correction could correct hundreds to thousands of affected embryos each year, offering a viable path to parenthood for families who currently lack unaffected embryos through IVF and PGT alone. While translation will require rigorous evaluation of safety, efficacy, and ethical governance, these findings underscore this technology’s potential to broaden reproductive autonomy and meaningfully reduce the burden of severe genetic disease.
Review
Medicine and Pharmacology
Reproductive Medicine

Agata Puszcz

,

Paulina Kozłowska

,

Justyna Wójcik

,

Anna Morawska

,

Małgorzata Wójcik

,

Katarzyna Plagens-Rotman

,

Monika Englert-Golon

,

Jakub Mroczyk

,

Małgorzata Mizgier

,

Ewa Jakubek

+5 authors

Abstract: Background/Objectives: Sexual health is shaped by lifestyle factors alongside biomedical determinants. This review synthesises evidence on physiotherapy, balneology/peloidotherapy and diet therapy as preventive and therapeutic adjuncts for female sexual dysfunctions and related gynaecological conditions. Methods: A structured narrative review of PubMed and Google Scholar (June–July 2025) was conducted by three independent reviewers using predefined keywords in English and Polish. Case reports, preprints and studies before 2015 were excluded. From 7322 records, 47 studies met inclusion criteria for qualitative synthesis. Results: Physiotherapy—particularly pelvic floor muscle training, multimodal manual therapy, neuromuscular electrical stimulation (including PTNS), magnetostimulation, short-wave diathermy and capacitive–resistive monopolar radiofrequency—was consistently associated with reductions in dyspareunia, chronic pelvic pain and urinary symptoms, with parallel improvements in sexual function and quality of life. Balneological procedures (brine baths/irrigations, crenotherapy, selected radon/sulphide/iodine–bromine applications) and peloidotherapy demonstrated analgesic, anti-inflammatory and perfusion-enhancing effects, with signals of benefit in vulvodynia, endometriosis and infertility support. Dietary measures—higher fruit intake (notably citrus), adequate vitamin D, targeted omega-3 use in PCOS, Mediterranean dietary pattern and prudent red-meat limitation—were associated with favourable endocrine–metabolic profiles and, in selected contexts, reduced disease risk. Conclusions: Integrating lifestyle-medicine modalities with standard care may meaningfully prevent and manage female sexual dysfunctions by addressing pain, perfusion, neuromuscular control and endocrine–metabolic drivers. Implementation frameworks and high-quality trials are warranted to refine indications, dosing and long-term effectiveness.
Review
Medicine and Pharmacology
Reproductive Medicine

József Bódis

,

József Berke

,

Bernadett Nagy

,

István Gulyás

,

Péter Hersics

,

Ákos Várnagy

,

Kálmán Kovács

Abstract: Background: Ultra-weak photon emission (UPE) from living systems has been reported and linked to oxidative reactions. Whether photons mediate communication—particularly at the level of DNA—remains unresolved. Objective: To review biochemical and quantum-biological bases of UPE, summarize measurement approaches, and evaluate whether DNA-related emission could support signalling; we also present pilot data on embryo UPE. Methods: We synthesise literature on sources (reactive oxygen species, lipid peroxidation, protein/DNA oxidation) and detectors (photomultiplier tubes, cooled CCD cameras, Complementary Metal-Oxide Semiconductor CMOS). We measured UPE from mouse embryos in a dark incubator using an ORCA-Quest CMOS system. Results: UPE is modulated by cellular state; mitochondria, membranes and peroxisomes are key contributors. Models posit DNA as a storage/emitter and potential resonator. In embryos, degenerated two-cell–stage embryos exhibited lower UPE than well-developed embryos. These findings motivate a Photon Emission Embryo Control System (PEECS) for non-invasive assessment. Conclusions: Ultra-weak cellular photon emission—especially the proposed DNA-linked mechanisms—remains a challenging yet promising field. Evidence does not convincingly show DNA acts as a biophotonic communication system, but the hypotheses suggest new ways to view biological information processing and cellular funcion.
Article
Medicine and Pharmacology
Reproductive Medicine

Grażyna Jarząbek-Bielecka

,

Agata Puszcz

,

Mariola Pawlaczyk

,

Katarzyna Plagens-Rotman

,

Małgorzata Mizgier

,

Magdalena Pisarska-Krawczyk

,

Jakub Mroczyk

,

Witold Kędzia

Abstract: Background/Objectives: Genital discomfort, manifested by vulvar itching and burning, is a frequent complaint among women of all ages and has multifactorial origins—including dermatoses, infections, allergies, and hormonal disorders. The study aimed to determine whether selected medical history factors—age, obstetric history, and body mass index (BMI)—influence the frequency of genital discomfort as a reason for gynecological consultation. Methods: A pilot study included 288 female patients aged 11–91 years who presented to outpatient gynecological clinics between September 2018 and February 2025 with symptoms of vulvar itching and genital discomfort. Qualitative data were expressed as numbers and percentages, and age was described using mean, median, quartiles, and range. Associations between categorical variables were assessed using Pearson’s chi-square test, with statistical significance set at p < 0.05. Results: The mean age of patients was 47.4 ± 20.3 years. Most were diagnosed with ICD-10 code N90 (82.6%), while 17.4% had N76. Genital discomfort was most frequently reported by women aged 41–50 years (p < 0.0001). Comorbidities (p < 0.0001) and obstetric history (p < 0.0001) significantly influenced the occurrence of genital discomfort, which was more prevalent among women with chronic conditions and those who had been pregnant. No significant associations were found with BMI (p = 0.2353) or menopausal status (p = 0.3458). Conclusions: Genital discomfort is a common and multifactorial condition requiring an interdisciplinary diagnostic and therapeutic approach. Collaboration among gynecologists, dermatologists, endocrinologists, and dietitians is crucial for effective management and prevention.
Hypothesis
Medicine and Pharmacology
Reproductive Medicine

Nicholaus Nelson-Goedert

Abstract: Female reproductive aging exemplifies accelerated, system-specific decline, with the ovary undergoing the earliest and most pronounced functional deterioration of any organ system. Traditional explanations centered on follicular depletion and oocyte aneuploidy fail to account for the interdependent biochemical pathways driving reproductive senescence. This paper extends the Conglomerate Theory of Aging to female reproductive biology, presenting a unified, systems-level framework in which reactive species-initiated processes— metal bioaccumulation, advanced glycation end product (AGE) formation, advanced lipoxidation end product (ALE) accumulation, and the emergence of metal-AGE/ALE hybrid complexes— interact as mutually reinforcing elements of a single damage network. Within this framework, bioaccumulated metals, AGEs, and ALEs function as interdependent drivers of molecular damage. Metal-catalyzed redox activity amplifies the production of reactive oxygen, nitrogen, and carbonyl species, fostering environments conducive to AGE and ALE formation, while AGEs and ALEs independently propagate redox cycling and inflammation through RAGE-mediated and mitochondrial feedback. These processes collectively erode ovarian cellular integrity, induce mitochondrial and enzymatic dysfunction, accelerate follicular depletion, and disrupt hypothalamic-pituitary-ovarian axis regulation. The model highlights the therapeutic potential of multi-target approaches addressing concurrent pathways of damage amplification. Candidate strategies include glutathione restoration with GlyNAC, selective metal chelation, carbonyl-stress inhibition via compounds such as carnosine, and γ-tocopherol for nitrosative stress. Priorities for future research include biomarker discovery and integrative clinical trials using multiomics platforms to track and modulate these overlapping mechanisms. By framing reproductive aging as a network of self-reinforcing oxidative, glycoxidative, and lipoxidative processes, the Conglomerate Theory of Female Reproductive Aging offers a cohesive biochemical explanation for reproductive decline and identifies convergent intervention points to sustain fertility and extend reproductive longevity.
Brief Report
Medicine and Pharmacology
Reproductive Medicine

Zalessky Alexandr Dmitrievich

,

Bachurin Alexey Vladimirovich

,

Osychenko Alina Anatolievna

Abstract: Near-infrared femtosecond laser is a promising tool for oocyte and embryo manipulation. In nuclear transfer and mitochondrial replacement therapy, this laser can be successfully applied for the enucleation. In addition, it can be used for zygote ploidy normalization by pronuclear destruction. The aim of this work was to develop a new technique for normalizing zygote ploidy. We applied 1033 nm femtosecond laser radiation to eliminate a pronucleus in three-pronuclear human zygotes. The study showed that destruction of pronuclear DNA occurred under the action of the femtosecond laser. At the same time, the zygotes retained their structure and even their ability to cleave. Thus, we suppose that femtosecond laser can be useful for pronuclear destruction and zygote ploidy normalization.
Article
Medicine and Pharmacology
Reproductive Medicine

Robert Milewski

,

Magdalena Skowrońska

,

Agnieszka Kuczyńska

,

Andrei Lebedzko

,

Waldemar Kuczyński

Abstract: Background/Objectives: Accurate prediction of reproductive outcomes remains a key challenge in assisted reproductive technologies (ARTs). While embryo quality assessment has been extensively studied, endometrial receptivity has received less attention despite its critical role in implantation. Endometrial compaction (EC), i.e., the reduction in endometrial thickness between ovulation and embryo transfer, has been proposed as a potential predictor, but the current literature data is inconclusive. This study aimed to develop and validate a novel implantation predictor (IMP), based on extended assessment of endometrial shape and dynamics, that would be useful in determining reproductive success. Methods: The study analyzed data from 61 couples undergoing infertility treatment at the Kriobank Clinic (Białystok, Poland) between December 2021 and February 2025. Endometrial measurements were taken at ovulation peak and on the day of embryo transfer. A set of normalized parameters describing endometrial dimensions was proposed and their changes over time measured. Based on the obtained data, a multivariable logistic regression model was constructed to create the IMP predictor. Results: The proposed model demonstrated high predictive power for implantation, with an AUC of 0.839 (95% CI: 0.739–0.938). Statistically significant differences in IMP values were observed between the pregnancy and no-pregnancy groups (p < 0.0001). Quartile analysis showed that implantation rates increased from 6.25% in the lowest IMP range to 93.3% in the highest, confirming the model’s strong predictive power. In the study group, the model is capable of predicting a quarter of cases in which implantation will almost certainly occur and another quarter in which implantation will almost certainly not occur. Conclusions: This study introduces a novel predictor (IMP) of implantation based on an extensive assessment of endometrial compaction, which may be used in predicting reproductive success. The findings show the importance of considering endometrial receptivity in ART success. They also indicate that integrating IMP with existing approaches may substantially improve predicting reproductive success.
Article
Medicine and Pharmacology
Reproductive Medicine

Othmane Adli

,

Noureddine Louanjli

,

Rachid Aboutaieb

Abstract: Infertility is a major health problem affecting about 15% of couples worldwide. Male etiology is found in almost one-third of cases. This study identified the nature of the relationship between sperm DNA fragmentation (SDF), sperm chromatin condensation (SCC) and sperm parameters. In this study, 80 samples were analyzed using two methods: the TUNEL technique to assess sperm DNA quality and aniline blue coloration to determine the level of chromatic condensation of spermatozoa. In addition, to specify the standard sperm parameters, the spermogram and the spermocytogram were analyzed. The main results revealed a significant difference between SDF and motility and, similarly, between SCC, motility, and teratozoospermia macrocephaly types (p < 0.0001, p < 0.0001, respectively), but no differences between SCC, SDF, and the other sperm parameters (p > 0.99).
Review
Medicine and Pharmacology
Reproductive Medicine

Grzegorz Mrugacz

,

Aleksandra Mospinek

,

Joanna Głowacka

,

Oskar Sprawski

,

Lidia Kawałek

,

Wiktoria Gąsior

,

Julita Machałowska

,

Yekaterina Sidorova

,

Patrycja Borecka

,

Aleksandra Bojanowska

+1 authors

Abstract:

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 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, 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.

Article
Medicine and Pharmacology
Reproductive Medicine

Yusaku Mori

,

Linji Chen

,

Shogo Nishii

,

Miwa Sakamoto

,

Makoto Ohara

,

Akihiko Sekizawa

,

Sho-ichi Yamagishi

Abstract: Background: Assisted reproductive therapy (ART) has been utilized as an effective therapeutic strategy for addressing infertility worldwide, and one of the key determinants of ART success is the acquisition of high-quality embryos through in vitro fertilization (IVF). We investigated here which male factors were associated with embryo formation and quality in conventional IVF (cIVF). Methods: This study was a sub-analysis of a trial conducted to examine the associations of clinical and lifestyle factors with sperm abnormalities in 42 men of infertile couples without identifiable male factor infertility. From the original cohort, 21 men whose partners underwent cIVF were included. Semen samples were evaluated for standard sperm parameters and DNA fragmentation index (DFI). Blood biochemical parameters and lifestyle habits were also evaluated. Blastocysts were assessed 5 days after cIVF, and implantation success was determined 10 days after embryo transfer. Results: Normospermia and oligospermia were observed in 67% and 33% of participants, respectively, with mild sperm DFI in 76%. Blastocysts were formed in 32% of the oocytes following cIVF. Among them, good blastocyst development and quality were observed in 71% and 39%, respectively. Eighteen women underwent blastocyst transfer, resulting in an implantation success rate of 50%. Multiple regression analysis identified sperm DFI as the only variable inversely associated with blastocyst outcomes. In contrast, only female age was associated with implantation success. Conclusions: The present findings suggest that sperm DNA fragmentation may negatively affect high-quality embryo formation in cIVF, even among normospermic and oligospermic men with non-severe sperm DFI.
Article
Medicine and Pharmacology
Reproductive Medicine

Csilla Kurdi

,

Dávid Hesszenberger

,

Dávid Csabai

,

Anikó Lajtai

,

Ágnes Lakatos

,

Rita Jakabfi-Csepregi

,

Krisztina Gödöny

,

Péter Mauchart

,

Ákos Várnagy

,

Gábor L. Kovács

+1 authors

Abstract: Background/Objectives: Endometriosis is a chronic gynecological condition associated with infertility, oxidative stress and altered metabolic regulation. Follicular fluid reflects the microenvironment of the developing oocyte and changes in its amino acid composition may affect reproductive outcomes. This study aimed to characterize alterations in the amino acid composition of the follicular fluid in endometriosis and to identify potential reproductive outcomes. Methods: Targeted metabolomic analysis of 20 amino acids was performed on follicular fluid samples from 56 women undergoing in vitro fertilization (17 with endometriosis, 39 controls). Amino acid concentrations were quantified and compared between groups, adjusting for age and body mass index. Pathway, biomarker and multivariate analyses were conducted to explore metabolic alterations and potential diagnostic markers. Results: Asparagine, histidine and glycine concentrations were significantly higher in the endometriosis group, independent of age and BMI. Pathway analysis indicated perturbations in glycine/serine metabolism, glutathione metabolism and porphyrin metabolism, consistent with oxidative stress and mitochondrial dysfunction. Multivariate modeling demonstrated partial separation between groups while biomarker analysis identified asparagine (AUC=0.76), along with glycine and histidine, as potential discriminators. Additional enrichment of bile acid and methylation-related pathways suggested broader systemic metabolic changes in endometriosis. Conclusions: Endometriosis is associated with distinct amino acid alterations in the follicular fluid, particularly elevated asparagine, histidine, and glycine, which may reflect oxidative stress and impaired mitochondrial function in the follicular environment. These metabolites seem to be potential biomarkers for endometriosis-related oocyte quality changes and may help individualized in vitro fertilization approaches.
Article
Medicine and Pharmacology
Reproductive Medicine

Junbiao Mao

,

Ben Yuan

Abstract: Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women, affecting 8–13 % of the population worldwide. It is defined by the 2003 Rotterdam criteria and is frequently accompanied by endometrial dysfunction, yet non-invasive molecular biomarkers for diagnosis remain scarce. This study aimed to identify a robust gene signature for PCOS endometrial dysfunction through comprehensive bioinformatic analyses. Methods Three public endometrial microarray datasets (GSE103465, GSE4888, GSE51901) were downloaded from the GEO database. Differential expression analysis was performed using limma (|log₂FC| > 1, FDR < 0.05). Functional enrichment analyses (GO and KEGG) were carried out using clusterProfiler. A Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model was constructed to screen the optimal gene signature, and its diagnostic performance was evaluated by receiver operating characteristic (ROC) curves in both training and validation sets. Results A total of 200 differentially expressed genes (DEGs) were identified, mainly enriched in extracellular matrix remodeling, inflammatory response and angiogenesis pathways. A 50-gene LASSO signature was established, achieving an AUC of 0.816 in the training cohort and 0.766 in the independent validation cohort. Conclusions The LASSO-derived gene signature exhibits strong discriminatory power for PCOS endometrial dysfunction and may serve as a novel diagnostic resource for clinical translation.
Review
Medicine and Pharmacology
Reproductive Medicine

Abdelmalek Sghiri

,

Michela Ciccarelli

,

Salman M Waqas

,

Abelhaq Anouassi

,

Ahmed Tibary

Abstract: Camelids are increasingly recognized as important livestock species. They are valuable sources of meat, fiber, and milk. Despite their growing popularity, many aspects of their reproductive physiology and pathology remain unclear. Their reproductive performance is reported to be low in many countries. Advances in camelid veterinary care have identified several disorders, some of which are species-specific. This article describes an approach and diagnosis of infertility and subfertility cases in alpacas, llamas, and camels referred to the authors over the past 35 years. Ultrasonography, endometrial cytology, and biopsy are the primary diagnostic tools for practitioners. However, laparoscopy, hysteroscopy, and cytogenetics are indicated for cases referred to theriogenologists. The incidence of congenital and acquired reproductive disorders is presented. A high incidence of congenital defects of the reproductive tract is found in South American camelids, which raises concerns about animal welfare. Acquired disorders are similar to those described in other species. Endometritis and endometrosis are major disorders contributing to infertility and early pregnancy loss. However, studies on uterine defense mechanisms and the pathogenesis of these disorders are lacking. Hydrobursitis, a common cause of infertility in dromedary camels, warrants further research. The implications of some contagious diseases (tuberculosis, campylobacteriosis, and brucellosis) in female infertility are discussed. These findings emphasize the importance of including camelid medicine in veterinary education to ensure a high standard of care for this species.
Review
Medicine and Pharmacology
Reproductive Medicine

Mona M. Makhamreh

,

Mei Ling Chong

,

Ignatia B. Van den Veyver

Abstract: Advancements in genomic technologies have transformed prenatal genetic testing, offering more accurate, comprehensive, and noninvasive approaches to reproductive care. This review provides an in-depth overview of current methodologies and emerging innovations, including expanded carrier screening (ECS), cell-free DNA (cfDNA) testing, chromosomal microarray analysis (CMA), and sequencing-based diagnostics. We highlight how next-generation sequencing (NGS) technologies have revolutionized carrier screening and fetal genome analysis, enabling detection of a broad spectrum of genetic conditions. The clinical implementation of cfDNA has expanded from common aneuploidies to include copy number variants (CNVs), and single-gene disorders. Diagnostic testing has similarly evolved, with genome sequencing outperforming traditional CMA and exome sequencing through its ability to detect both sequence and structural variants in a single assay. Emerging tools such as optical genome mapping, RNA sequencing, and long-read sequencing further enhance diagnostic yield and variant interpretation. This review summarizes major technological advancements, assesses their clinical utility and limitations, and outlines future directions in prenatal genomics.
Article
Medicine and Pharmacology
Reproductive Medicine

Kata Szilvia Papp

,

Péter Szakály

,

Szilard Kolumban

,

Kalman Kovacs

,

József Bódis

,

Nelli Farkas

,

Gabor Fazekas

,

Balint Farkas

Abstract: Background: Uterus transplantation (UTx) is a proven treatment for individuals affected by absolute uterine factor infertility (AUFI) who desire biological motherhood. Despite over 130 procedures performed worldwide in the past decade, UTx remains relatively unfamiliar, even among healthcare professionals. This study aimed to identify knowledge gaps and evaluate attitudes toward UTx among Hungarian obstetricians/gynecologists and transplantation providers, in anticipation of the first procedure to be performed in the country. Methods: A Microsoft Forms® questionnaire was distributed electronically among Hungarian medical professionals via e-mail, including members of the Hungarian Society of Obstetrics and Gynaecology and the Hungarian Transplantation Society. Additionally, participants of the “Update 2024” OB/GYN conference (held November 28–29, 2024, in Visegrád, Hungary) were invited to complete the survey through a QR code displayed during the event. Results: A total of 290 medical professionals completed the survey (response rate: 27.6%, 290/1,050). Most respondents specialized in obstetrics and gynecology (81.7%, n = 237), with the remainder representing transplantation fields (18.3%, n = 53). Over half (56.6%, n = 161) reported they would recommend UTx to patients with AUFI, and 64.1% (n = 186) agreed that UTx should be available as a treatment option. The medical risks associated with the procedure were deemed acceptable for both living donors (58.0%, n = 168) and recipients (54.8%, n = 159). Conclusion: This is the first study to explore perceptions of UTx among Hungarian medical professionals. The findings suggest a generally favorable professional attitude toward its future clinical implementation.
Article
Medicine and Pharmacology
Reproductive Medicine

Tomomi Kusakabe

,

Yoshiki Wada

,

Tomohiro Umezu

,

Masahiko Kuroda

,

Hitoshi Okochi

,

Toshiya Nishibe

,

Ayako Inoue

,

Takahiro Ochiya

,

Shoji Fukuda

Abstract: Background/Objectives: Critical limb ischemia (CLI) is a severe peripheral vascular disease with limited treatment options. We are conducting a clinical trial using intramuscular transplantation of autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) in CLI patients. Our previous work showed that transplanted BM-MSCs do not differentiate into endothelial cells in vivo, suggesting that secreted factors, including microRNAs (miRNAs), may contribute to therapeutic effects through paracrine mechanisms. This study aims to elucidate the angiogenic mechanisms of miRNAs derived from BM-MSC-derived extracellular vesicles (EVs) using an in vitro model reflecting our clinical protocol. Methods: BM-MSCs were co-cultured with human umbilical vein endothelial cells (HUVECs) in a tube formation assay to model the therapeutic environment. Total RNA was extracted from both BM-MSCs and their EVs, and angiogenesis-related miRNAs were analyzed. Three miRNAs (miR-126, miR-135b, and miR-210) were selected for further evaluation based on EV expression profiles. Synthetic miRNAs were transfected into HUVECs individually and in combination. Tube formation was quantified, and angiogenesis-related protein expression (e.g., VEGF, FGF, Endoglin) was assessed using antibody arrays. Results: Co-culture of BM-MSCs and HUVECs significantly enhanced tube formation in a dose-dependent manner. EV analysis revealed selective packaging of angiogenic miRNAs into EVs. Transfection of miR-126, miR-135b, and miR-210 promoted tube formation, with the combination of miR-126 and miR-135b or the triple combination producing the strongest effect. Protein analysis showed significant upregulation of VEGF, FGF, and Endoglin, indicating the activation of multiple angiogenic pathways. Conclusions: This study provides preliminary mechanistic insights into the pro-angiogenic effects of EV-derived miRNAs in BM-MSC-based therapy for CLI. While each miRNA has been individually reported, our data highlight their synergistic effects in combination, which better reflects the clinical context. These findings support the development of EV-based nucleic acid therapeutics for ischemic disease and provide a foundation for future drug discovery efforts.
Review
Medicine and Pharmacology
Reproductive Medicine

Denisa Oana Zelinschi

,

Alexandra Ursache

,

Eduard Cristian Mihoci

,

Emil Anton

,

Dan Bogdan Navolan

,

Dragos Nemescu

Abstract: Generative artificial intelligence (GenAI), particularly large language models (LLMs) like ChatGPT, is emerging as a tool to address declining birth rates and rising infertility. It enhances reproductive education, preventive interventions, and doctor-patient communication, providing personalized healthcare information discreetly. Sexual and reproductive health is a fundamental human right, yet many lack access to quality care. GenAI offers 24/7 access to reproductive health information through chatbots, aiding patients with diagnoses and lifestyle advice. While useful, AI tools sometimes lack depth for sensitive topics. AI can create educational content tailored to various literacy levels and cultural contexts, helping individuals understand complex medical information. AI tools can destigmatize menstruation and provide personalized insights through cycle tracking, improving health management and education. AI enhances in vitro fertilization (IVF) success through better diagnostics and personalized risk profiles, though it requires careful validation and regulation. AI can improve the accessibility and quality of sexual health education, offering personalized guidance on contraceptive methods. AI chatbots can bridge gaps in reproductive healthcare for marginalized groups by providing confidential, multilingual support. AI tools can enhance communication, helping patients prepare for consultations and engage in shared decision-making. Despite its potential, GenAI faces challenges such as accuracy, bias, privacy concerns, and accessibility issues. Regulatory oversight is still developing. GenAI is transforming reproductive health by providing personalized support and education. However, it must be implemented with a focus on safety, equity, and human connection, ideally through a hybrid approach that combines AI tools with human oversight.
Article
Medicine and Pharmacology
Reproductive Medicine

Walid Shaalan

,

Nourhan Hassan

,

Mohamed Gamal Ibrahim

,

Benedikt Schaefgen

,

Julia Gallwas

,

Ludwig Kiesel

,

Andreas N Schüring

,

Martin Götte

Abstract: Introduction: Adenomyosis, a prevalent gynecologic condition involving invasion of endometrial tissue into the myometrium, remains poorly understood in terms of its molecular pathogenesis. Numb, an important regulator of cellular destiny and stem cell maintenance, has been implicated in numerous proliferative diseases; however, no role for Numb in adenomyosis has been explored to date. This research examines the degree to which Numb protein may play a role in adenomyosis pathogenesis by regulating the regulation of endometrial and myometrial cells. Design: This study analyzed Numb protein expression in tissues from 21 adenomyosis patients and 14 controls using im-munohistochemistry. Numb levels were evaluated in eutopic endometrium, ectopic le-sions, and myometrium. Results: Compared to controls (p < 0.001), adenomyosis patients' eutopic endometrium and myometrium showed considerably higher levels of numb expression. It was predominantly observed in single cells rather than clusters. No sig-nificant variation was noted across menstrual cycle phases. Elevated Numb levels in the myometrium suggest a potential role in tissue invasion. Conclusion: This study presents new evidence of elevated Numb expression in adenomyosis, suggesting that it may play a part in the pathophysiology of the disease and that it is a useful marker for dysregulation of endometrial stem cells.
Article
Medicine and Pharmacology
Reproductive Medicine

Sudarsan Ghosh Dastidar

,

Biswanath Ghosh Dastidar

,

Ratna Chattopadhyay

,

Chandan Chakraborty

Abstract: Objectives: Gonadotropin releasing hormone (GnRH) antagonist protocols are preferred in polycystic ovary syn-drome (PCOS) patients undergoing in-vitro fertilization (IVF) as they provide the best combination of flexibility, acceptable outcomes, and safety. Numerous studies have compared outcomes between GnRH agonist long proto-col and standard flexible antagonist protocol. However, there are scant studies investigating effectiveness of an-tagonist administration from day 1 of ovarian stimulation in PCOS patients. Methods: We performed a retrospective cohort study to compare laboratory and clinical outcomes in IVF between standard flexible day 5/day 6 versus day 1 GnRH antagonist protocol in PCOS patients. Results: Our data indicates significantly superior oocyte yield and top-quality embryo proportion in patients with antagonist from day 1. Cumulative clinical pregnancy rates also tended to be superior in this group. Conclusions: Our findings indicate that administration of GnRH antagonists from day 1 of stimulation in PCOS patients undergoing IVF may lead to superior results.
Article
Medicine and Pharmacology
Reproductive Medicine

Magdalena Skowrońska

,

Michał Pawłowski

,

Aleksandra Dyszkiewicz

,

Angelika Buczyńska

,

Robert Milewski

Abstract: Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations between selected hormonal, anthropometric, and lifestyle-related parameters and serum asprosin concentration. As studies concerning fertility and asprosin have so far been limited to men–with its role in females largely unexplored. The direction of the exploration was pointed towards possible connections with female fertility. Methods: The case-control study group included 56 women of reproductive age (25–42 years), patients of the Reproductive Health Clinic and the Clinic of Endocrinology, Diabetology, and Internal Medicine of Medical University of Białystok, Poland. The levels of selected hormones, including anti-Müllerian hormone (AMH), estradiol, sex hormone-binding globulin (SHBG), and testosterone; body composition parameters; and a lifestyle parameter–night fasting duration–were assessed to test their associations with serum asprosin concentration. Results: A weak negative correlation was found between AMH level and serum asprosin concentration, suggesting a potential link between asprosin and ovarian reserve. In addition, a moderate positive correlation was found between the percentage of total body water (TBW) and serum asprosin concentration. No significant associations were observed between the levels of the other tested hormones and serum asprosin concentration, or between body composition parameters or night fasting duration, and serum asprosin concentration. The multivariate model designed in the study shows that AMH, TBW, and night fasting duration explain 23.4% of asprosin variability. Conclusions: Although the nature of the study is explorative, the findings indicate that the role of asprosin in the female population–particularly its role in fertility–requires further research. Not only is the number of available studies on asprosin insufficient, but the results of this study partly contradict what is known about the hormone from previous studies, largely performed in men. In addition, the results of this study suggest that asprosin may indeed be involved in mechanisms related to female fertility, particularly those connected with ovarian reserve. Nevertheless, studies performed in larger, more homogeneous populations are necessary to confirm the role of asprosin in women, including its associations with female fertility.

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