Medicine and Pharmacology

Abstract: Background. Endometriosis is a chronic gynecological disorder affecting a substantial proportion of women of reproductive age and is associated with impaired quality of life, absenteeism, presenteeism, and reduced work participation. Despite its potential occupational implications, evidence on how occupational physicians (OPs) manage workers affected by endometriosis remains scarce. This study aimed to assess knowledge, attitudes, and practices (KAP) regarding endometriosis among Italian OPs. Methods: A cross-sectional web-based survey was conducted between 1 and 18 April 2026 among members of an Italian discussion group restricted to occupational physicians. The questionnaire investigated demographic characteristics, knowledge of endometriosis, risk perception, perceived barriers to workplace management, and previous experience in issuing conditioned fitness-for-work appraisals. Multivariable logistic regression was performed to identify factors independently associated with having previously issued work restrictions because of endometriosis. Results: A total of 155 occupational physicians participated in the survey. Most respondents considered themselves adequately informed about endometriosis (78.1%) and reported previous professional experience with affected workers (81.3%). However, objective knowledge revealed important gaps, particularly regarding disease prevalence (26.5% correct responses), familial predisposition (34.8%), and diagnostic pathways (31.6%). The mean General Knowledge Score was 64.1% (95%CI 62.2–66.1), while only 11.0% of respondents reported awareness of occupational recommendations specifically addressing endometriosis. Overall, 65.8% of participants reported having previously issued conditioned fitness-for-work appraisals, most frequently recommending increased work breaks, avoidance of night shifts, or limitation of shift work. In multivariable analysis, male gender (aOR 5.69, 95%CI 1.84–17.58), participation in continuing medical education activities (aOR 85.72, 95%CI 6.60–1114.21), information obtained from colleagues (aOR 4.67, 95%CI 1.23–17.77), and employment in healthcare settings (aOR 5.91, 95%CI 1.92–18.16) were independently associated with previous issuance of restricted fitness-for-work judgments, whereas relying exclusively on undergraduate medical education was negatively associated with this outcome (aOR 0.07, 95%CI 0.01–0.39). Conclusions: Italian occupational physicians generally recognized endometriosis as a clinically relevant condition and frequently encountered affected workers in daily practice. Nevertheless, important deficiencies persist regarding epidemiological knowledge, diagnostic issues, and awareness of occupational management strategies. Continuous professional education, interdisciplinary exchange, and practical experience appear to contribute more substantially to occupational decision-making than undergraduate training alone. These findings support the development of targeted educational interventions and shared occupational recommendations aimed at improving workplace management and promoting the inclusion and retention of women affected by endometriosis in the workforce.

Abstract: Background/Objectives: Fertility preservation is a key component of cancer care in women of reproductive age, and controlled ovarian stimulation (COS) followed by oo-cyte/embryo cryopreservation is considered the standard strategy. Although COS pro-tocols are generally standardized, systemic effects related to different malignancies may interfere with ovarian reserve assessment and influence stimulation planning and counselling. This study aimed to evaluate COS outcomes across different malignancy types in women undergoing fertility preservation. Methods: This retrospective study included 331 oncological patients who underwent COS for fertility preservation at a single referral center between May 2008 and May 2025. Patients were stratified into three groups according to malignancy type: breast cancer, hematological malignancies, and other cancers. Ovarian reserve was assessed using serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). COS outcomes, including stimulation duration, total gonadotropin dose, number of retrieved and mature oocytes, follicular output rate (FORT), and follicle-to-oocyte index (FOI), were compared among groups. Results: Pa-tients with hematological malignancies were significantly younger and showed higher AFC values compared with the other groups, whereas AMH levels did not differ sig-nificantly. After adjustment for age and AFC, patients with hematological malignancies showed significantly lower AMH levels compared with breast cancer patients, supporting the presence of a relative AMH–AFC discordance. In unadjusted analyses, gonadotropin requirements were higher in breast cancer patients, whereas the number of retrieved and mature oocytes was higher in patients with hematological malignancies. However, after adjustment for age and AFC, malignancy type was not independently associated with retrieved oocytes, mature oocytes, total gonadotropin dose, or stimulation duration. FORT and FOI were comparable among groups. Conclusions: Malignancy type did not appear to independently impair ovarian responsiveness to stimulation. Patients with hemato-logical malignancies showed preserved stimulation outcomes despite AMH values not being proportionally higher than expected based on their younger age and higher AFC. These findings suggest that AMH should be interpreted with caution in systemic ma-lignancies and that AFC may be particularly useful for tailoring fertility preservation counselling and stimulation strategies when AMH and AFC are discordant.

Abstract: Background: The SPARK (Symptoms of PCOS ameliorated by responses to Ke-to-adaptation) pilot study investigates whether nutritional ketosis can improve repro-ductive and metabolic outcomes in women with Polyendocrine Metabolic Ovarian Syndrome (PMOS). PMOS is a common endocrinopathy characterized by anovulation, hyperandrogenism, and metabolic dysfunction. Objective: To evaluate if a ketogenic diet (KD) or exogenous ketone supplementation (KS) with Qitone™ (bis-octanoyl-(R)-1,3-butanediol) can restore ovulation and menstrual activity. Methods: This ongoing 12-week randomized trial assigns women with PMOS to either a KD or KS intervention. Assessments include body composition by DXA, metabolic and reproduc-tive biomarkers (e.g., insulin, testosterone, SHBG), and cycle tracking via basal body temperature. Results: Preliminary data from seven participants (KD: n=3; KS: n=4) show that 100% demonstrated spontaneous menstrual activity within 2–7 weeks. Full menstrual reinstatement occurred in 86% of participants (KD=3, KS=3), including those with long-standing amenorrhea. Ovulation was predicted in 43% of the cohort. Key metabolic improvements included significant insulin reductions, favorable body composition changes (fat mass loss with lean mass preservation), and enhanced neurobehavioral well-being, including reduced anxiety and improved cognitive clarity. Conclusion: Preliminary findings suggest that both sustained and intermittent ketogenic interven-tions can restore menstrual and ovulatory function through multi-node endo-crine-metabolic recovery, independent of significant weight loss. These results highlight the potential of ketogenic therapies for PMOS but require confirmation in larger trials.

Abstract: This systematic review of 25 original studies examined the efficacy of density gradient centrifugation (DGC) combined with magnetic-activated cell sorting using Annexin V (MACS) for improving sperm quality in infertile men undergoing ICSI. The evidence consistently demonstrates that DGC-MACS significantly reduces sperm DNA fragmentation, with reported reductions ranging from 2.82% to 21.9% in absolute terms, and relative reductions of 39%-83%. The combination of DGC followed MACS achieved superior outcomes compared to either technique alone, reducing DNA fragmentation index (DFI) 4.1 to ± 1.3% compared with 8.1 ± 4.1% for DGC alone and 7.4 ± 3.9% for MACS alone. The treatment improved sperm motility, membrane integrity and overall spermatozoa health by reducing protamine deficiency and chromosomal abnormalities. Clinical results in ICSI cycles showed that although fertilization rates were similar between the treated and control groups, DGC followed by subsequent MACS treatment significantly improved embryo quality (72.5% vs. 51.47% top-quality day-3 embryos), blastocyst formation rate (69.69% vs. 48%), pregnancy rates (60.7% vs. 51.5%, p=0.014), and live birth rates (47.4% vs. 31.2%, p=0.001) with a reduced miscarriage rate (14.7% vs. 20.6%, p=0.034). The technique proved most beneficial in patients with high baseline DNA fragmentation (≥30%) and in those with asthenozoospermia or asthenoteratozoospermia. Studies suggest, and consistently supported by our study results, that performing DGC before MACS (DGC-MACS) may yield superior results compared to the reverse sequence. This is because DGC leads to a primary separation of sperm based on density, motility, and morphology and thus producing a high-density fractions enriched in morphologically normal sperms. MACS by specifically binding to phosphatidylserine (PS) residues on sperm membranes selectively removes PS‑positive/apoptotic sperm in a subsequent purification step. Overall, the literature strongly supports the use of combined DGC-MACS as an effective sperm preparation technique for ICSI in infertile men with elevated sperm DNA fragmentation.

Abstract: The evaluation of peripheral pulmonary lesions (PPLs) represents a persistent clinical challenge, particularly in the context of rapidly expanding lung cancer screening programs generating unprecedented volumes of screen-detected nodules requiring tissue evaluation. Conventional bronchoscopic techniques and earlier navigation platforms, including electromagnetic navigation bronchoscopy (ENB), improved access to peripheral airways but demonstrated variable and generally suboptimal diagnostic performance—historically plateauing at 60–70%—attributable principally to CT-to-body divergence and the diagnostic drop-off phenomenon. Robotic-assisted bronchoscopy (RAB) has emerged as a significant advancement integrating robotic catheter control, shape-sensing or electromagnetic navigation, and adjunctive intraprocedural imaging—principally cone-beam computed tomography (CBCT)—to improve lesion localization and procedural stability. Available evidence suggests that RAB achieves improved diagnostic yields compared with conventional bronchoscopic techniques, particularly when combined with real-time CBCT-guided tool-in-lesion confirmation and multimodal biopsy strategies including transbronchial cryobiopsy. Reported diagnostic yields generally range from 70% to 87% across pooled meta-analytic datasets, with higher yields described in centers employing CBCT and cryobiopsy. A favorable safety profile—with pooled pneumothorax rates of approximately 2%, substantially below the 20–25% associated with CT-guided transthoracic needle biopsy—represents a clinically important differentiator, particularly in patients with emphysema, coagulopathy, or contralateral lung compromise [1,3]. RAB additionally enables procedural capabilities beyond peripheral lesion biopsy, including simultaneous mediastinal lymph node staging, bilateral same-session lesion sampling, fiducial marker placement for stereotactic body radiotherapy, and investigational therapeutic applications. However, current evidence is largely derived from observational studies and single-arm prospective cohorts, with limited randomized data directly comparing RAB with transthoracic biopsy approaches. Outcomes are meaningfully influenced by lesion characteristics, operator experience, institutional volume, and availability of advanced imaging infrastructure. This review summarizes current evidence on RAB platforms, procedural optimization, diagnostic performance, safety, molecular tissue adequacy, and emerging applications, while explicitly addressing limitations, controversies, and areas requiring further investigation. This review was conducted and reported in accordance with PRISMA 2020 guidelines adapted for narrative reviews (SANRA framework).

Abstract: Background: In recent years, time-lapse incubators (TLs) with the ability to maintain a stable culture environment have been developed for in vitro fertilization treatment. Methods: In this retrospective cross-sectional study, data from 1,200 women who visited the Creation and Love fertility center, between April 2021 and October 2023 were reviewed. Among them, electronic medical records of 400 women aged 22-45 who underwent in vitro fertilization treatment were selected and divided into 2 groups according to the type of incubator used: 100 in the TL group and 300 in the CI group to evaluate differences in embryo development. Out of these participants, pregnancy outcomes were compared in 150 who underwent fresh-embryo transfer. Controlled ovarian stimulation was performed by standard antagonist protocol. The primary outcome was live birth rate, and the secondary outcome was good embryo rate. Results: The mean age of the study population was 34.6±5.4. Groups had a similar good embryo rate (67.7% vs. 65.5%, p=0.84), clinical pregnancy rate (49.0% vs. 52.0%, p=0.86) and live birth rate (35.0% vs. 42.0%, p=0.76). Furthermore, subgroup analyses of the live birth rate in women aged >35 was higher in the TL group than the CI group (38.0% vs. 23.4%, p=0.03). Conclusions: Based on the comparative analysis of live birth rates between women cultured using TLs and those using CI during 3-day fresh embryo transfer cycles, our study demonstrated a statistically significant increase in live birth rates among women >35 yr of age in the TL group.

Abstract: Background/Objectives: Follitropin delta is an approved recombinant follicle stimulating hormone (rFSH) expressed in a human cell line. The FSH protein is a heterodimer containing α and β subunits. The FSH α-subunit (FSHα) contains five intramolecular disulfide bonds: C7‑C31, C10‑C60, C28‑C82, C32‑C84 and C59‑C87. The α subunit has four closely spaced cysteine residues that form disulfide bonds. These clustered sites resist protease cleavage, making it difficult to accurately characterize the disulfide bond pairing in this type of protein therapeutic. Methods: The study uses an X-ray crystallography method to determine a high-resolution three-dimensional model structure of the recombinant FSH α-subunit. Results: The crystal structure of FSHα at 2.29 Å resolution, containing the disulfide bonds, is presented. This high-resolution structure provides definitive structural evidence that the disulfide bonds in rFSH are consistent with the expected native structural conformation. Conclusions: The rFSH structure validates the expected cysteine connectivity, overcoming limitations of prior mass spectrometry-based disulfide mapping attempts.

Abstract: Ultrasound is the primary imaging modality for evaluation of the scrotum and male reproductive tract. While high-frequency linear probes allow detailed assessment of testicular parenchyma, comprehensive visualization of epididymal anatomy and its spatial relationship to the testis may be limited using conventional two-dimensional imaging alone . This limitation is clinically relevant in the evaluation of male infertility, where epididymal abnormalities may contribute to obstructive processes We present a clinical image demonstrating a novel external scrotal application of a conventional three-dimensional (3D) transvaginal ultrasound probe. The images were obtained in an adult male undergoing infertility evaluation. With generous coupling gel and minimal probe pressure, the transvaginal probe was applied externally over the scrotum. High-resolution 2D images were first obtained, followed by volumetric 3D acquisition. The acquired dataset was analyzed using multiplanar reconstruction and volume-rendering techniques. This approach enabled clear visualization of the epididymal head, body, and tail, along with their anatomical continuity and relationship to the adjacent testis. The volume-rendered images provided an intuitive 3D depiction of epididymal curvature and spatial orientation, features that can be challenging to appreciate using standard linear scrotal ultrasound alone. Importantly, no patient discomfort, adverse effects, or technical complications were observed during the examination. This clinical image highlights the feasibility of repurposing a 3D transvaginal probe for external scrotal imaging to improve anatomical depiction of epididymal structures. While the technique is not intended to replace conventional scrotal ultra-sound, it may offer additional anatomical insight in selected infertility cases. This re-port serves as a hypothesis-generating illustration and supports further evaluation of its diagnostic utility in larger studies.

Abstract: Backgound/Objective: Breast cancer (BC) management has traditionally relied on static clinicopathologic and immunohistochemical biomarkers (hormone receptor status, HER2 expression, and proliferative activity assessed at diagnosis. However, these biomarkers are typically evaluated at a single time point and may not reflect therapy-induced mo-lecular evolution. This study evaluates whether longitudinal molecular profiling before and after treatment better characterizes tumor dynamics and provides clinically ac-tionable insights into treatment response, resistance, and prognosis. Methods: Thirty-two patients with invasive breast carcinoma were analyzed using his-topathology, immunohistochemistry, tissue-based next-generation sequencing, and plasma circulating tumor DNA (ctDNA) analysis. Paired tumor tissue and plasma sam-ples were collected before and after treatment when available. Changes in biomarker expression, molecular subtype, and genomic alterations were assessed to characterize molecular plasticity under therapeutic pressure. Results: The cohort had a median age of 54 years (range 29–86), predominantly invasive ductal carcinoma (>85%) and high-grade disease. Hormone receptor–positive tumors accounted for 78.1%. Molecular subtypes were Luminal A (34.4%), Luminal B HER2− (40.6%), Luminal B HER2+ (6.3%), HER2-enriched (6.3%), and triple-negative breast cancer (12.5%). Initial tissue sequencing identified PI3K/AKT pathway alterations in 28.1% of cases. Post-treatment analyses revealed substantial molecular discordance, including progesterone receptor loss (33.3%), HER2 status changes (33.3%), and Ki67 variability (77.8%). Plasma ctDNA analysis was informative in 53.1% of patients and identified additional clinically relevant alterations, including FGFR1 amplification and BRCA1/2 variants not detected in tissue. Conclusion: BC molecular profiles are dynamic and frequently altered by therapy. Longitudinal molecular assessment reveals clinically actionable changes overlooked by static subtyping, supporting a dynamic model of molecular classification, highlighting the potential value of adaptive molecular subtyping to improve treatment stratification and resistance monitoring.

Abstract: Background/Objectives: Fertility preservation (FP) spans oncological and non‑oncological indications, including gonadotoxic therapies, benign haematological/metabolic disorders, conditions at risk of premature ovarian insufficiency, severe andrological disease, and elective plans to defer childbearing. We provide a sex‑integrated overview of established and emerging FP strategies and their real‑world effectiveness [1–10]. Methods: Narrative synthesis of guidelines and high‑quality studies (to 2025), prioritising ASCO/ESHRE guidance, systematic reviews, and multicentre/registry data covering oocyte/embryo cryopreservation, ovarian tissue cryopreservation (OTC), GnRH agonists, ovarian transposition, in vitro maturation (IVM), sperm banking, surgical sperm retrieval (SSR), testicular tissue cryopreservation (TTC), and spermatogonial stem‑cell (SSC) approaches [1–10]. Results: For women, oocyte vitrification is the first‑line option when time allows; OTC is established when stimulation is infeasible or in prepubertal girls, with endocrine recovery common and increasing pregnancy/live‑birth reports. For men, sperm cryopreservation before therapy is standard; SSR supports selected cases. Paediatric TTC is feasible but remains experimental, whereas paediatric OTC is clinically implemented. Random‑start COS and letrozole/tamoxifen protocols minimise treatment delay and hormonal exposure; GnRHa co‑treatment preserves ovarian function as an adjunct. Utilisation of banked gametes/tissue remains modest, underscoring the need for pathway optimisation [1–10]. Conclusions: FP should be embedded across oncology and non‑oncology pathways with timely referral, clear counselling on probabilities of live birth, and robust follow‑up. Standardisation, registry‑based evidence and long‑term offspring safety data are priorities to bridge the gap between laboratory potential and clinical effectiveness [1–10].

Abstract: Background: Optimizing intrauterine insemination (IUI) outcomes while minimizing gonadotropin exposure, treatment cost, and the risk of ovarian hyperstimulation syndrome (OHSS) remains a central challenge in ovulation induction, particularly among women with polycystic ovary syndrome (PCOS) or high antral follicle counts (AFC). Sequential stimulation protocols incorporating early letrozole followed by delayed recombinant follicle-stimulating hormone (rFSH) have been proposed as a strategy to improve clinical efficiency while preserving safety and pregnancy outcomes. Objective To compare pregnancy outcomes, gonadotropin consumption, and safety profiles of a letrozole plus late-onset rFSH protocol versus conventional rFSH stimulation in IUI cycles, with particular emphasis on patients with PCOS and high ovarian reserve. Methods: This retrospective comparative cohort study included 764 IUI cycles performed between January 2022 and December 2025 at a tertiary assisted reproductive technologies center. Cycles were stimulated either with early letrozole followed by late-onset rFSH (n = 392) or with conventional rFSH alone (n = 372). The primary outcome was pregnancy per cycle, defined by a positive serum β-hCG test. Secondary outcomes included total gonadotropin dose, endometrial thickness, cycle cancellation, OHSS incidence, and obstetric outcomes. Multivariable logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), mediation analysis, and doubly robust methods were applied to account for baseline imbalances and confounding. Results: In unadjusted analyses, different stimulation protocols influenced pregnancy rates, but the letrozole plus late-rFSH group used significantly lower gonadotropin doses. After accounting for factors like female age and ovarian reserve, stimulation protocol did not independently predict pregnancy outcomes; female age was the main predictor. The rates of cycle cancellation and OHSS were low and similar across protocols, including in women with PCOS and high AFC. Propensity score analyses verified that the letrozole-based protocol produced pregnancy outcomes comparable to standard rFSH stimulation while decreasing gonadotropin use. Conclusions: Sequential stimulation with letrozole plus late-onset rFSH provides pregnancy outcomes comparable to conventional rFSH stimulation while significantly reducing gonadotropin requirements and maintaining favorable safety profiles, even in high-risk populations such as PCOS and high AFC patients. These findings support individualized ovarian stimulation strategies that prioritize both clinical effectiveness and treatment efficiency in IUI cycles.

Abstract: Levonorgestrel (LNG) used in contraceptive methods, necessitates accurate pharmacokinetic (PK) profiling to ensure efficacy and safety. The objective of this study was to develop and validate a highly sensitive LC-MS/MS method for quantification of LNG in human serum and its application in a pharmacokinetic study. 500 µL sample was processed using a liquid-liquid extraction (LLE) protocol optimized for LNG recovery that yielded consistent analyte recovery while minimizing matrix interferences. Chromatographic separation was performed on Waters ACQUITY UPLC BEH C18 reverse-phase analytical column (2.1× 100 mm, 1.7 µm) using mobile phase consisting of acetonitrile and water with 0.1% formic acid (70:30, v/v), delivered under a gradient elution at 300 µL/min flow rate. These conditions provided sharp peak resolution and minimized run times. Mass spectrometric analysis was run with Waters XEVO TQ ABSOLUTE triple quadrupole instrument operating in positive electrospray ionization mode and monitored LNG using multiple reaction monitoring with precursor ion at m/z 312.98>81.468, 90.921, 108.963 amu. Optimized fragmentation parameters yielded high signal-to-noise ratios, enabling trace-level detection in biological matrices. The method demonstrated linearity over calibration ranges of 32.5–2000 pg/mL, with correlation coefficients (R²) exceeding 0.997. Precision and accuracy met bioanalytical method validation guidelines, confirming the robustness of assay for PKs. The validated method was successfully employed to measure serum LNG in a PK study among women implanted in Bangladesh. The method’s sensitivity facilitated LNG detection supporting assessment of drug-release performance in clinical settings. The method proved highly reliable, sensitive, and specific for quantifying LNG in human serum, supporting its use in both clinical monitoring and research applications.

Abstract: This study evaluated whether a gonadotropin-releasing hormone (GnRH) agonist can be effectively used for luteal phase support following a dual trigger in IVF. A total of 284 patients undergoing fresh embryo transfer were included: 116 received a dual trigger and 168 an hCG trigger. All patients received luteal support with Nafarelin nasal spray twice daily for two weeks, starting on the day of oocyte retrieval. Women in the dual trigger group were older (36.2 vs. 32.3 years, p <  0.01), had lower antral follicle counts (7.0 vs. 17.5, p = 0.03), and received higher total gonadotropin doses (3000 vs. 2041 IU, p <  0.01). There were no significant differences between groups in retrieved and mature oocytes, fertilization rate, or blastulation rate. Positive pregnancy rate (β-hCG ≥ 25 mIU/mL) was 46.6% in the dual trigger group and 41.1% in the hCG group, without a significant difference, with similar live birth and miscarriage rates. Logistic regression identified maternal age as a predictor of positive pregnancy (OR = 0.95; 95% CI: 0.90–0.99; p = 0.024), while trigger type was not. Propensity score matching confirmed comparable IVF and pregnancy outcomes between groups. These findings indicate that a dual trigger followed by luteal-phase GnRH agonist support yields IVF and pregnancy outcomes similar to an hCG trigger.

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.

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.

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.

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.

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.

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.

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.