Search Results (37)

A limited period of endometrial receptivity is defined by molecular interactions between the embryo and maternal tissues, which are crucial for successful implantation. The results of clinical studies assessing intrauterine human chorionic gonadotropin (hCG) as an endometrial priming agent in in vitro fertilisation (IVF) have been inconsistent, markedly affected by dose, timing, and cycle context. This narrative review summarises molecular data demonstrating that hCG modulates immunological, stromal, endothelial, and epithelial compartments in a coordinated manner, affecting essential endometrial processes. hCG promotes adhesion competence and proliferation in the epithelium via a microRNA-regulated signalling axis (miR-126-3p–PIK3R2–PI3K/Akt). Intrauterine hCG promotes controlled apposition and invasion at the vascular interface by selectively strengthening endothelial junctional cohesion via VE-cadherin and CD146, without promoting angiogenesis. hCG collaborates with ERK/mTOR signalling to regulate autophagy and apoptosis, alters steroid–receptor networks in the stroma, initiates early decidual and survival markers (ACTA2, NOTCH1, complement C3), and enhances stress resistance. hCG modifies the immunological milieu by enhancing the activity of regulatory T cells and altering the distribution of uterine natural killer cells. This facilitates immunological tolerance and the remodelling of spiral arteries. These pleiotropic effects together enhance biomarkers and provide a scientific justification for context-dependent clinical responses, including patient-chosen, directed methods for the delivery of intrauterine hCG during IVF. Full article

Objectives: Endometrial carcinoma is the most common gynaecological cancer in developed countries, with both incidence and mortality rates continuing to rise globally. For women of reproductive age diagnosed with early-stage disease or endometrial intraepithelial neoplasia, fertility-preserving treatment should be considered to maintain the possibility of future childbearing. Effective fertility-sparing management requires a multidisciplinary approach that includes patient education, reduction in risk factors, accurate molecular and histological classification to guide targeted therapies, assisted reproductive technologies to improve early conception rates, and attention to the psycho-sexual well-being of patients to support treatment adherence. Methods: This retrospective cohort study analysed the clinicopathological features and treatment outcomes of thirteen patients who received fertility-preserving therapy between 2018 and 2023. Results: The mean age of the patients (n = 13) was 34.4 years, with a range of 20 to 41 years. The overall treatment response rate was 76.9%, including 69.2% complete and 7.7% partial responses. Stable disease was observed in 15.4% of cases, while progression occurred in 7.7%. Among those who achieved complete remission, in vitro fertilisation (IVF) was initiated in four cases, with two ongoing as of the time of data analysis. In one of the cases, after two unsuccessful assisted reproductive attempts, spontaneous conception occurred, resulting in the birth of a child. Conclusions: Our findings support the feasibility and success of fertility-preserving treatment in carefully selected patients, allowing the preservation of reproductive potential alongside oncological care. Full article

Background/Objectives: Ultrasound-guided transvaginal follicular aspiration is a central procedure in in vitro fertilisation (IVF), aiming to collect oocytes necessary for the success of assisted reproduction treatments. Follicular flushing, proposed in the absence of cumulo-oocyte complex (COC) at initial aspiration, remains controversial regarding its real impact on oocyte quality and pregnancy rates. Methods: In this controlled study, conducted in 274 patients, we evaluated the effects of systematic follicular flushing up to 10 washes with a standardised medium (pH 7.3 ± 0.1; 37.2 ± 0.2 °C) on oocyte yield, oocyte morphology, embryo kinetics and clinical outcomes. Results: Flushing resulted in an additional 38% recovery of COCs, mostly between the second and fifth flush, with no significant increase in oocyte dysmorphisms or major embryonic abnormalities. A slight increase in slow cleavages was observed (27% vs. 23%, p = 0.04), as well as a lower oocyte maturation rate when ovulation was triggered by Ovitrelle alone. Clinically, pregnancy rates per transfer were comparable between groups (33.27% without flushing vs. 32.86% with flushing; p = 0.67), as were miscarriage rates (9.11% vs. 8.69%; p = 0.81). Conclusions: These results indicate that follicular flushing, when applied according to a standardised protocol, significantly increases oocyte yield without compromising oocyte morphological quality or embryonic development potential. Although the observed clinical benefits remain modest, this approach could constitute a relevant complementary strategy, particularly in patients with poor ovarian response or in the context of poor initial recovery. However, the controlled but non-randomised nature of this study requires cautious interpretation of the findings. Larger randomised trials, integrating dynamic assessment technologies, such as time-lapse imaging or oocyte transcriptomic analysis, are needed to refine the clinical indications of this technique and explore its underlying biological mechanisms. Full article

High non-esterified fatty acids (NEFAs) during negative energy balance in dairy cattle can impair reproduction. While their effects on oocyte maturation and preimplantation embryo development are known, their impact during fertilisation is largely unexplored. This study examined the effects of high NEFA exposure exclusively during in vitro fertilisation (IVF). Bovine oocytes were matured in vitro and fertilised under physiological or high NEFA concentrations. High NEFA concentrations decreased fertilisation, cleavage, and blastocyst rates. Reactive oxygen species production in zygotes was not affected, but blastocysts derived from the High-NEFA group had fewer cells. Spermatozoa exposed to high NEFA concentrations exhibited increased plasma membrane and acrosome damage, higher DNA fragmentation, and reduced mitochondrial membrane potential. The expression of H3K27me3, a repressive histone mark normally erased from fertilisation to embryonic genome activation, was higher in 2-cell than in 4-cell embryos on day 2 after IVF, but only in the High-NEFA group. This delayed H3K27me3 loss, along with increased DNA damage, could partially explain the reduced blastocyst formation observed. In conclusion, high NEFA concentrations can impair pre-implantation embryo development during zygote formation, potentially via effects on both the oocyte and spermatozoon. The latter warrants further investigation using an intracytoplasmic sperm injection model. Full article

Recent progress in assisted reproductive medicine has introduced novel therapeutic possibilities for couples experiencing various reproductive challenges or subfertility. A critical concern in this field is the diminished ovarian response to hormonal treatments preceding ovum pickup, necessitating personalised and optimised protocols to enhance ovarian response across different age groups. Furthermore, a common male factor in IVF couples, oligozoospermia, characterised by a low sperm count, significantly impacts the success rates of assisted reproductive technologies, posing an increasing challenge for in vitro fertilisation clinics. Lifestyle choices, dietary habits, and overall health behaviours have also demonstrably affected fertility outcomes in the 21st century. This original article aims to highlight the synergistic importance of both partners’ health, specifically addressing poor ovarian response and oligozoospermia, in achieving successful conception. Our study analysed intracytoplasmic sperm injection outcomes in couples affected by both aforementioned conditions and proposed an optimal management strategy. This study shows that oligozoospermia significantly reduced ICSI fertilisation and cleavage rates. Poor ovarian responders experienced more cancelled cycles due to fewer embryos. While blastocyst rates relative to zygotes were comparable, overall success was lower in groups with male factor infertility and poor ovarian response, necessitating personalised treatment approaches. Full article

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common reversible liver disorder linked to pregnancy, characterised by pruritus and elevated serum bile acids (BAs). Condition severity correlates with increased maternal and neonatal complications, and recent evidence highlights a significantly elevated risk of adverse perinatal outcomes, including stillbirth, when BA > 100 µmol/L. Methods: This retrospective study, conducted at a tertiary perinatology centre between 2019 and 2023, was performed in two phases. In the first phase, baseline group characteristics and pregnancy outcomes were compared between ICP and non-ICP (control) groups. In the second phase, outcomes were analysed across three ICP severity subgroups: mild (BA < 40 µmol/L), moderate (BA 40–99 µmol/L), and severe (BA ≥ 100 µmol/L). Results: A total of 210 patients diagnosed with ICP and 24,177 controls were included in the analysis. After multivariable regression, the results indicated that patients with severe ICP (BA ≥ 100 µmol/L) experienced significantly worse perinatal outcomes compared to those with mild or moderate disease: spontaneous preterm birth occurred in 26.7% of cases (p = 0.002), iatrogenic preterm birth in 36.7% (p < 0.001), meconium-stained amniotic fluid in 43.3% (p = 0.001), and neonatal intensive care unit (NICU) admission in 23.3% (p = 0.006). This subgroup also had the lowest mean birth weight (2830 g, p < 0.001). Notably, no stillbirths were recorded in any of the subgroups. Compared to controls, no major differences in maternal characteristics were noted, except in pregnancies conceived via in vitro fertilisation (IVF, p = 0.012) and those complicated by gestational diabetes (p = 0.040), both showing elevated risk for ICP development. Conclusions: This study confirms an association between ICP and increased perinatal complications, with severity of disease correlating with poorer outcomes. The findings highlight the need for standardised BA testing and improved strategies for perinatal management. Full article

Objective: To evaluate patient perceptions regarding ultrasound-guided embryo transfer, visualisation of embryos prior to transfer, and continuity of care with the same physician during in vitro fertilisation (IVF) treatments. Setting: Between January and September 2023, this study was conducted at the IVF MOMO’ FertiLIFE centre in Bisceglie, Italy. Design: Descriptive and observational study based on an anonymous survey administered to IVF patients at the time of embryo transfer. The goal was to assess the subjective emotional and psychological response to selected procedural elements of the embryo transfer process. Participants: Out of 284 distributed questionnaires, 200 were included in the final analysis. Inclusion required fully completed responses. Questionnaires with incomplete, unclear answers or patient refusal were excluded. The study group was compared with the general IVF patient population treated at the centre over the past 5 years to ensure representativeness. Methods: Patients completed a structured questionnaire using a five-point Likert scale. Statistical analysis included descriptive statistics, Spearman’s rank correlation, Friedman test, and exploratory factor analysis. Ethical approval was obtained (CELFer no. 07/2021), and all participants provided written informed consent. Results: The majority of patients reported a heightened sense of calm and reassurance during ultrasound-guided embryo transfer. Viewing embryos on a monitor before transfer was also positively perceived. A strong preference emerged for continuity of care with the same physician throughout the IVF process. While this study did not assess objective stress levels or clinical outcomes, the findings highlight the psychological comfort associated with these patient-centred practices. Limitations: This single-centre study is based on self-reported data and lacks objective assessments of psychological well-being. Therefore, results reflect personal perceptions rather than measurable clinical outcomes. Broader, multicentre research using validated psychological tools is needed to confirm and expand these findings. Furthermore, the questionnaire used in this study was developed internally and not validated externally with standardised psychometric instruments. Conclusions: This study provides insight into IVF patients’ subjective experiences, emphasising the perceived emotional benefits of specific procedural and relational aspects of care. These findings support the integration of patient-centred strategies—such as visual engagement and physician continuity—into routine IVF practice to enhance overall patient well-being. Full article

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

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

Introduction: Fertility is fundamental to human well-being, significantly impacting both individual lives and societal development. In particular, sperm morphology—referring to the shape, size, and structural integrity of sperm cells—is a key indicator in diagnosing male infertility and selecting viable sperm in assisted reproductive technologies such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). However, traditional manual evaluation methods are highly subjective and inconsistent, creating a need for standardized, automated systems. Objectives: This study aims to develop a robust and fully automated sperm morphology classification framework capable of accurately identifying a wide range of morphological abnormalities, thereby minimizing observer variability and improving diagnostic support in reproductive healthcare. Methods: We propose a novel ensemble-based classification approach that combines convolutional neural network (CNN)-derived features using both feature-level and decision-level fusion techniques. Features extracted from multiple EfficientNetV2 variants are fused and classified using Support Vector Machines (SVM), Random Forest (RF), and Multi-Layer Perceptron with Attention (MLP-Attention). Decision-level fusion is achieved via soft voting to enhance robustness and accuracy. Results: The proposed ensemble framework was evaluated using the Hi-LabSpermMorpho dataset, which contains 18 distinct sperm morphology classes. The fusion-based model achieved an accuracy of 67.70%, significantly outperforming individual classifiers. The integration of multiple CNN architectures and ensemble techniques effectively mitigated class imbalance and enhanced the generalizability of the model. Conclusions: The presented methodology demonstrates a substantial improvement over traditional and single-model approaches in automated sperm morphology classification. By leveraging ensemble learning and multi-level fusion, the model provides a reliable and scalable solution for clinical decision-making in male fertility assessment. Full article

Background: Chromosomal numerical and structural alterations are significant causes of various developmental disorders in foetuses. Non-invasive prenatal testing (NIPT) has emerged as an effective screening tool for detecting common aneuploidies, aiding in the identification of individuals who may require further diagnostic work-up. Methods: This retrospective, monocentric observational study evaluates the usage patterns, test choices, turnaround times (TAT), and outcomes of NIPT between 2013 and 2023 on a sample of 2431 pregnant women at a special hospital offering outpatient services and comprehensive gynaecological/obstetric inpatient care. We analysed the trends in NIPT usage, high-risk results, prior screening procedures, as well as factors such as age, gestational age and in vitro fertilisation (IVF) status. NIPT was performed using cell-free foetal DNA (cffDNA) extracted from maternal plasma, followed by library construction, sequencing and result analysis. The sequencing results were aligned with reference genomes, and z-scores were calculated to assess the likelihood of aneuploidy. Statistical significance was set at p < 0.05. Results: The average age of women undergoing NIPT decreased from 36.1 years in 2013 to 33.01 years in 2023 (p = 0.0287), and mean TAT dropped from 12.44 days in 2013 to 7.08 days in 2023 (p = 0.0121), with the most substantial reduction occurring between 2013 and 2019. The study identified a stable rate of women who underwent IVF seeking prenatal testing, with no statistically significant difference between the first half and the second half of the analysed period (p = 0.2659). Among high-risk results, there were 39 chromosomal abnormalities detected, most of them belonging to trisomy 21 (59%). Conclusions: Our findings demonstrate the increasing efficiency and accessibility of NIPT in prenatal care in Croatia, while the significant reduction in TAT and the decreasing age of women undergoing NIPT reflect enhanced operational practices and broader acceptance. Introducing NIPT into the public healthcare system in the Republic of Croatia could improve equitable access to advanced prenatal care and enhance pregnancy outcomes. Future advancements in technology and genetic counselling will further enhance its role, requiring careful attention to ethical and regulatory considerations. Full article

The effect of mycotoxin exposure on follicular fluid composition and reproductive outcomes in women undergoing in vitro fertilisation (IVF) was investigated in this study. Twenty-five patients were included, and follicular fluid and serum samples were analysed for various mycotoxins. Principal observations:1. Mycotoxin presence: All examined mycotoxins were detected in follicular fluid. Follicular fluid (ff) levels: Deoxynivalenol (DON), alfa-Zearalenol (α-ZOL), Zearalenone (ZEN), and total aflatoxin (AFs) were significantly higher in follicular fluid than in serum. 2. Follicular fluid and reproductive outcomes: A positive correlation was observed between the ratio of oocytes to total follicles and the follicular Fumonisin B1 (FB1) levels. Multiple linear regression analysis revealed a significant relationship between DON and T-2/HT-2 toxins (T2/HT2) levels in the follicular fluid. 3. Hormone levels: Follicular 17-beta estradiol (E2) and progesterone (P4) levels were higher than the serum levels. Follicular P4 correlated with serum P4 and Anti-Müllerian hormone (AMH) levels. In contrast, follicular E2 did not correlate with plasma E2 levels. 4. Mycotoxin–hormone interactions: A positive correlation was observed between follicular P4 and T2/HT2 toxin levels, whereas a negative correlation was found between ffE2 and ffT2/HT2, and a positive correlation was found between ZEN and E2. Conclusion: This study elucidated the presence of various mycotoxins in the follicular fluid and their potential influence on reproductive outcomes. Further research is warranted to clarify the specific mechanisms underlying these effects and develop strategies for detecting mycotoxin exposure in women undergoing IVF. Full article

Background/Objectives: Female infertility due to unexpected causes exhibits a great challenge for both clinicians and women who are trying to conceive. The present clinical case series study aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in women and improving reproductive health in unexplained infertility issues. The objectives were to assess the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; (3) and healthy live birth. The inclusion criteria were to related to females who failed to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from in vitro fertilisation (IVF) cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. Methods: Case series of three female subjects with unexplained age-related infertility issues, which included a failure to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from IVF cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. In each case, previous conditions were recorded and then compared with outcomes after the patient received a course of PBM treatments. In every case, fertility outcomes improved. Three cases resulted in a full-term pregnancy and the birth of a healthy baby. PBM treatments were given at weekly and/or at two-week intervals using IR and NIR wavelengths between 600 nm and 1000 nm in the lead up to natural conception, IVF oocyte retrieval, blastocyst/embryo implantation, and/or the production of viable embryos. Results: In every case, fertility outcomes improved. Improvements in reproductive health outcomes in each case give reason to suggest that PBM may help to improve unexplained age-related infertility. Conclusions: Our study demonstrated that multiwavelength of red and NIR PBM with either an LED or laser, or a combination, improved female fertility and reproductive health and contributed to healthy live births in females diagnosed with unexplained age-related infertility. Extensive studies with robust data are warranted to validate our PBM dosimetry and treatment protocols. Moreover, understanding the genetic and phenotype biomarkers is important to standardise a range of PBM light dosimetry. Full article

This study explores the proteomic composition of follicular fluid (FF) from women undergoing oocyte retrieval for in vitro fertilisation (IVF), with a focus on the effects of polycystic ovary syndrome (PCOS). FF samples were collected from 74 patients, including 34 with PCOS and 40 oocyte donors. Proteomic profiling using machine learning identified significant differences in protein abundance between the PCOS and control groups. Of the 484 quantified proteins, 20 showed significantly altered levels in the PCOS group. Functional annotation and pathway enrichment analysis pointed to the involvement of protease inhibitors and immune-related proteins in the pathophysiology of PCOS, suggesting that inflammation and immune dysregulation may play a key role. Additionally, HDL assembly was identified as a significant pathway, with apolipoprotein-AI (APOA1) and alpha-2-macroglobulin (A2M) as the major proteins involved. Notably, myosin light polypeptide 6 was the most downregulated protein, showing the highest absolute fold change, and may serve as a novel independent biomarker for PCOS. Full article

Introduction: Poor outcomes following IVF treatments are speculated to be due to the transfer of aneuploid embryos that cannot be identified based on morphological evaluation alone. This leads to patients requiring numerous embryo transfers and, consequently, a prolonged time interval before live birth. Embryo selection following preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS) has been suggested as an intervention to shorten time to pregnancy in women undergoing in vitro fertilisation (IVF). Past studies assessing the clinical efficacy of PGT-A in improving clinical outcomes have been conflicting and the associated clinical pregnancy rates and live birth rates following the transfer of a mosaic embryos have yet to be determined. None of the existing studies solely included women of advanced reproductive age (ARA). The pilot study and proposed RCT will determine if, compared to morphological evaluation alone, the use of PGT-A through NGS is a more clinically effective, safer, and more cost-effective way to provide IVF treatment in women of advanced reproductive age. Method and Analysis: The proposed pilot study will aim to randomise 100 patients within a single-centre study to evaluate recruitment, randomisation, and adherence to study protocol and allocated trail arms by participating patients. The results of the pilot study will enable us to determine the sample size for a larger study to establish the effectiveness of PGT-A in ARA women. Ethics and Dissemination: The study (Integrated Research Application System Number 236067) received approval from the Health Research Authority and Health and Care Research Wales (HCRW) and the East Midlands—Leicester South Research Ethics Committee (20/EM/0290). The results will be made available to patients, the funders, the Reproductive Medicine societies, and other researchers. Trial registration: ClinicalTrials.gov Identifier: NCT05009745, n. Full article