Female Health Research Articles

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial

Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. A total of 35 patients received 6×107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No.20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

The Key Role of Vitamin D in Female Reproductive Health: A Narrative Review.

Vitamin D, besides its crucial role in bone health and immune function, has received increased attention in recent years due to its possible impact on many processes related to female reproductive health. Recent research has tried to explain the role played by vitamin D in maintaining adequate hormonal status, fertility, and pregnancy outcomes. Our aim for this narrative literature review was to highlight and explain the mechanisms through which vitamin D status impacts female reproductive health. We believe this represents a very important subject of research, especially due to the increased incidence of infertility nowadays. Further studies are necessary on the association between vitamin D status and female reproductive health in order to fully understand its effects and to reach a consensus regarding vitamin D supplementation as a method to improve fertility status.

T-2 toxin exposure induces ovarian damage in sows: lncRNA CUFF.253988.1 promotes cell apoptosis by inhibiting the SIRT3/PGC1α pathway

T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-α pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c, Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-α pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-α pathway and promotion of cell apoptosis.

Sub-Chronic Methomyl Exposure Induces Oxidative Stress and Inflammatory Responses in Zebrafish with Higher Female Susceptibility.

The widespread use of carbamate pesticides has raised significant environmental and health concerns, particularly regarding water contamination and the disruption of defense systems in organisms. Despite these concerns, research on the differential impacts of pesticides on male and female organisms remains limited. This study focused on methomyl, investigating sex-specific differences in liver antioxidant defenses and inflammatory response indices in male and female zebrafish after 56 days of exposure to environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings indicate that methomyl exposure significantly increased ROS content in zebrafish livers, inducing oxidative stress and activating enzymatic antioxidant defenses such as SOD, CAT, and GSH-Px activities. Sub-chronic exposure altered the expression of apoptosis-related genes (Bax/Bcl2a and Caspases3a), resulting in liver cell apoptosis in a concentration-dependent manner, with the 0.20 mg/L concentration causing the most severe damage. Additionally, methomyl exposure at environmentally relevant concentrations triggered persistent inflammatory responses in liver tissues, evidenced by increased transcription levels of inflammatory factor genes and the activation of toll-like receptors, heightening susceptibility to exogenous allergens. It is noteworthy that oxidative damage indicators (AST, ROS, MDA) and inflammatory gene expressions (IL-1β, TNF-α) were significantly higher in female livers compared to male livers at 0.10-0.20 mg/L methomyl exposure. Consequently, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms and highlights the need for heightened consideration of the risks posed by environmental endocrine disruptors to female health and safety.

The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight.

Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation. Both cortisol and inflammatory cytokines stimulate the production of plasminogen activator inhibitor-1 (PAI-1), a potent fibrinolysis inhibitor. Chronic anxiety, fear, and depression are among the many hypofibrinolytic conditions increasing the risk of oligo-anovulation, miscarriage, fetal growth restriction, and preeclampsia. Although significant, the impact of negative emotions on implantation is not as obvious as on ovulation or placentation. Other hypofibrinolytic conditions that may affect female reproduction through mechanisms dependent or independent of PAI-1 include metabolic disturbances (e.g., due to consumption of highly palatable foods, often used to alleviate negative affect), inflammation, hyperhomocysteinemia, hypothyroidism, hypercortisolism, antiphospholipid antibodies, and the 4G allele of the PAI-1 gene. Benzodiazepines and antidepressants should be used with caution in the first trimester as this combination may cause malformations. Also, selective serotonin reuptake inhibitors have fibrinolytic properties that increase the risk of bleeding after surgical procedures. Psychological interventions, especially group therapy, are effective in the prevention of reproductive disorders. Controlled trials are needed to test the hypothesis that female reproductive health depends on psychological well-being, a balanced diet and physical activity, suppression of inflammation and autoantibodies, and homocysteine and hormonal homeostasis.

The state of female reproductive health in a city with a large petrochemical complex

Introduction. The demographic situation in the country is characterized by a natural decline in the population, which determines the special importance of the protection of motherhood and childhood. The system of obstetrics largely affects the health status of the population and the future generation. Therefore, the study of the state of obstetrics has a high social significance and is relevant. Purpose of the study. To assess the state of female reproductive health of the population living in a city with a large petrochemical complex. Materials and methods. An analysis of primary digital data characterizing the intensive and extensive indicators of the state of obstetric care in the city of Salavat for 2020 was performed. According to the report of the Ministry of Health of the Republic of Bashkortostan “The state of health of the population and the activities of medical institutions of the Republic of Bashkortostan in 2020” a comparative analysis was carried out. Results. An analysis of the state of obstetric care in the city of Salavat showed that women began to give birth less, they interrupted one third of the onset of pregnancies with abortions. The number of abortions per 1,000 women of childbearing age is 1.5 times higher than in the republic. Over the years, the number of abortions is growing against the background of their decline in the republic. Women who wish to give birth in the vast majority come under the supervision of an antenatal clinic until the 12-week gestation period. The results of the course of pregnancy, childbirth, and the postpartum period, the absence of maternal mortality indicate to a high level of obstetric care. However, he draws attention to the fact that 45.6±1.5% of deliveries and the postpartum period proceeded against the background of complications, among which the most significant were anemia, premature rupture of the amniotic membrane, and violations of labour activity. Every third woman in labour underwent a caesarean section, every fifth - vacuum extraction. The health indicators of the fetus and newborn in the trend in years are improving and more favourable than in the republic as a whole, but 58.9±1.3% of neonates were born sick and fell ill. Mainly in the form of asphyxia during childbirth (18.6±1.2%) and infectious diseases (39.5±4.4%). Preterm infants get sick 2 times more often than full-term ones and the main reason is asphyxia during delivery and respiratory disorders over the perinatal period. Limitations. The analysis of the primary digital values of obstetric care indicators of the forms of federal statistical observation and accounting of medical institutions in Salavat for 2020 was carried out. Conclusion. More favourable health indicators of pregnant women, mothers, fetuses in Salavat in comparison with republican and all-Russian ones indicate to the high-quality, qualified obstetric care. The higher incidence of respiratory diseases in infants during the first year of life living in a city of large petrochemistry determines the need for special in-depth studies.

Clinical Spectrum of Long COVID: Effects on Female Reproductive Health.

The COVID-19 pandemic caused by SARS-CoV-2 has presented numerous health challenges, including long-term COVID, which affects female reproductive health. This review consolidates the current research on the impact of SARS-CoV-2 on the menstrual cycle, ovarian function, fertility, and overall gynecological health. This study emphasizes the role of angiotensin-converting enzyme receptors in viral entry and the subsequent tissue-specific pathological effects. It also explores the potential influence of long COVID on hormonal balance and immune responses, contributing to menstrual irregularities and impaired ovarian function. The findings indicate a higher prevalence of long-term COVID-19 among women, highlighting the substantial implications for reproductive health and the need for sex-sensitive longitudinal studies. Enhanced surveillance and targeted research are essential to develop effective interventions that prioritize women's reproductive well-being following SARS-CoV-2 infection. This review advocates for a sex-informed approach to ongoing COVID-19 research and healthcare strategies, aiming to provide up-to-date and pertinent data for healthcare providers and the general public, ultimately improving outcomes for females affected by long COVID.

Evaluation of urban–rural difference in breast cancer mortality among Chinese women during 1987–2021: A hierarchical age-period-cohort analysis

BackgroundBreast cancer mortality varies in urban and rural areas in China. Studies have reported urban–rural difference across time period, however, the evaluation on urban–rural differences in age and birth cohort effects is limited. Our aim was to quantitatively assess urban–rural disparities in age, period and cohort effects in breast cancer mortality in China. MethodsWe collected age-specific breast cancer mortality rates for urban and rural females aged 20–84 years from 1987 to 2021. Hierarchical age-period-cohort (HAPC) models were used to evaluate the effect of area (urban, rural) on breast cancer mortality and investigate urban–rural differences in age, time period and birth cohort effects. ResultsWe found a significant area (urban, rural) effect on breast cancer mortality in that rural females had a lower mortality risk than urban females [−0.25 (95 % confidence interval (CI): −0.32, −0.17)]. Age trajectories of mortality based on the HAPC model showed nonlinear trends with adjustment for area variable. The urban–rural difference in age effect appeared to be divergent with age, and urban women had higher mortality risk in the senior age group. The urban–rural difference in birth cohort effect indicated a reversal around the birth cohort group of 1962–1966, after which rural females had a higher mortality risk than urban females. ConclusionThe area (urban, rural) could affect breast cancer mortality among women, and the effect of urban–rural difference varies with age and birth cohort. To promote the health of urban and rural females, the gap between urban and rural areas should be shorten.

Elucidating the reproductive toxicity mechanisms in female zebrafish: A transcriptomic study of lifetime tris(2-chloroethyl) phosphate exposure

Tris(2-chloroethyl) phosphate (TCEP), emerging as a predominant substitute for brominated flame retardants (BFRs), is now increasingly recognized as a prevalent contaminant in aquatic ecosystems. The extent of its reproductive toxicity in aquatic species, particularly in zebrafish (Danio rerio), remains insufficiently characterized. This study subjected zebrafish embryos to various concentrations of TCEP (0, 0.8, 4, 20, and 100 μg/L) over a period of 120 days, extending through sexual maturation, to assess its impact on female reproductive health. Notable reductions in body weight (0.59- and 0.76-fold) and length (0.71- and 0.77-fold) were observed at concentrations of 20 and 100 μg/L, with a concomitant decrease by 0.21- to 0.61-fold in the gonadal somatic index across all treatment groups. The reproductive output, as evidenced by egg production and hatchability, was adversely affected. Histopathological analysis suggested that TCEP exposure impedes ovarian development. Endocrine alterations were also evident, with testosterone and 11-ketotestosterone levels significantly diminished by 0.38- and 0.08-fold at the highest concentration tested, while 17β-estradiol was elevated by 0.09- to 0.14-fold in all exposed groups. Transcriptomic profiling illuminated numerous differentially expressed genes (DEGs) integral to reproductive processes, including hormone regulation, neuroactive ligand-receptor interactions, oocyte meiosis, and progesterone-mediated maturation pathways. Collectively, these findings indicate that lifelong exposure to TCEP disrupts ovarian development and maturation in female zebrafish, alters gene expression within the hypothalamic-pituitary-gonadal axis, and perturbs sex hormone synthesis, culminating in pronounced reproductive toxicity.

The shared mechanism and potential diagnostic markers for premature ovarian failure and dry eye disease

Premature ovarian failure (POF), which is often comorbid with dry eye disease (DED) is a key issue affecting female health. Here, we explored the mechanism underlying comorbid POF and DED to further elucidate disease mechanisms and improve treatment. Datasets related to POF (GSE39501) and DED (GSE44101) were identified from the Gene Expression Omnibus (GEO) database and subjected to weighted gene coexpression network (WGCNA) and differentially expressed genes (DEGs) analyses, respectively, with the intersection used to obtain 158 genes comorbid in POF and DED. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of comorbid genes revealed that identified genes were primarily related to DNA replication and Cell cycle, respectively. Protein–Protein interaction (PPI) network analysis of comorbid genes obtained the 15 hub genes: CDC20, BIRC5, PLK1, TOP2A, MCM5, MCM6, MCM7, MCM2, CENPA, FOXM1, GINS1, TIPIN, MAD2L1, and CDCA3. To validate the analysis results, additional POF- and DED-related datasets (GSE48873 and GSE171043, respectively) were selected. miRNAs-lncRNAs-genes network and machine learning methods were used to further analysis comorbid genes. The DGIdb database identified valdecoxib, amorfrutin A, and kaempferitrin as potential drugs. Herein, the comorbid genes of POF and DED were identified from a bioinformatics perspective, providing a new strategy to explore the comorbidity mechanism, opening up a new direction for the diagnosis and treatment of comorbid POF and DED.

Hsa_Circ_002144 Promotes Glycolysis and Immune Escape of Breast Cancer Through miR-326/PKM Axis.

Background: Breast cancer is a leading cause of cancer-related deaths in women worldwide, posing a significant threat to female health. Therefore, it is crucial to search for new therapeutic targets and prognostic biomarkers for breast cancer patients. Method: Bioinformatics analysis, quantitative real-time PCR (qRT-PCR), and fluorescence in situ hybridization (FISH) were employed to investigate the expression of hsa_circ_002144 in breast cancer. Transwell assay, Western blotting, and cell viability assay were utilized to assess the impact of hsa_circ_002144 on the proliferation, migration, and invasion of breast cancer cells. Additionally, a mouse model was established to validate its functionality. Flow cytometry, WB analysis, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, exosomes isolation, and co-culture system were employed to elucidate the molecular mechanism underlying macrophage polarization. Result: we have discovered for the first time that hsa_circ_002144 is highly expressed in breast cancer. It affected tumor growth and metastasis and could influence macrophage polarization through the glycolytic pathway. Conclusion: This finding provides a new direction for breast cancer treatment and prognosis assessment.

O-174 Marginal gains: can small actions in the ART lab improve the environmental impact of medically assisted reproduction?

Abstract Marginal gains can small actions in the ART laboratory improve the environmental impact of medically assisted reproduction? (Invitation) Study question Is it possible to reduce the environmental impact of assisted reproductive technology (ART) laboratories while maintaining quality and safety? Summary answer While individual interventions may yield modest results, their cumulative effect on a wider scale can lead to substantial reductions in resource consumption and emissions over time without compromising treatment outcomes or patient/staff safety. What is known already According to the World Health Organisation (WHO) the change in global climate is one of the gravest threats facing humanity, with pregnant women, new-born and child health considered highly vulnerable. In recent years growing evidence has linked climate change, air pollution, pollutant exposure and microplastics to compromised male and female reproductive health and even spontaneous and in vitro fertilisation (IVF) outcomes. Ironically, the healthcare industry is a major contributor of greenhouse gas emissions, and the rapidly increasing utilisation of ART has raised concerns regarding its environmental footprint. A field primarily driven by highly specialised, energy-intensive laboratory processes, continuous monitoring of hormone testing, single-use consumables and large amounts of waste; the quest for bringing awareness to sustainable practices within ART laboratories is critical, not just for the planet, but for our patients and future generations. Study design, size, duration Alongside a comprehensive review of existing literature, a panel of international professionals and enthusiasts within reproductive medicine, law and environmental science convened in a green conferencing format to discuss key environmental challenges associated with ART and explored potential avenues for enhancing sustainability in the laboratory. A survey and interviews with stakeholders also took place to understand current attitudes and provide real-time social, economic and environmental examples of sustainability in ART laboratories. Main Results I will present a roadmap for sustainability in the IVF laboratory so far. A selection of actions which result in marginal gains within the ART laboratory include but are not limited to: Participate in a ‘green certification’ programme specifically tailored to the IVF laboratory and consider forming a ‘green team’ Aim for energy efficiency, renewable energy, preventive maintenance and consider plug load of non-essential equipment for cost savings. Consider widening operating ranges for temperature and humidity, air circulation changes and HVAC design where possible for energy savings of 15–30% Correct waste management can result in > 30% reduction in clinical waste alongside €11,600 annual savings, with focus on prevention of unnecessary consumables (dishes, media), reducing use of plastics and other single-use items to the extent that is possible and safe, and reusing where appropriate (e.g., training vitrification straws). Adopt electronic platforms for consents/laboratory paperwork; avoiding the use of > 40 pages per cycle in the UK. Reuse packaging materials (cold gel packs, bubble wrap) or form partnerships with local businesses who can reuse. Manage inventory carefully, asking for products with longer expiry dates, and consolidate purchase order to minimise frequency. Minimise liquid nitrogen loss during routine activities and consider batching samples for cryo-transport to minimise frequency of shipments. Limitations Every country, region and laboratory is different and will have their own myriad of regulatory constraints and industry standards to adhere to. This may present barriers to the adoption of certain sustainability measures in ART laboratories and is therefore imperative to seek local guidance first. Wider implications of the findings The carbon footprint of ART extends beyond the laboratory and into the supply chain, encompassing transportation, pharmaceutical production, and waste disposal processes. In this way a holistic approach is necessary, with the need for partnerships between fertility clinics, manufacturers, and regulatory bodies continuously working together to drive the development and adoption of sustainable practices and technologies across the entire ART field.

O-038 Impact of maternal aging on the DNA repair landscape in mouse oocytes

Abstract Study question How does maternal aging impact DNA damage accumulation and DNA repair capacity in mammalian oocytes? Summary answer Age-related changes in DNA repair compartments and chromatin organisation drive DNA damage accumulation in aged oocytes, ultimately contributing to the decline in DNA repair capacity. What is known already Oocyte loss occurs progressively from birth and accelerates as women approach their mid-30s, posing a significant challenge to female reproductive health. Recent studies have highlighted the role of the DNA repair response in driving ovarian ageing and oocyte loss. Aged oocytes accumulate elevated levels of DNA damage. Unless repaired, persistent DNA damage activates DNA repair checkpoints, causing the elimination of defective oocytes. Although we know DNA double-strand breaks (DSBs) in oocytes increase with maternal age, surprisingly, little is known about why this damage is not repaired efficiently. Study design, size, duration Oocytes were isolated from ovaries of 8 weeks or 68-86-week-old CD1 mice, which correspond to reproductively young and old females respectively. Over 600 and 1000 oocytes from aged any young females were used to analyse DNA damage levels, DNA repair effciency, DNA repair compartments and for other live assays. Participants/materials, setting, methods DNA damage was induced in CD1 oocytes from young and aged mice using neocarzinostatin. Levels of DNA damage and DNA repair proteins were quantified using immunofluoresnce confocal/STED microscopy. High-resolution light sheet microscopy was used to perform live imaging of dynamics of DNA damage foci and chromosome segregation during meiosis. Main results and the role of chance Our work demonstrates that aged oocytes have a lower DNA repair capacity and reduced mobility of DNA damage sites compared to young oocytes. We further show that incomplete DNA repair results in defective chromosome integrity and partitioning, thereby compromising oocyte quality. To investigate the causes of the age-related decline in DNA repair, we systematically studied the localization and abundance of several DNA repair proteins in oocytes from young and aged mice. We found that DNA repair proteins localized in spatially distinct DNA repair compartments in oocyte nuclei, that form during the late stages of oocyte growth, accompanied by changes in the activity of DNA repair pathways. Several DNA repair proteins, their corresponding compartments, and their response to DNA damage were altered in aged oocytes. Lastly, we demonstrate that age-related cohesin loss increases DNA damage levels and reduces DNA repair capacity. We hypothesize that cohesin dissociation with maternal ageing may make chromosomes prone to accumulate DNA damage without proper DNA repair. Thus, age-related changes in DNA repair compartments and chromatin organisation drive DNA damage accumulation in aged oocytes, ultimately contributing to the decline in reproductive potential. Limitations, reasons for caution Neocarzinostatin, a radiomimetic drug used to induce DNA DSBs in mouse oocytes in vitro, may not fully represent sources of DNA damage during aging. The CD1 mouse model and ages were selected to recapitulate equivalent advanced maternal age in women. Further investigation is needed to confirm these findings in humans. Wider implications of the findings Overall, we propose that altered DNA repair machinery and cohesin loss contribute to persistent DNA damage and reduced DNA repair capacity in aged oocytes, which can cause chromosome defects and fragmentation, and eventually trigger oocyte death, thereby accelerating the loss of female fertility. Trial registration number Not Applicable

O-220 Ovarify: a deep learning model for automatic calculation of ovarian morphological features in pelvic ultrasonography

Abstract Study question Can a deep learning model accurately characterize ovarian features on pelvic ultrasounds? Summary answer We developed a deep learning model, Ovarify, that can accurately classify and segment ovarian features on pelvic ultrasounds. What is known already Ovarian morphology, as detected using pelvic ultrasonography, is used widely in the assessment of gynecological health. Morphological metrics such as ovarian volume and antral follicle count have known diagnostic and prognostic value for a variety of gynecological outcomes, ranging from risk for ovulatory disorders to likelihood of response to assisted reproductive technologies. However, a lack of standardization in the interpretation of ovarian features, and the time-intensive nature of validated image analysis techniques (such as 2D grid analysis), limits their utility in clinical practice. Deep learning provides an opportunity to overcome these limitations. Study design, size, duration The training dataset for the model comprised 426 3D pelvic ultrasounds obtained using the GE Voluson ultrasound platform, yielding 56,538 individual frames with potential ovarian content. In addition, a similarly collected validation dataset consisted of 95 ultrasounds, yielding 11,304 frames. The held-out test set comprised 107 ultrasounds with 14,767 frames. All frames were manually labeled with the associated 2D ovarian contour, and 163 of the ultrasounds had an associated ovarian volume label. Participants/materials, setting, methods Ovarify consists of two stages: 1) a lightweight classifier that labels ultrasound frames as either positive or negative (having or not having ovarian content) and 2) a subsequent U-Net-inspired segmentation module with an Xception backbone and attention-based decoder that segments the ovary and antral follicles in all frames previously classified as positive. Classification performance was evaluated using F1-score and area under the receiver operating characteristic curve (AUROC). Segmentation performance was evaluated using the Jaccard index. Main results and the role of chance For the classification stage, Ovarify achieved an AUROC of 0.980±0.002 and 0.976±0.004 on the training and validation sets, respectively. On the held-out test set, the model achieved an AUROC of 0.971±0.005. In addition, the model achieved an F1-score of 0.825±0.006, 0.810±0.013, and 0.784±0.014 on the training, validation, and held-out testing sets, respectively. The high AUROC and F1-scores across both seen and unseen datasets support a high-performing classifier. In the segmentation stage, Ovarify reached a median Jaccard index of 0.815±0.004 on the unseen test set when tasked with segmenting the ovary, and a median Jaccard index of 0.657±0.018 on the unseen test set when segmenting antral follicles. High agreement between the ground truth ovary and follicle labels and the predicted segmented regions increases confidence in the downstream morphological analysis. For example, the Pearson correlation coefficient between the Ovarify-calculated ovarian volume and manually-validated ovarian volume was 0.813, indicating that an automatic ovarian volume calculation highly aligns with the ground truth. Ovarify was able to provide predictions in under one minute for the entirety of the held-out test set. Limitations, reasons for caution Ovarify was trained on images generated by the GE Voluson platform and has not been evaluated for generalizability across ultrasound images generated using machines whose output does not match the DICOM format standard. Wider implications of the findings The model developed is relevant for automatically calculating ovarian morphological features from pelvic ultrasounds. This approach has implications in removing user-specific bias and error when calculating biomarkers associated with female reproductive health, including but not limited to ovulatory disorders such as polycystic ovary syndrome (PCOS). Trial registration number not applicable

P-293 Influence of the endometrial microbiota composition on the clinical outcomes of egg donation PGT-A cycles with controlled endometrial receptivity

Abstract Study question Does the endometrial microbiota composition and diversity influence embryo implantation and pregnancy evolution in assisted reproduction treatment (ART) cycles? Summary answer Endometrial microbiota composition influences ART success. Detection of endometrial pathogens is associated with poor outcomes whereas sterile endometria show the highest pregnancy and live-birth rates What is known already The endometrial microbiota has emerged as a possible influencing factor in the results of ART. Recent research suggests its impact on female reproductive health, particularly in patients with chronic endometritis (CE), where the presence of microbial pathogens associated with this condition has been linked to infertility. In turn, the bioregulatory role of species of Lactobacillus in this tissue has been explored, although its essentiality or benefit for female reproductive function continues to be topics of debate. Study design, size, duration This is a case-control retrospective study analysing for the first time the influence of the endometrial microbiota composition on the clinical outcomes of 220 women undergoing egg donation cycles with Preimplantation Genetic Testing for Aneuploidy (PGT-A) and controlled endometrial receptivity between March 2016 and April 2021 in IVF-Life Alicante (Spain). ART results after the transfer of a single euploid blastocyst in the WOI of patients with different endometrial microbiota profiles were analysed and compared. Participants/materials, setting, methods Presence of 18 microbial CE pathogens and 4 Lactobacillus species was determined by high-throughput qPCR (MicrobioMap®, iGLS) in endometrial samples obtained during the WOI of a hormone replacement therapy cycle. In all cases, PGT-A by next generation sequencing (NGS) (EmbryoMap, Vitrolife) and study of endometrial receptivity by gene expression analysis (ER Map, iGLS) were performed. Clinical outcomes (β-hCG+, β+ and live birth, LB) in relation to the endometrial microbiota profile were analysed and compared. Main results and the role of chance In the study, 31.8% of patientś endometria were identified without microbial detection, 40% exclusively with Lactobacillus, 13.2% with pathogens only, and 15% with both. Clinical results revealed significant differences in β+ rates among the groups (p < 0.05). The absence of microorganisms was associated with higher success rates (β + 72.9%), while the presence of pathogens significantly reduced pregnancy success (β + 41.4%). A similar trend was observed in LB rates, although it did not reach statistical significance (44.3% and 24.1%, respectively). The presence of Lactobacillus alongside pathogens improved clinical outcomes (β + 57.6% LB 48.5%). Interestingly, exclusive presence of Lactobacillus showed lower implantation rates than patients without microbial detection (β + 58%). These findings highlight the impact of microbial composition on the clinical outcomes of ART cycles, underlining the association between endometrial microbiota patterns and pregnancy success. Limitations, reasons for caution This study is constrained by its retrospective nature, emphasizing the need for further validation through randomized controlled trials, non-selection studies, or other investigative approaches to confirm the extent of any clinical benefits. Endometrial biopsies were obtained transcervically, while executed with utmost care, risk of contamination cannot be completely excluded. Wider implications of the findings The composition and diversity of the endometrial microbiota is key for ART success. A sterile endometrial environment offers optimal conditions for implantation and pregnancy. The study highlights the potential of Lactobacillus in counteracting the negative impact of pathogenic presence. Trial registration number not applicable

O-217 Evaluating the impact of obesity on oocyte quality, using 2 main factors in cumulus cells (CC) and follicular fluid (FF) which reflect oocyte quality

Abstract Study question How obesity impacts oocyte quality through analysis of mtDNA expression in CC and levels of proteins BMP-15 and HSPG2 in FF? Summary answer There is correlation between increased BMI and lower levels of BMP15 and a decreased expression of mtDNA that reflect decreased oocyte quality in overweight women. What is known already Obesity impacts female health and impairs fertility. There is limited evidence suggesting that obesity impairs oocyte quality. BMP-15 (Bone morphogenetic protein 15) is a protein synthesized by oocyte, is a factor predicting quality of the oocyte and female fertility. Heparan sulfate proteoglycan 2 (HSPG2) is a protein secreted from granulosa cells and there are limited studies regarding the function of HSPG2 in reproduction including oocyte quality. BMP-15 and HSPG2 secreted to FF. Oocyte quality was demonstrated to be influenced by mtDNA (mitochondrial DNA) content in CC. Study design, size, duration Prospective observational cohort study performed between February 2022 until June 2022 in a single university-affiliated hospital. Total of 50 patients were enrolled. Participants/materials, setting, methods Women who underwent IVF or ICSI cycles were included. Exclusion criteria were patients older than 40 years, fertility preservation, unbalanced endocrine disorders and less than 4 follicles at the time of OPU (oocyte pick-up). Follicular fluid and cumulus cells were collected following OPU. mtDNA was assessed by quantitative real-time PCR. BMP-15 and HSPG2 were measured with ELISA method quantitatively. Lipid profile, hormonal profile and C-reactive protein were evaluated in blood and follicular fluid samples. Main results and the role of chance Patients were divided based on BMI, 28 patients with BMI < 25 (Group 1) and 22 with BMI > 25 (Group 2). A significant increase in BMP-15 in FF (38.8 ± 32.5 vs. 14.3 ± 10.8 ng/ml; p = 0.001) and mitochondrial DNA in CC (1.10 ± 0.3 vs. 0.87 ± 0.18 Fold change expression; p = 0.016) were found in group 1. Significantly higher CRP in blood (7.1 ± 5.4 vs. 3.4 ± 4.3; p = 0.015) and FF (5.2 ± 3.8 vs. 1.5 ± 1.6; p = 0.002) and LDL level in blood (91 ± 27 vs. 71 ± 22; p = 0.008) in group 2. HDL levels were significantly higher in group 1 in the blood (50 ± 12 vs. 62 ± 18; p = 0.015) and FF (20.9 ± 7.2 vs. 34 ± 26; p = 0.05). The fresh clinical pregnancy rate demonstrated a trend toward better results in group 1 (47.8% vs. 28.6%: p = 0.31), as well as in FET (69.2% vs. 53.8; P = 0.69). Limitations, reasons for caution Research included relatively small number of participants. We can’t report our cumulative pregnancy rate since not all frozen embryos were transferred yet. Wider implications of the findings Obesity is an increasing worldwide problem and impairs fertility outcome. Our study demonstrates decreased oocyte quality in the group of overweight women through 2 important markers BMP-15 and mtDNA. We recommend our patients to lose weight and improve their lifestyle in order to overcome those impaired quality markers. Trial registration number Not applicable

Premature ovarian insufficiency: knowledge, attitudes, and quality of care offered by gynecologists.

Premature ovarian insufficiency (POI) affects up to 3% of the global female population, influencing metabolic, cardiovascular, and reproductive health. Medical expertise in diagnosis, effects, and treatment strategies, particularly for gynecologists, is crucial for ensuring improved healthcare for women. The objective of this study is to assess the state of medical knowledge regarding the diagnosis, treatment, and follow-up of POI among Brazilian gynecologists. A cross-sectional study was conducted using online questionnaires administered to 16,000 members of the Brazilian Federation of Gynecology and Obstetrics. In total, 460 questionnaires were received from gynecologists who had an average age of 44.49 ± 12.57 years and 19.37 ± 12.95 years of professional experience. Fifty-three percent of gynecologists diagnosed POI correctly, and 49% requested karyotype analysis, while fewer than 10% identified all POI etiologies. Over 90% of gynecologists understood the long-term consequences of POI for bone and cardiovascular health. Despite being a consequence of hypoestrogenism, hormone therapy was recommended only by 20% of doctors, with no more than 50% of them prescribing appropriate doses for young women. Regarding self-perception, 60% of gynecologists declared deficient knowledge regarding how to offer care and guidance to women, with hormone therapy being reported as the most important reason (47%). Current concepts and guidelines for POI are not adequately understood or applied in Brazilian clinical practice, leading to suboptimal care.

Modulatory Effects of Vitamin D: A Possible Approach to Mitigate Air Pollution Related Pregnancy Complications.

Approximately 99% of people on the planet breathe air that exceeds the World Health Organization's permitted threshold for pollution. South Asia is home to the world's most polluted cities. Population-based studies have suggested that women's reproductive health outcomes are worsening due to air pollution. Preeclampsia, miscarriage, gestational diabetes, high blood pressure, and unfavorable birth outcomes, including preterm birth, low birth weight, or even stillbirth are all linked to exposure to air pollution during pregnancy. It is estimated that 0.61 million deaths in India alone were related to indoor air pollution. Females frequently cook in the household using solid fuel as a primary combustion source. Women in the regions with the highest population density are disproportionately affected by high levels of poor-quality indoor air. Recently, it has been proposed that air pollution has a distinct role in the onset of vitamin D deficiency. Numerous studies have explored associations between low vitamin D level and various female reproductive health conditions since the discovery of the vitamin D receptor. It is worthy to note that some of these reproductive health conditions positively correlate with the severity of air pollution. In this study, the evidence has been synthesized on vitamin D's protective properties and dietary and pharmaceutical interventions have been discussed to show their beneficial effects in decreasing the long-term negative impacts of air pollution on women's health.

Interval training and cardiometabolic health in reproductive-aged females.

Physical activity and exercise training are especially important for reproductive-aged females as exercise-induced health benefits can also affect their infants. However, levels of physical inactivity remain high among females in this age group, before, during, and after pregnancy. There is a great need for practical and feasible exercise modes to increase adherence to exercise in this population, and interval training may be a time-efficient training modality. Interval training is a form of exercise involving intermittent bouts of intense effort interspersed with recovery periods of rest or lower-intensity exercise. A substantial amount of research indicates that interval training induces superior cardiometabolic health benefits compared with iso-energetic moderate-intensity continuous exercise. This review provides a comprehensive overview of research on interval training interventions in reproductive-aged females across various life stages, focusing on the cardiometabolic health benefits. We discuss the potential role of interval training in premenopausal females with overweight/obesity, polycystic ovary syndrome, and subfertility, as well as the potential influence of oral contraceptives on cardiometabolic adaptations to interval training. Furthermore, this review also highlights recent findings supporting the beneficial role of high-intensity interval training for cardiometabolic health outcomes during pregnancy. In summary, the existing evidence suggests that interval training can improve several cardiometabolic and reproductive outcomes in females spanning different life stages. However, more research is needed to further strengthen the evidence-base for physical activity recommendations for females in their reproductive years of life.

Inventory of Medicinal Plants for Male and Female Reproductive Health by Ethnic Javanese and Ethnic Dayak Seberuang in Balai Harapan Village, Tempunak District, Sintang Regency

Inventory of Medicinal Plants for Male and Female Reproductive Health by Ethnic Javanese and Ethnic Dayak Seberuang in Balai Harapan Village, Tempunak District, Sintang Regency