Is the composition of microRNAs (miRNAs) in uterine fluid (UF) of women with recurrent implantation failure (RIF) different from that of healthy fertile women? The composition of miRNAs in UF of women with RIF is different from that of healthy fertile women and the dysregulated miRNAs are associated with impaired endometrial receptivity and embryo implantation. It has previously been demonstrated that the miRNAs secreted from endometrial cells into the UF contribute to the achievement of endometrial receptivity. Endometrial miRNAs are dysregulated in women with RIF. In this descriptive laboratory case–control study, miRNA abundancy was compared between UF collected during implantation phase from healthy fertile women (n = 17) and women with RIF (n = 34), which was defined as three failed IVF cycles with high-quality embryos. Recruitment of study subjects and sampling of UF were performed at two university clinics in Stockholm, Sweden and Tartu, Estonia. The study participants monitored their menstrual cycles using an LH test kit. The UF samples were collected on Day LH + 7–9 by flushing with saline. Samples were processed for small RNA sequencing and mapped for miRNAs. The differential abundance of miRNAs in UF was compared between the two groups using differential expression analysis (DESeq2). Further downstream analyses, including miRNA target gene prediction (miRTarBase), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis (g:Profiler) and external validation using relevant published data, were performed on the dysregulated miRNAs. Two miRNAs were technically validated with quantitative real-time PCR (RT-PCR). After processing of the sequencing data, there were 15 samples in the healthy fertile group and 33 samples in the RIF group. We found 61 differentially abundant UF miRNAs (34 upregulated and 27 downregulated) in RIF compared to healthy women with a false discovery rate of <0.05 and a fold change (FC) of $≤$−2 or $≥$2. When analyzed with published literature, we found that several of the differentially abundant miRNAs are expressed in endometrial epithelial cells and have been reported in endometrial extracellular vesicles and in association with endometrial receptivity and RIF. Their predicted target genes were further expressed both in the trophectodermal cells of blastocyst-stage embryos and endometrial mid-secretory epithelial cells, as assessed by publicly available single-cell transcriptome-sequencing studies. Pathway analysis further revealed that 25 pathways, having key roles in endometrial receptivity and implantation, were significantly enriched. Hsa-miR-486-5p (FC −20.32; P-value = 0.004) and hsa-miR-92b-3p (FC −9.72; P-value = 0.004) were successfully technically validated with RT-PCR. The data are available in Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/ with GEO accession number: GSE173289. This is a descriptive study with a limited number of study participants. Moreover, the identified differentially abundant miRNAs should be validated in a larger study cohort, and the predicted miRNA target genes and enriched pathways in RIF need to be confirmed and further explored in vitro. RIF is a major challenge in the current IVF setting with no diagnostic markers nor effective treatment options at hand. For the first time, total miRNAs have been extensively mapped in receptive phase UF of both healthy women with proven fertility and women diagnosed with RIF. Our observations shed further light on the molecular mechanisms behind RIF, with possible implications in future biomarker and clinical treatment studies. This work was financially supported by the Swedish Research Council (2017-00932), a joint grant from Region Stockholm and Karolinska Institutet (ALF Medicine 2020, FoUI-954072), Estonian Research Council (PRG1076), Horizon 2020 innovation (ERIN, EU952516) and European Commission and Enterprise Estonia (EU48695). The authors have no competing interests to declare for the current study.

(1) Background: Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. This study aimed to identify differentially expressed miRNAs in endometriosis and study their functions in the disease. (2) Methods: Endometrial tissue was collected from women with endometriosis (n = 15) and non-endometriosis controls (n = 17). Dysregulated miRNAs were identified through small RNA-sequencing, and their biological significance was explored by target gene prediction and pathway analysis. Selected miRNAs were examined in paired ectopic endometriomas and eutopic endometrium (n = 10) using qRT-PCR. Their roles in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing on transfected cells and the endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in the eutopic endometrium of women with endometriosis compared to endometrial tissue from women without endometriosis. Pathway analysis indicated enrichment in cell migration and proliferation-associated pathways. Further ex vivo studies of miR-193b-5p and miR-374b-5p showed that both miRNAs were upregulated in endometrioma. Overexpression of these two miRNAs in vitro inhibited cell migration, and mRNA sequencing revealed several migration-related genes that are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration.

Pericytes are versatile cells integral to the blood vessel walls of the microcirculation, where they exhibit specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, and maintaining homeostasis and are involved in the tissue repair process. The human endometrium is a unique and complex tissue that serves as a natural scar-free healing model with its cyclical repair and regeneration process every month. The regulation of pericytes has gained increasing attention due to their involvement in various physiological and pathological processes. However, endometrial pericytes are less well studied compared to the pericytes in other organs. This review aims to provide a comprehensive overview of endometrial pericytes, with a focus on elucidating their physiological function and potential implications in uterine disorders.

Infertility caused by a thin endometrium remains a significant challenge in assisted reproduction and is often associated with a low success rate after treatment with assisted reproductive technology. There is a lack of consensus in the field concerning both its diagnostic criteria and clinical management. The currently available treatment options are few with limited efficacy. Recent advances in cell therapy and bioengineering have, however, shown promising results for the treatment of a thin endometrium. Notably, these novel interventions have demonstrated the ability to increase endometrial thickness, restore endometrial function, and improve reproductive outcomes. In this comprehensive review, we focus on a critical evaluation of these emerging therapeutic strategies for a thin endometrium including platelet-rich plasma, exosomes derived from stem cells, and bioengineering-based techniques. By synthesizing the findings from available clinical trials, we highlight the promising outcomes achieved so far and underscore the importance of robust clinical trials in assessing the safety and efficacy of these interventions in the future. Continued research efforts to unravel the intricate mechanisms involved in endometrial repair and regeneration will also be essential to enhance our understanding of this multifactorial condition and to identify novel treatment targets for future therapeutic interventions.

This chapter examines the potential of natural estrogens, particularly estradiol and estetrol, in combined hormonal contraceptive pills as alternatives to the widely used synthetic ethinyl estradiol. Current evidence highlights the promise of these natural estrogens in providing effective contraception with improved safety profiles and maintained tolerability. Estradiol and estetrol exhibit favorable safety and efficacy profiles compared to ethinyl estradiol. Initial studies suggest that estetrol combined with drosperinone provide effective contraception with a predictable bleeding patternand reduced risk for venous thromboembolism compared to ethinyl estradiol containing pills. Such risk may also be further mitigated by non-oral administration of estradiol. Long-term efficacy and safety data are needed to confirm the benefits of natural estrogens and their impact on diverse populations and comorbid conditions. By addressing these gaps, future research can enhance our understanding of natural estrogens in hormonal contraception, ultimately refining their use in clinical practice.

Background Mifepristone is a selective progesterone receptor modulator with decades of data demonstrating its potential as a highly effective emergency as well as non-emergency contraceptive. Despite considerable evidence pointing to the potential effectiveness of mifepristone as a non-emergency contraceptive, no systematic review has been conducted to synthesise the available evidence. This systematic review aims to synthesise the current evidence on the use of mifepristone as a non-emergency contraceptive to prevent pregnancy among cisgender girls and women of reproductive age. Methods We developed an electronic search strategy in collaboration with the research librarian. We will search five databases (Ovid Medline, CINAHL, EMBASE, Cochrane-Central Trials and Global Health) from inception and identify additional studies using several grey literature search strategies. All databases will be searched from inception, and we planned to complete the search by 30 June 2024. An Ovid Medline search strategy conducted on 24 May 2024 is provided as an example. We will include all studies that involve cisgender girls and/or women of reproductive age (defined as 54 years or younger), which assessed mifepristone as a non-emergency contraceptive to prevent pregnancy. The primary outcome is contraceptive effectiveness. Two independent reviewers will screen studies for eligibility through title, abstract, and full-text review. We will extract data with Covidence software using a Cochrane Effective Practice and Organisation of Care (EPOC)-adapted data-extraction tool and will assess risk of bias using the EPOC risk of bias tool and the Newcastle–Ottawa Scale. If sufficient data are available, we will conduct a meta-analysis using fixed and/or random effect models. However, if we are unable to conduct a meta-analysis, we will present the results narratively using the synthesis without meta-analysis guidelines and the EPOC table recommended for presenting findings without meta-analysis. Grades of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of the evidence. We will report this review according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Ethics and dissemination This review is focused on secondary data and does not require any ethical approval. We aim to publish the review in a peer-reviewed scientific journal to promote knowledge transfer and present results using other knowledge translation mediums. PROSPERO registration number CRD42024554720.