Search

Objective Methods Results Conclusion Thin endometrium caused by various factors affects the conception rate of females worldwide; however, current medications are still insufficient. Therefore, a novel approach is needed. We previously reported the effect of menstrual blood‐derived mesenchymal stem cells (MenSCs) in ameliorating ethanol‐induced endometrial injuries. In the present study, we aimed to investigate whether the effect of MenSCs is enhanced by a combination of platelet‐rich plasma (PRP) infusion.An endometrial injury mouse model was established by infiltrating 95% ethanol for 15 s into the uterus, followed by MenSCs, PRP, or MenSCs + PRP treatment. Pathological changes were observed by HE staining. The expression of CK18, vimentin, ItgαVβ3, and VEGF was determined using IHC staining and WB blotting.Compared with the model, MenSCs, PRP, and MenSCs + PRP treatments significantly improved endometrial damage and thickness, with the combined therapy displaying the most pronounced efficacy. The density of CK18‐, vimentin‐, and ItgαVβ3 positive cells increased most significantly in the MenSCs + PRP group of mice. In addition, the protein expression of CK18, vimentin, and VEGF was significantly upregulated after MenSCs + PRP, MenSCs, and PRP treatment, with MenSCs + PRP therapy showing the best efficacy.MenSCs + PRP therapy is more beneficial for ameliorating ethanol‐induced endometrial damage than MenSCs or PRP alone, providing a basis for the investigation of novel approaches for treating thin endometria. [ABSTRACT FROM AUTHOR]

Reproductive disorders are common events in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies on the molecular mechanisms of implantation disorders in thin endometria, including the study of gene transcriptional activities, have shed light on the identification of the potential biological markers of endometrial receptivity. Background/Objectives: The goal of this study was to reveal the significantly dysregulated selected gene expressions between RIF and RPL patients with thin endometria. Methods: Endometrial samples were collected from RIF patients (n = 20) and RPL patients (n = 19) during the implantation window days (LH + 7—LH + 10) of their natural menstrual cycles. Ten genes were chosen as the target genes regarding their possible relations with the implantation process. The total RNA was purified and reverse-transcribed, and gene expressions were quantified by RT-PCR. Results: The expressions of the IL-15, INFG, and HPRT1 genes were significantly decreased in the RIF patients with thin endometria compared to the RPL patients (log2 fold change = 0.92, p = 0.023 for IL-15; log2 fold change = 1.24, p = 0.046 for INFG; and log2 fold change = 0.579, p = 0.046 for HPRT1). There were no significant differences in the expressions of the CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB, and HAND2 genes between the groups. Conclusions: Decreased expressions of the IL-15, INFG, and HPRT1 genes were found in patients with RIF with thin endometria compared to the endometria of women with RPL. This has practical significance for clinicians for the differentiated prescription of immunomodulatory therapy in patients undergoing ART programs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine whether intrauterine infusion of autologous platelet-rich plasma (PRP) gel increases endometrial thickness (EMT) and improves the outcomes of frozen-thawed embryo transfer (FET) in women with thin endometrium. Methods: This study included 111 women (aged 25–44 years) who had thin endometrium. All patients had at least one previous cycle canceled because of thin endometrium or previous embryo transfer cycles and an EMT < 7 mm. Forty-seven women underwent intrauterine infusion of autologous PRP gel on three occasions during endometrial preparation and the remaining women served as controls. The final EMT was measured by ultrasound before the start of the luteal phase, and FET-related outcome parameters were monitored. Results: Mean EMT was greater in women who received PRP gel than in those who did not (6.7 mm vs. 6.3 mm, respectively, p < 0.05). FET was attempted in all women. The 47 women who underwent infusion of PRP had a significantly higher pregnancy rate (18 pregnancies (38.3%), with 17 (36.2%) ongoing) compared with 64 control women (ten pregnancies (18.5%), nine (16.7%) ongoing). However, there was no significant reduction in the miscarriage rate. Conclusion: Intrauterine infusion of autologous PRP gel during endometrial preparation for FET cycles can improve the EMT, clinical pregnancy rate, and ongoing pregnancy rate in women with thin endometrium. [ABSTRACT FROM AUTHOR]

Purpose: Multiple factors have been shown to influence the rate of clinical pregnancy after FET in IVF treatment, including embryo quality, synchronization of embryo and endometrium, and endometrial receptivity (ER). The subendometrial blood flow conditions could also contribute potentially major effects toward the establishment and maintenance of pregnancy. We conducted a retrospective cohort study to examine the correlation between subendometrial blood flow, as determined by Doppler ultrasound, and pregnancy outcomes in IVF patients with a thin endometrium (endometrium thickness [EMT] ≤ 0.7 cm). Methods: This was a retrospective cohort study conducted at a university-affiliated reproductive hospital from January 2017 to April 2023. The EMT and subendometrial blood flows were assessed using transvaginal color Doppler ultrasound and evaluated by experienced clinical ultrasound physicians on the endometrial transformation day. The pregnancy outcomes were followed up and documented in clinical medical records through the IVF cohort study at our center. Results: In the patients with 0.5 cm ≤ EMT ≤ 0.7 cm, the embryo implantation rate was statistically significant increased in the patients with the presence of subendometrial blood flow (OR 1.484; 95% CI, 1.001–2.200; P = 0.049; aOR 1.425; 95% CI, 1.030–2.123; P = 0.003). Patients with discernible subendometrial blood flow have superior live birth (P = 0.028), clinical pregnancy (P = 0.049), and embryo implantation (P = 0.027) compared to the patients without subendometrial blood flow when the EMT is ≤ 0.7 cm. Conclusions: The presence of subendometrial blood flow detected by ultrasound was positively associated with successful embryo implantation and favorable pregnancy outcomes in patients with thin endometrium undergoing FET. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the effects of intrauterine infusion of autologous blood cell derivative (ABCD) on endometrial thickness and pregnancy outcomes in a group of patients who underwent IVF with recurrent implantation failure (RIF) and who had either a normal endometrium or thin endometrium. Methods: This retrospective study included 63 patients who experienced RIF at the Department of Reproductive Medicine and Surgery, KMC, Manipal, between January 2021 and March 2024 and who received three doses of intrauterine ABCD infusion to prepare the endometrium for frozen embryo transfer (FET). Results: We enrolled 63 RIF patients, 30 with a normal endometrium (NEM) and 33 with a thin endometrium (TEM). The endometrial thickness (EMT) significantly increased across all the groups. After 3 cycles of intrauterine ABCD infusion, the mean increases in EMT in the NEM and TEM groups were 0.77 mm and 1.36 mm, respectively, which were statistically significant. Among the 62 completed FET cycles, 40.3% were positive for beta-hCG. The clinical pregnancy rate was 33.8% (40% in the NEM group, 28.1% in the TEM group), and the live birth rate was 24.2% (30% in the NEM group, 18.8% in the TEM group). A total of 9.7% of pregnancies had spontaneous miscarriages. Moreover, the EMT did not differ between the pregnant and nonpregnant groups. Conclusion: Intrauterine ABCD infusion improves the pregnancy outcomes of patients with RIF, regardless of the EMT. The results of this study revealed that endometrial receptivity improved significantly along with the EMT. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does recombinant Lactobacillus expressing granulocyte colony-stimulating factor (G-CSF) have a better protective effect than the current treatment of thin endometrium (TE)? SUMMARY ANSWER This study suggested that the intrauterine injection of Lactobacillus crispastus (L. crispastus)-pPG612-G-CSF has a positive effect on preventing TE induced by 95% alcohol in mice. WHAT IS KNOWN ALREADY TE has a negative impact on the success rate of ART in patients, and is usually caused by intrauterine surgery, endometrial infection, or hormone drugs. Exogenous G-CSF can promote endometrial vascular remodelling and increase endometrial receptivity and the embryo implantation rate. Moreover, Lactobacillus plays a crucial role in maintaining and regulating the local microecological balance of the reproductive tract, and it could be a delivery carrier of the endometrial repair drug G-CSF. STUDY DESIGN, SIZE, DURATION We constructed engineered L. crispastus strains expressing G-CSF. The mice were divided into five groups: (i) Control group (C, n = 28), uteri were treated with preheated saline solution via intrauterine injection on the third and sixth day of oestrus; (ii) Model group (M, n = 35), where uteri were treated with 95% alcohol on the third day of oestrus and preheated saline solution on the sixth day of oestrus via intrauterine injection; (iii) L. crispatus -pPG612-treatment group (L, n = 45), where uteri were treated with 95% alcohol on the third day of oestrus and 0.1 ml × 108 CFU/ml L. crispatus -pPG612 on the sixth day of oestrus via intrauterine injection; (iv) L. crispatus -pPG612-treatment group (LG, n = 45), where uteri were treated with 95% alcohol on the third day of oestrus and 0.1 ml × 108 CFU/ml L. crispatus -pPG612-G-CSF on the sixth day of oestrus via intrauterine injection; (v) G-CSF-treatment group (G, n = 52), where uteri were treated with 95% alcohol on the third day of oestrus and 30 µg/kg G-CSF on the sixth day of oestrus via intrauterine injection. Then, we compared the effects of L. crispastus , L. crispatus -pPG612-G-CSF and G-CSF on endometrial thickness, angiogenesis, fibrosis, and inflammation in the TE mouse. PARTICIPANTS/MATERIALS, SETTING, METHODS We collected uterine tissues for haematoxylin–eosin staining, immunohistochemical staining, Western blot and RT–PCR, as well as serum for ELISA and uterine flushing solution for high-throughput sequencing. MAIN RESULTS AND THE ROLE OF CHANCE Compared with those in the M group (the mice of the group were intrauterine injected 95% alcohol and treated with saline solution), the L. crispatus -pPG612-G-CSF strain increased the thickness of the endometrium (P  <   0.001) and the number of blood vessels and glands (both P  <   0.001), enhanced the expression of cytokeratin 19 (CK19) (P  <   0.001), vimentin (Vim) (P  <   0.001), vascular endothelial growth factor-A (P  <   0.001), and CD34 (P  <   0.001), and decreased fibrosis levels (P  =   0.004). In addition, the high-throughput sequencing results indicated that the L. crispatus -pPG612-G-CSF strain could decrease the abundance of Pseudomonas (P  =   0.044) and Actinomyces spp. (P  =   0.094) in TE mice and increased the average number of embryos (P  =   0.036). Finally, the L. crispatus -pPG612-G-CSF strain was preliminarily confirmed to activate the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signalling pathway and enhance the mRNA expression of hypoxia-inducible factor-1α (P  <   0.001), vascular endometrial growth factor (P  =   0.003), and endothelial cell nitric oxide synthase (P  =   0.003) in mouse uterine tissue. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Therapy with the L. crispatus -pPG612-G-CSF strain has tremendous potential to accelerate the reparative processes of TE. However, we have reported only the expression of genes and proteins related to the PI3K/AKT pathway, and numerous other mechanisms may also be involved in the restoration of the endometrium by L. crispatus -pPG612-G-CSF. WIDER IMPLICATIONS OF THE FINDINGS The results from the study provide new ideas and suggest new methods for TE treatment. STUDY FUNDING/COMPETING INTEREST(S) This work was financially supported by the Project of Science and Technology Development Plan of Jilin Province (grant number 20210101232JC), the Science and Technology Plan Item of Jilin Provincial Education Department (grant number JT53101022010), and the Doctoral Research Start-up Fund of Jilin Medical University (grant numbers JYBS2021014LK and 2022JYBS006KJ). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. [ABSTRACT FROM AUTHOR]

Introduction: Intrauterine transfusion of platelet-rich plasma (PRP) has become a new treatment for thin endometrium (TE) in recent years, but its low efficacy due to rapid release of growth factors limits its clinical use. Platelet-rich fibrin (PRF) starts the coagulation cascade reaction immediately after the blood comes into contact with the test tube. The natural coagulation process results in stable platelet activation and the slow release of growth factors. Methods: In our study, primary human endometrial stromal cells (hESCs) were extracted from endometrial tissue. PRP and PRF were prepared from the patient cubital vein blood. Stromal cells were cultured in conditioned medium supplemented with PRP and PRF. Differences in cell behavior were observed by cell proliferation test and cell migration test. The relative expression levels of apoptotic Bax and antiapoptotic Bcl-2 genes were measured by qRT-PCR. The release of growth factors from PRP and PRF was detected by ELISA. Results: We found that both PRP and PRF inhibited apoptosis of hESCs, which favored cell proliferation and migration. In addition, PRF releases growth factors for a longer period of time compared to PRP. Discussion: PRF offer a more sustained therapeutic effect compared to PRP, which provides a new idea for endometrial regeneration and repair. [ABSTRACT FROM AUTHOR]

Currently, recurrent implantation failure (RIF) after in vitro fertilization is a problem that is commonly faced by reproductive specialists. The phenomenon of a thin endometrium in RIF patients is not yet completely understood or sufficiently treated. This study aimed to reveal the dysregulated expression of selected genes between RIF patients with a thin endometrium and fertile women. Endometrial samples were collected in the implantation window (21–24 days of the natural menstrual cycle) from RIF patients (n = 20) and fertile women (n = 14). Ten genes were chosen as target genes regarding their possible relations with the implantation process. The endometrial gene expression levels showed differences in RIF samples compared to fertile samples. Significant downregulation was observed for the CXCL1 (p = 0.005) and C4BPA (p = 0.03) genes. There was no statistically significant difference between the RIF group and the fertile group in the expression of eight genes: CXCL8, HPRT1, MMP10, INFG, VEGFB, HAND2, IL-15, and TNC (p > 0.05). The use of a combination of two markers (C4BPA + CXCL1) allows for the good discrimination of RIF patients from fertile women (AUC 0.806). [ABSTRACT FROM AUTHOR]

BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested. WIDER IMPLICATIONS Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis. REGISTRATION NUMBER https://osf.io/th8yf/ [ABSTRACT FROM AUTHOR]

Endometrial infertility is the cause of inadequate implantation and serves as an obstacle to the onset and progression of spontaneous pregnancy and the implementation of assisted reproductive technology (ART) programs. One of the most common mechanisms for the development of infertility is endometrial thinning. Despite the abundance of publications, today there are no generally accepted diagnostic criteria and treatment and rehabilitation approaches for this pathology, which encourages continued scientific research in this direction. Aim was to highlight the problem of decreased fertility caused by “thin endometrium”. To create the review, the bibliographic method was applied and domestic and foreign literary sources from the Pubmed, MedLine, RSCI, e-library and Cyberleninka search engine databases were used. The search depth was 10 years. The following search phrases were used: “uterine factor of infertility”, “endometrial factor of infertility”, “thin endometrium”. Seventy five sources that were included in this review were studied and analyzed. Data presented in the literature indicate that endometrial causes of infertility are associated with incompetence of the uterine cavity mucosa, which may manifest itself as a phenomenon of ”thin endometrium”, the development mechanisms of which have not yet been fully studied. Determining the functional status of the endometrium is very important for predicting the onset of pregnancy in the natural cycle or in ART programs, since even in the presence of a good quality embryo, endometrial deficiency can prevent adequate implantation. Thus, before planning a subsequent pregnancy, it is necessary to diagnose and, if possible, neutralize or correct endometrial causes of infertility. One of the main markers of readiness for implantation at the moment is the thickness of the endometrium.

Background: Thin endometrium, described as endometrial thickness below 7 mm on embryo transfer day in assisted reproduction cycles, is associated with decreased pregnancy rates. Granulocyte colony-stimulating factor (G-CSF) and oestrogen (E) are two medications used for treatment. Aim: The aim of this study is to demonstrate the effect of combined G-CSF+E treatment on thin endometrium in a rat model. Settings and Design: Gazi University Laboratory Animals Breeding and Experimental Researchers Center provided the veterinary care. Materials and Methods: Forty-eight female rats were divided into 8 groups (6 rats/group). Groups were named as group 1: control, group 2: control that received G-CSF, group 3: control that received E, group 4: control that received G-CSF+E, group 5: thin endometrium model, group 6: thin endometrium model that received G-CSF, group 7: thin endometrium model that received E and group 8: thin endometrium model that received G-CSF+E. Twelve days after the establishment of thin endometrium model, G-CSF and/or E treatment was started and continued for 5 days according to the groups. Tissue specimens were collected at the end of the treatment period. Proliferation, apoptosis and angiogenesis were evaluated. Statistical Analysis Used: The data were analysed using one-way analysis of variance and Tamhane post hoc test. Results: Significant increase in uterine wall and endometrial thickness was detected in the thin endometrium + G-CSF group when compared to the thin endometrium group. G-CSF was demonstrated to cause an extensive proliferative response and induction of angiogenesis in thin endometrium without restoration of endometrial glands. E alone restored thin endometrium to almost normal histology. Morphological changes representing the dominant effects of G-CSF were observed in thin endometrium model receiving G-CSF+E. Conclusion: G-CSF+E is not an effective treatment modality in thin endometrium rat model.

Abstract Background Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). Methods We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included “Platelet-Rich Plasma,” “thin endometrium,” “endometrial thickness,” “infertility,” “pregnancy,” “reproduction,” and “adverse reactions”. RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. Results Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. Conclusion Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. Trial registration The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.

Abstract Background Reduced endometrium thickness and receptivity are two important reasons for recurrent implantation failure (RIF). In order to elucidate differences between these two types of endometrial defects in terms of molecular signatures, cellular interactions, and structural changes, we systematically investigated the single-cell transcriptomic atlas across three distinct groups: RIF patients with thin endometrium (≤ 6 mm, TE-RIF), RIF patients with normal endometrium thickness (≥ 8 mm, NE-RIF), and fertile individuals (Control). Methods The late proliferative and mid-secretory phases of the endometrium were collected from three individuals in the TE-RIF group, two in the NE-RIF group, and three in the control group. The study employed a combination of advanced techniques. Single-cell RNA sequencing (scRNA-seq) was utilized to capture comprehensive transcriptomic profiles at the single-cell level, providing insights into gene expression patterns within specific cell types. Scanning and transmission electron microscopy were employed to visualize ultrastructural details of the endometrial tissue, while hematoxylin and eosin staining facilitated the examination of tissue morphology and cellular composition. Immunohistochemistry techniques were also applied to detect and localize specific protein markers relevant to endometrial receptivity and function. Results Through comparative analysis of differentially expressed genes among these groups and KEGG pathway analysis, the TE-RIF group exhibited notable dysregulations in the TNF and MAPK signaling pathways, which are pivotal in stromal cell growth and endometrial receptivity. Conversely, in the NE-RIF group, disturbances in energy metabolism emerged as a primary contributor to reduced endometrial receptivity. Additionally, using CellPhoneDB for intercellular communication analysis revealed aberrant interactions between epithelial and stromal cells, impacting endometrial receptivity specifically in the TE-RIF group. Conclusion Overall, our findings provide valuable insights into the heterogeneous molecular pathways and cellular interactions associated with RIF in different endometrial conditions. These insights may pave the way for targeted therapeutic interventions aimed at improving endometrial receptivity and enhancing reproductive outcomes in patients undergoing ART. Further research is warranted to validate these findings and translate them into clinical applications for personalized fertility treatments. Trial registration Not applicable.

Background: Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). Methods: We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included "Platelet-Rich Plasma," "thin endometrium," "endometrial thickness," "infertility," "pregnancy," "reproduction," and "adverse reactions". RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. Results: Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. Conclusion: Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. Trial registration: The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the pathological mechanism involved in a thin endometrium, particularly under ischaemic conditions? SUMMARY ANSWER Endometrial dysfunction in patients with thin endometrium primarily results from remodelling in cytoskeletons and cellular junctions of endometrial epithelial cells under ischemic conditions. WHAT IS KNOWN ALREADY A healthy endometrium is essential for successful embryo implantation and subsequent pregnancy; ischemic conditions in a thin endometrium compromise fertility outcomes. STUDY DESIGN, SIZE, DURATION We recruited 10 patients with thin endometrium and 15 patients with healthy endometrium. Doppler ultrasound and immunohistochemical results confirmed the presence of insufficient endometrial blood perfusion in patients with thin endometrium. Organoids were constructed using healthy endometrial tissue and cultured under oxygen–glucose deprivation (OGD) conditions for 24 h. The morphological, transcriptomic, protein expression, and signaling pathway changes in the OGD organoids were observed. These findings were validated in both thin endometrial tissue and healthy endometrial tissue samples. PARTICIPANTS/MATERIALS, SETTING, METHODS Endometrial thickness and blood flow were measured during the late follicular phase using transvaginal Doppler ultrasound. Endometrial tissue was obtained via hysteroscopy. Fresh endometrial tissues were used for the generation and culture of human endometrial organoids. Organoids were cultured in an appropriate medium and subjected to OGD to simulate ischemic conditions. Apoptosis and cell death were assessed using Annexin-V/propidium iodide staining. Immunofluorescence analysis, RNA sequencing, western blotting, simple westerns, immunohistochemistry, and electron microscopy were conducted to evaluate cellular and molecular changes. MAIN RESULTS AND THE ROLE OF CHANCE Patients with thin endometrium showed significantly reduced endometrial thickness and altered blood flow patterns compared to those with healthy endometrium. Immunohistochemical staining revealed fewer CD34-positive blood vessels and glands in the thin endometrium group. Organoids cultured under OGD conditions exhibited significant morphological changes, increased apoptosis, and cell death. RNA-seq identified differentially expressed genes related to cytoskeletal remodeling and stress responses. OGD induced a strong cytoskeletal reorganization, mediated by the RhoA/ROCK signaling pathway. Additionally, electron microscopy indicated compromised epithelial integrity and abnormal cell junctions in thin endometrial tissues. Upregulation of hypoxia markers (HIF-1α and HIF-2α) and activation of the RhoA/ROCK pathway were also observed in thin endometrial tissues, suggesting ischemia and hypoxia as underlying mechanisms. LARGE SCALE DATA none. LIMITATIONS AND REASONS FOR CAUTION The study was conducted in an in vitro model, which may not fully replicate the complexity of in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS This research provides a new three-dimensional in vitro model of thin endometrium, as well as novel insights into the pathophysiological mechanisms of endometrial ischaemia in thin endometrium, offering potential avenues for identifying therapeutic targets for treating fertility issues related to thin endometrium. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Natural Science Foundation of China (81925013); National Key Research and Development Project of China (2022YFC2702500, 2021YFC2700303, 2021YFC2700601); the Capital Health Research and Development Project (SF2022-1-4092); the National Natural Science Foundation of China (82288102, 81925013, 82225019, 82192873); Special Project on Capital Clinical Diagnosis and Treatment Technology Research and Transformation Application (Z211100002921054); the Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation(TFJC2023010001). The authors declare that no competing interests exist. [ABSTRACT FROM AUTHOR]

• Self-controlled study of PRP effects on endometrial thickness in menstrual cycles. • PRP increases key endometrial biomarkers: HOXA-10, Ki67, and αvβ3 integrin. • PRP treatment significantly increased endometrial thickness. • Two successful pregnancies post-PRP suggest improved fertility potential. Thin endometrium (TE) compromises endometrial receptivity, often leading to implantation failure and lower clinical pregnancy rates. As autologous platelet-rich plasma (PRP) emerges as a potential remedy, the present study focused on its therapeutic effects on TE in infertile women who underwent frozen embryo transfer. Patients with TE who underwent frozen embryo transfer treatment in our hospital were included. To diminish individual variability, a self-controlled series approach was used. Two menstrual study cycles were arranged for each participant before the actual embryo transfer cycle; PRP treatment was conducted in the second cycle. Key metrics analyzed included endometrial thickness and the expression of specific endometrial biomarkers including HOXA-10, Ki67, and αvβ3 integrin. Transvaginal ultrasound was employed to measure endometrial thickness on Days 11 and 14, and an endometrial biopsy was conducted on progesterone Day 5 of the first two cycles. Pregnancy outcomes were observed after the embryo transfer cycle. PRP treatment significantly increased the median endometrial thickness, from 5.8 mm to 6.5 mm (P = 0.0066). Additionally, PRP treatment resulted in a statistically significant increase in the H-score for all endometrial markers. Importantly, during the subsequent embryo transfer cycle with PRP treatment, two patients successfully achieved pregnancies, both culminating in live births. These findings emphasize the potential of PRP in improving endometrial conditions, especially for individuals grappling with thin endometrium issues, as underscored by this self-comparison methodology. [ABSTRACT FROM AUTHOR]

Background: Reduced endometrium thickness and receptivity are two important reasons for recurrent implantation failure (RIF). In order to elucidate differences between these two types of endometrial defects in terms of molecular signatures, cellular interactions, and structural changes, we systematically investigated the single-cell transcriptomic atlas across three distinct groups: RIF patients with thin endometrium (≤ 6 mm, TE-RIF), RIF patients with normal endometrium thickness (≥ 8 mm, NE-RIF), and fertile individuals (Control). Methods: The late proliferative and mid-secretory phases of the endometrium were collected from three individuals in the TE-RIF group, two in the NE-RIF group, and three in the control group. The study employed a combination of advanced techniques. Single-cell RNA sequencing (scRNA-seq) was utilized to capture comprehensive transcriptomic profiles at the single-cell level, providing insights into gene expression patterns within specific cell types. Scanning and transmission electron microscopy were employed to visualize ultrastructural details of the endometrial tissue, while hematoxylin and eosin staining facilitated the examination of tissue morphology and cellular composition. Immunohistochemistry techniques were also applied to detect and localize specific protein markers relevant to endometrial receptivity and function. Results: Through comparative analysis of differentially expressed genes among these groups and KEGG pathway analysis, the TE-RIF group exhibited notable dysregulations in the TNF and MAPK signaling pathways, which are pivotal in stromal cell growth and endometrial receptivity. Conversely, in the NE-RIF group, disturbances in energy metabolism emerged as a primary contributor to reduced endometrial receptivity. Additionally, using CellPhoneDB for intercellular communication analysis revealed aberrant interactions between epithelial and stromal cells, impacting endometrial receptivity specifically in the TE-RIF group. Conclusion: Overall, our findings provide valuable insights into the heterogeneous molecular pathways and cellular interactions associated with RIF in different endometrial conditions. These insights may pave the way for targeted therapeutic interventions aimed at improving endometrial receptivity and enhancing reproductive outcomes in patients undergoing ART. Further research is warranted to validate these findings and translate them into clinical applications for personalized fertility treatments. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Thin endometrium (TE), which mainly occurs as a result of severe damage to the endometrial basalis, is one of the prominent etiologies of menstrual abnormalities, infertility, and recurrent miscarriage in women. Previous studies have demonstrated that mesenchymal stem cells (MSCs) are considered ideal cells with multipotency for regenerative medicine and exhibit therapeutic effects on TE through their cellular secretions. However, there is limited research on strategies to enhance MSC secretion to improve their therapeutic efficacy. Herein, we isolated menstrual blood–derived mesenchymal stem cells (MenSCs) from menstruation and transformed them into decidualized stromal cells (DSCs), which are specialized cells with enhanced secretory functions. To assess the therapeutic potential of DSCs compared to MenSCs, we conducted a series of experiments in cells and animals. The results demonstrated that DSCs exhibited changes in morphology compared to MenSCs, with a decrease in cell proliferation but a significant improvement in secretion function. Furthermore, DSCs facilitated the restoration of endometrial thickness and increased the number of glands and blood vessel formation. Most importantly, the pregnancy rates in rats were effectively restored, bringing them closer to normal levels. These findings greatly contribute to our understanding of stem cell therapy for TE and strongly suggest that DSCs could hold significant promise as a potential treatment option for TE. [ABSTRACT FROM AUTHOR]

Royal jelly (RJ) is rich in various nutrients, including proteins and amino acids. RJ consumption improves sexual and urinary function in postmenopausal women, possibly owing to its hormone-like effects. Currently, hormone regulation and assisted reproductive technologies are widely used to treat thin endometria; however, high doses of these drugs can add to liver burden. In this study, RJ proteins and fatty acids were isolated, and their therapeutic effects on thin endometria were investigated in vivo and in vitro to verify their hormone-like regulatory effects. The results showed that RJ and its extracts could regulate endometrial receptivity-related factor expression levels in rats with a thin endometrium, accelerate MCF-7 cell apoptosis, and increase estrogen receptor expression in MCF-7 cells wherein. The estrogen-like effects of RJ and the fatty acids may be the main contributors. RJ may be a potential natural hormone replacement therapy.

Background This study aimed to determine the effect and mechanism of the Decoction of Yougui Wan combined with Wuzi Yanzong Wan (DYWWYW), a traditional Chinese herbal formula, in a mouse model with thin endometrium induced by 95% ethanol.Methods Thin endometrium mice were treated with progynova (0.002 mg) as well as a low and high dose of DYWWYW (0.05 and 0.5 mL DYWWYW, respectively, diluted in 2 mL normal saline). Western blotting and qRT-PCR analyses were performed to determine the protein and mRNA expression levels, respectively, of integrin αγβ3 and leukaemia inhibitor factor (LIF) in uterus tissues. Serum oestradiol and progesterone concentrations were determined via ELISA. The remaining thin endometrium mice were mated with male mice, and the number of embryos implanted in the different groups was calculated.Results A high dose of DYWWYW effectively ameliorated the injury of endometrium caused by 95% ethanol. The levels of oestradiol, progesterone, αγβ3 and LIF in thin endometrium mice treated with a high dose of DYWWYW were also significantly elevated. Additionally, a high dose of DYWWYW remarkably increased the number of embryo implantations in mice with thin endometrium.Conclusion DYWWYW has improvement effects on thin endometrium by elevating the levels of endogenous oestradiol, progesterone, αγβ3, and LIF in a mouse model.

Obejective To compare the effectiveness of endometrial receptivity and pregnancy outcomes of four common immunomodulatory therapies for patients with thin endometrium.Method This systematic review and network meta-analysis using a literature search up to January 2024, to identify relevant trials comparing endometrial receptivity and pregnancy outcomes of human chorionic gonadotropin (hCG), platelet-rich plasma (PRP), infusion of granulocyte colony-stimulating factor (IG-CSF), and peripheral blood mononuclear cell (PBMC) for patients with thin endometrium. We used surface under the cumulative ranking (SUCRA) to ranked four common immunomodulatory therapies on endometrium thickness, implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR). RoB2 and ROBINS-I were used to assess the certainty of evidence.Results The pooled results of 22 studies showed that hCG (mean difference [MD]: 3.05, 95% confidence interval [CI]: 1.46–4.64) and PRP (MD: 0.98, 95% CI: 0.20–1.76) significantly increase endometrium thickness. The hCG was the best among the IG-CSF (MD = −2.56, 95% CI = −4.30 to −0.82), PBMC (MD = −2.75, 95% CI = −5.49 to −0.01), and PRP (MD = −2.07, 95% CI = −3.84 to −0.30) in increasing endometrium thickness. However, IG-CSF and PRP significantly improved IR (IG-CSF: risk ratio (RR; IG-CSF: RR = 1.33, 95% CI = 1.06–1.67; PRP: RR = 1.63, 95% CI = 1.19–2.23), and LBR (IG-CSF: RR = 1.53, 95% CI = 1.16–2.02; PRP: RR = 1.59, 95% CI = 1.08–2.36).Conclusions Available evidence reveals that hCG and subcutaneous or intrauterine CSF (SG-CSF) may be the best treatment options for current thin endometrium patients. However, future high-quality and large-scale studies are necessary to validate our findings.

Objectives: To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods: This prospective case–control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results: After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions: Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Sichuan University (Medical Science Edition) is the property of Editorial Board of Journal of Sichuan University (Medical Sciences) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In the process of assisted reproductive technology assisted pregnancy, infertile patients often have their cycles canceled due to a thin endometrium, which can lead to repeated embryo implantation failures, which are associated with lower implantation, ongoing pregnancy, and live birth rates. At present, the treatment of thin endometrium is currently ineffective and the improvement of thin endometrium remains an unresolved clinical challenge. Platelet-rich plasma（PRP） is a potential new therapy that could have a positive effect on patients with underdeveloped or thin endometrium and no response to standard therapy. This article reviews the latest research progress on the effects of PRP on thin endometrium with the hope of informing the clinical management of infertile patients with thin endometrium in the field of assisted reproduction. [ABSTRACT FROM AUTHOR]

Currently, recurrent implantation failure (RIF) after in vitro fertilization is a problem that is commonly faced by reproductive specialists. The phenomenon of a thin endometrium in RIF patients is not yet completely understood or sufficiently treated. This study aimed to reveal the dysregulated expression of selected genes between RIF patients with a thin endometrium and fertile women. Endometrial samples were collected in the implantation window (21–24 days of the natural menstrual cycle) from RIF patients (n = 20) and fertile women (n = 14). Ten genes were chosen as target genes regarding their possible relations with the implantation process. The endometrial gene expression levels showed differences in RIF samples compared to fertile samples. Significant downregulation was observed for the CXCL1 (p = 0.005) and C4BPA (p = 0.03) genes. There was no statistically significant difference between the RIF group and the fertile group in the expression of eight genes: CXCL8, HPRT1, MMP10, INFG, VEGFB, HAND2, IL-15, and TNC (p > 0.05). The use of a combination of two markers (C4BPA + CXCL1) allows for the good discrimination of RIF patients from fertile women (AUC 0.806).

The endometrium is a resilient and highly dynamic tissue, undergoing cyclic renewal in preparation for embryo implantation. Cyclic endometrial regeneration depends on the intact function of several cell types, including parenchymal, endothelial, and immune cells, as well as adult stem cells that can arise from endometrial or extrauterine sources. The ability of the endometrium to undergo rapid, repeated regeneration without scarring is unique to this tissue. However, if this tissue renewal process is disrupted or dysfunctional, women may present clinically with infertility due to endometrial scarring or persistent atrophic/thin endometrium. Such disorders are rate-limiting in the treatment of female infertility and in the success of in vitro fertilization because of a dearth of treatment options specifically targeting the endometrium. A growing number of studies have explored the potential of adult stem cells, including mesenchymal stem cells (MSCs), to treat women with disorders of endometrial regeneration. MSCs are multipotent adult stem cells with capacity to differentiate into cells such as adipocytes, chondrocytes, and osteoblasts. In addition to their differentiation capacity, MSCs migrate toward injured sites where they secrete bioactive factors (e.g. cytokines, chemokines, growth factors, proteins and extracellular vesicles) to aid in tissue repair. These factors modulate biological processes critical for tissue regeneration, such as angiogenesis, cell migration and immunomodulation. The MSC secretome has therefore attracted significant attention for its therapeutic potential. In the uterus, studies utilizing rodent models and limited human trials have shown a potential benefit of MSCs and the MSC secretome in treatment of endometrial infertility. This review will explore the potential of MSCs to treat women with impaired endometrial receptivity due to a thin endometrium or endometrial scarring. We will provide context supporting leveraging MSCs for this purpose by including a review of mechanisms by which the MSC secretome promotes regeneration and repair of nonreproductive tissues. [ABSTRACT FROM AUTHOR]

Purpose: To study effect of intrauterine infusion of platelet-rich plasma (PRP) on endometrial growth in the setting of thin endometrial lining in patients with prior cancelled or failed frozen embryo transfer (FET) cycles. Materials and methods: Single-arm cohort study of forty-six patients (51 cycles) with endometrial lining thickness (EMT) < 6 mm in prior cancelled or failed FET cycles requesting intrauterine PRP treatment in upcoming FET cycle. The primary outcomes were final EMT in FET cycle and change in EMT after PRP. The secondary outcomes were overall pregnancy rate, clinical pregnancy rate, miscarriage rate, ongoing pregnancy, and live birth rates. Results: The mean pre-PRP EMT in all FET cycles was 4.0 ± 1.1 mm, and mean post-PRP EMT (final) was 7.1 ± 1.0 mm. Of 51 cycles, 33 (64.7%) reached ≥ 7 mm after PRP administration. There was a significant difference between pre-PRP EMT and post-PRP EMT in all FET cycles, with mean difference of 3.0 ± 1.5 mm. Three cycles were cancelled for failure to reach adequate lining. Total pregnancy rate was 72.9% in our cohort of 48 cycles that proceeded to transfer. Clinical pregnancy rate was 54.2% (26/48 FET cycles); clinical miscarriage rate was 14.3% (5/35 pregnancies). Twenty six women had live birth (18 with EMT ≥ 7 mm and 8 with EMT < 7 mm). Response to PRP was not correlated with any pre-cycle characteristics. Conclusion: We demonstrate a significant improvement in lining thickness and pregnancy rates in this challenging cohort of women after PRP infusion, with no adverse events. Cost-effectiveness of PRP with benefits and alternatives should be carefully considered. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effects of a collagen endometrial patch (EM patch) loaded with adipose-derived mesenchymal stem cells (ADSCs) on endometrial regeneration in a rat model with thin endometrium. Materials and methods: Thin endometrium was induced in female rats and divided into treatment groups as outlined: control, group 1(G1), local injection of ADSCs into the uterus, group 2 (G2), an EM patch without ADSCs, group 3 (G3), and an EM patch loaded with ADSCs, group 4 (G4). The rats were euthanized at either two weeks or four weeks after modeling and treatment followed by histological and biochemical analyses to examine the regenerative effects on the injured endometrium. Results: Transplantation of the ADSC-loaded EM patch significantly promoted endometrial proliferation and increased the luminal epithelial area. Two weeks after treatment, the mean number of von Villebrand factor (vWF)+ or cluster of differentiation (CD) 31+-stained blood vessels was significantly higher in G4 than in G1 and G2. The mRNA and protein expression levels of TGF-b and FGF2 were significantly upregulated in G4 compared to those in the control. G4 exhibited significantly increased LIF mRNA levels and immunoreactivity compared with the other groups at both two weeks and four weeks after treatment. Cell tracking after ADSCs treatment revealed the presence of a substantial number of ADSCs grafted in the uterine tissues of G4, whereas a low number of ADSCs that were focally clustered were present in G2. Conclusion: Transplantation of EM patches loaded with ADSCs resulted in the histological and biochemical restoration of an injured endometrium. The strategic integration of EM patches and ADSCs holds significant promise as an innovative therapeutic approach for effectively treating impaired endometrial conditions. [ABSTRACT FROM AUTHOR]

To evaluate whether Zi Gui Nv Zhen capsules (ZGNZC) can increase the fertility rate of Chinese women with infertility due to thin endometrium. Prospective, randomized, open-labeled 3-monthly study; 104 patients (aged 20–40 years) receiving either ZGNZC (experimental group, n = 55) or not (control group, n = 49). Main outcomes: thickness/type of the endometrium during ovulation and pregnancy rate. Between-group analysis (A) compares the experimental vs. control group, and within-group analysis (B) compares data at baseline and after study in the experimental group. (A) Between-group-analysis: Patients with ZGNZC had a higher endometrium thickness (0.8 ± 0.27 vs. 0.68 ± 0.10; p <.05) and higher type A endometrium rates (34.2% vs. 13.2%; p <.05) than the control group. Pregnancy rates were higher in the experimental than in the control group (43.6% vs. 22.4%; p <.05). (B) Within-group-analysis: ZGNZC increased endometrium thickness (0.58 ± 0.13 vs. 0.87 ± 0.24 vs. 0.83 ± 0.26 vs. 0.80 ± 0.27), and type A endometrium rates (10.9% vs. 60.0% vs. 49.0% vs. 34.2%) (all p <.05). Univariate analysis of pregnancy with other study parameters showed positive and significant correlations between pregnancy and administration of ZGNZC (p <.05). All hepato-renal biomarkers remained within the norm. There were no adverse events. In infertile women with thin endometrium who wish to conceive, two months' application of ZGNZC can improve endometrial properties and proliferation, which is necessary for a healthy pregnancy, and increase the clinical pregnancy rate in our prospective randomized observational study. [ABSTRACT FROM AUTHOR]

(1) Background: During IVF (in vitro fertilization) procedures, endometrial thickness has a significant role in the success of pregnancy outcomes for embryo transfers. Endometrial thickness, a crucial component of endometrial receptivity, is a contentious issue. The regenerative properties of PRP have been shown in recent research to have positive effects on the endometrium. PRP increases the pregnancy rate in IVF patients with thin endometrium and recurrent implantation failure. In order to demonstrate the efficacy of PRP therapies, this work compares the administration of injectable and infusible PRP during endometrial preparation. (2) Methods: This prospective single-arm control study was conducted at an IVF center in Oradea, Romania. This study included 50 patients; 27 were included in the group with Injectable PRP and 23 in the group with Infusible PRP. The outcome was compared between the two groups, with the primary outcome being the endometrial thickness after the PRP infusion or injection and the secondary outcome being the pregnancy rate in both groups. (3) Results: Patients who were treated with Injectable PRP had a higher pregnancy rate. An improvement in the quality of the endometrium, in terms of thickness, was also observed in the patients who were injected with PRP. (4) Conclusions: Compared to PRP infusions inside the uterus, sub-endometrial PRP injections in frozen embryo transfer methods have a greater pregnancy rate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Thin endometrium (TE) is defined as a mid-luteal endometrial thickness ≤7mm. TE can affect endometrial tolerance, leading to lower embryo implantation rates and clinical pregnancy rates, and is also associated with impaired outcomes from assisted reproductive treatment. Herein, we systematically review TE causes, mechanisms, and treatments. TE pathogenesis has multiple causes, with the endometrium becoming thinner with age under hormonal influence. In addition, uterine cavity factors are important, as the inflammatory environment may affect expressions of certain genes thereby inhibiting endometrial stromal cell proliferation and promoting apoptosis. Long-term oral contraceptive use or the use of ovulation-promoting drugs are also definite factors contributing to endometrial thinning. Other patients have primary factors, for which the clinical etiology remains unknown. The main therapeutic strategies available for TE are pharmacological (including hormonal and vasoactive drugs), regenerative medicine, intrauterine infusion of growth factor-granulocyte colony-stimulating factor, autologous platelet-rich plasma, and complementary alternative therapies (including traditional Chinese herbal medicine and acupuncture). However, the associated mechanisms of action are currently unclear. Clinical scholars have proposed various approaches to improve treatment outcomes in patients with TE, and are exploring the principles of efficacy, offering potentials for novel treatments. It is hoped that this will improve TE tolerance, increase embryo implantation rates, and help more couples with infertility with effective treatments.

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.

Lei Zhang,1,&ast; Honglin Li,1,&ast; Liang Zhang,2 Zhihui Zu,1 Dinglin Xu,1 Jianwei Zhang1,2 1The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Gynecology, Obstetrics and Reproductive Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianwei Zhang, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42, Wenhua West Road, Jinan, Shandong Province, People’s Republic of China, Tel +8653168901404, Email zhangjianwei1970@sina.comPurpose: Yangjing Zhongyu Tang (YJZYT) is a classic Chinese prescription for infertility treatment and exerts therapeutic effects via activity on the thin endometrium (TE). However, the major components and underlying mechanisms of YJZYT actions remain to be established. The main objectives of this study were to clarify the effects of YJZYT on the TE and provide insights into the related mechanisms based on network pharmacology and molecular docking analyses.Methods: Network pharmacology was employed to explore the main bioactive components and targets of YJZYT. TE-related genes were obtained from the Genecards database and screened for intersections with YJZYT. The Cytoscape 3.8.2 was used to build a “compounds-disease-targets” network and molecular docking analysis performed on key targets. The mechanism of action of YJZYT was further validated in vivo using a rat model.Results: A total of 98 YJZYT active ingredients, 2409 thin endometrium-associated genes, and 186 common targets were obtained. Through topological analysis, 10 core objectives were screened. Data from the PPI network suggest that AKT1, TNF, VEGFA, IL-6, TP53, INS, ESR1, MMP9, ALB, and ACTB serve as key targets in the action of YJZYT on TE. PI3K-Akt, TNF, apoptosis, IL-17 and MAPK were established as the main functional pathways. Molecular docking analysis revealed high affinity of the active ingredients of YJZYT, specifically, ursolic acid, palbinone, stigmasterol, and beta-sitosterol, for TNF, VEGFA, IL-6, AKT, and MMP9. YJZYT improved endometrial recovery, promoted endometrial angiogenesis, and upregulated protein expression of VEGF, PI3K, AKT, and p-AKT in the TE rat model.Conclusion: Network pharmacological and animal studies facilitated the prediction and validation of the active components and key targets of YJZYT potentially contributing to TE. Preliminary evidence from in vivo experiments showed that YJZYT promotes angiogenesis and thin endometrial repair via regulation of the PI3K/AKT pathway, providing a reference for further research.Keywords: network pharmacology, molecular docking, Yangjing Zhongyu Tang, thin endometrium, PI3K/AKT signaling pathway

The endometrium is a resilient and highly dynamic tissue, undergoing cyclic renewal in preparation for embryo implantation. Cyclic endometrial regeneration depends on the intact function of several cell types, including parenchymal, endothelial, and immune cells, as well as adult stem cells that can arise from endometrial or extrauterine sources. The ability of the endometrium to undergo rapid, repeated regeneration without scarring is unique to this tissue. However, if this tissue renewal process is disrupted or dysfunctional, women may present clinically with infertility due to endometrial scarring or persistent atrophic/thin endometrium. Such disorders are rate-limiting in the treatment of female infertility and in the success of in vitro fertilization because of a dearth of treatment options specifically targeting the endometrium. A growing number of studies have explored the potential of adult stem cells, including mesenchymal stem cells (MSCs), to treat women with disorders of endometrial regeneration. MSCs are multipotent adult stem cells with capacity to differentiate into cells such as adipocytes, chondrocytes, and osteoblasts. In addition to their differentiation capacity, MSCs migrate toward injured sites where they secrete bioactive factors (e.g. cytokines, chemokines, growth factors, proteins and extracellular vesicles) to aid in tissue repair. These factors modulate biological processes critical for tissue regeneration, such as angiogenesis, cell migration and immunomodulation. The MSC secretome has therefore attracted significant attention for its therapeutic potential. In the uterus, studies utilizing rodent models and limited human trials have shown a potential benefit of MSCs and the MSC secretome in treatment of endometrial infertility. This review will explore the potential of MSCs to treat women with impaired endometrial receptivity due to a thin endometrium or endometrial scarring. We will provide context supporting leveraging MSCs for this purpose by including a review of mechanisms by which the MSC secretome promotes regeneration and repair of nonreproductive tissues.

Objective To evaluate whether Zi Gui Nv Zhen capsules (ZGNZC) can increase the fertility rate of Chinese women with infertility due to thin endometrium.Methods Prospective, randomized, open-labeled 3-monthly study; 104 patients (aged 20–40 years) receiving either ZGNZC (experimental group, n = 55) or not (control group, n = 49). Main outcomes: thickness/type of the endometrium during ovulation and pregnancy rate. Between-group analysis (A) compares the experimental vs. control group, and within-group analysis (B) compares data at baseline and after study in the experimental group.Results (A) Between-group-analysis: Patients with ZGNZC had a higher endometrium thickness (0.8 ± 0.27 vs. 0.68 ± 0.10; p

Endometrial receptivity is key to clinical pregnancy by in vitro fertilization-embryo transfer （IVF-ET） technique. Endometrial thickness （EMT） is a major index for pregnancy monitoring, but the optimal time indicating endometrial receptivity is controversially uncertain. Multiple studies have demonstrated the correlation between EMT and IVF pregnancy outcomes and EMT of a moderate range is essential for good pregnancy outcomes and a thin endometrium produces negative pregnancy outcomes. In this paper, we reviewed the research on the impact of EMT on IVF-ET pregnancy outcomes in terms of timing of EMT measurement, clinical pregnancy rate, live birth rate, ectopic pregnancy rate, placenta praevia, and low birth weight, investigating the mechanism of occurrence and treatment of thin endometrium so as to provide clinical references for improving IVF pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers or recurrent implantation failure during assisted reproductive treatment. Small proteoglycans regulate intracellular signaling cascades by bridging other matrix molecules and tissue elements, affecting cell proliferation, adhesion, migration, and cytokine concentration. The aim of the study is to investigate the role of small leucine-rich proteoglycans in the pathogenesis of thin and thick human endometrium and their differences from normal endometrium in terms of fine structure properties. Normal, thin, and thick endometrial samples were collected, and small leucine-rich proteoglycans (SLRPs), decorin, lumican, biglycan, and fibromodulin immunoreactivities were comparatively analyzed immunohistochemically. The data were compared statistically. Moreover, ultrastructural differences among the groups were evaluated by transmission electron microscopy. The immunoreactivities of decorin, lumican, and biglycan were higher in the thin endometrial glandular epithelium and stroma compared to the normal and thick endometrium (p < .001). Fibromodulin immunoreactivity was also higher in the thin endometrial glandular epithelium than in the normal and thick endometrium (p < .001). However, there was no statistical difference in the stroma among the groups. Ultrastructural features were not profoundly different among cases. Telocytes, however, were not seen in the thin endometrium in contrast to normal and thin endometrial tissues. These findings suggest a possible role of changes in proteoglycan levels in the pathogenesis of thin endometrium. [ABSTRACT FROM AUTHOR]

Endometrial injury is one of the leading causes of female infertility and is caused by intrauterine surgery, endometrial infection, repeated abortion, or genital tuberculosis. Currently, there is little effective treatment to restore the fertility of patients with severe intrauterine adhesions and thin endometrium. Recent studies have confirmed the promising therapeutic effects of mesenchymal stem cell transplantation on various diseases with definite tissue injury. The aim of this study is to investigate the improvements of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on functional restoration in the endometrium of mouse model. Therefore, ethanol-induced endometrial injury mouse models were randomly divided into two groups: the PBS-treated group, and the MenSCs-treated group. As expected, the endometrial thickness and gland number in the endometrium of MenSCs-treated mice were significantly improved compared to those of PBS-treated mice (P < 0.05), and fibrosis levels were significantly reduced (P < 0.05). Subsequent results revealed that MenSCs treatment significantly promoted angiogenesis in the injured endometrium. Simultaneously, MenSCs enhance the proliferation and antiapoptotic capacity of endometrial cells, which is likely contributed by activating the PI3K/Akt signaling pathway. Further tests also confirmed the chemotaxis of GFP-labeled MenSCs towards the injured uterus. Consequently, MenSCs treatment significantly improved the pregnant mice and the number of embryos in pregnant mice. This study confirmed the superior improvements of MenSCs transplantation on the injured endometrium and uncovered the potential therapeutic mechanism, which provides a promising alternative for patients with serious endometrial injury. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to optimize the treatment methods of infertility, which is suggested to be mainly caused by thin endometrium, using a special form of traditional Chinese medicine, the Dingkun pill (DKP), to increase the beneficial endometrial effect of conventional hormone/progestogen therapy. Methods: A total of 307 patients visiting our specialized gynecological endocrinology department because of infertility, which we suggested to be caused by thin endometrium [endometrial thickness (EMT) < 7 mm], were randomly assigned to the experimental group and the control group. The experimental group was treated with estradiol + sequential dydrogesterone + DKP (every day); the control group received hormonal treatment without the Chinese medicine. All patients were monitored in terms of follicle diameter, EMT, and endometrial type every 2 days from the 8th to the 10th day of the menstrual cycle until ovulation day during three menstrual cycles. Serum progesterone levels on 7-8 days after ovulation were measured, and the cumulative pregnancy rate during three menstrual cycles between the two groups was compared. Results: EMT on ovulation day in the experimental group was significantly higher than that in the control group (7.88 vs. 7.15 mm; p < 0.001). The proportion of type A and type B endometrium in total was significantly higher in the experimental group than that in the control group (83.2% vs. 77.7%; p < 0.05). Progesterone levels were significantly higher in the experimental group than those in the control group (10.874 vs. 10.074 ng/mL; p < 0.001). The cumulative pregnancy rate, the main outcome of the study, was significantly higher in the experimental group than that in the control group (29.2% vs. 15.7%; p < 0.05). Conclusion: DKP added to conventional estrogen/progestogen therapy can significantly improve EMT and luteal function in patients attending due to infertility. Because this regimen increased the cumulative pregnancy rate in our study, we conclude that DKP can be used to increase the so-called "thin endometrium infertility". [ABSTRACT FROM AUTHOR]

Context: Thin endometrium during the frozen embryo transfer cycles leads to cycle cancellation. The embryo transfer cycle getting deferred is an unpleasant experience for the patients and the fertility specialist. Aims: The purpose of this study is to evaluate the effectiveness of Autologous Blood Cell Derivative (ABCD) growth factor concentrate to obtain an optimal thickness of endometrium for embryo transfer during IVF treatments, where rapid regeneration is crucial for the expected therapeutic outcome. Settings and Design: A retrospective cohort study was conducted in Manipal Assisted Reproduction Center, a referral center in Southern India. Methods and Material: Fifty-six patients with thin endometrium were administered three doses of ABCD growth factor concentrate as per the protocol after informed consent. All of them had a history of embryo transfer (ET) cancellation in frozen-thawed embryo cycles due to inadequate growth of the endometrium despite therapy with estrogens and drugs for improving uterine blood circulation. Results: The endometrium thickness during the implantation window in the patients included in the study averaged 6.48 ± 1.19 mm. After the intervention, 55 out of 56 patients (98.2%) showed a considerable change in the thickness of the endometrium layer with an average thickness of 8.48 ± 1.32 mm (< 0.0001, SE 0.233, 95% CI 1.58–2.5). Out of the 55 patients, 20 got pregnant, i.e., 36.4% pregnancy rate. Till date, thirteen pregnancies had live births (65%), three pregnancies (15%) were biochemical pregnancies, 1 (5%) was ectopic, and three pregnancies (15%) had spontaneous miscarriage before eight weeks. When we compared the endometrial thickness (EMT) in the pregnant and non-pregnant groups pre- and post-ABCD instillation, (6.47 ± 1.31 mm vs 6.48 ± 1.4 mm, p = 0.98 and 8.68 ± 1.32 mm vs 8.48 ± 1.32 mm, p value 0.59) the p value was not statistically significant. Conclusions: The implantation, clinical pregnancy and live birth rates were 36.4, 30 and 65%, respectively. This result is a significant improvement for patients with thin endometrium for whom we would otherwise cancel the frozen transfer. An autologous resource is a safe, readily available and inexpensive treatment modality. [ABSTRACT FROM AUTHOR]

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03–9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12–3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) for infertility and recurrent spontaneous abortion. Methods Existing research was searched in PubMed, Embase and Cochrane Library till Dec 2021. Randomized control trials (RCTs) that compared G-CSF administration with the control group in infertility women undergoing IVF were included. The primary outcomes included clinical pregnancy rate; the secondary outcomes included live birth rate, abortion ratebiochemical pregnancy rate, embryo implantation rate, as well as endometrial thickness. Result(s) 20 RCTs were included in this study. G-CSF increased the clinical pregnancy rate (RR = 1.85; 95% CI: 1.07, 3.18) and the endometrial thickness (MD = 2.25; 95% CI: 1.58,2.92;) in patients with thin endometrium undergoing IVF. G-CSF increased the biochemical pregnancy rate (RR = 2.12; 95% CI: 1.54, 2.93), the embryo implantation rate (RR = 2.51; 95% CI: 1.82, 3.47) and the clinical pregnancy rate (RR = 1.93; 95% CI: 1.63, 2.29) in patients with a history of repeated implantation failure undergoing IVF. No differences were found in pregnancy outcomes of general IVF patients. Conclusions Granulocyte colony-stimulating factor is likely to be a potential option for infertility women undergoing IVF with thin endometrium or recurrent implantation failure . Trial registration Retrospectively registered (The PROSPERO registration number: CRD42022360161).

Background and Aim: Endometrium is one of the main factors in implantation and pregnancy. Adequate thickness of the endometrium is crucial for successful embryo implantation. Thin endometrium significantly increases the risk of embryo implantation failure, as the pregnancy rate in women. Intrauterine infusion of platelet rich plasma (PRP) is a new approach that has been suggested for the treatment of thin endometrium. This meta-analysis was conducted systematically to evaluate the efficacy of PRP therapy on endometrial thickness and pregnancy rates. Methods: We conducted a systematic review and meta-analysis of the retrieved randomized controlled trial (RCT). Studies on the intra uterine infusion of PRP in women undergoing frozen thawed embryo transfer (FET) in assisted reproductive technology (ART), identified by conducting a systematic search, using PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar. Data were extracted and analyzed independently using random effects model or common effects model according to heterogeneity. Risk of bias assessment was assessed using RoB 2 tools. Results: Five RCTs involving 377 patients were included in the endometrial thickness outcome. The endometrial thickness between PRP and control group showed a significant probability of increasing endometrial thickness in PRP group (MD 0,83, 95% CI 0,40-1,26, I 2 84%, p

Tissue‐specific decellularized extracellular matrix recapitulates the complexity of natural ECMs, creating an organ‐specific microenvironment based on its intrinsic characteristics. Here, hydrogels containing uterus‐derived decellularized extracellular matrix (UdECMs) from the endometrium‐specific layer or the entire uterus are developed. UdECMs serve as effective organ‐specific biomaterials, displaying that intrauterine UdECM administration induces endometrial regeneration and fertility enhancement. Moreover, UdECM administration alters the profile of natural killer cell subpopulations to exhibit more mature and less cytotoxic features, providing a favorable uterine environment for successful implantation and decidualization. Interestingly, insulin‐like growth factor 1 and insulin‐like growth factor‐binding protein 3 as key regulatory factors that contribute to UdECM‐mediated endometrial regeneration are discovered. Furthermore, ex vivo culture of human uterine tissues reveals that UdECMs of different origins exhibit distinct therapeutic effects based on the endometrial conditions of patients, suggesting their uses as a therapeutic intervention providing personalized regenerative medicine for infertile patients with a poor uterine environment. [ABSTRACT FROM AUTHOR]

Acute chorioamnionitis complicates 1–2% of all pregnancies and might increase the prevalence of endometritis that can cause Asherman syndrome or adhesions, but little is known about the direct effects of chorioamnionitis on future fertility. We aimed to evaluate the effect of chorioamnionitis on future fertility and obstetrics complications in patients diagnosed with chorioamnionitis during their pregnancy. We performed an observational, case–control retrospective study of pregnant women aged 18–40 years old, hospitalized with a diagnosis of chorioamnionitis between January 2013 and December 2017. The control group consisted of patients with similar demographic/obstetrics characteristics, matched with a ratio of 1:2 without chorioamnionitis. The prevalence of post gestational diagnostic hysteroscopy was significantly higher in the study group as compared to the control group (22.9% versus 9.0%, respectively; p = 0.005). Moreover, the study group underwent significantly more operative hysteroscopy compared to the control group (10.8% versus 3.6%, respectively; p = 0.04). The patients in the study group had significantly higher prevalence of miscarriages (27% versus 13.2%, respectively; p < 0.01). We conclude that chorioamnionitis may cause endometritis with the consequent impaired fertility, necessitating comprehensive evaluations for secondary infertility, including hysteroscopy aiming to treat intrauterine adhesions that may affect and impair fertility. [ABSTRACT FROM AUTHOR]

Disruption of endometrial regeneration, fibrosis formation, and intrauterine adhesions underlie the development of "thin" endometrium and/or Asherman's syndrome (AS) and are a common cause of infertility and a high risk for adverse obstetric outcomes. The methods used (surgical adhesiolysis, anti-adhesive agents, and hormonal therapy) do not allow restoration of the regenerative properties of the endometrium. The experience gained today with cell therapy using multipotent mesenchymal stromal cells (MMSCs) proves their high regenerative and proliferative properties in tissue damage. Their contribution to regenerative processes is still poorly understood. One of these mechanisms is based on the paracrine effects of MMSCs associated with the stimulation of cells of the microenvironment by secreting extracellular vesicles (EVs) into the extracellular space. EVs, whose source is MMSCs, are able to stimulate progenitor cells and stem cells in damaged tissues and exert cytoprotective, antiapoptotic, and angiogenic effects. This review described the regulatory mechanisms of endometrial regeneration, pathological conditions associated with a decrease in endometrial regeneration, and it presented the available data from studies on the effect of MMSCs and their EVs on endometrial repair processes, and the involvement of EVs in human reproductive processes at the level of implantation and embryogenesis. [ABSTRACT FROM AUTHOR]