Thin Endometrium Research Articles

Perinatal and obstetric-neonatal outcomes following frozen embryo transfer cycles with a thinner endometrium: a retrospective study.

The purpose of this study was to evaluate the relationship of thin endometrial thickness (EMT) on the maternal and child health outcome of frozen-thawed embryo transfer (FET) cycles with singletons. The retrospective cohort study included 1,771 live singleton deliveries, with 273 in the thin endometrium group (EMT ≤ 7.5mm) and 1,498 in the control group (EMT > 7.5mm). Pregnancy, perinatal complications and neonatal outcomes were compared between the two groups. Women in the thinner endometrium group had higher rates of preeclampsia (7.69% vs. 7.00%), placenta previa (4.39% vs. 2.43%), postpartum haemorrhage (15.38% vs. 11.42%) than the control groups, although they were not significantly different. Significant difference was observed in the rates of placental abruption (1.09% vs. 0.07%, P = 0.001), abnormal placental cord insertion (3.66% vs. 1.74%, P = 0.011), placental adherence (15.38% vs. 7.14%, P < 0.001) between the two groups. No significant difference could be found regarding preterm labour, macrosomia, Apgar ≤ 7, large for gestational age (LGA) and appropriate for gestational age (AGA), and singletons from the thinner endometrium group had a significantly lower birthweight than those from the controls. Then after adjusting for confounders, thinner endometrium was still statistically significantly associated with placental adherence, postpartum haemorrhage and low birthweight (LBW). These findings highlight the important role of endometrial thickness in influencing perinatal and obstetric-neonatal outcomes in FET cycles. The study contributes to the growing body of evidence supporting the clinical relevance of endometrial thickness in FET cycles and underscores the need for close monitoring and management of pregnancies in women with a thin endometrium. Future research should focus on elucidating the underlying mechanisms and identifying effective interventions to improve endometrial thickness and pregnancy outcomes in this patient population.

Effect of Different Concentrations of PRP on the Expression of Factors Involved in the Endometrial Receptivity in the Human Endometrial Cells from RIF Patients Compared to the Controls.

Platelet-rich plasma (PRP) has been suggested for the improvement of endometrial growth and receptivity in the patients with recurrent implantation failure (RIF). The aim of present study was to investigate the impact of different concentration of PRP on the expression of genes involved in the endometrial receptivity in the human endometrial cells from RIF and controls with thin and normal endometrium in vitro. In this cross-sectional study, endometrial biopsies were obtained from 14 healthy fertile women and 14 women with RIF. Endometrial cells from 4 different group (RIF and control with endometrial thickness < 7mm and > 7mm) were cultured with three different concentration of PRP 3%, 5% and 10%. Expression of leukemia inhibitory factor (LIF), COX2 and P53, estrogen receptors (ERs) and progesterone receptors (PRs) genes were measured using quantitative real-time polymerase chain reaction (PCR). Protein expression levels of LIF, COX2 and p53 were evaluated using Western Blot method (WB). There was a significant decrease in the expression of PROA/b, ER2/b, LIF/b, COX2/b and P53/b genes in the RIF groups compared to the controls. Treatment with 5% and 10% PRP caused a significant increase in the gene expression of PRs, ERs, LIF/b, COX2/b and p53 in the RIF groups. Moreover, protein expression of COX2/b, LIF/b and p53/b increased following treatment with PRP in the RIF group with the endometrium thickness < 7mm. PRP enhances expression of LIF, COX2, p53, ERs and PRs in the RIF patients with thin endometrium which may improve endometrium receptivity.

Menstrual blood-derived mesenchymal stem cells combining with platelet-rich plasma infusion in endometrium repair.

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.

Evaluation of the effect of an amniotic membrane derived bio-nano product (LifeCell) on human endometrial cells proliferation and gene expression: An in-vitro study

ObjectiveSuccessful assisted reproductive technology (ART) requires a receptive endometrium with appropriate thickness and the presence of specific cytokines, chemokines, and growth factors. Despite advancements in ART, the success rates remain suboptimal, particularly in individuals with thin endometrium resistant to treatment. In this study, we evaluated the potential effects of LifeCell, a product of BioNano Technology, on the growth, development, and acceptance of endometrial cells. Study designWe cultured endometrial cells in a defined medium with different concentrations of LifeCell and examined cell growth, development, and the expression of genes involved in endometrial receptivity. ResultsCo-culture of primary human endometrial cells with 5 % Life cell solution significantly stimulated the endometrial cell growth, development and receptivity genes expression. The expression levels of FGF2 and CSF in the 72 h co-cultured were significantly increased compared with other groups (P < 0.01). HOXA10 and LIF significantly increased in the 72 h co-cultured compared with 24 h co-cultured and control groups but had no significant level compared with 48 h cocultured. HOXA10 significantly increased in the 48 h cocultured compared with control group. IL-6 and Hb-EGF increased in the 48 h co-cultured compared to other groups but had no significant level. VEGF increased in the treated groups compared to control but had no significant level. The expression of OPN, unlike the other genes, decreased in the treated group compared to the control, which was not significant. ConclusionsThese findings suggest that LifeCell may be a potential option for patients with treatment-resistant thin endometrium in cases of infertility.

Justification of the necessity, value, and role of diagnostic hysteroscopy in the management plan for abnormal uterine bleeding. A teaching hospital experience

Aims: The crucial purpose of this study is to pay thoughtfulness to the filmic inspection of the uterine cavity and circumstantial operative amenities have provided the gynecologist with the perfect 'diagnostic' tool, making it conceivable to inspect the cavity and biopsy distrusted areas under direct visualization for patients presented with abnormal uterine bleeding AUB in the perimenopausal or postmenopausal periods. Materials and methods: We retrospectively reviewed the medical records of 123 perimenopausal and postmenopausal women who presented with abnormal uterine bleeding (AUB) at Jordan University Hospital (JUH) between January 1, 2022, and August 1, 2024. Participants underwent diagnostic hysteroscopy followed by endometrial biopsy. The hysteroscopic findings were compared with the final histopathological diagnoses to evaluate diagnostic accuracy. Results: In this study of 123 women, clinical indications for hysteroscopy differed by menopausal status, with heavy menstrual bleeding being the most common indication among premenopausal women (74.6%), while postmenopausal bleeding was predominant in postmenopausal women (80.8%). Hysteroscopy revealed a regular uterine cavity in 92.7% of cases, with endometrial abnormalities such as thickened or thin endometrium observed in a significant number of women. Histopathological analysis found normal endometrium in 47.2% of cases, with endometrial polyps (16.3%) and other conditions such as hormonal imbalance and endometritis also frequently noted. A significant relationship was observed between menopausal status and both uterine cavity condition (p = .025) and endometrial state (p = .002), with postmenopausal women more likely to exhibit a thin or abnormal endometrium. The diagnostic value of hysteroscopy was high for fibroids (100% detection) but lower for endometrial polyps (50% detection). Conclusion: Hysteroscopy must be used as the second-line diagnostic tool after vaginal ultrasound assessment for evaluating the endometrial status in cases of AUB and a necessary step before the decision of surgical removal of the uterus. However, hysteroscopy is not very reliable for ruling out endometrial hyperplasia or cancer in women who have postmenopausal bleeding. Because of this, an endometrial biopsy is crucial for an accurate diagnosis.

Modern concepts about the problem of endometrial infertility against the backdrop of the "thin endometrium" (literature review)

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.

8314 Masculinizing Hormone Therapy and Gynecological Neoplasm: a Single Institution Cohort

Abstract Disclosure: S. Korpaisarn: None. T. Ngaothepphurktharam: None. Y. Tingthanatikul: None. Background: Gynecological neoplasm/malignancy is one of the concerned areas among transgender men on masculinizing hormone therapy (MHT). Long-term MHT and gynecological neoplasm/malignancy remain unclear. Methods: A retrospective cohort chart review was done on all transgender men (TM) who underwent hysterectomy with or without oophorectomy between January 2014 and October 2022. Intraoperative findings and pathological results of genital organs, including the cervix, endometrium, myometrium, and fallopian tubes, were extracted. The pathological results were classified as benign, precancerous, and malignant. Descriptive statistical analysis was used to demonstrate the prevalence of gynecological neoplasm and malignancy. Results: A total of 30 TM underwent hysterectomy with oophorectomy. Twenty-eight (93%) had bilateral oophorectomy, and 7% had unilateral oophorectomy due to gynecological conditions. The mean age when TM underwent surgery was 32.1 ± 5.1 years, and the mean age of gender-affirming hormone initiation was 28.7± 5.1 years. The median duration of MHT before gynecological surgery was 32 months (IQR 22-59). Most TM (73%) used testosterone enanthate, 17% testosterone undecanoate, and 2 transgender men did not start MHT before genital surgery. All TM who used GHT became amenorrheic before surgery. The median preoperative testosterone level was 561.5 ng/dL (IQR 776-1189). Intraoperative findings revealed that most TM (86.7%) had unremarkable uterus size, and 13% showed enlarged uterus size. In the latter, all were from myoma uteri. Most intraoperative findings of ovaries showed 93% unremarkable. One TM had intraoperative polycystic ovarian morphology, and one showed a unilateral ovarian cyst. Cervical pathological reports showed unremarkable results in 67%. Five TM (17%) had chronic cervical inflammation. There was 1 TM (3%) who showed low-grade squamous intraepithelial lesion (LSIL) with squamous metaplasia. Regarding endometrial pathology, the mean endometrial thickness was 0.13 ± 0.08 cm. Most endometrial reports (66%) were in a proliferative phase, 27% were in an atrophic or inactive endometrium, and 7% were in the secretory phase. Regarding pathological reports of ovaries, 80% had cystic ovaries. None of the TM showed precancerous or malignant conditions of endometrium, ovaries, and fallopian tubes. PAP smear was available in 27 TM; all were negative for intraepithelial lesions or malignancy. Conclusion: Among a cohort of TM who received MHT for 32 months, there is no evidence of precancerous or malignant pathology of the endometrium, ovaries, and fallopian tubes. Most of them had thin endometrium with cystic ovaries. One TM showed LSIL with squamous metaplasia of the cervix. Healthcare providers should follow local gynecological cancer screening guidelines developed for cisgender women in their clinical practice. Presentation: 6/2/2024

EFFECT OF PHYSIOTHERAPY ON THE IMPLANTATION POTENTIAL OF THIN ENDOMETRIUM

The article is dedicated to the urgent problem of infertility associated with thin endometrium. The mechanisms of action of various physiotherapeutic methods on the endometrium, such as magnetotherapy, laser therapy, ultrasound therapy, and electrical stimulation, are discussed. The beneficial effects of physiotherapy are described in detail, including improved blood flow, reduced inflammation, and stimulation of tissue regeneration. The results of clinical trials confirming the effectiveness of physiotherapy in increasing the thickness and improving the structure of the endometrium are presented. The article also includes indications and contraindications for the use of physiotherapy and emphasizes the importance of an individualized approach to treatment.

Enhancing predictions of embryo implantation in thin endometrium: a comparative analysis of endometrial thickness in frozen versus fresh IVF cycles

This study investigated whether the difference between endometrial thickness in the frozen embryo transfer (FET) cycle and the preceding fresh stimulated cycle predicts clinical pregnancy in women with thin endometrium. A retrospective analysis of 335 cycles in 227 women (age < 43) with endometrium < 8 mm in the FET cycle was conducted. Endometrial thickness was assessed using the ratio (ETfrozen/fresh) and absolute difference (ETfresh-frozen) between the maximal endometrial thickness measured during the stimulated IVF cycle and that measured in the FET cycle. We hypothesized that a smaller difference and higher ratio during FET will be associated with higher pregnancy rate. No embryo implantation occurred in women with an FET endometrial thickness < 5.9 mm and an ETfrozen/fresh < 0.86. Cycles with a positive beta-human chorionic gonadotropin (ß-hCG) showed a significantly lower mean ETfresh-frozen (1.89 ± 1.78 vs 2.30 ± 1.81, p = 0.03), and a significantly higher ETfrozen/fresh ratio (0.82 ± 0.17 vs. 0.77 ± 0.15, p = 0.024). Endometrial thickness in the FET cycle normalized to the preceding stimulated cycle is associated with implantation and may constitute a novel predictor of FET success in women with thin endometrium.

Subendometrial blood flow detected by Doppler ultrasound associates with pregnancy outcomes of frozen embryo transfer in patients with thin endometrium.

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] ≤ 0.7cm). 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. In the patients with 0.5cm ≤ EMT ≤ 0.7cm, 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 ≤ 0.7cm. 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.

Effects of intrauterine infusion of autologous platelet-rich plasma gel on endometrial thickness and outcomes of frozen-thawed embryo transfer in women with thin endometrium.

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. This study included 111 women (aged 25-44years) 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 < 7mm. 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. Mean EMT was greater in women who received PRP gel than in those who did not (6.7mm vs. 6.3mm, 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. 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.

Effects of royal jelly and its extracts on endometrial receptivity and MCF-7 cell growth in rats with thin endometrium

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.

Altered Expression of C4BPA and CXCL1 Genes in the Endometrium of Patients with Recurrent Implantation Failure after In Vitro Fertilization and Thin Endometrium.

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).

Efficacy of intrauterine autologous blood cell derivatives in enhancing endometrial thickness and IVF outcomes for women with recurrent implantation failure: a retrospective cohort study

PurposeThe 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.MethodsThis 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).ResultsWe 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.ConclusionIntrauterine 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.

Angiogenic factor-driven improvement of refractory thin endometrium with autologous platelet-rich plasma intrauterine infusion in frozen embryo transfer cycles.

A beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP. This study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient's whole blood (WB) and PRP by utilizing a commercial screening kit. The live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB. Intrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement.

Effects of platelet-rich fibrin on human endometrial stromal cells behavior in comparison to platelet-rich plasma.

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. 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. 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. PRF offer a more sustained therapeutic effect compared to PRP, which provides a new idea for endometrial regeneration and repair.

A Dopamine-Modified Hyaluronic Acid-Based Mucus Carrying Phytoestrogen and Urinary Exosome for Thin Endometrium Repair.

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1β and Wnt-β catenin-TGFβ-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.

Efficacy of platelet-rich plasma in the treatment of thin endometrium: a meta-analysis of randomized controlled trials

BackgroundThin 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).MethodsWe 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.ResultsEight 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.ConclusionIntrauterine 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 registrationThe review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.

Injectable GelMA Hydrogel Microspheres with Sustained Release of Platelet-Rich Plasma for the Treatment of Thin Endometrium.

Platelet-rich plasma (PRP) intrauterine infusion has been demonstrated to be effective in treating thin endometrium and achieving pregnancy. However, the rapid release of growth factors limits its effectiveness in clinical applications, and thus, multiple intrauterine infusions are often required to achieve therapeutic efficacy. In this study, a GelMA hydrogel microsphere biomaterial is developed using droplet microfluidics to modify the delivery mode of PRP and thus prolong its duration of action. Its biocompatibility is confirmed through both in vivo and in vitro studies. Cell experiments show that PRP-loaded microspheres significantly enhance cell proliferation, migration, and angiogenesis. In vivo experiments show that the effects of PRP-loaded microspheres on repairing the endometrium and restoring fertility in mice could achieve the impact of triple PRP intrauterine infusions. Further mechanistic investigations reveal that PRP could facilitate endometrial repair by regulating the expression of E2Fs, a group of transcription factors. This study demonstrates that hydrogel microspheres could modify the delivery of PRP and prolong its duration of action, enabling endometrial repair and functional reconstruction. This design avoids repeated intrauterine injections of PRP in the clinic, reduces the number of patient visits, and provides a new avenue for clinical treatment of thin endometrium.

Semiconducting polymer nanoparticles laden with platelet-rich plasma for endometrium regeneration via regulating macrophage M1/M2 type polarization

Thin endometrium is linked to recurrent miscarriage and infertility. Reliable clinical strategies for endometrium regeneration are lacking. Human platelet-rich plasma (PRP), especially derived from umbilical cord blood, shows promising regenerative capabilities. Here, we designed a construct of the human umbilical cord blood-derived PRP and the as-synthesized semiconducting polymer nanoparticles (SPNs) for promoting endometrial regeneration and fertility restoration following in situ microinjection in a rat model of endometrial damage. The mechanistic basis for the regenerative benefits of these PRP-SPNs was also assessed, with a particular focus on the regulation of macrophage activity. In vitro, PRP-SPNs treatment was sufficient to enhance the proliferation of human endometrial stromal cells. In vivo, PRP-SPNs administration induced robust endometrial proliferation, re-epithelialization, and angiogenic activity while inhibiting localized fibrosis. Critically, the regenerated endometrium exhibited enhanced receptivity such that it was conducive to higher rates of implantation and fetal development. At the cellular level, PRP-SPNs were found to promote the polarization of CD163+ M2 macrophages while coordinating the induction of more effective anti-inflammatory responses in vivo and in vitro. Together, these results suggest that PRP-SPNs represent a safe, effective, noninvasive approach that can be conveniently implemented to remediate thin endometrium and restore fertility for patients in need.