Endometrial Receptivity In Patients Research Articles

P-414 Evaluation of small non-coding RNAs in uterine fluid in the diagnosis of endometrial receptivity in assisted reproductive technology programs

Abstract Study question To analyze endometrial receptivity in patients undergoing frozen-thawed embryo transfer (FET) based on the expression of small non-coding RNAs (sncRNAs): microRNAs and piwiRNAs. Summary answer According to our studies, the expression of sncRNAs in uterine aspirate may become an additional non-invasive and effective way to determine endometrial receptivity. What is known already Today, infertility remains an important medical and social problem. According to statistics, the effectiveness of ART programs remains at the level of 30-40%. Violation of the implantation mechanism is associated with a shift in the “implantation window” period and endometrial receptivity. Therefore, the search for an ideal marker of endometrial receptivity is a priority. Studying the expression of sncRNAs in endometrial secretions or uterine aspirate may become a potential marker of endometrial receptivity. Study design, size, duration The study included 102 infertile couples with women aged from 23 to 40 years. The patients were divided into two groups depending on the preparation of the endometrium for the FET: group 1 - 42 patients with natural cycle (NC); group 2 - 60 patients with hormone replacement therapy (HRT). SncRNAs were assessed in uterine aspiration on the day of FET. Participants/materials, setting, methods Uterine fluid was carried out in a volume of 5 to 50 μl with noninvasive technique. Next, the material was sent to the laboratory of applied transcriptomics for identification of sncRNAs. Quantitative assessment of sncRNAs in the endometrial secretion on the day of FET was carried out by deep sequencing on the NextSeq 500/550 platform (Illumina). Main results and the role of chance Logistic regression models were constructed for predicting pregnancy and endometrial receptivity based on the expression profiles of microRNAs and piwiRNAs in uterine aspirate, which are with 95% sensitivity and 74% specificity in the case of a combination of miR-34c-5p, miR-363–3p, miR-1180–3p, miR-361–3p, miR-183–5p (AUC = 0.91, p < 0.001) or with 74% sensitivity and 87% specificity in the case of a combination of molecules piR_004152, piR_020541, piR_001318, piR_014923, piR_017716 (AUC = 0.81, p < 0.001) determine the readiness of the endometrium for embryo implantation in the FET. In the NC and HRT groups, statistically significant differences were established between patients who became pregnant and patients with a negative result of the ART program in terms of baseline progesterone levels (p < 0.001). In the HRT group, positive correlations were revealed between endometrial thickness on the day of embryo transfer and the baseline level of progesterone (p = 0.04, r = 0.28). Limitations, reasons for caution The study was limited in sample size of patients and requires further randomized studies. Wider implications of the findings For the first time, a test system has been developed for assessing endometrial receptivity based on the expression of sncRNAs in patients both in the NC and in the HRT during the FET. It was found that increased initial progesterone levels correlate with positive outcomes of ART programs. Trial registration number not applicable

Excessive proliferating cell nuclear antigen attenuates endometrial adhesive capacity and decidualization in patients with recurrent implantation failure.

Does the expression of proliferating cell nuclear antigen (PCNA) in the endometrium regulate endometrial receptivity in patients with recurrent implantation failure (RIF)? A high abundance of PCNA attenuates endometrial adhesive capacity and decidualization in patients with RIF. Aberrant expression of PCNA has been discovered in multiple infertility-related disorders. However, the expression pattern and role of PCNA in the establishment of endometrial receptivity and endometrial decidualization in patients with RIF remain unclear. We analysed the expression of PCNA in mid-secretory endometrial tissues from 24 patients with RIF and 24 healthy women. Additionally, PCNA expression levels were measured in proliferative and mid-secretory phase endometrial tissue samples from women with regular menstrual cycles and in decidual tissue samples taken from ten women during normal early pregnancy (n = 10 per phase for each group). The function and regulatory mechanisms of PCNA in endometrial adhesive capacity and endometrial decidualization were investigated using BeWo spheroids, Ishikawa cells, and human endometrial stromal cells (HESCs). The expression of PCNA in mid-secretory endometrial tissues of patients with RIF and women with normal endometrium and in endometrial tissue at different stages of the menstrual cycle and in decidualized tissues was analysed by RT-qPCR, western blot, and immunohistochemistry staining (IHC). Furthermore, the number of BeWo spheroids directly attached to the Ishikawa cell monolayers, and the potential molecular mechanisms involved, were compared between cells overexpressing PCNA and a control group. Additionally, the effect and regulatory mechanisms of PCNA on the decidualization of HESCs in vitro were investigated. Our findings indicated that the abundance of PCNA was dramatically greater in mid-secretory endometrial tissues from patients with RIF than in those from women with healthy endometrium. The expression of PCNA increased in the proliferative phase of the menstrual cycle but decreased gradually in the mid-secretory phase and in decidual tissues. Interestingly, PCNA was expressed in both human endometrial epithelial cells (HEECs) and HESCs. In Ishikawa cells, PCNA overexpression dramatically reduced the endometrial adhesive capacity by inhibiting the expression of adhesion molecules (E-cadherin and integrin β3) and activating the FAK/paxillin signalling pathway. Furthermore, in HESCs, PCNA overexpression attenuated endometrial decidualization by activating the AKT/β-catenin signalling pathway and increasing tight junctions between cells by upregulating ZO-1 and occludin expression. In addition, PCNA-ELAVL1 interactions were confirmed by coimmunoprecipitation in decidualized HESCs. N/A. The functional analysis of PCNA was limited by the number of human endometrial tissues. A larger sample size is required to further explore the potential roles of PCNA during embryo implantation. Moreover, the present results should be taken with caution, as only a few of the embryos that were transferred in RIF patients population underwent preimplantation genetic testing for embryonic chromosome aneuploidies (PGT-A), despite embryo ploidy testing being significant in the diagnosis of unexplained RIF. High PCNA expression attenuates endometrial adhesive capacity and decidualization in patients with RIF. These findings provide new insights into the potential mechanisms underlying the occurrence of implantation failure. This work was supported by the National Natural Science Foundation of China (82101698), Shandong Provincial Natural Science Foundation (ZR2021MH012), and the Science and Technology Plan of Yantai (2023YD021 and 2022YD031). The authors have no conflicts of interest to disclose. N/A.

SIRT3 protects endometrial receptivity in patients with polycystic ovary syndrome.

The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls (P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS (P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.

Long noncoding RNA BMPR1B-AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway.

Endometriosis (EMs)-related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative real-time PCR. Here we identified an lncRNA, named BMPR1B-AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B-AS1 positively regulates decidual formation through interaction with the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B-AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2-BMPR1B-AS1-SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs.

The Comparison Between The Effect of Different Medical Drugs used To Improve Endometrial Receptivity in patients with Thin Poorly Vascularized Endometrium

In a perfect world, the peak of receptivity of the endometrial lining would occur simultaneously with the entry into the uterine cavity of a healthy blastocyst, which would then be able to adhere, attach, invade, and develop protected until the time of delivery. This would be the ideal scenario. The study was carried out on 200 infertile women who have thin , poorly vascularized endometrium, those patients were divided into five groups ; 40 patients in each group, group A received esterofem oral, group B received vagifem vaginal tablets, group C received sildenafil citrate gel, group D received pentoxifylline oral and group E received 4 grams of pentoxifylline vaginal gel. The endometrial thickness, vascularity zones, sub endometrial flow, and both uterine arteries resistance and pulsatility indices were assessed at the middle of the menstrual cycle (day 11–14) on a monthly basis for six cycles or until a positive pregnancy test was obtained. Pentoxifylline vaginal gel, pentoxifylline+ vitamin E capsule, and sildenafil vaginal gel have improved the vascularity indeces of endometrium and uterine arteries, while the vagifem and esterofem were less effective in terms of improving the vascularity indeces of endometrium and uterine arteries. The study also showed that 57.5% of women succeed to get pregnant after six months of receiving pentoxifylline vaginal gel, 35% of women succeed to get pregnant after six months of Pentoxifylline+vit E, while 22.5% of women succeed to get pregnant after six months of sildenafil, about 10% of women got pregnant after six months of vagifem, and finally 2.5% of women got pregnant after six months of receiving estrofem tablets. It was discovered that pentoxifylline vaginal gel, pentoxifylline tablet plus vitamin E capsule, and sildenafil vaginal gel were able to improve the vascularity index of the endometrium, the uterine arteries and endometrial thickness, and enhance the pregnancy rates in patients with thin poorly vascularized endometrium

OC15.03: Application of multimodal ultrasound to evaluate endometrial receptivity in patients with unexplained infertility

OC15.03: Application of multimodal ultrasound to evaluate endometrial receptivity in patients with unexplained infertility

P-322 Single-cell transcriptome analysis reveals endometrial immune microenvironment in minimal/mild endometriosis

Abstract Study question This study aimed to systematically understand the endometrial leukocyte types, inflammatory environment, and impaired receptivity at single-cell resolution. Summary answer These results provide new insights into the endometrial immune microenvironment and impaired endometrial receptivity in infertile women with minimal/mild endometriosis. What is known already Endometriosis is a common inflammatory disorder in women of reproductive age due to an abnormal endometrial immune environment and is associated with infertility. Study design, size, duration We profiled single-cell RNA transcriptomes of 138,057 endometrial cells from endometriosis patients (n = 6) and control (n = 7), respectively, using 10x Genomics platform. Participants/materials, setting, methods We profiled single-cell RNA transcriptomes of 138,057 endometrial cells from endometriosis patients (n = 6) and control (n = 7), respectively, using 10x Genomics platform. Main results and the role of chance We found that one cluster of epithelial cells that expressed PAEP and CXCL14 was mostly from the control during the window of implantation (WOI). This epithelial cell type is absent in the eutopic endometrium during the secretory phase. The proportion of endometrial immune cells decreased in the secretory phase in the control group, whereas the cycle variation of total immune cells, NK cells, and T cells was absent in endometriosis. Endometrial immune cells secreted more IL-10 in the secretory phase than in the proliferative phase in the control group; the opposite trend was observed in endometriosis. Proinflammatory cytokines levels in the endometrial immune cells were higher in endometriosis than in the control group. Trajectory analysis revealed that the secretory phase epithelial cells decreased in endometriosis. Ligand–receptor analysis revealed that 11 ligand-receptor pairs were upregulated between endometrial immune and epithelial cells during WOI. Limitations, reasons for caution Our study had some limitations, such as the small sample size and lack of validation experiments. Further studies are needed to demonstrated the conclusions of our bioinformatic analysis, like in situ validation of receptor-ligand pairs analysis. Therefore, more evidence is needed to clearly state the pathogenesis of endometriosis-associated infertility. Wider implications of the findings This database will provide an essential resource for understanding the eutopic endometrial inflammatory environment and defective endometrial receptivity in patients with endometriosis-associated infertility. Trial registration number 82071625

Analysis of the impact of uterine fibroids of different locations and sizes on the perfusion and metabolic characteristics of the endometrium

BACKGROUND:Uterine fibroids are the most common benign tumor of the female reproductive system. A number of factors affect endometrial receptivity in patients with uterine fibroids such as transcription factorsHOXA10andHOXA11, cytokines (growth factors and inflammatory markers), etc. The negative effect of myomatous nodes, which deform the uterine cavity, on endometrial receptivity has been well studied and is beyond doubt, while the influence of intramural and intramural-subserosal fibroids on the endometrium is debatable. An important point is to define clear criteria that justify myomectomy in patients without clinical symptoms of the disease who are planning pregnancy, in particular, with the help of assisted reproductive technology. This article presents the results of studies on the impact of uterine fibroids of different locations on the endometrium. The data were obtained from foreign literature sources and such electronic databases as PubMed, CyberLeninka, and Google Scholar in the period from 2000 to 2022. This survey also reflects the main aspects of federal clinical recommendations and demonstrates the results of our own research.&#x0D; AIM:The aim of this study was to determine the effect of intramural and intramural-submucosal myomatous nodes nodes on the perfusion and metabolic characteristics of the endometrium.&#x0D; MATERIALS AND METHODS:We conducted a comprehensive examination of 20 patients of reproductive age with uterine fibroids who underwent surgical treatment in Gynecological Department One with Operating Unit of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott (Saint Petersburg, Russia) and the Gynecological Department of N.A. Semashko City Hospital No. 38 (Saint Petersburg, Russia). Two groups were formed: group I consisted of 10 patients with multiple uterine fibroids (FIGO types 2 and 3); group II included 10 patients with intramural and intramural-subserosal myomatous nodes (FIGO types 4 to 6). Studies of endometrial perfusion and metabolism were carried out using a fiber optic system that implements fluorescence spectroscopy and laser Doppler flowmetry, including the LAKK-M diagnostic complex (Lazma Ltd., Russia) and a laparoscopic fiber optic probe, followed by registration of optical signals.&#x0D; RESULTS:In the group of patients with uterine fibroids that deform the uterine cavity, we revealed a statistically significant decrease in the microcirculation index in endometrial tissues and an increase in fluorescence signals at a wavelength of 365 nm. This may indicate hypoxic phenomena in endometrial tissues of patients with FIGO types 2 and 3 fibroids. These findings are some of the significant pathogenetic causes of implantation disorders and abnormalities in the physiological course of pregnancy in patients of this study group.&#x0D; CONCLUSIONS:The data obtainedsubstantiate the need to continue research in this direction in order to develop perfusion-metabolic criteria that allow for optimizing the choice of treatment strategies in patients with uterine fibroids.

Downregulation of SEPTIN11 inhibits endometrial epithelial cell adhesive function in patients with elevated peripheral blood natural killer cell counts

Research questionWhat is the underlying mechanism of IVF and embryo transfer (IVF-ET) failure in patients with elevated peripheral blood natural killer cell (pNK) counts? DesignPatients undergoing IVF-ET cycles for tubal obstruction or pelvic adhesion (n = 486) were assigned to three groups: high (CD56+CD16+pNK >30% [n = 49]); medium (15< CD56+CD16+pNK ≤30% [n = 211]); and normal pNK groups (5≤ CD56+CD16+pNK ≤15% [n = 226]). Their general condition, previous pregnancy history and IVF outcomes were compared. Uterine fluid and endometrial tissue from patients in the high and normal pNK groups were collected during the mid-secretory phase and studied to elucidate the molecular mechanism underlying impaired endometrial receptivity. ResultsThe highest incidence of IVF-ET cycles (P < 0.0001) and biochemical pregnancy losses (P < 0.0001), and lowest implantation and clinical pregnancy rates (both P < 0.0001), were observed in patients with pNK over 30%. No significant difference was found in the number of previous miscarriages and rate of spontaneous miscarriage in IVF outcomes. Lower Septin11 (SEPT11) expression in the uterine fluid and endometrial epithelial cells (EEC), and higher endometrial IFN-γ, was observed in patients with high pNK. Ishikawa cell and human endometrial epithelial cell (HEEC) adhesion was inhibited after SEPT11 knock-down. Elevated IFN-γ decreased the SEPT11 protein levels in Ishikawa cells and HEECs. ConclusionsCD56+CD16+pNK above 30% may be a threshold for adverse IVF-ET outcomes. Low SEPT11 expression in EEC inhibits cell adhesion, which may cause impaired endometrial receptivity in patients with elevated pNK. The level of SEPT11 in mid-secretory uterine fluid could serve as a non-invasive marker to assess endometrial receptivity in these patients.

Comparison between the effect of different medical drugs used to improve endometrial receptivity in patients with thin poorly vascularized endometrium

Background: Pregnancy has been one of life’s great mysteries. The endometrium is where life begins, and a receptive endometrium lies at the crossroads of menstruation and pregnancy. Aim of the study: To evaluate the effects of different medical drugs used routinely to improve endometrial thickness, vascularity, and pregnancy rates and to find out the best medical protocol could be used to improve endometrial thickness, vasculature, and pregnancy rate for patient with thin and poorly vascularized endometrium regardless the cause. Materials and methods: The study was carried out on 200 infertile women who have thin , poorly vascularized endometrium, after they matched the inclusion and exclusion criteria , those patients were divided randomly into five groups ; 40 patient in each group, group A received esterofem oral 2mg tablet every 12 hours from day 2 of menstrual cycle till the day of ovulation trigger , group B received vagifem vaginal tablets 25 microgram from the fourth day of menstrual cycle for 15 days or till the day of ovulation trigger, group C received sildenafil citrate gel 3 gm which containing 37.5 mg sildenafil every 12 hours from the 2nd day of menstruation till the day of ovulation trigger.

MLL1:EZH2 Ratio in Uterine Secretions and Endometrial Receptivity in Patients with Endometriosis.

To establish a novel approach for diagnosing endometriosis (EM) in patients with impaired endometrial receptivity. Mixed lineage leukemia 1 (MLL1) and enhancer of zeste homolog 2 (EZH2) levels were analyzed. The MLL1:EZH2 ratio in identifying impaired endometrial receptivity has been established and validated. In normal endometrial tissue, the MLL1:EZH2 ratio increased significantly in the midsecretory phase, compared with that in the proliferative phase. In the midsecretory phase, the MLL1:EZH2 ratio in endometrial tissues and uterine secretions accurately identifies patients with EM who have impaired endometrial receptivity. In the validation group, the sensitivity and specificity of the MLL1:EZH2 ratio in the uterine secretions of the midsecretory phase, in diagnosing patients EM who have impaired endometrial receptivity, were 100% and 96.55%, respectively. The MLL1:EZH2 ratio in uterine secretions of the midsecretory phase may serve as a marker to diagnose EM in patients with impaired endometrial receptivity.

Intracavitary physiotherapy combined with acupuncture mediated AMPK/mTOR signalling to improve endometrial receptivity in patients with thin endometrium

ObjectiveTo explore the mechanism of intracavitary physiotherapy combined with acupuncture to improve the receptivity of thin endometrium. MethodsFrom October 2020 to April 2021, 40 patients diagnosed with thin endometrium and preparing for hormone replacement cycle freeze–thaw embryo transfer in our centre for Reproduction were included, 40 patients were randomized to treatment group and control group. 20 patients with normal endometrium during the same period were selected as the normal group.All patients underwent freeze–thaw embryo transfer using hormone replacement cycles.The treatment group added endovascular physiotherapy combined with acupuncture. ResultsThe endometrial receptivity of the patients with thin endometrium was significantly lower than that of the normal group(P < 0.01). Endovascular therapy combined with acupuncture can significantly increase endometrial thickness in patients with thin endometrium and the proportion of patients with type A endometrium, reduce bilateral Uterine arterial pulsatilityindex (PI), Uterine arterial resistance index (RI), and peaksystolicvelocity/diastolicvelocity (S/D), upregulate the expression of HOXA10 protein and mRNA in endometrium tissue, and improve the rate of embryo implantation and clinical pregnancy(P < 0.01).there was no significant difference between the treatment group and the normal group (P > 0.05). This may be related to the regulation of the AMPK/mTOR signalling pathway by intracavitary physiotherapy combined with acupuncture, downregulation of the expression of the AMPK gene and protein and upregulation of the expression of the mTOR gene and protein. Conclusions1. Abnormal energy metabolism is present in the endometrium of patients with thin endometrium, which affects the autophagy process and leads to a decrease in the receptivity of thin endometrium. 2. Intracavitary physiotherapy combined with acupuncture mediated the AMPK/mTOR pathway to improve energy metabolism, promote the autophagy process, improve endometrial morphology and ultrasonic indicators of patients, upregulate the expression of endometrial receptivity-related HOXA10 genes and proteins, and improve the embryo implantation rate and clinical pregnancy rate.

Proteomic alteration of endometrial tissues during secretion in polycystic ovary syndrome may affect endometrial receptivity

Embryo implantation is a complex developmental process that requires coordinated interactions among the embryo, endometrium, and the microenvironment of endometrium factors. Even though the impaired endometrial receptivity of patients with polycystic ovary syndrome (PCOS) is known, understanding of endometrial receptivity is limited. A proteomics study in three patients with PCOS and 3 fertile women was performed to understand the impaired endometrial receptivity in patients with PCOS during luteal phases. Through isobaric tags for relative and absolute quantitation (iTRAQ) analyses, we identified 232 unique proteins involved in the metabolism, inflammation, and cell adhesion molecules. Finally, our results suggested that energy metabolism can affect embryo implantation, whereas inflammation and cell adhesion molecules can affect both endometrial conversion and receptivity. Our results showed that endometrial receptive damage in patients with PCOS is not a single factor. It is caused by many proteins, pathways, systems, and abnormalities, which interact with each other and make endometrial receptive research more difficult.

Increased expression of HMGB1 in the implantation phase endometrium is related to recurrent implantation failure.

Impaired endometrial receptivity was the main cause of recurrent implantation failure (RIF); however, its underlying mechanisms had not been elucidated. This study aimed to determine the expression level of high-mobility group box protein 1 (HMGB1) in the endometrium with RIF and its effect on endometrial receptivity. Genome-wide expression profiling, real-time reverse transcription PCR, immunohistochemical staining, western blot, and in vitro assays were performed in this study. We found that HMGB1 expression was significantly decreased in the implantation phase endometrium in the control group (patients with tubal infertility and successfully achieve conception after the first embryo transfer) (P = 0.006). However, the expression levels of HMGB1 mRNA and protein were significantly upregulated during the implantation phase in endometrial tissues obtained from patients with RIF compared to that in the control group (P = 0.001), consistent with the results of the genome-wide expression profiling. Moreover, in vitro assays showed that increased expression of HMGB1 in human endometrial epithelial cells dramatically displayed a marked deficiency in supporting blastocysts and human embryonic JAR cells adhesion, which mimic the process of embryo adhesion. These findings strongly indicated that increased HMGB1 levels suppressed the epithelial cell adhesion capability, therefore contributing to impaired endometrial receptivity in patients with recurrent implantation failure, which can be used as a target for the recognition and treatment of recurrent implantation failure in clinical practice.

Impact of metabolic disorders on endometrial receptivity in patients with polycystic ovary syndrome.

The present study investigated the expression of endometrial receptivity-related molecules in patients with polycystic ovary syndrome (PCOS) and different androgen status, insulin resistance (IR) levels, and body mass indexes (BMI) to identify the mechanism underlying their effects on pregnancy outcomes. The present study recruited 43 participants from November 2020 to January 2021, which were classified into five groups: i) Hyperandrogenemia (HA) combined with impaired glucose tolerance group (n=8); ii) HA combined with diabetes mellitus group (n=8); iii) HA combined with non-IR (NIR) group (n=10); iv) non-HA (NHA) androgen combined with IR group (n=8); and v) NHA combined with NIR group (n=9). In addition, according to their BMIs, patients were sub-grouped into lean/normal (n=27), overweight (n=8) or obese (n=8) groups. The mRNA expression levels of endometrial receptivity-related molecules were detected using reverse transcription-quantitative PCR. In addition, flow cytometry was used to determine the phenotype and percentage of uterine natural killer cells (uNK). According to the results, patients with PCOS and IR status, HA and obesity (BMI ≥24 kg/m2) demonstrated significantly decreased mRNA expression levels of adiponectin, adiponectin receptor (AdipoR)1, AdipoR2, adapter protein containing PH domain, PTB domain and leucine zipper motif 1, estrogen receptor (ER) α, ERβ, progesterone receptor (PR), IL-15, integrin β3 avβ3, and insulin-like growth factor binding protein-1, but increased mRNA expression levels of IL-6 and IL-8 compared with NHA + NIR group or lean/normal group, respectively. In addition, obese patients with PCOS demonstrated increased mRNA expression levels of PR compared with overweight patients. This suggested that insulin resistant status, HA, and obesity could alter the endometrial receptivity of patients with PCOS, which may explain poorer embryo implantation and pregnancy outcomes in clinics.

Double daily doses of cetrorelix may raise follicular phase progesterone more compared to single doses in poor ovarian response patients

PurposeThere is evidence that follicular phase progesterone rise [FPPR] adversely affects fresh in vitro fertilization [IVF] cycles. A single daily dose of cetrorelix has been used to prevent early luteinizing Hormone (LH) surge. We speculated that doubling the daily dose might have a positive effect in patients who have early LH surges despite receiving the single daily dose treatment. However, a double daily dose of cetrorelix seems to cause FPPR in poor ovarian response (POR) patients. Materials and MethodsOn human chorionic gonadotropin [hCG] injection days, the progesterone levels of POR patients who received a single daily dose of cetrorelix (group 1, n = 59) were compared with progesterone levels of the patients who received a double daily dose of cetrorelix (group 2, n = 75). The two groups had statistically similar demographic data. The patients who had FPPR were detected, and a comparison of progesterone levels, using 0.8, 1.0, and 1.2 [ng/mL] of progesterone as cut-off levels, was made between patients of both groups. ResultsFPPR patients in group 2 had significantly higher progesterone levels during hCG day, contrary to expectations. When progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 1 patients, 15.3%, 13.6%, and 6.8% of the patients developed FPPR, respectively When the progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 2, the results detected were 45.3%, 30.7%, and 21.3%, respectively. A significant statistical difference in progesterone levels was observed between the groups. ConclusionWhile the double daily dose of cetrorelix was initially thought to more effectively suppress early LH rise by some authors, we have seen that it increases the FPPR more when compared to a single daily dose regime. We suggest using frozen cycles instead of fresh cycles in order to have better endometrial receptivity in patients who seem to benefit from higher daily doses of cetrorelix.

Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window

BackgroundPoor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window.MethodsEndometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway.ResultsThe presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r2 = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF.ConclusionsMiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure.

Effect of electroacupuncture combined with ginger-isolated moxibustion on endometrial receptivity in infertile patients with polycystic ovarian syndrome: 电针联合隔姜灸对多囊卵巢综合征不孕患者子宫内膜容受性的影响

ObjectiveTo observe the effect of the combined therapy of electroacupuncture (EA) and ginger-isolated moxibustion on endometrial receptivity in the patients with polycystic ovarian syndrome (PCOS). MethodsA total of 70 subjects of PCOS were randomized into two groups, 35 cases in each one. In the western medication group, letrozole and human chorionic gonadotropin (HCG) were administered. In the combined therapy group, on the base of the treatment as the western medication group, the artificial cycle therapy with EA and ginger-isolated moxibustion was provided. The treatment duration was 3 menstrual cycles in two groups. After treated for 3 menstrual cycles, the symptom score of traditional Chinese medicine (TCM), endometrial thickness, the number of ovulation cycle, endometrial morphology, bilateral uterine artery pulsatility index (PI), resistance index (RI), the sum of peak systolic velocity/end diastolic velocity (S/D) and pregnancy were compared in the patients between two groups. Results(1) After treatment, the endometrial thickness was better (0.21 ± ± 0.13 vs 0.14 ± 0.08, P < 0.01), TCM symptom score reducing range was larger (5.00 ± 2.24 vs 0.52 ± 1.66, P < 0.01), the reducing degrees of bilateral uterine artery PI, RI and S/D sum were better (0.62 ± 0.26 vs 0.04 ± 0.15, 0.08 ± 0.05 vs 0.01 ± 0.05, 0.61 ± 0.33 vs 0.07 ± 0.17, 0.11 ± 0.05 vs 0.01 ± 0.05, 4.80 ± 1.14 vs 0.15 ± 0.89, all P < 0.01) in the combined therapy group respectively as compared with the western medication group. After treatment, the number of ovulation cycle and the proportion of A + B type of endometrial morphological were higher in the combined therapy group (2.09 ± 0.78 vs 1.27 ± 0.84, 87.5% vs 60.61%, P < 0.01, P < 0.05) as compared with the western medication group respectively. (2) The clinical pregnancy rate was 56.25% in the combined therapy group, better than 30.30% in the western medication group (P < 0.05). The early abortion rate was 10.53% in the combined therapy group, lower than 50.00% in the western medication group (P < 0.05). ConclusionThe combined treatment of electroacupuncture and ginger-isolated moxibustion with western medication effectively improves endometrial receptivity, increases clinical pregnancy rate and reduces early abortion rate in the patients with PCOS.

Low‐dose aspirin treatment improves endometrial receptivity in the midluteal phase in unexplained recurrent implantation failure

AbstractObjectiveTo compare endometrial receptivity in patients with and without unexplained recurrent implantation failure (URIF) and the benefits of low‐dose aspirin treatment in women with URIF.MethodsA retrospective study was conducted at Ren Ji Hospital, Shanghai, from January 2014 to January 2017. Endometrial thickness, pulsatility index (PI), resistive index (RI), and systolic‐to‐diastolic ratio (S/D) values of endometrial and uterine perfusion were recorded and compared between women with and without URIF. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive accuracy of the risk of URIF. Ultrasonography examination was repeated after 2 months of treatment with low‐dose aspirin.ResultsPI, RI, and S/D values for endometrial blood flow were significantly higher in URIF patients than the control group (P &lt; 0.001). The predictive indexes were 0.833, 0.857, and 0.839, respectively. Differences between the groups for endometrial thickness and impedance of uterine perfusion were not significant (P &gt; 0.05). After low‐dose aspirin treatment, endometrial and uterine arterial blood flow resistance in URIF patients was significantly lower than before treatment (P &lt; 0.05).ConclusionURIF patients had inappropriate endometrial blood flow. Doppler parameters are promising for predicting women at high risk of URIF. Low‐dose aspirin treatment can improve endometrial receptivity.

Овариальный резерв и имплантационные свойства эндометрия у пациенток после органосберегающих операций по поводу эндометриоидных образований яичников

Objective. To analyze the significance of the ovarian reserve (OR) in the assessment of endometrial receptivity in patients after cystectomy for ovarian endometriotic cysts (OECs). Patients and methods. We examined 172 patients after organ-sparing surgeries for OECs. The mean patient age was 28.7 ± 4.8 years. Group I included 114 women with low OR. Group II comprised 58 patients with unchanged OR. All study participants underwent pelvic ultrasonography in the middle luteal phase 6 and 12 months postoperatively. We evaluated endometrial thickness and its echostructure, as well as Doppler-angle-independent flow indices, including resistance index, pulsatility index, and systolic/diastolic ratio. Reduced OR was diagnosed according to the ESHRE recommendations (2011 Anti-Müllerian hormone ≤ 0.5–1.1 ng/mL and ≤5–7 antral follicles in one ultrasound section. Results. Impairments in the morphological and functional state of the ovaries were associated with changes of the endometrial thickness, its ultrasonic structure, and hemodynamic parameters in the terminal branches of the uterine arteries (hypovascularization, increased flow indices). Simultaneous use of various methods for the assessment of ovarian tissue and endometrium allowed the detection of a decreased reproductive potential. Patients with a reduced OR after surgeries for OECs demonstrated improvement of both morphological/functional characteristics of ovarian tissue and endometrial receptivity, which allows pregnancy planning. Patients with extremely thin endometrium (3.0–5.0 mm) that does not improve are recommended to resort to assisted reproductive technologies. Key words: ovarian reserve, endometrium, ovarian endometriotic cysts