P–392 Clinical outcomes of endometrium receptivity analysis(ERA) testing in patients with repeated IVF failures

Study question Is ERA testing different between RIF patients with control group? Summary answer In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. What is known already: The endometrium receptivity analysis testing might have the ability to detect the implantation window. In repeat implantation failure patients, detecting of precisely implantation window may have some benefits. Study design, size, duration This was a single-center retrospective observational study. Two hundred and forty-nine patients who underwent ERA testing following frozen-thawed embryo transfer in our center were including in this study between January 2019 and May 2020. Participants/materials, setting, methods 181 patients having unexplained repeated IVF failure (RIF group, at least tow implantation failure) and 68 patients having no experience with embryo transfer (Control group) who underwent ERA testing were including in this study. Both of Patients having a receptive (R) ERA and having a non-receptive (NR) ERA underwent a personalized embryo transfer (pET) on ERA. ERA results and clinical outcomes compared between RIF group and control group were analyzed by Chi-square test. Main results and the role of chance The proportion of R/NR results were 33:35 for the RIF group and 118:63 for the Control group, demonstrating the displacement of the window of implantation in patients with RIF. Our results revealed an endometrial factor in 51% RIF patients, which was significantly greater than the Control group 34.8% (P = 0.02). Among the patients with NR ERA result, there are not significantly difference in clinical pregnancy rate in the RIF group compared with control group (57.1%. vs. 61.9%). The clinical pregnancy rate of the patients with receptive ERA result also is comparable in both group (70.3% vs. 66.7%). Limitations, reasons for caution This is a retrospective, single center study with limited case number. There were may some bias with ERA testing errors. Wider implications of the findings: In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. Larger randomized studies are required to validate these results. Trial registration number 18MMHISO70e

P–297 Endometrium receptivity test in patients with failed embryo implantation

Study question Studying the receptivity of the endometrium for improving the synchronicity between the embryo and the condition of the endometrium. Summary answer Determination of the level of endometrial receptivity with PGT may significantly increase the effectiveness of IVF in patients with recurrent implantation failure What is known already Modern approach to the treatment of patients with recurrent implantation failure, using assisted reproductive technologies imply preimplantation genetic testing (PGT) of embryos for chromosomal abnormalities. However, in some cases, even with the transfer of a genetically complete embryo, pregnancy does not occur. A possible reason is a violation of embryo implantation due to a shift in the period of the “implantation window” . The ERA (Endometrium Receptivity Assay) is a personalized molecular genetic test specifically designed to analyze the level of endometrium receptivity for determine the period of the “implantation window”. Study design, size, duration ERA test is carried out for patients with idiopathic infertility, in cases where repeated transfer of a genetically complete embryo does not lead to implantation and pregnancy: at least three attempts in the case of women under 37 years old and two attempts - for older women (without pathological morphological changes in the endometrium). The test was performed in a cycle with hormone replacement therapy (HRT) or a natural cycle. Participants/materials, setting, methods Were investigated the endometrial Pipell biopsy specimen in a cycle of hormone replacement therapy (HRT) or a natural cycle. Endometrial examination was implemented using the Endometrium Receptivity Assay, the analysis of mRNA of 238 genes was carried out, which showed a difference in the level of expression when analyzing samples of prereceptive, receptive and postreceptive endometrium. Main results and the role of chance The results of the studies of the level of endometrial receptivity revealed a shift in the period of the “implantation window” in 28% of patients. The results obtained make it possible to carry out the transfer of embryos in an individual order for each patient, taking into account the data on the level of receptivity of the endometrium, which makes it possible to implement the so-called Personalized Embryo Transfer (pET) principle. In 72% of cases, the study showed the “receptive” status of the endometrium. The result means that the period of the “implantation window” for a particular type of cycle falls on the moment of biopsy and this period of time is the most favorable for implantation of the embryo. For patients from this group, embryo transfer is carried out at the next repetition of the cycle option selected for the study of receptivity, while the blastocyst transfer occurs on the same day of the cycle when the endometrial biopsy was performed. Limitations, reasons for caution The ERA test is unique technique. Wider implications of the findings: Using the ERA test allow to determine the state of maturity of the endometrium. Unlike other methods for receptivity of the endometrium, the ERA test allows not only to accurately determine the period of the “implantation window”, but also to reliably predict its displacement to an earlier or later time. Trial registration number Not applicable

Endometrium receptivity and the dose-related effects of Acupuncture therapies in infertile women: a protocol for systematic review and meta analysis

Introduction:The aim of the systematic review (SR) is to evaluate the efficacy of Acupuncture in endometrium receptivity(ER) of infertile women and find out dose-related between Acupuncture and clinical pregnancy rate. Methods and analysis: We will search four English databases: PubMed, Embase, Cochrane Library, Web of Science, and five Chinese databases: SinoMed (formerly Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), Wanfang Data, and China Biomedical Literature Database (CBM), China Science Journal Database (VIP database) from inception to February 2021 in English and Chinese. Also, we will manually retrieve other resources, including reference lists of identified publications, conference articles, and grey literature. All clinical randomized controlled trials related to Acupuncture for endometrium receptivity of infertile women will be included. Two review authors will perform all research selection, data extraction, and research quality assessment. According to suggestions, data will be synthesized in a fixed-effect model, or random effect model due to the heterogeneity test. The primary outcomes include ER (endometrial thickness and endometrial hemodynamic parameters) and clinical pregnancy rate(CPR). Secondary outcomes include a dose of the interventions( the starting time of Acupuncture, the duration, and frequency of Acupuncture sessions), and adverse events will be assessed. We will use the statistical package (RevMan5.4.0) provided by The Cochrane Collaboration to analyze data. The quality of evidence will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Ethics and dissemination: Since this article does not contain patient personal information, ethical approval is not required. The contract is distributed by a peer-review Systematic review registration: PROSPERO, CRD42020206790

Uterine fluid transcriptome as potential non-invasive biomarker for predicting endometrial receptivity

BackgroundThe synchrony between the embryo and the receptive endometrium is essential for successful implantation. Therefore, a reliable non-invasive ER prediction method is highly demanded. We aimed to establish a method that could be used to predict endometrium receptivity non-invasively and to evaluate its clinical application potential in patients undergoing IVF.MethodsThe non-invasive RNA-seq based endometrial receptivity test (nirsERT) was established by sequencing and analyzing the RNA of uterine fluid from 48 IVF patients with normal ER. Subsequently, 22 IVF patients were recruited and analyzed the correlation between the predicted results of nirsERT and pregnancy outcomes.Results87 marker genes and 3 hub genes were selected to establish the nirsERT. 10-fold cross-validation resulted in a mean accuracy of 93.0%. A small cohort retrospective observation showed that 77.8% (14/18) of IVF patients predicted with normal WOI had successful intrauterine pregnancies, while none of the 3 patients with displaced WOI had successful pregnancy.ConclusionsnirsERT is potential for a non-invasive, accurate and same cycle testing for ER in reproductive clinic.FundingFunded by the National Natural Science Foundation of China (grant no. 8187061497) and the National Key Research and Developmental Program of China (grant no. 2018YFC1004800).Clinical trial numberChiCTR-DDD-17013375.

Pathogenesis of Implantation Incompetence of Endometrium in Endometriosis-Associated Infertility

Study Objective: To expand the idea of the pathogenesis of implantation incompetence of endometrium in women with endometriosis-associated infertility. Study Design: open perspective comparative study. Materials and Methods. The study enrolled 78 women. The study group included 32 patients with endometriosis genitalis externa (EGE) and infertility; the comparison group included 33 patients with EGE who used their reproductive function not more than 3 years before the study and who were not diagnosed with infertility; the group of morphological control made 13 fertile women without EGE. The subject of the study was endometrium biopsy material obtained on day 5–7 of menstruation, following the peak blood concentration of luteinizing hormone during the expected implantation window. Study Results. When patients with endometriosis-associated infertility were compared to fertile women with EGE, we noted increased expression of GATA2 — 1.6-fold, GATA6 — 1.7-fold, SF-1 — 1.5-fold and reduced HOXA10 expression by 2.9 times (p < 0.05 in all cases) in stroma of infertile women. When patients with endometriosis-associated infertility were compared to fertile women without EGE, we recorded statistically significant (р < 0.05) increase in expression of GATA2 in stroma (2.5-fold) and glands (2.2-fold), GATA6 and SF-1 in stroma (2-fold in both cases), and reduced HOXA10 expression both in stroma (3.6-fold) and glands (2.8-fold). Conclusion. Pathogenesis of implantation incompetence of endometrium in endometriosis-associated infertility is caused by impaired endometrium receptivity because of aberrant expression of transcription factor affecting local hormonal balance. Keywords: endometriosis-associated infertility, implantation incompetence of endometrium

Impaired Expression of Estrogen and Progesteron Receptors During the Implantation Window in Eutopic Endometrium of Infertile Women Associated with Endometriosis Genitalis Externa

Study Objective: To study impaired expression of estrogen (ER) and progesteron (PR) receptor isoforms during the implantation window in eutopic endometrium of infertile women associated with endometriosis genitalis externa (EGE). Study Design: open perspective comparative study. Materials and Methods. The study included 32 patients with endometriosis-associated infertility and implantation failures within the scope of assisted reproductive technology programme (study group), and 33 fertile women with EGE rAFS (stages I to IV) (comparison group). We performed morphological and immunohistochemical examination of endometrium biopsy samples (pipelle biopsy) during an expected implantation window. Study Results. Eutopic endometrium of women with EGE and infertility during the implantation window demonstrated statistically higher (р < 0.05) expression of ERα (19-fold), ERβ (2.3-fold) in stroma and PR-B in glands (1.7-folds) as compared to fertile women win EGE with lower PR-A expression in stroma (2.5-fold). Conclusion. The morphofunctional condition of endometrium and its receptive properties during the implantation window in women with endometriosis-associated infertility reflect the nature of ER (α and β) and PR (А and В) isoforms expression, the abnormalities underlying the endometrium receptivity disorders, with clinical manifestations being absent pregnancy. Keywords: endometriosis-associated infertility; implantation window; endometrium receptivity

Obstetric Complications and Pregnancy Outcomes in Patients with Endometriosis

Objective of the Review: To study the impact of endometriosis on the course and outcomes of pregnancy; to propose methods for prevention of obstetrics complications in pregnant women with endometriosis. Key Points. Pregnant women with endometriosis are at a high risk of miscarriage, preterm delivery, preeclampsia, placental disorders, intranatal and postnatal bleeding, still birth, high rates of caesarean section; and at a risk of acute complications from endometriosis, e.g., spontaneous hemoperitoneum. Endometriosis is associated with progesterone resistivity, impaired endometrium receptivity; therefore, prescription of progesterone to pregnant women with endometriosis can be a key to prevention of not only miscarriages and preterm delivery, but also of preeclampsia and placental disorders. Folic acid has favourable effect for placenta formation. Low doses (75–150 mg/day) of acetylsalicylic acid prevent placentation disorders. Conclusion. In order to prevent impaired implantation, placentation, cytotrophoblastic invasion, and uteroplacental perfusion with a high risk of obstetric complications, pregnant women with endometriosis should take progesterone, folic and acetylsalicylic acids. Keywords: endometriosis, obstetric complications, pregnancy follow-up

Application of autologous endometrial mesenchymal stromal/stem cells increases thin endometrium receptivity: a case report

Background Pregnancy in cycles with the use of assisted reproductive technologies is possible only with the availability of good-quality embryos and a healthy receptive endometrium. The problem of lack of sensitivity of the endometrium is related to the syndrome of thin endometrium, which is caused by a number of factors. However, there is no single protocol for the treatment of this syndrome, the return/improvement of normal functionality of endometrial tissue, and obtaining the desired pregnancy. Case presentation We report a case of a 38-year-old Ukrainian woman with a number of unsuccessful tries at pregnancy in cycles with the use of assisted reproductive technologies. We describe a clinical case of the use of mesenchymal stem cells of the human endometrium for a woman with thin endometrial syndrome to increase its receptivity for pregnancy. The basic steps of patient management, protocol of sampling material for obtaining a cell product based on endometrial stem cells, their basic morphofunctional characteristics, and post-treatment procedures to obtain the desired pregnancy are described. Conclusion Application of autologous endometrial mesenchymal stem cells increases endometrial receptivity and the chance for pregnancy with use of assisted reproductive technologies.