[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658371":3},{"organization":4,"outcomesModule":7,"designInfo":21,"detailedDescription":24,"studyPopulation":25,"armGroups":26,"interventions":20,"overallOfficials":33,"centralContacts":41,"locations":49,"responsibleParty":61,"collaborators":63,"id":71,"slug":72,"hasResults":73,"nctId":74,"briefTitle":75,"officialTitle":76,"acronym":20,"eligibilityCriteria":77,"healthyVolunteers":78,"sex":79,"minAge":80,"maxAge":81,"enrollmentInfo":82,"targetDuration":20,"studyType":85,"phases":20,"briefSummary":86,"conditions":87,"keywords":90,"overallStatus":104,"whyStopped":20,"lastUpdateSubmitDate":105,"lastUpdatePostDateStruct":106,"startDateStruct":109,"completionDateStruct":111,"leadSponsor":113,"locationsCount":114},{"fullName":5,"class":6},"King's College London","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":20},[9],{"measure":10,"description":11,"timeFrame":12},"Th17\u002FTreg ratio in the endometrium","Ratio of T helper 17 (Th17) cells to regulatory T (Treg) cells in endometrial tissue, measured by flow cytometry and single-cell RNA sequencing\u002FCITE-seq, compared between participants with recurrent implantation failure (RIF) and fertile controls.","Through study completion, up to 27 months",[14,17],{"measure":15,"description":16,"timeFrame":12},"Reference atlas of endometrial immune cell populations","High-resolution profiling of endometrial-resident immune cell populations, including uterine natural killer cells, macrophages, B cells, and T cells, by single-cell RNA sequencing and CITE-seq, to identify transcriptomic and phenotypic patterns associated with implantation failure.",{"measure":18,"description":19,"timeFrame":12},"Candidate immune targets for future therapeutic research","Identification of immune cell populations, activation states, or clonal T-cell expansions that covary with the Th17\u002FTreg axis and may represent candidate targets for future therapeutic research in recurrent implantation failure.",null,{"allocation":20,"interventionModel":20,"interventionModelDescription":20,"primaryPurpose":20,"observationalModel":22,"timePerspective":23,"maskingInfo":20},"CASE_CONTROL","CROSS_SECTIONAL","Recurrent implantation failure (RIF) is a phenomenon specific to assisted reproductive technology, defined using the ESHRE threshold where the calculated cumulative chance of pregnancy exceeds 60 percent yet pregnancy does not occur without a known cause. True incidence is estimated at around 5 percent. While embryonic factors affecting implantation have been substantially addressed through developments such as preimplantation genetic testing for aneuploidy (PGT-A), there remains a lack of robust research into the uterine environment itself, hampered by inconsistent definitions and investigations without established evidence of benefit.\n\nThe immune system is known to mediate implantation by balancing pro-inflammatory and anti-inflammatory activity, both to permit implantation and to avoid rejection of the embryo. This study characterises the local, tissue-resident immune cell populations of the endometrium, examining not only the number of each immune cell type present but also their phenotype and function, using surface protein expression, transcriptomic profiling, and T cell receptor sequencing to assess activation state, functional subtype, and clonal expansion within each population.\n\nRecruitment: RIF participants are identified at King's Fertility through internal database searches and clinical record review. Control participants who have had a spontaneous pregnancy are identified through review of 36 week gestation scan appointments at the Harris Birthright Centre, King's College Hospital, between 12 and 36 months prior. Eligible individuals are approached by a member of their direct care team by email and invited to a consent appointment, which can take place remotely.\n\nStudy procedure: The mid-luteal phase is identified using twice daily home urinary ovulation prediction tests from day 9 of the menstrual cycle. Participants attend a study visit 7 days after the luteinising hormone (LH) surge, where transvaginal ultrasound and venepuncture are used to confirm a corpus luteum and serum progesterone level consistent with the mid-luteal phase. An endometrial biopsy is then performed at the same visit under transabdominal ultrasound guidance. Where a participant consents to optional future use of samples, an additional blood sample of up to 18ml is collected on the same day, bringing total blood volume to up to 25ml where this option is taken. All procedures take place at King's Fertility, First Floor, The Fetal Medicine Research Institute, 16 to 20 Windsor Walk, Denmark Hill, London SE5 8BB.\n\nSample processing and analysis: Endometrial tissue and blood samples are transported to the King's College London Immunoregulation Laboratory, Guy's Campus, where endometrial biopsies are immediately cryopreserved and blood is processed to isolate cells from plasma before cryopreservation. Conventional flow cytometry and fluorescence activated cell sorting (FACS) are used for cell sorting and characterisation. CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by sequencing) allows simultaneous analysis of transcriptomic and surface protein expression profiles. Single cell RNA sequencing on the 10x Genomics platform, including T cell receptor (TCR) sequencing, is performed to assess immune cell phenotype and clonal expansion. Raw sequencing data are processed using CellRanger and analysed in Seurat (R environment), producing transcriptomic profile, surface protein expression, and TCR repertoire data. Differential expression and clonality analyses compare immune cell phenotypes between the RIF and control groups, integrating gene expression, surface phenotype, and lineage.\n\nTranslational aim: This work is intended to build a high resolution reference atlas of the non-receptive endometrium, allowing stratification of individuals affected by RIF according to underlying immune aetiology, and to identify immune cells or pathways that could inform future immune modulating therapeutic approaches, whether through upregulation or downregulation of a specific immune pathway.","Women under 40 with recurrent implantation failure following IVF, identified through clinical records at King's Fertility (Denmark Hill and Harley Street), and women with a history of spontaneous pregnancy resulting in live birth, identified through 36-week gestation scan records at the Harris Birthright Centre, King's College Hospital. Both groups are drawn from patients already attending these services, approached by their direct care team if they have previously consented to research contact.",[27,30],{"label":28,"type":20,"description":29,"interventionNames":20},"Recurrent implantation failure (RIF)","Women meeting the ESHRE definition of recurrent implantation failure (failure to achieve pregnancy despite an estimated cumulative chance of implantation exceeding 60%), with unexplained infertility, recruited through King's Fertility.",{"label":31,"type":20,"description":32,"interventionNames":20},"Fertile controls","Women with a history of at least one spontaneous pregnancy resulting in live birth, at least 12 months postpartum, with no history of subfertility, recruited through the Harris Birthright Centre, King's College Hospital.",[34,37],{"name":35,"affiliation":5,"role":36},"Panicos Shangaris, MRCOG, PhD","STUDY_CHAIR",{"name":38,"affiliation":39,"role":40},"Ippokratis Sarris, DM, FRCOG","King's Fertility","PRINCIPAL_INVESTIGATOR",[42,47],{"name":43,"role":44,"phone":45,"phoneExt":20,"email":46},"Nicole Ryan, MBBCh, MRCOG","CONTACT","020 3957 7950","nicole.ryan@kingsfertility.co.uk",{"name":35,"role":44,"phone":20,"phoneExt":20,"email":48},"panicos.shangaris@kcl.ac.uk",[50],{"facility":39,"status":20,"city":51,"state":51,"zip":52,"country":53,"countryCode":54,"cosmosGeoPoint":55,"geoPoint":60,"contacts":20},"London","SE5 8BB","United Kingdom","UK",{"type":56,"coordinates":57},"Point",[58,59],-0.12574,51.50853,{"lat":59,"lon":58},{"type":62,"investigatorFullName":20,"investigatorTitle":20,"investigatorAffiliation":20,"oldNameTitle":20,"oldOrganization":20},"SPONSOR",[64,66,68],{"name":65,"class":6},"King's College Hospital NHS Trust",{"name":67,"class":6},"Rosetrees Trust",{"name":69,"class":70},"The Stoneygate Trust","UNKNOWN","100658371","endometrial-immune-profile-in-recurrent-implantation-failure-100658371",false,"NCT07848399","Endometrial Immune Profile in Recurrent Implantation Failure","Immunological Fingerprints of the Non-receptive Endometrium in IVF Failure: Identifying the Barriers to Pregnancy","Inclusion Criteria:\n\nRecurrent Implantation Failure (RIF) Cohort:\n\n* Meets ESHRE threshold for recurrent implantation failure (failure to achieve pregnancy despite an estimated cumulative chance of implantation exceeding 60%)\n* Age under 40\n* Regular menstrual cycles (24 to 38 days)\n* Normal transvaginal ultrasound scan\n* BMI under 30 kg\u002Fm²\n* Otherwise in good general health\n* Unexplained infertility\n\nControl Cohort:\n\n* Age under 40\n* Regular menstrual cycles (24 to 38 days)\n* Normal transvaginal ultrasound scan\n* BMI under 30 kg\u002Fm²\n* Otherwise in good general health\n* History of at least one spontaneous pregnancy resulting in live birth\n* At least 12 months post partum\n\nExclusion Criteria:\n\nRecurrent Implantation Failure (RIF) Cohort:\n\n* Age 40 or above\n* Actively trying to conceive during the study\u002Fbiopsy cycle\n* Significant uterine pathology (e.g. fibroid uterus, abnormal uterine shape, adenomyosis, large Caesarean section defect)\n* Endometriosis\n* Uterine infection within the preceding 3 months\n* Significant systemic illness or infection in the preceding 3 months\n* Use of steroid hormones or other medications known or suspected to affect immune function or endometrial receptivity within the preceding 3 months\n* Current smoker\n* Haematological disorders\n* Inability to detect ovulation using at-home ovulation prediction tests\n* Participation in another interventional research study within the preceding 3 months\n* Inability to provide informed consent\n* Insufficient understanding of English to provide informed consent\n\nControl Cohort (in addition to all RIF cohort exclusions above):\n\n* History of infertility or subfertility\n* Current pregnancy\n* Current breastfeeding",true,"FEMALE","18 Years","40 Years",{"count":83,"type":84},64,"ESTIMATED","OBSERVATIONAL","The goal of this observational study is to learn whether differences in the immune cells of the womb lining (endometrium) help explain why some women do not become pregnant despite several IVF attempts using good-quality embryos, a condition known as recurrent implantation failure (RIF). The study compares women with RIF to women who have had a natural, healthy pregnancy. The main question it aims to answer is:\n\nDo immune cells in the endometrium, including uterine natural killer cells, macrophages, B cells, and T cells, differ in number or function between women with RIF and fertile controls?\n\nResearchers will compare endometrial tissue and blood samples from the RIF group to samples from the fertile control group to see whether specific immune cell patterns are linked to implantation failure, and whether these differences could point to future treatment targets.\n\nParticipants will:\n\n* Attend a consent appointment to discuss the study\n* Have a transvaginal ultrasound scan, if one has not already been done in the past 6 months\n* Confirm the timing of their cycle using a home ovulation test, an ultrasound scan, and a blood test\n* Have an endometrial tissue sample and a blood sample taken at the point in their cycle when the womb lining would normally be ready to accept an embryo",[88,89],"Recurrent Implantation Failure","Infertility (IVF Patients)",[91,92,93,94,95,96,97,98,99,100,101,102,103],"recurrent implantation failure","infertility","assisted reproductive technologies","immunology","immune profile","endometrial environment","endometrial biopsy","flow cytometry","CITE-sequencing","transcriptomic profiles","surface protein expression","T cell receptor","IVF failure","NOT_YET_RECRUITING","2026-09-28",{"date":107,"type":108},"2026-09-30","ACTUAL",{"date":110,"type":84},"2026-10",{"date":112,"type":84},"2028-12",{"name":5,"class":6},1]