protocolSection identificationModule nctId: NCT06280560, orgStudyIdInfo id: 2109-FIVI-087-FD, secondaryIdInfos id: PI23/00860, type: OTHER_GRANT, domain: Instituto de Salud Carlos III, co-funded by European Union, briefTitle: Impact of IVF Hormonal Therapy on Endometrial Receptivity and Endometrial Senescent Cell Pathological Accumulation, acronym: HormoSenoRec, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-02-01, primaryCompletionDateStruct date: 2024-06-30, completionDateStruct date: 2024-06-30, studyFirstPostDateStruct date: 2024-02-28, lastUpdatePostDateStruct date: 2024-02-28, sponsorCollaboratorsModule leadSponsor name: Fundación IVI, class: OTHER, collaborators name: Instituto Valenciano de Infertilidad, IVI VALENCIA, descriptionModule briefSummary: Both controlled ovarian stimulation (COS) and frozen embryo transfer has become an integral part of in vitro fertilization (IVF) treatment. Fresh embryo transfer is usually performed by providing Luteal Phase Support (LPS) with progesterone after COS. Frozen embryo transfer (FET) is usually performed in artificial cycles with hormone replacement treatment (HRT), in which exogenous progesterone is administered, although it can also be performed in a Natural Cycle (without hormone supplementation) (NC). There is evidence that the supraphysiologic levels of estradiol and progesterone during COS+LPS and HRT could lead to morphologic and biochemical endometrial modifications, altering endometrial receptivity and lowering implantation and pregnancy rates.We hypothesize that the supraphysiologic hormone levels required for both COS+LPS, and HRT may be inducing alterations in endometrial composition and function, specifically the chronic accumulation of senescent cells; either due to an excessive hormonal induction, a lack of clearance due to a deficit of uNKs, or a combination of both, ultimately affecting both endometrial receptivity and decidualization, worsening IVF outcomes.The in vitro clearance of endometrial senescent cells by selective induction of apoptosis has been found to enhance the decidualization capacity of the rest of Endometrial Stromal Cells (EnSC), which could represent in a future adjuvant strategy to reduce the potentially deleterious effects of supraphysiologic hormone levels and improve reproductive outcomes in IVF patients.The results derived from this project would have a direct impact on clinical practice. First, the results would allow us to evaluate, based on experimental data, potential endometrial side effects of stimulation protocols commonly used in IVF treatments. In addition, in the case of finding a pathological accumulation of senescent cells affecting endometrial receptivity, we will be able to in vitro evaluate the effectiveness of adjuvant senolytic (drugs designed to specifically remove senescent cells) compounds to in vitro improve the expression of endometrial receptivity markers, as a first step to demonstrate the effectiveness of their use in improving the reproductive outcomes of IVF patients., conditionsModule conditions: Endometrial Receptivity, designModule studyType: OBSERVATIONAL, designInfo observationalModel: CASE_CONTROL, timePerspective: PROSPECTIVE, enrollmentInfo count: 60, type: ESTIMATED, armsInterventionsModule interventions name: Controlled Ovarian Stimulation + Luteal Phase Support, interventions name: Hormonal Replacement Therapy programmed artificial cycle, interventions name: Natural Cycle (NC), interventions name: Endometrial receptivity reference group, outcomesModule primaryOutcomes measure: Endometrial receptivity, secondaryOutcomes measure: Senescent Cell Pathological Accumulation, eligibilityModule sex: FEMALE, minimumAge: 18 Years, maximumAge: 45 Years, stdAges: ADULT, contactsLocationsModule locations facility: IVI-RMA Valencia Clinic, status: RECRUITING, city: Valencia, zip: 46015, country: Spain, contacts name: Laura Caracena, PhD, role: CONTACT, phone: 651791000, email: Laura.Caracena@ivirma.com, geoPoint lat: 39.46975, lon: -0.37739, hasResults: False