{"paper_id":"ffb199c2-0ec9-48bb-a859-fa65f59ce9fc","body_text":"Review began\n 06/30/2026 \nReview ended\n 07/08/2026 \nPublished\n 07/24/2026\n© Copyright \n2026\nSarli et al. This is an open access article\ndistributed under the terms of the Creative\nCommons Attribution License CC-BY 4.0.,\nwhich permits unrestricted use, distribution,\nand reproduction in any medium, provided\nthe original author and source are credited.\nDOI:\n 10.7759/cureus.113299\nEndometriosis-Associated Implantation Failure:\nPathophysiology, Biomarkers, and Emerging\nTherapeutic Strategies\nVaia Sarli \n, \nCharikleia Papageorgiou \n, \nChrysi Christodoulaki \n, \nPeriklis Panagopoulos \n,\nNikolaos Machairiotis \n1.\n Third Department of Obstetrics and Gynecology, Attikon University General Hospital, Athens, GRC \n2.\n Department of\nObstetrics and Gynecology, General Hospital of Chania, Chania, GRC \n3.\n Third Department of Obstetrics and\nGynecology, National and Kapodistrian University of Athens Medical School, Attikon University General Hospital,\nAthens, GRC\nCorresponding author: \nVaia Sarli, \nvanasarli@yahoo.gr\nAbstract\nImplantation failure remains a major challenge in assisted reproductive technology (ART) and is a\nsignificant contributor to infertility in women with endometriosis. Beyond mechanical distortion and\novarian dysfunction, increasing evidence suggests that endometriosis profoundly alters endometrial\nreceptivity through complex inflammatory, immunological, and molecular mechanisms. Chronic\ninflammation, progesterone resistance, dysregulated immune cell populations, and aberrant cytokine\nsignaling converge to create a hostile endometrial microenvironment that compromises embryo-\nendometrial crosstalk and implantation success.\nThis narrative review provides a comprehensive overview of the pathophysiological pathways linking\nendometriosis to implantation failure, with particular emphasis on immune dysregulation and defects in\nendometrial receptivity. We summarize the current evidence regarding key immune cell populations,\nincluding uterine natural killer (uNK) cells and macrophages, and their role in modulating implantation. We\nfurther discuss established and emerging biomarkers of impaired receptivity, including BCL6, integrins,\nendometrial receptivity assays, and epigenetic markers, highlighting their diagnostic potential and current\nlimitations.\nFinally, we review contemporary and emerging therapeutic strategies aimed at restoring endometrial\nreceptivity in women with endometriosis-associated implantation failure. These include hormonal\npretreatment protocols, immunomodulatory approaches, and novel regenerative therapies such as platelet-\nrich plasma (PRP) and granulocyte colony-stimulating factor (G-CSF). By integrating mechanistic insights\nwith clinical evidence, this review aims to provide a practical framework for the personalized management\nof implantation failure in women with endometriosis and to identify key directions for future research in\nthis rapidly evolving field.\nCategories:\n Obstetrics/Gynecology, Medical Education, Internal Medicine\nKeywords:\n bcl6, endometrial receptivity, endometriosis, implantation failure, uterine natural killer cells\nIntroduction And Background\nEndometriosis is a chronic inflammatory disease affecting approximately 10% of women of reproductive age\nand represents one of the leading causes of female infertility. Beyond its well-established association with\npelvic pain and anatomical distortion, endometriosis has increasingly been recognized as a systemic and\nendometrial disorder that profoundly interferes with reproductive function. Women with endometriosis\nexhibit reduced spontaneous conception rates and significantly lower success rates following assisted\nreproductive technology (ART), even in the absence of severe pelvic adhesions or ovarian compromise \n[1]\n.\nImplantation failure remains a major limiting factor in ART outcomes and constitutes a particularly\nchallenging clinical entity in women with endometriosis. Traditionally, impaired fertility in endometriosis\nhas been attributed to mechanical factors, altered folliculogenesis, and compromised oocyte quality.\nHowever, accumulating evidence indicates that defective endometrial receptivity plays a central role in\nimplantation failure in this population. Alterations in hormonal responsiveness, chronic inflammation,\nimmune dysregulation, and aberrant molecular signaling converge to create a hostile endometrial\nmicroenvironment that impairs embryo-endometrium crosstalk and compromises implantation.\nEndometrial receptivity is a finely regulated process that depends on coordinated endocrine, immune, and\nmolecular events occurring within a narrow window of implantation. In women with endometriosis,\nprogesterone resistance, altered expression of receptivity markers, dysregulated immune cell populations,\nand persistent inflammatory activation have been consistently reported. These abnormalities not only\n1\n1\n2\n3\n3\n \nOpen Access Review Article\nHow to cite this article\nSarli V, Papageorgiou C, Christodoulaki C, et al. (July 24, 2026) Endometriosis-Associated Implantation Failure: Pathophysiology, Biomarkers, and\nEmerging Therapeutic Strategies. Cureus 18(7): e113299. \nDOI 10.7759/cureus.113299\n\ndisrupt decidualization and trophoblast invasion but may also lead to repeated implantation failure (RIF),\neven when high-quality embryos are transferred. A range of molecular and immune biomarkers have been\nproposed to identify impaired endometrial receptivity in this population. Nevertheless, their clinical utility\nremains controversial, and standardized diagnostic algorithms are still lacking \n[2]\n.\nTherapeutic strategies aiming to restore endometrial receptivity in women with endometriosis-associated\nimplantation failure have evolved substantially over the past decade. Hormonal pretreatment protocols,\nimmunomodulatory interventions, and novel regenerative approaches such as platelet-rich plasma (PRP)\nand granulocyte colony-stimulating factor (G-CSF) have been increasingly explored, with heterogeneous\nand often conflicting results. The absence of consensus regarding optimal patient selection and treatment\nsequencing continues to represent a major unmet need in clinical practice.\nThis narrative review aims to provide a comprehensive overview of the pathophysiological mechanisms\nlinking endometriosis to implantation failure, with particular emphasis on immune dysregulation and\nendometrial receptivity defects. We further summarize current evidence regarding established and emerging\nbiomarkers of impaired receptivity and critically discuss available and novel therapeutic strategies. By\nintegrating mechanistic insights with clinical data, this review seeks to propose a practical framework for the\npersonalized management of implantation failure in women with endometriosis.\nReview\nEndometriosis and impaired endometrial receptivity: progesterone\nresistance and molecular alterations\nProgesterone signaling is a central determinant of endometrial receptivity and successful implantation,\norchestrating decidualization, immune tolerance, and trophoblast invasion. In women with endometriosis,\nmounting evidence indicates the presence of progesterone resistance, characterized by impaired\nprogesterone receptor signaling and downstream transcriptional dysregulation. This phenomenon has\nemerged as a key pathophysiological mechanism underlying defective endometrial receptivity and\nimplantation failure in this population \n[1]\n.\nAt the molecular level, altered expression and an imbalance in the progesterone receptors (PR-A and PR-B)\nhave been consistently demonstrated in the eutopic endometrium of women with endometriosis. A relative\npredominance of PR-A over PR-B has been associated with attenuated progesterone responsiveness and\ndefective decidualization. These alterations are further compounded by epigenetic modifications, including\npromoter hypermethylation and changes in histone acetylation, which impair progesterone-dependent gene\ntranscription and contribute to persistent estrogenic dominance within the endometrial environment.\nOne of the most extensively studied downstream targets of progesterone signaling is the homeobox gene\nHOXA10, a critical regulator of endometrial differentiation and embryo implantation. Reduced HOXA10\nexpression has been repeatedly observed in the mid-luteal endometrium of women with endometriosis and\ncorrelates with impaired decidualization and decreased implantation potential. Similar dysregulation has\nbeen reported for HOXA11, further supporting the concept of a globally altered transcriptional program\ngoverning endometrial receptivity \n[3,4]\n. Integrins constitute another key group of molecular mediators\naffected in endometriosis-associated implantation failure. The alpha-v-beta-3 integrin, widely regarded as a\ncanonical marker of endometrial receptivity, exhibits reduced or delayed expression during the window of\nimplantation in women with endometriosis.\nThis aberrant integrin profile disrupts embryo adhesion and compromises early implantation events,\nindependently of embryo quality \n[5]\n. Beyond receptor and adhesion molecule dysregulation, endometriosis\nis associated with profound alterations in the decidualization cascade. Decreased expression of prolactin,\ninsulin-like growth factor binding protein-1, and forkhead box O1 reflects defective stromal cell\ndifferentiation and impaired acquisition of a receptive phenotype. These abnormalities are further\nexacerbated by persistent inflammatory activation and oxidative stress, which interfere with progesterone-\nmediated transcription and perpetuate a hostile endometrial microenvironment.\nInflammatory and oxidative stress pathways\nEndometriosis is increasingly recognized as a chronic inflammatory condition characterized by sustained\nactivation of immune and inflammatory pathways within both ectopic lesions and the eutopic endometrium.\nThis persistent inflammatory state profoundly alters the endometrial microenvironment and represents a\nmajor determinant of impaired receptivity and implantation failure. At the cellular level, eutopic\nendometrium from women with endometriosis exhibits increased infiltration of activated macrophages,\nneutrophils, and mast cells, accompanied by excessive production of pro-inflammatory mediators.\nElevated concentrations of interleukins, tumor necrosis factor-\nα\n, and chemokines have been consistently\ndetected during the peri-implantation period, disrupting the tightly regulated inflammatory balance\nrequired for successful embryo implantation. While physiological implantation requires a transient and\nfinely tuned inflammatory response, the chronic inflammatory state observed in endometriosis leads to\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n2\n of \n12\n\nsustained activation that becomes detrimental to endometrial function \n[5]\n.\nCyclooxygenase-2 (COX-2) overexpression represents a central molecular hallmark of endometriosis-\nassociated inflammation. Increased COX-2 activity results in excessive prostaglandin synthesis, particularly\nprostaglandin E2, which promotes angiogenesis, vascular permeability, and leukocyte recruitment. In the\ncontext of implantation, prostaglandin dysregulation interferes with endometrial differentiation, alters\nvascular remodeling, and perturbs the molecular dialogue between the embryo and the endometrium.\nExperimental models have further demonstrated that aberrant prostaglandin signaling compromises\ntrophoblast invasion and impairs early placentation. Oxidative stress constitutes an additional and closely\ninterconnected pathogenic pathway. Increased generation of reactive oxygen species and impaired\nantioxidant defenses have been documented in both peritoneal fluid and the eutopic endometrium of\nwomen with endometriosis.\nExcessive oxidative stress induces lipid peroxidation, protein oxidation, and DNA damage, thereby altering\ncellular signaling and transcriptional programs essential for receptivity. Importantly, oxidative stress\ndirectly interferes with progesterone signaling pathways and amplifies progesterone resistance, further\naggravating molecular defects in decidualization and implantation. Beyond their direct cellular effects,\ninflammatory and oxidative pathways profoundly remodel the endometrial extracellular matrix and vascular\narchitecture. Altered matrix metalloproteinase activity, aberrant angiogenesis, and endothelial dysfunction\nhave been described in the receptive phase, leading to impaired stromal remodeling and suboptimal\ntrophoblast anchoring. These microenvironmental alterations compromise embryo apposition and adhesion\nindependently of embryo competence.\nImmunological mechanisms linking endometriosis to implantation\nfailure\nUterine natural killer (uNK) cells represent the predominant immune cell population within the\nendometrium during the peri-implantation period and play a pivotal role in regulating implantation,\ndecidualization, and early placentation. Unlike peripheral cytotoxic NK cells, uNK cells exhibit a specialized\nphenotype characterized by reduced cytotoxicity and enhanced secretory capacity, contributing to vascular\nremodeling, immune tolerance, and trophoblast invasion. In women with endometriosis, both quantitative\nand functional alterations in uNK cells have been increasingly implicated in the pathogenesis of\nimplantation failure \n[6]\n.\nSeveral studies have demonstrated aberrant uNK cell density and distribution within the eutopic\nendometrium of women with endometriosis, particularly during the mid-luteal phase. Increased numbers of\nuNK cells have been reported in a subset of patients with RIF, whereas other investigations have identified\nqualitative defects rather than numerical abnormalities. These discrepancies likely reflect methodological\nheterogeneity and highlight the importance of functional profiling over absolute cell counts.\nAt the functional level, uNK cells in endometriosis exhibit altered cytotoxic potential and impaired secretion\nof angiogenic and immunoregulatory mediators. Dysregulated expression of killer-cell immunoglobulin-like\nreceptors and their cognate human leukocyte antigen ligands on trophoblast cells disrupts the finely tuned\nreceptor-ligand interactions required for immune tolerance and vascular adaptation. Aberrant KIR-HLA\ncombinations have been associated with defective spiral artery remodeling, shallow trophoblast invasion,\nand compromised placentation, thereby predisposing to implantation failure and early pregnancy loss \n[7,8]\n.\nIn addition to receptor-mediated signaling, endometriosis-associated inflammation profoundly modulates\nuNK cell function.\nElevated local concentrations of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis\nfactor-\nα\n, shift uNK cells toward a more cytotoxic phenotype and attenuate their pro-angiogenic activity.\nThis phenotypic reprogramming disrupts the balance between immune surveillance and immune tolerance\nthat is essential for successful implantation. Emerging evidence further suggests that progesterone\nresistance contributes to uNK cell dysregulation in endometriosis. Progesterone-dependent induction of key\nimmunomodulatory molecules, such as glycodelin and galectin-1, is attenuated in the receptive\nendometrium, thereby impairing uNK-mediated immune tolerance and trophoblast accommodation. These\nhormonal-immune interactions provide an additional mechanistic link between endocrine dysfunction and\nimmune-mediated implantation failure.\nMacrophages and antigen-presenting cells\nMacrophages constitute a major immune cell population within the endometrial stroma and play a central\nrole in tissue remodeling, angiogenesis, immune tolerance, and regulation of trophoblast invasion. During\nnormal implantation, macrophages undergo dynamic polarization toward an anti-inflammatory and pro-\nreparative M2 phenotype, facilitating decidualization, extracellular matrix remodeling, and vascular\nadaptation. In women with endometriosis, profound quantitative and qualitative alterations in endometrial\nmacrophage populations have been increasingly recognized as key contributors to implantation failure \n[9]\n.\nEndometriosis is characterized by increased recruitment and activation of macrophages within both ectopic\nlesions and eutopic endometrium.\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n3\n of \n12\n\nElevated macrophage density has been consistently reported during the peri-implantation period, reflecting\nsustained inflammatory activation and aberrant immune surveillance. Importantly, beyond numerical\nexpansion, endometrial macrophages in endometriosis exhibit a marked polarization imbalance, with a\npredominance of pro-inflammatory M1 phenotypes and relative deficiency of immunoregulatory M2\nsubsets. This skewed polarization disrupts the physiological immune tolerance required for embryo\nimplantation and promotes persistent tissue inflammation \n[10,11]\n.\nAt the molecular level, M1-polarized macrophages secrete high concentrations of pro-inflammatory\ncytokines, reactive oxygen species, and matrix-degrading enzymes that impair stromal differentiation and\ncompromise extracellular matrix integrity. Excessive production of tumor necrosis factor-\nα\n, interleukin-1\nβ\n,\nand nitric oxide interferes with decidualization and inhibits trophoblast migration, thereby directly\nimpairing early implantation events. In parallel, reduced M2 macrophage activity attenuates the secretion of\nangiogenic and growth-promoting factors, including vascular endothelial growth factor and transforming\ngrowth factor-\nβ\n, which are essential for spiral artery remodeling and placental anchoring.\nMacrophage-mediated fibrosis represents an additional pathogenic mechanism linking endometriosis to\nimplantation failure. Activated macrophages promote fibroblast proliferation and collagen deposition\nthrough the release of profibrotic mediators, resulting in increased stromal stiffness and altered\nbiomechanical properties of the endometrium. Such fibrotic remodeling compromises embryo apposition\nand invasion and has been associated with reduced implantation potential independently of hormonal and\nembryonic factors.\nAntigen-presenting cells, including dendritic cells, further contribute to immune dysregulation in\nendometriosis. Under physiological conditions, uterine dendritic cells participate in antigen tolerance and\npromote regulatory T-cell expansion, thereby facilitating maternal-fetal immune adaptation. In\nendometriosis, aberrant maturation and activation of dendritic cells have been reported, leading to\nenhanced antigen presentation, impaired tolerogenic signaling, and defective induction of regulatory T cells.\nThis shift toward immunostimulatory phenotypes perpetuates chronic inflammation and undermines\nimmune tolerance at the maternal-embryonic interface. Taken together, macrophage polarization imbalance\nand antigen-presenting cell dysfunction represent central immunopathological mechanisms underlying\ndefective implantation in endometriosis. Their wide-ranging effects on inflammation, fibrosis, angiogenesis,\nand immune tolerance highlight their pivotal role in the pathogenesis of endometriosis-associated\nimplantation failure and support their potential as diagnostic biomarkers and therapeutic targets.\nCytokine and chemokine networks\nSuccessful implantation requires a finely regulated cytokine and chemokine milieu that orchestrates\nimmune tolerance, stromal differentiation, angiogenesis, and trophoblast invasion. This tightly controlled\nnetwork ensures a transient pro-inflammatory phase during embryo apposition, followed by a rapid shift\ntoward an anti-inflammatory and immunotolerant environment that supports decidualization and placental\ndevelopment. In women with endometriosis, profound dysregulation of cytokine and chemokine signaling\nhas emerged as a central mechanism underlying impaired receptivity and implantation failure.\nMultiple studies have demonstrated an aberrant cytokine profile within the eutopic endometrium and\nperitoneal fluid of women with endometriosis, characterized by sustained elevation of pro-inflammatory\nmediators throughout the menstrual cycle. Increased concentrations of interleukin-1\nβ\n, interleukin-6, tumor\nnecrosis factor-\nα\n, and interferon-\nγ\n have been consistently reported during the peri-implantation period,\nreflecting persistent immune activation that disrupts the physiological temporal pattern required for\nimplantation. These cytokines directly impair decidualization, inhibit trophoblast invasion, and alter\nendothelial function, thereby compromising multiple steps of early implantation.\nThe Th1/Th2 balance represents a critical determinant of implantation success. Under physiological\nconditions, a transient Th1-dominant inflammatory response facilitates embryo attachment, followed by a\nTh2-biased immunotolerant state that supports trophoblast invasion and placental development. In\nendometriosis, a persistent Th1-skewed immune profile has been observed, with excessive production of\nTh1 cytokines and relative suppression of Th2 and regulatory mediators. This sustained pro-inflammatory\npolarization impairs immune tolerance at the maternal-embryonic interface and predisposes to implantation\nfailure and early pregnancy loss \n[12]\n.\nChemokine signaling further contributes to immune dysregulation in endometriosis. Altered expression of\nchemokines such as CXCL12, CCL2, and CCL5 disrupts the spatial recruitment and positioning of immune\ncells within the endometrial stroma. Aberrant chemokine gradients impair the coordinated trafficking of\nuNK cells, macrophages, and regulatory T cells, thereby perturbing local immune architecture and\ncompromising the establishment of a receptive microenvironment. Dysregulated chemokine signaling has\nadditionally been implicated in defective angiogenesis and abnormal vascular patterning during the window\nof implantation \n[13]\n.\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n4\n of \n12\n\nBeyond classical inflammatory mediators, emerging evidence highlights the role of regulatory cytokines in\nmodulating implantation competence. Reduced expression of interleukin-10 and transforming growth\nfactor-\nβ\n has been reported in the receptive endometrium of women with endometriosis, reflecting impaired\ninduction of immune tolerance and defective expansion of regulatory T-cell populations. These deficiencies\nexacerbate local immune activation and undermine the establishment of maternal-fetal tolerance during the\nearliest stages of pregnancy \n[14]\n. Importantly, cytokine and chemokine networks interact closely with\nhormonal and metabolic signaling pathways. Progesterone resistance amplifies pro-inflammatory cytokine\nproduction and attenuates the anti-inflammatory effects of progesterone-dependent mediators, thereby\nreinforcing immune dysregulation.\nIn parallel, oxidative stress further activates nuclear factor-\nκ\nB and other transcription factors that drive\ncytokine gene expression, sustaining chronic inflammatory activation throughout the implantation window.\nCollectively, dysregulated cytokine and chemokine networks represent a central integrative mechanism\nlinking hormonal resistance, immune activation, and microenvironmental remodeling in endometriosis-\nassociated implantation failure. Their diverse effects on immune cell recruitment, angiogenesis, stromal\ndifferentiation, and trophoblast invasion highlight their potential as both diagnostic biomarkers and\ntherapeutic targets.\nBiomarkers of endometrial dysfunction in endometriosis\nTranscriptomic and Molecular Biomarkers\nThe identification of reliable biomarkers of impaired endometrial receptivity represents a major priority in\nthe management of implantation failure associated with endometriosis. Advances in transcriptomic\nprofiling and molecular diagnostics have revealed profound alterations in gene expression within the\neutopic endometrium of affected women, reflecting the underlying hormonal resistance, inflammatory\nactivation, and immune dysregulation that characterize this condition. Among the proposed molecular\nbiomarkers, transcription factors and progesterone-responsive genes have emerged as particularly\ninformative indicators of defective receptivity.\nOne of the most extensively investigated biomarkers in this context is B-cell lymphoma 6 (BCL6), a\ntranscriptional repressor that has been increasingly implicated in progesterone resistance and endometrial\ndysfunction. BCL6 is overexpressed in the eutopic endometrium of women with endometriosis, particularly\nduring the mid-luteal phase, and has been shown to inhibit progesterone receptor signaling and\ndownstream decidualization pathways \n[15]\n. Mechanistically, BCL6 suppresses the expression of key\nprogesterone-regulated genes, including HOXA10 and Indian hedgehog, thereby disrupting stromal\ndifferentiation and impairing the acquisition of a receptive phenotype.\nClinical studies have demonstrated a strong association between endometrial BCL6 overexpression and RIF,\neven in women without laparoscopically confirmed endometriosis. Elevated BCL6 expression has been\nproposed as a surrogate marker of occult endometriosis and inflammatory progesterone resistance,\nidentifying a subset of patients with otherwise unexplained implantation failure who may benefit from\ntargeted pretreatment strategies. Importantly, BCL6 expression has been shown to normalize following\nmedical or surgical suppression of endometriosis, further supporting its role as a dynamic biomarker\nreflecting disease activity and treatment response \n[16,17]\n.\nBeyond BCL6, multiple progesterone-responsive genes involved in decidualization and implantation are\ndysregulated in endometriosis. Reduced expression of HOXA10 and HOXA11, leukemia inhibitory factor,\nand glycodelin has been consistently reported during the window of implantation, reflecting defective\ntranscriptional programming of endometrial stromal cells. These alterations impair embryo adhesion,\ntrophoblast invasion, and immune tolerance, thereby directly compromising implantation competence \n[3,4]\n.\nHigh-throughput transcriptomic analyses have further revealed global reprogramming of endometrial gene\nexpression in women with endometriosis. Differential expression of genes involved in cell adhesion,\nangiogenesis, immune regulation, and extracellular matrix remodeling has been documented,\ndemonstrating the multifactorial nature of receptivity defects. Notably, aberrant activation of inflammatory\nsignaling pathways, including nuclear factor-\nκ\nB and signal transducer and activator of transcription\nnetworks, has been identified as a recurrent molecular signature linking inflammation to progesterone\nresistance and implantation failure \n[18]\n.\nDespite their strong biological rationale, the clinical implementation of transcriptomic biomarkers remains\nchallenging. Variability in sampling timing, menstrual cycle heterogeneity, and methodological differences\nin gene expression platforms contribute to inconsistent diagnostic performance across studies.\nFurthermore, the absence of standardized cut-off values and prospective validation limits the widespread\nadoption of these biomarkers in routine clinical practice. Among them, BCL6 has emerged as a particularly\nrobust indicator of inflammatory progesterone resistance and represents a potential cornerstone biomarker\nin the diagnostic algorithm for implantation failure in women with endometriosis \n[15,16]\n.\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n5\n of \n12\n\nEndometrial Receptivity Testing\nThe concept of a personalized window of implantation has led to the development of endometrial\nreceptivity assays aimed at identifying temporal displacement or molecular dysfunction of the receptive\nphase in women with implantation failure. Among these, transcriptomic-based endometrial receptivity\ntesting has gained considerable attention as a potential tool for optimizing embryo transfer timing and\nimproving ART outcomes. In the context of endometriosis, however, the diagnostic performance and clinical\nutility of such assays remain controversial \n[19]\n.\nThe endometrial receptivity array (ERA) represents the most extensively studied receptivity assay and\nevaluates the expression profile of a predefined panel of genes associated with the receptive endometrial\nphenotype. By classifying endometrial samples as receptive or non-receptive, ERA aims to identify a\npersonalized window of implantation and guide individualized embryo transfer timing. Several studies have\nreported a higher prevalence of displaced windows of implantation in women with RIF and in those with\nendometriosis, suggesting that temporal asynchrony may contribute to implantation failure in this\npopulation \n[20]\n.\nIn women with endometriosis, transcriptomic analyses have consistently demonstrated altered expression of\nreceptivity-related genes during the mid-luteal phase, reflecting underlying progesterone resistance and\ninflammatory activation. These molecular perturbations raise the possibility that conventional timing based\non hormonal exposure may not adequately capture the receptive phase in affected patients. Accordingly, a\nsubset of studies has reported improved implantation and pregnancy rates following personalized embryo\ntransfer guided by receptivity testing in women with endometriosis and RIF.\nNevertheless, substantial limitations undermine the routine clinical application of receptivity assays in this\nsetting. Inter-cycle variability in gene expression, hormonal fluctuations, and inflammatory activity may\nlead to inconsistent receptivity profiles, particularly in women with chronic inflammatory conditions such\nas endometriosis. Furthermore, the transcriptomic signature of receptivity in endometriosis may reflect a\nqualitative defect rather than a purely temporal displacement, thereby limiting the corrective potential of\ntiming adjustments alone \n[21,22]\n.\nImportantly, receptivity assays do not capture the full spectrum of pathophysiological alterations associated\nwith endometriosis. Immune dysregulation, cytokine imbalance, and microenvironmental remodeling,\nwhich play central roles in implantation failure, are only partially reflected in current transcriptomic panels.\nEvidence from randomized controlled trials and meta-analyses has failed to demonstrate a consistent\nbenefit of receptivity-guided embryo transfer in unselected ART populations, and available data in women\nwith endometriosis remain limited by small sample sizes and lack of standardized protocols \n[22,23]\n.\nIntegration of receptivity testing with immune profiling and biomarker-guided pretreatment strategies may\nrepresent a more comprehensive approach for patient stratification and personalized management.\nMicroRNAs and Epigenetic Regulation\nEpigenetic regulation has emerged as a fundamental mechanism governing endometrial receptivity, immune\ntolerance, and decidualization. Increasing attention has focused on the role of microRNAs (miRNAs) and\nepigenetic modifications in mediating the molecular alterations associated with endometriosis and\nimplantation failure. These regulatory layers provide a mechanistic link between chronic inflammation,\nprogesterone resistance, and persistent transcriptional reprogramming of the endometrium \n[23]\n. MicroRNAs\nare small non-coding RNAs that post-transcriptionally regulate gene expression by targeting messenger\nRNA stability and translation. In the receptive endometrium, tightly coordinated miRNA expression patterns\nmodulate key pathways involved in cell adhesion, angiogenesis, immune regulation, and hormonal\nresponsiveness. In women with endometriosis, aberrant miRNA profiles have been consistently identified\nwithin eutopic endometrium, reflecting disease-specific epigenetic reprogramming that compromises\nimplantation competence.\nAmong the most extensively studied miRNAs, miR-135a has been shown to directly suppress HOXA10\nexpression, thereby impairing progesterone-dependent transcriptional programming and decidualization.\nOverexpression of miR-135a in the mid-luteal endometrium of women with endometriosis correlates with\nreduced HOXA10 levels and decreased implantation potential, highlighting a direct epigenetic mechanism\nlinking endometriosis to defective receptivity. Similarly, dysregulation of miR-451 and miR-29 family\nmembers has been implicated in altered inflammatory signaling and extracellular matrix remodeling,\nfurther compromising stromal differentiation and embryo adhesion \n[24]\n.\nBeyond individual miRNAs, global alterations in epigenetic landscapes have been documented in\nendometriosis-associated endometrial dysfunction. Aberrant DNA methylation patterns affecting\nprogesterone receptor promoters, HOXA gene clusters, and immune-regulatory loci contribute to sustained\nprogesterone resistance and persistent inflammatory activation. Histone modifications, including altered\nacetylation and methylation states, further modulate chromatin accessibility and transcription factor\nbinding, reinforcing pathological gene expression programs during the window of implantation \n[25]\n.\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n6\n of \n12\n\nImportantly, epigenetic dysregulation in endometriosis appears to be dynamic and potentially reversible.\nMedical and surgical suppression of disease activity has been shown to partially restore normal methylation\npatterns and miRNA expression profiles, suggesting that epigenetic biomarkers may reflect both disease\nburden and treatment response. This plasticity confers particular clinical relevance to epigenetic profiling as\na tool for patient stratification and monitoring of therapeutic efficacy. From a translational perspective,\nmiRNAs and epigenetic signatures offer several advantages as biomarkers of implantation failure. Their\nrelative stability, detectability in endometrial tissue and uterine fluid, and close association with key\npathogenic pathways render them attractive candidates for non-invasive diagnostics and personalized\ntreatment selection. However, significant challenges remain, including inter-cycle variability, technical\nheterogeneity, and the lack of standardized analytical platforms \n[26]\n.\nImmune and Inflammatory Biomarkers\nImmune and inflammatory biomarkers have emerged as promising tools for the identification of\nendometrial dysfunction in women with endometriosis-associated implantation failure. Given the central\nrole of immune dysregulation and chronic inflammation in the pathogenesis of defective receptivity,\nprofiling of immune cell populations and inflammatory mediators has been increasingly explored as a\nmeans of refining diagnosis, stratifying patients, and guiding personalized therapeutic interventions.\nAssessment of uNK cell density and activity represents one of the most extensively investigated immune\nbiomarkers in implantation failure.\nIncreased uNK cell numbers, altered phenotypic profiles, and enhanced cytotoxic activity have been\nreported in subsets of women with RIF and endometriosis. Immunohistochemical quantification of CD56-\npositive cells and flow cytometric analysis of NK receptor expression have been proposed as diagnostic tools;\nhowever, substantial methodological variability and lack of standardized reference ranges limit their clinical\napplicability. Moreover, uNK cell number alone fails to capture functional competence, and discordance\nbetween cell density and cytotoxic potential has been frequently observed \n[6,7]\n.\nCytokine profiling constitutes another widely studied approach to immune biomarker development.\nElevated endometrial and uterine fluid concentrations of pro-inflammatory cytokines, including\ninterleukin-6, interleukin-1\nβ\n, tumor necrosis factor-\nα\n, and interferon-\nγ\n, have been consistently associated\nwith implantation failure and adverse reproductive outcomes. Conversely, reduced levels of regulatory\nmediators such as interleukin-10 and transforming growth factor-\nβ\n reflect impaired immune tolerance and\ndefective expansion of regulatory T-cell populations \n[13,14]\n. Recent advances in immune profiling\ntechnologies have enabled more comprehensive characterization of endometrial immune landscapes.\nMultiparametric flow cytometry, single-cell RNA sequencing, and spatial transcriptomics have revealed\ncomplex immune cell heterogeneity within the receptive endometrium and identified disease-specific\nimmune signatures in endometriosis.\nAltered proportions of regulatory T cells, dysfunctional macrophage subsets, and aberrant dendritic cell\nmaturation profiles have been correlated with implantation failure and disease severity. These high-\ndimensional approaches provide unprecedented resolution but remain largely confined to research settings\ndue to cost, technical complexity, and limited standardization. Importantly, immune biomarkers are\ninherently dynamic and influenced by hormonal milieu, inflammatory activity, and therapeutic\ninterventions. The absence of validated cut-off values and prospective outcome-driven studies precludes\nroutine clinical implementation. Integration of immune profiling with molecular and transcriptomic\nbiomarkers may enable the identification of biologically distinct endotypes of implantation failure,\nfacilitating tailored therapeutic strategies.\nTherapeutic strategies for endometriosis-associated implantation\nfailure\nHormonal Pretreatment Approaches\nHormonal pretreatment represents one of the most extensively investigated strategies for improving\nimplantation outcomes in women with endometriosis-associated implantation failure. The rationale for\nhormonal suppression is grounded in the pathophysiology of the disease, aiming to attenuate inflammatory\nactivity, reverse progesterone resistance, and restore endometrial receptivity before embryo transfer. Among\navailable approaches, gonadotropin-releasing hormone (GnRH) agonist-based protocols have received the\ngreatest attention.\nProlonged pituitary suppression with GnRH agonists, commonly referred to as ultra-long protocols, has\nbeen proposed as a means of reducing ectopic lesion activity, suppressing inflammatory mediators, and\nnormalizing endometrial gene expression. Several observational studies and randomized trials have\nreported improved implantation, clinical pregnancy, and live birth rates in women with moderate to severe\nendometriosis undergoing in vitro fertilization following two to six months of GnRH agonist pretreatment.\nThese benefits appear to be particularly pronounced in patients with advanced disease and in those with a\nhistory of RIF \n[27]\n.\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n7\n of \n12\n\nAt the molecular level, GnRH agonist suppression has been shown to downregulate inflammatory cytokines,\nreduce prostaglandin synthesis, and partially restore progesterone responsiveness within the eutopic\nendometrium. Normalization of key receptivity markers, including HOXA10 and integrins, has been\ndocumented following prolonged suppression, supporting a mechanistic basis for improved implantation\ncompetence. Furthermore, medical suppression has been associated with reduced BCL6 expression,\nsuggesting reversal of inflammatory progesterone resistance in selected patients.\nDespite these promising findings, the efficacy of GnRH agonist pretreatment remains heterogeneous and\npatient-dependent. Meta-analyses have demonstrated a modest but significant improvement in clinical\npregnancy rates; however, substantial variability in study design, disease stage, pretreatment duration, and\nART protocols limits the generalizability of results. The benefit of ultra-long suppression appears less\nconsistent in women with minimal or mild endometriosis and in those without overt inflammatory activity\n[28]\n.\nAlternative hormonal strategies, including oral progestins, combined oral contraceptives, and dienogest-\nbased suppression, have been explored with variable success. Progestin pretreatment may exert anti-\ninflammatory and anti-proliferative effects on ectopic lesions and improve luteal-phase endometrial\ndifferentiation; however, evidence regarding implantation outcomes remains limited and largely derived\nfrom small observational cohorts. Dienogest, in particular, has shown efficacy in reducing pain and lesion\nburden, but its impact on endometrial receptivity and ART success remains incompletely defined \n[29]\n.\nImportantly, hormonal pretreatment is not devoid of limitations. Prolonged suppression may adversely\naffect ovarian reserve, delay treatment, and increase patient burden. Hypoestrogenic side effects and\nimpaired endometrial recovery following extended suppression may further compromise implantation if\ninadequate washout intervals are applied. These considerations emphasize the need for careful patient\nselection and individualized protocol design \n[30]\n.\nImmunomodulatory Therapies\nGiven the central role of immune dysregulation in the pathogenesis of endometriosis-associated\nimplantation failure, immunomodulatory therapies have been widely explored as adjunctive strategies in\nassisted reproduction. These interventions aim to attenuate excessive inflammatory activation, restore\nimmune tolerance at the maternal-embryonic interface, and modulate aberrant immune cell function.\nHowever, despite their widespread clinical use, robust evidence supporting their efficacy remains limited\nand controversial.\nCorticosteroids represent the most commonly employed immunomodulatory agents in reproductive\nmedicine. By suppressing pro-inflammatory cytokine production and inhibiting lymphocyte activation,\ncorticosteroids are theoretically expected to improve implantation by restoring immune balance and\nreducing endometrial inflammation \n[31]\n. Several small observational studies have reported improved\nimplantation and pregnancy rates in women with RIF and elevated immune activation markers.\nNevertheless, randomized controlled trials and meta-analyses have failed to demonstrate consistent benefit\nin unselected ART populations. Intralipid therapy has been proposed as a means of modulating uNK cell\nactivity and reducing cytotoxic immune responses. Experimental data suggest that intralipids may\ndownregulate NK cell cytotoxicity and alter cytokine secretion profiles. However, evidence supporting its\nuse remains largely derived from uncontrolled studies and retrospective analyses, with conflicting results\nregarding implantation and live birth rates \n[32]\n. Reliable biomarkers for patient selection and treatment\nmonitoring are lacking, limiting the rational application of this intervention.\nIntravenous immunoglobulin (IVIG) has been investigated as a more potent immunomodulatory strategy in\nselected patients with severe immune dysregulation. IVIG exerts multifaceted effects on both innate and\nadaptive immunity, including modulation of NK cell activity, suppression of autoantibody production, and\nenhancement of regulatory T-cell function. Several early studies suggested improved pregnancy outcomes\nin women with RIF and abnormal immune profiles; however, subsequent trials yielded inconsistent results.\nThe high cost, limited availability, and potential for adverse reactions further restrict the routine use of IVIG\nin clinical practice.\nA major limitation of immunomodulatory therapies lies in the lack of standardized diagnostic criteria for\nimmune-mediated implantation failure. Immune biomarkers exhibit substantial inter-cycle variability, and\nconsensus regarding clinically relevant thresholds is lacking. Consequently, immunomodulation is\nfrequently applied empirically, without clear mechanistic justification or evidence-based patient selection.\nCarefully designed trials incorporating immune phenotyping, biomarker-guided patient selection, and\nstandardized outcome measures are urgently needed to define the role of targeted immunomodulation in\npersonalized reproductive medicine \n[31,32]\n.\nRegenerative and Growth Factor-Based Therapies\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n8\n of \n12\n\nThe recognition of endometrial dysfunction as a central mechanism of implantation failure has stimulated\ngrowing interest in regenerative and growth factor-based therapies aimed at restoring receptivity and\nmicroenvironmental integrity. Among these approaches, PRP and G-CSF have emerged as the most\nextensively investigated regenerative interventions in women with RIF and endometrial insufficiency,\nincluding those with endometriosis. PRP represents an autologous concentration of platelets suspended in\nplasma and enriched with a broad spectrum of bioactive mediators, including platelet-derived growth factor,\ntransforming growth factor-\nβ\n, vascular endothelial growth factor, epidermal growth factor, and insulin-like\ngrowth factor. These factors exert wide-ranging effects on angiogenesis, stromal proliferation, extracellular\nmatrix remodeling, and immune modulation, thereby recapitulating key pathways involved in physiological\nendometrial regeneration and receptivity \n[33]\n.\nAt the mechanistic level, PRP has been shown to enhance endometrial stromal cell proliferation, promote\ndecidualization, and upregulate the expression of receptivity markers, including HOXA10, leukemia\ninhibitory factor, and integrins. In parallel, PRP exerts potent immunomodulatory effects by attenuating\npro-inflammatory cytokine production, promoting macrophage polarization toward anti-inflammatory\nphenotypes, and enhancing regulatory T-cell activity. These combined regenerative and immunoregulatory\nproperties render PRP particularly attractive for the treatment of endometriosis-associated implantation\nfailure, in which inflammation, progesterone resistance, and immune dysregulation coexist.\nClinical studies evaluating intrauterine PRP administration in women with RIF have reported encouraging\nimprovements in endometrial thickness, implantation rates, and clinical pregnancy outcomes. Several\nprospective and retrospective cohorts have demonstrated higher implantation and live birth rates following\nPRP infusion in patients with thin endometrium or RIF, including subsets with suspected or confirmed\nendometriosis \n[34,35]\n. Despite these promising findings, available evidence remains limited by\nmethodological heterogeneity, small sample sizes, and variable PRP preparation protocols. Well-designed\nrandomized controlled trials focusing specifically on endometriosis-associated implantation failure are\ncurrently scarce \n[36]\n.\nG-CSF represents an alternative growth factor-based strategy with both hematopoietic and\nimmunomodulatory properties. Beyond its classical role in neutrophil proliferation, G-CSF exerts direct\neffects on endometrial angiogenesis, stromal proliferation, and immune tolerance. Clinically, intrauterine\nand systemic G-CSF administration has been primarily investigated in women with thin endometrium and\nRIF. Several studies have reported increased endometrial thickness and improved implantation rates\nfollowing G-CSF treatment, whereas others have failed to demonstrate significant benefit.\nIn women with endometriosis, evidence remains extremely limited, and the specific contribution of G-CSF\nto reversing inflammatory and epigenetic alterations of the endometrium has not been adequately explored\n[37,38]\n. Importantly, regenerative therapies may exert maximal benefit in biologically selected patient\npopulations. Women exhibiting inflammatory progesterone resistance, elevated BCL6 expression, immune\nactivation, or refractory endometrial thinning may represent optimal candidates for PRP or G-CSF\nintervention. Integration of regenerative therapies with biomarker-guided patient stratification holds\nparticular promise for enhancing therapeutic efficacy and minimizing unnecessary treatment exposure.\nEndometrial Scratching and Mechanical Interventions\nMechanical endometrial injury, commonly referred to as endometrial scratching, has been proposed as an\nadjunctive intervention aimed at enhancing implantation through induction of a localized inflammatory\nresponse and modulation of endometrial receptivity. Initial observational studies and small randomized\ntrials suggested improved implantation and pregnancy rates in women with RIF. However, subsequent large\nrandomized controlled trials and meta-analyses failed to confirm a consistent benefit in unselected ART\npopulations, leading to a substantial reevaluation of its clinical utility \n[39]\n.\nIn the context of endometriosis, the role of endometrial scratching remains particularly controversial. Given\nthe chronic inflammatory state already present within the eutopic endometrium, additional mechanical\ninjury may exacerbate immune activation and oxidative stress rather than restore receptivity. Available\nstudies specifically addressing scratching in women with endometriosis are scarce and heterogeneous, and\nrobust evidence supporting routine application in this population is lacking \n[40]\n. Current evidence does not\nsupport its routine use in this setting.\nClinical implications and management framework\nThe complex and multifactorial nature of endometriosis-associated implantation failure necessitates an\nintegrated and personalized approach to diagnosis and treatment. A stepwise diagnostic framework should\nbegin with careful phenotyping of patients presenting with RIF and suspected or confirmed endometriosis.\nIn addition to conventional clinical and imaging assessment, evaluation of endometrial function through\nmolecular and immune biomarkers - including progesterone resistance markers, BCL6 expression,\ninflammatory activity, and immune profiles - may facilitate identification of biologically distinct endotypes\nof implantation failure \n[41]\n.\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n9\n of \n12\n\nPretreatment strategies should be guided by disease severity, inflammatory burden, and biomarker profiles.\nAdjunctive therapies such as PRP or G-CSF should be considered selectively and within a biomarker-guided\nframework. Routine use of empiric immunomodulatory therapies in unselected patients should be\ndiscouraged in the absence of clear immune-mediated pathology. Endometrial receptivity testing and\nimmune profiling should be interpreted cautiously and integrated with clinical context rather than applied\nas isolated diagnostic tools.\nTable \n1\n presents a proposed stepwise management framework based on patient phenotype, informed by\ncurrent evidence. Prospective validation is required before formal guideline adoption \n[41,42,43]\n.\nPatient phenotype\nRecommended pretreatment\nAdjunctive therapy\nAdvanced endometriosis (stage III-IV) or\npronounced inflammatory phenotype\nGnRH agonist ultra-long protocol (2-6\nmonths)\nConsider PRP if endometrial thinning or\nrefractory dysfunction present\nElevated BCL6 or inflammatory progesterone\nresistance\nGnRH agonist suppression; target BCL6\nnormalization before transfer\nBiomarker-guided reassessment; repeat\nendometrial sampling if needed\nMinimal/mild endometriosis (stage I-II), no\novert inflammation\nStandard FET preparation; shorten or omit\nsuppression phase\nERA testing if ≥2 prior unexplained failures\nRIF with confirmed immune activation\n(elevated uNK, cytokine profile)\nHormonal suppression; consider targeted\nimmunomodulation\nIntralipid or corticosteroids only if immune\nbiomarker criteria met\nThin endometrium (≤7 mm) refractory to\nstandard preparation\nOptimized oestrogen support protocol;\nextended preparation\nIntrauterine G-CSF or PRP infusion\nTABLE\n 1: Proposed stepwise management framework for endometriosis-associated implantation\nfailure\nERA: endometrial receptivity array; FET: frozen embryo transfer; G-CSF: granulocyte colony-stimulating factor; GnRH: gonadotropin-releasing hormone;\nPRP: platelet-rich plasma; RIF: repeated implantation failure; uNK: uterine natural killer\nLimitations of current evidence and future perspectives\nDespite substantial advances in understanding the pathophysiology of endometriosis-associated\nimplantation failure, important limitations constrain the translation of current evidence into routine\nclinical practice. Most available studies are characterized by small sample sizes, heterogeneous patient\npopulations, variable diagnostic criteria, and inconsistent outcome definitions, limiting reproducibility and\ngeneralizability. The lack of standardized biomarkers and validated thresholds represents a major barrier to\nprecision medicine. Inter-cycle variability, technical heterogeneity, and incomplete understanding of\ntemporal dynamics compromise the reliability of single-time-point measurements. Furthermore, the\nmajority of therapeutic trials lack biomarker-guided patient selection, precluding identification of\nresponders and obscuring true treatment effects.\nFuture research should prioritize prospective, multicenter trials incorporating rigorous phenotyping,\nstandardized biomarker panels, and mechanistic endpoints. Integration of multi-omics approaches,\nincluding transcriptomics, epigenomics, and immune profiling, holds particular promise for defining\nbiologically distinct endotypes of implantation failure and guiding targeted intervention. Emerging\ntechnologies such as single-cell sequencing, spatial transcriptomics, and minimally invasive diagnostic\nplatforms, including uterine fluid biomarkers and peripheral immune signatures, may facilitate broader\nclinical implementation. Ultimately, the transition from empiric treatment paradigms to biomarker-driven,\npersonalized reproductive care represents a central objective for improving outcomes in women with\nendometriosis-associated implantation failure.\nConclusions\nEndometriosis-associated implantation failure represents a complex clinical entity driven by the interaction\nof hormonal resistance, chronic inflammation, immune dysregulation, and persistent molecular\nreprogramming of the endometrium. Beyond mechanical distortion and oocyte impairment, defective\nendometrial receptivity emerges as a central determinant of reproductive failure in this population.\nAdvances in reproductive immunology and molecular diagnostics have provided critical insights into the\nmechanisms linking endometriosis to impaired implantation. Alterations in progesterone signaling, immune\ncell function, cytokine networks, and epigenetic regulation collectively shape a hostile endometrial\nmicroenvironment that compromises embryo-endometrium crosstalk and placentation. While emerging\nbiomarkers and regenerative therapies offer promising avenues for personalized intervention, current\n \n2026 Sarli et al. Cureus 18(7): e113299. DOI 10.7759/cureus.113299\n10\n of \n12\n\nevidence emphasizes the need for cautious interpretation and selective clinical application. Integration of\nmolecular, immune, and clinical parameters into individualized treatment algorithms represents the most\nrational strategy for optimizing implantation outcomes. Future progress will depend on rigorous\nmechanistic studies, biomarker-guided clinical trials, and multidisciplinary collaboration aimed at\ntranslating pathophysiological insights into precision reproductive medicine.\nAdditional Information\nAuthor Contributions\nAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the\nwork.\nConcept and design:\n  \nVaia Sarli, Nikolaos Machairiotis\nAcquisition, analysis, or interpretation of data:\n  \nVaia Sarli, Charikleia Papageorgiou, Chrysi\nChristodoulaki, Periklis Panagopoulos\nDrafting of the manuscript:\n  \nVaia Sarli, Nikolaos Machairiotis\nCritical review of the manuscript for important intellectual content:\n  \nVaia Sarli, Charikleia\nPapageorgiou, Chrysi Christodoulaki, Periklis Panagopoulos, Nikolaos Machairiotis\nSupervision:\n  \nVaia Sarli, Chrysi Christodoulaki, Nikolaos Machairiotis\nDisclosures\nConflicts of interest:\n In compliance with the ICMJE uniform disclosure form, all authors declare the\nfollowing: \nPayment/services info:\n All authors have declared that no financial support was received from\nany organization for the submitted work. \nFinancial relationships:\n All authors have declared that they have\nno financial relationships at present or within the previous three years with any organizations that might\nhave an interest in the submitted work. \nOther relationships:\n All authors have declared that there are no\nother relationships or activities that could appear to have influenced the submitted work.\nReferences\n1\n. \nShapiro BS, Daneshmand ST, Restrepo H, Garner FC, Aguirre M, Hudson C: \nEfficacy of induced luteinizing\nhormone surge after \"trigger\" with gonadotropin-releasing hormone agonist\n. 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