{"paper_id":"cfeed38a-d09c-4256-b29b-35ecdf6acc04","body_text":"Endometriosis is a chronic, benign, estrogen-dependent inflammatory disease\ncharacterized by the presence of endometrial-like tissue outside the uterine cavity.\nIts pathogenesis is most commonly attributed to the retrograde menstruation of\nviable endometrial cells into the pelvic cavity. Endometriosis affects 5 to 10% of\nreproductive-age women worldwide and, to date, there is no medical or surgical cure\n( Ghiasi  et al. , 2020 ;\n As-Sanie  et al. , 2025 ;\n La Marca  et al. ,\n2025 ).\nEndometriosis is classified into four subtypes, which may coexist and have\nimplications for diagnosis and treatment: (1) superficial peritoneal endometriosis,\ninvolving lesions located on the peritoneal surface; (2) deep endometriosis,\ncharacterized by lesions infiltrating pelvic structures such as the uterosacral\nligaments, bowel, or urinary tract; (3) endometriomas, cystic ovarian formations\nlined by endometrial tissue; and (4) extrapelvic endometriosis, involving sites\nbeyond the pelvis, including the diaphragm, abdominal wall, and central nervous\nsystem ( As-Sanie  et al. ,\n2025 ). Moreover, the American Society for Reproductive Medicine (ASRM)\nclassifies endometriosis into four stages (Stages I-IV) based on the extent,\nlocation, depth of the lesions, and the presence of adhesions ( Canis  et al. , 1997 ).\nDysmenorrhea, nonmenstrual pelvic pain, and dyspareunia are the most common symptoms\nof endometriosis and have frequently been associated with infertility ( As-Sanie  et al. , 2025 ).\nApproximately 30-50% of women with endometriosis are estimated to experience\ninfertility ( Meuleman  et al. ,\n2009 ;  Evans & Decherney,\n2017 ). Moreover, according to a recent systematic review, the prevalence of\nendometriosis among women diagnosed with unexplained infertility is approximately\n44% ( Van Gestel  et al. ,\n2024 ). As a result, many couples pursue assisted reproductive technologies\n(ART) for infertility treatment, with endometriosis representing approximately 10%\nof the indications for in vitro fertilization (IVF) ( Somigliana  et al. , 2017 ).\nThis review critically examines the evidence on the relationship between\nendometriosis and infertility, aiming to challenge prevailing assumptions and\nencourage a more nuanced understanding of its impact on oocyte quality and\ncompetence, ovarian reserve, and endometrial receptivity. This article was conceived\nas an interpretative narrative review aimed at conceptually integrating molecular,\ncellular, and clinical evidence related to endometriosis-associated infertility. The\nliterature search was conducted in PubMed for studies published up to January 2025,\nusing combinations of the following keywords: endometriosis, endometrioma, deep\nendometriosis, oocyte quality, oocyte competence, embryo quality, ovarian reserve,\nendometrial receptivity and IVF outcomes. References were selected based on their\nscientific relevance and contribution to conceptual and mechanistic discussion.\n\nSeveral factors have been proposed as contributors to endometriosis-related\ninfertility, including: (i) dyspareunia, (ii) mechanical factors such as adhesions\nor anatomical distortion, (iii) diminished ovarian reserve due to endometrioma, (iv)\nreduced oocyte quality, (v) sperm dysfunction, (vi) impaired tubo-ovarian\ninteraction or embryo transport difficulties, (vii) disrupted ovulation, and (viii)\nendometrial receptivity dysfunction, among others. Many of these potential causes of\ninfertility in endometriosis are associated with the systemic inflammatory\nenvironment induced by the disease ( Bonavina &\nTaylor, 2022 ).\nReactive oxygen species, immune system dysregulation, and disruption of cellular\narchitecture due to impaired differentiation, proliferation, and apoptosis are\ncritical mechanisms that could negatively impact the reproductive environment ( Simopoulou  et al. , 2021 ).\nThe direct causal relationship between tubal dysfunction secondary to adhesions in\nendometriosis and infertility has been extensively documented and considered\nirrefutable within the scientific community. Likewise, dyspareunia attributed to\nendometriosis is widely acknowledged as a critical factor compromising sexual\nfunction and quality of life. However, outside the context of tubal dysfunction and\npain, the association between endometriosis and infertility has been called into\nquestion, as some authors have highlighted the lack of supporting evidence ( Ata & Somigliana, 2024 ).\nGenerating high-quality scientific evidence on the true impact of endometriosis on\nfertility remains a major challenge. Several methodological limitations complicate\nthe interpretation of existing studies. First, there is considerable heterogeneity\nin disease stage, lesion phenotype, and prior surgical history, which makes patient\npopulations difficult to compare. Second, isolating the specific contribution of\nendometriosis itself is often problematic, as adenomyosis frequently coexists and\nmay independently influence reproductive outcomes. Moreover, differences in the\ntype, extent, and timing of surgical interventions can significantly affect ovarian\nreserve and endometrial function, further confounding results. Finally, when\nconsidering evidence derived from ART cycles, additional variability arises from the\ndiversity of treatment strategies applied at different stage of the cycle (before\novarian stimulation or prior to embryo transfer). Together, these factors make it\ndifficult to accurately determine the extent to which endometriosis itself\ncontributes to infertility.\n\nIn the scientific literature, the concepts of quality and competence are often\nconfused or used interchangeably. However, although related, these terms have\ndistinct definitions and encompass independent characteristics that are essential to\nconsider ( Figure 1 ). Oocyte competence refers\nto the oocyte’s functional ability to successfully undergo and complete critical\nreproductive processes, including maturation, fertilization, early embryonic\ndevelopment, and progression to a viable blastocyst ( Rienzi  et al. , 2012 ;  Palomba  et al. , 2017 ). Thus, a competent oocyte is\ndefined by its ability to successfully complete these critical developmental\nmilestones. In contrast, oocyte quality is generally associated with the\nmorphological and cytoplasmic features of the oocyte, observable structural and\nfunctional characteristics of a cell, including structural integrity and organelle\ndistribution ( Rienzi  et al. ,\n2012 ;  Palomba  et al. ,\n2017 ). Distinguishing between these concepts is crucial, as certain\npathological conditions, including endometriosis, may impact oocyte quality (e.g.,\naltering morphology or specific organelle patterns) without necessarily compromising\noocyte competence, such as its ability to reach the blastocyst stage. This\nconceptual distinction is frequently neglected in the literature, where the terms\n“quality” and “competence” are often used interchangeably, leading to\nmisinterpretation of findings and clinical implications.\nFigure 1 Conceptual distinction between cellular quality and competence in\nreproduction. Quality reflects intrinsic cellular features, including\nnuclear and cytoplasmic morphology, organelle integrity, chromosomal\nstability, and key molecular components. Competence denotes the\nfunctional capacity to achieve key developmental endpoints\nConceptual distinction between cellular quality and competence in\nreproduction. Quality reflects intrinsic cellular features, including\nnuclear and cytoplasmic morphology, organelle integrity, chromosomal\nstability, and key molecular components. Competence denotes the\nfunctional capacity to achieve key developmental endpoints\nEndometriosis is associated with alterations in the follicular microenvironment that\nmay impair cumulus cell function and compromise oocyte quality at both the cellular\nand molecular levels. The importance of the follicular environment for ensuring\noocyte quality and developmental competence is well established. Cumulus cells,\nwhich are directly exposed to this environment, support oocyte growth throughout\nfolliculogenesis via transzonal projections, extracellular vesicles, and gap\njunctions. This intimate communication enables the regulation of oocyte meiotic\nreactivation, the transfer of key metabolic substrates such as pyruvate, and the\ndelivery of molecules essential for maintaining intracellular homeostasis ( Del Collado  et al. , 2018 ).\nConsequently, it is plausible that disruptions to the follicular environment may\nadversely affect oocyte quality and competence.\nEndometriosis has been associated with decreased levels of estrogen and testosterone\nand increased levels of progesterone in the follicular fluid. These alterations are\nthought to result from local inflammation and impaired steroidogenesis in theca and\ngranulosa cells, leading to reduced estradiol and testosterone production.\nConversely, the elevated progesterone levels are likely a consequence of premature\nluteinization and altered steroid metabolism within the inflammatory\nmicroenvironment ( Fan  et al. ,\n2023 ). Additionally, studies have demonstrated enhanced activation of\napoptotic pathways and a higher number of apoptotic bodies in follicular cells of\npatients with endometriosis ( Demirel  et\nal. , 2001 ;  Goud  et\nal. , 2014 ;  Sanchez\n et al. , 2016 ). A larger prospective study involving\npatients with stage III and IV endometriosis identified distinct profiles of\npro-inflammatory and anti-inflammatory cytokine signaling within the follicular\nfluid ( Singh  et al. , 2016 ).\nEndometriosis has also been linked to increased endoplasmic reticulum stress and\noxidative stress in granulosa and cumulus cells ( Scutiero  et al. , 2017 ;  Kunitomi  et al. , 2020 ;  Lin  et al. , 2020 ).\nAt the oocyte level, transcriptomic profiling of cumulus cells from nine patients\nwith stage I-II endometriosis identified 26 differentially expressed genes\nimplicated in the regulation of inflammatory and immune pathways when compared to\ncontrols ( Da Luz  et al. ,\n2022 ). Additionally, transcriptomic analysis of individual metaphase II\n(MII) oocytes from seven patients with endometriosis, contrasted with oocytes from\nhealthy donors, revealed widespread gene expression alterations independent of\novarian laterality, affecting pathways involved in steroid metabolism, oxidative\nstress response, and cell cycle regulation ( Ferrero\n et al. , 2019 ). Endometriosis has also been\nassociated with mitochondrial dysfunction and morphological changes ( Xu  et al. , 2015 ), as well as\ndisruptions in cortical granule dynamics and meiotic spindle integrity within\noocytes during an in vitro maturation (IVM) experiment ( Goud  et al. , 2014 ).\nBeyond cellular and molecular alterations, endometriosis has further been related to\ncompromised oocyte quality, including an increased proportion of oocytes presenting\nmorphological abnormalities ( Shebl  et\nal. , 2017 ;  Kasapoglu\n et al. , 2018 ;  Robin\n et al. , 2021 ). Notably, the influence on oocyte\nquality could be affected by endometriosis stage, as indicated by  Shebl et al. (2017) , who reported a much severe\nphenotype regarding oocyte morphology in stage IV. Moreover, a retrospective cohort\nstudy of more than 6,000 oocytes concluded that besides a decrease in the number of\nrecovered oocytes and increase in some morphological abnormality in endometriosis\noocytes, mainly by a presence of endometrioma, the oocyte quality scores Average\nOocyte Quality Index (AOQI) and metaphase II oocyte morphological scoring system\n(MOMS) did not differ between endometriosis and control patients ( Robin  et al. , 2021 ).\nHowever, the critical question remains whether these alterations in oocyte quality\ntranslate into impaired developmental competence. A recent retrospective study\nincluding 248 patients with endometriosis, matched by age, stimulation protocol,\ntreatment date, and anti-Müllerian hormone (AMH) levels to 248 controls,\nfound no significant differences in the number of oocytes retrieved, 2PN embryos,\nblastocysts, or high-quality blastocysts ( Invernici\n et al. , 2022 ). Furthermore, the euploidy rate\nappears unaffected by endometriosis, as demonstrated by an analysis of 1,873\nbiopsied embryos from 261 patients, which showed no differences between\nendometriosis and male factor infertility groups. Clinical pregnancy rates following\neuploid embryo transfers were also comparable ( Bishop\n et al. , 2021 ). Conversely, a larger retrospective\nmatched cohort study encompassing 3,071 IVF cycles reported that endometriosis\nnegatively influences pregnancy outcomes, being associated with lower cumulative\nbirth rates and diminished oocyte and embryo quantity and quality. This study\nadditionally revealed increased macrophage infiltration and an imbalance between\nproand anti-inflammatory cytokines in follicular fluid from patients with\nendometriosis, indicating an altered follicular microenvironment as a potential\nmechanism ( Zhou  et al. ,\n2022 ). Nevertheless, the meta-analyses available to date have not identified\nsignificant differences in total or good quality blastocyst numbers, nor in clinical\npregnancy or live birth rates between women with and without endometriosis or\nendometrioma undergoing ART, suggesting no adverse impact on oocyte competence\n( Qu  et al. , 2022 ;  Gayete-Lafuente  et al. ,\n2024 ).\nAlthough there is evidence supporting the impact of endometriosis on oocyte quality,\nits effect on oocyte competence remains less well defined, with most available data\nsuggesting no significant impairment. It is also important to acknowledge that the\nlack of consistent evidence for reduced oocyte competence in cohort studies and\nmeta-analyses may partly reflect the heterogeneity of the study populations,\nincluding differences in disease phenotype, stage, prior surgical history, and\nclinical management. Nevertheless, it cannot be excluded that oocyte competence may\nindeed be affected in specific phenotypes or in advanced stages of the disease, such\nas stage III and IV endometriosis.\n\nIn addition to oocyte quality and competence, endometriosis may also influence the\nnumber of oocytes retrieved. In theory, endometriosis may impair ovarian reserve\nthrough chronic systemic inflammation and direct disruption of ovarian function,\ncontributing to reduced follicular recruitment and ovulatory alterations ( Cobo  et al. , 2021 ).\nA meta-analysis, including 26 studies, confirmed that women with endometriosis\nproduce fewer oocytes; however, the analysis did not control for the bias of prior\nsurgical intervention, which limits the causal interpretation of the isolated role\nof endometriosis ( Qu  et al. ,\n2022 ). On the other hand, a recent meta-analysis demonstrates that\novarian endometriosis, endometriomas, reduce both the total oocyte and the number of\nMII, showing no significant differences in fertilization or blastulation rates\n( Gayete-Lafuente  et al .,\n2024 ).\nAs reviewed by  La Marca  et al .\n(2025) , the reduction in ovarian reserve observed in women with\nendometriomas may result from elevated concentrations of proinflammatory cytokines,\nproteolytic enzymes, and oxidative stress agents within the endometrioma fluid.\nThese harmful substances can infiltrate the adjacent healthy ovarian cortex, causing\ndamage or loss of primordial follicles and leading to a subsequent decline in AMH\nlevels. Some authors have proposed that, in addition to inflammation and oxidative\nstress, an increased activation of the PI3K-AKT pathway associated with\nendometriosis may lead to the premature activation of dormant primordial follicles,\nthereby accelerating follicular depletion and contributing to a reduced ovarian\nreserve. According to this hypothesis, the local inflammatory response and\nsubsequent fibrosis at endometriotic sites, alongside Wnt signaling dysregulation,\ncould impair ovarian vascularization, nutrient supply to developing follicles and\npromote cell death and follicular atresia ( Demirel\n et al. , 2001 ;  Takeuchi  et al. , 2019 ;  Fan  et al. , 2023 ).\nFurthermore, the presence of large endometriomas may impose mechanical stress on\novarian tissue, further compromising the ovarian reserve. Moreover, a pragmatic\nstudy by  Cobo et al. (2021)  showed that the\nmost direct and measurable detrimental impact of endometriomas on ovarian reserve\nappears to be associated with cystectomy, particularly when performed in young\nwomen, showing lower cumulative live birth rates than nonoperated women in\nage-matched groups.\nTo date, available evidence suggests that the impact of endometriosis lies more in\nthe quantity of oocytes retrieved rather than in their quality or competence. As a\nconsequence of a reduced number of oocytes, fewer blastocysts become available for\ntransfer, ultimately leading to a lower cumulative live birth rate in patients with\nendometriosis as shown in  Zhou  et\nal . (2022) .\nGiven this quantitative decline, fertility preservation has been increasingly\ndiscussed as a potential strategy in the management of endometriosis. The ESHRE\nguideline (2022) recommends that, in cases of extensive ovarian endometriosis,\nclinicians should discuss fertility preservation with affected women, as its actual\nbenefit in this population remains uncertain ( Becker\n et al. , 2022 ). In contrast, the most recent ASRM\nCommittee Opinion on endometriosis and infertility does not specifically address\nfertility preservation, as its focus is mainly on the management of existing\ninfertility rather than on preventive strategies ( Practice Committee of the American Society for Reproductive Medicine,\n2012 ). Despite the absence of formal recommendations from reproductive\nsocieties or clinical guidelines, fertility preservation has been proposed for\npatients over 35 years, those with bilateral or unilateral endometriomas (prior to\nsurgery), diminished ovarian reserve, a history or risk of multiple surgeries, large\nendometriomas (>4 cm), severe endometriosis (stages III and IV), low\nendometriosis fertility index (EFI) scores, and a low probability of natural\nconception following surgery ( La Marca  et\nal. , 2025 ).\n\nOne of the major challenges in reproductive physiology, and consequently in IVF, is\nto understand the key factors that determine successful embryo implantation and to\nelucidate the complex cross-talk between the embryo and the endometrium, often\nreferred to as the ‘black box’ of implantation. Implantation failure, particularly\ninvolving euploid embryos, remains one of the most enigmatic and complex issues in\nassisted reproductive technologies ( Cimadomo\n et al. , 2023 ). Therefore, any condition that might\nimpair endometrial receptivity is a consistent focus of investigation, as is the\ncase with endometriosis.\nIn endometriosis, alterations in molecular pathways, such as those related to\nepigenetic regulation, immune and inflammatory responses, hormonal signaling, and\nepithelial-mesenchymal transition, have been suggested to impair embryo endometrium\ncross-talk, potentially contributing to implantation failure ( Guo  et al. , 2023 ). Moreover, endometriosis is\ncommonly associated with an increased inflammation-related in-situ production of\nestradiol and progesterone resistance ( de Ziegler\n et al. , 2010 ).\nSingle-cell transcriptomic analyses have revealed that even the eutopic endometrium\nof women with endometriosis displays distinct cellular and molecular alterations\ncompared to healthy controls. These changes involve transcriptional reprogramming\nand structural remodeling of epithelial and stromal cells, as well as dysregulation\nof immune related pathways ( Fonseca  et\nal. , 2023 ). Likewise, a proinflammatory immune profile in\nthe eutopic endometrium of women with endometriosis is affected, with increased CD8+\nT cells linked to a higher risk of infertility ( Wu\n et al. , 2021 ). Several studies have reported\nalterations alterations in the endometrium, ranging from dysregulation of immune\npathways to epigenetic factors (Hromadnikova  et al. , 2022;  Shi  et al. , 2025 ).\nNonetheless, while several studies have reported changes in the endometrial quality,\nit remains to be clarified whether such alterations compromise endometrial\ncompetence, the ability to support implantation and achieve a live birth.\nOne of the most widely discussed studies on this topic is the meta-analysis published\nin JAMA Network Open by  Paffoni  et\nal . (2024)  which evaluated live birth rates in women with\nendometriosis who received donor oocytes, as it provides robust data on endometrial\nreceptivity by excluding the potential confounding factor of impaired embryo quality\nin these patients. This systematic review and meta-analysis included data from four\nindividual studies (two prospective and two retrospective) as well as from two major\nIVF registries: the Human Fertilization and Embryology Authority (HFEA, UK) and the\nSociety for Assisted Reproductive Technology (SART, USA). In total, 7,212 donor\noocyte cycles derived from the studies were examined, in addition to 162,082 cycles\nreported by the registries (137,182 from SART and 24,900 from HFEA). The adjusted\nlive birth outcome showed a small, but statistically significant, difference in\npatients with endometriosis (OR, 0.89; 95% CI, 0.81-0.97), observed exclusively in\nthe registry data, not in the meta-analysis of prospective or retrospective studies.\nThe authors conclude that there appears to be a minimal reduction in live birth\nrates among recipients with a history of endometriosis undergoing ART cycles with\ndonor oocytes. They also suggest that a marginal impairment of uterine receptivity\nmay be present in women affected by endometriosis. However, whether this impairment\nis related to comorbidities or confounding factors remains unclear and should be\nfurther investigated in future studies.\nThese findings are consistent with those reported reported by  Bishop et al. (2021) , which showed no statistically significant\ndifferences in clinical outcomes following single euploid embryo transfer among\npatients with endometriosis, male factor infertility, and PGT-M cycles, as well as\nwith a recent meta-analysis on clinical outcomes in endometriosis patients\nundergoing IVF ( Qu  et al. ,\n2022 ). On the other hand, an interesting meta-analysis identified an\napproximately 12% reduction in live birth rates following ART specifically among\npatients with stage III-IV endometriosis, highlighting that the phenotypic\nexpression and clinical impact of the disease may vary according to its stage and\nsubtype ( Horton  et al. ,\n2019 ).\nRegarding cumulative live birth rates, when analyses control for confounding factors\nsuch as the number of oocytes retrieved and the number and quality of embryos\nobtained, it becomes more appropriate to assess the potential impact of\nendometriosis on endometrial receptivity. A recent matched cohort study, which\nincluded 100 women with endometriosis and 100 controls matched for age, as well as\nthe number and quality of blastocysts, reported comparable cumulative live birth\nrates between the groups ( Casalechi  et\nal. , 2023 ). These findings support the hypothesis that\nendometriosis does not significantly compromise endometrial receptivity in affected\nindividuals.\nThis apparent discrepancy between molecular alterations and preserved clinical\noutcomes may reflect a certain degree of endometrial resilience, in which\ncompensatory mechanisms maintain implantation capacity despite local disturbances.\nLikewise, it is plausible that compensatory molecular pathways or redundant\nmechanisms involved in implantation and early placentation mitigate the functional\nimpact of the transcriptomic and proteomic disturbances observed in\nendometriosis.\nDespite the lack of robust evidence supporting a negative impact of endometriosis on\nclinical pregnancy or live birth rates, a recent meta-analysis highlights that\nsevere forms of the disease (stage III-IV and deep endometriosis) represent\nsignificant risk factors for placenta previa and preterm birth ( Busnelli  et al ., 2024 ),\nsuggesting that the impact of endometriosis may manifest later in pregnancy.\n\nThe appropriate timing, indication, and type of treatment for endometriosis in\ninfertile patients remain topics of ongoing debate. Some authors have proposed\nstructured management approaches to guide clinical decision-making in this\npopulation ( Di Spiezio Sardo  et\nal. , 2025 ). In summary, for women under 35 years of age\nexperiencing pelvic pain, conservative surgical treatment may be considered, and if\nspontaneous pregnancy does not occur within one year postoperatively, IVF (with or\nwithout prior medical therapy) may be indicated. For women over 35 years of age with\npain, or for asymptomatic women, proceeding directly to IVF with possible\npre-treatment using medical therapy is generally recommended. Furthermore, in cases\nof repeated IVF failure, surgical intervention may be considered ( Di Spiezio Sardo  et al. ,\n2025 ).\nFor selected patients, hormonal or surgical treatment may precede IVF or embryo\ntransfer. GnRH agonists have demonstrated anti-inflammatory, anti-angiogenic, and\npro-apoptotic effects beyond their hypoestrogenic mechanism ( Khan  et al. , 2010 ), while progestins may\nimprove the endometrial environment by reducing inflammatory cytokines and oxidative\nstress ( Tamura  et al. ,\n2019 ). However, evidence remains inconsistent. The most recent Cochrane\nmeta-analysis, including eight RCTs, found low-certainty evidence and concluded that\nprolonged GnRH agonist pretreatment does not clearly improve pregnancy or live birth\nrates ( Georgiou  et al. ,\n2019 ). Similarly, a network meta-analysis of nine RCTs found no benefit of\nhormonal pretreatment before ovarian stimulation, with higher live birth rates\nobserved in women who did not receive pretreatment ( Riemma  et al. , 2025 ).\nConsistently, the ESHRE guideline states that neither hormonal nor surgical\ninterventions should be routinely used before IVF to improve live birth rates ( Becker  et al. , 2022 ). Surgery\nmay be considered only to alleviate pain or improve follicle accessibility in\nspecific cases, such as endometrioma or deep lesions. Overall, the absence of\nconsistent benefit from pre-IVF interventions reinforces the notion that\nendometriosis exerts a limited direct impact on ART outcomes.\n\nMost of the current evidence linking endometriosis and (in)fertility originates from\nART cycles, which may not fully represent physiological reproductive conditions.\nFurthermore, many studies reporting clinical pregnancy rates aggregate data from\nwomen attempting natural conception and those undergoing ART, across varying stages\nof endometriosis, with or without comorbidities such as adenomyosis, and under\nhighly heterogeneous treatment protocols, all factors that complicate the\ninterpretation of definitive conclusions.\nAlthough it is well established that endometriosis alters the reproductive tract\nmilieu and, consequently, the local microenvironment, the precise repercussions of\nthese alterations on gamete and endometrial function remain incompletely understood\n( Figure 2 ).\nFigure 2 Schematic representation of the possible mechanisms by which\nendometriosis affects reproductive outcomes in assisted reproductive\ntechnology (ART) at multiple levels. The upper panel depicts alterations\nin ovarian, oocyte, and endometrial quality, including hormonal\nimbalances, oxidative stress, apoptosis, mitochondrial and spindle\ndefects, and transcriptional dysregulation. The lower panel illustrates\nthe downstream consequences on ovarian reserve, embryo development, and\nclinical outcomes, such as reduced numbers of mature oocytes and embryos\nand compromised embryo developmental and implantation rates.\nSchematic representation of the possible mechanisms by which\nendometriosis affects reproductive outcomes in assisted reproductive\ntechnology (ART) at multiple levels. The upper panel depicts alterations\nin ovarian, oocyte, and endometrial quality, including hormonal\nimbalances, oxidative stress, apoptosis, mitochondrial and spindle\ndefects, and transcriptional dysregulation. The lower panel illustrates\nthe downstream consequences on ovarian reserve, embryo development, and\nclinical outcomes, such as reduced numbers of mature oocytes and embryos\nand compromised embryo developmental and implantation rates.\nUndeniably, endometriosis can lead to infertility when pelvic adhesions cause tubal\nobstruction or when severe pain interferes with sexual intercourse. In the context\nof ART. However, large-scale studies have not consistently demonstrated a\ndetrimental effect of endometriosis on reproductive competence, although more severe\nphenotypes (stages III-IV) may be associated with greater adverse outcomes.\nIn summary, until new and robust evidence emerges to challenge current assumptions,\nreasonable doubt persists regarding the true extent to which endometriosis\ninfluences fertility outcomes in IVF cycles. It may now be time to broaden the\ninvestigative lens from a micro-level focus on cellular quality to a more integrated\nperspective that also encompasses cellular competence. Future research should employ\nmatched-cohort designs that control for the type and stage of endometriosis, as well\nas for oocyte yield, to better isolate disease-specific effects. Ideally, these\nstudies should integrate molecular and clinical analyses, linking oocyte quality\nassessments with measures of developmental and clinical competence, such as live\nbirth and cumulative live birth rates. Moreover, studies using donor oocytes may\nhelp clarify whether endometrial receptivity is genuinely impaired in women with\nendometriosis. Collectively, such approaches may ultimately determine whether\nendometriosis compromises oocyte or embryonic competence and/or endometrial\nreceptivity, thereby providing a more comprehensive understanding of its true impact\non reproductive outcomes.","source_license":"public-domain-us","license_restricted":false}