{"paper_id":"746bb6f9-ac9e-4b35-a6f7-6285b4c4d8ba","body_text":"146\nCopyright© 2026 The Author(s). Published by Galenos Publishing House on behalf of Turkish Society of Obstetrics and Gynecology .\nThis is an open access article under the Creative Commons AttributionNonCommercial 4.0 International (CC BY-NC 4.0) License.\nTurk J Obstet Gynecol 2026;23(2):146-52\nClinical Investigation / Araştırma\nFollicular fluid cytokine and homocysteine profiles in \npoor ovarian responders with and without sonographic \nendometrioma: A comparative study\nSonografik endometrioması olan ve olmayan düşük over \nrezervli kadınlarda foliküler sıvı sitokin ve homosistein \nprofilleri: Karşılaştırmalı çalışma\n1Acıbadem Mehmet Ali Aydınlar University, Department of Molecular Biology and Genetics, İstanbul, Türkiye\n2Kütahya City Hospital, Kütahya, Türkiye\n3Acıbadem Maslak Hospital, Assisted Reproductive Technologies Unit, İstanbul, Türkiye\n4Acıbadem Labmed Clinical Laboratories, İstanbul, Türkiye\n5Koç University Hospital, Assisted Reproductive Technologies Unit, İstanbul, Türkiye\n6Acıbadem Mehmet Ali Aydınlar University, Department of Obstetrics and Gynecology, İstanbul, Türkiye\nCorresponding Author/Sorumlu Yazar: Prof. Yiğit Çakıroğlu, MD ,\nKoç University Hospital, Assisted Reproductive Technologies Unit, İstanbul, Türkiye\nE-mail: dryigit1@yahoo.com ORCID ID: orcid.org/0000-0002-2779-8599\nReceived/Geliş Tarihi: 08.04.2026 Accepted/Kabul Tarihi: 28.05.2026 Publication Date/Yayınlanma Tarihi: 04.06.2026\nCite this article as: Şanlı BE, Tığlı E, Özer Aslan İ, Yıldırım Saral N, Çakıroğlu Y, Tıraş B. Follicular fluid cytokine and homocysteine profiles in poor ovarian responders with and without \nsonographic endometrioma: a comparative study. Turk J Obstet Gynecol. 2026;23(2):146-52\n Bülent Erdem Şanlı1,  Esra Tığlı2,  İlke Özer Aslan3,  Neslihan Yıldırım Saral4,  Yiğit Çakıroğlu5, \n Bülent Tıraş3,6\nAbstract\nObjective: To compare follicular fluid (FF) cytokine and homocysteine profiles in women with poor ovarian response (POR) undergoing in vitro \nfertilization (IVF), with and without sonographic endometrioma, and to explore potential inflammatory alterations associated with endometrioma in \nthis population. \nMaterials and Methods:  This prospective comparative study was conducted among 60 women diagnosed with POR who were undergoing IVF \ntreatment. Participants were divided into two groups according to the presence of sonographic endometrioma: Group I included women without \nsonographic endometrioma (n=30) and Group II included women with sonographic endometrioma (n=30). FF samples were collected during oocyte \nretrieval and analyzed for inflammatory biomarkers. Concentrations of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, \ninterferon-α2 (IFN-α2), IFN-γ, tumor necrosis factor- α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and homocysteine were measured \nusing LEGENDplex multiplex assays and flow cytometry . Cytokine and homocysteine levels were compared between groups. \nResults: Most inflammatory cytokines, including IL-1β, IL-6, IL-8, IFN-γ, and MCP-1, showed lower levels in women with sonographic endometrioma \ncompared with women without sonographic endometrioma. In contrast, TNF- α and IL-33 levels tended to be higher in the endometrioma group. \nHomocysteine levels were also lower in women with sonographic endometriomas. However, none of the observed differences reached statistical \nsignificance. Overall, the findings suggested distinct, albeit non-significant, inflammatory trends in the FF microenvironment of women with POR \nand sonographic endometrioma.\nConclusion: Women with POR and sonographic endometrioma showed altered trends in FF inflammatory-marker profiles compared with women \nwithout sonographic endometrioma; however, these differences were not statistically significant. Since the absence of sonographic endometrioma does \nnot exclude endometriosis, the findings should be interpreted cautiously . Larger prospective studies that include IVF and assess embryological and \nreproductive outcomes are required to clarify the clinical significance of FF biomarkers in women with POR and endometrioma. \nKeywords: Endometrioma, poor ovarian response, follicular fluid, cytokines, homocysteine, IVF\nPRECIS: Women with poor ovarian response and sonographic endometrioma showed directional but non-significant differences in selected \nfollicular fluid cytokines. The findings are exploratory and require validation using in vitro fertilization outcomes.\nDOI: 10.4274/tjod.galenos.2026.14867\n\n147\nŞanlı et al. Endometrioma and follicular fluid in POR\n Turk J Obstet Gynecol 2026;23(2):146-52\nIntroduction\nEndometriosis is a chronic inflammatory condition \ncharacterized by the presence of endometrial-like tissue \noutside the uterus, affecting approximately 10-15% of women \nof reproductive age and up to 40% of infertile women (1,2). \nDespite significant advances in diagnostic imaging and \nsurgical treatment, the pathophysiology of endometriosis \nremains complex and multifactorial, involving hormonal, \nimmunological, and genetic factors(3-5).\nSeveral immunological abnormalities have been implicated \nin the development and progression of endometriosis, \nincluding altered macrophage activity , cytokine imbalance, \nand impaired natural killer cell function (6-8). The local \nperitoneal and follicular environment in affected individuals \nis often enriched with pro-inflammatory cytokines such as \ntumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), IL-8, \nand monocyte chemoattractant protein-1 (MCP-1), which \nmay contribute to abnormal folliculogenesis, impaired oocyte \nquality , and reduced implantation potential(9-13).\nThe follicular fluid (FF) is a key microenvironment \nsupporting oocyte development and maturation. It contains \na wide array of soluble factors—cytokines, growth factors, \nmetabolites—that mediate paracrine signaling and reflect \nboth systemic and local ovarian conditions(14). In women with \nendometriosis, the FF may exhibit a disrupted immunological \nmilieu, potentially compromising oocyte competence and \nembryo development during in vitro fertilization (IVF)(15).\nPoor ovarian response (POR) to controlled ovarian \nstimulation, defined by the Bologna criteria or more recently \nthe POSEIDON classification, presents an additional challenge \nin assisted reproductive technologies(16,17). Women with POR \noften show altered inflammatory and metabolic signaling \nin FF , with higher levels of oxidative stress markers and \nreduced concentrations of growth-promoting cytokines (18). \nThe coexistence of POR and endometriosis may further \nexacerbate this unfavorable follicular environment, although \nfew studies have examined this specific subgroup in detail.\nRecent studies suggest that evaluating FF cytokines and \nmetabolic markers such as homocysteine may offer insight \ninto the pathophysiology of oocyte competence, particularly \nin complex infertility cases (19,20). Homocysteine, a sulfur-\ncontaining amino acid involved in methylation pathways, has \nbeen linked to impaired follicular angiogenesis, mitochondrial \ndysfunction, and increased oxidative stress, all of which may \naffect oocyte and embryo quality(21).\nThe present study aims to compare the cytokine and \nhomocysteine profiles in FF from women with POR, both \nwith and without sonographically confirmed endometrioma. \nBy focusing on this underexplored intersection, we hope \nto identify immunological or metabolic differences that \nmay contribute to reduced fertility outcomes and may help \ngenerate hypotheses for individualized strategies in IVF .\nMaterials and Methods \nStudy Design and Participants\nThis prospective comparative study was conducted at the \nAssisted Reproductive Technologies Unit of Acıbadem Maslak \nHospital, İstanbul, Türkiye, as an exploratory biomarker \nanalysis in women with POR comparing patients with and \nwithout sonographic endometrioma. No single primary \nbiomarker was predefined; a predefined inflammatory \nmarker panel and homocysteine levels were evaluated to \ngenerate hypotheses. A total of 60 infertile women diagnosed \nwith POR were recruited and divided into two groups: those \nÖz\nAmaç: Bu çalışmanın amacı, in vitro fertilizasyon (IVF) tedavisi gören düşük over rezerv (DOR) tanılı kadınlarda, sonografik endometrioma varlığına \ngöre follikül sıvısı (FS) sitokin ve homosistein profillerini karşılaştırmak ve endometrioma ile ilişkili olası enflamatuvar değişiklikleri araştırmaktır. \nGereç ve Yöntemler:  Bu prospektif karşılaştırmalı çalışmaya IVF tedavisi gören ve DOR tanısı bulunan toplam 60 kadın dahil edildi. Katılımcılar \nsonografik endometrioma varlığına göre iki gruba ayrıldı: Grup I, sonografik endometrioması olmayan kadınlardan (n=30); Grup II ise sonografik \nendometrioması bulunan kadınlardan (n=30) oluştu. FS örnekleri oosit toplama işlemi sırasında elde edildi ve inflamatuvar biyobelirteçler açısından \nanaliz edildi. İnterlökin-1β (IL-1β), IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon- α2 (IFN-α2), IFN-γ, tümör nekroz faktörü-α \n(TNF-α), monosit kemoatraktan protein-1 (MCP-1) ve homosistein düzeyleri LEGENDplex multipleks analiz yöntemi ve akım sitometrisi kullanılarak \nölçüldü. Sitokin ve homosistein düzeyleri gruplar arasında karşılaştırıldı. \nBulgular: IL-1β, IL-6, IL-8, IFN- γ ve MCP-1 dahil olmak üzere çoğu enflamatuvar sitokin düzeyi, sonografik endometrioması bulunan kadınlarda, \nsonografik endometrioması olmayan kadınlara kıyasla daha düşük bulundu. Buna karşılık TNF- α ve IL-33 düzeyleri endometrioma grubunda daha \nyüksek eğilim gösterdi. Homosistein düzeyleri de sonografik endometrioması bulunan kadınlarda daha düşük saptandı. Ancak gözlenen farklılıkların \nhiçbiri istatistiksel anlamlılığa ulaşmadı. Genel olarak bulgular, DOR ve sonografik endometrioması bulunan kadınların FS mikroçevresinde belirgin \nancak istatistiksel olarak anlamlı olmayan inflamatuvar eğilimler olduğunu düşündürdü. \nSonuç: DOR ve sonografik endometrioması bulunan kadınlarda, sonografik endometrioması olmayan kadınlara kıyasla FS enflamatuvar belirteç \nprofillerinde değişmiş eğilimler gözlenmiş, ancak istatistiksel olarak anlamlı farklılık saptanmamıştır. Sonografik endometrioma yokluğunun \nendometriozisi dışlamadığı göz önünde bulundurularak bulgular dikkatli yorumlanmalıdır. IVF , embriyolojik ve üreme sonuçlarını içeren daha geniş \nprospektif çalışmalara, DOR ve endometriomalı kadınlarda FS biyobelirteçlerinin klinik önemini daha iyi açıklığa kavuşturmak için ihtiyaç vardır.\nAnahtar Kelimeler: Endometrioma, düşük over rezervi, foliküler sıvı, sitokinler, homosistein, IVF\n\n148\nŞanlı et al. Endometrioma and follicular fluid in POR\nTurk J Obstet Gynecol 2026;23(2):146-52\nwith a sonographically confirmed diagnosis of endometrioma \n(n=30) and those without (n=30) (Figure 1).  This was a \npilot exploratory study . No a priori sample size calculation \nwas performed. The target sample size of 30 per group was \ndetermined based on feasibility within the study period. All \nparticipants had a history of infertility of at least one year and \nat least one functional ovary . \nInclusion criteria followed the POSEIDON classification \n[Groups 3 and 4: antral follicle count (AFC) <5 and anti-\nMüllerian hormone (AMH) <1.2 ng/mL, stratified by age]\n(17) . Exclusion criteria included severe male factor infertility \n(azoospermia, cryptozoospermia), congenital or acquired \nuterine anomalies, polycystic ovary syndrome, recurrent \npregnancy loss, and recurrent implantation failure.\nEndometriosis Characterization:  In the endometrioma \ngroup, endometriomas were identified using standard \ntransvaginal ultrasound criteria (thick-walled, homogeneous, \nlow-level internal echoes). Where available, endometrioma \nsize (maximum diameter, mm) and laterality (unilateral/\nbilateral) were abstracted from clinical records. Deep \ninfiltrating endometriosis was not systematically assessed. \nPrior endometriosis surgery and medical/hormonal treatments \nwere recorded where available. The  duration of infertility \n(months) was recorded at enrollment. All assessments were \nperformed by experienced clinicians at the beginning of the \novarian stimulation cycle.\nOvarian Stimulation Protocol and Oocyte Retrieval\nAll participants underwent a controlled ovarian \nhyperstimulation protocol. Stimulation was initiated on \ndays 2-4 of the menstrual cycle using recombinant follicle-\nstimulating hormone (FSH; 150-300 IU daily), with or without \nthe addition of human menopausal gonadotropin, based on \nclinical judgment. Serial transvaginal ultrasonography and \nserum estradiol (E2) measurements guided dose adjustments.\nFinal oocyte maturation was triggered with 6500 IU human \nchorionic gonadotropin in combination with 0.2 mg \ngonadotropin-releasing hormone agonist when at least one \nfollicle reached ≥18 mm or three follicles were ≥17 mm in \ndiameter. Oocyte retrieval was performed 36 hours post-\ntrigger under sedation.\nFF Collection and Analysis\nImmediately following oocyte retrieval, FF was aspirated \nfrom the first accessible ≥18 mm follicle prior to any flushing. \nWhen multiple mature follicles were present, only the first \naspirated follicle was used; follicles were not pooled. Tubes \nwere inspected immediately; samples with visible blood \ncontamination (reddish discoloration, hemolysis) were \ndiscarded. Cumulus-oocyte complexes were separated, and \nthe remaining FF was centrifuged at 450 g for 5 minutes at \nroom temperature. The supernatant was aliquoted and stored \nat -20 °C within 60 minutes of retrieval; a single freeze -thaw \ncycle was permitted for analysis, and no aliquot underwent \nmore than one cycle. Assays were performed at the Acıbadem \nLabmed Clinical Laboratory using the LEGENDplex Human \nInflammation Panel 1 (BioLegend, Germany), a bead-based \nmultiplex flow cytometry assay , on a BD FACSCanto II flow \ncytometer. Standard curves and controls were run on each \nplate. Analysts and laboratory personnel were blinded to \nclinical data and group assignment. Concentrations of IL-1β, \nIL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, \nIFN-α2, IFN- γ, TNF- α, MCP-1, and homocysteine were \nmeasured and analyzed with LEGENDplex Data Analysis \nSoftware. \nEthical Approval\nThe study protocol was approved by the Institutional Review \nBoard and the Ethics Committee of Acıbadem University \n(approval number: 2023-03/59, date: 24.02.2023). Written \ninformed consent was obtained from all participants prior to \nenrollment. This study was conducted in accordance with the \nprinciples of the “Declaration of Helsinki-Ethical Principles \nfor Medical Research Involving Human Participants”.\nStatistical Analysis\nCytokine and homocysteine distributions were assessed using \nthe Shapiro-Wilk test and visual inspection (histograms and \nQ-Q plots). Given the typical right skewness of the data, we \nalso analyzed log10-transformed values. Continuous variables \nare presented as mean±SD and, where appropriate, median \ninterquartile range (IQR). Between-group comparisons used \nindependent-samples t-tests when assumptions were met, \nand Mann-Whitney U tests otherwise. Potential outliers \nwere screened visually using box plots and the IQR rule; \nFigure 1. The flowchart of the study\nIVF: In vitro fertilization, POR: Poor ovarian response\n\n149\nŞanlı et al. Endometrioma and follicular fluid in POR\n Turk J Obstet Gynecol 2026;23(2):146-52\nsensitivity checks did not change the inference. Alongside \np-values, we interpret the direction of effects using two-sided \n95% confidence intervals where applicable. Given multiple \nbiomarkers, analyses were treated as exploratory; we did not \nclaim statistical significance after adjustment for multiplicity , \nand we interpreted findings in light of the increased risk of \nfalse positives.\nResults\nA total of 60 women with POR undergoing IVF were included \nin the study (Figure 1). The mean age of patients in the POR \nwith sonographic endometrioma group was slightly higher \nthan the POR without sonographic endometrioma group \n(37.9±5.8 vs. 35.1±5.1 years, respectively; p=0.06), although \nthe difference was not statistically significant. Partner age, \nbody mass index, and baseline ovarian reserve markers, \nincluding FSH, AMH, and AFC were comparable between \ngroups. A higher number of previous IVF cycles was observed \namong patients with POR with sonographic endometrioma, \nbut again, this did not reach statistical significance (3.0±3.1 vs. \n1.8±2.1; p=0.07). Demographic and baseline characteristics \nare summarized in Table 1.\nRegarding the FF analysis, homocysteine levels were lower in \nthe POR with sonographic endometrioma group compared \nto the POR without sonographic endometrioma (1.65±1.53 \nvs. 4.85±4.14 μmol/L), although the difference was not \nstatistically significant (p=0.277).\nAmong the 13 inflammatory markers analyzed, most cytokine \nlevels—including IL-1 β, IFN- α2, IFN- γ, MCP-1, IL-6, IL-8, \nIL-10, IL-12p70, IL-17A, IL-18, and IL-23—were lower in the \nPOR group with sonographic endometrioma than in women \nwithout sonographic endometrioma. None of these differences \nreached statistical significance (p>0.05 for all comparisons). \nInterestingly , two markers—TNF- α and IL-33—were slightly \nelevated in the POR with sonographic endometrioma \ngroup, though again without statistical significance \n(TNF-α: 10.19±17.38 vs. 6.54±8.72 pg/mL, p=0.761; IL-33: \n47.43±72.82 vs. 40.97±61.62 pg/mL, p=0.912).\nAcross all 14 biomarkers, no between-group differences \nreached conventional statistical significance. Given right-\nskewed distributions and multiple comparisons, we \nconducted complementary nonparametric tests and log10-\ntransformed analyses; both approaches yielded the same \ninference. Accordingly , we interpret all observed patterns as \ndirectional and exploratory rather than definitive. Consistent \nwith this approach, we did not claim statistical significance \nfor any isolated trend after accounting for multiplicity . \nDespite numerically large mean differences for some \nbiomarkers (e.g., MCP-1, IL-6, IL-18, and homocysteine), \nwide variances, skewed distributions, and the modest sample \nsize likely reduced statistical power, yielding non-significant \np-values; non-parametric and log-transformed analyses led to \nthe same inference.\nA full comparison of cytokine and homocysteine levels in FF \nbetween the two groups is presented in Table 2.\nAlthough none of the measured biomarkers showed \nstatistically significant differences, the trend toward elevated \nTNF-α and IL-33 in the POR with sonographic endometrioma \ngroup may be consistent with localized inflammatory \nsignaling; however, given the non-significant and imprecise \nestimates, these observations are exploratory . Conversely , the \nlower levels of most other cytokines, including IL-6 and MCP-\n1, suggest a potentially suppressed or dysregulated immune \nresponse in the follicular environment of these patients.\nDiscussion\nThis exploratory study compared FF cytokines and \nhomocysteine between women with POR who had sonographic \nendometrioma and those who did not. Across 14 biomarkers, \nno between-group differences reached conventional statistical \nsignificance. Observed patterns were directional: TNF- α and \nIL-33 tended to be higher, while several cytokines tended to \nbe lower in the endometrioma group,  and should be regarded \nas hypothesis-generating.\nTNF-α and IL-33 trends align with proposed inflammatory \nmechanisms in endometriosis; however, the estimates \nTable 1. Socio-demographic parameters (values are mean ± SD unless otherwise specified)\nPOR without sonographic \nendometrioma (n=30)\nPOR with sonographic \nendometrioma (n=30) p-value\nAge (years) 35.1±5.1 37.9±5.8 0.06\nPartner’s age (years) 38.3±6.3 38.1±6.4 0.90\nBMI (kg/m2) 24.7±5.3 25.6±4.8 0.50\nFSH (mIU/mL) 17.7±14.3 14.6±9.9 0.32\nAMH (ng/mL) 0.47±0.27 0.35±0.31 0.12\nAFC (n) 3.1±1.5 2.9±1.5 0.66\nNumber of previous IVF trials (n) 1.8±2.1 3.0±3.1 0.07\nValues are mean ± SD. Units: years (age, partner’s age); kg/m 2 (BMI); mIU/mL (FSH); ng/mL (AMH); count (AFC, previous IVF trials)  \nPOR: Poor ovarian response, BMI: Body mass index, FSH: Follicle-stimulating hormone, AMH: Anti-Müllerian hormone, AFC: Antral follicle count, SD: Standard deviation, IVF: In \nvitro fertilization\n\n150\nŞanlı et al. Endometrioma and follicular fluid in POR\nTurk J Obstet Gynecol 2026;23(2):146-52\nwere imprecise and not statistically significant; therefore, \nthey should not be interpreted as evidence of a distinct \ninflammatory profile in POR with endometrioma.\nTNF-α has been widely implicated in the inflammatory \ncascade associated with endometriosis and has been shown to \nimpair oocyte maturation and granulosa cell function (8,12,19). \nIL-33, a member of the IL-1 cytokine family , has gained \nincreasing attention for its role in tissue remodeling and \nimmune activation in chronic inflammatory diseases (20). \nOur findings align with these observations and suggest a \npotentially heightened inflammatory state within the  follicles \nof women with both POR and endometriomas.\nIn contrast, levels of IL-6, IL-1 β, IL-8, and MCP-1 \nwere generally lower in the endometrioma group. This \ncounterintuitive finding may indicate an immunological \nadaptation or exhaustion resulting from chronic local \ninflammation(20). Previous studies have suggested that the \nfollicular immune microenvironment in endometriosis may \nvary depending on disease stage, ovarian reserve, or previous \ntreatment history , all of which could influence cytokine \nexpression profiles(11,18).\nImportantly , none of the between-group differences reached \nconventional statistical significance, and the estimates were \nimprecise, with wide confidence intervals. Given skewed \ndistributions and multiple biomarker comparisons, these \nanalyses are best considered exploratory . Accordingly , \nwe refrain from inferring a distinct inflammatory profile \nand instead interpret the observed patterns as directional \nsignals requiring confirmation in larger, outcome-linked \ncohorts. We note that several large numerical differences \nwere accompanied by wide standard deviations and \nskewness, which, together with the modest sample size, limit \nstatistical power. The concordance of non-parametric and \nlog-transformed analyses supports the inference that these \nare directional, non-significant trends.\nFF homocysteine levels were also lower in the POR with \nendometrioma group. Elevated homocysteine is typically \nconsidered a negative factor in IVF due to its association with \noxidative stress, mitochondrial dysfunction, and impaired \nmethylation capacity(21,22). The reduced levels in our cohort \nmay reflect an altered metabolic phenotype associated with \nendometriosis or differences in folate metabolism, although \nthe clinical significance remains unclear.\nIn addition to cytokine imbalance, alterations in FF \ncomposition—including amino acids, lipids, and oxidative \nstress markers—have been shown to significantly affect \noocyte competence and embryo development (14). Recent \napproaches using metabolomics support the notion that \nFF is a dynamic, integrative reflection of both local ovarian \nphysiology and systemic health, making it a promising focus \nfor personalized IVF strategies(14).\nOur results are partially consistent with those of Yland et \nal.(22), who reported differential cytokine patterns in the FF \nof endometriosis patients, including increased IL-15 and IL-\n13 and decreased IFN- γ and TNF- α. However, discrepancies \nmay be due to population differences, as their study included \nTable 2. Comparison of follicular fluid cytokine and homocysteine levels between groups\nPOR without sonographic endometrioma \n(n=30) mean ± SD\nPOR with sonographic endometrioma \n(n=30) mean ± SD p-value\nHomocysteine (μmol/L) 4.85±4.14 1.65±1.53 0.277\nIL-1β (pg/mL) 34.70±32.12 4.37±4.59 0.181\nIFN-α2 (pg/mL) 1.44±1.16 0.72±1.25 0.509\nIFN-γ (pg/mL) 34.58±31.64 11.10±12.45 0.298\nTNF-α (pg/mL) 6.54±8.72 10.19±17.38 0.761\nMCP-1 (pg/mL) 895.87±625.14 195.37±193.56 0.137\nIL-6 (pg/mL) 26.86±7.54 8.57±13.91 0.116\nIL-8 (pg/mL) 1477.26±694.62 756.85±1310.90 0.448\nIL-10 (pg/mL) 4.67±3.79 1.34±2.32 0.264\nIL-12p70 (pg/mL) 1.10±0.69 0.23±0.03 0.095\nIL-17A (pg/mL) 3.41±5.36 0.21±0.22 0.360\nIL-18 (pg/mL) 326.61±141.34 94.07±124.85 0.100\nIL-23 (pg/mL) 1.80±2.11 0.58±0.00 0.374\nIL-33 (pg/mL) 40.97±61.62 47.43±72.82 0.912\nCytokine symbols are standardized as IL-1β, IFN-γ, TNF-α, and MCP-1. Values are mean ± SD. Units are pg/mL for cytokines and μmol/L for homocysteine. Analyses were treated as \nexploratory given multiple biomarker comparisons. Complementary non-parametric tests and log10-transformed analyses yielded consistent inferences\nPOR: Poor ovarian response, IL: Interleukin, IFN: Interferon, TNF: Tumor necrosis factor, MCP: Monocyte chemoattractant protein, SD: Standard deviation\n\n151\nŞanlı et al. Endometrioma and follicular fluid in POR\n Turk J Obstet Gynecol 2026;23(2):146-52\nwomen with normal ovarian reserve, whereas our cohort \nconsisted exclusively of POR patients. The coexistence of \nendometrioma and poor ovarian reserve likely contributes \nto a unique immunometabolic profile that warrants further \ninvestigation. \nImportantly , none of the between-group differences reached \nconventional statistical significance, and estimates were \nimprecise with wide confidence intervals. Given skewed \ndistributions and multiple biomarker comparisons, these \nanalyses are best considered exploratory . Accordingly , \nwe refrain from inferring a distinct inflammatory profile \nand instead interpret the observed patterns as directional \nsignals that require confirmation in larger, outcome-linked \ncohorts. We note that several numerically large differences \nwere accompanied by wide standard deviations and \nskewness, which, together with the modest sample size, limit \nstatistical power. The concordance of non-parametric and \nlog-transformed analyses supports the inference that these \nare directional but non-significant trends. \nWe did not collect embryological or clinical IVF outcomes \n(e.g., MII rate, fertilization, blastulation, clinical pregnancy), \nwhich precludes correlating FF markers with treatment \nsuccess in this cohort.\nPotential confounders merit consideration. The \nendometrioma group was slightly older and had undergone \nmore prior IVF cycles, which may influence ovarian response \nand FF composition. Protocol-related factors (e.g., total \ngonadotropin dose, trigger-day E2, and follicle counts) can \nalso modulate biomarker levels. In this exploratory dataset, \nrobust multivariable adjustment was not feasible; therefore, \nwe interpret directional patterns with these potential \nconfounders in mind and recommend adjusted analyses in \nlarger cohorts.\nTaken together, these non-significant directional findings \nwarrant confirmation in larger, well-phenotyped cohorts that \nincorporate standardized IVF and pregnancy outcomes and, \nwhere possible, detailed endometriosis staging.\nStudy Limitations\nThis study has several limitations. First, group allocation \nrelied on the presence of a sonographic endometrioma; the \nabsence of endometrioma does not exclude endometriosis, \nand occult disease may be present in controls. We did not \nsystematically stage endometriosis or quantify lesion burden \nbeyond the presence of a sonographic endometrioma. Data on \nendometrioma size, laterality , and prior surgical or medical \ntherapy were incomplete, which may have introduced \nheterogeneity . \nSecond, the sample size is modest, increasing imprecision and \nthe risk of type II error, particularly across multiple biomarker \ncomparisons. The modest sample size, in the absence of an a \npriori power calculation, likely limited our ability to detect \nsmall-to-moderate effects. \nThird, cytokine distributions are typically skewed. Although \nwe used complementary non-parametric and log-transformed \nanalyses, residual distributional issues cannot be fully \nexcluded. \nMoreover, multiple biomarker comparisons increase the risk \nof false-positive findings; therefore, we treated the analyses \nas exploratory and claims of statistical significance without \nadjustment for multiplicity . Residual pre-analytical variability \n(e.g., subtle blood contamination, storage time, and freeze-\nthaw effects)cannot be fully excluded despite standardized \nhandling. In addition, residual confounding by age, prior IVF \nexposure, and stimulation variables cannot be excluded.\nFourth, IVF outcome parameters (e.g., MII rate, fertilization, \nblastulation, clinical pregnancy) were not collected or \nreported, which limits clinical interpretability of the findings. \nFuture  larger studies should integrate standardized assay \nperformance metrics, correlate FF markers with oocyte, \nembryo, and pregnancy outcomes, and, where possible, \ninclude surgical staging or lesion burden to refine phenotype \ndefinitions.\nDespite these limitations, our findings underscore the \nimportance of considering both immunological and metabolic \nmarkers when evaluating the follicular microenvironment in \ncomplex infertility cases. Future research with larger cohorts \nand functional assays may help elucidate the mechanisms \nlinking endometriosis, ovarian reserve, and follicular health.\nConclusion \nIn this exploratory study of women with POR undergoing \nIVF , FF cytokine and homocysteine levels did not differ \nsignificantly between patients with and without sonographic \nendometrioma. Non-significant trends toward higher \nTNF-α and IL-33 levels and lower homocysteine levels in \nthe endometrioma group should be considered hypothesis-\ngenerating. Confirmation in larger, well-phenotyped cohorts \nincorporating standardized embryological and pregnancy \noutcomes is needed before  clinical inferences can be drawn.\nEthics \nEthics Committee Approval:  The study protocol was \napproved by the Institutional Review Board and the Ethics \nCommittee of Acıbadem University (approval number: 2023-\n03/59, date: 24.02.2023).\nInformed Consent: Written informed consent was obtained \nfrom all participants prior to enrollment.\nFootnotes \nAuthorship Contributions \nSurgical and Medical Practices: B.E.Ş., Concept: B.E.Ş., E.T., \nN.Y.S., Y.Ç., B.T., Design: B.E.Ş., Y.Ç., B.T., Data Collection \nor Processing: B.E.Ş., E.T., İ.Ö.A., N.Y.S., Analysis or \nInterpretation: B.E.Ş., E.T., N.Y.S., Y.Ç., Literature Search: \nB.E.Ş., İ.Ö.A., Y.Ç., Writing: B.E.Ş., İ.Ö.A., Y.Ç., B.T.\n\n152\nŞanlı et al. Endometrioma and follicular fluid in POR\nTurk J Obstet Gynecol 2026;23(2):146-52\nConflict of Interest:  No conflict of interest was declared by \nthe authors. \nFinancial Disclosure:  This work has been supported by \nAcıbadem Mehmet Ali Aydınlar University Scientific Research \nProjects Coordination Unit under grant number TSA-2023-\n99.\nReferences\n1. Mehedintu C, Plotogea MN, Ionescu S, Antonovici M. Endometriosis \nstill a challenge. J Med Life. 2014;7:349-57.\n2. Parasar P , Ozcan P , Terry KL. Endometriosis: epidemiology , diagnosis \nand clinical management. Curr Obstet Gynecol Rep. 2017;6:34-41.\n3. Rocha AL, Reis FM, Taylor RN. Angiogenesis and endometriosis. \nObstet Gynecol Int. 2013;2013:859619.\n4. Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis \nof endometriosis. Int J Reprod Med. 2014;2014:179515.\n5. Vercellini P , Vigano P , Somigliana E, Fedele L. Endometriosis: \npathogenesis and treatment. Nat Rev Endocrinol. 2014;10:261-75.\n6. 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