Serum Adipokines as Predictive Biomarkers of Endometrial Receptivity in Women with Unexplained Infertility: A Cross-Sectional Study
Adipokines as Biomarkers of Endometrial Receptivity
DOI:
https://doi.org/10.69750/dmls.03.06.0213Keywords:
adiponectin, endometrial receptivity, leptin, resistin, unexplained infertilityAbstract
Background: Even when fertility tests are normal, there can be undetectable metabolic, vascular, and inflammatory changes that affect the receptivity of the endometrium.
Objective: To determine the association of serum leptin, adiponectin, resistin, and the leptin-to-adiponectin ratio with ultrasonographic indicators of endometrial receptivity in women with unexplained infertility.
Methods: This cross-sectional analytical study included 80 women with unexplained infertility at Ghurki Trust Teaching Hospital, Lahore, from January to December 2025. During the mid-luteal implantation window, serum leptin, adiponectin, and resistin were determined by enzyme-linked immunosorbent assays. Transvaginal ultrasound and Doppler were used to measure endometrial thickness, endometrial volume, subendometrial vascularity, and PI of the uterine artery. Logistic regression and receiver operating characteristic analyses were carried out.
Results: A total of 80 women had a receptive and non-receptive endometrial phenotype in 49 (61.3%) and 31 (38.8%) patients, respectively. The non-receptive group had higher leptin, resistin, leptin/adiponectin ratio, body mass index, and insulin resistance but lower adiponectin (all p<0.05). Leptin, adiponectin, resistin, and the leptin-to-adiponectin ratio were each independently associated with non-receptivity after adjusting for age, BMI, duration of infertility, and insulin resistance. The leptin/adiponectin ratio was the best individual discriminatory test with an AUC of 0.86, a sensitivity of 80.6%, and a specificity of 79.6%.
Conclusions: There was a strong association between an adverse serum adipokine profile and impaired ultrasonographic endometrial receptivity. The leptin to adiponectin ratio can be viewed as an easy-to-use non-invasive biomarker, but further prospective validation with implantation and live-birth outcomes is needed before its routine clinical use in the assessment, counselling, and treatment planning of infertile patients.
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Tang F, Wang W, Wang L, Wang Y, Xie P, Fang Y, et al. Obesity reduces endometrial receptivity by downregulating the Ob-Rb/STAT-3 signaling pathway in women and female mice. J Endocr Soc. 2026;10(2):bvaf220. doi:10.1210/jendso/bvaf220.
Li J, Liu H, Lim J, Xing H, Chen Y, Yang S, et al. Molecular and biological markers for assessing endometrial receptivity in infertile women: a narrative review. J Int Med Res. 2025;53(4):3000605251328893. doi:10.1177/03000605251328893.
Sarankhuu BE, Jeon HJ, Jeong DU, Park SR, Kim TH, Lee SK, et al. Adiponectin receptor 1 regulates endometrial receptivity via the adenosine monophosphate-activated protein kinase/E-cadherin pathway. Mol Med Rep. 2024;30(4):184. doi:10.3892/mmr.2024.13308.
Ouyang Y, Peng Y, Mao Y, Zheng M, Gong F, Li Y, et al. An endometrial receptivity scoring system evaluated by ultrasonography in patients undergoing frozen-thawed embryo transfer: a prospective cohort study. Front Med (Lausanne). 2024;11:1354363. doi:10.3389/fmed.2024.1354363.
Hiraoka T, Osuga Y, Hirota Y. Current perspectives on endometrial receptivity: a comprehensive overview of etiology and treatment. J Obstet Gynaecol Res. 2023;49(10):2397-2409. doi:10.1111/jog.15759.
Wu J, Sheng J, Wu X, Wu Q. Ultrasound-assessed endometrial receptivity measures for the prediction of in vitro fertilization-embryo transfer clinical pregnancy outcomes: a meta-analysis and systematic review. Exp Ther Med. 2023;26(3):453. doi:10.3892/etm.2023.12152.
Guideline Group on Unexplained Infertility, Romualdi D, Ata B, Bhattacharya S, Bosch E, Costello M, et al. Evidence-based guideline: unexplained infertility. Hum Reprod. 2023;38(10):1881-1890. doi:10.1093/humrep/dead150.
Galio L, Bernet L, Rodriguez Y, Fourcault C, Dieudonné MN, Pinatel H, et al. The effect of obesity on uterine receptivity is mediated by endometrial extracellular vesicles that control human endometrial stromal cell decidualization and trophoblast invasion. J Extracell Biol. 2023;2(7):e103. doi:10.1002/jex2.103.
Qin L, Sitticharoon C, Petyim S, Keadkraichaiwat I, Sririwichitchai R, Maikaew P, et al. A longitudinal study of the relationship of adiponectin with reproduction in infertile women undergoing IVF/ICSI treatment, and an experimental study in human granulosa cells. Life (Basel). 2023;13(4):994. doi:10.3390/life13040994.
Li R, Qiu X, Chen XF, He M, Wang W, Qiao J, et al. Effects of hysterosalpingo-contrast sonography examination on endometrial receptivity among women with unexplained infertility. Arch Gynecol Obstet. 2022;306(3):893-900. doi:10.1007/s00404-022-06620-2.
Sun B, Yeh J. Non-invasive and mechanism-based molecular assessment of endometrial receptivity during the window of implantation: current concepts and future prospective testing directions. Front Reprod Health. 2022;4:863173. doi:10.3389/frph.2022.863173.
Chen P, Jia R, Liu Y, Cao M, Zhou L, Zhao Z. Progress of adipokines in the female reproductive system: a focus on polycystic ovary syndrome. Front Endocrinol (Lausanne). 2022;13:881684. doi:10.3389/fendo.2022.881684.
Neykova K, Tosto V, Giardina I, Tsibizova V, Vakrilov G. Endometrial receptivity and pregnancy outcome. J Matern Fetal Neonatal Med. 2022;35(13):2591-2605. doi:10.1080/14767058.2020.1787977.
Jafari-Gharabaghlou D, Vaghari-Tabari M, Oghbaei H, Lotz L, Zarezadeh R, Rezaei YR, et al. Role of adipokines in embryo implantation. Endocr Connect. 2021;10(11):R267-R278. doi:10.1530/EC-21-0288.
Bellver J, Marín C, Lathi RB, Murugappan G, Labarta E, Vidal C, et al. Obesity affects endometrial receptivity by displacing the window of implantation. Reprod Sci. 2021;28(11):3171-3180. doi:10.1007/s43032-021-00631-1.
Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril. 2020;113(2):305-322. doi:10.1016/j.fertnstert.2019.10.014.
Galgani M, Insabato L, Calì G, Della Gatta AN, Mirra P, Papaccio F, et al. Regulatory T cells, inflammation, and endoplasmic reticulum stress in women with defective endometrial receptivity. Fertil Steril. 2015;103(6):1579-1586.e1. doi:10.1016/j.fertnstert.2015.03.014.
El-Mazny A, Abou-Salem N, Elshenoufy H. Doppler study of uterine hemodynamics in women with unexplained infertility. Eur J Obstet Gynecol Reprod Biol. 2013;171(1):84-87. doi:10.1016/j.ejogrb.2013.08.026.
Takemura Y, Osuga Y, Yamauchi T, Kobayashi M, Harada M, Hirata T, et al. Expression of adiponectin receptors and its possible implication in the human endometrium. Endocrinology. 2006;147(7):3203-3210. doi:10.1210/en.2005-1510.
Cervero A, Horcajadas JA, Martín J, Pellicer A, Simón C. The leptin system during human endometrial receptivity and preimplantation development. J Clin Endocrinol Metab. 2004;89(5):2442-2451. doi:10.1210/jc.2003-032127.
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