{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:31:58Z","timestamp":1789061518035,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objectives: To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Methods: Fifty-eight patients aged 23\u201334 who were planned to have intracytoplasmic sperm injection due to clomiphene citrate-resistant PCOS were included in the study. Participants were divided into two groups according to whether they used metformin or not. While 30 of 58 PCOS patients were using short-term metformin in combination with controlled ovarian stimulation, 28 PCOS patients were not using metformin. Metformin was started in the mid-luteal period and continued until the day before oocyte retrieval at 850 mg twice daily. To determine FF-NF-kB, TAS, TOS and OSI values, a dominant follicle \u226517\u201318 mm in diameter was selected for aspiration. Results: The number of mature follicles and fertilization rates of the metformin group were significantly higher than those not taking metformin. FF-TOS and OSI of the metformin group were significantly lower than those of the group not receiving metformin. Patients receiving metformin had higher FF-TAS than the group not receiving metformin. FF-NF-kB levels of the metformin group were significantly lower than the group not receiving metformin. Insulin resistance, FF-NF-kB and FF-TOS were negatively correlated with the number of mature oocytes. FF-TAS was positively correlated with the number of oocytes. Conclusions: Short-term metformin treatment in clomiphene-resistant PCOS improves the number of mature follicles and fertilization rates by regulating the intra-follicle redox balance.<\/jats:p>","DOI":"10.3390\/diagnostics14192215","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T06:00:57Z","timestamp":1728021657000},"page":"2215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Short-Term Metformin Therapy in Clomiphene Citrate Resistant PCOS Patients Improves Fertility Outcome by Regulating Follicular Fluid Redox Balance: A Case-Controlled Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7183-0026","authenticated-orcid":false,"given":"Mustafa","family":"Tas","sequence":"first","affiliation":[{"name":"Kayseri Ac\u0131badem Hospital IVF-Unit, Kayseri 38030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"ref_1","first-page":"CD006105","article-title":"Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome","volume":"12","author":"Tso","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/j.fertnstert.2005.01.096","article-title":"Phenotypic spectrum of polycystic ovary syndrome: Clinical and biochemical characterization of the three major clinical subgroups","volume":"83","author":"Chang","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1093\/humrep\/dew268","article-title":"A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: A randomised placebo-controlled trial","volume":"31","author":"Jacob","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejogrb.2009.11.017","article-title":"IVF outcome in women with PCOS, PCO and normal ovarian morphology","volume":"149","author":"Swanton","year":"2010","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Thessaloniki ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group (2008). Consensus on infertility treatment related to polycystic ovary syndrome. Fertil. Steril., 89, 505\u2013522.","DOI":"10.1016\/j.fertnstert.2007.09.041"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.rbmo.2011.09.017","article-title":"Meta-analysis of GnRH antagonist protocols: Do they reduce the risk of OHSS in PCOS?","volume":"24","author":"Pundir","year":"2012","journal-title":"Reprod. Biomed. Online"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1016\/j.fertnstert.2010.03.077","article-title":"Fertility treatment in women with polycystic ovary syndrome: A decision analysis of different oral ovulation induction agents","volume":"94","author":"Jungheim","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1530\/EJE-09-0733","article-title":"Metformin: An old medication of new fashion: Evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome","volume":"162","author":"Christakou","year":"2010","journal-title":"Eur. J. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/S0015-0282(99)00208-3","article-title":"Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome","volume":"72","author":"Ditto","year":"1999","journal-title":"Fertil. Steril."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1210\/endrev\/bnaa023","article-title":"Cellular and Molecular Mechanisms of Metformin Action","volume":"42","author":"LaMoia","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liu, Y., Liu, H., Li, Z., Fan, H., Yan, X., Liu, X., Xuan, J., Feng, D., and Wei, X. (2021). The Release of Peripheral Immune Inflammatory Cytokines Promote an Inflammatory Cascade in PCOS Patients via Altering the Follicular Microenvironment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.685724"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod., 19, 41\u201347.","DOI":"10.1093\/humrep\/deh098"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"Erel","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A new automated colorimetric method for measuring total oxidant status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/2041-210X.13384","article-title":"Methane: An R package for multi-environment trial analysis","volume":"11","author":"Olivoto","year":"2020","journal-title":"Methods Ecol. Evol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mai, Z., Liu, M., Pan, P., Li, L., Huang, J., Chen, X., and Yang, D. (2021). Comparison of Cumulative Live Birth Rate Between Aged PCOS Women and Controls in IVF\/ICSI Cycles. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.724333"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jia, R., Liu, Y., Jiang, R., Zhu, X., Zhou, L., Chen, P., Cao, M., and Zhao, Z. (2022). The Optimal Number of Oocytes Retrieved from PCOS Patients Receiving IVF to Obtain Associated With Maximum Cumulative Live Birth Rate and Live Birth After Fresh Embryo Transfer. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.878214"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/cen.12294","article-title":"The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment","volume":"80","author":"An","year":"2014","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0015-0282(00)01766-0","article-title":"Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors","volume":"75","author":"Stadtmauer","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s12978-021-01207-7","article-title":"Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: A network meta-analysis","volume":"18","author":"Zhao","year":"2021","journal-title":"Reprod. Health"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dubey, P., Reddy, S., Boyd, S., Bracamontes, C., Sanchez, S., Chattopadhyay, M., and Dwivedi, A. (2021). Effect of Nutritional Supplementation on Oxidative Stress and Hormonal and Lipid Profiles in PCOS-Affected Females. Nutrients, 13.","DOI":"10.3390\/nu13092938"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/humrep\/dep466","article-title":"Systemic and local eBects of metformin administration in patients with polycystic ovary syndrome (PCOS): Relationship to the ovulatory response","volume":"25","author":"Palomba","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.4103\/japtr.JAPTR_18_20","article-title":"Metformin and\/or vildagliptin mitigate type II diabetes mellitus induced-oxidative stress: The intriguing effect","volume":"11","author":"Sami","year":"2020","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_26","first-page":"FC21","article-title":"Erectile dysfunction and low sex drive in men with type 2 DM: The potential role of diabetic pharmacotherapy","volume":"10","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1038\/s41591-018-0125-4","article-title":"Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo","volume":"24","author":"Madiraju","year":"2018","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1093\/humrep\/deaa077","article-title":"Metformin inhibits testosterone-induced endoplasmic reticulum stress in ovarian granulosa cells via inactivation of p38 MAPK","volume":"35","author":"Jin","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00404-013-2804-1","article-title":"Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin-releasing hormone agonist and antagonists, on follicular fluid stem cell factor and serum urocortin 1 levels on the day of oocyte retrieval","volume":"288","author":"Celik","year":"2013","journal-title":"Arch. Gynecol. Obstet."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/19\/2215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:31Z","timestamp":1760112631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/19\/2215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":29,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["diagnostics14192215"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics14192215","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]}}}