{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:52:38Z","timestamp":1791420758175,"version":"4.3.3"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility in women, and patients often exhibit ovarian hyperresponse during controlled ovarian hyperstimulation (COH) in assisted reproductive technology. Kisspeptin is a key upstream regulator of the hypothalamic-pituitary-ovarian axis (HPOA). This study aims to explore the dynamic changes in serum and follicular fluid (FF) Kisspeptin levels during COH in PCOS patients and analyze their correlation with COH outcomes and pregnancy outcomes, in order to evaluate the potential value of Kisspeptin as a predictive biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective cohort study included 100 patients undergoing IVF-ET treatment (50 in the PCOS group and 50 in the control group). Serum samples were collected at four time points during the COH cycle (the day of starting Gn treatment, the fifth day of Gn stimulation, the day of hCG injection, the day of oocyte pickup [dOPU]), and FF samples were obtained on dOPU. Baseline characteristics, Kisspeptin levels, COH and pregnancy outcomes were compared between groups. Correlation and ROC curve analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum and FF Kisspeptin levels were significantly higher in the PCOS group at all time points (P&amp;lt;0.001). Both groups showed significantly elevated Kisspeptin levels on dOPU compared with dGn (P&amp;lt;0.001). Correlation analysis revealed that serum and FF Kisspeptin levels were positively correlated with AFC, AMH, E2 on dhCG, number of retrieved oocytes, and number of available embryos, but negatively correlated with the top-quality embryo (TQE) rate (P&amp;lt;0.01). Although the PCOS group had higher numbers of retrieved oocytes and available embryos, their TQE rate, cumulative pregnancy rate (40.00% vs. 60.00%, P\u00a0=\u00a00.046), and live birth rate (8.54% vs. 35.06%, P\u00a0=\u00a00.014) were significantly lower than those of the control group. ROC curve analysis indicated that serum Kisspeptin levels on dOPU had a certain predictive value for pregnancy outcomes (AUC\u00a0=\u00a00.655, 95% CI: 0.547\u20130.763).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Kisspeptin may be involved in the pathological processes of ovarian hyperresponse and asynchronous follicular development in PCOS and possesses a certain predictive value for pregnancy outcomes. It provides an important basis for understanding the mechanisms of reproductive dysfunction in PCOS and for developing future multifactorial predictive models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1835699","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:35:25Z","timestamp":1779251725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dynamic changes of Kisspeptin during controlled ovarian hyperstimulation (COH) in polycystic ovary syndrome patients and its correlation with COH outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"Lu","family":"Han","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Female Reproductive Health and Eugenic, Tianjin Medical University General Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"39.e1","DOI":"10.1016\/j.ajog.2023.04.010","article-title":"Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019","volume":"229","author":"Yu","year":"2023","journal-title":"Am J Obstet Gynecol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108284","article-title":"Targeting adipokines in polycystic ovary syndrome and related metabolic disorders: from experimental insights to clinical studies","volume":"240","author":"Xu","year":"2022","journal-title":"Pharmacol Ther"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dead241","article-title":"Global, regional, and national burden of infertility attributable to PCOS, 1990-2019","volume":"39","author":"Liu","year":"2024","journal-title":"Hum Reprod"},{"key":"B4","doi-asserted-by":"publisher","first-page":"10414","DOI":"10.1038\/s41467-024-54795-w","article-title":"Maternal polycystic ovary syndrome and Offspring\u2019s risk of cardiovascular diseases in childhood and young adulthood","volume":"15","author":"Yang","year":"2024","journal-title":"Nat Commun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.03.009","article-title":"Polycystic ovary syndrome: a \u201crisk-enhancing\u201d factor for cardiovascular disease","volume":"117","author":"Guan","year":"2022","journal-title":"Fertil Steril"},{"key":"B6","doi-asserted-by":"publisher","first-page":"CD006606","DOI":"10.1002\/14651858.CD006606.pub5","article-title":"In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction","volume":"2","author":"Siristatidis","year":"2025","journal-title":"Cochrane Database Syst Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.615957","article-title":"Factors associated with ovarian hyperstimulation syndrome (OHSS) severity in women with polycystic ovary syndrome undergoing IVF\/ICSI","volume":"19","author":"Sun","year":"2021","journal-title":"Front Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.11.008","article-title":"Oocyte competence in women with polycystic ovary syndrome","volume":"28","author":"Palomba","year":"2017","journal-title":"Trends Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41574-025-01131-x","article-title":"Endocrine-disrupting chemicals and female reproductive health: a growing concern","volume":"21","author":"Parent","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104850","article-title":"Overactivation of GnRH neurons is sufficient to trigger polycystic ovary syndrome-like traits in female mice","volume":"97","author":"Silva","year":"2023","journal-title":"EBioMedicine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2022.101006","article-title":"Kisspeptin neuron electrophysiology: intrinsic properties, hormonal modulation, and regulation of homeostatic circuits","volume":"66","author":"Jamieson","year":"2022","journal-title":"Front Neuroendocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deae153","article-title":"Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome","volume":"39","author":"Coutinho","year":"2024","journal-title":"Hum Reprod"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2019.1597343","article-title":"Effects of kisspeptin on pathogenesis and energy metabolism in polycystic ovarian syndrome (PCOS)","volume":"35","author":"Wang","year":"2019","journal-title":"Gynecol Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac195","article-title":"Extended LH administration as a strategy to increase the pool of recruitable antral follicles in hypothalamic amenorrhea: evidence from a case series","volume":"37","author":"La Marca","year":"2022","journal-title":"Hum Reprod"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa199","article-title":"Loss of anti-M\u00fcllerian hormone (AMH) immunoactivity due to a homozygous AMH gene variant rs10417628 in a woman with classical polycystic ovary syndrome (PCOS)","volume":"35","author":"Hoyos","year":"2020","journal-title":"Hum Reprod"},{"key":"B16","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1017\/s1466252324000021","article-title":"Role of anti-M\u00fcllerian hormone in different reproductive aspects of female mammals: women, cow and mare","volume":"24","author":"Mu\u00f1oz-Jurado","year":"2023","journal-title":"Anim Health Res Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0342158","article-title":"Kisspeptin improves local ovarian insulin resistance in PCOS by modulating the PI3K\/AKT\/GLUT4 signaling pathway","volume":"21","author":"Sun","year":"2026","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab287","article-title":"Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure","volume":"37","author":"Ruohonen","year":"2022","journal-title":"Hum Reprod"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/jog.14767","article-title":"Serum kisspeptin levels in polycystic ovary syndrome: a meta-analysis","volume":"47","author":"Liu","year":"2021","journal-title":"J Obstet Gynaecol Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105689","article-title":"Intranasal kisspeptin administration rapidly stimulates gonadotropin release in humans","volume":"115","author":"Mills","year":"2025","journal-title":"EBioMedicine"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.12.005","article-title":"Rerouting of follicle-stimulating hormone secretion and gonadal function","volume":"119","author":"Kumar","year":"2023","journal-title":"Fertil Steril"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2024","article-title":"Kisspeptin and neurokinin B: roles in reproductive health","volume":"105","author":"Koysombat","year":"2025","journal-title":"Physiol Rev"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155556","article-title":"Dissecting the KNDy hypothesis: KNDy neuron-derived kisspeptins are dispensable for puberty but essential for preserved female fertility and gonadotropin pulsatility","volume":"144","author":"Velasco","year":"2023","journal-title":"Metabolism"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deac069","article-title":"Transcriptomic landscape of granulosa cells and peripheral blood mononuclear cells in women with PCOS compared to young poor responders and women with normal response","volume":"37","author":"Cozzolino","year":"2022","journal-title":"Hum Reprod"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2021.02.023","article-title":"In vitro fertilization outcomes in women with polycystic ovary syndrome: a meta-analysis","volume":"259","author":"Tang","year":"2021","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1093\/humrep\/deaa305","article-title":"Transfer of fresh or frozen embryos: a randomised controlled trial","volume":"36","author":"Wong","year":"2021","journal-title":"Hum Reprod"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab240","article-title":"In vitro maturation without gonadotropins versus in vitro fertilization with hyperstimulation in women with polycystic ovary syndrome: a non-inferiority randomized controlled trial","volume":"37","author":"Zheng","year":"2022","journal-title":"Hum Reprod"},{"key":"B28","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.tem.2023.02.002","article-title":"Gonadotropins as pharmacological agents in assisted reproductive technology and polycystic ovary syndrome","volume":"34","author":"Singh","year":"2023","journal-title":"Trends Endocrinol Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/jci182669","article-title":"Astrocytes: a star emerges in the control of reproductive hormones","volume":"134","author":"Abbara","year":"2024","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","first-page":"5591","DOI":"10.1038\/s41467-024-49749-1","article-title":"Systematic review and meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome","volume":"15","author":"Bahri Khomami","year":"2024","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121069","article-title":"Polycystic ovary syndrome (PCOS) increases the risk of subsequent gestational diabetes mellitus (GDM): a novel therapeutic perspective","volume":"310","author":"Choudhury","year":"2022","journal-title":"Life Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1007\/s00018-024-05362-5","article-title":"Decreased AMPK\/SIRT1\/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS","volume":"81","author":"Hong","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaf113","article-title":"PCOS endometrium-derived epithelial organoids as a novel model to study endometrial dysfunction","volume":"40","author":"Luyckx","year":"2025","journal-title":"Hum Reprod"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-015-0105-1","article-title":"The pregnant mouse uterus exhibits a functional kisspeptin\/KISS1R signaling system on the day of embryo implantation","volume":"13","author":"Fayazi","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaab060","article-title":"Uterine kisspeptin receptor critically regulates epithelial estrogen receptor \u03b1 transcriptional activity at the time of embryo implantation in a mouse model","volume":"27","author":"Schaefer","year":"2021","journal-title":"Mol Hum Reprod"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2021.04.031","article-title":"Performance of plasma kisspeptin as a biomarker for miscarriage improves with gestational age during the first trimester","volume":"116","author":"Abbara","year":"2021","journal-title":"Fertil Steril"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/obr.70008","article-title":"Exploring the role of kisspeptin in polycystic ovary syndrome and its associated pregnancy complications","volume":"27","author":"Zhang","year":"2026","journal-title":"Obes Rev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03984-1","article-title":"Data-driven subtypes of polycystic ovary syndrome and their association with clinical outcomes","volume":"31","author":"Gao","year":"2025","journal-title":"Nat Med"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1835699\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:35:31Z","timestamp":1779251731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1835699\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":38,"alternative-id":["10.3389\/fendo.2026.1835699"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1835699","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1835699"}}