{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:29:00Z","timestamp":1792301340396,"version":"4.4.0"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Obstetrics and Gynecology of the Amsterdam UMC"},{"name":"Amsterdam Reproduction and Development Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein\/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.<\/jats:p>","DOI":"10.3390\/ijms24087011","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T02:02:33Z","timestamp":1681178553000},"page":"7011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids\u2014A Systematic Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0782-8578","authenticated-orcid":false,"given":"Emma E.","family":"Don","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-An","family":"Middelkoop","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter J. K.","family":"Hehenkamp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velja","family":"Mijatovic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan W.","family":"Griffioen","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A. F.","family":"Huirne","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/01443610802149863","article-title":"The incidence of uterine leiomyoma and other pelvic ultrasonographic findings in 2,034 consecutive women in a north London hospital","volume":"28","author":"Lawal","year":"2008","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16043","DOI":"10.1038\/nrdp.2016.43","article-title":"Uterine fibroids","volume":"2","author":"Stewart","year":"2016","journal-title":"Nat. Rev. Dis. 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