{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:45:11Z","timestamp":1789962311591,"version":"4.0.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"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. Reprod. Health"],"abstract":"<jats:p>Persistently thin endometrium remains one of the hardest challenges in reproductive medicine, often linked to implantation failure and poor pregnancy outcome. Growing evidence implicates deficient uterine blood supply in the pathogenesis of an inadequately thin endometrial lining. This narrative review synthesizes current knowledge on how endometrial vascularization influences endometrial thickness (EMT) and receptivity. We outline the normal endometrial structure and vascular physiology, then examine the pathophysiological features of thin endometrium, highlighting mechanistic studies that demonstrate impaired angiogenesis, reduced microvessel density, and tissue hypoxia in thin endometrial tissue. Doppler ultrasound studies consistently show that women with thin endometrium have reduced endometrial and subendometrial blood flow and higher resistance indices. Clinical correlations indicate that poor endometrial perfusion is associated with lower implantation and pregnancy rates in assisted reproduction. We review diagnostic tools for assessing endometrial perfusion, including two-dimensional (2D) and three-dimensional (3D) Doppler ultrasound measures of uterine and subendometrial blood flow. Therapeutic strategies aiming to improve uterine blood supply, such as vasoactive medications, intrauterine infusion of platelet-rich plasma (PRP), stem cell therapies, and other angiogenic treatments, often result in a marginal improvement of EMT and pregnancy outcomes. While these interventions show promise, limitations include small sample sizes and heterogeneous study designs. We discuss future directions, emphasizing the need for larger trials and a deeper understanding of angiogenic signaling in the endometrium. In conclusion, converging evidence supports poor endometrial blood supply as a key contributor to persistently thin endometrium. Future therapies that specifically target enhancement of endometrial blood supply may prove to be effective tools for improving endometrial growth and fertility outcomes.<\/jats:p>","DOI":"10.3389\/frph.2025.1732672","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T06:39:29Z","timestamp":1764743969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Endometrial hypoperfusion: the missing link in refractory thin endometrium"],"prefix":"10.3389","volume":"7","author":[{"given":"I.","family":"Weizel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lasri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hersko Klement","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Bentov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1477-7827-6-37","article-title":"The correlation between endometrial thickness and outcome of in vitro fertilization and embryo transfer (IVF-ET) outcome","volume":"2","author":"Al-Ghamdi","year":"2008","journal-title":"Reprod Biol Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1093\/humupd\/dmu011","article-title":"Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis","volume":"20","author":"Kasius","year":"2014","journal-title":"Hum Reprod Update"},{"key":"B3","doi-asserted-by":"publisher","first-page":"814648","DOI":"10.3389\/fendo.2021.814648","article-title":"The effect of endometrial thickness on pregnancy, maternal, and perinatal outcomes of women in fresh cycles after IVF\/ICSI: a systematic review and meta-analysis","volume":"12","author":"Liao","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.fertnstert.2021.12.025","article-title":"Optimal endometrial thickness in fresh and frozen-thaw in vitro fertilization cycles: an analysis of live birth rates from 96,000 autologous embryo transfers","volume":"117","author":"Mahutte","year":"2022","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.fertnstert.2024.12.032","article-title":"Association of endometrial thickness with live birth rate: a study using the society for assisted reproductive technology clinic outcome reporting system","volume":"124","author":"Schmiech","year":"2025","journal-title":"Fertil Steril"},{"key":"B6","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s10815-019-01407-y","article-title":"Obstetrical complications of thin endometrium in assisted reproductive technologies: a systematic review","volume":"36","author":"Mouhayar","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.rbmo.2019.02.013","article-title":"Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian fertility and andrology society","volume":"39","author":"Liu","year":"2019","journal-title":"Reprod Biomed Online"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1007\/s10815-019-01576-w","article-title":"Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review","volume":"36","author":"Ranisavljevic","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1530\/rep.0.1210181","article-title":"Human endometrial angiogenesis","volume":"121","author":"Gargett","year":"2001","journal-title":"Reproduction"},{"key":"B10","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.fertnstert.2008.01.029","article-title":"Pathophysiologic features of \u201cthin\u201d endometrium","volume":"91","author":"Miwa","year":"2009","journal-title":"Fertil Steril"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1016\/j.fertnstert.2008.12.062","article-title":"Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium","volume":"93","author":"Takasaki","year":"2010","journal-title":"Fertil Steril"},{"key":"B12","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1111\/j.1471-0528.1970.tb03592.x","article-title":"The blood supply of the uterus. 1. 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