ENDOMETRIAL RECEPTIVITY: MOLECULAR MECHANISMS, THIN ENDOMETRIUM SUBTYPES, AND MECHANISM-BASED THERAPEUTIC APPROACHES

Öz

Endometrial receptivity is a transient and highly coordinated biological state regulated by hormonal, molecular, vascular, metabolic, and immune pathways that collectively enable embryo implantation. This narrative review aims to synthesize contemporary evidence on the mechanisms governing endometrial receptivity and the heterogeneous etiologies of thin endometrium. A comprehensive literature search of PubMed, Scopus, and Web of Science published between 1998 and 2025 identified studies addressing morphological, molecular, metabolic, immunological, and microbiota-related determinants of receptivity. Current evidence demonstrates that receptivity is orchestrated through the interplay of the HOXA10–LIF–αvβ3 integrin axis, angiogenic signaling, extracellular matrix dynamics, mitochondrial bioenergetics, and AMPK–mTOR–mediated cellular energy regulation. Thin endometrium represents not a simple proliferative deficiency but a multifactorial phenotype shaped by vascular insufficiency, downregulation of key receptivity markers, metabolic stress, oxidative imbalance, fibrosis, immune disruption, and alterations in the uterine microbiota. Mechanism–directed therapeutic strategies including sildenafil, granulocyte colony-stimulating factor, platelet-rich plasma, mesenchymal stem cell–based regeneration, antioxidants, folate supplementation, and ERA-guided personalized embryo transfer target these underlying biological phenotypes rather than endometrial thickness alone. Shifting from thickness–based evaluation to a phenotype- and mechanism-oriented clinical framework is essential for improving implantation and pregnancy outcomes in assisted reproductive technologies.

Anahtar Kelimeler

• Endometrial receptivity
• thin endometrium
• AMPK
• mTOR
• ERA
• implantation

Endometrial reseptivite: moleküler mekanizmalar, ince endometrium alt tipleri ve mekanizma-temelli tedavi yaklaşımları

Öz

Endometrial reseptivite, embriyo implantasyonunu mümkün kılan hormonal, moleküler, vasküler, metabolik ve immün yolakların eşzamanlı etkileşimiyle düzenlenen geçici ve yüksek derecede koordineli bir biyolojik durumdur. Bu derleme, endometrial reseptiviteyi yöneten mekanizmalar ile ince endometriyumun heterojen etiyolojilerini kapsayan güncel kanıtları sentezlemektedir. PubMed, Scopus ve Web of Science veri tabanlarında 1990–2025 yılları arasında yayımlanan çalışmalar taranarak morfolojik, moleküler, metabolik, immünolojik ve mikrobiyota temelli reseptivite belirleyicilerini ele alan yayınlar incelenmiştir. Güncel veriler, reseptivitenin HOXA10–LIF–integrin αvβ3 ekseni, anjiyojenik sinyalizasyon, ekstrasellüler matriks dinamikleri, mitokondriyal biyogenezi ve AMPK–mTOR aracılı hücresel enerji düzenlenmesi üzerinden yürüyen karmaşık bir etkileşimle oluştuğunu göstermektedir. İnce endometriyum basit bir proliferatif yetersizlik değil; vasküler yetmezlik, temel reseptivite belirteçlerinin baskılanması, metabolik stres, oksidatif dengesizlik, fibrozis, immün disfonksiyon ve uterin mikrobiyotadaki değişikliklerin şekillendirdiği multifaktöriyel bir fenotiptir. Sildenafıl, granülosit koloni uyarıcı faktör, platelet-rich plasma, mezenkimal kök hücre temelli rejeneratif yaklaşımlar, antioksidan destek, folat takviyesi ve ERA temelli kişiselleştirilmiş embriyo transferi gibi mekanizmaya yönelik tedaviler, endometrial kalınlıktan ziyade bu biyolojik alt fenotipleri hedef almaktadır. Sonuç olarak, ince endometriyumun değerlendirilmesinde kalınlık odaklı yaklaşımdan mekanizma ve fenotip odaklı klinik karar süreçlerine geçiş, yardımcı üreme tekniklerinde implantasyon ve gebelik sonuçlarının iyileştirilmesi açısından kritik öneme sahiptir.

Anahtar Kelimeler

• Endometrial reseptivite
• ince endometriyum
• AMPK
• mTOR
• ERA
• Endometrial reseptivite; ince endometriyum; AMPK; mTOR; ERA; implantasyon

Kaynakça

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