Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review

Author:

Rodríguez-Eguren Adolfo12ORCID,Bueno-Fernandez Clara13ORCID,Gómez-Álvarez María1ORCID,Francés-Herrero Emilio13ORCID,Pellicer Antonio34,Bellver José135,Seli Emre26ORCID,Cervelló Irene1ORCID

Affiliation:

1. IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe) , Valencia, Spain

2. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine , New Haven, CT, USA

3. Department of Paediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia , Valencia, Spain

4. IVIRMA Global Research Alliance, IVI Rome , Rome, Italy

5. IVIRMA Global Research Alliance, IVI Valencia , Valencia, Spain

6. IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, NJ, USA

Abstract

Abstract BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested. WIDER IMPLICATIONS Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis. REGISTRATION NUMBER https://osf.io/th8yf/

Funder

Instituto de Salud Carlos III

European Union

Fondo Social Europeo

El FSE invierte en tu futuro

Miguel Servet Program

Spanish Ministry of Science, Innovation, and Universities

Generalitat Valenciana

Publisher

Oxford University Press (OUP)

Reference259 articles.

1. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies—a report of 20 cases;Acharya;Hum Fertil (Camb),2009

2. In vitro evidence that platelet-rich plasma stimulates cellular processes involved in endometrial regeneration;Aghajanova;J Assist Reprod Genet,2018

3. Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience;Aghajanova;J Assist Reprod Genet,2021

4. Platelet rich plasma following hysteroscopic adhesolysis: a randomized clinical trial;Ahmed;Int J Reprod Contracept Obstet Gynecol,2021

5. Successful twin pregnancy in a donor oocyte recipient despite a maximum endometrial thickness in the late proliferative phase of 4 mm;Amui;Clin Exp Obstet Gynecol,2011

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3