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SYSTEMATIC REVIEW article

Front. Endocrinol.

Sec. Reproduction

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1694025

This article is part of the Research TopicOvarian Aging: Pathophysiology and Recent Development of Maintaining Ovarian Reserve, Volume IVView all 13 articles

Endocrine and Regenerative Mechanisms of Adipose-Derived Stem Cells in Female Infertility

Provisionally accepted
Zaher  MerhiZaher Merhi1*Bhavika  GargBhavika Garg2
  • 1Albert Einstein College of Medicine, New York City, New York, United States
  • 2University at Buffalo, Buffalo, United States

The final, formatted version of the article will be published soon.

Infertility remains a global health challenge, particularly in cases involving endometrial damage, diminished ovarian reserve, or poor embryo quality where conventional therapies often fail. Adipose-derived stem cells (ADSCs) have emerged as a promising regenerative option due to their accessibility, multipotency, and paracrine signaling capacity. This review evaluated preclinical and clinical studies investigating ADSCs and their derivatives for uterine, ovarian, and embryo applications in reproductive medicine. Literature searches were conducted in PubMed to July 2025, focusing on studies involving ADSCs, ADSC exosomes, and ADSC mitochondria in animal models and human studies. Results demonstrated that intrauterine ADSC administration improved endometrial thickness, vascularization, and receptivity, with some studies showing increased implantation and pregnancy rates in patients with thin endometrial lining thickness or Asherman's syndrome. Ovarian applications showed partial restoration of function in premature ovarian insufficiency and chemotherapy-induced damage, with evidence of menstrual recovery, hormonal improvements, and enhanced folliculogenesis in both animal and early human studies. At the gamete and embryo level, ADSC-derived mitochondria, exosomes, and conditioned media improved oocyte maturation, reduced oxidative stress, enhanced blastocyst development, and increased embryo survival in vitro. Collectively, these findings highlight ADSCs' therapeutic potential in addressing multiple infertility etiologies. However, current evidence is limited by small sample sizes, heterogeneous methodologies, short follow-up periods, and incomplete mechanistic insight. Most evidence to date comes from animal studies, while human clinical data remain limited to small early-phase trials. Large, well-designed clinical studies with standardized protocols and long-term safety evaluation are essential before ADSC-based therapies can be responsibly considered for full integration into assisted reproductive technologies.

Keywords: adipose-derived stem cells, Endometrium, Ovary, embryo, Infertility, Regenerative Medicine

Received: 27 Aug 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Merhi and Garg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zaher Merhi, zaher.merhi@rfcfertility.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.