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Human oocyte capacitation culture: Essential step toward hormone-free assisted reproductive technology

DOI: 10.1002/rmb2.12640

Published: 12 Mar 2025

Johan Smitz 1Flor Sánchez 2Sergio Romero 3Heidi Van Ranst 1Ellen Anckaert 1Robert B Gilchrist 4Tuong M Ho 5 6Lan N Vuong 7Yoshiharu Morimoto 8

Authors information

1Follicle Biology Laboratory, Faculty of Medicine and Pharmacy Vrije Universiteit Brussel Brussels Belgium.

2Centro de Estudios e Investigaciones en Biología y Medicina Reproductiva Lima Peru.

3Centro de Fertilidad y Reproducción Asistida Lima Peru.

4Fertility & Research Centre, Discipline of Women’s Health, School of Clinical Medicine University of New South Wales Sydney Sydney New South Wales Australia.

5IVFMD My Duc Hospital Ho Chi Minh City Viet Nam.

6HOPE Research Center Ho Chi Minh City Viet Nam.

7Department of Obstetrics and Gynecology University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City Viet Nam.

8HORAC Grand Front Osaka Clinic Osaka Japan.

Abstract

Background: In vitro oocyte maturation (IVM) is not a novel concept; however, its wide-scale practice has been limited because of the lower clinical outcomes compared to conventional assisted reproductive technologies.

Methods: This comprehensive review addresses the significant advances made in oocyte in vitro maturation with the biphasic capacitation (CAPA)-IVM strategy applied to small ovarian antral follicles in humans over the last 10 years. CAPA-IVM consists of a prematuration phase wherein immature oocytes are temporarily meiotically arrested to gain competence before undergoing meiotic resumption.

Main findings: The integration of knowledge from basic research in animal models into clinical practice has led to a reevaluation of IVM for policystic ovary syndrome (PCOS) and onco-fertility patients. The introduction of meticulously conceived growth factors, hormonal supplements, and culture conditions led to an integrated biphasic CAPA-IVM system that promotes oocyte competence. A series of prospective randomized controlled studies validated the reproducible improvements in clinical outcomes and the safety of CAPA-IVM. So far, nearly 1000 babies have been born using this approach.

Conclusion: The use of CAPA-IVM in clinical studies has set the tone for major progress in the field and is achieving a safer, less expensive, and less emotionally loaded IVF experience, currently validated for PCOS patients.

Keywords: CAPA‐IVM; IVM; biphasic in vitro maturation; cumulus–oocyte complexes; in vitro maturation.