虽然卵母细胞体外成熟（IVM）的应用仍不普遍，但最近动物研究对卵母细胞生物学和排卵的基本机制的理解有了一些重要的突破，从而提出了一些创新的IVM方法。IVM技术的一项重要进展是采用两阶段的IVM方法。这种方法包括从轻度刺激的患者/动物中收集未成熟的卵母细胞（无需hCG预处理）以及在先进培养系统中对卵母细胞进行约24小时的预培养（“预-IVM”），然后进行常规的IVF程序。如果这种新的方法安全有效，则可能对人类辅助生殖技术产生重大影响。本综述的目标是审查卵巢生物学的重大科学进展，重点关注预-IVM方法的发展，介绍两阶段IVM程序，并报道动物和临床人体数据的结果，包括安全数据。讨论了两阶段IVM对辅助生殖技术实践可能产生的潜在未来影响。对这篇综述，我们通过在PubMed和Web of Science上进行检索，选择了同行评审的原始和综述文章。检索使用以下关键词：卵母细胞IVM、预-IVM、两阶段IVM、CAPA-IVM、hCG触发/预处理IVM、自然周期IVF/M、离体IVM、OTO-IVM、卵母细胞成熟、减数分裂能力、卵母细胞发育能力、卵母细胞顺应能力、卵泡大小、卵丘细胞（CC）、颗粒细胞、卵母细胞颗粒细胞复合体、间隙连接、跨中区过程、cAMP和IVM、cGMP和IVM、CNP和IVM、EGF样肽和IVM、轻度刺激辅助生殖技术、多囊卵巢综合症。通过减少促性腺激素的使用，IVM卵母细胞将从含有仍在发育的小的环突囊泡的卵巢中收集。使用这种卵母细胞进行标准IVM会得到次优的临床结果，而通过预-IVM对卵母细胞在体外的发育进行延续是预-IVM的目标。通过使卵母细胞的颗粒细胞发生深刻的细胞变化，预-IVM阶段中的颗粒细胞继续满足卵母细胞的发育需求。文献中包含了25年的关于不同预-IVM和两阶段IVM程序的动物研究，这为新的人类IVM方法提供了丰富的知识基础。基于c型利钠肽的预-IVM程序（称为“活性化-IVM”（CAPA-IVM））已经进行了临床前人体安全性和有效性试验，并且其在临床实践中的应用导致了与常规IVF无明显差异的健康活产率。在多年的时间里，临床IVM的改进是渐进而逐步的，但在过去几年中，动物卵母细胞生物学方面的突破性发现终于在临床实践中取得了改善患者预后的成果。CAPA-IVM实现了良好的临床结果，作为首个经临床测试的两阶段IVM系统，从而引起了人们对IVM作为一种替代的、低干预、低成本、安全、患者友好的辅助生殖技术方法的重新关注，特别是对多囊卵巢综合症患者而言。同样的新方法也正在用于患有癌症的患者的生育保留，并为社会卵子冷冻提供了希望。 © Oxford University Press代表欧洲人类生殖与胚胎学学会 2023年出版。保留所有权利，如需权限，请发送电子邮件至：journals.permissions@oup.com。

While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices.The objectives of this review are to examine the major scientific advances in ovarian biology with a unique focus on the development of pre-IVM methodologies, to provide an insight into biphasic IVM procedures, and to report on outcomes from animal and clinical human data, including safety data. The potential future impact of biphasic IVM on ART practice is discussed.Peer review original and review articles were selected from PubMed and Web of Science searches for this narrative review. Searches were performed using the following keywords: oocyte IVM, pre-IVM, biphasic IVM, CAPA-IVM, hCG-triggered/primed IVM, natural cycle IVF/M, ex-vivo IVM, OTO-IVM, oocyte maturation, meiotic competence, oocyte developmental competence, oocyte capacitation, follicle size, cumulus cell (CC), granulosa cell, COC, gap-junction communication, trans-zonal process, cAMP and IVM, cGMP and IVM, CNP and IVM, EGF-like peptide and IVM, minimal stimulation ART, PCOS.Minimizing gonadotrophin use means IVM oocytes will be collected from small antral (pre-dominant) follicles containing oocytes that are still developing. Standard IVM yields suboptimal clinical outcomes using such oocytes, whereas pre-IVM aims to continue the oocyte's development ex vivo, prior to IVM. Pre-IVM achieves this by eliciting profound cellular changes in the oocyte's CCs, which continue to meet the oocyte's developmental needs during the pre-IVM phase. The literature contains 25 years of animal research on various pre-IVM and biphasic IVM procedures, which serves as a large knowledge base for new approaches to human IVM. A pre-IVM procedure based on c-type natriuretic peptide (named 'capacitation-IVM' (CAPA-IVM)) has undergone pre-clinical human safety and efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF.Over many decades, improvements in clinical IVM have been gradual and incremental but there has likely been a turning of the tide in the past few years, with landmark discoveries in animal oocyte biology finally making their way into clinical practice leading to improved outcomes for patients. Demonstration of favorable clinical results with CAPA-IVM, as the first clinically tested biphasic IVM system, has led to renewed interest in IVM as an alternative, low-intervention, low-cost, safe, patient-friendly ART approach, and especially for patients with PCOS. The same new approach is being used as part of fertility preservation in patients with cancer and holds promise for social oocyte freezing.© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.