The Improvement and Clinical Application of Human Oocyte In Vitro Maturation (IVM).
Oocyte in vitro maturation (IVM) is a technology with a long history that was established before IVF. Although it has been studied extensively, the efficiency of IVM has been poor for almost 30 years. In terms of the benefits of IVM, the efficiency and adoption of IVM are being improved by some notable improvements that have occurred in recent years. The establishment of biphasic IVM is the most important advancement in recent years. Biphasic IVM includes the pre-IVM culturing phase and IVM phase. The CNP-mediated pre-IVM culturing system is specifically tailored for non/minimally stimulated immature oocytes, and its efficiency has been shown. This is the most significant improvement made in recent decades in this area. In the clinic, IVM can be used for PCOS patients to avoid the occurrence of ovarian hyperstimulation syndrome (OHSS). Additionally, this method can solve the reproductive problems of some patients with special diseases (resistant ovary syndrome) that cannot be solved by IVF. In most fertility preservation procedures, oocytes in small antral follicles are lost. However, IVM has the ability to capture this kind of oocyte and save reproductive potential. IVM can be easily combined with fertility preservation strategies that have been applied in the clinic and improve the efficiency of fertility preservation. IVM is a useful and attractive technology and may be used widely worldwide in the near future.
Gong X
,Li H
,Zhao Y
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A fresh start for IVM: capacitating the oocyte for development using pre-IVM.
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.
Gilchrist RB
,Ho TM
,De Vos M
,Sanchez F
,Romero S
,Ledger WL
,Anckaert E
,Vuong LN
,Smitz J
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