The time is ripe for oocyte in vitro maturation

Abstract

When it comes to welcome transitions, 2021 seems to have started on a promising note. From the ushering in of COVID19 vaccination programs to a renewed appreciation of evidence-based policy in many countries, progress manifested itself in swift and emphatic manners. The same can be said of the field of assisted reproduction techniques (ART), home to a recent practice committee document on oocyte in vitro maturation (IVM) [1]. In this landmark document, the practice committees of the American Society for Reproductive Medicine (ASRM), the Society of Reproductive Biologists and Technologists, and the Society for Assisted Reproductive Technology (SART) present a considerable (and compelling) body of published evidence supporting the conclusion that IVM should no longer be considered an experimental technique. This coming of age for IVM may be a surprise to many. Indeed, the initial attempts of promoting meiotic resumption under fully controlled conditions were met with fairly underwhelming results. On hindsight, we can speculate whether our knowledge of oocyte physiology and development was, at the time, sufficientlymature to support the design of truly effective IVM. Quite tellingly, it was precisely an investment on the basic aspects of reproductive biology — particularly on how intrafollicular cell signaling primes the oocyte to successfully navigate past its prophase I arrest — that opened the door to a new generation of more efficient IVM protocols [2–5]. Regardless of the hows and whys, it is clear that IVM did not translate, from the start, into an immediate clinical success like ICSI, and that initial wave of disappointment has clouded the technique ever since. In light of the above, the transition of IVM from a niche approach to mainstream ART has not been a smooth ride. Other, more practical, reasons have also complicated this transition. For starters, the technical aspects, of the procedure: the small size of the targeted antral follicle population makes oocyte retrieval more challenging. Likewise, isolating nonexpanded immature cumulus-oocyte complexes (COCs; Fig. 1) from an often convoluted mix of cellular debris and body fluids demands greater training and technical proficiency from the clinical embryologist. This additional workload for both medical doctors and clinical embryologists may have hindered a faster adoption of IVM across the board, particularly in light of the lower numbers of transferable embryos associated with the technique (a reflection of the increased attrition to get from immature COCs to high-quality embryos). Such technical aspects have been further compounded by an inconsistent (and sometimes outright anarchic) use of the term IVM, an acronym that has been employed to label procedures ranging from mild ovarian stimulation to the extended culture of primingirresponsive immature oocytes denuded of their cumulus cells [6]. This inconsistent terminology complicates inter-study comparisons and obfuscates the difference between valuable procedures and those that should be considered largely inefficient at best. Again, it is important to emphasize that IVM protocols have been significantly improved in the last few years, translating into higher take-home baby rates and a more informed appreciation of their overall safety [7, 8]. Among these recent * Carlos E. Plancha [email protected]; [email protected]