Page 20 - Focus on reproduction january 2016

concept that immature human oocytes can resume meiosis spontaneously and reach metaphase II within 36 hours was acknowledged 50 years ago by Robert Edwards, who remained an advocate of IVM throughout his entire career.2 Indeed, the historical observation of Edwards and others that approximately 50% of human oocytes, when removed from their follicular environment, reach metaphase II spontaneously is still valid and constitutes the basis of oocyte maturation in vitro as we apply it today.
So it is disappointing to realise that maturation rates of oocytes incubated in currently available IVM systems registered for clinical use have not really evolved since those early experiments of Edwards back in the sixties, and low maturation rates are still a major obstacle to the efficiency of IVM.
In contrast, the technology of hormone-driven ART has seen tremendous advances in the past decades, fuelled by the development of pharmaceutical compounds to produce high quality oocytes following ovarian stimulation. The development of stimulation protocols has led to major improvements in conventional hormone-driven ART results since the beginning of the nineties. Similarly, GnRH antagonist protocols with GnRH agonist trigger and efficient vitrification systems have seen an overall reduction in the incidence of OHSS in high responders. Thus, a lack of incentive to develop alternative methods to ART has been one major impediment to the progress of IVM.
However, it would be unfair to say that IVM is an orphan technology and neglected by the scientific community. For IVM is widely applied in animal breeding, where maturation rates after IVM appear to be much higher than in human IVM; indeed, yearly cattle embryo production using IVM has been estimated to exceed 500,000. Furthermore, IVM has attracted enormous interest from reproductive biologists keen to unravel the complexity of human oocyte maturation and translate the physiological process to the in-vitro setting. Finally, the improved success rates of IVM treatment in patients with PCO/PCOS reported by some groups and the succesful use of IVM in fertility preservation programmes have fuelled renewed interest in this technology.3,4
How it works
Strictly speaking, IVM involves the aspiration of immature oocytes from antral follicles after minimal
Patient selection criteria for IVM

Robert Edwards remained an advocate of IVM throughout his career. His observation that approximately 50% of human oocytes, when removed from their follicular environment, reach metaphase II spontaneously is still valid and the basis of oocyte maturation today.
or no exogenous gonadotrophin administration. Oocyte collection is typically performed from follicles of up to 12 mm and selection of a single dominant follicle is avoided to prevent any negative impact on development of subordinate follicles.
Oocyte maturation rates in vitro are generally lower than maturation rates of oocytes retrieved in a conventional IVF programme after administration of an ovulation trigger, suggesting that a considerable proportion of immature oocytes from small antral follicles are still meiotically incompetent and would have required more time within their follicular environment to accomplish physiological nuclear and cytoplasmic maturation.
Higher oocyte maturation rates can be obtained when a bolus of hCG is administered, typically 36-38 hours before oocyte retrieval. In these cases, meiotic resumption is initiated in vivo and a proportion of oocytes are found to have reached metaphase II at the time of oocyte retrieval - they are oocytes which have thus completed meiosis in vivo and can readily be inseminated. As such, the hCG triggered IVM system may represent a semantical contradiction, but it is applied more often than the ‘pure’ non-hCG triggered system, where all oocytes are at GV stage at the time of egg collection. Nevertheless, there is ongoing debate as to the most efficient clinical and laboratory protocol for patients undergoing IVM.
Because of the lower maturation rate and lower developmental potential of in vitro matured oocytes retrieved from antral follicles - at least using registered IVM media - IVM is currently not a suitable option for every patient requiring IVF. Thus, the cornerstone of an efficient IVM programme is proper patient selection - and it seems that women with polycystic
20 Focus on Reproduction // JANUARY 2016