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Use of immature oocytes in infertility treatment
Since the first case of pregnancy by in vitro matured oocyte was reported (Cha et al., 1991), in vitro maturation (IVM) could be used as an alternative choice for the treatment of infertile women with polycystic ovary syndrome (PCOS) and poor responders to ovarian stimulation and as one of the strategies for fertility preservation (Chian, 2004). Immature oocyte retrieval followed by IVM is a promising potential treatment option, especially for women who are infertile through PCOS. Although the pregnancy and implantation rates of IVM treatment are not as high as conventional IVF treatment, IVM treatment has many advantages for infertile women with PCOS, because this group of patients is extremely sensitive to stimulation with exogenous gonadotropins and is at increased risk of developing ovarian hyperstimulation syndrome (OHSS). Different protocols have been used before immature oocyte retrieval, indicating that there are beneficial effects with FSH or LH priming on oocyte maturation. To date, the clinical pregnancy and implantation rates obtained from IVM treatment in infertile women with PCOS are approximately 30-35% and 10-15% respectively (Chian, 2004). The clinical outcome has substantially improved in recent years with pregnancy rates between 20 and 54% and the postnatal follow-up studies of the children have been reassuring (Suikkari, 2008). Currently, more than 400 healthy infants have been reported with IVM method (Jurema and Nogueira, 2006; Suikkari, 2008). Although good results have been reported by some clinics, IVM has not yet become a mainstream fertility treatment. The most important reason for this is the lower chance of a live birth per treatment compared with conventional IVF. Despite its clinical success, there has been little information about the suitable conditions for human IVM. Therefore, improving developmental competency of immature oocytes continues to be an important concern of most IVM centers. Among many factors which affect efficacy of IVM, culture conditions are believed to be the most important factor, because different culture medium with changes of constituents can affect the oocyte maturation potential and subsequent embryonic development (Trounson et al., 2001). Currently, many different types of commercially available maturation media have been used in clinical IVM. They are commonly supplemented with hormone (recombinant FSH, hCG) and protein sources. Protein component may serve as a nitrogen source and act as a chelator of toxic metal ions and an antioxidant within culture media. In this respect, a development of well defined maturation medium supplemented with an efficient and safe protein source would improve IVM results. We previously reported that developmental competency of immature oocytes (either GV or MI) obtained from stimulated IVF cycles was comparable when matured in vitro with commercial G2 media supplemented by either human follicular fluids (hFF) or human serum albumin (HSA) (Jee et al., 2008). Our results suggest that hFF as a protein supplement for human in vitro maturation can be replaced by highly defined HSA. A development of well defined maturation medium should be continued in the effort to improve IVM results. More research is also needed to determine the roles of specific components and optimal culture conditions required in maturing oocytes. IVM of human oocytes retrieved from antral ovarian follicles is an emerging procedure quickly being incorporated into the realm of assisted reproductive technologies (ART). This new technology has several potential advantages over traditional controlled ovarian hyperstimulation for IVF, such as reduction of costs by minimizing gonadotropin and GnRH analogue use, elimination of OHSS, and simplicity of protocol. IVM of oocytes for ART in human beings still is undergoing refinement but currently is providing efficacy and safety outcome comparable to that of traditional IVF in recent selected studies. Implementing IVM into an established IVF practice is feasible and requires only a few simple adjustments. Crucial to the advancement and optimization of the technology is a better understanding of how to maximize immature oocyte developmental competence and endometrial receptivity.
