Oocyte in-vitro maturation and follicle culture: current clinical achievements and future directions.

This paper reviews two recent developments in the field of assisted reproduction: in-vitro culture (IVC) of follicles and in-vitro maturation (IVM) of oocytes. Both in-vitro procedures for oocytes and immature follicles were developed so as to enable storage of ovarian cortical tissue and oocyte-cumulus complexes (OCC) from small follicles. Until now, complete in-vitro development from a primordial follicle up to ovulation has been achieved only in mice. Culture of ovarian cortex from large mammals and humans has revealed that the proliferation and differentiation of pre-granulosa cells is easily switched on, but that within a few days oocyte growth is often compromised. Culture of OCC from preantral follicles from sheep yielded antral follicles after 1 month in a serum-free system and the enclosed oocytes had almost doubled their diameter. Similar work in humans is ongoing, but no consistent successes have been reported as yet. In-vitro maturation of OCC from antral follicles has already been used clinically for more than 10 years. Inspired by the work on bovines, several in-vitro fertilization (IVF) clinics have applied IVM on OCC from different sizes of follicles. The culture conditions needed to provide a reasonable yield of developmentally competent oocytes have not been clearly defined, although some IVF groups have reported live births. To enable the development of consistent techniques of IVC and IVM, a more systematic and scientific approach is needed: use of defined culture media in combination with follicle stage-dependent supplements might improve our understanding of the minimal requirements for oocyte growth and maturation.