THE MEIOTIC COMPETENCE OF IN-VITRO MATURED HUMAN OOCYTES IS INFLUENCED BY DONOR AGE - EVIDENCE THAT FOLLICULOGENESIS IS COMPROMISED IN THE REPRODUCTIVELY AGED OVARY

The human oocyte appears to be particularly prone to meiotic errors, a nd the incidence of these errors is strongly influenced by maternal ag e, We have initiated studies of human oocytes from unstimulated ovarie s and have observed age-related effects on the meiotic process in oocy tes from unselected antral follicles, Specifically, in oocytes obtaine d from donors over the age of 35 years, the majority of oocytes that e xtruded a first polar body in culture and arrested at second meiotic m etaphase had aberrations in spindle formation and chromosome alignment , Similarly, observations of a limited number of oocytes at first meio tic metaphase suggest disturbances at this stage of meiosis as well, F inally, preliminary results of nondisjunction studies suggest that the frequency of errors in chromosome segregation at the first meiotic di vision is influenced by donor age in in-vitro matured oocytes as it is in oocytes undergoing meiotic maturation in vivo. These data provide direct evidence that the meiotic competence of oocytes from unstimulat ed ovaries declines with donor age. Similarly, studies of in-vitro fer tilization (IVF) pregnancies in older women indicate that the developm ental competence of the human oocyte declines with age. Since both mei otic and developmental competence are acquired during the late stages of oocyte growth, we postulate that an age-related decline in the proc ess of folliculogenesis results in reduced oocyte quality and that the well characterized age-related increase in meiotic non-disjunction is one symptom of compromised oocyte growth.