Age-related decline in fertility: a link to degenerative oocytes?

Objective: To determine whether the age-related decline in fertility is due to degenerative oocytes or to aneuploidy. Design: Retrospective. Setting: Fertility center of a public and tertiary institution. Patient(s): One hundred fifty-one women (ages 24 to 44 years) undergoing 158 cycles of conventional IVF or IVF with intracytoplasmic sperm injection (ICSI) between January 1993 and December 1995 were divided into three age groups (group 1, less than or equal to 34 years; group 2, between 35 and 39 years; and group 3, greater than or equal to 40 years). They were selected on the basis of available oocytes that remained unfertilized after IVF and that had analyzable chromosomes. Intervention(s): Standard pituitary down-regulation and ovarian stimulation with FSH and hMG were done for both IVF and ICSI patients. In addition, all patients were given luteal phase support with P, administered orally, via pessaries, or by IM injections from the day of transfer. Main Outcome Measure(s): Fertilization rates and pregnancy rates (PRs), and cytogenetic analyses of unfertilized oocytes. Result(s): Although fertilization rates were not different among women in groups 1, 2, and 3 (50.9%, 49.3%, and 37.9%, respectively), PRs were significantly lower between groups 1 and 3 (43.2% versus 14.3%). A total of 383 oocytes were examined, of which 287 (75%) could be karyotyped. Of these, 201 oocytes showed a normal 23,X karyotype (70%), 40 (13.9%) were aneuploid, 24 (8.4%) were diploid, 12 (4.2%) had structural aberrations, and 13 (4.5%) had single chromatids only. No increase in the aneuploidy rate was detected between groups 1 and 2 (14.8% versus 12.4%). However, highly significant differences in the rate of oocyte chromosome degeneration, characterized by chromosomes splitting into unassociated chromatids, were observed with increasing age (group 1, 23.7%; group 2, 52.0%; and group 3, 95.8%). Conclusion(s): It seems that the age-related decline in fertility may be due more to degenerative oocytes than to aneuploidy. A decline in the number of oocytes retrieved with age may be of less importance than the decline in oocyte quality. Women in the older age group have a higher chance of achieving pregnancy from ovum-donation programs than by persisting in using their own aged oocytes, which have a very poor prognosis for success. (C) 1997 by American Society for Reproductive Medicine.