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Fertil Steril. 1997 Aug;68(2):265-71.

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

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Department of Obstetrics and Gynecology, Singapore General Hospital, Singapore.



To determine whether the age-related decline in fertility is due to degenerative oocytes or to aneuploidy.




Fertility center of a public and tertiary institution.


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, < or = 34 years; group 2, between 35 and 39 years; and group 3, > or = 40 years). They were selected on the basis of available oocytes that remained unfertilized after IVF and that had analyzable chromosomes.


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.


Fertilization rates and pregnancy rates (PRs), and cytogenetic analyses of unfertilized oocytes.


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%).


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.


The hypothesis that the fertility decline observed in women over 40 years old is linked more to degenerative oocytes than to age-associated aneuploidy was investigated in 151 women 24-44 years old who underwent a total of 158 in vitro fertilization (IVF) cycles at Singapore General Hospital during 1993-95. Fertilization rates were 50.9% in women 34 years or younger, 49.3% in those 35-39 years old, and 37.9% in women 40 years or older. The pregnancy rates were 43.2%, 32.7%, and 14.3%, respectively. 287 (74.9%) of the 383 unfertilized oocytes could be karyotyped fully. The total chromosome abnormality rate was 30.3%; this included aneuploidy (13.9%), diploidy (8.4%), structural aberrations (4.2%), and single chromatids only (4.5%). A relationship between increased maternal age and an increase in the aneuploidy rate could not be assessed because of the small sample size in the oldest age group. The rate of chromatid separation increased significantly from 23.8% in the youngest age group to 95.8% in the oldest age group. This rate did not differ between in vitro fertilization and intracytoplasmic sperm injection. The degeneration evident in the majority of oocytes of older women presumably reflects decades of metabolic arrest at the dictyate stage. These findings suggest that the 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 greater likelihood of achieving pregnancy from ovum donation programs.

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