Hum. Reprod. Advance Access published online on January 11, 2008
Human Reproduction, doi:10.1093/humrep/dem408
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A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause
1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190, USA 2 NSK Statistical Solutions LLC, Choctaw, OK, USA 3 Seattle Reproductive Medicine, Seattle, WA 98109, USA 4 Stereotome NW, Issaquah, WA 98027, USA
5 Correspondence address. Tel: +1-405-271-8722; Fax: +1-405-271-1655; E-mail: karl-hansen{at}ouhsc.edu
BACKGROUND: The primary determinant of reproductive age in women is the number of ovarian non-growing (primordial, intermediate and primary) follicles (NGFs). To better characterize the decline in NGF number associated with aging, we have employed modern stereology techniques to determine NGF number in women from birth to menopause.
METHODS: Normal human ovaries were collected from 122 women (aged 0–51 years) undergoing elective oophorectomy, organ donation or autopsy. After gross pathologic examination, systematic random sampling was utilized to obtain tissue for analysis by the fractionator/optical disector method. Models to describe the resulting decay curve were constructed and evaluated.
RESULTS: NGF decay was best described by a simple power function: log (y) = axb + c, where a, b and c are constants and y = NGF count at age x (R2 = 0.84, Sums of Squares Error = 28.18 on 119 degrees of freedom). This model implies that follicles decay faster with increasing age.
CONCLUSIONS: Unlike previous models of ovarian follicle depletion, our model predicts no sudden change in decay rate, but rather a constantly increasing rate. The model not only agrees well with observed ages of menopause in women, but also is more biologically plausible than previous models. Although the model represents a significant improvement compared with earlier attempts, a considerable percentage of the variation in NGF number between women cannot be explained by age alone.
Key words: reproductive aging/human ovary/optical fractionator/disector/stereology
Submitted on August 23, 2007; resubmitted on November 16, 2007; accepted on December 4, 2007.
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