Abstract

Reproductive aging involves complex changes in the hypothalamic-pituitary-ovarian axis. These changes and their effects on the ovarian follicular environment are poorly understood. FF hormone content in response to controlled ovarian hyperstimulation (COH) may vary with age. In addition, the FF steroid profile may serve as a marker of follicle maturation in response to COH in women undergoing IVF. To evaluate the effect of aging and follicle maturation on human ovarian follicular fluid (FF) steroid content and fertility potential, we analyzed the steroid and hormone content of follicular fluid across different ages and follicle sizes to determine the relationship between steroid profile on fertilization and pregnancy rates. Basic science laboratory in a large academic center. Women aged 25-43 years undergoing IVF were enrolled according to an institutional review board approved protocol. Subjects were divided into two groups, Group A, age 34 years and younger, and Group B, age 40 years and older. Follicles were measured in two dimensions by transvaginal ultrasound prior to aspiration. Fluid from three lead (mature) follicles, average size greater than 14mm, and three small (immature) follicles, size less than 12mm, was collected and processed separately. Following oocyte isolation, the FF was centrifuged to separate cellular components. Estradiol (E2), estrone (E), progesterone (P), testosterone (T), androstendione (A), follicle stimulating hormone (FSH), and leutinizing hormone (LH) were measured by enzyme-linked immunosorbent assay (ELISA). The fertilization rates for our subjects are, 0.67 and 0.69, for groups A and B respectively. The pregnancy rates are 0.45 and 0.23. Mean values for steroid hormones by age and follicle size are shown in Table 1 (Note: not all assays were run for each sample.)Tabled 1 The follicular fluid steroid environment varies with age in response to COH. In addition, the hormone profile differs with follicle maturation. As seen by others, we found differences in the hormone levels in small and lead follicles, with significant differences in E2 and A. In addition, there are changes in fluid composition with age though statistical significance is limited by sample size. The contribution of these factors to fertilization rates and pregnancy rate is uncertain. While we know that age-associated variation in serum steroid levels and reduced number of follicles may account for some reduction in fertility, the steroid content of the FF may be a response to and a marker of these changes In addition, factors such as aging of the oocyte, function of the follicular somatic cells, and molecular FF composition including cytokines and other peptides may account for differences in outcome.

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