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Age-related changes in major ovarian follicle wave dynamics: morphologic and endocrinologic characteristics



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Context: Reproductive aging results from depletion of the ovarian reserve and is marked by profound changes in hormone production and menstrual cyclicity. Age-related changes in antral follicle count and hormone production are well-documented. However, follicle wave dynamics and associated changes in hormone production have not been evaluated as women age. Overall Objective: To test the overall hypothesis that major follicle wave dynamics change as women age, and underlie changes in hormone production as women approach menopause. Materials and Methods: A prospective, observational study was conducted in 58 women of Reproductive Age (RA; 18-35 years; n=27), Advanced Reproductive Age-1 (ARA1; 36-44 years; n=10) and Advanced Reproductive Age-2 (ARA2; 45-55 years; n=21). The numbers and diameters of all follicles >2mm were recorded ultrasonographically every 2-3 days for 1 interovulatory interval. In a subset of women (RA, n=10; ARA2, n=17) blood samples were collected at each visit and serum was assayed for FSH, LH, estradiol, inhibin A and B, AMH and progesterone concentrations. Changes in AFC, follicle wave dynamics, and hormone production were compared between groups (SPSS v19.0, α=0.05). Results: The prevalence of Follicular and Luteal Phase Major Waves (FPMWs, LPMWs) was not different between RA, ARA1, and ARA2 groups [FPMW: 27/27(100%), 10/10(100%), 20/21(95%); LPMW: 10/17(37%), 3/10(30) %, 10/21(48%); P>0.050). All FPMWs were ovulatory. One LPMW ovulated at the time of menses in the ARA2 group; all other LPMWs were anovulatory. Dominant follicles in LPMWs emerged earlier (day -6, -2, -2; P=0.049), grew longer (11, 3, 6 days; P=0.005) and developed to a larger diameter (24, 11, 11 mm; P=0.032) in the ARA2 versus ARA1 and RA groups. In both RA and ARA2 groups, peak luteal phase estradiol concentrations were greater in women with (139.1, 177.8 pg/mL) versus without (78.0, 95.0 ng/mL) LPMWs (P=0.016, 0.074). In the RA group, 5/10 women developed LPMWs in association with higher mean (90.5 versus 53.3 pg/mL, P=0.028) and peak (139.1 versus 78.0 pg/mL, P=0.016) luteal phase estradiol concentrations versus women in the RA group without LPMWs, respectively. In the ARA2 group, LPMWs developed in association with atypical (>200ng/mL) elevations in estradiol concentrations in 4/8 women (50%). In all women (RA and ARA2 combined), the max diameter of the LPMW dominant follicle positively correlated with luteal phase estradiol (r=0.71, P<0.01) and negatively correlated with max luteal phase LH (r=-.52, P<0.05). In the ARA2 group, max LPMW dominant follicle diameter was negatively correlated with mean luteal phase progesterone (r=-.78, P<0.05). Progesterone was lower in women with (9.65 ng/mL) versus without (13.0 ng/mL, P=0.027) LPMWs in the ARA2, but not RA, group. Women in the RA group with LPMWs had a higher mean AFC >6mm and inhibin B versus those without LPMWs. Polyovulatory FPMWs (n=3) were detected only in the ARA2 group and were associated with higher maximum follicular phase estradiol production and elevated luteal phase progesterone when polyovulation occurred at ovulation #1 of the IOI (n=2). Conclusions: The prevalence of FPMWs and LPMWs did not differ as women age. However, in women of advanced reproductive age, dominant follicles in LPMWs emerged earlier, grew longer and to a larger diameter. Approximately 50% of cases of LPMWs that developed in women of advanced reproductive age were associated with atypically high luteal phase estradiol and decreased progesterone. Women of reproductive age with a higher AFC >6mm and inhibin B were more likely to develop LPMWs.



Ovarian follicle - Aging - Menstrual Cycle - Ovary - Estradiol



Master of Science (M.Sc.)


Obstetrics, Gynecology


Health Sciences


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