The goal of this study is to identify factors that influence ovarian age. We define """"""""ovarian age"""""""" as the size of oocyte pool. Ovarian follicle (oocyte) counts are highest before birth and decrease as women age; similarly, the number of follicles that develop during each menstrual cycle decreases as women age. At any particular chronologic age, women vary in both the size of their oocyte pools and the number of antral (developing) follicles. These variations may reflect differences in the size of the pool at its formation or in rates of oocyte atresia. Increasing numbers of women are deferring childbearing to the later years. Since ovarian aging is accompanied by conception delay and an increased risk of infertility and trisomic conception, the identification of risk factors for accelerated ovarian aging would have significant implications for reproductive research and primary prevention. The proposed study draws on data from two already completed studies to identify risk factors for ovarian age. In the first study, ovarian age is measured by age at onset of the menopausal transition and at menopause in 494 women. In the second study. ovarian age is measured shortly after an index pregnancy by counts of ovarian antral follicles and three hormonal indicators of ovarian age-follicle stimulating hormone, inhibin B and estradiol-in 173 women. Both studies include extensive data on maternal characteristics and exposures that might influence ovarian aging. They thus provide an excellent and unique opportunity to (i) identify determinants of ovarian age in fertile women during natural cycles and (ii) examine whether determinants of ovarian age during the reproductive years differ from determinants during the menopausal transition.
The specific aims are: 1. To examine whether maternal characteristics (e.g., body mass index) or exposures (e.g., smoking) are associated with ovarian age measured by (i) antral follicle counts, (ii) selected hormonal indicators, (iii) age at onset of the menopausal transition, and (iv) age at menopause. 2. To conduct exploratory studies, using data from the Oocyte study, to assess whether or not skewed X-inactivation is associated with advanced ovarian age.
| Kline, Jennie K; Kinney, Ann M; Levin, Bruce et al. (2014) Intermediate CGG repeat length at the FMR1 locus is not associated with hormonal indicators of ovarian age. Menopause 21:740-8 |
| Kline, J; Kinney, A; Brown, S et al. (2012) Trisomic pregnancy and intermediate CGG repeat length at the FMR1 locus. Hum Reprod 27:2224-32 |
| Kline, J K; Kinney, A M; Levin, B et al. (2011) Trisomic pregnancy and elevated FSH: implications for the oocyte pool hypothesis. Hum Reprod 26:1537-50 |
| Kinney, A; Kline, J; Kelly, A et al. (2007) Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years. Hum Reprod 22:1175-85 |
| Kinney, Ann; Kline, Jennie; Levin, Bruce (2006) Alcohol, caffeine and smoking in relation to age at menopause. Maturitas 54:27-38 |
| Kline, Jennie; Kinney, Ann; Levin, Bruce et al. (2006) X-chromosome inactivation and ovarian age during the reproductive years. Fertil Steril 85:1488-95 |
| Kline, J; Kinney, A; Kelly, A et al. (2005) Predictors of antral follicle count during the reproductive years. Hum Reprod 20:2179-89 |
| Warburton, D (2005) Biological aging and the etiology of aneuploidy. Cytogenet Genome Res 111:266-72 |
| Kline, J; Kinney, A; Reuss, M L et al. (2004) Trisomic pregnancy and the oocyte pool. Hum Reprod 19:1633-43 |
| Warburton, Dorothy; Dallaire, Louis; Thangavelu, Maya et al. (2004) Trisomy recurrence: a reconsideration based on North American data. Am J Hum Genet 75:376-85 |
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