The long-term goal is to elucidate the processes leading to trisomy. Trisomy is the most frequent chromosomal aberration among births and clinically recognized spontaneous abortions and gives rise (as trisomy 21) to the most prevalent form of severe or moderate mental retardation. Advancing chronologic maternal age is the primary risk factor for trisomy. The proposed project tests whether trisomy arises as a function of the size of the oocyte pool and, in particular, the hypothesis that risk at given chronologic ages is increased in women with accelerated rates of oocyte atresia and hence smaller oocyte pools. Since atresia rate is a determinant of age at menopause, this hypothesis leads to the prediction that menopause occurs earlier among women with trisomic pregnancies than women with chromosomally normal pregnancies at the same chronologic age. The study draws on private patients who enrolled in a previous study over the period 1974-1986. The sample includes women with spontaneous abortions of known karyotype and a control group of women with deliveries at 28 weeks or later. Women who are 45 years or older who had trisomic spontaneous abortions (n=149), chromosomally normal spontaneous abortions (n=210), or chromosomally normal live births (n=261) will be located and interviewed about menstrual function and other factors. The roughly two- thirds (n=397) who will not yet have reached menopause will be followed at six-month intervals over 48 months. The specific aims are: 1. To test whether age at menopause is earlier among women with prior trisomic spontaneous abortions than among women with chromosomally normal spontaneous abortions or with chromosomally normal live births, controlling both by design and analysis for chronologic age at study pregnancy and follow-up. 2. To take advantage of menstrual data collected during follow-up to explore whether onset of menstrual cycle irregularity, an indicator related both to size of the oocyte pool and to hormonal changes, is earlier among women with prior trisomic spontaneous abortions than among women with chromosomally normal spontaneous abortions or live births.