Maternal ageing is a very important factor in aneuploidy. It is associated with an increased risk of a liveborn trisomy, especially Down's syndrome, and with a dramatic increase in trisomic conceptions, the majority of which miscarry. A total of 585 volunteer couples who were planning pregnancies participated in a prospective study of reproduction. The couples answered extensive questionnaires and early pregnancy tests (day 28) were conducted each month. The number of years of contraceptive pill use was correlated with pregnancy outcome. Lowered rates of miscarriage were found with increased years of pill use. The cut-off point for this positive effect appeared to be 9 years. Use of oral contraceptives for > or = 9 years was associated with a spontaneous abortion rate of 11.3%, which is about half the rate (23%) which was found in couples who had not used the pill. However, the effect of pill taking was correlated with female age, and when age was examined as an independent factor, the reduction in miscarriage was only statistically significant in women > 30 years old, where the rate of abortion reduced from 28 to 7%. Because age-related aneuploidy in humans probably occurs as a direct or an indirect result of follicle depletion, it is proposed that the long-term use of the oral contraceptive pill protects against abortion due to aneuploidy by preserving the number of follicles.
PIP: The impact of oral contraceptive use on ovarian follicular dynamics--considered to be a key determinant of trisomic conceptions--was investigated in a prospective study of 585 Australian women who were planning pregnancy. Urine samples were collected on the last day of each menstrual cycle in which conception was attempted; outcomes were classified as live birth of a normal infant, spontaneous abortion, or persisting infertility. Only 39 women had never used oral contraceptives (OCs); the majority had used the pill for at least six months. The age-related miscarriage rate was 13.4% in women aged 25-29 years, 17.3% in those aged 30-34 years, and 28.3% in those aged 35-39 years. The frequency of miscarriage showed a pattern of decline with increasing years of OC use: 0-2, 22.2%; 3-4, 17.3%; 5-6, 19.6%; 7-8, 16.7%; and 9 or more, 11.4%. However, the addition of maternal age to the logistic regression model revealed that the association between OC use duration and miscarriage was significant (p 0.001) only for women 30 years of age and over. In this latter group. the mean miscarriage rate decreased from 28% with 0-2 years of OC use to 7% with 9 or more years of use. It is hypothesized that the decrease of about 15% in the rate of miscarriage among longterm pill users aged 30 years or over is attributable to OC-related preservation of ovarian follicles and a subsequent reduction in spontaneous abortion due to aneuploidy--a defect related to pre-menopausal declines in follicle numbers.