O'Connor K A, Holman D J, Wood J W
Population Research Institute, Pennsylvania State University, University Park 16802, USA.
Maturitas. 1998 Oct 12;30(2):127-36. doi: 10.1016/s0378-5122(98)00068-1.
Worldwide, human fertility declines with increasing maternal age, after contraceptive-use patterns and behavioral factors are taken into consideration. Here, we summarize some of our theoretical and empirical work examining the biological factors contributing to this age pattern of fertility. We undertook an 11 month prospective endocrinological study in a natural fertility (non-contracepting) population (rural Bangladesh) to estimate the contributions of fetal loss and fecundability (the probability of conception) to declining fecundity with age. Prospective interviews and urine samples for pregnancy tests were collected twice weekly from up to 700 women. These data were used to test mathematical models of the underlying biological processes contributing to changing fecundability and fetal loss risk with maternal age. The results indicate that much of the decline in fecundity can be attributed to an increasing risk of fetal loss with maternal age. Much of this fetal loss is due to chromosomal abnormalities--a result of ageing oocytes. Fecundability, on the other hand, does not begin to decline until the early 40s. We hypothesize that this is also a result of ageing at the ovarian level, namely follicular atresia, in the years just prior to menopause. The irregularity of menstrual cycles--longer cycles and increasingly variable hormonal patterns--at these ages may be a direct result of the small and rapidly dwindling remaining pool of follicles. We present a simple mathematical model of this process, and some preliminary laboratory results that support the model.
在全球范围内，在考虑了避孕使用模式和行为因素之后，人类生育率会随着母亲年龄的增长而下降。在此，我们总结了一些我们的理论和实证研究工作，这些工作探讨了导致这种生育率年龄模式的生物学因素。我们在一个自然生育（未采取避孕措施）的人群（孟加拉国农村）中进行了一项为期11个月的前瞻性内分泌学研究，以评估胎儿丢失和受孕能力（受孕概率）对随着年龄增长生育能力下降的影响。每周两次对多达700名女性进行前瞻性访谈并收集用于妊娠试验的尿液样本。这些数据被用于测试有助于解释受孕能力和胎儿丢失风险随母亲年龄变化的潜在生物学过程的数学模型。结果表明，生育能力的下降很大程度上可归因于随着母亲年龄增长胎儿丢失风险的增加。这种胎儿丢失大多是由于染色体异常——这是衰老卵母细胞的结果。另一方面，受孕能力直到40岁出头才开始下降。我们推测这也是卵巢水平衰老的结果，即在绝经前几年出现卵泡闭锁。这些年龄段月经周期的不规律——周期延长和激素模式变化越来越大——可能是卵泡数量少且迅速减少的直接结果。我们提出了这个过程的一个简单数学模型，以及一些支持该模型的初步实验室结果。
