title: Too old to have children? Lessons from natural fertility populations.
abstract: OBJECTIVE
  Is it possible to construct an age curve denoting the ages above which women are biologically too old to reproduce?
  
  
  CONCLUSIONS
  We constructed a curve based on the distribution of female age at last birth in natural fertility populations reflecting the ages above which women have become biologically too old to have children.
  
  
  BACKGROUND
  The median age at last birth (ALB) for females is ∼40-41 years of age across a range of natural fertility populations. This suggests that there is a fairly universal pattern of age-related fertility decline. However, little is known about the distribution of female ALB and in the present era of modern birth control, it is impossible to assess the age-specific distribution of ALB. Reliable information is lacking that could benefit couples who envisage delaying childbearing.
  
  
  METHODS
  This study is a review of high-quality historical data sets of natural fertility populations in which the distributions of female age at last birth were analysed. The studies selected used a retrospective cohort design where women were followed as they age through their reproductive years.
  
  
  METHODS
  Using a common set of eligibility criteria, large data files of natural fertility populations were prepared such that the analysis could be performed in parallel across all populations. Data on the ALB and confounding variables are presented as box and whisker plots denoting the 5th, 25th, 50th, 75th and 95th percentile distribution of the age at last birth for each population. The analysis includes the estimation of Kaplan-Meier curves for age at last birth of each population. The hazard curve for ALB was obtained by plotting the smoothed hazard curve of each population and taking the lowest hazard within a time period of at least 5 years. This lowest hazard curve was then transformed into a cumulative distribution function representing the composite curve of the end of biological fertility. This curve was based on the data from three of the six populations, having the lowest hazards of end of fertility.
  
  
  RESULTS
  We selected six natural fertility populations comprising 58 051 eligible women. While these populations represent different historical time periods, the distribution of the ages at last birth is remarkably similar. The curve denoting the end of fertility indicates that <3% of women had their last birth at age 20 years meaning that almost 98% were able to have at least one child thereafter. The cumulative curve for the end of fertility slowly increases from 4.5% at age 25 years, 7% at age 30 years, 12% at age 35 years and 20% at age 38 years. Thereafter, it rises rapidly to about 50% at age 41, almost 90% at age 45 years and approaching 100% at age 50 years.
  
  
  CONCLUSIONS
  It may be argued that these historical fertility data do not apply to the present time; however, the age-dependent decline in fertility is similar to current populations and is consistent with the pattern seen in women treated by donor insemination. Furthermore, for reproductive ageing, we note that it is unlikely that such a conserved biological process with a high degree of heritability would have changed significantly within a century or two.
  
  
  CONCLUSIONS
  We argue that the age-specific ALB curve can be used to counsel couples who envisage having children in the future. Our findings challenge the unsubstantiated pessimism regarding the possibility of natural conception after age 35 years.
  
  
  BACKGROUND
  No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Frans
authors.initials: F
authors.lastname: van Poppel
authors.forename: Dik F
authors.initials: DF
authors.lastname: Habbema
authors.forename: Ken R
authors.initials: KR
authors.lastname: Smith
authors.forename: Henri
authors.initials: H
authors.lastname: Leridon
authors.forename: Egbert R
authors.initials: ER
authors.lastname: te Velde
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies
keywords: delay of childbearing; natural fertility; ovarian ageing; reproductive demography; reproductive epidemiology