Age and fecundability in a North American preconception cohort study

Abstract

Background: There is a well-documented decline in fertility treatment success with increasing female age; however, there are few preconception cohort studies that have examined female age and natural fertility. In addition, data on male age and fertility are inconsistent. Given the increasing number of couples who are attempting conception at older ages, a more detailed characterization of age-related fecundability in the general population is of great clinical utility.

Objective: The purpose of this study was to examine the association between female and male age with fecundability.

Study design: We conducted a web-based preconception cohort study of pregnancy planners from the United States and Canada. Participants were enrolled between June 2013 and July 2017. Eligible participants were 21-45 years old (female) or ≥21 years old (male) and had not been using fertility treatments. Couples were followed until pregnancy or for up to 12 menstrual cycles. We analyzed data from 2962 couples who had been trying to conceive for ≤3 cycles at study entry and reported no history of infertility. We used life-table methods to estimate the unadjusted cumulative pregnancy proportion at 6 and 12 cycles by female and male age. We used proportional probabilities regression models to estimate fecundability ratios, the per-cycle probability of conception for each age category relative to the referent (21-24 years old), and 95% confidence intervals.

Results: Among female patients, the unadjusted cumulative pregnancy proportion at 6 cycles of attempt time ranged from 62.0% (age 28-30 years) to 27.6% (age 40-45 years); the cumulative pregnancy proportion at 12 cycles of attempt time ranged from 79.3% (age 25-27 years old) to 55.5% (age 40-45 years old). Similar patterns were observed among male patients, although differences between age groups were smaller. After adjusting for potential confounders, we observed a nearly monotonic decline in fecundability with increasing female age, with the exception of 28-33 years, at which point fecundability was relatively stable. Fecundability ratios were 0.91 (95% confidence interval, 0.74-1.11) for ages 25-27, 0.88 (95% confidence interval, 0.72-1.08) for ages 28-30, 0.87 (95% confidence interval, 0.70-1.08) for ages 31-33, 0.82 (95% confidence interval, 0.64-1.05) for ages 34-36, 0.60 (95% confidence interval, 0.44-0.81) for ages 37-39, and 0.40 (95% confidence interval, 0.22-0.73) for ages 40-45, compared with the reference group (age, 21-24 years). The association was stronger among nulligravid women. Male age was not associated appreciably with fecundability after adjustment for female age, although the number of men >45 years old was small (n=37).

Conclusion: In this preconception cohort study of North American pregnancy planners, increasing female age was associated with an approximately linear decline in fecundability. Although we found little association between male age and fecundability, the small number of men in our study >45 years old limited our ability to draw conclusions on fecundability in older men.

Keywords: age; fecundability; fertility; preconception cohort.

Figure 1

Association between female and male age and fecundability, fitted by restricted cubic splines, PRESTO, 2013–2017. The reference value was 21 years, the youngest age in the cohort. Both unadjusted (dotted line) and adjusted (solid line; adjusted for female education, female smoking, female alcohol use, female BMI, female vigorous physical activity, male education, male BMI, male smoking, household income, using methods to improve chances of conception, intercourse frequency, last method of contraception, and partner age) results are presented. Knots are located at the 10^th, 25^th, 75^th, and 90^th percentiles (25, 27, 33, and 36 years for females; 26, 28, 35, and 39 years for males). The spline for male age is trimmed at the 99^th percentile (50 years).