Bernardo Colombo

Increased infertility with age in men and women.

OBJECTIVE: To estimate the effects of aging on the percentage of outwardly healthy couples who are sterile (completely unable to conceive without assisted reproduction) or infertile (unable to conceive within a year of unprotected intercourse). METHODS: A prospective fecundability study was conducted in a sample of 782 couples recruited from 7 European centers for natural family planning. Women aged 18–40 years were eligible. Daily intercourse records were used to adjust for timing and frequency of intercourse when estimating the per-menstrual-cycle probability of conception. The number of menstrual cycles required to conceive a clinical pregnancy and the probability of sterility and infertility were derived from the estimated fecundability distributions for men and women of different ages. RESULTS: Sterility was estimated at about 1%; this percent did not change with age. The percentage infertility was estimated at 8% for women aged 19–26 years, 13–14% for women aged 27–34 years and 18% for women aged 35–39 years. Starting in the late 30s, male age was an important factor, with the percentage failing to conceive within 12 cycles increasing from an estimated 18–28% between ages 35 and 40 years. The estimated percentage of infertile couples that would be able to conceive after an additional 12 cycles of trying varied from 43–63% depending on age. CONCLUSION: Increased infertility in older couples is attributable primarily to declines in fertility rates rather than to absolute sterility. Many infertile couples will conceive if they try for an additional year. LEVEL OF EVIDENCE: II-2

Cervical mucus symptom and daily fecundability: first results from a new database

With the collaboration of Italian centres providing services on natural family planning, a prospective study collected data on 2755 menstrual cycles of 193 women. A database was constructed using information on the daily characteristics of cervical mucus and episodes of intercourse. Taking the day of peak mucus as a conventional marker of ovulation, the database identified the length (12 days) and location of a ‘window’ of potential fertility, the highest level of conception probability being confined to the central five to six days. Univariate analysis provided evidence of the impact on fecundability of the woman’s age and the basic infertile pattern of a cycle. Several analytical approaches highlighted the relationship between daily mucus characteristics and levels of fecundability.

Reduced fertilization rates in older men when cervical mucus is suboptimal.

OBJECTIVE: Cervical mucus is vital in the regulation of sperm survival and transport through the reproductive tract. The goal of this study is to assess whether the lowered fertility for men in their late 30s and early 40s is related to the nature of cervical mucus on the day of intercourse. METHODS: In a prospective study of 7 European family planning centers, 782 couples not using birth control recorded daily observations of intercourse and the nature of cervical mucus. Using data from 1,459 menstrual cycles, 342 ending in pregnancy, we estimate day-specific conception probabilities in relation to mucus and male and female age. RESULTS: On days where cervical mucus was not evident, intercourse for men in their late 30s and early 40s was 50% less likely to result in a clinical pregnancy, adjusting for intercourse timing and female age. As secretions become more conducive to sperm transport, the effect of male age diminishes steadily from 21% on days with damp secretions, to 11% on days with thick mucus, to only 4% on days with most fertile-type mucus. CONCLUSION: The effect of male age on fecundability can be minimized by timing intercourse on days with optimal secretions. LEVEL OF EVIDENCE: II-2

Bayesian Modeling of Markers of Day-Specific Fertility

Cervical mucus hydration increases during the fertile interval before ovulation. Because sperm can only penetrate mucus having a high water content, cervical secretions provide a reliable marker of the fertile days of the menstrual cycle. This article develops a Bayesian approach for modeling of daily observations of cervical mucus and applies the approach to assess heterogeneity among women and cycles from a given woman with respect to the increase in mucus hydration during the fertile interval. The proposed model relates the mucus observations to an underlying normal mucus hydration score, which varies relative to a peak hydration day. Uncertainty in the timing of the peak is accounted for, and a novel weighted mixture model is used to characterize heterogeneity in distinct features of the underlying mean function. Prior information on the mucus hydration trajectory is incorporated, and a Markov chain Monte Carlo approach is developed. Based on data from a study of daily fecundability, there appears to be substantial heterogeneity among women in detected preovulatory increases in mucus hydration, but only minimal differences among cycles from a given woman.

Age effect : results from a detailed prospective study on daily fecundability

BACKGROUND Demographers, epidemiologists and clinicians have long been interested in the estimation of age-specific fecundability. With the progressive postponement of age at family formation in Western countries, this topic has recently become the focus of renewed attention. METHODS In order to correctly estimate the effect of biological ageing on fecundability it is crucial to collect detailed information through a rigorous study design and to apply suitable models for analysing time to pregnancy data. In this article we discuss some methodological problems concerning the study of fecundability and its dependence on biological ageing. We also present the Multinational Study in Daily Fecundability which has produced a very rich database with detailed behavioural and physiological information prospectively collected on every cycle. Finally, we review some results on age effects obtained from these data. RESULTS Our findings show that the decline in fecundability from age 28 to age 33 is not statistically significant and very modest. CONCLUSION The results presented here do not appear to be particularly alarming with regard to the postponement of conception of the first child from age 28 to 33. This postponement could however lead to attempts to conceive a second child after age 35, when fecundability starts to decrease rapidly and when the risk of genetic disorders increases.