Conceptions involving aging gametes are of relevance to natural family planning (NFP) because women using NFP to avoid pregnancy abstain from intercourse during the fertile time of the cycle. To help verify the safety of pregnancies occurring among NFP practitioners, our group has, since 1986, conducted a large cohort study involving six experienced NFP centers. Timing of conception was determined from NFP charts, in which women recorded days on which intercourse occurred. The number of days from the most probable conception intercourse to probable day of ovulation was first determined, and used as an estimate of the time gametes remained in the genital tract before fertilization. Several studies have already been completed, cohort as well as case-control in nature. 1. Spontaneous abortions. Three hundred and sixty-one conceptions occurred during the optimal time (day -1 or 0 relative to ovulation), and of these 33 resulted in spontaneous abortion (9.1%). Five hundred and seven conceptions occurred at non-optimal times during the cycle, and of these 55 resulted in spontaneous abortions (10.9%). These differences were not statistically significant (relative risk 1.19, 95% CI, 0.79-1.80). 2. Anomalies. Among 780 singleton births in 868 cohort pregnancies, 24 infants had major anomalies (3.1%) as of the present analysis. This frequency is comparable to the general population. To further assess anomalies we employed a case-control approach. All consecutive births (live and stillborn) weighing 500 g or more taking place in 18 participating South American hospitals were examined for minor and major congential anomalies. Mothers of malformed and control infants did not differ with respect to the reported frequency of NFP use, which overall was 6.3% of the 10,642 mothers interviewed (5277 having a malformed infant; 5371 controls). Of 262 discordant pairs, there were 28 or 10.69% mothers within the Down syndrome case group vs. 16/262 or 6.11% among matched controls. The odds ratio was 1.84, 95% CI, 0.99-3.96; however, even this non-significant difference narrowed substantially when adjusted for maternal age (OR, 1.78; 95% CI, 0.84-3.75); parity (OR, 1.68; 95% CI, 0.87-3.24); maternal educational level (OR, 1.71; 95% CI, 0.86-3.44); or all three together (OR, 1.74; 95% CI, 0.83-3.64). Conclusions. Our findings should be reassuring to natural family planning users. The overall rate of spontaneous abortion was not increased in NFP users who became pregnant, nor to date was the rate of anomalies. Any contribution to Down syndrome or abortion due to aging gametes would have to be small.