How Would a Decline in Sperm Concentration Over Time Influence the Probability of Pregnancy?

Background: Reports have suggested a decline in sperm concentration during the second half of the 20th century. The effect of this decline on fecundability (the monthly probability of pregnancy) could be detected in principle by a study of time to pregnancy. In practice, the amplitude of this expected effect is not well known and the statistical power of time-to-pregnancy studies to detect it has not been explored. Methods: We developed a nonparametric model to describe a temporal decline in sperm concentration using data on French semen donors. We then applied this model to 419 Danish couples planning a first pregnancy in 1992, to predict their time to pregnancy as if the pregnancy attempt had begun during earlier decades with higher sperm concentrations. Finally, we used bootstrap simulations to estimate the statistical power of prospective or retrospective studies that compared fecundability (estimated from time to pregnancy) across these time periods. We express the change in fecundability over time as a fecundability ratio (FR), with values less than 1 indicating decreased fecundability. Results: We estimate that the median sperm concentration decreased by 21% from 1977 to 1992 and by 47% from 1947 to 1992. The estimated decline in fecundability with those semen changes was 7% from 1977 to 1992 (FR = 0.93, adjusted) and 15% from 1947 to 1992 (FR = 0.85, adjusted). The total numbers of couples that would be needed in prospective studies of time to pregnancy to detect these changes in fecundability (with a power of 80%) were 12,000 when comparing 1977 to 1992, and 2000 when comparing 1947 to 1992. Retrospective studies of the same size that excluded childless couples had much lower statistical power and were biased toward the null. Conclusion: The effect of realistic declines in sperm concentration on time to pregnancy may be observed only with studies that include several thousand couples.

[1]  T. K. Jensen,et al.  Germ cell cancer and disorders of spermatogenesis: An environmental connection? , 1998, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[2]  T. K. Jensen,et al.  A follow-up study of environmental and biologic determinants of fertility among 430 Danish first-pregnancy planners: design and methods. , 1998, Reproductive toxicology.

[3]  Niels Keiding,et al.  Estimating time to pregnancy from current durations in a cross-sectional sample. , 2002, Biostatistics.

[4]  R. Gray Modeling Survival Data: Extending the Cox Model , 2002 .

[5]  N. Keiding,et al.  Declining human fertility? [editorial] , 2000 .

[6]  J. Bonde,et al.  Environmental semen studies--is infertility increased by a decline in sperm count? , 1999, Scandinavian journal of work, environment & health.

[7]  J. Auger,et al.  Debate about sperm count decline. , 1998, Environmental health perspectives.

[8]  D D Baird,et al.  Use of time to pregnancy to study environmental exposures. , 1986, American journal of epidemiology.

[9]  T. K. Jensen,et al.  A discrete survival model with random effects: an application to time to pregnancy. , 1997, Biometrics.

[10]  Lone Storgaard,et al.  Does Smoking During Pregnancy Affect Sons’ Sperm Counts? , 2003, Epidemiology.

[11]  R. M. Sharpe,et al.  Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? , 1993, The Lancet.

[12]  Fan Liu,et al.  Geographic differences in semen quality of fertile U.S. males. , 2002, Environmental health perspectives.

[13]  Tx Station Stata Statistical Software: Release 7. , 2001 .

[14]  N Keiding,et al.  Evidence for decreasing quality of semen during past 50 years. , 1992, BMJ.

[15]  S. Irvine,et al.  Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years , 1996, BMJ.

[16]  David Handelsman Sperm output of healthy men in Australia: magnitude of bias due to self-selected volunteers. , 1997, Human reproduction.

[17]  W. James Secular Trend in Reported Sperm Counts , 2009, Andrologia.

[18]  Tina Kold Jensen,et al.  Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners , 1998, The Lancet.

[19]  J. Olsen,et al.  Can a negative time trend of sperm density be explained by changes in reproductive pattern? , 2002, Epidemiology.

[20]  S Cnattingius,et al.  Human fertility does not decline: evidence from Sweden. , 1999, Fertility and sterility.

[21]  M. Joffe ARE PROBLEMS WITH MALE REPRODUCTIVE HEALTH CAUSED BY ENDOCRINE DISRUPTION? , 2001, Occupational and environmental medicine.

[22]  K. Rothman,et al.  Does relaxed reproductive selection explain the decline in male reproductive health? A new hypothesis. , 2002, Epidemiology.

[23]  C. Weinberg,et al.  Reporting errors in time-to-pregnancy data collected with a short questionnaire. Impact on power and estimation of fecundability ratios. , 1991, American journal of epidemiology.

[24]  M. Joffe Invited commentary: the potential for monitoring of fecundity and the remaining challenges. , 2003, American journal of epidemiology.

[25]  N Keiding,et al.  Declining human fertility? , 2000, Fertility and sterility.

[26]  P. Andersen,et al.  We should monitor human fecundity, but how? A suggestion for a new method that may also be used to identify determinants of low fecundity. , 1999, Epidemiology.

[27]  Niels Jørgensen,et al.  East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. , 2002, Human reproduction.

[28]  J. H. Olson,et al.  Semen analyses in 1,283 men from the United States over a 25-year period: no decline in quality. , 1996, Fertility and sterility.

[29]  N. Keiding,et al.  Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities. , 2002, Human reproduction.

[30]  Time trends in biological fertility in Britain , 2000, The Lancet.

[31]  H. Léridon,et al.  Human Fertility: the basic components , 1978 .

[32]  Niels Keiding,et al.  Regional differences in semen quality in Europe , 2001, Human reproduction.

[33]  D. Baird,et al.  Epidemiologic studies of human semen quality: considerations for study design. , 2002, American journal of epidemiology.

[34]  J. Bonde Environmental fertility research at the turn of the century. , 1999, Scandinavian journal of work, environment & health.

[35]  R. Slama,et al.  How much of the decline in sperm counts can be explained by relaxed reproductive selection? , 2002, Epidemiology.

[36]  J. Olsen,et al.  Invited commentary: monitoring fecundity over time--if we do it, then let's do it right. , 2003, American journal of epidemiology.

[37]  A. Czeizel,et al.  No teratogenic effect after clotrimazole therapy during pregnancy. , 1999, Epidemiology.

[38]  J W Overstreet,et al.  Sperm morphology, motility, and concentration in fertile and infertile men. , 2001, The New England journal of medicine.

[39]  S. Swan,et al.  The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996. , 2000, Environmental health perspectives.

[40]  J. Olsen,et al.  Reproductive Epidemiology , 2005, Handbook of Epidemiology.