Offspring sex ratio of subfertile men and men with abnormal sperm characteristics

Rune Jacobsen1, Erik Bostofte, Niels E. Skakkebæk, Johnni Hansen and Henrik Møller

Department of Epidemiology, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Previous work has suggested an association between male subfertility and a female-biased offspring sex ratio. This study of the reproduction of men who had a semen analysis at the Sperm Analysis Laboratory in Copenhagen in the period 1963–1993 showed that the subfertile men had an offspring sex ratio as expected (51.0% boys versus 51.3%, P = 0.56), and within the cohort, the offspring sex ratio had no material association with particular semen characteristics. Our results thus suggest that no important association exists between general male subfertility and a female-biased offspring sex ratio.

Key words: female-biased/male subfertility/offspring sex ratio


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The decrease in the sex ratio (proportion of males) among newborn infants in many populations (Møller, 1996Go) and the possible decrease in semen quality (Carlsen et al., 1992Go) lead to the question of whether these temporal trends are independent phenomena or, alternatively, somehow connected to each other (Møller, 1996Go, 1998Go; James, 1997Go). Associations have been indicated between testicular cancer and a female-biased offspring sex ratio (Møller, 1998Go) and between subfertility and subsequent risk of testicular cancer (Møller and Skakkebæk, 1999Go). In the present study we examined on a cohort basis the influence of subfertility and abnormal semen characteristics on the offspring sex ratio.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Information on men (born 1945–1980) with possible fertility problems, who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen in the period 1963–1993, was obtained. The cohort comprised 32440 men of whom 15218 had one or more children either before attending the laboratory or after. The cohort was linked with information on reproduction from the Fertility Database at Statistics Denmark. Men who visited the laboratory for a reason other than fertility problems (e.g. semen examination following a vasectomy) were excluded from the analysis. For men who had multiple semen tests, only the first test was used in the analysis. The total population of Danish men born in the period 1945–1980 (n = 1488957) served as a basis of comparison. The number of children of the men who had attended the Sperm Analysis Laboratory was 25738 and the number of children of men in the comparison group was 1250952.

Following the linkages, information for each man was available on date of birth, dates of birth of children, date of first semen analysis, sperm concentration (million/ml), sperm motility (poor, good), morphologically abnormal spermatozoa (%) and date of death. The cohort was stratified with respect to the semen characteristics according to the World Health Organization classification of subfertility (WHO, 1999Go). The statistical analyses were done by contingency tables and {chi}2 tests.


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The results are shown in Table IGo. Overall, the cohort members produced offspring with a sex ratio that was about as expected, both before attending the Sperm Analysis Laboratory [51.1% males, not significant (NS)] and after (50.7% males, NS). Similarly, internal comparisons within the cohort showed no statistically significant dependence of the offspring sex ratio on the measured semen concentration, semen motility or on the proportion of morphologically abnormal spermatozoa. The data were suggestive of a weak to moderate association with low semen concentration (50.6% male offspring versus 51.1% in the men with 20 million/ml or higher), but also this contrast was far from reaching statistical significance (P = 0.48).


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Table I. Sex ratio of 25738 children, born in the period 1958–1993, fathered by 15218 men, born 1945–1980, who had semen analysis in the period 1963–1993
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The present study found no association between semen characteristics and sex ratio. This suggests that no material association exists between general male subfertility and a female-biased offspring sex ratio, as had been hypothesized (Møller, 1996Go, 1998Go; Møller and Skakkebæk, 1999Go). In consequence, the temporal trends in sex ratio (Møller, 1996Go) and in sperm concentrations (Carlsen et al., 1992Go) may have no or only limited biological association with each other, despite the apparent links of both subfertility and female-biased offspring sex ratios to testicular cancer. However, heterogeneity among subfertile men in regard to their offspring sex ratio may exist, for example subfertile men destined to suffer testicular cancer are expected to have an excess of daughters (Jacobsen et al., 2000Go).


    Acknowledgments
 
We are grateful to Birgitte Antoniades, Gerda Engholm and Jørgen H.Olsen for their contributions to this work.


    Notes
 
1 To whom correspondence should be addressed at: Department of Epidemiology, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Panum Institute,Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.E-mail: R.jacobsen{at}pubhealth.ku.dk Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Carlsen, E., Giwercman, A., Keiding, N. and Skakkebæk, N.E. (1992) Evidence for decreasing quality of semen during past 50 years. Brit. Med. J., 305, 609–613.[ISI][Medline]

Jacobsen, R., Bostofte, E., Engholm, G. et al. (2000) Fertility and offspring sex ratio of men who develop testicular cancer: a record linkage study. Hum. Reprod., 15, 1958–1961.[Abstract/Free Full Text]

James, W.H. (1997) Secular trends in monitors of reproductive hazard. Hum. Reprod., 12, 417–421.[ISI][Medline]

Møller, H. (1996) Change in male:female ratio among newborn infants in Denmark. Lancet, 348, 828–829.[Medline]

Møller, H. (1998) Trends in sex-ratio, testicular cancer and male reproductive hazards: are they connected? APMIS, 106, 232–238.[ISI][Medline]

Møller, H. and Skakkebæk, N.E. (1999) Risk of testicular cancer in subfertile men: case-control study. Brit. Med. J., 318, 559–562.[Abstract/Free Full Text]

WHO (1999) Laboratory manual for examination of human semen and sperm-cervical mucus interaction. 4th edn, Cambridge University Press, Cambridge, UK.

Submitted on April 5, 2000; accepted on July 28, 2000.