Professor Roger Robinson
British Medical Journal
BMA House
Tavistock Square
London WC1H 9JR
United Kingdom
Tuesday, 06 June 2000
Dear Professor Robinson
Regarding manuscript 001508:
Following our previous correspondence, we have the pleasure of submitting a revised manuscript.
We are grateful for a number of helpful suggestions from the committee and from Professor David Forman.
The committee:
1) The sentence has been modified as suggested.
2) The sentences have been omitted as suggested.
3) In the present study we show an association between abnormal semen characteristics and subsequent risk of testicular cancer in a cohort of men from infertile couples. Our findings suggest that abnormal semen characteristics increase the risk of testicular cancer. It in not plausible that this association is conditioned by the female partner; this would require an association between abnormal semen characteristics and the choice of a female partner with fertility problems. We find this scenario rather unlikely.
4) We have used the same terminology as in the WHO laboratory manual for examination of human semen and sperm-cervical mucus interaction, Cambridge University Press, 1999. The classification of men according to their semen characteristics were done according to this manual, as referenced in the Materials and Methods section.
Referee Professor David Forman:
1) Importance to general readers: A note on public health implications has been added to the Discussion section and the Abstract.
2) Research question: The term abnormal semen characteristics refers to the conventional standardisation given by the WHO laboratory manual for examination of human semen and sperm-cervical mucus interaction, Cambridge University Press, 1999, as mentioned and referenced in the Introduction and the Materials and Methods section. The word "quality" has been replaced with "characteristics".
3) Research question: See item 1 above.
4) Methods: The 32442 males are all the males having their semen analysed in the period 1963-1995, except men who visited the laboratory for other reason than fertility problems (e.g. semen analysis following vasectomy). This is stated in the first lines of the Materials and Methods section. Men are referred to the clinic from general practitioners and urologists, and the investigations are paid from the public health system. This information has been added to the Materials and Methods section. A short general description of the Sperm Analysis Laboratory in Copenhagen, has been added to the Materials and Methods section.
5) Methods: The criteria for the cut off points are given by the WHO laboratory manual for examination of human semen and sperm-cervical mucus interaction, Cambridge University Press, 1999, as referenced in the Materials and Methods section.
6) Results: Table 2 show the effect of time since first semen analysis on the risk of testicular cancer. Based on Table 2 one can easily calculate standardised incidence ratios (observed/expected) when one excludes the observed cases at various time periods. We find that Table 2 is sufficient to show the relationship between time since first semen analysis and testicular cancer risk.
7) Results: Standardised incidence ratios and 95% confidence intervals have been computed separately for seminoma and non-seminoma; the estimates are given in the Results section.
8) Results: Case 1 died from myeloid leukaemia, which is seen as secondary to testicular cancer (result of treatment). The germ cell tumour located in the retroperitoneum, could be a primary extragonadal germ cell tumor or a metastasis from the testicular tumour. In Table 5 this is mentioned and has further been mentioned in the Results section.
9) Results: Standardised incidence ratio has been used instead of standardised morbidity ratio.
10) Discussion: The sentence has been changed to "Some indications exist for the hypothesis that testicular cancer has its origin in foetal life".
11) Interpretation and conclusions: A part on public health implications has been added to the Abstract and Discussion section.
12) Abstract: A part on public health implications has been added to the Abstract and Discussion section.
We hope that you will find the revised manuscript satisfactory, and we hope to see this work in print soon in BMJ.
Yours sincerely
Rune Jacobsen
Scientist