Requirements for controlled therapeutic trials in male infertility.

The majority of men who present with infertility have oligospermia or asthenospermia which renders them subfertile; pregnancies occur at lower than normal rates. Currently available treatments for this group are of uncertain value. This paper outlines an approach to controlled trials to test old and new methods for their ability to improve semen quality and increase pregnancy rates. As well as careful design, the need for control groups and large numbers of subjects is emphasized. Control groups are necessary because pregnancies and apparent or real spontaneous improvements in semen test results occur without treatment. Trials to evaluate differences in pregnancy rates need to be large because pregnancy rates are low and the margin for improvement narrow. Most untreated infertile couples have average pregnancy rates of less than 5% per month, whereas pregnancy rates in the general community average 20% per month. Under these circumstances, small trials with less than 20 pregnancies are unhelpful as they are not sensitive enough to detect less than threefold differences in pregnancy rates between groups. The number of subjects required for a trial can be calculated or determined from tables or graphs. A 50% difference in pregnancy rates in two groups given alternative treatments only has a high chance of being statistically significant if there are hundreds of subjects achieving a total of approximately 200 pregnancies in the trial. Such large trials can only be performed by several centres collaborating.