Detection of Effects on Male Reproduction—A Literature Survey

Abstract

The 1CH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) Guideline for Detection of Toxicity to Reproduction for Medicinal Products, adopted at the Second ICH Conference in Orlando, FL, U.S.A., emphasized the need for research into the suitability of various methods for the detection of effects on fertility in males. The current project was undertaken to compare the efficiency of methods by evaluating reports in the open literature. The results of the examination of 117 substances or substance classes support the view that histopathology and organ weight analysis provide the best general-purpose means of detecting substances with the potential to affect male fertility. Examinations at up to 4 weeks of treatment appear to be as effective as examinations conducted at later times. Mating with females for detection of effects unrelated to interference with sperm production appears to provide an optimal combination because adding other methodologies does not materially improve the detection rate. As to the timing of the mating trial, a 2-week premating period is as efficient as mating at 4 weeks and apparently more efficient than mating after prolonged premating treatment.