ABSTRACT
These studies are designed to identify toxic effects resulting from treatment from before mating (both males and females) and continuing through mating and implantation. These studies also assess potential changes in the estrous cycle of females and possible functional effects that may not be detected in acute toxicity testing by histological examinations of the male reproductive organs. Whereas the guidelines recommend physical mating for testing fertility – albeit feasible - this is not being done routinely in NHPs mainly for two reasons: (i) The default number of offspring per pregnancy in macaques is one, so checking for implantation sites is not necessary, as twin pregnancies/births are extremely rare in macaques. We have encountered only five twin pregnancies among more than 4000 pregnancies (10). (ii) As stated earlier, spontaneous fertility rates in macaques are relatively low, and pre-implantation losses are often high (14). Compared to the sophisticated clinical parameters available, fertility test by mating is rather insensitive and is therefore not recommended except for specific indications that the test item might affect mating behavior. A request for physical mating in NHP fertility studies may be related to differential interpretation of ICH guidelines (40).
