ARTs in action in nonhuman primates: Symposium summary – advances and remaining issues

Abstract

It is clear from the presentations at this symposium that Assisted Reproductive Technologies (ARTs) in nonhuman primates have made substantial progress since 1984, when the first reports appeared of successful births following in vitro fertilization (IVF) [1,2]. It can truly be said that nonhuman primate ARTs have come of age because these births occurred 21 years ago (Figure ​(Figure1).1). Initial research efforts were almost entirely directed at establishing appropriate culture conditions for in vitro production (IVP) of monkey embryos, and subsequently at devising workable embryo transfer techniques. The latter efforts illustrate one of the significant differences between macaque and human IVP in its broadest sense (embryo production and births). Although several species of nonhuman primate have been used to study ARTs, the great majority of studies have been with the rhesus macaque, Macaca mulatta, because it is (or was) widely available and because of its general similarity to humans. However, with the heavy emphasis on the use of rhesus monkeys for AIDS-related research during the past ten years, limited availability of animals is restricting reproductive research efforts, almost to the point of blocking research in some cases. Figure 1 Petri, the first IVF macaque monkey, shown here at about 5 years of age. He has since fathered numerous normal offspring, showing that he is healthy and fertile. Until recently, the primary rationale for ARTs research with nonhuman primates has been to provide information and new technologies that could assist human ARTs. Because basic research, and to some extent the development of new technologies, cannot or should not be done on humans, the nonhuman primate model ought to play a central role in these efforts. Paradoxically, this role to date has been minimal, for several reasons. First, human ART (IVF/IVP/ET) was established before ART in nonhuman primates. Human ART has been developing since 1969, when the first IVF was reported [3], culminating in the birth of Louise Brown in 1978, five years before the first nonhuman primate IVF births. Because of the social importance and commercialization of human ART, it has progressed much faster than nonhuman primate ART. This has made it difficult to present the case for nonhuman primate ART as a model for human ART, because the former is usually perceived as playing catch-up to the latter. Second, nonhuman primate ART presently owes more to human ART than vice-versa, e.g., the development and availability of human recombinant gonadotropins, without which monkey ART would be very difficult and perhaps prohibitively expensive. As a result, there has been very little technology transfer from basic research with nonhuman primates to the human clinical arena. Nevertheless, there are several key areas in which progress in human ART has virtually stalled, and quantum improvements in ART success will need new information and technology that can only be obtained using suitable experimental animal models, i.e., nonhuman primates. The efficiency of human ART is rather low – on average, about 12% per embryo transferred, and <5% per embryo produced [4,5]. Improvements could be made, for example, by devising even better culture media for IVP and objective methods for selecting the most viable embryos for transfer. Moreover, as this symposium demonstrates, there is great potential for nonhuman primate ART to make a major contribution to embryonic stem cell biology and technology, avoiding difficult ethical and logistical problems inherent in human ES cell studies and applications. Because nonhuman primate ART is now well established, and most of the technical problems have been resolved, it is now timely to directly apply it to solving problems in human infertility and stem cell research. That is why this symposium is most opportune.