The Importance of Reproductive Management
The genetic health and sustainability of AZA animal populations relies on successful reproductive management. Breeding recommendations from the AZA Population Management Center (at Lincoln Park Zoo in Chicago) and other approved scientific advisors include not only those pairs genetically appropriate for breeding but those individuals or groups that should not breed at that particular time. Most females do receive a breeding recommendation and have an opportunity to reproduce during their lifetimes, but not every year. Closely spaced pregnancies can be difficult for some mothers, but another reason for limiting the number of pregnancies is that AZA zoos want to avoid production of more offspring than can be well cared for. Thus, it is often necessary to temporarily prevent reproduction, which can be accomplished by separating males from females or by using contraception.
Because of the diverse species managed in zoos, AZA long ago recognized that a centralized facility and staff would be the most effective and efficient approach to developing contraception recommendations and monitoring the use of contraceptive products in zoo animals. In 1989 AZA approved the first task force to study contraceptive use in zoos. That initiative led eventually to creation of the AZA Wildlife Contraception Center (WCC) at the Saint Louis Zoo in 1999. In 2015, the WCC was renamed the Reproductive Management Center (RMC) to reflect an increase in scope beyond contraception, to other aspects of reproductive management, including fertility.The RMC provides information on contraceptive methods and their application to zoos in the U.S. and around the world. Those zoos then provide data to the RMC on the effectiveness of the contraceptives, which is entered into a database that now contains over 40,000 records. Potential side effects are closely monitored through the RMC in partnership with the Reproductive Health Surveillance Program at Michigan State University Veterinary School.
Apes and monkeys are perhaps the easiest species to treat with contraceptives. Many products developed for humans are safe and effective in non-human primates. These include birth-control pills containing synthetic forms of estrogen and progesterone, as well as injections and implants with only synthetic progesterone. (Estrogen and progesterone are steroid hormones naturally produced by a female’s ovaries during the ovulatory cycle). The only common side effect is weight gain in females treated with the synthetic progesterone products (something that also occurs in women), a condition that can be managed through diet and activity. Reversal rates following contraception are high as long as the female is still in her reproductive prime. Fertility declines with advancing age whether previously treated with contraception or not.
Products with synthetic progesterone (progestin) are also safe and effective in ungulates, and reversal rates are high, with the same caveat about advancing age as with primates. Some changes in uterine fluid content have been documented during progestin treatment, but evidence indicates that it resolves after treatment ends. Another safe and effective option for this taxonomic group is the zona pellucida (PZP) vaccine, which interferes with fertilization. However, with repeated PZP treatment across many years, the period of infertility is extended and eventually may become permanent.
This group of species has presented the greatest challenges to development of safe and effective contraception, which emphasizes the importance of recognizing profound species differences in the response of both uterine and mammary tissue to reproductive hormones. In primates, progestins are used to cause regression of the uterine lining, but in carnivores the same hormones stimulate the uterus, which can result in tumor growth or the inability to sustain a pregnancy. This important difference was carefully documented in the 1990s in studies of wild felids (cat-like species such as lions and tigers) conducted by the Reproductive Health Surveillance Program in partnership with the RMC.
Contraceptive recommendations for felids were hastily revised to limit exposure to progestins. Because the various carnivore species seem to respond generally in the same way to progestin contraception, these cautions were extended to all carnivores. Fortuitously, in the late 1990s another contraceptive option became available, a non-steroidal method that acts by suppressing the animal’s own steroid hormone production, as would happen if the ovaries were removed (as in spaying). This GnRH agonist (a synthetic form of gonadotropin releasing hormone, which stimulates the production of estrogen and progesterone) when administered continuously in implant form briefly stimulates the reproductive system but then effectively shuts down steroid hormone production so ovulation doesn’t occur.
The GnRH agonist product we use was developed in Australia for domestic dogs; then a similar product was tested in Europe using domestic cats. Both studies showed them to be safe and effective contraceptives, suggesting this would be a good alternative for wild canids, felids and other carnivores. The first challenge in using the new product in wildlife species was finding the effective dose. But then as treated animals began to receive breeding recommendations, it became apparent that the time it takes for return to fertility varies widely among individuals, which is complicated by the difficulty in removing the rice-grain-sized implant. In response, the RMC working with zoo veterinarians devised a strategy for implant placement to ease removal, which seems to speed return to fertility.
A different problem emerged in wild canids (cousins to the domestic dog) related to the GnRH agonist stimulation phase, which was causing them to ovulate before suppression occurred. That ovulation was followed by a long period of naturally produced progesterone, and that progesterone seems to over-stimulate the uterine lining, which can lead to infection or infertility. The solution appears to be an approach that prevents the stimulation phase so that suppression occurs immediately.
There aren’t nearly as many contraceptive options for males. Luckily, the hormone GnRH controls reproduction in both males and females, which means that GnRH agonists should work in males also. That seems to be the case for primates and carnivores, although males need a higher dose than females. However, GnRH agonists aren’t effective in male ungulates for reasons not yet known. A newer product, a vaccine against GnRH, is now on the market in the U.S. Developed for domestic male pigs (boars), it may well be effective in other ungulate species.
Even if these products were perfectly safe, perfectly effective, and 100 percent reversible immediately, we would continue to search for additional contraceptive options for zoo managers and veterinarians. Individual animals can present special cases. Some products may be more suitable for very young or very old individuals; health problems may dictate one method over another. In addition, it can be more difficult to administer contraceptives in some species or some individuals, especially those that live in herds or large social groups. Zoos need options to best meet the needs of each animal and each situation.
Through our active research program and partnerships with scientists and pharmaceutical companies, the RMC hopes to continue to improve the products already available and bring new products to the zoo community to support successful reproductive management and enhanced well-being of the animals in the care of the more than 220 AZA accredited zoos and other conservation organizations that the RMC serves.