Contraceptive effect of a gonadotropin-releasing hormone vaccine on captive male brown bears (Ursus arctos).

Fertility control has traditionally been applied in zoos to control captive populations, and reversible contraception is important. However, contraceptive methods for male bears have not been reported. We aimed to establish a reversible contraceptive for male brown bears by investigating the effects of a gonadotropin-releasing hormone (GnRH) vaccine (Improvac®) that was developed for the immune castration of pigs. We vaccinated six bears with two sequential doses of 400 (n = 2) or 600 µg Improvac® (n = 4) with a 1-month interval during the pre-breeding season (February to April). We compared the reproductive parameters (testosterone levels and semen parameters) of the six vaccinated and four non-vaccinated (control) bears once during the breeding season (May or June). To investigate whether the reproductive performance could be restored in the following year of contraception, we also compared the reproductive parameters once during the breeding season in two bears between the year with GnRH vaccination and the following year without vaccination. Vaccination treatments suppressed reproductive parameters in 5 bears, although vaccination with 400 µg of Improvac® was not effective in one bear. Testosterone levels and the rate of progressive sperm motility were significantly lower, and total sperm count and testis size tended to be lower in vaccinated bears, compared with the controls. Blood biochemical findings and direct observations after Improvac® vaccination did not reveal side effects. Moreover, testosterone levels and spermatogenic scores of two bears were restored in the following year. We confirmed that the Improvac® vaccine elicited a reversible contraceptive effect in male brown bears.

Laparoscopic salpingectomy in Papio hamadryas for birth control in captivity.

OBJECTIVE: To evaluate the feasibility of laparoscopic salpingectomy in baboons (Papio hamadryas). We hypothesized that laparoscopic salpingectomy could be performed in baboon species within a reasonable amount of surgical time, with minor complications occurring at low rates. STUDY DESIGN: Case series and technique description. ANIMALS: Sixteen baboons (n = 16). METHODS: The surgical procedures were performed using the 3-port technique, with 5 mm instruments and a telescope placed at the umbilical and hypogastric regions. A salpinx dissection was performed, using a radiofrequency bipolar vessel sealing device, from the fimbriae to the uterine attachments. We evaluated the surgical duration, learning curve, and intraoperative and early postoperative complications. RESULTS: Ten adult and 6 subadult baboons with a mean weight of 9.32 kg, a range of 4-14.2 kg, and a standard deviation (SD) of 3.09 kg were included in the study. The total duration of surgery was 28.75 min (range, 16-50 min; SD, 9.60 min). The installation phase was completed in a mean time of 7.68 min (range, 3-15 min; SD, 3.43 min), and the time to complete the salpingectomy of both salpinges was 9.68 min (range, 4-20 min; SD, 3.97 min). No complications were observed in the postoperative period. CONCLUSION: Laparoscopic salpingectomy in Papio hamadryas was feasible, with an acceptable surgical time, low invasiveness, and only minor technical perioperative complications. CLINICAL SIGNIFICANCE: Laparoscopic salpingectomy could be a viable and safe therapeutic option in nonhuman primate birth-control programs.

Surgical contraception of free-ranging female capybaras: Description and comparison of open and minimally invasive techniques.

OBJECTIVE: To develop, describe, and evaluate 2 surgical techniques for contraception of free-ranging female capybaras. STUDY DESIGN: Prospective study. ANIMALS: Cadaveric (n = 3) and free-ranging female capybaras (n = 21). METHODS: Preliminary studies of surgical anatomy were performed on 3 capybara cadavers. Two different techniques for partial salpingectomy were evaluated in free-ranging female capybaras: bilateral minilaparotomy (LTG; n = 11) or bilateral laparoscopy (LCG; n = 10). Data concerning body weight, tubal ligation time, total surgical time, incision size, and intraoperative and postoperative complications were analyzed, as well as the clinical status and incisional healing 1 week postoperatively. RESULTS: Body weight (P = .214), ligation time of the left uterine tube (P = .901), and total surgical time (P = .473) were similar between the experimental groups. The ligation time of the right uterine tube was shorter in the LCG group (P = .0463). In the LTG, no differences were observed between the sides regarding the incision size (P = .478). No major intraoperative or postoperative complications occurred in either group. One LCG procedure had to be converted to LTG due to technical issues. All skin incisions healed without complication. CONCLUSION: Both procedures showed similar and satisfactory outcomes. CLINICAL SIGNIFICANCE: The proposed techniques may be a suitable alternative to conventional laparotomy for contraception of female capybaras, especially under field conditions.

Effects of GnRH agonists on testosterone and testosterone-stimulated parameters for contraception and aggression reduction in male lion-tailed Macaques (Macaca silenus).

Managing social groups in zoos requires controlling reproduction in individuals that do not have a current breeding recommendation, while simultaneously maintaining social harmony and animal well-being. Contraceptives, such as gonadotropin releasing-hormone (GnRH) agonists, that suppress testosterone production, offer a potential solution. They achieve infertility by interrupting spermatogenesis and may ameliorate androgen-induced aggression. This study investigated the effects of two GnRH agonists, histrelin and deslorelin, on testosterone, testis size, body weight and sperm production in male lion-tailed macaques, along with subjective observations of aggressive behavior. Five trials at three institutions with 14 males demonstrated that 100 mg histrelin or 9 to 12 mg of deslorelin could at least temporarily reduce testosterone, but a lower 6 mg dose was ineffective. However, ability of deslorelin to produce azoospermia varied among males, even at the highest dose. In general, a higher dose was needed (1) to achieve than to maintain suppression of any measured parameter and (2) to suppress sperm production than testosterone concentration. Testosterone production was also more likely than sperm production to recover, suggesting possible damage to seminiferous tubules but not to Leydig cells. Aggressive behavior was reduced in all but the group receiving the lowest dose. This allowed social groups to be maintained for many years despite recovery of testosterone in some males, suggesting that new social roles had been learned and become independent of androgen influence.

Melengestrol acetate contraceptive implant use in colobus monkeys (Colobus guereza): Patterns through time and differences in reproductive potential and live births.

Melengestrol acetate (MGA) implants are progestin-based reversible contraceptives used to manage fertility in zoo populations. Although it is recommended that MGA implants should be replaced every 2 years, the duration of efficacy has not been systematically evaluated in most species. Anecdotal reports for Old World monkeys indicate that reproduction may be suppressed longer if the implant is not removed. This study uses Guereza colobus monkey (Colobus guereza) as a model Old World monkey species to examine the effects of MGA implants on reproductive potential. In particular, we investigate whether the probability of reproducing (pR) and rates of stillbirth differ among (1) non-implanted females, (2) females who have had MGA implants removed, and (3) females whose implants were left in past expiration. We found no significant difference in pR between non-implanted and implant-removed groups, but when implants were left in past expiration, the pR was significantly lower than in other groups. Both parity and age significantly impacted pR for the non-implanted group (i.e., younger females and those who were parous increased pR), but neither were significant factors for the implant-removed group. Stillbirth rates were significantly higher post-contraception as compared with pre-contraception. These results support similar analyses in other taxa that show a shorter time to reversal after MGA contraception when implants are removed, making this a good contraceptive option for females likely to receive a breeding recommendation, especially when a more predictable time to reversal is important.

Deslorelin acetate implant induces transient sterility and behavior changes in male olive baboon (Papio anubis): A case study.

This case study evaluates the effects of a 4.7 mg deslorelin acetate implant on one male olive baboon (Papio anubis). Implantation induces transient azoospermia after which the subject was able to conceive again. Behavior was also impacted with a decrease in our proxies of aggressiveness and sexual arousal.

Oleanolic acid causes reversible contraception in male mice by increasing the permeability of the germinal epithelium.

The effects of oleanolic acid (OA) on the fertility of male mice were investigated using both invivo and invitro experimental models. The experimental group (n=12) was treated with a daily dose of 30mgOAkg-1 bodyweight (i.p.), while the control group (n=6) received a daily dose of 10% ethanol solution (1mLkg-1 bodyweight). The effect of OA on the permeability status of TM4 Sertoli monolayers was investigated by measuring the transepithelial electrical resistance (TER), intracellular electrical resistance and semiquantitative RT-PCR. After 45 days, OA-treated males produced no pregnancies but in the control group, all 12 females were impregnated (69 offspring). Male mice, which demonstrated sterility when exposed to OA, recovered their fertility after 30 days (78 offspring). Testicular histological observations of OA-treated mice showed detachment of adjacent Sertoli-Sertoli cells. A control monolayer developed TER of 300-400 Ω.cm2, but OA (50, 100, 200µgL-1) treated monolayers developed TER of approximately 100Ω.cm2. Intracellular electrophysiological and RT-PCR data supported the premise that OA compromised tight junctional permeability. The study demonstrated reversible contraception in male mice by increasing the permeability of the germinal epithelium and further postulates that contraceptive reversibility is brought about by the reconstitution of the paracellular junctions between adjacent Sertoli cells.

Fertility Control in Wildlife: Review of Current Status, Including Novel and Future Technologies.

Wildlife conservation requires varying degrees of management of endangered species as well as management of their potential predators and competitors. Conservation also depends on ameliorating human-wildlife conflict, especially where there is a threat to the safety of people and of their pets and livestock. In addition, sustainability of wildlife populations can be affected by feral domestic animals or invasive species, that require removal or control. With the increasing concern for animal welfare, non-lethal methods of limiting population size and distribution, such as fertility control, are gaining favor. Breeding programs in zoos depend on highly effective and selective contraception to manage sustainable insurance populations. This review covers fertility control methods currently in use, those that have not lived up to past promises, and others that are under development and present hope for addressing remaining challenges.

Contraception within an elasmobranch captive breeding programme: a case report on the eagle ray Aetobatus ocellatus using gonadotrophin-releasing hormone (GnRH) agonist deslorelin (Suprelorin).

This study describes the first case of contraception within a captive elasmobranch breeding programme where an implant of Suprelorin, containing a long-acting gonadotrophin-releasing hormone (GnRH) analogue Deslorelin, was implanted in an eagle ray Aetobatus ocellatus, which successfully halted breeding.

Manipulation of the oestrous cycle of the bitch-what works for now.

Manipulation of the oestrous cycle of the bitch is a common request of pet owners for different reasons. On one side, clients may be interested in temporally preventing oestrus until the bitch has finished the performance career, or to manage the kennel in the presence of a stud dog and to avoid undesirable breeding. Additionally, clients with no interest to use their animal for breeding, may, for ethical reasons, prefer to avoid elective surgery such as ovariectomy, to control reproduction. On the other side, clients may want to induce oestrus to better control the time of birth, to use a male with limited availability during a specific time, or to reduce the duration of the interoestrous interval in bitches with a long oestrous cycle (>8 months). Both these options for oestrous manipulation are based on hormonal treatments. For oestrous prevention, synthetic progesterone has been used since the 1960s. Induction of oestrus has been established with reliable results using dopamine agonists in the late 1980s and more recently using GnRH agonists. This review is focusing on the current and recently available treatments to manipulate the oestrous cycle in the bitch.

ASSESSING THE EFFICACY OF DESLORELIN ACETATE IMPLANTS (SUPRELORIN) IN ALTERNATIVE PLACEMENT SITES.

Hormonal contraception is being increasingly used to manage captive animals in zoological collections. Many of the animals placed on contraception are of genetic importance within captive breeding programs; therefore, it is imperative that the application of contraceptive products minimize potential side effects and facilitate a return to fertility if required. Deslorelin acetate implants (Suprelorin®) are one example of a hormonal contraceptive that is frequently used in captivity as they are easy to use and effective in most species. It is hypothesized that removing implants may hasten reversal of contraception treatment; therefore, placement in a location where they can easily be recovered is advocated. In this report, the efficacy and safety of Suprelorin implants placed in their recommended site between the scapulae is compared with alternative placement sites where implants can more easily be located for removal. Using the European Association of Zoos and Aquariums (EAZA) Group on Zoo Animal Contraception (EGZAC) Contraception Database, rates of success, failure, and reversal in 561 records of Suprelorin use in European collections are compared. Of these, 357 have information relating to the location of implant placement. When correctly applied, rates of efficacy were high (>99%) irrespective of placement site. Rates of reversal were 33.3% higher in alternative placement sites, although in most cases it is unknown whether implants were removed or not. In conclusion, the placement of Suprelorin implants in alternative sites does not negatively affect the efficacy, facilitating at the same time implant removal, minimizing potential side effects, and reducing reversal time, allowing for effective use in captive conservation breeding programs.

Safety and effectiveness of a single and repeat intramuscular injection of a GnRH vaccine (GonaCon™) in adult female domestic cats.

Sterilization is a key strategy to reduce the number of domestic cats entering and killed in shelters each year. However, surgical sterilization is expensive and labour-intensive and cannot fully address the 70 million free-roaming cats estimated to exist in the United States. GonaCon™ is a gonadotropin-releasing hormone vaccine originally developed for use as a wildlife immunocontraceptive. An earlier formulation was tested in domestic cats and found to be safe and effective for long-term contraception. However, the current Environmental Protection Agency (EPA)-registered formulation consists of a different antigen-carrier protein and increased antigen concentration and has never been tested in cats. A pilot study was undertaken to evaluate the short-term safety of a single GonaCon immunization, assess the consequences of vaccinated cats receiving an accidental second GonaCon injection and determine the humoral immune response to immunization. During Phase 1, cats in Group A (n = 3) received a single intramuscular injection of GonaCon and Group B (n = 3) received a single intramuscular injection of saline. During Phase 2, Group A received a second GonaCon injection and Group B received their initial GonaCon injection. All cats developed GnRH antibodies within 30 days of vaccine administration. The endpoint titre (1:1,024,000) was similar among all cats, and levels remained high throughout the duration of the study. Four cats developed a sterile, painless, self-limiting mass at the site of injection. The mean number of days to mass development was 110.3 (range, 18-249 days). In conclusion, this preliminary study suggests that the EPA-registered GonaCon formulation is safe for continued testing in domestic cats, an accidental revaccination should not increase the risk of a vaccine reaction and the EPA-registered formulation effectively elicits a strong humoral immune response.

New approaches to non-surgical sterilization for dogs and cats: Opportunities and challenges.

Over the last 40 years, researchers have explored methods to non-surgically suppress fertility in animals. Immunocontraception has been used to control wildlife populations but does not confer long-term immunity. The gonadotropin-releasing hormone (GnRH) agonist deslorelin, formulated as an implant to provide 6-month to 1-year suppression of fertility in male dogs, is available commercially in some countries. Neither of these approaches provide permanent sterility. A single-dose, permanent treatment would be a valuable tool in dog and cat population control. The Michelson Prize and Grants (MPG) programme was initiated "to eliminate shelter euthanasia of healthy, adoptable companion animals and reduce populations of feral and free-roaming cats and dogs" offering a $25 million US prize for a non-surgical sterilant that is effective as a single treatment in both male and female dogs and cats. Michelson Prize and Grants programme has offered US $50 million in grant money for research and has attracted scientists worldwide. Approaches under study include gene therapy, small interfering RNA to inhibit reproductive targets and delivery of cytotoxins to pituitary gonadotrophs or GnRH producing neurons in the hypothalamus. Research in implant technology that could deliver compounds over an animal's lifetime is also underway. Details of funded grants and results to date can be found at: http://www.michelsonprizeandgrants.org/michelson-grants/research-findings. The next steps are translating the most promising research into products. The Alliance for Contraception of Cats and Dogs (ACC&D) is helping to research practical methods of marking sterilized animals to avoid costly retreatment and population modelling that will help guide field workers in use of resources for sterilization programmes.

Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update.

The intent of this contribution is to provide an update of the progress we have made towards developing a method/treatment to permanently sterilize cats. Our approach employs two complementary methodologies: RNA interference (RNAi) to silence genes involved in the central control of reproduction and a virus-based gene therapy system intended to deliver RNAi selectively to the hypothalamus (where these genes are expressed) via the systemic administration of modified viruses. We selected the hypothalamus because it contains neurons expressing Kiss1 and Tac3, two genes essential for reproduction and fertility. We chose the non-pathogenic adeno-associated virus (AAV) as a vector whose tropism could be modified to target the hypothalamus. The issues that must be overcome to utilize this vector as a delivery vehicle to induce sterility include modification of the wild-type AAV to target the hypothalamic region of the brain with a simultaneous reduction in targeting of peripheral tissues and non-hypothalamic brain regions, identification of RNAi targets that will effectively reduce the expression of Kiss1 and Tac3 without off-target effects, and determination if neutralizing antibodies to the AAV serotype of choice are present in cats. Successful resolution of these issues will pave the way for the development of a powerful tool to induce the permanent sterility in cats.

Long-term effects of GnRH agonists on fertility and behaviour.

This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin. Following an initial stimulation of gonadotropin and testosterone secretion possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option to predict castration-related effects on behaviour and to identify animals where surgical castration will not be beneficial. No effect has been seen in reducing aggression towards humans indicating the need for behavioural therapy to control this problem. Effects on spermatogenesis, steroidogenesis and behaviour have by now been shown to be fully reversible. Knowledge in females is more limited, and particularly, the initial induction of a possibly fertile oestrus and individual variation in duration of efficacy remain problems in bitches and queens treated for suppression of fertility. However, long-term suppression of oestrous cycle and fertility seems to be possible with induced effects shown to be reversible including restoration of normal fertility after the end of efficacy/GNRH A-SRI removal.

A survey of bonobo (Pan paniscus) oral contraceptive pill use in North American zoos.

Contraception is an essential tool in reproductive management of captive species. The Association of Zoos and Aquariums (AZA) Reproductive Management Center (RMC) gathers data on contraception use and provides recommendations. Although apes have been given oral contraceptive pills (OCPs) for at least 30 years, there have been no published reports with basic information on why the pill is administered, formulations and brands used, and effects on physiology and behavior. Here, we report survey results characterizing OCP use in bonobos (Pan paniscus) housed in North American zoos, as well as information accumulated in the RMC's Contraception Database. Of 26 females treated, there have been no failures and nine reversals. The most commonly administered OCP formulation in bonobos contained ethinyl estradiol (EE) 35 µg/norethindrone 1 mg. Few females on combined oral contraceptives (COCs) were given a continuous active pill regimen; a hormone-free interval of at least 5 days was allowed in most. Crushing the pill and mixing with juice or food was common. Females on COCs seldom experienced breakthrough estrus or bleeding, while these conditions were sometimes observed for females on continuous COCs. All females on COCs exhibited some degree of perineal swelling, with a mean score of 3 or 3+ most commonly reported. Behavioral changes included less sexual behavior, dominant females becoming subordinate, and a negative effect on mood. No appreciable change in weight was noted. Taken together, these results indicate that OCPs are an effective and reversible contraceptive option for bonobos that can be used by zoos and sanctuaries to limit reproduction. Zoo Biol. 35:444-453, 2016. © Wiley Periodicals, Inc.

Therapeutic Ultrasound as a Potential Male Dog Contraceptive: Determination of the Most Effective Application Protocol.

Ultrasound is one of the most promising forms of non-invasive contraception and has been studied in several animal models. The objective of the current investigation was to determine the most practical and effective application protocol for dog sterilization. A total of 100 dogs were divided into five equal groups. Group A received 5-min applications three times performed at 48-hr intervals and covering the entire testicular area at frequency of 1 MHz; Group B received 5-min applications three times performed at 48-hr intervals over the dorso-cranial area of the testis at frequency of 3 MHz; Group C received three sequential 5-min applications (at 5-min intervals between applications) covering the entire testicular area at frequency of 1 MHz; Group D received 15-min applications two times performed at 48-hr intervals and covering the entire testicular area at frequency of 1 MHz. The experimental groups' ultrasound had an intensity of 1.5W/cm(2) . The Control Group had the same procedure as Group A, but with the transducer switched-off. Dogs were surgically castrated 40 days following the treatment for histological examination. Azoospermia, testicular volume reduction and apparently irreversible testicular damage were achieved by Group A. No effects were noticed in the other groups. Testosterone levels remained within physiological range with all application protocols. A regimen of three applications of ultrasound at 1 MHz, and 1.5 W/cm(2) , lasting 5 min with an interval of 48 h was effective as permanent sterilization in the dog without hormonal impact.

COMPARISON OF CHEMICAL AND SURGICAL VASECTOMY ON TESTICULAR ACTIVITY IN FREE-ROAMING HORSES (EQUUS CABALLUS).

Free-roaming horse (Equus caballus) management is a complex issue incorporating social, economic, emotional, political, and environmental factors. Currently, few proven field techniques exist for managing free-roaming horse population growth, which can reach 20-25% annually. Although there are several strategies available for sterilizing mares when managing free-roaming horse populations, surgical vasectomy is the only method used in the field for stallions. Some managers believe that surgically vasectomizing dominant stallions would have significant effects on reducing horse populations. However, sterilizing only dominant harem stallions results in a relatively modest reduction in population growth as substantial reproduction may occur even when 100% of the dominant harem stallions are sterilized if other males perform as little as 10% of the breeding. The overall goal of the current project was to evaluate the efficacy of a novel nonsurgical method for sterilizing free-roaming horses (chemical vasectomy). In September of 2013, stallions that had been previously surgically vasectomized (SURG, n = 25), previously chemically vasectomized (CHEM, n = 16), or untreated (CONT, n = 32) were captured and surgically castrated in preparation for adoption. When comparing both sterilization methods to CONT, serum testosterone and estrone sulfate concentrations did not differ (P > 0.05), suggesting that these methods for sterilizing free-roaming stallions would not disrupt herd social hierarchy. However, similar to the CONT, all CHEM stallions had sperm present within the vas deferens seminal fluid samples. CHEM stallions had more morphologically abnormal sperm than did CONT stallions but it is not known if this affected the actual fertility. Additional research is needed using alternative sclerosing agents for chemical vasectomy in free-roaming horse populations.

Suppression of fertility in adult dogs.

Unfortunately, the overpopulation of dogs is still a problem in the majority of countries and even though surgical methods of sterilization, the most traditional and commonly used technique, have been intensively performed, the impact on the dog population is negligible. The neutering of companion animals as ovariohysterectomy (spaying) or orchidectomy (castration) has its limitations because of the cost, the need of a surgical environment and the risk of surgical and/or anaesthetical complications (ACCD 2009). In fact, surgical castration has been banished in some northern European countries and has limited acceptance in other countries. In a survey performed in Sao Paulo, Brazil, 56.5% of the owners of adopted shelter dogs were against the surgical procedure for different reasons (Soto et al. 2005). Currently, the options for contraception, defined as suppression of fertility are based on hormonal treatment. The treatments can be divided into analogues of gonadotropin releasing hormone (GnRH), progestins and androgens. Other possibilities of contraception are via the immunological system with vaccinations against GnRH, the luteinizing hormone (LH) receptor and the zona pellucida proteins. Finally, there is also the intra-epididymal or intratesticular injection of sclerosing substances in dogs. Mechanical devices to disrupt fertility are not used anymore due to the side effects. Suppression of fertility in adult dogs will be reviewed in order of use and possible impact on the dog population.

Factors associated with uterine endometrial hyperplasia and pyometra in wild canids: implications for fertility.

The ability to safely and effectively manage reproduction is central to the success of AZA captive-breeding programs. Although the AZA Wildlife Contraception Center routinely monitors contraceptive safety, there have been no studies that compare the effects of contraceptive use to separation of males from females, the other option for preventing reproduction. We used retrospective medical records and pathology reports submitted by AZA and related facilities for the seven AZA-managed canid species to assess rates of uterine pathology relative to female reproductive life histories. Our results showed that the prevalence of both pyometra and endometrial hyperplasia (EH) was associated not only with treatment with the two most common contraceptives (Suprelorin® and MGA implants) but also with the number of years barren (i.e., not producing a litter and not contracepted). Rates of pyometra and EH were especially high in African painted dogs and red wolves, but lowest in swift and fennec foxes. The number of years producing a litter had a low association, suggesting it could be protective against uterine pathology. A more recently developed Suprelorin® protocol using Ovaban® to prevent the initial stimulation phase, followed by implant removal when reversal is desired, may be a safer contraceptive option. These results concerning the relationship between reproductive management and uterine health have important implications for AZA-managed programs, since the unsustainability of many captive populations may be due at least in part to infertility. Managing a female's reproductive lifespan to optimize or maintain fertility will require a reconsideration of how breeding recommendations are formulated.