Environmental Effects on Reproduction

The most important environmental factor to stimulate reproductive activity is photoperiod. Photoreceptors in the retina and pineal gland become sensitized, which stimulates release of gonadotropin-releasing hormone (GnRH) from the hypothalamus.⁹ Most species respond to increasing day length, and maximum stimulation occurs with 12–14 hours of light. Rainfall stimulates reproductive activity in certain species such as zebra finches and cockatiels. The presence of a mate, or perceived mate (mirror or human caregiver), is another powerful reproductive stimulus in many avian species. While birds with physical contact with a mate will have the most stimulation,⁴ auditory contact with a male conspecific has also been shown to induce cycling in females of certain species such as budgerigars and ring-necked doves. Nesting material and/or the presence of a nesting box has also been shown to stimulate egg laying and plasma luteinizing hormone (LH) secretion in cockatiels and other cavity-nesting species.⁷

Surgical Management

Ovocentesis

Medical management of the avian dystocia involves supportive care including heat support, fluid therapy, and analgesics. Oxytocin is usually not efficacious in birds as the avian equivalent, mesotocin, does not stimulate uterine contraction - arginine vasotocin (AVT) controls oviposition in avian species. The exact mechanism of AVT-induced uterine contraction is unknown, but it likely stimulates local production of prostaglandins including E₁. Commercially available prostaglandin E₂ creams (Prepidil® Gel, dinoprostone) can be utilized topically on the vent of an affected bird to help with egg expulsion. These medications are expensive (thousands of dollars per tube) and have variable efficacy in the author's experience.

If medical management fails, or if the bird is decompensating, ovocentesis is recommended. This involves aspiration of the egg contents with a large gauge (16 or 18 gauge) needle with the patient under general anesthesia. Ideally, the egg would be manipulated such that the shell is visible through the cloaca with the assistance of a speculum. If this is not possible, percutaneous ovocentesis can be performed by aspirating the contents of the egg through the coelomic wall. The remaining shell fragments are manually removed if visible, or should pass on their own within several days. If they do not, surgical removal is often indicated. Broad-spectrum antibiotics and analgesics should be administered following this procedure due to the risk of salpingitis.

Salpingohysterectomy

Indications for removal of the uterus and oviduct include dystocia, ruptured or diseased oviduct, prolapsed oviduct, and chronic egg laying (see medical therapy section below). This is considered a high-risk procedure and is not recommended as routine preventative therapy. The ovary is not commonly removed in birds due to concerns for fatal hemorrhage from the multiple, short ovarian vessels in close proximity to aorta. A presumed hormonal feedback loop exists from the uterus to the ovary, thus intracoelomic ovulation following salpingohysterectomy is not common in psittacines. However, continued ovulation and subsequent egg-yolk peritonitis has been noted in several galliform and anseriform species.¹

A left lateral celiotomy is the most common approach and will give the surgeon the best visualization of the oviduct. The patient is positioned in right lateral recumbency with the left pelvic limb extended cranially or caudally - the author prefers cranial. After the skin and coelomic wall musculature is transected, one or several of the last ribs may also need to be transected for adequate exposure depending on the size of the patient and oviduct. The oviduct is identified in the left dorsal aspect of the coelom and gently elevated away from the caudal vena cava. The non-vascular ventral ligament of the oviduct can be transected at this stage to help facilitate straightening of the entire oviduct. The infundibulum is elevated to expose the dorsal ligament of the oviduct. Often a small vessel is present traveling from the ovary to the infundibulum - this should be coagulated or occluded with a hemostatic clip. A branch of the ovarian artery is present along the length of the dorsal ligament and should be ligated during transection of this ligament. As the dissection approaches the cloaca, identify and avoid the ureter (small, white tubular structure originating from the kidney). The uterus is then ligated and removed at the junction with the cloaca with hemostatic clips or appropriate-size monofilament suture. Be careful not to entrap the ureter in this location. Closure is achieved in two layers - the coelomic wall musculature and skin.

Medical Management

Neuroendocrine Control of Reproduction

The hypothalamic-pituitary-gonadal axis controls avian reproduction, similar to most other vertebrates. The initiating factors in this hormonal cascade are gonadotropin-releasing hormones (GnRH). These peptide hormones are transported to the anterior pituitary gland, which in turn, stimulates the release of luteinizing hormone (LH). The ability of GnRH to stimulate follicle-stimulating hormone (FSH) is unclear in avian species; therefore, some references use the term luteinizing hormone-releasing hormone (LHRH) rather than GnRH for birds.¹⁵ Most vertebrates, including birds, possess multiple forms of GnRH, which can be classified into three major forms - GnRH-I, GnRH-II, GnRH-III. Their ability to stimulate LH, and possibly FSH, release from the anterior pituitary is variable depending on species, sex, and reproductive status of the bird. In addition, multiple types of GnRH receptors have been identified, which are subdivided into mammalian and non-mammalian receptors. The incongruities between avian and mammalian GnRH peptides and their receptors may explain the reduced efficacy of synthetic GnRH-agonists including leuprolide acetate and deslorelin acetate in avian species.

Leuprolide Acetate

Leuprolide acetate (Lupron®, TAP Pharmaceuticals Inc.) is a synthetic, GnRH agonist available as a depot formulation to provide long-term treatment for various reproductive diseases in humans including prostatic hyperplasia and precocious puberty. In avian species, it is used most commonly for treatment of excessive egg laying and to decrease undesired reproductive behavior. In addition, there are several published reports which describe its use for management of ovarian neoplasia in cockatiels along with periodic coelomocentesis.^5,11

Although leuprolide acetate has been used extensively in many avian species, few controlled clinical trials exist which examine the efficacy of this drug. Leuprolide acetate was found to reversibly prevent egg laying in cockatiels after a single intramuscular injection. Specifically, the treated cockatiels had a 12–19-day delay in egg laying compared with a control group.⁸ A single injection of leuprolide acetate administered to nonbreeding adult Hispaniolan Amazon parrots at a dose of 800 μg/kg IM reduced plasma sex hormone levels for less than 21 days.⁶ In addition to unknown efficacy in most avian species, the published dose range is wide, from 100 to 1200 μg/kg IM. The recommended dose range and treatment interval for most psittacines is 400 to 1000 μg/kg IM every 2–3 weeks.¹⁰ This may not be financially feasible for all clients, as long-term treatment is usually required.

Deslorelin Acetate

Deslorelin acetate (Suprelorin®, Peptech Animal Health) is another GnRH agonist that is formulated into a subcutaneous, controlled-release implant designed for use in dogs for reversible suppression of testosterone production, and thus contraception, for six to twelve months, depending on implant size. It is commercially available as a 4.7-mg or 9.4-mg implant and is considerably less expensive than repeated treatments with leuprolide acetate. Recently, the 4.7-mg deslorelin implants have become available in the United States as an FDA Indexed Minor Use/Minor Species product for management of adrenal cortical disease in domestic ferrets. The implants come from the manufacturer in a preloaded needle with a separate applicator syringe, similar to a microchip.

Similar to leuprolide acetate, deslorelin acetate is primarily utilized to decrease reproductive behaviors and egg laying in avian species. It has also been used successfully for long-term management of non-resectable ovarian neoplasia in cockatiels^5,12 and Sertoli cell tumors in budgerigars¹⁶. In addition to treatment of ovarian neoplasia, there is evidence that GnRH agonists, such as deslorelin acetate, have chemopreventative effects in domestic chickens against development of ovarian neoplasia.³ There are several published case reports and retrospective studies describing the use of deslorelin acetate in psittacines; however, the only prospective controlled studies to date on deslorelin acetate in birds are in chickens, quail, and pigeons. Chickens treated with a 4.7-mg deslorelin acetate implant had reduced egg production for a mean of 180 days whereas a 9.4-mg implant inhibited egg production for 319 days.¹³ In Japanese quail, a single 4.7-mg deslorelin acetate implant reversibly decreased egg production in 6 out 10 birds for 70 days.¹⁴ Pigeons implanted with a single 4.7-mg deslorelin implant had reduced egg production for 5–7 weeks and reduced serum LH concentrations for 84 days compared with control birds.²

Determining an effective dose to prevent contraception for deslorelin acetate has proven challenging across several species, even those of similar weight and taxonomy. Despite dramatically higher doses administered to Japanese quail compared to dogs, the efficacy and duration were both less in quail. A single 4.7-mg implant had a longer period of effect in chickens than in quail, both of which are Galliformes. This suggests there is also a substantial interspecies variation, in addition to individual variation with deslorelin acetate implants. Based on this information, extrapolation of these results to other avian species, such as psittacines, should be done with caution.

In addition to selecting an effective dose, another challenge clinicians face with long-acting GnRH agonists is appropriate dosing interval. Return of reproductive behaviors and/or egg laying have been utilized as the best indicators for reimplantation. In the prospective studies mentioned previously, egg laying was the most consistent sign of cessation of efficacy for deslorelin implants as the plasma hormone measurements were often highly variable and did not accurately reflect the reproductive status of the bird. A recent retrospective case series in the non-peer-reviewed literature reviewed the use of 4.7-mg deslorelin acetate implants in 96 psittacine patients.¹⁷ The most common interval between implants for that group of birds was 3 months with a range of 2–5 months. In addition to behavioral and environmental modifications, treatment with repeated implantation of a single 4.7-mg deslorelin implant consecutively over a period of 6–9 months led to a successful resolution of chronic egg laying. As with leuprolide acetate, there is anecdotal evidence of decreased efficacy over time after repeated administration of deslorelin implants in several avian species.

Deep sedation or general anesthesia is recommended for placement due to the large size of the needle relative to the small size of most psittacine patients. The recommended implantation site is subcutaneously in the mid-scapular region. Plucking of the feathers and sterile preparation of the site are recommended prior to implant placement. A small amount of tissue adhesive can be used on the skin defect created by the application needle to prevent loss of the implant. In the author's experience, the most common side effect of placement is treatment failure.

References

1.  Bennett R, Harrison G. Soft tissue surgery. In: Ritchie BW, Harrison G, Harrison L, eds. Avian Medicine: Principles and Application. Lake Worth, FL: Wingers Publishing, Inc.; 1994:1096–1136.

2.  Cowan ML, Martin GB, Monks DJ, Johnston SD, Doneley RJT, Blackberry MA. Inhibition of the reproductive system by deslorelin in male and female pigeons (Columba livia). J Avian Med Surg. 2014;28:102–108.

3.  de Matos R. Investigation of the chemopreventative effects of deslorelin in domestic chickens with a high prevalence of ovarian cancer. In: Proceedings from the International Conference on Avian, Herpetological & Exotic Mammal Medicine; 2013: 90.

4.  Joyner K. Theriogenology. In: Ritchie B, Harrison G, Harrison L, eds. Avian Medicine: Principles and Application. Lake Worth, FL: Wingers Publishing Inc.; 1994:748–773.

5.  Keller KA, Beaufrère H, Brandão J, McLaughlin L, Bauer R, Tully TN. Long-term management of ovarian neoplasia in two cockatiels (Nymphicus hollandicus). J Avian Med Surg. 2013;27:44–52.

6.  Klaphake E, Fecteau K, DeWit M, et al. Effects of leuprolide acetate on selected blood and fecal sex hormones in Hispaniolan Amazon parrots (Amazona ventralis). J Avian Med Surg. 2009;23:253–262.

7.  Millam JR, Roudybush TE, Grau CR. Influence of environmental manipulation and nest-box availability on reproductive success of captive cockatiels (Nymphicus hollandicus). Zoo Biol. 1988;7:25–34.

8.  Millam JR, Finney H. Leuprolide acetate can reversibly prevent egg laying in cockatiels (Nymphicus hollandicus). Zoo Biol. 1994;13:149–155.

9.  Millam JR. Reproductive physiology. In: Altman RB, Clubb SL, Dorrestein GM, Quesenberry K, eds. Avian Medicine and Surgery. Philadelphia, PA: WB Saunders; 1997:12–28.

10. Mitchell MA. Leuprolide acetate. Semin Avian Exotic Pet Med. 2005;14:153–155.

11. Nemetz L. Leuprolide acetate control of ovarian carcinoma in a cockatiel (Nymphicus hollandicus). In: Proceedings from the Annual Association of Avian Veterinarians Conference; 2010: 333–338.

12. Nemetz L. Deslorelin acetate long-term suppression of ovarian carcinoma in a cockatiel (Nymphicus hollandicus). In: Proceedings from the Annual Association of Avian Veterinarians Conference; 2012: 37–42.

13. Noonan B, Johnson P, de Matos R. Evaluation of egg-laying suppression effects of the GnRH agonist deslorelin in domestic chickens. In: Proceedings from the Annual Association of Avian Veterinarians Conference; 2012: 321.

14. Petritz OA, Sanchez-Migallon Guzman D, Paul-Murphy J, et al. Evaluation of the efficacy and safety of single administration of 4.7-mg deslorelin acetate implants on egg production and plasma sex hormones in Japanese quail (Coturnix coturnix japonica). Am J Vet Res. 2013;74:316–323.

15. Pollock CG, Orosz SE. Avian reproductive anatomy, physiology and endocrinology. Vet Clin North Am Exot Anim Pract. 2002;5:441–474.

16. Straub J, Zenker I. First experience in hormonal treatment of Sertoli cell tumors in budgerigars (Melopsittacus undulatus) with absorbable extended-release GnRH chips (Suprelorin®). In: Proceedings from the International Conference on Avian, Herpetological & Exotic Mammal Medicine; 2013: 299–300.

17. Van Sant F, Sundaram A. Retrospective study of deslorelin acetate implants in clinical practice. In: Proceedings from the Annual Association of Avian Veterinarians Conference; 2013: 211–220.