Abstract
Since its first use 1990s, the progestin altrenogest (Regu-Mate®) has become the primary method of hormonal contraception for bottlenose dolphins.1 While generally regarded as a safe and effective compound, no controlled studies with bottlenose dolphins have been accomplished evaluating altrenogest's pharmacokinetics, effectiveness, and/or side effects. For contraception, a 20+ year old, multiparous female bottlenose dolphin was placed on altrenogest (0.044 mg/kg PO SID) on June 4, 2009. Serum progesterone concentrations on day -8, day -4 and day 23 (day 0 = first day of altrenogest treatment) were < 0.3 ng/ml. Ovarian ultrasonography on day -14 indicated no follicular activity or evidence of uterine abnormalities. The animal was placed with a known breeding male two days after the start of altrenogest. No further reproductive sonographic evaluations were conducted post-introduction. Altrenogest was inadvertently discontinued for 7 days from days 145 to 153. On day 159, the animal was started on amoxicillin/clavulanic acid (7 mg/kg PO 30 d) due to inappetence and a mixed serosanquinous fluid and tissue discharge from the vagina. Blood work revealed normal hematology with decreased serum iron (26 µg/dl), slightly elevated ESR (10 mm/60 min) and baseline serum progesterone (0.7 ng/ml). Ultrasound exam revealed hyperechoic masses within both uterine horns. The animal continued to pass tissue and fetal parts for 2 weeks post-abortion. A follow-up hysteroscopy on day 202 revealed multiple fetal bones lodged deep within both uterine horns. Two more hysteroscopic exams were conducted (day 241; day 271) in an effort to remove the fetal remnants from the uterine horn. The animal was treated with 2 to 4 mg estradiol PO for 5 to 7 days and peri-hysteroscopic parental amikacin (15 mg/kg IM once) was administered prior to each hysteroscopy. A variety of graspers (4 prong, and rat tooth, Hysteroscopic Support Service [ESS], Brewster, NY) and baskets (4 wire, Roth Net retriever, ESS) were used to remove fetal remnants. The uterus was lavaged with 1 liter sterile saline and the animal placed on amoxicillin/clavulanic acid and levofloxacin (5 mg/kg PO SID) for 7 days and meloxicam (0.15 mg/kg PO once, then 0.1 mg/kg 24 h later) post-hysteroscopy. During the second exam on day 241, all bones were removed from the "right" uterine horn, but fragmented bones could not be completely removed from the left. For the third exam on day 271, small bone fragments were removed; however, a larger piece (2 x 2 cm; plus multiple smaller, proximally-located pieces) remained adhered to the uterine horn and could not be removed. Since May of 2011, the animal has ovulated 3 times in the presence of a breeding male and has not become pregnant. A follow-up exam on January 25, 2012 (day 965) revealed occlusion of the "left" uterine horn by an adhered fetal bone piece. The case demonstrates the potential for female bottlenose dolphins to ovulate and become pregnant during altrenogest treatment. These findings also illustrate the importance of regular reproductive assessment, particularly ultrasonographic examination, just prior to and during the use of altrenogest as a contraceptive.
Acknowledgements
We thank the animal training staff, Wayne Phillips, Alex Garcia, and Ricardo Farkas of Dolphin Adventures and Cabo dolphins. In addition, we thank Dr. Jesus Villalobos (Hospital Veterinario del Valle) for use of his hysteroscopic equipment and Dr. Martin Haulena (Vancouver Aquarium) for his advice. We thank Dr. Justine O'Brien (SeaWorld Parks and Entertainment, SEA) for comments and Mr. Brad Andrews (SEA) for his support of this work.
References
1. Robeck TR, Atkinson S, Brook F. Chap 11: reproduction. In: Dierauf L, Gulland F, eds. CRC Handbook in Marine Mammal Medicine. 2nd ed. Boca Raton, FL: CRC Press; 2001:193–236.