Long-acting reversible contraception with etonogestrel implants in female macaques (Macaca mulatta and Macaca fascicularis)

Abstract

Introduction: Contraception is often required for management and population control purposes in group-housed and free-roaming non-human primates. Long-acting reversible contraceptives, including subdermal progestin-releasing implants, are preferred as they eliminate challenges associated with frequent administration. Etonogestrel (ENG)-releasing subdermal implants are reversible and long-acting for a minimum of 3 years, and are commercially available for human use as Implanon^® or Nexplanon^®.

Methods: A retrospective analysis was performed detailing the contraceptive effectiveness and reversibility of subdermal placement of one-fourth or one-third of an ENG implant (68 mg/implant) in 129 female rhesus macaques (Macaca mulatta) and 67 cynomolgus macaques (Macaca fascicularis) at the Biomedical Primate Research Centre (Rijswijk, Netherlands). Furthermore, single cross-sectional ENG serum concentrations were measured for 16 rhesus and 10 cynomolgus macaques, and hemoglobin and blood chemistry pre-ENG and at timepoints >0.5, >1.5, and > 2.5 years post-ENG insertion were evaluated for 24 rhesus macaques. Finally, data were obtained using trans-abdominal ultrasound regarding the influence of ENG on uterine volume and endometrial thickness in 14 rhesus and 11 cynomolgus macaques.

Results: As a contraceptive ENG was in 99.80% (CI 93.50-99.99) and 99.95% (CI 99.95-100) effective in rhesus and cynomolgus macaques, respectively. Prolonged ENG durations of implant use in 14 rhesus macaques (range 3.1-5.0 years) and eight cynomolgus macaques (range 3.2-4.0 years) resulted in no unintended pregnancies. A total of 17 female macaques were allowed to breed after ENG removal, and among them, 14 female macaques (82%) had an uneventful delivery. Serum ENG concentrations with a median ENG duration of 1.2 years (range 0.1-6.0 years) and 1.9 years (range 0.6-4.7 years) resulted in median concentrations of 112 pg./mL (range 0-305 pg./mL) and 310 pg./mL (range 183-382 pg./mL) for rhesus and cynomolgus macaques, respectively. ENG had no clinical effect on hemoglobin and blood chemistry parameters nor on the thickness of the endometrial lining or uterus volume.

Conclusion: This study indicates that both one-fourth and one-third of the ENG implants are effective, long-acting, reversible, and safe contraceptive to use in macaques.

Keywords: Implanon; contraception; etonogestrel; fertility; long-acting contraception; macaques; non-human primates; reversibility.