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. 2024 Jan 8:10:1319862.
doi: 10.3389/fvets.2023.1319862. eCollection 2023.

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

Annemiek Maaskant  1   2 , Kimberly K Scarsi  3 , Lisette Meijer  1 , Sandra Roubos  1 , Annet L Louwerse  1 , Edmond J Remarque  1 , Jan A M Langermans  1   2 , Marieke A Stammes  1 , Jaco Bakker  1
Affiliations

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

Annemiek Maaskant et al. Front Vet Sci. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Photograph of the subcutaneous located implant, indicated by the arrow, which is visible through the unshaved skin on the medial side of the upper arm of a rhesus macaque. (B) on a X-ray image the implant (arrow) is also visible as the implant contains barium sulfate.
Figure 2
Figure 2
Sera concentrations (pg./mL) of etonogestrel (ENG) in rhesus (left) and cynomolgus macaques (right) with one-third ENG implant in relation to the duration of ENG implant measured in days starting from the day of insertion.
Figure 3
Figure 3
Boxplots showing median, 25 and 75 percentiles, and the whiskers represent minimum and maximum value of uterine volume and endometrial thickness of both female rhesus and cynomolgus macaques. Each plot shows the data from the control group (non-ENG) and the in-treatment ENG females. For each in-treatment animal, a representative control animal is shown.
See this image and copyright information in PMC

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