Contraception Overview Mary Agnew
Outline of Talk
History and Background What is the WCC? New World Primate Recommendations Product Overview Mode of Action Choice and Perspective New Research and Theories What this means for SSPs and TAG
Contraception Advisory Group (CAG) AZA Wildlife Contraception Center (WCC) Late 1970’s: First identified “need” 1989: Task Force identified by AZA 1991: CAG created 2001: WCC officially recognized as an AZA Center
Mission: The WCC works to ensure that contraceptives are safe and effective by: Managing database with 28,000+ records Conducting pathological examinations Coordinating research trials for new methods Working with the AZA community to assist with Repro Management of all species
Who Are We? Director: Cheryl Asa
Veterinarians Asst. Director: Ingrid Porton
Animal Managers Program Coordinator: Mary Agnew Curators Reproductive physiologists MDs and OBGYNs Pathologists Endocrinologists Nutritionists etc…
What do we do? Hotline: Respond to 200+ emails/phone calls a month Manage Contraception Database (28,000+ records) Request and enter data daily Develop and supervise research projects Attend meetings and inform zoo community about products and safety Data collected from zoos worldwide Primates ALL Primates MGA Implants Suprelorin® (deslorelin) Depo-Provera Implanon Birth Control Pills
Progestin Progestins: Mode of Action
Inhibit ovulation May not inhibit follicular development, so may still observe estrus behaviors even though female is not ovulating Cervical mucous changes/thickens to inhibit sperm entry Prevent implantation by altering the uterine lining Progestin
Progestins Used in NW Primates
MGA Implant Depo-Provera Implanon Megestrol Acetate (Ovaban or Megace) P-only pills Progestin MGA Implants Advantages Disadvantages Proven effective Requires surgical placement 2 year duration (minimum) Abscesses have been Safety (low side effects) documented Reversibility data available Conspecifics may pick out Hundreds of historical Needs surgical removal records for NW primates Can change dimorphic species NW Primates MGA Implants Total Records: 2,567 Total Individuals: 1,376 Progestin Depo-Provera® Advantages Disadvantages Easy and fast to administer Variable duration of effect Takes effect quickly Cannot be removed! Proven effective Can change dimorphic Safety (low side effects) species
NW Primates Depo-Provera Total Records: 703 Total Individuals: 226 Progestin Implanon® (Nexplanon®) Advantages Disadvantages Easy to place Conspecifics may pick out Good efficacy (depending on Requires OBGYN approval for dose) purchasing (USA) Very popular in Europe Nexplanon is radio-opaque
NW Primates Implanon Total Records: 70 Total Individuals: 51 Alternatives to Progestins
GnRH Agonists (Suprelorin® and Lupron) Combination birth control pills GnRH Agonist
GnRH Agonists Used in NW Primates
Suprelorin (deslorelin) Lupron Leuprolide Supprelin LA GnRH Agonist GnRH Agonists: Mode of Action 1. Stimulates reproductive system a. Stimulation phase (animals are considered FERTILE during this time) i. Lasts 2-3 weeks ii. Can stimulate estrus and ovulation in females iii. Stimulates testosterone (and spermatogenesis) in males 2. Down-regulates pituitary GnRH receptors so that LH and FSH are not stimulated a. Without LH and FSH, gonadal steroid production is not supported
GnRH Agonist Suprelorin®: Two Choices
Two formulations: MINIMUM suppression 6+ months (4.7mg) 12+ months (9.4mg) Varies significantly among individuals But, duration is consistent by individual Important Note: Placing 2 x 4.7mg implants ≠ 1 x 9.4mg implant • So, number of implants indicates DOSE • Formulation indicates duration of effect GnRH Agonist Suprelorin® (deslorelin) Advantages Disadvantages Easy and noninvasive Variable duration of effect placement Difficult (but possible) to Effective remove If removed, this could hasten Reversibility unknown in reversal many species
NW Primates Suprelorin Implants Total Records: 278 Total Individuals: 146 Combo: Progestin & Estrogen Birth Control Pills Advantages Disadvantages Simple administration Requires daily compliance Removal is quick and easy (controlled)
NW Primates Birth Control Pills Total Records: 7 Total Individuals: 7 Combo: Progestin & Estrogen Mode of Action – Progestin + Estrogen Inhibits ovulation Inhibits follicular development (except during placebo week) Cervical mucous changes Prevents implantation So…..how do you decide? Time frame needs Short-term (< 1 yr) Long-term (>1 yr) Social situations Dominance in group / hierarchy Aggression in group Bachelor groups Medical conditions Diabetes Anesthesia risks Stress Dosing in NWP NWP have higher endogenous levels of steroid hormones than OWP and apes Need relatively huge doses for suppression Example: Depo-Provera Dose in NWP: 20mg/kg body weight Dose in OWP: 2.5-5mg/kg body weight Large MGA implant size might be a consideration for some of the smaller NWP Research Ongoing monitoring for Implanon doses ½ implant 1/3 implant ¼ implant (failures have been documented)
Suprelorin dosing and efficacy Number of implants Duration of effect
Pathology monitoring for side effects & long-term effects on reproduction (uterine & ovarian tissue) Reproductive Health Surveillance Program
Reversibility of all products
Reversibility Stages of reversibility Breeding/sexual behavior Hormone cycling Sperm evaluation Pregnancy confirmed Birth (miscarriage, spontaneous abortion) Live Birth
Why use any other measurement of reversal, other than the gold standard? No breeding recommendation for individual No male (or female) present Medical condition prohibits breeding Etc…
Factors Affecting Reversibility Age At start of first offspring birth At start of contraception At end of contraception Breeding partner Fertility of partner Sexual interest from partner Compatibility Medical Conditions Previous breeding history How long individual has been on contraception What product(s) were used New World Primate Reversals in Females: Average time to conception from ‘stop date*’
Product Average Time to Conception NW Sample Size Depo-Provera 11.5 months 13 MGA Implant 8.8 months 112 Implanon 0 months 1 Suprelorin 19.8 months 6 Birth Control Pills N/A 0
*Stop date defined as day when method was removed or presumed expired. Suprelorin Reversals (n = 6 NWP) Black-Handed Spider Monkey 1. MGA, MGA, Suprelorin: Reversal 2. Depo-Provera, Suprelorin: Reversal 3. Suprelorin, Suprelorin, Suprelorin: Reversal 4. Suprelorin, Suprelorin, Suprelorin: Reversal Pygmy Marmoset 1. Depo-Provera, MGA, Suprelorin: Reversal Golden Lion Tamarin 1. Suprelorin: Reversal New World Primate Contraception Failures
Product Number of Number of Reported Animals Treated Failures Depo-Provera 226 11 MGA Implant 1376 60 Implanon 51 0 Suprelorin 146 6 Birth Control Pills 7 0 Research Project: Callimico and Deslorelin
Past recommendation: MGA Implants Problem: study reported female Callimico implanted with MGA are more susceptible to uterine pathologies (Murnane et al. 1996)
Current Recommendation: Deslorelin Problem: what is the actual suppression time for Callimico treated with deslorelin? Do they reverse after treatment? Research Project: Callimico and Deslorelin Research Question: How long are Callimico suppressed following treatment with deslorelin?
Methods: 1. Collection of fecal samples from six Callimico previously implanted with deslorelin • 24 months or until cycling resumes 2. Hormone data will be analyzed to determine average length of suppression
Research Project: Callimico and Deslorelin Preliminary Data: Two females treated with 1 x 9.4mg implant (min 12 month suppression time) each in Nov 2010 Hormone monitoring: still suppressed as of June 2012 Current suppression time = 19 months
Next steps: Process samples from 4 additional females Evaluate time to reversal following deslorelin treatment in Callimico Reproductive Life Management Use it or Lose it Data presented at 2011 AZA Annual Conference Females have prime breeding ages If females do not reproduce relatively early, they may have difficulty conceiving when they’re older Examples: Cheetah, Elephant, Wolves, Primates?
Considerations Increasing generation time Long generation time = less genetic loss in population How to incorporate into Master Plans?
Master Planning Every species will have different needs Ultimate goal: plan a female’s reproductive life when she is born (or becomes sexually mature)
Endangered Species Condoms Questions?
www.stlzoo.org/contraception