Fertility following extended depo provera treatment in sooty mangabeys (Cercocebus atys) 公开
Cappelletti, Maurand Madilyn (2013)
Abstract
ABSTRACT
The injectable contraceptive
medroxyprogesterone acetate (depo provera, DMPA), a synthetic
progestin that suppresses ovulation, is currently approved for
human use in over 90 countries. DMPA is also widely used for the
reproductive management of animal populations. Studies examining
fertility after DMPA treatment in both human and nonhuman animals
have focused on the resumption of ovulation after treatment
cessation, but neglected potential long-term effects of DMPA
exposure on successful reproduction. DMPA is frequently
administered as a contraceptive agent for adolescent girls,
however, the possibility of differential long-term fertility
effects of DMPA exposure during adolescence have not been explored.
We investigated the effects of extended DMPA treatment on the
post-treatment fertility of a species of old world nonhuman
primate, the sooty mangabey (Cercocebus atys). Female sooty
mangabeys (N=31) in a large breeding group at the Yerkes National
Primate Research Center Field Station received DMPA treatment for
between 4-8yr. At the time of first DMPA injection, females were
either parous (N=14) or nulliparous (N=17), with
nulliparous-treated females consisting of pubertal (N=10) and
prepubertal adolescents (N=7). After cessation of DMPA treatment,
nulliparous-treated females had a significantly higher incidence of
stillbirth than did age-matched or experience-matched controls,
whereas parous-treated females did not differ from matched
controls. Looking exclusively within treated females,
nulliparous-treated females placed on DMPA prepubertally had a
significantly higher incidence of stillbirth than either pubertal
nulliparous-treated females or parous-treated females. The majority
of stillbirths to nulliparous-treated females included difficult
and/or prolonged labor (dystocia) culminating in infant death. In
humans, dystocia is associated with weak uterine contractions, and
progestins are known to suppress uterine contractility. It is
possible that exposure to elevated levels of progestin throughout
puberty, a critical period of uterine development, permanently
reduced uterine contractility for females placed on DMPA in early
adolescence. These results indicate that the post-treatment effects
of chronic DMPA exposure vary with the developmental timing of
treatment onset, and raise concerns about the use of DMPA as a
contraceptive for adolescent girls.
Table of Contents
TABLE OF CONTENTS
I. Introduction 1
II. Methods 4
a. Treated Subjects 4
b. Controls 6
c. Data Collection 8
d. Following Reproduction 9
e. Statistical Analyses 11
III. Results 12
a. Return of Fertility 12
b. Reproductive Output 13
c. Pregnancy Outcomes 13
IV. Discussion 16
a. Return of Fertility 17
b. Reproductive Output 17
c. Pregnancy Outcomes 19
d. Stillbirths 20
V. References 23
VI. Tables 27
VII. Figure Captions 32
VIII. Figures 34
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