CHAPTER 41 Induced Abortion
Therapeutic abortion may be indicated during normal or abnormal pregnancy in the cow. Misidentification of a breeding female, accidental breeding of a very young heifer, and unwanted pregnancy in feedlot heifers are indications for abortion during normal gestation. Induced abortion can be included in treatment protocols for pathologic conditions of pregnancy, including fetal maceration, fetal mummification, hydramnios, and hydroallantois.
Gestation in the cow extends 270 to 292 days after breeding. Once conception has occurred, progesterone is essential for pregnancy maintenance. Both luteal and extraovarian sources of progesterone must be eliminated for successful induction of abortion. Although the maternal endocrine events of the first 15 days of cycle and of pregnancy are similar, the conceptus secretes a range of products, including steroids, prostaglandins, and proteins, beginning at 12 to 13 days of gestation. At least one of these products, interferon-γ, results in maternal recognition of pregnancy by inhibition of luteolysis and prolonged luteal lifespan.1–3 These effects are mediated by attenuation of endogenous prostaglandin F2 alpha (PGF2α) secretion.4
The functional life of the corpus luteum (CL) is controlled by a balance of luteotropic factors, including luteinizing hormone, and luteolytic factors, including PGF2α. PGF2α is the naturally occurring luteolysin, acting both directly and indirectly on the CL. PGF2α may cause local vasoconstriction of luteal blood flow; however, PGF2α receptors are present on luteal cells, and PGF2α has a direct effect on luteal progesterone secretion.5 Endogenous luteolysis occurs in response to a cascade of hormonal events that result in pulsatile PGF2α secretion. It has been proposed that as part of this cascade, estradiol induces oxytocin receptors on endometrial cells.6 Oxytocin activates those receptors, resulting in the synthesis and secretion of PGF2α.
Peripheral progesterone levels fluctuate between 6 and 15 ng/mL throughout gestation,7 with a gradual decline in the 2 to 4 weeks preceding parturition.8 Pregnant cows that undergo ovariectomy before the first 3 to 5 months of gestation will abort. In cows ovariectomized after 200 days of gestation, progesterone secretion is maintained, although at significantly lower levels than before ovariectomy.9 These cows do not abort, but parturition is advanced by 2 weeks and may be accompanied by dystocia and retained fetal membranes. The adrenal gland may contribute 1 to 4 ng/mL of progesterone.10
In summary, progesterone is luteal in origin for the first 150 days of gestation. Between 150 and 250 days, the placenta acts as additional source of progesterone. In the final month of gestation, placental progesterone declines and pregnancy is again dependent on luteal progesterone. Successful treatment to induce abortion must lower circulating progesterone below 1 ng/mL, which is the threshold necessary to maintain pregnancy,11 and must be directed specifically at the source of progesterone appropriate for the stage of gestation at the time of treatment.
The CL is sensitive to PGF2α beginning 5 to 7 days after ovulation. In both normal and abnormal pregnancy, administration of PGF2α after that time results in luteolysis at any stage of pregnancy; however, PGF2α treatment alone induces abortion only up to 5 months of gestation. Rarely, luteolysis is incomplete, in which case luteal progesterone remains above the threshold, and partial cervical dilation and abdominal straining may occur before the cow resumes normal gestation.11
Glucocorticoid treatment appears to reduce placental progesterone secretion from 150 days of gestation. Luteal progesterone is unaffected, however, and abortion does not result from glucocorticoid treatment until the last month of gestation. During the final month of gestation, glucocorticoids act at the fetoplacental unit to increase the production of estradiol and PGF2α, resulting in induced parturition. A combination of PGF2α and glucocorticoids will induce abortion from 150 days of gestation.
Treatment with estrogens during the first 2 to 3 days after ovulation alters oviductal transport of the bovine embryo and terminates pregnancy. After the development of the CL, estrogens cause luteolysis by inducing the endogenous PGF2α luteolytic cascade from the endometrium, as described earlier. The endometrium must be intact for estrogens to induce abortion. Estrogen is an exogenous luteolysin with unknown effects on the fetoplacental unit; therefore, abortion can be induced reliably at up to 150 days of gestation. Treatment of cows between 200 and 220 days of gestation with 30 mg estradiol valerate, alone or in combination with dexamethasone, has not been shown to decrease serum progesterone or result in abortion, however.11
Treatment with estradiol or its synthetic derivatives results in prolonged estrous behavior, vulvar swelling, mucopurulent discharge, and relaxation of parts of the posterior reproductive tract. The function of the uterotubal junction as a sphincter may be impaired, possibly allowing ascending infection and salpingitis. Time to return to fertile estrus after estrogen treatment may be longer than after prostaglandin treatment.