Mid-trimester abortion with 15 (S) methyl prostaglandin F 2 alpha

The efficacy of intramuscular administration of 15 methyl (15S) prostaglandin F2alpha (PGF2a) in midtrimester pregnancy termination was evaluated in 16 healthy patients (mean age, 23.3; mean parity, 1.4; mean number of menstrual weeks, 16.1) by measuring dose response; oxytocin conversion; abortion time; side effects; intrauterine dynamics and progesterone withdrawal. Labor was monitored using extraovular balloon placed transvaginally; transcervically; and connected to a Physiograph machine. Patients not aborting within 48 hours after the first dose were considered failures. Blood samples were collected at 0, 3, and 6 hours and at abortion time for plasma progesterone measurement. Average dose given was 789 +or- 60 micrograms. Only 9 of 10 patients aborted within the prescribed 48 hours: 7 were complete abortions, and 2 were incomplete and required suction curettage. Mean induction to abortion time was 20.2 +or- 2.7 hours. Nausea, vomiting and diarrhea were the main side effects. The findings suggest that 15 methyl PGF2a in the dosages and routes prescribed is not as efficient as PGF2a. It is also suggested that prostaglandin affects the myometrium at 2 levels: 1) a membrane effect, and 2) a more fundamental intracellular regulatory effect which is necessary to initiate labor.     

Effect of early postpartum treatment with prostaglandin F2alpha on subsequent fertility in the dairy cow

Eighty Holstein dairy cows were treated with 25 mg of prostaglandin F2alpha (PGF2alpha) on Days 14 to 16 post calving. Eighty-four herd mates served as saline controls in the double blind study. The reproductive parameters used to measure fertility were mean days to first service on all cows and mean days open, first service conception rates and services per pregnancy on cows that became pregnant. Mean days to first service was similar in both groups (71.8 +/- 27, treated; 68.5 +/- 28.6, controls; P = 0.5352). The mean days open was 98.6 +/- 52.0 d for treated cows compared to 118.8 +/- 71.2 d for controls (P = 0.0680). First service pregnancy rates (treated, 41.3%; control, 35.7%) were not significantly different (P = 0.0630); however, the mean services per pregnancy (treated, 1.64; control, 2.33) were significantly (P = 0.0021) improved in the treated group. Ten cows in the treated group and twelve cows in the control group were diagnosed as having retained fetal membranes and/or metritis. For treated and control cows mean days to first service were 82.2 +/- 34.8 d and 82.8 +/- 58.7 d (P = 0.5652). Days open were 97.0 +/- 32.5 d and 133.4 +/-58.4 d (P = 0.3636); services per conception were 1.83 and 2.50 (P = 0.3178), respectively. In all treated cows reproductive parameters were similar whether cows had high serum progesterone ( > 1 ng/ml) or low serum progesterone ( < 1 ng/ml) on the treatment day. This study suggests that early postpartum treatment of lactating dairy cows with prostaglandin produces an improvement in fertility.     

Induction of parturition in swine with prostaglandin F(2)alpha, estradiol benzoate and oxytocin

Pregnant sows and gilts were administered either 0, 2.5, 5, 10 or 20 mg prostaglandin F(2)alpha (PGF(2)alpha) intramuscularly on Day 112 or 113 of gestation at 0800 h in an effort to induce parturition. The average interval from PGF(2)alpha injection to farrowing was 55.1 +/- 5.7, 29.4 +/- 3.1, 32.1 +/- 4.6, 27.8 +/- 1.8 and 26.9 +/- 1.1 h for 0, 2.5, 5, 10 and 20 mg, respectively. All PGF(2)alpha treatments increased (P < 0.01) over controls the number of sows farrowing 23 to 33 h after injection. The average gestation length was significantly shorter in treated gilts; however, no detrimental effect on pig performance or pig survivability was observed. A second trial evaluated the effect of a 10-mg dose of PGF(2)alpha on the induction of parturition in sows in order to obtain a majority of sows farrowing within normal working hours (0700 to 1700 h). The interval from injection to farrowing was decreased (P < 0.05) by PGF(2)alpha treatment (66.2 +/- 5.3 vs 28.1 +/- 2.2 h). Fifty-seven percent (P < 0.05) of PGF(2)alpha-treated sows farrowed between 0700 and 1700 h as compared to 13.6% for control sows. A third trial was conducted to examine a sequential treatment of PGF(2)alpha and oxytocin to control the time of parturition more precisely. Sows receiving only 10 mg of PGF(2)alpha farrowed on an average 31.1 +/- 1.4 h after injection. The injection of 40 IU oxytocin 24 to 28 h after PGF(2)alpha decreased (P < 0.05) the interval from PGF(2)alpha to farrowing (28.1 +/- 0.9 h). The addition of oxytocin increased (P < 0.05) the number of sows farrowing within 3 h of injection (33 vs 86% for PGF(2)alpha and PGF(2)alpha + oxytocin treatments, respectively). A fourth trial was designed to determine if the addition of exogenous estradiol benzoate (EB) to a sequential treatment of PGF(2)alpha and oxytocin would improve the predictability and synchronization of the induced parturition. Sows were assigned to receive either saline, 10 mg PGF(2)alpha + 40 IU oxytocin or 10 mg PGF(2)alpha + 5 mg EB + 40 IU oxytocin. The addition of EB reduced (P < 0.01) the variance in the interval from oxytocin to farrowing and added precision to the predicted time of induced parturition.     

Mid-trimester abortion with intra-amniotic prostaglandin F2 alpha and intravenous oxytocin infusion

Induction of abortion in mid-trimester pregnancies were performed on 26 patients. The first 12 patients were treated by intra-amniotic instillation of Prostaglandin F2 alpha, with a mean dosage of 40.2 mg. and mean abortion time of 24 hours and 41 minutes (ten patients). Fourteen additional mid-trimester abortions were performed using identical protocol plus the addition of oxytocin by intravenous infusion two hours after injection of the prostaglandin. All patients aborted, with mean dosage of PGF2 alpha of 28.2 mg. and mean abortion time of 15 hours and 37 minutes.     

Induction of abortion by intra- and extra-amniotic prostaglandin F2 administration

PGF2 alpha was administered intrauterine in 115 patients during the 11th to 20th week of pregnancy for abortion induction. An intra-amniotic method was used in 61 cases, an extra-amniotic one in 54 cases. Average total dose administered was 35.1 (range 5 to 65 mg) in the amniotic group and 6358 mcg (range 1500 to 14000 mcg) in the extra-amniotic group. The intra-amniotic group had an abortion rate of 92% and a 74% rate of side effects, mainly gastrointestinal irritation. Corresponding figures for the extra-amniotic group were 72% and 54% respectively. In the extra-amniotic group, doses of 4750 mcg or more increased the abortion rate up to 80% and side effects up to 64%. There were no serious complications. The intra-amniotic approach of prostaglandin induction is suitable for second trimester therapeutic abortions. The extra-amniotic approach is useful in cases of fetus mortuus and hydatiform mole.     

Farrowing induction with a combination of prostaglandin F(2alpha) and a peripherally acting alpha(2)--adrenergic agonist AGN 190851 and a combination of prostaglandin F(2alpha) and oxytocin

We studied the effect of prostaglandin (PG) F(2alpha)-AGN 190851 on farrowing induction and compared it with that of PGF(2alpha)-oxytocin. Eighty crossbred, multiparous sows were randomly assigned to the following 4 treatment groups of 20 sows each: 1) control, saline-saline; 2) PGF(2alpha) (10 mg/sow)-oxytocin (30 IU/sow); 3) PGF(2alpha) (10 mg/sow)-AGN 190851 (0.06 mg/kg); and 4) PGF(2alpha) (10 mg/sow)-AGN 190851 (0.1 mg/kg). Either PGF(2alpha) or saline was administered intramuscularly on Day 111 of gestation at 11:30 h; AGN 190851, oxytocin or saline was administered intramuscularly 20 h after the first injection. The PGF(2alpha)-AGN 190851 (0.1 mg/kg) treated sows had the shortest mean farrowing interval (2.1 +/- 1.6 h, mean +/- SD) compared with the remaining treatment groups (control: 67.1 +/- 26.2 h; PGF(2alpha)-oxytocin: 5.6 +/- 6.7 h; PGF(2alpha)-AGN 190851 [0.06 mg/kg]: 3.0 +/- 2.8 h). Duration of farrowing, litter size, litter weight and interval from weaning to first estrus in sows were not significantly changed by these treatments. The PGF(2alpha)-oxytocin group had a significantly higher stillbirth rate than the control group, whereas the PGF(2alpha)-AGN 190851 (0.1 mg/kg) group had the lowest number of pigs born dead and stillbirth rate among the 4 treatment groups. These results suggested that the PGF(2alpha)-AGN 190851 combination can be used as an alternative method to PGF(2alpha)-oxytocin for synchronizing farrowing.     

Canine prostaglandin F2alpha receptor (FP) and prostaglandin F2alpha synthase (PGFS): molecular cloning and expression in the corpus luteum

In the dog luteolysis is not affected by hysterectomy. This observation led to the hypothesis that paracrine/autocrine rather than endocrine mechanisms of PGF2alpha are responsible for luteal regression in the dioestric bitch. The present experiments tested for the capacity of canine CL to produce and respond to PGF2alpha by qualitatively and quantitatively determining the expressions of PGFS, the enzyme converting PGH2 into PGF2alpha, and the PGF2alpha-receptor (FP) in CL of non-pregnant dogs during dioestrus. Canine PGFS and FP were isolated and cloned; both genes show a high homology (82-94%) when compared to those of other species. Relatively weak FP mRNA expression was detected on day 5 of dioestrus. It had increased by day 25 and remained constant thereafter. In situ hybridization (ISH) localized FP solely to the cytoplasm of the luteal cells, suggesting that these cells are the only luteal targets of PGF2alpha in this species. Only negative results were obtained for the expression of PGFS in canine CL by routine qualitative RT-PCR. When Real Time (TaqMan) PCR was applied, repetitively more negative than positive results were obtained at all timepoints. Any positive measurements observed at any point were neither repeatable nor related to the stage of dioestrus. This led us to conclude that expression of PGFS is either absent or present at very low level only. These data suggest that luteal regression in non-pregnant bitches is not modulated by PGF2alpha. However, the FP seems to be constitutionally expressed, explaining the receptivity of canine CL to exogenous PGF2alpha.     

Cardiovascular effects of prostaglandin F(2 alpha) and prostaglandin E(2) in Atlantic cod (Gadus morhua)

Little is known of the cardiovascular functions of prostaglandins in non-mammalian vertebrates. There are indications that prostaglandins may have a function in haemostasis by constricting blood vessels in filament arteries in the fish gill after injury. Our aim was to examine the cardiovascular effect of the prostaglandins F(2 alpha) (PGF(2 alpha)) and E(2) (PGE(2)) with emphasis on branchial circulation. Intra-arterial injections of PGF(2 alpha) (10, 40, 160, 400 nmol kg(-1)) in cod caused a dose-dependent increase in ventral aortic blood pressure, a reduction in cardiac output, and an increase in gill vascular resistance. A contraction of filament arteries was observed with in vivo microscopy only seconds after injection. PGF(2 alpha) may therefore possibly be involved in a haemostatic vasoconstriction. In contrast, the most significant effects of PGE(2) appeared to be on the heart. PGE(2) also reduced dorsal aortic blood pressure.     

Induction of estrus in cattle by intraovarian injection of prostaglandin F2alpha

An effective, reduced dosage (1 10 to 1 20 the systemic dose) method for administering prostaglandin F(2alpha) in heifers to induce estrus is presented in this study. The PGF(2alpha) was injected intraovarially in five heifers at a dose of 2 mg and in another five heifers at a dose of 1 mg. Five additional heifers were injected intraovarially with 0.5 ml of distilled water and served as the controls. Regression of the corpus luteum (CL) occurred in all PGF(2alpha)-treated heifers resulting in marked decline of the peripheral levels of progesterone 24 h after treatment. Estrus was expressed 1 to 3 d later. Regression of the CL, estrus, and decline in the peripheral levels of progesterone were not observed in the control heifers. Conception rates in the heifers given either 2 mg and 1 mg PGF(2alpha) were 60 and 100%, respectively. Seven calves were born at the end of the normal gestation period while one calf was aborted.     

Response and fertility of dairy heifers following injection with prostaglandin F(2alpha) during early, middle or late diestrus

After an observed estrus, 250 dairy heifers were injected once with 25 mg of PGF(2alpha) either on cycle days 5 through 7 (E), 8 through 11 (M) or 12 through 15 (L). For five days after the PGF(2alpha) injection, heifers were inseminated at about 12 h after estrus was first observed. Observed estrual response rates were 43.0%, 83.6% and 100% for E, M and L, respectively. Average time from PGF(2alpha) to observation of estrus for E, M and L was 59, 70 and 72 h. Conception rates for heifers responding to PGF(2alpha) were 56.8%, 62.1% and 78.3% for E, M and L, respectively. Based on blood samples drawn at the time of PGF(2alpha) injection, progesterone concentration was significantly correlated with response rate but not with conception rate. When compared with M and L, E had a significantly lower response rate and conception rate as well as a shorter period between injection of PGF(2alpha) and observation of estrus.     

Coupling between cyclooxygenases and prostaglandin F(2alpha) synthase. Detection of an inducible,glutathione-activated,membrane-bound prostaglandin F(2alpha)-synthetic activity

Distinct functional coupling between cyclooxygenases (COXs) and specific terminal prostanoid synthases leads to phase-specific production of particular prostaglandins (PGs). In this study, we examined the coupling between COX isozymes and PGF synthase (PGFS). Co-transfection of COXs with PGFS-I belonging to the aldo-keto reductase family into HEK293 cells resulted in increased production of PGF(2alpha) only when a high concentration of exogenous arachidonic acid (AA) was supplied. However, this enzyme failed to produce PGF(2alpha) from endogenous AA, even though significant increase in PGF(2alpha) production occurred in cells transfected with COX-2 alone. This poor COX/PGFS-I coupling was likely to arise from their distinct subcellular localization. Measurement of PGF(2alpha)-synthetic enzyme activity in homogenates of several cells revealed another type of PGFS activity that was membrane-bound, glutathione (GSH)-activated, and stimulus-inducible. In vivo, membrane-bound PGFS activity was elevated in the lung of lipopolysaccharide-treated mice. Taken together, our results suggest the presence of a novel, membrane-associated form of PGFS that is stimulus-inducible and is likely to be preferentially coupled with COX-2.     

Hormone changes occurring during second trimester abortion induced with 15 (S)-15-methyl prostaglandin F2alpha.

Changes in progesterone, human placental lactogen (HPL), cortisol and estradiol-17B were measured during second trimester abortion induced by I.M. 15-methyl PGF2alpha. A rapid decline in progesterone and HPL was found, indicating perhaps an initial effect on the placenta. A rapid rise in cortisol was found, but it is not clear if this is due to stress or part of the termination mechanism. The changes of estradiol were not as distinct and may reflect opposite effects of the prostaglandin on the placenta and adrenals. Similar hormonal changes were observed regardless of the duration of gestation.