Prostaglandin Treatment Research Articles

Multivariate analysis of factors associated with calving interval and calving rate in dairy cows

We collected data on reproductive events of cows (n = 2116) that included dates of calving, first service, last artificial insemination before pregnancy examination, pregnancy examination, abortion, diagnosis of cystic ovary, and treatment with prostaglandin. We used multivariate analysis to evaluate the relationship between the interval from insemination to pregnancy examination and the length of calving interval, adjusting for other factors affecting the calving interval. The effect of the interval from insemination to pregnancy examination on calving rate was estimated using logistic regression analysis. The calving interval was long for cows with a short interval from artificial insemination to first pregnancy examination, it was at a minimum at 55 d and increased thereafter. Other factors affecting the calving interval were cystic ovaries, prostaglandin treatment, abortion, number of artificial inseminations, and days to first service. The calving rate was low among cows with a short interval to pregnancy examination, reached a maximum at 48 d, and then declined. Other factors affecting the calving rate were abortion, number of artificial inseminations and whether the cow was bred by a clean-up bull.

Estrous synchronization in the gaur (Bos gaurus): Behavior and fertility to artificial insemination after prostaglandin treatment

The gaur (Bos guarus) is an endangered species that is a wild ancestor of domestic cattle. This study was conducted to evaluate 1) the efficacy of prostaglandin F2α (PG) to synchronize estrus in gaur, 2) behavior of male and female gaur around estrus, and 3) fertility after artificial insemination (AI) at the PG-induced estrus. Six female gaur were utilized, along with a vasectomized gaur bull used to aid in detecting estrus. All females were given two i.m. injections of PG (25 mg/injection) 11 days apart, and monitored for estrus for 120 hr (48 hr via chinball marks, followed by 72 hr continuous observation) after the second PG injection. Three of the six females were in estrus during the 120-hr evaluation period. One female was in estrus prior to 48 hr after the second PG injection, and two females were observed in estrus during the 72-hr continuous observation period. When a female was observed in estrus (standing to be mounted by the vasectomized bull), she was bred by AI at 12 and 24 hr after the onset of estrus. The four females not observed in estrus, including the one marked during the first 48 hr, were bred by AI at 80 and 92 hr after the second PG injection. Of the two gaur females observed in estrus, one female was first mated by the vasectomized bull at 77 hr and the second female was mated at 98 hr after PG. Both females exhibited very short durations of receptivity (less than 4 hr). The second female observed in estrus became pregnant after AI and gave birth to a healthy gaur calf after a 299-day gestation. It appears that female gaur can be synchronized with PG techniques developed for domestic cattle. These data should provide useful information for programs studying and maintaining this endangered species and may have relevance for the cattle industry, since the gaur could provide a source of diverse ancestral genetic material.

Treatment of tubal pregnancies with prostaglandins: Correlation between hormone profile and success

SummaryTo assess the treatment of tubal pregnancy with prostaglandins, serial analysis of β-hCG, prolactin, oestradiol and progesterone was performed in 42 patients. A total of 30 patients (71 per cent) were managed successfully with prostaglandins. Below an initial serum β-hCG value of 2500 miu/ml the success rate was 86 per cent; above 2500 miu/ml the rate dropped to 39 per cent. In the low β-hCG group serum prolactin values decreased after successful treatment but there was no decrease in the failure group. Oestradiol and progesterone levels did not differ between the groups. In patients with initial β-hCG values < 2500 miu/ml prostaglandin treatment seems to produce favourable results. Patients with β-hCG values < 2500 miu/ml should be treated by alternative surgical methods.

The use of antiprogestin (RU 486) for termination of second trimester pregnancy

Pretreatment with laminaria tent is often used in prostaglandin-induced second-trimester abortion to increase efficacy and shorten induction-to-abortion time. In the present study, two alternatives to soften the cervix and dilate the cervical canal, the antiprogestin RU 486 and intra-cervical application of PGE2, were studied. The study included 71 women requesting legal abortion in the 15th to 23rd week of pregnancy who were treated with repeated vaginal applications of 9-methylene PGE2 in a hydrophilic gel (5 mg every 4th hour) following pretreatment with 200 mg of RU 486 and/or intracervical administration of 0.5 mg of PGE2 gel. The mean interval from start of vaginal prostaglandin treatment to abortion was 13.2 h after intracervical PG-treatment, 10.0 h after antiprogestin and 6.6 h after the combined pretreatment. Patients who received pretreatment with RU 486 alone or in combination with intracervical PGE2 experienced the lowest frequency of episodes of vomiting. Of these two pretreatment alternatives, RU 486 alone has the advantage of a shorter hospital stay. It can be concluded that vaginal administration of 9-methylene PGE2 after pretreatment with RU 486 was a highly effective, safe and rapid procedure for termination of mid-trimester pregnancy, was well tolerated by the patients and was associated with few side effects.

Management of intra-uterine fetal death with vaginal administration of gemeprost or prostaglandin E2: A random allocation controlled trial

SummarySixty-nine patients with a confirmed intra-uterine fetal death in the second or third trimester of pregnancy were allocated at random to receive the prostaglandin E, analogue gemeprost, 1 mg vaginally three hourly for three doses, or a single vaginal insertion of prostaglandin E2, 25 mg as a pessary or as a gel. Intravenous oxytocin was given 15–20 h later if necessary. All pregnancies were successfully expelled using each of the three regimens employed. There were no differences between the induction-expulsion intervals between the three groups: the median interval for all the patients was 14–4 ± 9–6 h (s.d.). Delivery within 24 h of prostaglandin treatment occurred in 16/20 of the gemeprost patients and 20/27 and 19/22 respectively in the prostaglandin E2 pessary and gel groups. There were no differences in the incidences of gastrointestinal side effects or analgesic requirements between the three groups. Overall 17/69 patients required surgical evacuation of the uterus for immediate incomplete a...

Aspects of the Role of Prostaglandins in Gastrin Histamine Regulation of Gastric Acid Secretion

There is convincing evidence from in vitro studies that prostaglandins interfere with the gastrin histamine regulation of gastric acid secretion in an opposing manner. They can inhibit the action of histamine on the parietal cell when given as single-dose treatment. Conversely, when given at high doses, they liberate endogenous histamine, probably from nonparietal cells. In in vivo experiments prostaglandins are potent inhibitors of acid secretion when studied with single-dose treatment but are capable of stimulating basal acid secretion when chronically applied to rats. Studies performed in whole animal preparations on the effect of cyclooxygenase inhibitors have not fully clarified which of these two histamine-modulating effects of prostaglandins is of prime physiologic significance but favour suppression of histamine activity with subsequent acid inhibition. It appears that somatostatin release is the mechanism through which prostaglandin can simultaneously inhibit acid secretion and release plasma gastrin. At least in the rat, the pattern of plasma gastrin and somatostatin release is, similarly to acid secretion, partly reversed during prolonged prostaglandin treatment.

Estrus synchronization and fertility behavior in Black Bengal goats following either progesterone or prostaglandin treatment

Thirty-six Black Bengal female goats were in the study. They were divided into three groups of 12 goats each. Group I served as the control, Group II was treated with progesterone, Group III was administered prostaglandin F2alpha. There was 100% estrus synchronization in the PGF2alpha treated group and 90% in the progesterone treated group. The total number of kids produced in the PGF2 alpha treated group was 15 followed by 12 in the progesterone - treated group and 6 in the control group. The gestation length was found to be similar in all three groups.

Prostaglandin induced cervical ripening under tocolytic cover in primiparae: results of a double blind placebo controlled trial

In a double blind trial, 60 nulliparae with a modified Bishop score of less than or equal to 5 requiring induction of labour, received either 8 mg of salbutamol or an identical placebo orally, 30 min before vaginal administration of 2 mg prostaglandin E2 gel. Women in the salbutamol group experienced less uterine activity over the subsequent 12 h compared with those given placebo, and fewer (35%) commenced labour compared with the placebo group (62%). However, the change in cervical score was significantly less in the salbutamol group (mean 3.0, SD 3.1) than that in the placebo group (mean 5.8, SD 3.2), and the prostaglandin treatment to delivery time in the salbutamol group (mean 26.1 h, SD 6.49) was significantly longer than that in the placebo group (mean 19.3 h, SD 7.95). The first stage of labour lasted greater than 10 h in 11 women in the salbutamol group compared with five in the placebo group. Side effects attributable to salbutamol occurred in 10% of the treated women but in none of their fetuses and fetal outcome was satisfactory and similar in both groups. Our findings show that salbutamol can suppress prostaglandin-induced uterine activity during cervical ripening, which could be an advantage in induction of labour where a planned delivery is preferred. However, the poorer outcome of labour in salbutamol-treated women mitigates against this approach.

Behavioral and Endocrine Responses of Sows to Prostaglandin F2α and Cloprostenol

Behavioral and endocrine changes in the sow following injection with prostaglandin F2 alpha (PGF2 alpha) or its analogue, cloprostenol (CLO), were monitored to identify endocrine correlates of prepartum activity (nest-building). On Day 112 postcoitum, within 15 min after injection with 10 mg PGF2 alpha, sows offered straw in pens engaged in intense prepartum activity, but few behavioral changes occurred during the first 2 h following administration of 175 micrograms CLO. The temporal pattern of prepartum activity, however, was affected by both prostaglandins. In control sows, most prepartum activity came during Hours 16-0 before delivery of first piglet (delivery). After CLO, sows engaged in nest-building more during Hours 32-17 and less during Hours 16-0. In another experiment, sows in farrowing crates were injected with saline, 175 micrograms CLO, or 10 mg PGF2 alpha on Day 112 and blood was collected 0, 15, 30, 60, and 90 min later. Another sample was collected when spontaneous prepartum activity was first observed. For approximately 90 min after PGF2 alpha treatment, sows rooted, pawed, and bit and rubbed faces on crate bars; after saline and CLO, this behavior was rarely observed. After prostaglandin treatment, plasma progesterone tended to decline, a 10-fold rise in relaxin came within 15 min, but estrone did not change. Plasma prolactin rose 10-fold within 30 min after PGF2 alpha treatment, and rose more gradually after CLO treatment. When sows exhibited spontaneous prepartum activity (approximately 7 h before delivery), endocrine status was characterized by low progesterone, high estrone:progesterone ratio, and high prolactin.(ABSTRACT TRUNCATED AT 250 WORDS)

Preovulatory plasma estradiol-17β concentrations and ovulation rates in PMSG/anti-PMSG treated heifers

Possibilities for early characterization of the superovulatory response were studied in 41 PMSG/PG-treated dairy heifers, of which 21 received an additional treatment of PMSG-antiserum. Plasma was obtained at 33, 36, 41, 47 and 51 h after PG for hormone analyses. After slaughter at 6 or 7 d after insemination, the number of follicles and corpora lutea (CL) were recorded, and ova were recovered for morphological evaluation. Significant correlations were demonstrated between plasma concentrations of estradiol-17β (E2) at 33, 36 and 41 h after PG and the ovulation rate (number of CL). Each of these correlations was equal to the one found by using the peak concentration of E2 achieved during the preovulatory E2 surge. In heifers with preovulatory E2 surges, as determined with the blood sampling scheme used, both the ovarian response (number of CL and follicles) and the quality of ova recovered (number of transferable embryos) was clearly better compared to heifers without this surge. None of the parameters studied was affected significantly by treatment with PMSG-antiserum. It is concluded that plasma E2 determinations at fixed times in relation to prostaglandin treatment can be used to characterize the superovulatory response in donor cattle in terms of the ovulation rate and the quality of ova recovered. No evidence was found in favor of using PMSG-antiserum for improving either the superovulatory response or such characterization.

Early termination of pregnancy: medical induction with prostaglandins versus surgical aspiration under local anesthetic

Termination of pregnancy at 4–8 weeks gestation in 1085 patients using either local prostaglandin instillation (n = 820) or uterine aspiration under local anesthetic (n = 265) have been analyzed. Morbidity for both methods was similar although the incidence of side-effects (0.4%) and the transfusion rate (0%) were lower after aspiration than the respective rates of 59% and 1.3% after prostaglandin treatment. However the rates of genital tract trauma (0.75%) and uterine sepsis (1.8%) after aspiration were higher than the respective rates of 0.3% and 0.9% after prostaglandin treatment. The major disadvantage of prostaglandin treatment was the rate of re-admission for evacuation (8.5%) compared with (0.9%) after aspiration, although patient acceptability for both techniques was similar. In view of the advantages, more widespread use of both methods of termination is indicated.

Comparison of techniques for synchronisation of oestrus and subsequent fertility in beef cattle

Abstract One hundred and seventy-eight heifers and 275 suckling cows were allocated to either a control (untreated) group or to one of three groups treated to synchronise oestrus. The treatments were either a progestagen ear implant (SMB), a progesterone intravaginal device (PRID + PMSG), or two injections of aprostaglandin analogue (PG). Progestagen treatments effectively synchronised oestrus with similar numbers of animals exhibiting oestrus within 2 days of treatment, as were observed over 21 days in the control group. The prostaglandin treatment was much less effective (control 79%, SMB 72%, PRID + PMSG 71%, and PG 45%). Conception to timed insemination in the SMB- and PG- synchronised heifers was lower than that obtained in the other treatments (control 33%, SMB 17%, PRID + PMSG 33%, and PG 25%). In the suckling cows the conception rates of the progestagen-treated groups (48 and 50%) were better than that following PG (20%) with the controls (37%) intermediate. Plasma progesterone levels indicated that anoestrus was not the major reason for the poor performance of the PG-treated cows. An additional group of 36 cows treated with progestagen and PMSG before Day 30 postpartum indicated some advantage from this procedure in reducing the interval from calving to conception. Techniques based on the administration of progestagens appear to offer a practical means of synchronising oestrus for artificial insemination (AI) in suckling beef cows.

Morphologic study of changes of collagenous tissue in the amnion and cervix during prostaglandin-induced abortion and delivery

Marked dissociation of the cervical collagenous tissue during prostaglandin-induced abortion is well recognized, but the response of collagenous tissue of the amnion to prostaglandin treatment is not known. A morphologic study of amniotic collagenous tissue was performed after prostaglandin-induced abortion and prostaglandin-induced term delivery. The collagenous fibers of the amnion were found to be closely packed with no ground substances and formed in a thick layer. Cervical collagenous tissue of the same patients showed a marked dissociation of fibers and abundant ground substance. The fetus was often delivered within a complete sac at midtrimester. These findings suggest differences in collagenous tissue responses to prostaglandin treatment between the amnion and cervix.

10 Acceptability of abortion methods

This chapter has reported the findings of acceptability of prostaglandin pessaries compared with vacuum aspiration as methods for inducing abortion in a very early stage of pregnancy. Acceptability has been defined by the WHO as the degree with which a treatment method has attributes that make it perceived by a user or potential user to be consonant with his or her own sense of well-being and therefore will be used or preferred. The acceptability of the medical and surgical procedures for inducing abortion was studied in Swedish abortion patients using a pre- and post-abortion design for obtaining observations. Methods used included interview schedules, questionnaires, rating scales and attitude measuring techniques. Patients consenting to take part in the acceptability study had agreed to be randomly assigned to prostaglandin treatment, given at the clinic or self-administered by the patient at home, or to vacuum aspiration. A high degree of acceptability for the prostaglandin treatment was obtained in this group of patients who had applied for an abortion very soon after one missed menstrual period. This was indicated from the finding that the very high preference for this procedure remained unchanged in the group randomly assigned to it. Other measures of attitudes to prostaglandin treatment also indicated the unchanged positive attitude. There was a significant change in the attitude to vacuum aspiration among those assigned to this treatment, indicating that post-abortion it was more acceptable to these patients. However, 30% of them would still prefer the prostaglandin treatment, especially self-administered, in the event of another abortion. There were consistent and significant relationships found between the degree of negative emotional arousal before and after abortion and preference for the medical or surgical procedure and also the amount of complaints after abortion. Those patients who pre-abortion had preferred the self-administered procedure were, regardless of which treatment they had been assigned to, those who were least emotionally upset both before and after the treatment and also complained the least. This chapter also reported on findings of how acceptable the medical and surgical procedures can be inferred to be from comparisons of preferences and attitude measures obtained from abortion patients before treatment and from women in the same age group (who would not exclude an abortion if pregnant) in samples from outside the clinical setting. In the non-patient groups about half the subjects would prefer the medical alternative.(ABSTRACT TRUNCATED AT 400 WORDS)

5 Medical methods to terminate early pregnancy

The medical methods of terminating early pregnancy, i.e., prostaglandins, progesterone synthesis inhibitors and progesterone receptor antagonists are reviewed and compared to vacuum aspiration from the research literature. All of these methods have decreasing effectiveness up to the 9th week, when rates of incomplete abortions increase to about 40%. 1 PGF analogue and 3 PGE analogues are available and feasible for clinical use as early abortifacients. Gastrointestinal side effects are universal with the PGF, but only 20-40% with the PGE analogues. Epostane is a progesterone synthesis inhibitor, blocking 3beta-OH-steroid dehydrogenase. RU-486 and ZK 98734 are progesterone receptor antagonists. These drugs cause progesterone withdrawal over a few days, causing detachment of the trophoblast, impaired beta-hCG production, increased sensitivity of the myometrium to PGs and possibly ripening of the cervix. A single 800 mg dose of RU-486 induced complete abortion in 85% of women up to 10 days after the missed period. For routine clinical use RU-486 is taken for 3 days and sulprostone or gemeprost (PG analogs) are given intramuscularly or vaginally, with results comparable to vacuum aspiration. Bleeding lasts longer with the combined medical treatment, averages 62-81 ml, but may be severe enough to require transfusion in 0.15%. About 40% of women had nausea and vomiting. Progesterone and hCG levels declined rapidly after 3 days, and prolactin levels rose. With PGs, cortisol levels rise and the pregnancy hormones fall more rapidly. The antiprogestins decrease glucocorticoid activity but not enough to affect the feedback system. While no psychological studies have been reported comparing the combined medical abortion treatment with vacuum aspiration, prostaglandin treatment was preferred over aspiration. Home treatment with PGs, however, reduced proportion of women needing morphine analgesia from 40 to 5% compared to hospitalization.

AMELIORATION OF LUNG ISCHEMIC INJURY WITH PROSTACYCLIN

The single-flush technique of lung preservation is thought to be enhanced by prostaglandin treatment. In order to test this hypothesis, ten beagle dogs underwent thoracotomy and in situ flush perfusion of the excluded left lung with 30 ml/kg of cold, modified Euro-Collins' solution. Group 1 (n = 5) received pretreatment with 30 ng/kg/min of PGI2 by infusion and as an additive to the flush (20 micrograms/L). Group 2 (n = 5) received no PGI2 and served as controls. Following 60 min of warm ischemia, the left lung was reperfused, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. The severity of reperfusion injury was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain and bronchoalveolar lavage and ultrastructural studies. PGI2 therapy resulted in significant amelioration of reperfusion injury, with superior oxygenation at both 1 and 4 hr (PaO2 at 1 and 4 hr, respectively; PGI2: 145 mmHg +/- 17.0 and 114 +/- 11.2; no PGI2: 59 mmHg +/- 5.8 and 51 +/- 4.5; P less than 0.01 at both times), lower pulmonary vascular resistance index at 4 hr (PVRI; PGI2: 913 dynes sec cm-5m-2 +/- 91; no PGI2: 1239 +/- 68; P less than 0.05) and lower lung weight (PGI2: 76 g +/- 4; no PGI2: 146 +/- 10; P less than 0.001). Bronchoalveolar lavage studies revealed an influx of neutrophils following reperfusion that was less marked in the PGI2 group (increase in % neutrophils; PGI2: 50.4 +/- 6.7; no PGI2: 76.9 +/- 6.0; P less than 0.05). Lung injury score assessed by electron microscopy was lower in the PGI2 group (PGI2: 5.2 +/- 1.1; no PGI2; 8.1 +/- 0.5; P less than 0.05). It is concluded that PGI2 treatment is protective against ischemic lung injury in this model.

The effect of prostaglandin administration to Holstein-Friesian cows at Day 26 postpartum on clinical findings, and histological and bacteriological results of endometrial biopsies at Day 40

Ninety-two cows that calved between April and August 1984 in a commercial dairy herd were studied. The cows were randomly assigned to receive either cloprostenol (500 mug) or saline placebo on Day 26 postpartum. In addition, each cow was examined per rectum, had three endometrial biopsies taken and milk progesterone level determined. Double-blind techniques were used in administering treatments and in assessing response to treatment. The results of histological and bacteriological assessment of endometrial biopsies and clinical findings at Day 40 were compared between the cows that received prostaglandin at Day 26 and those that did not. Each Day 40 variable which was significantly associated with prostaglandin treatment at Day 26 was regressed against the treatment variable and progesterone level at Day 26 as well as a prostaglandin progesterone interaction term. Prostaglandin-treated cows had less vaginal discharge, smaller diameter uterine horns, less inflammation and fibrosis in the endometrium, and were less likely to have Actinomyces pyogenes isolated from a biopsy at Day 40 than untreated cows. These effects were independent of progesterone level at the time of treatment.

Morphological effects of aspirin and prostaglandin on the canine gastric mucosal surface

Abstract An iodoplatinate technique that selectively stains phospholipid was used to evaluate morphologically the effects of aspirin and 16,16-dimethyl prostaglandin E 2 on canine gastric mucosa in an in vitro Ussing chamber system. The association between these morphological alterations and the changes in mucosal surface hydrophobicity as determined by contact angle analysis was also investigated. Prostaglandin (1 μg/ml) did not alter aspirin-induced cell injury, although it reduced (45%) the detachment of damaged cells from the lamina propria. Mucus release appeared to be stimulated independently both by aspirin and prostaglandin treatment and by the blotting and drying procedure routinely performed before contact angle analysis. When an extracellular mucus gel coat was present, it contained numerous iodoplatinate-reactive vesicles and myelinated or lamellated structures. Iodoplatinate-reactive substances also appeared at the luminal surface of the mucus gel as a filamentous band. This band of reactivity was frequently seen after simultaneous treatment with prostaglandin and aspirin but only sporadically observed after aspirin treatment alone. The hydrophobic nature of the canine gastric mucosa under the above experimental conditions correlated well (r = 0.743, p

Morphological effects of aspirin and prostaglandin on the canine gastric mucosal surface: Analysis with a phospholipid-selective cytochemical stain

An iodoplatinate technique that selectively stains phospholipid was used to evaluate morphologically the effects of aspirin and 16,16-dimethyl prostaglandin E2 on canine gastric mucosa in an in vitro Ussing chamber system. The association between these morphological alterations and the changes in mucosal surface hydrophobicity as determined by contact angle analysis was also investigated. Prostaglandin (1 μg/ml) did not alter aspirin-induced cell injury, although it reduced (45%) the detachment of damaged cells from the lamina propria. Mucus release appeared to be stimulated independently both by aspirin and prostaglandin treatment and by the blotting and drying procedure routinely performed before contact angle analysis. When an extracellular mucus gel coat was present, it contained numerous iodoplatinate-reactive vesicles and myelinated or lamellated structures. Iodoplatinate-reactive substances also appeared at the luminal surface of the mucus gel as a filamentous band. This band of reactivity was frequently seen after simultaneous treatment with prostaglandin and aspirin but only sporadically observed after aspirin treatment alone. The hydrophobic nature of the canine gastric mucosa under the above experimental conditions correlated well (r = 0.743, p < 0.005) with the percentage of mucosal surface covered by this filamentous band, and less so with the density of iodoplatinate-reactive structures within the mucus gel. We conclude that phospholipid structures in the mucus gel may account for the hydrophobic nature of the gastric mucosal surface and the ability of damaging and “cytoprotective” agents to influence both surface wettability and barrier integrity.

The efficacy of oral Mifepristone (RU 38,486) with a prostaglandin E 1 analog vaginal pessary for the termination of early pregnancy: Complications and patient acceptability

Outpatient terminations were performed on 100 ultrasonographically confirmed pregnancies of less than or equal to 63 days with a single oral dose of RU 38,486 (600 mg) and a single vaginal pessary of 16,16-dimethyl-trans-delta 2-prostaglandin E1 (1 mg) 48 hours later. Abortion occurred in all patients; in 95 it was complete, in four it was incomplete, and one resulted in a missed abortion. In 88% the abortion occurred within 4 hours of prostaglandin treatment. A total of 25% of patients had nausea and 15% vomited after RU 38,486 treatment. After prostaglandin-treatment, 13% vomited, 10% had diarrhea, and 23% required administration of an opiate analgesic agent. No patient was transfused and there was no genital tract trauma; one case of suspected pelvic infection occurred. If the need for termination arose again, 88% would elect to use the method again, 9% would not. The combination of the antiprogestin RU 38,486 and a vaginal prostaglandin pessary appears to offer a safe, efficient, acceptable nonsurgical outpatient method of termination. Further studies on dosage and treatment protocols would be justified.