Pregnancy termination

During pregnancy, the antiprogestin mifepristone will induce uterine contractions, increase the sensitivity of the myometrium to prostaglandin, and ripen the cervix. These effects indicate that mifepristone can be used for termination of pregnancy. The clinical experience has shown that mifepristone is sufficiently effective for this purpose only if combined with a suitable prostaglandin, e.g. gemeprost or misoprostol. The combined treatment has been used for termination of early pregnancy (up to 63 days of amenorrhea) and for termination of second trimester pregnancy. During early pregnancy, the recommended dose of mifepristone is 600 mg (although 200 mg seems sufficient), followed 36-48 h later by 0.4-0.8 mg misoprostol administered either orally or vaginally, or vaginal administration of 1.0 mg gemeprost. For termination of second trimester pregnancy, the treatment with mifepristone is most commonly combined with 1.0 mg gemeprost repeated at 3-6-h intervals. The combined treatment is as effective and safe during early pregnancy as is the alternative vacuum aspiration and is also equally acceptable if the woman is allowed to choose the method she prefers. During the second trimester, the pretreatment will significantly reduce the duration of labor, dose of prostaglandin, and the frequency of side effects.     

Prostaglandin-induced pregnancy termination: further studies using gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries in the early second trimester

The use of gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries for the termination of pregnancy in the early second trimester has been further investigated. Of 113 women between 12 and 16 weeks gestation, 93 (82%) aborted within 24 hours of the administration of 4.4 +/- 0.1 1 mg gemeprost pessaries. The mean induction-abortion interval was 881 +/- 31 minutes. Successful abortion was achieved in 16 of the remaining 20 women after a second course of gemeprost pessaries without the need for oxytocin supplementation. There were no serious complications. Crampy abdominal pain and vaginal bleeding started after 275 and 756 minutes respectively. Twenty-two (19%) patients did not require pain relief during treatment, but 90 (80%) required parenteral opiates. Vomiting and diarrhoea occurred in 16 (14%) and 23 (20%) cases respectively. The safe induction of therapeutic abortion in 96% of women using vaginal prostaglandin alone offers an acceptable alternative to surgical evacuation in the early second trimester.     

Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment.

OBJECTIVES--To assess women''s preferences for, and the acceptability of, medical abortion and vacuum aspiration in the early first trimester. DESIGN--Patient centred, partially randomised trial. Medical abortion was performed with mifepristone 600 mg followed 48 hours later by gemeprost 1 mg vaginal pessary. Vacuum aspiration was performed under general anaesthesia. SETTING--Teaching hospital in Scotland. PATIENTS--363 women undergoing legal induced abortion at less than nine weeks'' gestation. MAIN OUTCOME MEASURES--Women''s preferences for method of abortion before abortion; acceptability judged two weeks after abortion by recording the method women would opt to undergo in future and by semantic differential rating technique. RESULTS--73 (20%) women preferred to undergo medical abortion, and 95 (26%) vacuum aspiration; 195 (54%) were willing to undergo either method, and were allocated at random. Both procedures were highly acceptable to women with preferences. Gestation had a definite effect on acceptability in randomised women; at less than 50 days there were no differences, but between 50 and 63 days vacuum aspiration was significantly more acceptable. CONCLUSIONS--Women who wish to use a particular method should be allowed their choice, regardless of gestation. Women of 50-63 days'' gestation without preferences for a particular method are likely to find vacuum aspiration more acceptable. A patient centred, partially randomised trial design may be a useful tool in pragmatic research.     

A retrospective study of 932 second trimester terminations using gemeprost (16,16 dimethyl-trans delta 2 PGE1 methyl ester).

A retrospective study of 932 second trimester terminations between 12-27 weeks gestation was carried out to determine the efficacy of gemeprost for second trimester termination. A single course of 5 x 1 mg gemeprost pessaries was administered every three hours. If abortion had not occurred after the first course of pessaries, a further course of 5 x 1 mg pessaries was administered. Intravenous oxytocin was administered after 36 hours if abortion had not occurred. Eighty per cent and ninety five per cent of patients aborted within 24 and 48 hours respectively. Of the remaining 5 per cent of women, 3 per cent aborted with escalating doses of oxytocin. In the remaining 18 (2 per cent) women, the pregnancies were electively terminated with an alternative method. The median induction-abortion interval was 18.0 hours and 15.0 hours in nulliparous and parous women respectively (P less than 0.0001). The number of pessaries required to induce abortion was not influenced by parity. Significantly more parous women bled more than 500 ml. The incidence of pelvic sepsis (0.1 per cent) and cervical tear (0.1 per cent) was low. Twenty six per cent of women had diarrhoea and 23 per cent vomited following administration of prostaglandin. This study confirmed the efficacy of gemeprost for second trimester termination of pregnancy. This method of termination is safe, non-invasive, simple and has a low complication rate.     

Prostaglandin-induced pregnancy termination: Further studies using gemeprost (16, 16 dimethyl-trans-Δ-PGE1 methyl ester vaginal pessaries in the early second trimester

The use of gemeprost (16, 16 dimethyl-trans-Δ²-PGE₁ methyl ester) vaginal pessaries for the termination of pregnancy in the early second trimester has been further investigated. Of 113 women between 12 and 16 weeks gestation, 93 (82%) aborted within 24 hours of the administration of 4.4 ± 0.1 1mg gemeprost pessaries. The mean induction — abortion interval was 881 ± 31 minutes. Successful abortion was achieved in 16 of the remaining 20 women after a second course of gemeprost pessaries without the need for oxytocin supplementation. There were no serious complications. Crampy abdominal pain and vaginal bleeding started after 275 and 756 minutes respectively. Twenty-two (19%) patients did not require pain relief during treatment, but 90 (80%) required parenteral opiates. Vomiting and diarrhoea occured in 16 (14%) and 23 (20%) cases respectively. The safe induction of therapeutic abortion in 96% of women using vaginal prostaglandin alone offers an acceptable alternative to surgical evacuation in the early second trimester.     

The use of progesterone antagonists and progesterone receptor modulators in contraception

Progesterone antagonists (PAs) and progesterone receptor modulators (PRMs) have contraceptive potential by suppressing follicular development, delaying the surge of luteinizing hormone (LH), retarding endometrial maturation, and promoting endometrial bleeding. Mifepristone, in daily doses of 2-10 mg, blocks the LH surge and ovulation. Many of the studies were conducted in women not at risk of pregnancy, and thus the contraceptive efficacy is not yet known. Nevertheless, there is evidence that daily doses of 2 or 5 mg of mifepristone have contraceptive potential. Because of anovulation, there may be an unopposed estrogen effect on the endometrium, although this risk may be mitigated by the noncompetitive anti-estrogenic activity exhibited by both PAs and PRMs. Low doses of PAs and PRMs, which do not affect ovulation, retard endometrial maturation, indicating that the endometrium is exquisitely sensitive to these compounds. This raises the prospect of endometrial contraception, i.e. prevention of endometrial maturation without disturbing ovulation or producing alterations in bleeding patterns. This approach works well in monkeys but was not found to be very promising when given to women not using contraception. On the other hand, 200 mg mifepristone administered 48 h after the LH surge, which has minimal or no effect on ovulation and bleeding patterns, is an effective contraceptive; yet, it is not a practical approach to contraception. Late luteal phase administration of mifepristone produces menstrual bleeding. However, when mifepristone was administered every month at the end of the cycle either alone or together with prostaglandins, it was not very effective in preventing pregnancy. In contrast, a mifepristone-prostaglandin combination has been shown to be a very effective treatment for occasional menstrual regulation, with vaginal bleeding induced in 98% of pregnant women, with menses delay of 11 days or less. Mifepristone is an excellent agent for emergency contraception when used within 120 h of unprotected intercourse. It is also possible that PAs and PRMs may be used to reduce the occurrence of bleeding irregularities induced by progestin-only contraceptive methods. Both classes of progesterone receptor ligands may also have contraceptive efficacy by having a pharmacological effect on the embryo or altering tubal transport or other aspects of tubal physiology.     

Cervical mucus concentration of prostaglandins E2 and F2α after pretreatment with mifepristone in the first trimester of pregnancy

Cervical dilatation and softening after pretreatment with mifepristone are well documented. As this effect is similar to that observed after local application of prostaglandin E₂ (PGE₂) it is tempting to speculate that the effect of mifepristone is mediated via an increase of the endogenous secretion of prostaglandins from the cervical mucosa. Eighteen healthy women in the first trimester of pregnancy were treated with oral mifepristone (200 mg) 48 and 24 hours before legal abortion by vacuum aspiration and 18 women in the same age of gestation without any pretreatment served as controls. Cervical mucus was collected for measurement of prostaglandins by radioimmunoassay before administration of the drug and in connection with vacuum aspiration. The cervical dilatation at the time of surgery was significantly increased in women given mifepristone as compared with untreated women (7.6 versus 5.8 mm). The wet weight of collected cervical mucus was significantly increased in mifepristone treated women. The amount of PGE₂ and prostaglandin F_2α per sample was unchanged in mifepristone-treated women, whereas the concentration was lower as an effect of dilution due to an increased yield in cervical secretion observed after mifepristone treatment. The present observation does not give any support to the hypothesis that mifepristone-induced cervical maturation is mediated via an increase in cervical prostaglandin production.     

Comparison of Yuzpe regimen,danazol, and mifepristone (RU486) in oral postcoital contraception.

OBJECTIVE--To compare the effectiveness and acceptability of three regimens of postcoital contraception. DESIGN--Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. SETTING--Community family planning clinic. SUBJECTS--616 consecutive women with regular cycles aged 16 to 45 years. MAIN OUTCOME MEASURES--Number of pregnancies, incidence of side effects, and timing of next period. RESULTS--The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. CONCLUSIONS--Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.     

Comparison of intra-amniotic prostaglandin F2 alpha and hypertonic saline for induction of second-trimester abortion.

The efficacy and safety of intra-amniotic prostaglandin (PG) F2 alpha (25 mg repeated in six hours) and hypertonic saline (200 ml 20% NaC1) were compared in an international multicentre randomised study organised by the World Health Organisation''s prostaglandin task force. Both hypertonic saline and PGF2alpha were found to be effective in terminating second-trimester pregnancy. The main advantage of PGF2alpha however, was its greater efficacy, with significantly higher success rates in the first 48 hours. Out of 717 women given PGF2alpha 614 (85-6%) aborted within 48 hours; by 24 hours 439 (61-2%) had aborted, and by 36 hours 574 (80-1%) had aborted. Out of 796 women given hypertonic saline 641 (80-5%) aborted within 48 hours; however, by 24 and 36 hours, respectively, only 161 (20-2%) and 462 (58%) had aborted. Although PGF2alpha was associated with a somewhat higher frequency of minor side effects than hypertonic saline, notably vomiting and diarrhoea, these were within acceptable limits. Only 59 women (8-2%) in the prostaglandin group had more than four episodes of vomiting and 11 (1-5%) more than four episodes of diarrhoea. Ohter side effects occurred only occasionally. No difference was found between the two groups in the frequency of incomplete abortion or excessive bleeding.     

Influence of past reproductive performance on risk of spontaneous abortion.

OBJECTIVE--To investigate the incidence of spontaneous abortion in a population of women in order to establish their risk of spontaneous abortion and the obstetric factors predisposing to it. DESIGN--Prospective study of women recruited by radio and poster appeal and from hospital outpatient clinics. SETTING--English provincial community. PATIENTS--630 Women from the general population intending to become pregnant. INTERVENTIONS--The viability of the pregnancy was assessed by abdominal ultrasonography before completion of the eighth week, and the assessment was repeated if vaginal bleeding occurred. MAIN OUTCOME MEASURE--Spontaneous abortion or live births in women with or without a previous history of spontaneous abortion. RESULTS--The overall incidence of clinically recognisable spontaneous abortion before 20 weeks of gestation was 12% (50/407 pregnancies). The risk of spontaneous abortion in each category of patient was classified with respect to the patient''s past reproductive performance and found to be influenced greatly by her previous obstetric history. In primigravidas and women with a history of consistently successful pregnancies the incidences of abortion were low (5% (4/87) and 4% (3/73) respectively), whereas women with only unsuccessful histories had a much greater risk of aborting the study pregnancy (24% (24/98)), even when their sole pregnancy had ended in abortion (20% (12/59)). The outcome of the last pregnancy also influenced the outcome of the study pregnancy; only 5% of women (5/95) whose previous pregnancy had been successful aborted, whereas the incidence of loss of pregnancy among women whose last pregnancy had aborted was 19% (40/214). CONCLUSIONS--A knowledge of the patient''s reproductive history is essential for the clinical assessment of her risk of spontaneous abortion. As the most important predictive factor for spontaneous abortion is a previous abortion, the outcome of a woman''s first pregnancy has profound consequences for all subsequent pregnancies.     

Mifepristone: a novel estrogen-free daily contraceptive pill

When the first synthetic progesterone antagonist (mifepristone) was synthesized over 20 years ago, it was clear that it had a potential as an antifertility agent. Research into the use of antiprogestogens for contraception have concentrated on three general approaches: (1) inhibition of ovulation, (2) inhibition of implantation and (3) disruption of implantation or "menstrual induction". The effect of mifepristone on the ovarian and endometrial cycle depends on dose, timing and frequency of administration. Doses of 10 mg per day or more suppress follicular development and estradiol levels. Ovulatory cycles are maintained in the dose of less than 2 mg although there is increased variability in cycle length. The endometrium shows some minor asynchronous changes, although these are not sufficient to prevent pregnancy. We have chosen to investigate daily doses between 2 and 5 mg which inhibit ovulation and menstruation in over 90% of cycles while still maintaining follicular development and levels of estradiol within the range found during the follicular phase. The endometrium shows proliferative or cystic changes lined by a layer of inactive glandular epithelium set in densely packed stroma. There is, however, an absence of proliferative activity as reflected by a reduced mitotic index and Ki67 staining. These unusual histological appearances are associated with downregulation of PR but a massive upregulation of AR in particularly glandular epithelium. The antiproliferative effect of mifepristone is reassuring suggesting that the risk of atypical hyperplasia due to the effect of prolonged exposure to estrogen unopposed by progesterone is low. In a pilot study, there were no pregnancies in 200 months of exposure in 50 women who used this method as their sole method of contraception. Daily mifepristone could provide a novel contraceptive method which should be devoid of the risks associated with estrogen containing combined oral contraceptive (COC), e.g. venous thromboembolism. The health benefits of avoiding the morbidity associated with menstruation are considerable. Recent surveys suggest that amenorrhoea would be popular with many women.     

Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2.

A group of 84 women at 39-43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E2. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE2 and 85.7% of those treated with 0.4 mg PGE2. The mean Apgar scores in the three groups were the same. The mean total dose of PGE2 were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE2 is an effective and acceptable method of inducing labor at term.     

Single intraamniotic injections of prostaglandin F-2-alpha as an abortifacient agent: size of effective dose and effect of parity

This report discusses the authors' experience with intraamniotic administration of single doses of the prostaglandin PGF2alpha as an abortifacient agent. 98 healthy women between the 12th and 26th week of pregnancy admitted to the Clinical Research Unit of the North Carolina Memorial Hospital were given a single intraamniotic dose of PGF2a administered through an indwelling polyethelene catheter inserted either transabdominally or transvaginally. The drug was given as Tham salt with the first 5 mg of any dose being given at the rate of 1 mg/minute for 5 minutes, followed by more rapid administration of the balance of the dose. Abortion which did not occur within 48 hours was considered a failure. Each patient received 1 of the following dosages: 25, 40, 50, and 75. 9 (64%) of 14 patients given 25 mg PGF2a aborted within the 48-hour period. The percentages of abortion in the doses 40, 50, and 75 mg were 88.9% (9 patients), 96.7% (60 patients) and 93.3% (15 patients) respectively. As these figures were almost similar, the 84 patients were combined as a single group (84 patients) relative to the injection-abortion time, effect of parity, and stage of gestation at which the abortion was carried out. Half of the patients in this combined group aborted in approximately 21 hours; more than 90% at the end of 32 hours; and 95% at the end of the 48 hours post-injection. For comparison, the cumulative abortion curve of 552 patients who had intraamniotic saline for abortion showed that 50% of the women aborted within 31 hours, 84% within 48 hours, and 97% within 72 hours. Prostaglandin induced abortions thus are shown to reach the 50% level 10 hours before the saline patients, and the 90% level about 21 hours before the saline patients. Significant side effects (presented elsewhere) were observed in all groups, with the incidence increasing at higher dosages. Mean induction-abortion time for nulliparas at all dosages was 17.4 hours; for multiparas, 20.4 hours. There was no clear relationship between gestational age and parity. The study shows that the effective dose for inducing abortion with PGF2a lies within the 40 to 50 mg dose range.     

Menstrual induction with PGF2 alpha and PGE2.

The "prostaglandin impact" (PGI), a massive intrauterine dose of PG, converts the refractory pregnant uterus into a reactive organ by provoking a regulatory imbalance. This regulatory conversion releases the endogenous mechanism of menstruation or abortion. During initial studies, PGI successfully provoked menstrual induction (MI) in 22 and subsequently in 65 volunteers. These results were confirmed and complemented by 2 independent trials in 14 and 36 gravidas respectively. The best clinical outcome was obtained in 20 volunteers, when a "PG-Pellet" (a mini-suppositorium) was inserted in utero, containing only 2.5 mg PGF2alpha. These 157 trials in sedated volunteers had the common features of over 90% efficiency, transient and medically acceptable side effects and infrequent complications. The present study of 542 volunteers focused upon the collection of clinical data regarding efficacy, side effects and complications of MI. All patients had committee approval for legal abortion, during the 2nd week of their missed menstrual period. They volunteered to participate because of their preference for pharmacological rather than surgical pregnancy termination. The clinical outcome of the 542 MI with 5 mg PGF2alpha (428 cases) and 1.5 mg PGE2 (114 cases) was identical. On the average, 95% of the gravidas had complete evacuation of the uterus with the clinical symptoms of delayed menstruation rather than abortion; they experienced spontaneous menstruation in 34 days after having received a single dose of PG.     

Effects of legal termination on subsequent pregnancy.

Two hundred and eleven patients who had undergone vaginal termination and were pregnant again were investigated; 43-2% had become pregnant within one year of termination. The overall fetal loss in the 211 patients was 17-5% compared with 7-5% in a group matched for parity but consisting of patients who were pregnant after a spontaneous abortion. Altogether 4-3% of pregnancies after legal abortion ended as first trimester abortions, 8-5% as second trimester abortions, and 13-7% in premature delivery. Among 11 women whose cervices had been lacerated at the time of legal termination the fetal loss in subsequent pregnancy was 45-5%, and only one pregnancy went beyond 36 weeks. Routine Shirodkar suture may be beneficial when the cervix is known to have been damaged at legal abortion. Several patients had asked that their general practitioner should not be told of their termination, and such patients may not admit their termination during a subsequent pregnancy, which could thus be jeopardised. No evidence was found to suggest that infants of patients with a history of legal termination are small for dates.     

Treatment with a single vaginal suppository containing 15-methyl PGF2 alpha methyl ester at expected time of menstruation.

Termination of early pregnancy, by vaginal administration of prostaglandin analogues, one to three weeks after the first missed menstrual period, has advantages and disadvantages in comparison with vacuum aspiration. Some of these may be reduced if the patient is treated earlier. In the present study the effect and safety of one vaginal administration of 2.5 to 3 mg 15-methyl-PGF2 alpha methyl ester around the expected time of menstruation was evaluated in 16 women exposed to the risk of pregnancy. The overall number of treatment cycles was 35 and pregnancy was confirmed by plasma beta-HCG in eight. The treatment resulted in bleeding in all the pregnant cycles while in the nonpregnant ones it only provoked spotting and bleeding did not begin until the expected time of menstruation. Treatment with 2.5 mg 15-methyl-PGF2 alpha methyl ester resulted in complete abortion in one of three women. If the dose was increased to 3 mg all five treated women aborted. In nonpregnant patients no changes in the levels of estradiol-17 beta or progesterone at any time during the 24-hour observation period were found. Serum cortisol and prolactin but not TSH levels started to increase two hours after the start of treatment and reached a maximum after five hours. The increase coincided with the onset of uterine pain. Ovulatory cycles as judged from basal body temperature occurred in the first menstrual cycle following treatment in all nonpregnant patients. Although possible to use as a "once a month treatment" it seems preferable since the dose is the same, to postpone treatment until menstruation is delayed for a week or more.     

Dydrogesterone in threatened abortion: pregnancy outcome

OBJECTIVE: To determine whether therapy with dydrogesterone in threatened abortion during the first trimester of pregnancy will improve pregnancy outcome. DESIGN: Prospective open study. SUBJECTS: Pregnant women presenting to the obstetric and gynaecology clinic admitting center with vaginal bleeding before 13 weeks gestation were evaluated for entry into the study. Women were excluded if they had a history of recurrent miscarriage. METHOD: Eligible subjects were randomized to receive either dydrogesterone 40 mg stat dose followed by 10 mg twice a day for one week or conservative therapy. RESULTS: One hundred and 54 women were recruited. There was no statistically significant differences between the two groups with regard to pre-treatment status. The continuing pregnancy success rate was significantly (p=0.037) higher in women treated with dydrogesterone (95.9%) compared with women who received conservative treatment (86.3%). The odds ratio of the success rate between dydrogesterone treatment and non-treatment was 3.773 (95% confidence interval: 1.009-14.108). CONCLUSION: Corpus luteal support with dydrogesterone has been shown to reduce the incidence of pregnancy loss in threatened abortion during the first trimester in women without a history of recurrent abortion.     

Abortion induced by RU 486: importance of its combination with a prostaglandin derivative

The antiprogesterone steroid RU 486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl l)-17 alpha-(prop-1-ynyl) estra-4,9-dien-3-one), orally administered once (600 mg), is an efficient contragestive agent in approximately 80% of pregnant women who have been amenorrheic for up to 41 days. Later on, its use is not recommended since after 41 day of amenorrhea there is an increase in the number of incomplete expulsions. A vaginal suppository of 1 mg Gemeprost, a synthetic PG-E1 analogue, has been prescribed 36-48 hrs. after the administration of RU 486. Such a suppository cannot provoke the interruption of the pregnancy by itself. In 106 women seeking for the interruption of pregnancy, and who were amenorrheic for 49 days or less, RU 486 plus prostaglandin association led to the interruption of pregnancy in all cases, and no further instrumental intervention was required. This preliminary report suggests that this method is an efficient alternative to conventional techniques available presently.     

The concurrent in vitro and in vivo release of PGE2 from a controlled-release hydrogel polymer pessary for cervical ripening

Twenty five patients booked for induction of labour, at 38 weeks or more gestation, were administered a controlled release vaginal polymer pessary containing 10 mg prostaglandin E2 (PGE2), designed to release 0.6 mg per hour in vivo. The release profile from the polymer was linear throughout the eight hour observation period with a correlation coefficient of 0.81, and regression slope of 0.93 mg/hr. with 95% confidence intervals of 0.63 mg/hr. to 1.23 mg/hr. This compared with a concomitant release profile in vitro which was uniform with time for the first five hours, but then continued at a decreasing rate with a correlation coefficient of 0.98. The relationship between PGE2 release and cervical score change was linear, with a correlation coefficient of 0.65. The results show that PGE2 release from the pessary in vivo is predictable, and suggest that the controlled release pessary offers the advantages of greater control of cervical ripening than alternative vehicles currently available.     

Effect of mifepristone on pregnancy,pregnancy-specific protein B (PSPB), progesterone,estradiol-17beta,prostaglandin F2alpha (PGF2alpha) and prostaglandin E (PGE) in ovariectomized 90-day pregnant ewes

The objective of this experiment was to determine the effect of mifepristone, a progesterone receptor antagonist, on pregnancy and secretion of steroids, pregnancy-specific protein B (PSPB) and prostaglandins at mid-pregnancy in ewes. Ninety-day pregnant ewes were ovariectomized (OVX) and treatments were initiated 72 h post-OVX. Ewes received (1) vehicle, (2) prostaglandin F2alpha (PGF2alpha, 8 mg/58 kg/bw, i.m.) 84 h post-OVX, (3) mifepristone (50 mg intrajugular at 72, 84, 96, and 108 h post-OVX), (4) mifepristone (50mg) + PGF2alpha, (5) mifepristone (100 mg intrajugular at 72, 84, 96, and 108 h), and (6) mifepristone (100 mg) + PGF2alpha. Ewes treated with vehicle or PGF2alpha alone did not abort (P > or = 0.05). But, 60, 80, 60, and 100% of ewes treated with mifepristone (50 mg), mifepristone (50 mg) + PGF2alpha, mifepristone (100 mg), and mifepristone (100 mg) + PGF2alpha, respectively, aborted (P < or = 0.05). Profiles of progesterone, estradiol-17beta, prostaglandin E (PGE), or PSPB did not differ (P > or = 0.05) among treatment groups. Profiles of PGF2alpha of treatment groups receiving mifepristone with or without PGF2alpha differed (P < 0.05) from vehicle or PGF2alpha alone-treated ewes. It is concluded that progesterone actions are necessary to suppress uterine/placental secretion of PGF2alpha and that maintenance of critical progesterone: estradiol-17beta and PGE:PGF2alpha ratios are necessary for maintenance of pregnancy.