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Background: The effect of misoprostol administered by different routes on pregnant uterine contractility was investigated.Methods: Thirty-two women with a pregnancy between 8 and 11 weeks of gestation requesting termination of pregnancy were recruited. Misoprostol was administered either orally (0.4 mg), vaginally (0.4 mg) or sublingually (0.2 or 0.4 mg) according to consecutive allocation. Intrauterine pressure was recorded using a Grass polygraph connected to a pressure transducer 30 min before misoprostol was given and for 4 h thereafter. At the end of the recording, suction curettage was performed.Results: The first effect observed was an increase in uterine tonus, which occurred after a significantly shorter time following oral (7.8 min) and sublingual (10.7-11.5 min) than after vaginal (19.4 min) treatment. The time to maximum tonus elevation was also significantly shorter (39.5, 47.1-51.7 and 62.2 min for the three groups respectively). Regular uterine contractions developed in all subjects following sublingual and vaginal administration but not after oral administration. The increase in uterine activity measured in Montevideo Units was significantly higher after 2 h and thereafter for sublingual and vaginal treatment than for oral misoprostol.Conclusions: Based on recording of uterine activity, sublingual misoprostol acts as rapidly as oral treatment, while development of contractions was similar to that seen following vaginal administration. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of the anti-progestogen Org 31710 in improving cycle control in healthy women using the desogestrel progestogen-only pill was investigated in this randomized, double-blind, placebo-controlled study.Methods: A total of 103 women using the 75 micro g desogestrel progestogen-only pill daily also received either 150 mg Org 31710 or placebo once every 28 days, starting on day 1, for a duration of 4-7 treatment cycles.Results: The percentage of women with bleeding or spotting (B/S) every day in the placebo group was on average 30% during the whole treatment period and no days without reported B/S occurred. In contrast, a cyclic pattern was observed for the Org 31710 group; a peak incidence of B/S was observed on day 3 or 4 of each cycle, followed by a sharp decrease on cycle days 9-15. Compared with controls, less subjects in the Org 31710 group reported irregular, frequent or prolonged bleeding. These differences were clearly observed in the initial cycles, but were somewhat less pronounced during the later cycles of the treatment period. A relatively high incidence of B/S episodes starting in the second section of the cycle was also observed.Conclusion: The addition of Org 31710 once a month improved cycle control in women using daily treatment with 75 micro g desogestrel. [ABSTRACT FROM AUTHOR]

In this two centre study, the efficacy of 200 mg mifepristone orally followed 48 h later by 0.4 mg misoprostol orally for menstrual regulation was investigated. The dose of mifepristone was taken the day before the expected day of menstruation. Each volunteer was planned to participate for up to 6 months. A plasma β human chorionic gonadotrophin (HCG) was measured on the day of mifepristone intake. The study was disrupted prematurely due to low efficacy. In 125 treatment cycles the overall pregnancy rate was 17.6% (22 pregnancies) and the rate of continuing pregnancies (failure) was 4.0%. Eight women discontinued the study due to bleeding irregularities which were seen in 15 cycles (12%). These effects on bleeding pattern made the timing of treatment day difficult. Late luteal phase treatment with a combination of mifepristone and misoprostol is not adequately effective for menstrual regulation. [ABSTRACT FROM PUBLISHER]

Human fetal spinal cord tissue was recovered from elective abortions and grafted to the anterior chamber of the eye of adult athymic nude rats. The transplants slowly became vascularized from the host iris during the first months. There was a clear cut stage-dependent survival and growth along a more 'human' time-table. Fetal spinal cord tissue from embryos younger than gestational week 8 showed a much better survival and growth than tissue from older stages. Using laminin immunohistochemistry blood vessels could be visualized in the grafts. The pattern of vascularization was, however, clearly abnormal; there were fewer vessels which had abnormally thick walls as compared to those in the normal spinal cord. Similar to rat spinal cord allografts the human spinal cord xenografts displayed a relative gliosis and were surrounded by a glial layer visualized with antibodies against glial fibrillary acidic protein. Neurofilament-immunoreactive fibres were found inside the glial layer. A variety of neurons were found including large polygonal motoneuron-shaped cells, albeit with CGRP and AChE negative cell bodies. Both Substance P and enkepha-lin-immunoreactive cells and fibres were found. It is concluded that xenografted fetal human spinal cord survives, grows and may provide a useful model for experimental studies of human spinal cord development and connectivity. [ABSTRACT FROM AUTHOR]

The potential for growth and development of human tissue grafts was explored by transplantation to the anterior chamber of the eye of rats and mice. Tissues were obtained from therapeutic abortions, performed in the eighth to twelfth week of gestation, using a slight modification of routine vacuum aspirations. Recipients were either adult rats immunosuppressed with cyclosporin A and protected with antibiotics, or nude immunodeficient Balb C mice. Catecholamine-rich tissues such as chromaffin cells from the adrenal medulla, sympathetic ganglia, central dopamine neuroblasts from the substantia nigra, and noradrenaline neuroblasts from the locus coeruleus all survived grafting, and in many cases formed nerve fibers that invaded the host iris. Similarly, central serotonin neurons from developing raphe nuclei grafts were able to innervate host irides. Human fetal cerebellar and cerebral cortical transplants continued their development in rat host eyes. Extracellular recordings from such cerebellar and cortical grafts revealed spontaneously active cells with immature action potential waveforms. Spinal cord grafts also survived and contained substance P-immunoreactive neurons. Dorsal root ganglia were able to form nerve fibers invading the host iris, as evidenced by neurofilament immunohistochemistry. Heart tissue survived and manifested spontaneous rhythmic contractions in oculo. Both human cortex cerebri and heart tissue grafts became innervated by sympathetic adrenergic nerve fibers from the rat host iris. Thus both graft-to-host and host-to-graft neuronal connections may be established between man and rat. Taken together, these data suggest that transplantation of human fetal nervous tissues to the anterior chamber of immunosuppressed or immunodeficient rodent hosts yields a unique model system for studies of human brain development, developmental disturbances, connectivity, and the action of drugs. [ABSTRACT FROM AUTHOR]

The effect of a low dose of mifepristone (RU486) on ovarian and endometrial function was studied in 14 healthy women. The study included one control and two treatment cycles. During the treatment cycles, either 2.5 mg (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly. The concentration of ovarian steroids and luteinizing hormone (LH) in urine was measured daily, cortisol in blood once weekly and glycodelin (placental protein 14; PP14) at the time of menstruation. Ovarian function was monitored by vaginal ultrasound. An endometrial biopsy was taken in each cycle in the mid-luteal phase, based on self-measurement of the LH peak, or on cycle day 22 if no LH peak could be detected. In the evaluation of the results, the outcome of the enzyme immunoassay of LH was used to date the biopsy. Endometrial progesterone and oestrogen receptors and Dolichus biflorus agglutmin (DBA) lectin binding were measured. Ovulation was not inhibited by treatment with mifepristone, and an LH peak could be determined in all control and treatment cycles. However, in four subjects (one with the higher and three with the lower dose) the follicular phase was prolonged by 6–13 days. The duration of the luteal phase and the concentrations of pregnanediol and oestrone glucuronide were not affected by treatment A dose of 5 mg, and to a lesser extent 2.5 mg, mifepristone once weekly caused desynchron-ization of endometrial development Endometrial progesterone receptor, but not oestrogen receptor, concentration was significantly increased by the higher dose. A significant reduction in DBA-lectin binding and in serum glycodelin concentrations was also found. Thus, low doses of mifepristone do not inhibit ovulation but delay endometrial development and impair secretory activity. Whether these effects are sufficient to prevent implantation remains to be established. [ABSTRACT FROM PUBLISHER]

The effect of a single post-ovulatory dose of RU486 on endometrial maturation was studied in the implantation phase. A total of 11 healthy women were followed for one control and one or two treatment cycles. In treatment cycles, a dose of 200 or 400 mg RU486 was administered on day luteinizing hormone (LH)+2. In both control and treatment cycles, an endometrial biopsy was obtained on LH+6 to LH+8. These biopsies were assessed by morphometric and immunohistochemical analyses. The treatment with RU486 did not disturb the normal menstrual rhythm but caused a significant inhibition in the endometrial development. Glandular progesterone receptor staining was significantly more pronounced after RU486 treatment, while there was a reduction in the Dolichos biflorus agglutinin lectin binding, indicating inhibition of the normal secretory transformation of the endometrium. It is likely that these effects on endometrial development and secretory activity represent the basis of the contraceptive effect of post-ovulatory RU486 treatment. [ABSTRACT FROM AUTHOR]

Mifepristone (RU 486) is an antiprogestin which interacts with progesterone at the receptor level. Administration of mifepristone immediately after ovulation does not upset the menstrual cycle. However, the maturation and function of the endometrium is inhibited and uterine contractility is changed. To test if these effects are sufficient to prevent implantation, 21 women agreed to use one single treatment with 200 mg mifepristone on day luteinizing hormone (LH) + 2 monthly as their only contraceptive method. The women were treated for 1– 12 months. The time of the LH peak was determined in the urine by the women themselves using a rapid LH test (Ovu-quick, Organon). The overall number of cycles studied was 169. In 12 cycles the women were unable to detect the LH peak. In these cycles no treatment was given and the women advised to use barrier methods during the time to menstruation. The remaining 157 cycles with a detectable LH peak were all ovulatory based on plasma progesterone measurement. One pregnancy occurred. On the basis of the time of the LH peak, it was retrospectively calculated that in 124 cycles at least one act of intercourse occurred during the period 3 days before to 1 day after ovulation. The probability of pregnancy in this period of the menstrual cycle is thus 0.008. The women did not complain of any treatment-related side-effects apart from slight bleeding for 2–3 days starting a few days after the day of treatment in 35% of the cycles. The results show that the effect of mifepristone on the endometrium is sufficent to prevent pregnancy and indicate that treatment with antiprogestin can also be used for contraceptive purposes. [ABSTRACT FROM PUBLISHER]

The effects of RU 486 combined with tamoxifen and tamoxifen alone on hormonal parameters and endometrial development at the time of implantation were studied. Measurements of cytosolic oestrogen and progesterone receptors in endometrium and placental protein 14 (PP14) in plasma were also included. Three dosage schedules were used: single oral dose of 40 mg tamoxifen alone and in combination with 200 mg RU 486, and 40 mg tamoxifen for three consecutive days starting on the first day after the luteinizing hormone (LH) surge. The combined treatment prolonged the luteal phase (P < 0.05) and increased the plasma levels of progesterone. A single dose of tamoxifen did not affect the bleeding pattern and plasma hormone levels, but raised plasma oestradiol and LH with the 3-day treatment. The endometrium was retarded after the combined and the 3-day treatment with tamoxifen. Concentrations of cytosolic progesterone receptors were higher after the combined therapy, but were unaffected after tamoxifen only. PP14 levels were higher (P < 0.05) after repeated tamoxifen doses than in controls, but were lower with combined treatment. Progesterone and oestrogen are evidently necessary for endometrial maturation during the secretory phase of the menstrual cycle. PP14 levels in plasma cannot be used for clinical assessments of endometrial function because high levels coincide with disturbed endometrial development. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the effect of a single dose of RU 486 administered very early in the secretory phase on endometrial development and levels of progesterone receptors, on plasma levels of gonadotrophins and ovarian hormones and on the pattern of menstrual bleeding. Twenty-four regularly menstruating subjects participated and were studied during a control, a treatment and a follow-up cycle. In the treatment cycle, a single dose of 200 mg RU 486 was given in the evening of the second day after the urinary LH peak. Plasma was collected from cycle day 10 until menstruation in both control and treatment cycles. The lengths of the control, treatment and follow-up cycles were equal. Three of the subjects had slight vaginal bleeding in association with RU 486 intake which, however, did not disturb their normal menstrual rhythm. Plasma levels of oestradiol, progesterone and FSH were not affected in the treatment cycle, whereas LH levels increased slightly. The elimination half-life of RU 486 was 28.6 h. An endometrial biopsy was taken 12, 36 or 84 h (LH + 3, LH + 4 and LH + 6) after drug intake (eight subjects in each group) and another biopsy was taken on the corresponding day in the control cycle. The specimens were assessed by morphometric analysis and for cytosolic progesterone receptor concentrations. Endometrial biopsies taken 12 h (on LH + 3) after RU 486 intake contained significantly ( < 0.001) lower levels of cytosolic progesterone receptors than in the control cycle, but levels at 36 and 84 h were similar. Morphometric analysis revealed a retardation of endometrial development as early as 12 h after RU 486 intake. The degree of retardation was more marked after 36 and 84 h. These results suggest that the effect on the endometrium of a single dose of RU 486 immediately after the LH peak, may be sufficient to prevent implantation. Thus, treatment with RU 486 in the early secretory phase of the menstrual cycle might be considered for use as a once-a-month pill for fertility control. [ABSTRACT FROM PUBLISHER]

It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone. Overall, 25 of 42 women (59%) had a complete abortion, 15 women (36%) did not abort and the remaining two had incomplete abortions. Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort. Thus oral PGE2, when given in clinically acceptable doses, is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy. [ABSTRACT FROM AUTHOR]

Seventeen healthy women aged 24–45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P-G), oestrone glucuronide (E-G), oestradiol (E), progesterone (P), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7–10 ( = 7) or on cycle days 20–23 ( = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21–28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women ( = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment. In four of these women the bleeding was scanty and followed by a menstrual-like bleeding at expected time, while in the remaining five volunteers the treatment bleeding was heavier and not followed by a new bleeding until a month later. The duration of the secretory phase was 16.5 ± 1.3 days in women with two bleeding episodes and 11.8 ± 1.9 days in women with one bleeding episode ( < 0.05). The hormonal parameters were similar in both groups up to the start of the treatment. In the patients with one bleeding episode, the treatment was associated with a reduction in progesterone concentration, while in the patients with two bleeding episodes the progesterone concentration remained elevated until the second bleeding episode. Light microscopic examination of the endometrium revealed unique changes in the endometrial morphology. The results indicate that RU486 acts mainly on the endometrium but a direct or indirect effect on the corpus luteum cannot be excluded. The age of the corpus luteum may be of importance for its susceptibility to RU486 treatment. [ABSTRACT FROM PUBLISHER]

Seventeen healthy women aged 24-45 years with regular menstrual periods, proven fertility and not using steroidal contraceptives or IUD were recruited for the study. The volunteers were followed during one control, one treatment and one follow-up cycle. Daily morning urine samples were obtained during the control and the treatment cycle. The samples were analysed with regard to pregnanediol glucuronide (P2-G), oestrone glucuronide (E1-G), oestradiol (E2), progesterone (P4), LH and creatinine. During the entire 3-month study the subjects kept a record of uterine bleeding and side effects. The subjects received 50 mg RU486 daily either on cycle days 7-10 (n = 7) or on cycle days 20-23 (n = 10). An endometrial biopsy was taken on cycle day 10 in the first group and on cycle days 21-28 in the second group of patients. Treatment during the proliferative phase caused significant prolongation of the cycle length due to a delay of the oestrogen and LH surge. However, once the oestrogen concentration started to increase, the remaining part of the cycle was normal. The length of the follow-up cycle was similar to that of the control cycle. The morphology of the endometrium did not differ from control samples taken from untreated women at the same time of the cycle. All ovulating women (n = 9) treated in the mid-luteal phase started to bleed on the 3rd to 4th day of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

The effects of intravenous infusions of the stable prostaglandin analogue 9-deoxo-16,16-dimethyl-9-methylene-PGE (9-methylene-PGE) in a dosage of 10 or 24 μg/min were studied in the consicious euhydrated, dehydrated, and hyperhydrated with the simultaneous administration of exogenous arginine vasopressin (AVP), sheep. The infusions decreased urine osmolality and increased urine flow and renal free water clearance. The results indicate that 9-methylene-PGE exhibits its diuretic effect by antagonizing the antidiuretic action of AVP. In the hyperhydrated sheep receiving AVP the syndrome of inappropriate antidiuretic hormone release (SIADH) was simulated. As the prostaglandin analogue effectively blocked the antidiuretic effect of the AVP-administration it appears that 9-methylene-PGE may play a future role as a diuretic agent, especially in conditions characterized by water retention and dilutional hyponatremia such as SIADH. [ABSTRACT FROM AUTHOR]

In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE in gel given intracervically and 2.0 mg PGE given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE-gel compared to two out of 19 patients given placebo ( p < 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 ( p < 0.05) after PGE-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE-gel intracervically. The results were consistent with those obtained in patients receiving PGE-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE-gel treatment. The hyperactivity was readily countered with the β-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy. [ABSTRACT FROM AUTHOR]

An industrially manufactured ready-to-use PGE gel for cervical ripening was clinically evaluated. The study included 42 primiparous and eight multiparous women with an unfavourable cervix (Bishop score ⩽ 5) admitted to hospital for induction of labour on medical grounds. PGE, 0.5 mg, in 2 ml triacetin gel was instilled into the cervical canal. In nine patients (18%) the gel induced labour and subsequent delivery. In the remaining women the mean Bishop score increased from 3.0 to 7.7 during a 24-h period and labour was induced by either i.v. oxytocin or PGF. None of the 50 patients experienced gastrointestinal side effects during pretreatment with PGE. In 50% of the patients slight uterine contractility was noticed. All patients went into labour. The incidence of Cesarean section was 10%. Except for two patients treated because of intrauterine fetal death there was no perinatal mortality. The 5-min Apgar score was 8 or more in all newborn but 1. The main advantage of the new gel is that it is ready to use without any mixing procedure. Moreover, the stability of PGE is sufficient to allow routine clinical use. [ABSTRACT FROM AUTHOR]

A new PGE-gel, based on a cross-linked starch powder, has been developed. This gel seems to have solved several of the pharmaceutical and practical problems connected with local administration of prostaglandins. In a three-center study 120 nulliparous patients were given 0.5 mg PGE in 2.2 ml gel intracervically prior to dilatation of the cervix and evacuation of the uterus in late first trimester. Considerable cervical dilatation was obtained within 15 h. The frequency of side effects, including pain and gastro-intestinal discomfort was low. The technique can be recommended for outpatients. [ABSTRACT FROM AUTHOR]

Leukaemia inhibitory factor (LIF) is a cytokine which plays an obligatory role in mouse blastocyst implantation. In human endometrium, LIF expression is significantly increased in the mid-luteal phase indicating that LIF may also play an important role in the human. We have previously shown that a single dose of 200 mg of mifepristone immediately post-ovulation is an effective contraceptive method, probably due to inhibition of endometrial development and function. The purpose of this study was to investigate the effect of various doses of mifepristone on endometrial LIF expression. A total of 22 fertile, regularly-menstruating women were studied during control and treatment cycles. The subjects were divided into four groups: group I received a single dose of 200 mg of mifepristone on cycle day LH + 2 (n = 7). The subjects in groups II and III were treated with either 5 mg (n = 5) or 2.5 mg (n = 5) once a week for 2 months. Group IV subjects received 0.5 mg per day (n = 5) of mifepristone for 3 months. LIF was measured immunohistochemically in endometrial tissue specimens taken on the corresponding day (cycle day LH + 6 to LH + 8) in hormonally-characterized control and treatment cycles. LIF immunostaining was observed in all controls and located to the cytoplasm of the luminal and glandular epithelial cells and stromal cells. In the treatment cycles the staining of luminal epithelium and stroma was similar to controls, while the glandular staining was reduced in all treatment groups. This study reveals that early luteal phase treatment as well as intermittent or daily low dose treatment with mifepristone reduces endometrial glandular LIF expression at the expected time of implantation. The results further support the contraceptive potential of mifepristone in low doses. [ABSTRACT FROM PUBLISHER]

The effects of low daily doses of the antiprogestin mifepristone (RU 486) on ovarian and endometrial function were studied. The study included one control cycle, three treatment cycles and one follow-up cycle. During the treatment cycles, either 0.1 (n = 5) or 0.5 (n = 5) mg of mifepristone was administered once daily. Urine samples were collected three times weekly during the control and treatment cycles and pregnanediol glucuronide and oestrone glucuronide and luteinizing hormone (LH) were quantified by radioimmunoassay. Blood samples for cortisol measurement were collected once weekly and for serum glycodelin at the onset of menstruation. An endometrial biopsy was obtained in the mid-luteal phase in the control cycle and in the first and third treatment cycles and analysed by morphometric and histochemical methods. Binding of Dolichus biflorus agglutinin (DBA) lectin was measured and expression of progesterone and oestrogen receptors and glycodelin were analysed immunohistochemically. All cycles studied were ovulatory with an LH peak and elevated pregnanediol glucuronide concentrations. Follicular development seemed normal as judged by ultrasound examination. The length of the menstrual cycle and the menstrual bleeding were not significantly altered. Following administration of 0.5 mg mifepristone/day, endometrial development appeared to be slightly retarded and glandular diameter was significantly reduced. Furthermore, significant decreases in DBA lectin binding and endometrial expression of glycodelin were observed. Daily doses of 0.1 mg did not have any significant effect on the endometrium. No differences in oestrogen or progesterone receptor immunoactivity between control and treatment cycles were seen. This study provides further evidence that endometrial function is sensitive even to doses of antiprogestin that are low enough not to disturb ovulation. It remains to be established whether these effects are sufficient to prevent implantation. [ABSTRACT FROM PUBLISHER]

Prostaglandin F2x was administered intravenously to 166 women for induction of legal abortion. The patients were subdivided into different treatment groups to investigate the relative importance of the administered dose and the duration of infusion at various stages of pregnancy. The results of different parameters were analysed statistically. The details of the clinical outcome were analysed according to a defined scoring system describing the actual events following a certain treatment plan. Early pregnancies (7-8 weeks) were more susceptible to induction by PGF2α infusion than later stages of gestation. The success rate in the 9th-20th week of pregnancy was dose dependant as demonstrated by termination of pregnancy in 75% of the high dose (100 μg PC min) group and only 27% in the low dose group (50 μg per min). The duration of infusion was the second parameter of vital importance to achieve a satisfactory outcome. Infusion of a moderate dose (75 μg per min) for a period of 15 hours could induce a valuable clinical response in the form of cervical dilatation, yet the duration was too short to complete the abortion process. The frequency of vomiting and diarrhoea was an important complicating feature in the high dose group. The high dose necessary for an acceptable success rate is accompanied by a high incidence of distressing symptoms (an episode of vomiting or diarrhoea every second hour). This fact limits the routine clinical use of intravenous PGF2α prostaglandins for induction of abortion. [ABSTRACT FROM AUTHOR]

The influence of prostaglandin E1 (PGE1), oxytocin and methyl ergometrin maleate (Mether-gin®) on the contractility of the pregnant human uterus was compared in in vivo experiments on 8 early pregnant and 14 midpregnant women. The substances were administered intravenously in separate injections. With the doses used PGE1 and oxytocin caused a marked elevation of tone whereas Methergin® had a less significant effect. The duration of the elevation of tone after PGE1 was approximately three times longer than that after oxytocin but considerably shorter than after Methergin®. The motility pattern following Methergin® was characterized by small irregular contractions which differed completely from that after PGE1 and oxytocin. The pharmacological effect of PGE1 on the midpregnant uterus suggests that this substance might reduce blood loss and shorten the period of time for placental separation during the third stage of labour. However, this assumption could not be confirmed as judged from a small clinical pilot study carried out on 188 women. [ABSTRACT FROM AUTHOR]

The effect on uterine contractility of prostaglandin E1 (PGF2α) and F2α (PGF2α) was studied in 19 non-pregnant women. Uterine motility was recorded by the micro balloon method and the prostaglandins administered by single intravenous injections in increasing doses. Doses above threshold levels of both PGE1 and PGF2α always resulted in stimulation of the uterus primarily in terms of tone elevation., A short drop of tone during 40-60 seconds immediately following the injection was obtained in a few experiments after high doses of PGE1. This response preceeded the normal stimulatory effect., The threshold dose for PGE1 was approximately 20 μg and that for PGF2α around 50 μg or lower., The non-pregnant uterus is probably more sensitive to PGF2α than the midpregnant uterus., The number of experiments were too few to allow conclusions as to differences in uterine sensitivity during the various phases of the menstrual cycle., Administration of oxytocin and vasopressin did not enchance the uterine sensitivity to stimulation by PGE1. [ABSTRACT FROM AUTHOR]

The antiprogestin mifepristone has shown potential to be used as a contraceptive. If 200 mg mifepristone is administered immediately after ovulation, the endometrium shows sufficient impairment of secretory development to prevent implantation. Low daily doses of mifepristone have been shown to reduce several of the local factors regarded as crucial for implantation in human endometrium. To find out if this regimen is sufficient to prevent pregnancy, 32 women were recruited for a study where 0.5 mg mifepristone was administered daily. A total of 141 cycles were studied. Five pregnancies occurred, which was significantly less than if no contraceptive method had been used. However, the dose chosen did not seem sufficient to act as a contraceptive although it is probably not possible to increase the dose without disturbing ovulation and bleeding pattern. [ABSTRACT FROM AUTHOR]

Investigates the effect of various doses of the antiprogestin mifepristone on the endometrial expression of integrins in human during the implantation phase. Endometrial biopsies from fertile women; Administration of mifepristone; Treatment groups of mifepristone; Integrin distribution; Impaired endometrial receptivity; Regulation of integrin.