Clinical Update on Uses for Mifepristone in Obstetrics and Gynecology.

Importance: Mifepristone (RU-486) is a selective progesterone receptor modulator that has antagonist properties on the uterus and cervix. Mifepristone is an effective abortifacient, prompting limitations on its use in many countries. Mifepristone has many uses outside of induced abortion, but these are less well known and underutilized by clinicians because of challenges in accessing and prescribing this medication. Objectives: To provide clinicians with a history of the development of mifepristone and mechanism of action and safety profile, as well as detail current research on uses of mifepristone in both obstetrics and gynecology. Evidence Acquisition: A PubMed search of mifepristone and gynecologic and obstetric conditions was conducted between January 2018 and December 2021. Other resources were also searched, including guidelines from the American College of Obstetricians and Gynecologists and the Society of Family Planning. Results: Mifepristone is approved by the Food and Drug Administration for first-trimester medication abortion but has other off-label uses in both obstetrics and gynecology. Obstetric uses that have been investigated include management of early pregnancy loss, intrauterine fetal demise, treatment of ectopic pregnancy, and labor induction. Gynecologic uses that have been investigated include contraception, treatment of abnormal uterine bleeding, and as an adjunct in treatment of gynecologic cancers. Conclusions and Relevance: Mifepristone is a safe and effective medication both for its approved use in first-trimester medication abortion and other off-label uses. Because of its primary use as an abortifacient, mifepristone is underutilized by clinicians. Providers should consider mifepristone for other indications as clinically appropriate.

Network pharmacology-based study on immunomodulatory mechanism of danggui-yimucao herb pair for the treatment of RU486-induced abortion.

ETHNOPHARMACOLOGICAL RELEVANCE: The Danggui-Yimucao herb pair (DY) is a classic combination in Chinese herbal formulas, consisting of the root of Angelica sinensis (Oliv.) Diels and the aerial parts of Leonurus japonicus Houtt. DY first appeared in "Zhulinsi fuke mifang" in the Jin Dynasty, and it has a long history as a drug for the treatment of abortion. However, its underlying immunomodulatory mechanisms involved are still unclear. AIM OF THE STUDY: In this study, network pharmacology and pharmacological experiments were used to explore the role and mechanism of DY in the treatment of medical abortion. MATERIALS AND METHODS: Network pharmacology was used to establish the relationship between the components of DY and abortion-related targets, and to enrich important pathways and biological process for verification. ELISA was used to assess progesterone levels. Flow cytometry was used to detect the degree of differentiation of Th1/Th2 cells. Immunohistochemical methods and qPCR were used to measure the expression levels of T-bet, GATA-3 and IL-4. RESULTS: Through the prediction analysis of network pharmacology, we found that key pathway for DY treatment of abortion, such as anemia, pelvic infection, immune disorders, and coagulation disorders, was Th1/Th2 cell differentiation pathway. The pharmacological results revealed that DY greatly corrected the imbalance of Th cell subsets in abortion mice, significantly inhibited the differentiation of Th2 cells, and resulted in an increase in the Th1/Th2 ratio. In addition, the concentration of progesterone in the serum of mice after abortion was significantly reduced. We also found that DY upregulated spleen T-bet and downregulated IL-4 gene expression in mice. Besides, immunohistochemical results showed that DYE could up-regulate T-bet but inhibit GATA-3 expression. CONCLUSIONS: Our results showed that after RU486-induced abortion, progesterone and Th1/Th2 paradigm were disordered in mice, but DY could make mice recover more quickly, which indicated that DY had great development value in immunoregulation.

Embedding similarities between embryos and circulating tumor cells: fundamentals of abortifacients used for cancer metastasis chemoprevention.

BACKGROUND: The global epidemiological studies reported lower cancer risk after long-term use of contraceptives. Our systematic studies demonstrated that abortifacients are effective in preventing cancer metastases induced by circulating tumor cells (CTCs). However, the molecular and cellular mechanisms by which abortifacients prevent CTC-based cancer metastases are almost unknown. The present studies were designed to interdisciplinarily explore similarities and differences between embryo implantation and cancer cell adhesion/invasion. METHODS: Biomarker expressions on the seeding embryo JEG-3 and cancer MCF-7 cells, as well as embedding uterine endometrial RL95-2 and vascular endothelial HUVECs cells were examined and compared before and after treatments with 17ß-estradiol plus progesterone and abortifacients. Effects of oral metapristone and mifepristone on embryo implantation in normal female mice and adhesion/invasion of circulating tumor cells (CTCs) in BALB/C female mice were examined. RESULTS: Both embryo JEG-3 and cancer MCF-7 cells expressed high sLex, CD47, CAMs, while both endometrial RL95-2 and endothelial HUVECs exhibited high integrins and ICAM-1. Near physiological concentrations of 17ß-estradiol plus progesterone promoted migration and invasion of JEG-3 and MCF-7 cells via upregulating integrins and MMPs. Whereas, mifepristone and metapristone significantly inhibited migration and invasion of JEG-3 and MCF-7 cells, and inhibited JEG-3 and MCF-7 adhesion to matrigel, RL95-2 cells and HUVECs, respectively. The inhibitions were realized by downregulating sLex, MMPs in JEG-3 and MCF-7 cells, and downregulating integrins in RL95-2 cells and HUVECs, respectively. Mifepristone and metapristone significantly inhibited both embryo implantation and cancer cell metastasis in mice. CONCLUSIONS: The similarities between the two systems provide fundamentals for abortifacients to intervene CTC adhesion/invasion to the distant metastatic organs. The present studies offer the rationale to repurpose abortifacients for safe and effective cancer metastasis chemoprevention.

Azadirachta indica A. Juss (neem) as a contraceptive: An evidence-based review on its pharmacological efficiency.

BACKGROUND: Azadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action. PURPOSE: The present review aims to summarize the efficiency of A. indica treatment as a contraceptive. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. RESULTS: A total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 2005 and 2009. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles. CONCLUSION: Although A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive.

Medication Abortion Up to 70 Days of Gestation: ACOG Practice Bulletin Summary, Number 225.

Medication abortion, also referred to as medical abortion, is a safe and effective method of providing abortion. Medication abortion involves the use of medicines rather than uterine aspiration to induce an abortion. The U.S. Food and Drug Administration (FDA)-approved medication abortion regimen includes mifepristone and misoprostol. The purpose of this document is to provide updated evidence-based guidance on the provision of medication abortion up to 70 days (or 10 weeks) of gestation. Information about medication abortion after 70 days of gestation is provided in other ACOG publications ().

Medication Abortion Up to 70 Days of Gestation: ACOG Practice Bulletin, Number 225.

Medication abortion, also referred to as medical abortion, is a safe and effective method of providing abortion. Medication abortion involves the use of medicines rather than uterine aspiration to induce an abortion. The U.S. Food and Drug Administration (FDA)-approved medication abortion regimen includes mifepristone and misoprostol. The purpose of this document is to provide updated evidence-based guidance on the provision of medication abortion up to 70 days (or 10 weeks) of gestation. Information about medication abortion after 70 days of gestation is provided in other ACOG publications ().

Closing the gap: actualising shared decision-making through effective medication abortion patient follow-up care.

BACKGROUND: Effective care dearth in USA healthcare systems can be augmented by patient engagement and shared decision-making (SDM). These effective care strategies can facilitate medical abortion follow-up care (ensuring patients are not experiencing a continuing pregnancy) and follow-up options access. LOCAL PROBLEM: The quality improvement project clinic had a state-mandated waiting period, requiring additional visits. This delayed care for all abortion patients, creating travel, and cost barriers. The clinic had some of the lowest medical abortion follow-up rates out of its entire national network. METHODS: Four 'Plan-Do-Study-Act' (PDSA) cycles built on clinical changes, implementing an Agency for Healthcare Research and Quality serum human chorionic gonadotropin guideline. Medical abortion patient cohort size doubled during each PDSA cycle. INTERVENTIONS: Through four interventions (team engagement, patient engagement, Beta follow-up and contraception SDM), standardised follow-up care was integrated into clinic workflow with contraception SDM tools and an Option Grid. RESULTS: Most intervention measures were successful, with staff offering follow-up options counselling to all medical abortion patients by the end of the project. The Beta follow-up rate (84%) was higher than the overall follow-up rate (52%-73%), but the goal of a 92% overall follow-up rate was not met. Contraception SDM streamlined counselling but long-acting reversible contraception insertion rates did not increase. CONCLUSIONS: Effective care enabled the majority of medical abortion patients to choose Beta follow-up as their preferred follow-up method, especially those with a travel barrier. Beta follow-up gives assurance to close the follow-up gap over time.

Ex-vivo abortifacient activity of Androsace foliosa n-hexane leaves extract on isolated rabbit uterus.

Androsace foliosa is a medicinal herb utilized in different areas of Pakistan for abortifacient, diabetic and liver complications. In the current research, the possible action of the n-hexane leaves extract of the Androsace foliosa on isolated rabbit uterus was examined. Abortifacient activity was examined in the existence of standard antagonist e.g. atropine and salbutamol and a uterine tonic like oxytocin. The isolated rabbit uterus is initially treated with 1mg/kg stilboesterol for 1 complete day. The consequence of oxytocin as uterine contraction agonist was observed. Additionally, antagonists e.g. salbutamol (2µg) and atropine (1-2mg) on the uterine contractile action of the extract were also examined. The A. foliosa n-hexane leaves extract fashion dose correlated amplification in the force of uterine contraction comparable to oxytocin. The drug oxytocin was pragmatic to amplify the uterine contractile action of the extract. Meanwhile pre-treating the tissue with either atropine or salbutamol earlier than administrating the extract indicates the inhibitory action of the drugs on the action of the extract.

Ginger causes subfertility and abortifacient in mice by targeting both estrous cycle and blastocyst implantation without teratogenesis.

BACKGROUND: Due to renowned medicinal properties, Ginger rhizomes (Zingiber officinale Roscoe) used traditionally in the treatment of arthritis, rheumatism, muscular aches, constipation, indigestion, hypertension, dementia, fever, and infectious diseases. As an antiemetic, Ginger is consumed by approximately 80% of pregnant women to treat nausea and vomiting of early pregnancy. PURPOSE: The aim of this study is to evaluate the impact of ginger extract on the oestrous cycle and implantation in female mice. STUDY DESIGN AND METHODS: Four experimental episodes were identified. One considered the main study of outcomes and lasted 90 days; one lasted 35 days and considered the oestrous cycle; while the third and fourth intended antifertility and abortifacient and continued 20 days for each. Mice dosed Ginger orally at 0, 250, 500, 1000 or 2000  mg/kgbw/day (GNC, GN1, GN2, GN3, GN4, respectively). RESULTS: GN3 and GN4 dams showed maternal toxicity. High dose significantly reduced the number of live fetuses and increased fetal death and resorption. Mice treated with 2000  mg/kgbw/day displayed significant decreases in implantation sites. At a dose of 2000  mg/kgbw/day, Ginger prolonged the length of oestrous cycle with a significant decrease in the duration of diestrous-metestrus (luteal) phase, prolonged proestrus-estrus (ovulatory) phase and reduced the number of cycles as well. Therefore, Ginger impairs the normal growth of corpus luteum because of progesterone insufficiency during early pregnancy. The observed-adverse-effect dose set at 2000  mg/kgbw, but no-observed-adverse-effect dose set at 250 and 500  mg/kgbw. CONCLUSION: These findings suggest that Ginger can disrupt the oestrous cycle and blastocyst implantation without teratogenesis.

Early medical abortion with self-administered low-dose mifepristone in combination with misoprostol.

AIM: The aim of the present study was to investigate the safety and efficacy of low-dose mifepristone combined with self-administered misoprostol for termination of early pregnancy. METHODS: A total of 533 women seeking medical abortion in early pregnancy (≤49 days since the last menstrual period) were divided randomly into hospital- (H-Mis, 250) and self- (S-Mis, 283) administered misoprostol groups. Women in two groups took 100 mg of oral mifepristone in hospital followed by 200 µg of sublingual misoprostol 24 h later in hospital or home. The primary outcome parameter was complete abortion without surgical intervention. Secondary outcomes were uterine bleeding, return of regular menses, side effects and patient acceptability. RESULTS: High rates of complete abortion were observed for both the H-Mis group (243/250; 94.8%) and the S-Mis group (266/283; 94.0%). No significant differences in outcomes (complete abortion/failure rates) or side effects were observed between the two groups. General satisfaction rates were similar for the two groups (H-Mis, 231/250, 92.4%; S-Mis, 263/283, 92.9%; P > 0.05). Higher convenience of administration (H-Mis, 211/250, 84.4%; S-Mis, 270/283, 95.4%; P < 0.05) and privacy protection (H-Mis, 214/250, 85.6%; S-Mis, 267/283, 94.3%; P < 0.05) satisfaction rates were obtained for the S-Mis group than for the H-Mis group. CONCLUSION: Self-administered sublingual misoprostol is as safe and effective as hospital-administered misoprostol following low-dose mifepristone to terminate early pregnancy (≤49 days of amenorrhoea) with fewer side effects.

Functional implications of the utero-placental relaxin (RLN) system in the dog throughout pregnancy and at term.

Relaxin (RLN) is a key hormone of pregnancy in mammals best known for its involvement in connective tissue remodeling. In the domestic dog, placental RLN is the only known endocrine marker of pregnancy. However, knowledge is sparse regarding the spatio-temporal expression of RLN and its receptors (RXFP1 and RXFP2) in the canine uterus and placenta. Here, their expression was investigated in the pre-implantation uterus and utero-placental compartments (UtPl) at selected time points during gestation: post-implantation, mid-gestation, and at normal and antigestagen-induced luteolysis/abortion. Immunohistochemistry with newly generated, canine-specific antisera, in situ hybridization and semi-quantitative PCR were applied. In compartmentalization studies, placental and endometrial RLN increased continuously toward prepartum. The placental RXFP1 was time-related and highest during post-implantation and decreased together with RXFP2 at prepartum luteolysis. The endometrial levels of both receptors did not vary greatly, but myometrial RXFP2 decreased from mid-gestation to prepartum luteolysis. Antigestagen treatment resulted in suppression of RLN in UtPl and decreased RXFP1 and RXFP2 in the uterus. The placental RLN was localized mainly in the cytotrophoblast. Additionally, RXFP1 stained strongly in placental endothelial cells while RXFP2 was found mainly in maternal decidual cells. Uterine staining for all targets was found in epithelial cellular constituents and in myometrium. Finally, besides its endocrine functions, RLN seems to be involved in auto-/paracrine regulation of utero-placental functions in dogs in a time-dependent manner. New insights into feto-maternal communication was provided, in particular regarding the localization of RXFP2 in the maternal decidual cells, implying functional roles of RLN during the decidualization process.

Cells expressing CD4, CD8, MHCII and endoglin in the canine corpus luteum of pregnancy, and prepartum activation of the luteal TNFα system.

In the dog, knowledge about involvement of the immune system in controlling luteal function is restricted to observations showing a time-dependent invasion of immune cells into the corpus luteum (CL) of non-pregnant bitches. Therefore, this study investigated the presence of CD4-, CD8-, MHCII- and endoglin-expressing cells in CL collected throughout pregnancy from pre-implantation until prepartum luteolysis. Immunohistochemistry and semi-quantitative RT-PCR were applied. The time-dependent expression of CD4, CD8 and endoglin was more strongly related to formation of the CL, whereas MHCII was induced during luteolysis. Next, the luteal expression of TNFα and its receptors, TNFR1 and TNFR2, was analyzed in non-pregnant dogs between days 5-65 after ovulation and during pregnancy. Moreover, the effects of progesterone withdrawal were investigated in mid-pregnant dogs treated with an antigestagen aglepristone. The TNFα system was induced in the early CL of non-pregnant dogs. In pregnant dogs, expression of TNFα did not vary much, contrasting with increased expression of both receptors in the post-implantation period and significantly decreased expression at mid-gestation; prepartum luteolysis was characterized by increased TNFR2 expression. Apart from the downregulated expression of TNFR1, the changes observed following antigestagen treatment resembled those observed during normal prepartum luteolysis. A modulatory function of the TNFα system during formation of the canine CL is suggested, possibly related to the strong accompanying vascularization and luteal infiltration with activated macrophages. Contrasting with the slow luteal regression in non-pregnant dogs, in pregnant animals the upregulation of TNFR2 expression during prepartum luteolysis implies functional involvement of the TNFα system during that time.

Abortifacient metapristone (RU486 derivative) interrupts CXCL12/CXCR4 axis for ovarian metastatic chemoprevention.

Recent global epidemiological studies revealed the lower ovarian cancer death from long-term use of oral contraceptives. However, the underlying mechanism of action is not clear. Here, we use the abortifacient metapristone (RU486 derivative) to test the hypothesis that the contraceptives might interrupt CXCL12/CXCR4 chemokine axis to inhibit ovarian cancer metastasis. Metapristone at concentrations (

Progesterone and ultrasonographic changes during aglepristone or cloprosternol treatment in queens at 21 to 22 or 35 to 38 days of pregnancy.

Progesterone (P4) is a requirement for pregnancy development. Previous reports observed a maximal value of serum P4 concentration on 21 days after the first mating after which it slowly declines throughout the rest of pregnancy. Ultrasound examination should be performed to ensure that pregnancy interruption is complete. Limited information is available on the ultrasonic appearance of conceptuses during pregnancy termination in cats The objective was to study serum P4 concentration and ultrasonographic changes during aglepristone (ALI) or cloprostenol (CLO) treatment and to evaluate the fertility after treatment. Two experiments (EXP) were carried out to accomplish this aim. Sixty queens, 12- to 36-month-old, were used. On Days 21 to 22 of pregnancy (EXP I) or 35 to 38 of pregnancy (EXP II), queens were divided into three groups (G). Queens in G1 received ALI (10 mg/kg, sc; EXP I, n = 10; EXP II, n = 10) for 2 consecutive days. Queens in G2 received CLO (5 µg/kg, sc; EXP I, n = 10; EXP II = 10) for 3 consecutive days. Queens in G3 received 1 mL of saline solution (PLA, sc; EXP I, n = 10; EXP II = 10). Blood samples were taken before treatment (Day 0) and every day during 10 days after the treatment to measure serum P4 concentrations. Likewise, after treatment, queens were monitored daily by ultrasonography for 10 days and weekly until the end of gestation to obtain gestational sacs measurements (GS), fetal measurements, and fetal biophysical profile. Data were analyzed by ANOVA. Serum P4 concentrations were significantly different on Day 6 (EXP I) and on Day 1 (EXP II) in ALI and CLO groups compared with PLA group (P < 0.05 and P < 0.01; respectively). The ultrasonographic monitoring during treatment allowed assessing changes in the GS and fetal measurements, embryo-fetal viability, and risk of pregnancy loss. In conclusion, the results from this study reported changes in serum P4 concentration and in ultrasonography measurements during pregnancy interruption with ALI or CLO treatment. Also it was observed that ALI and CLO are safe drugs and can preserve posttreatment queen fertility. Therefore, the results obtained in our work will be applied in feline reproduction practice.

Investigation of uterotonic properties of Ananas comosus extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: In folklore medicine Ananas comosus (pineapple) is reputed to act as an abortifacient and in expectant women as a means of inducing labor. Several reports have claimed abortifacient property of A. comosus fruit (ripe or unripe). Ripe fruit has been used orally as traditional medicine in inducing abortion in Kerala state of India while the juice of unripe fruit was used for abortion in Bangladesh. However, scientific evidence supporting the efficacy of pineapple extracts in inducing uterine contractions is clearly lacking. AIM OF THE STUDY: This study investigated the pharmacological effects of different fractions of pineapple extract with a range of maturities to identify the most potent uterotonic fraction. MATERIALS AND METHODS: The ethanolic crude extracts of pineapple (edible part) were prepared and fractionated through a series of liquid-liquid partitions. Fractions were separately tested on isolated uterine muscle from pregnant SD rats and human pregnant myometrium, which were cut into strips along the longitudinal axis of uterus. The strips were mounted vertically in organ baths (37°C) and exposed to cumulative addition of fractions (0.1-10mgml-1), serotonin (0.05-5µM) and different inhibitors to delineate the mechanism of action of the active ingredients of the extract. RESULTS: Aqueous fraction (F4) possesses uterine stimulant property which was blocked by verapamil but unaffected by indomethacin, prazosin and atosiban. Notably, ketanserin (10µM) diminished the maximal contractile response induced by both F4 and 5HT by 74.3% and 92.1% respectively. CONCLUSIONS: These results may indicate the presence of 5HT or 5HT-like compound(s) and serotonergic pathways may contribute to the uterotonic activity of pineapple extract.

"In patient" medical abortion versus surgical abortion: patient's satisfaction.

OBJECTIVE: To compare patients' satisfaction with medical and surgical abortion, implementing the Italian guidelines on medical abortion entailing an "in patient" procedure. METHODS: A total of 1832 pregnant chose between surgical (vacuum aspiration) or medical abortion (mifepristone p.o. followed after 3 days by sublingual misoprostol) and expressed their expected satisfaction on a visual analog scale (VAS). A total of 885 women chose surgical and 947 medical abortion. The primary end-point was satisfaction VAS score 20 days after the procedure. Secondary end-points were: difference between pre- and post-abortion VAS score; difference in satisfaction VAS scores according to parity and previous abortion; incidence of side effects. RESULTS: VAS score was high in each group but significantly higher for the 1-day surgical than for the 3-day medical abortion procedure (7.9 ± 1.0 versus 7.2 ± 1.2; p < 0.0001). In the surgical group the VAS score increased after the treatment (6.9 ± 1.6 versus 7.9 ± 1.0, p < 0.0001), while it decreased in the medical group (7.5 ± 1.0 versus 7.2 ± 1.2; p < 0.0001). Multiparous women reported higher satisfaction with medical abortion; women with a previous abortion preferred surgical abortion. CONCLUSIONS: Both procedures are considered satisfactory by the patients. Performing medical abortion as a 3-day "in patient" procedure, decreased women's satisfaction scores from their baseline expectations.

[Methods of induction of labor in termination of pregnancy after 22weeks: About 3procedures]. / Modalités d'induction du travail des interruptions médicales de grossesse après 22SA : à propos de 3protocoles.

OBJECTIVES: To propose a protocol for induction of labor to terminate pregnancy after 22weeks of amenorrhea allowing to decrease the duration of labor and of hospitalization but also, allowing to reduce the number of emergency pretreatment-induced fetal death, to improve the experience of the patients and to limit the cost. METHODS: We realized a retrospective single-center study including 269patients and comparing three protocols, with and without laminaria and with various intervals mifepristone-misoprostol (14 and 38hours). The outcome measures were the misoprostol-delivery interval, the delivery time and the number of emergency pretreatment-induced fetal death. RESULTS: We showed that the misoprostol-delivery interval and the delivery time were comparable for the three periods of our study, even after decrease of 24hours of the mifepristone-misoprostol interval and in the absence of laminaria. The misoprostol-delivery interval was between 7h30 and 8h35 between protocols (P=0.055). The delivery time was between 5:18pm and 6:48pm between protocols (P=0.252). The early administration of misoprostol allowed the patients to give birth earlier (P=0.001). Finally, we showed that the increase of the size and the number of laminarias were risk factors of emergency pretreatment-induced fetal death (respectively P=0.013 and P=0.002). CONCLUSION: The absence of laminaria and the reduction of the interval mifepristone-misoprostol of 24hours do not change the time to delivery and allow to reduce the duration of hospitalization, the number of emergency pretreatment-induced fetal death and the cost of the TOP.

Aglepristone: A review on its clinical use in animals.

Aglepristone (RU 46534) is a competitive progesterone antagonist that is indicated for the treatment of various progesterone-dependent physiological or pathologic conditions. Aglepristone has proven to be an effective means of terminating pregnancy in most species. When used to induce parturition, aglepristone was effective in all cases in the bitch, cow, and goat, with no apparent adverse effects on neonatal health or milk production. When used to schedule an elective cesarean section, aglepristone treatment was deemed safe for dams and puppies, providing that the ovulation date had been accurately assessed at the time of breeding. Irrespective of the stage of pregnancy at injection, treatment with aglepristone has no apparent negative effects on subsequent fertility. Aglepristone is also a safe and relatively effective means of treating pyometra. However, given the high level of septic risk and the likelihood of rapid deterioration, such therapy is not recommended in emergency situations. Treatment of feline fibroadenomatosis using aglepristone has given promising results, but repeat treatment may be necessary in cats previously treated with long-acting progestagens. The use of aglepristone in other progesterone-dependent diseases has yet to be fully evaluated but may prove valuable, especially in the treatment of insulin-resistant diabetes mellitus, acromegaly, and the treatment of some vaginal tumors in the bitch.

Abortifacient potential of methanolic extract of Anthocephalus cadamba stem bark in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants possessing abortifacient activity have been used traditionally for a long time in folk medicine. Anthocephalus cadamba, is one such herb that has been known to possess abortifacient potential in ethnobotanical literature, but has not been validated scientifically. MATERIALS AND METHODS: The methanolic extract of Anthocephalus cadamba stem bark (MEAC) was prepared and tested for abortifacient, estrogenic and uterotrophic activity. Pregnant Swiss albino mice were randomized into 5 groups (1-5). Group 1 (negative control) received 0.2% w/v agar, group 2-4 (received extract at the dose of 500, 1000 and 1500mg/kg b.w.) and group 5 received mifepristone at a dose of 5.86mg/kg b.w. respectively, by oral route from 10(th) to 18(th) day post-coitum daily, and various parameters recorded. The uterotrophic bioassay was performed in bilaterally ovariectomized mice dosed from 9(th) to 15(th) day of ovariectomy and change in uterotrophic parameters was observed. RESULTS: Preliminary phytochemical screening revealed presence of glycosides, alkaloids, steroids, saponins, triterpenoids, flavonoids and tannins. No signs of clinical toxicity were observed at any time during the period of treatment. The extract significantly reduced (P<0.05) the number of live fetus, weight and survival ratio of the fetus, number of corpora lutea, progesterone, estradiol and luteinizing hormone whereas the number of dead fetus, number of mice that aborted, percentage vaginal opening and post-implantation loss increased significantly (P<0.05). The estrogenicity experiments showed increase in uterine weight (P<0.05), ballooning of uterus, uterine glucose (P<0.05) and ALP (P<0.001) in extract treated group dose dependently. In addition, the extract also induced vaginal bleeding preceding parturition. CONCLUSION: This study has substantiated the abortifacient potential of the methanolic extract of Anthocephalus cadamba stem bark. The activity was more marked in 1000 and 1500mg/kg b.w. of the extract and was comparable to that of mifepristone. The mechanism of abortion could possibly be through changes in the uterine mileu, altered hormone levels, luteolysis and partly, estrogenicity. This study thus justifies the ethnobotanical claim of MEAC as an abortifacient.